Projections for Achieving the Lancet Commission Recommended Surgical Rate of 5000 Operations per 100,000 Population by Region-Specific Surgical Rate Estimates.
We previously identified a range of 4344-5028 annual operations per 100,000 people to be related to desirable health outcomes. From this and other evidence, the Lancet Commission on Global Surgery recommends a minimum rate of 5000 operations per 100,000 people. We evaluate rates of growth and estimate the time it will take to reach this minimum surgical rate threshold. We aggregated country-level surgical rate estimates from 2004 to 2012 into the twenty-one Global Burden of Disease (GBD) regions. We calculated mean rates of surgery proportional to population size for each year and assessed the rate of growth over time. We then extrapolated the time it will take each region to reach a surgical rate of 5000 operations per 100,000 population based on linear rates of change. All but two regions experienced growth in their surgical rates during the past 8 years. Fourteen regions did not meet the recommended threshold in 2012. If surgical capacity continues to grow at current rates, seven regions will not meet the threshold by 2035. Eastern Sub-Saharan Africa will not reach the recommended threshold until 2124. The rates of growth in surgical service delivery are exceedingly variable. At current rates of surgical and population growth, 6.2 billion people (73% of the world's population) will be living in countries below the minimum recommended rate of surgical care in 2035. A strategy for strengthening surgical capacity is essential if these targets are to be met in a timely fashion as part of the integrated health system development.


A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.
It is essential to understand the network of transcription factors controlling self-renewal of human embryonic stem cells (ESCs) and human embryonal carcinoma cells (ECs) if we are to exploit these cells in regenerative medicine regimes. Correlating gene expression levels after RNAi-based ablation of OCT4 function with its downstream targets enables a better prediction of motif-specific driven expression modules pertinent for self-renewal and differentiation of embryonic stem cells and induced pluripotent stem cells.We initially identified putative direct downstream targets of OCT4 by employing CHIP-on-chip analysis. A comparison of three peak analysis programs revealed a refined list of OCT4 targets in the human EC cell line NCCIT, this list was then compared to previously published OCT4 CHIP-on-chip datasets derived from both ES and EC cells. We have verified an enriched POU-motif, discovered by a de novo approach, thus enabling us to define six distinct modules of OCT4 binding and regulation of its target genes.A selection of these targets has been validated, like NANOG, which harbours the evolutionarily conserved OCT4-SOX2 binding motif within its proximal promoter. Other validated targets, which do not harbour the classical HMG motif are USP44 and GADD45G, a key regulator of the cell cycle. Over-expression of GADD45G in NCCIT cells resulted in an enrichment and up-regulation of genes associated with the cell cycle (CDKN1B, CDKN1C, CDK6 and MAPK4) and developmental processes (BMP4, HAND1, EOMES, ID2, GATA4, GATA5, ISL1 and MSX1). A comparison of positively regulated OCT4 targets common to EC and ES cells identified genes such as NANOG, PHC1, USP44, SOX2, PHF17 and OCT4, thus further confirming their universal role in maintaining self-renewal in both cell types. Finally we have created a user-friendly database (http://biit.cs.ut.ee/escd/), integrating all OCT4 and stem cell related datasets in both human and mouse ES and EC cells.In the current era of systems biology driven research, we envisage that our integrated embryonic stem cell database will prove beneficial to the booming field of ES, iPS and cancer research.


Embryo cell allocation patterns are not altered by biopsy but can be linked with further development.
It has been suggested that first embryo cleavage can be related with the embryonic-abembryonic axis at blastocyst stage in mice. Thus, cells of the 2-cell embryo might be already biased to form the inner cell mass or trophectoderm. This study was conducted to observe the possible effects of embryo biopsy on cell allocation patterns during embryo preimplantation in two different mouse strains and the effects of these patterns on further development. First, one blastomere of the 2-cell embryo was injected with a lipophilic tracer and cell allocation patterns were observed at blastocyst stage. Blastocysts were classified into orthogonal, deviant or random pattern. For the first experiment, embryos were biopsied at 8-cell stage and total cell counts (TCC) were annotated. Furthermore, non-biopsied blastocysts were transferred into foster mothers. Then, pups and their organs were weighed two weeks after birth. Random pattern was significantly recurrent (≈60%), against orthogonal (<22%) and deviant (<22%) patterns among groups. These patterns were not affected by biopsy procedure. However, TCC on deviant embryos were reduced after biopsy. Moreover, no differences were found between patterns for implantation rates, litter size, live offspring and organ weights (lungs, liver, pancreas and spleen). However, deviant pups presented heavier hearts and orthogonal pups presented lighter kidneys among the group. In conclusion, these results suggest that single blastomere removal does not disturb cell allocation patterns during pre-implantation. Nonetheless, the results suggest that embryos following different cell allocation patterns present different coping mechanisms against in vitro manipulations and further development might be altered.


APOEε4 potentiates the relationship between amyloid-β and tau pathologies.
APOEε4 is the most well-established genetic risk factor for sporadic Alzheimer's disease and is associated with cerebral amyloid-β. However, the association between APOEε4 and tau pathology, the other major proteinopathy of Alzheimer's disease, has been controversial. Here, we sought to determine whether the relationship between APOEε4 and tau pathology is determined by local interactions with amyloid-β. We examined three independent samples of cognitively unimpaired, mild cognitive impairment and Alzheimer's disease subjects: (1) 211 participants who underwent tau-PET with [18F]MK6240 and amyloid-PET with [18F]AZD4694, (2) 264 individuals who underwent tau-PET with [18F]Flortaucipir and amyloid-PET with [18F]Florbetapir and (3) 487 individuals who underwent lumbar puncture and amyloid-PET with [18F]Florbetapir. Using a novel analytical framework, we applied voxel-wise regression models to assess the interactive effect of APOEε4 and amyloid-β on tau load, independently of age and clinical diagnosis. We found that the interaction effect between APOEε4 and amyloid-β, rather than the sum of their independent effects, was related to increased tau load in Alzheimer's disease-vulnerable regions. The interaction between one APOEε4 allele and amyloid-β was related to increased tau load, while the interaction between amyloid-β and two APOEε4 alleles was related to a more widespread pattern of tau aggregation. Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-β and tau aggregation. These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.


Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts.
Camostat mesilate (CM) possesses potential anti-viral and anti-inflammatory activities. However, it remains unknown whether CM is involved in lipopolysaccharide (LPS)-mediated inflammatory responses and cell injury. In this project, differentially expressed proteins (DEPs, fold change ≥ 1.2 or ≤ 0.83 and Q value ≤ 0.05) in response to LPS stimulation alone or in combination with CM were identified through tandem mass tags (TMT)/mass spectrometry (MS)-based proteomics analysis in DF-1 chicken embryo fibroblasts. The mRNA expression levels of filtered genes were determined by RT-qPCR assay. The results showed that CM alleviated the detrimental effect of LPS on cell viability and inhibited LPS-induced TNF-α and IL-6 secretions in DF-1 chicken embryo fibroblasts. A total of 141 DEPs that might be involved in mediating functions of both LPS and CM were identified by proteomics analysis in DF-1 chicken embryo fibroblasts. LPS inhibited milk fat globule EGF and factor V/VIII domain containing (MFGE8) expression and induced high mobility group nucleosome binding domain 1 (HMGN1) expression, while these effects were abrogated by CM in DF-1 chicken embryo fibroblasts. MFGE8 knockdown facilitated TNF-α and IL-6 secretions , reduced cell viability, stimulated cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. HMGN1 loss did not influence TNF-α and IL-6 secretions, cell viability, and cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. In conclusion, CM exerted anti-inflammatory and pro-survival activities by regulating MFGE8 in LPS-stimulated DF-1 chicken embryo fibroblasts, deepening our understanding of the roles and molecular basis of CM in protecting against Gram-negative bacteria.


Basal Ganglia-A Motion Perspective.
The basal ganglia represent an ancient part of the nervous system that have remained organized in a similar way over the last 500 million years and are of importance for our ability to determine which actions to choose at any given moment in time. Salient or reward stimuli act via the dopamine system and contribute to motor or procedural learning (reinforcement learning). The input stage of the basal ganglia, the striatum, is shaped by glutamatergic input from the cortex and thalamus and by the dopamine system. All intrinsic neurons of the striatum are GABAergic and inhibitory except for the cholinergic interneurons. Too little dopamine and all vertebrates show symptoms similar to that of a Parkinsonian patient, whereas too much dopamine results in hyperkinesia with involuntary movements. In this article, we discuss the detailed organization of the basal ganglia, with the different cell types, their properties, and contributions to basal ganglia functions. The striatal projection neurons represent 95% of all neurons in the striatum and are subdivided into two types, one that projects directly to the output stage, referred to as the "direct" pathway that promotes action, and the other subtype that targets the output nuclei via intercalated basal ganglia nuclei. This "indirect" pathway has an opposite effect. The striatal projection neurons express a set of ion channels that give them a high threshold for activation, whereas neurons in all other parts of the basal ganglia have a resting discharge that allows for modulation in both an increased and decreased direction. © 2020 American Physiological Society. Compr Physiol 10:1241-1275, 2020.


Ultradeformable liposomes with terpenes for delivery of hydrophilic compound.
Ultradeformable liposomes containing penetration enhancers were created to deliver NaFl. Vesicles were investigated for their particle size, zeta potential, NaFl entrapment efficiency (%EE), loading efficiency, and in vitro skin penetration. The vesicles obtained were spherical in shape, with a particle size of less than 100 nm and a negative surface charge (-6 to -11 mV). The %EE of NaFl loaded in vesicles ranged from 37 to 48%. Ultradeformable liposomes with monoterpenes (d-limonene, 1,8-cineole and geraniol) significantly improved NaFl penetration through the skin. Confocal laser scanning microscopy analysis confirmed skin-penetration results and was used to evaluate the behavior of hydrophilic compounds penetrating through the skin.


Proteome analysis of the fathead minnow (Pimephales promelas) reproductive testes.
Proteomics is becoming more widely used as a tool in fish physiology and toxicology and can offer mechanistic insight into organism responses to environmental signals and stressors. Using a LTQ Orbitrap Velos MS/MS, we detected 1075 proteins in the reproductive testis of fathead minnow. Proteins localized to the testis included those with a role in spermatogenesis, DNA repair, gamete meiosis, and proteins that have methylation and phosporylation activity, which are important regulatory mechanisms required for sperm maturation. Enrichment analysis revealed that proteins involved in translation, excision DNA repair, and chromatin remodeling were significantly enriched in the testis (>25% protein coverage of the cellular pathways). Proteins involved in RNA metabolism, spliceosome assembly, metabolism, and DNA unwinding were localized to the testis, and the DEAD (Asp-Glu-Ala-Asp) box RNA-dependent helicase family was well represented in this reproductive tissue. Based upon common detected proteins and functional processes between FHMs and the more ancient sharks, other ray-finned fishes, and mammals, we hypothesize that biological processes involved in the testis (DNA unwinding, RNA processing, spliceosome assembly) have been conserved throughout vertebrate evolution. This study provides the foundation for more in depth proteomics studies investigating the effects of hormones and endocrine disruptors in the teleostean testes.


Dupilumab in the management of moderate-to-severe asthma: the data so far.
Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs). It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future.


Characteristics of office-based physician visits for cutaneous fungal infections. an analysis of 1990 to 1994 National Ambulatory Medical Care Survey Data.
To our knowledge, visits in the ambulatory setting due to cutaneous fungal infections have not been recently characterized. To provide descriptive epidemiology on ambulatory cutaneous fungal infection visits, we analyzed office-based physician visits for cutaneous fungal infections recorded in the National Ambulatory Medical Care Survey (NAMCS) from 1990 to 1994. The International Classification of Diseases (ICD-9) was used to define the cutaneous fungal infections. Sampling weights were applied to achieve the nationally representative estimates. From 1990 to 1994, an estimated 21.6 million physician office visits at an estimated cost of $216 million/y (office visit plus medication costs) were made for cutaneous fungal infection diagnoses. The total cost of office visits (without medication costs) was approximately $116 million/y. The total cost of the top 5 medications was approximately $68 million/y. According to an analysis of visits per physician specialist, dermatologists had the largest proportion of visits for cutaneous fungal infections. The cost associated with the diagnosis and management of cutaneous fungal infections is significant. Of all the physician specialists, dermatologists treated the most cutaneous fungal infections.


The Epstein-Barr virus-induced Ca2+/calmodulin-dependent kinase type IV/Gr promotes a Ca(2+)-dependent switch from latency to viral replication.
The switch from latency to viral replication in Epstein-Barr virus (EBV)-transformed human B cells is mediated by Zta, the protein product of immediate-early EBV gene BZLF1. BZLF1 transcription is normally suppressed in EBV-transformed B cells but can be induced in some cell lines upon ligation of surface immunoglobulin by mechanisms that include the activation of Ca(2+)-dependent signaling pathways. The multifunctional Ca2+/calmodulin-dependent kinase type IV/Gr (CaMKIV/Gr) is normally absent in primary human B cells, but its expression is induced by the EBV oncoprotein LMP1 in the course of B-cell growth transformation by EBV. In this study, we demonstrate that activated CaMKIV/Gr induces transcription from the BZLF1 promoter and upregulates the expression of Zta in permissive cells. Transcriptional activation of the BZLF1 promoter by CaMKIV/Gr is dependent on the CREB/AP1 binding element ZII and is greatly augmented by the Ca2+/calmodulin-dependent phosphatase calcineurin. These results outline a virus-regulated mechanism involving CaMKIV/Gr which promotes transition from latency to productive viral replication in response to Ca(2+)-mobilizing extracellular signals.


Less is more: an adaptive branch-site random effects model for efficient detection of episodic diversifying selection.
Over the past two decades, comparative sequence analysis using codon-substitution models has been honed into a powerful and popular approach for detecting signatures of natural selection from molecular data. A substantial body of work has focused on developing a class of "branch-site" models which permit selective pressures on sequences, quantified by the ω ratio, to vary among both codon sites and individual branches in the phylogeny. We develop and present a method in this class, adaptive branch-site random effects likelihood (aBSREL), whose key innovation is variable parametric complexity chosen with an information theoretic criterion. By applying models of different complexity to different branches in the phylogeny, aBSREL delivers statistical performance matching or exceeding best-in-class existing approaches, while running an order of magnitude faster. Based on simulated data analysis, we offer guidelines for what extent and strength of diversifying positive selection can be detected reliably and suggest that there is a natural limit on the optimal parametric complexity for "branch-site" models. An aBSREL analysis of 8,893 Euteleostomes gene alignments demonstrates that over 80% of branches in typical gene phylogenies can be adequately modeled with a single ω ratio model, that is, current models are unnecessarily complicated. However, there are a relatively small number of key branches, whose identities are derived from the data using a model selection procedure, for which it is essential to accurately model evolutionary complexity.


Cost-Effectiveness of a Health System-Based Smoking Cessation Program.
Project CLIQ (Community Link to Quit) was a proactive population-outreach strategy using an electronic health records-based smoker registry and interactive voice recognition technology to connect low- to moderate-income smokers with cessation counseling, medications, and social services. A randomized trial demonstrated that the program increased cessation. We evaluated the cost-effectiveness of CLIQ from a provider organization's perspective if implemented outside the trial framework. We calculated the cost, cost per smoker, incremental cost per additional quit, and, secondarily, incremental cost per additional life year saved of the CLIQ system compared to usual care using data from a 2011-2013 randomized trial assessing the effectiveness of the CLIQ system. Sensitivity analyses considered economies of scale and initial versus ongoing costs. Over a 20-month period (the duration of the trial) the program cost US $283 027 (95% confidence interval [CI] $209 824-$389 072) more than usual care in a population of 8544 registry-identified smokers, 707 of whom participated in the program. The cost per smoker was $33 (95% CI 28-40), incremental cost per additional quit was $4137 (95% CI $2671-$8460), and incremental cost per additional life year saved was $7301 (95% CI $4545-$15 400). One-time costs constituted 28% of costs over 20 months. Ongoing costs were dominated by personnel costs (71% of ongoing costs). Sensitivity analyses showed sharp gains in cost-effectiveness as the number of identified smokers increased because of the large initial costs. The CLIQ system has favorable cost-effectiveness compared to other smoking cessation interventions. Cost-effectiveness will be greatest for health systems with high numbers of smokers and with the high smoker participation rates. Health information systems capable of establishing registries of patients who are smokers are becoming more prevalent. This economic analysis illustrates the cost implications for health care systems adopting a proactive tobacco treatment outreach strategy for low- and middle-income smokers. We find that under many circumstances, the CLIQ system has a favorable cost-per-quit compared to other population-based tobacco treatment strategies. The strategy could be widely disseminable if health systems leverage economies of scale.


Macroporous monolithic supports for affinity chromatography.
In the early 1990s, three research groups simultaneously developed continuous macroporous rod-shaped polymeric systems to eliminate the problem of flow through the interparticle spaces generally presented by the chromatography columns that use particles as filler. The great advantage of those materials, forming a continuous phase rod, is to increase the mass transfer by convective transport, as the mobile phase is forced to go through all means of separation, in contrast to particulate media where the mobile phase flows through the interparticle spaces. Due to their special characteristics, the monolithic polymers are used as base-supports in different separation techniques, those chromatographic processes being the most important and, to a greater extent, those involving the separation of biomolecules as in the case of affinity chromatography. This mini-review reports the contributions of several groups to the development of macroporous monoliths and their modification by immobilization of specific ligands on the products for their application in affinity chromatography.


Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences.
Ginkgo biloba extract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 microL 6-OHDA (10 microg in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 microL of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism.


The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation.
Intracranial implants elicit neurodegeneration via the foreign body response (FBR) that includes BBB leakage, macrophage/microglia accumulation, and reactive astrogliosis, in addition to neuronal degradation that limit their useful lifespan. Previously, monocyte chemoattractant protein 1 (MCP-1, also CCL2), which plays an important role in monocyte recruitment and propagation of inflammation, was shown to be critical for various aspects of the FBR in a tissue-specific manner. However, participation of MCP-1 in the brain FBR has not been evaluated. Here we examined the FBR to intracortical silicon implants in MCP-1 KO mice at 1, 2, and 8 weeks after implantation. MCP-1 KO mice had a diminished FBR compared to WT mice, characterized by reductions in BBB leakage, macrophage/microglia accumulation, and astrogliosis, and an increased neuronal density. Moreover, pharmacological inhibition of MCP-1 in implant-bearing WT mice maintained the increased neuronal density. To elucidate the relative contribution of microglia and macrophages, bone marrow chimeras were generated between MCP-1 KO and WT mice. Increased neuronal density was observed only in MCP-1 knockout mice transplanted with MCP-1 knockout marrow, which indicates that resident cells in the brain are major contributors. We hypothesized that these improvements are the result of a phenotypic switch of the macrophages/microglia polarization state, which we confirmed using PCR for common activation markers. Our observations suggest that MCP-1 influences neuronal loss, which is integral to the progression of neurological disorders like Alzheimer's and Parkinson disease, via BBB leakage and macrophage polarization.


Markedly elevated levels of an endogenous sarc protein in a hemopoietic precursor cell line.
The src gene product of Harvey murine sarcoma virus is a 21,000-dalton guanine nucleotide-binding protein. We have recently shown that a wide variety of vertebrate cell strains and cell lines express much lower levels of an endogenous p21 immunologically related to the Harvey murine sarcoma virus-coded p21. In this report, we have examined the levels of endogenous p21 in a unique hemopoietic precursor cell line, 416B, which was originally described as a continuous cell line of a hemopoietic stem cell, CFU-S. The currently available 416B cells express markedly elevated levels of endogenous p21. The level of endogenous p21 in the 416B cells is 5- to 10-fold higher than the level of p21 in Harvey murine sarcoma virus-infected cells and more than 100 times higher than the level of endogenous p21 that we have observed in a variety of other fresh or cultured cells. The results indicate that marked regulation of the levels of an endogenous sarc gene product can occur, and speculation about a possible role for endogenous p21 in normal hemopoietic stem cells is discussed.


Correction: Saeed, A., et al. Incidence of Vancomycin-Resistant Phenotype of the Methicillin-Resistant Staphylococcus aureus Isolated from a Tertiary Care Hospital in Lahore. Antibiotics 2020, 9, 3.
Staphylococcus aureus (S. aureus)-associated infections are one of the major threats to public health. The aim of the present study was to determine the antibiotic resistance pattern, as well as the genetic characterization, of methicillin and vancomycin-resistant S. aureus (VRSA) isolated from a tertiary care hospital in Lahore. The S. aureus isolates were isolated from different clinical samples, identified by biochemical testing, and subjected to antibiotic susceptibility testing via the disc diffusion method or broth microdilution method. The methicillin resistance gene (mecA) and vancomycin resistance gene (vanA) were amplified by the polymerase chain reaction. The S. aureus isolates showed high incidences of resistance against methicillin (76%) and moderate incidences of resistance to vancomycin (14%). Isolates were also resistant to several other drugs, such as cefoxitin (76%), ertapenem (83%), ampicillin (81%), tobramycin (78%), moxifloxacin (76%), and tetracycline (74%). An encouraging finding was that 98% of isolates were susceptible to tigecycline, indicating its possible role in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) and VRSA, as well as the multi-drug resistant S. aureus. The mecA gene was detected in 33.3% of tested isolates (10/30), while the vanA gene was also detected in 30% (9/30) of the tested isolates. In conclusion, the frequent presence of methicillin and vancomycin resistance in S. aureus appraises the cautious use of these antibiotics in clinical practices. Furthermore, it is suggested that there should be continuous monitoring of tigecycline treatments in clinical setups in order to delay the development of resistance against it.


Thermal rejuvenation in metallic glasses.
Structural rejuvenation in metallic glasses by a thermal process (i.e. through recovery annealing) was investigated experimentally and theoretically for various alloy compositions. An increase in the potential energy, a decrease in the density, and a change in the local structure as well as mechanical softening were observed after thermal rejuvenation. Two parameters, one related to the annealing temperature, Ta/Tg, and the other related to the cooling rate during the recovery annealing process, Vc/Vi, were proposed to evaluate the rejuvenation phenomena. A rejuvenation map was constructed using these two parameters. Since the thermal history of metallic glasses is reset above 1.2Tg, accompanied by a change in the local structure, it is essential that the condition of Ta/Tg ≥ 1.2 is satisfied during annealing. The glassy structure transforms into a more disordered state with the decomposition of icosahedral short-range order within this temperature range. Therefore, a new glassy structure (rejuvenation) depending on the subsequent quenching rate is generated. Partial rejuvenation also occurs in a Zr55Al10Ni5Cu30 bulk metallic glass when annealing is performed at a low temperature (Ta/Tg ~ 1.07) followed by rapid cooling. This behavior probably originates from disordering in the weakly bonded (loosely packed) region. This study provides a novel approach to improving the mechanical properties of metallic glasses by controlling their glassy structure.


The recruitment of acetylated and unacetylated tropomyosin to distinct actin polymers permits the discrete regulation of specific myosins in fission yeast.
Tropomyosin (Tm) is a conserved dimeric coiled-coil protein, which forms polymers that curl around actin filaments in order to regulate actomyosin function. Acetylation of the Tm N-terminal methionine strengthens end-to-end bonds, which enhances actin binding as well as the ability of Tm to regulate myosin motor activity in both muscle and non-muscle cells. In this study we explore the function of each Tm form within fission yeast cells. Electron microscopy and live cell imaging revealed that acetylated and unacetylated Tm associate with distinct actin structures within the cell, and that each form has a profound effect upon the shape and integrity of the polymeric actin filament. We show that, whereas Tm acetylation is required to regulate the in vivo motility of class II myosins, acetylated Tm had no effect on the motility of class I and V myosins. These findings illustrate a novel Tm-acetylation-state-dependent mechanism for regulating specific actomyosin cytoskeletal interactions.


Necropsy survey of metacarpal fusion in the horse.
Paired metacarpi obtained at necropsy from 100 horses ranging in age from term fetus to 35 years were examined to estimate the prevalence and sites of metacarpal fusion. Metacarpal fusion was seen in 192 of 200 metacarpi, and 78% of all horses 2 years or older had 2 or more fusions. Fusion of the second metacarpal bone to the third metacarpal bone was significantly (P < 0.001) more common than was fusion of the fourth to the third metacarpal bone. Fusions appeared for the most part in pairs and were bilaterally symmetric. Rooney-Prickett type-A carpometacarpal joint configurations (in which there is no measurable articulation between the third carpal and second metacarpal bones) were rare in this population, and Rooney-Prickett type-B configurations (in which there is a measurable articulation between the third carpal and second metacarpal bones) were observed in 98.5% of metacarpi. Medial metacarpal fusion was positively correlated with age, occupation, and proportion of the proximal projection of the carpometacarpal distal joint surface that was taken by the second metacarpal bone. Lateral metacarpal fusion was positively correlated with age and the proportion of the proximal projection of the carpometacarpal distal joint surface taken by the fourth metacarpal bone. Horses in performance careers (racing, race training, or show ring occupations) had an earlier development of the first 2 fusions than did horses in other or unknown occupations; development of the third and fourth fusions were not significantly different between occupation groups. The rate of metacarpal fusion per horse-year appeared to be at least 10 times higher than a clinically evident rate. A variety of gross morphologic features was observed in the fusions from this sample, some of which were small, subtle, and possibly difficult to detect in vivo. It is hypothesized that many instances of metacarpal fusion may be a result of functional adaptation of the metacarpus to increased or changed loading conditions, rather than a response to isolated traumatic events.


Director of nursing and midwifery leadership: informed through the lens of critical social science.
Highlight the use of critical social science theories, practice development principles and a situational leadership framework within transformational leadership to inform Directors of Nursing and Midwifery (DoNM) practices as leaders. Healthcare is constantly changing, unpredictable, strives for quality service and cost containment, which can result in stress and crisis for healthcare workers. DoNM leadership is critical to supporting and leading staff through these complex times within healthcare. Understanding theories, frameworks and their application to real-world practice can assist in supporting individuals and teams to navigate through the changing healthcare environment. Blending critical social science theories with practice development principles and the situational leadership framework can assist the DoNM to enact transformational leadership to support the development of individuals and teams to meet the complex healthcare needs of patients within the clinical setting. IMPLICATIONS FOR NURSE MANAGEMENT: This article contributes through the practical application of critical social science theories, practice development principles and situational leadership framework within transformational leadership as an approach for enacting DoNM leadership. To further understand and develop in the role of the contemporary DoNM in leadership, these directors are encouraged to publish their work.


Sedation in outpatient bronchoscopy.
Bronchoscopy is a procedure that is likely to provoke anxiety as the patient is surrounded by monitoring and bronchoscopy equipment, and care is administered by strangers who perform intimate, invasive, and sometimes, painful procedures. Sedation is needed, therefore, to allay anxiety and reduce stress, improve patient comfort and co-operation, provide amnesia and facilitate the bronchoscopic procedure. In this review we try to summarize the current knowledge on currently used sedation protocols with special reference to the commonly used pharmacological agents. We believe sedation should be used routinely in fiberoptic bronchoscopy in order to achieve a safe and pleasant procedure for both the patient and the pulmonologist.


The ferrule effect.
When the supra-marginal dentine of a root-filled tooth is engaged by a crown, it may create a stronger tooth/restoration complex. This has been termed the ferrule effect. This paper reviews the current evidence for this effect and examines the influence various post and core materials have on it. Means of achieving a ferrule are discussed and the importance of planning for failure is considered. Provision for the ferrule effect when restoring root-filled teeth with a post-retained crown may optimize the strength of the restored tooth.


Atrial remodeling after the Fontan operation.
The hemodynamics after Fontan surgery are notable for hypertension and dilation of the right atrium (RA). The effect of this stress on atrial cytoarchitecture has not been systematically studied and might be relevant to arrhythmias and their treatment. Morphologic and histopathologic analyses were performed on tissue from the RA and left atrium (LA) from autopsy specimens of Fontan hearts (n = 47). The findings were compared to those from control samples from young patients with normal atrial hemodynamics (n = 15). Most Fontan specimens were from young patients who died after a relatively short duration of Fontan physiology. The tissues were analyzed for wall thickness, fibrosis content, and fibrosis pattern. The mean wall thickness for the RA (3.0 +/- 1.0 mm) and LA (2.3 +/- 0.6 mm) in the Fontan hearts was significantly greater than that in the control hearts (RA, 1.8 +/- 0.4 mm; LA, 1.8 +/- 0.5 mm; p <0.001 and p = 0.024, respectively). The predictors for thickening of the RA included (1) older age at Fontan surgery, (2) older age at death, and (3) longer duration of Fontan circulation. The Fontan hearts and control hearts exhibited nearly identical fibrosis patterns in the RA and LA. Neither wall thickness nor fibrosis varied with the underlying heart defect or style of Fontan connection. In conclusion, atrial remodeling after Fontan surgery for univentricular heart physiology involves increased wall thickness in both the RA and LA. Interstitial fibrosis was also observed in the Fontan atria; however, because a similar pattern was present in the control tissue, this likely represented normal fibroelastic atrial structure, rather than a specific response to Fontan hemodynamics. The degree of wall thickening observed in the Fontan atria was not so excessive as to preclude transmural lesions during catheter or surgical ablation of reentrant arrhythmias.


Cervical intraepithelial neoplasia and associated condylomatous lesions. A preliminary report on 4,764 women from Northern Israel.
During the period spanning the years 1973 to 1981, 4,764 women visited the Gynecology Out-Patient Clinics and Colposcopy Unit of the Nahariyya Hospital to be examined colposcopically and cytologically (and histologically whenever indicated) for precancerous and cancerous lesions of the cervix. Of these women, 2,614 (55%) were referred because of symptoms of cervical pathology and 2,150 (45%) for other (prophylactic) reasons. The subdivision of all women according to their demographic backgrounds afforded a comparison of the findings in Israeli-born Jewesses with those of foreign-born Jewesses and non-Jewish females living in the same geographic area of the Western Galilee district of Israel. Despite the low prevalence of cervical cancer in Jewesses throughout the world, the preliminary report of our pilot study demonstrated that the percentage rates of all degrees of dysplasia/cervical intraepithelial neoplasia (CIN I, II and III) of the uterine cervix of Israeli-born Jewesses was 5.4% in patients with cervical pathology and 3.24% in noncervical-pathology patients. These rates were the highest recorded for any of the demographic groups: 2.06% and 0.33%, respectively, in Moslem women; 1.23% in Christian women with cervical pathology; 2.38% and 1.78%, respectively, in European/American-born Jewesses; and 1.63% and 0.48%, respectively, in Asian/African-born Jewesses. The highest proportion of CIN lesions occurred in the 15- to 30-year-old age groups. Of 100 CIN lesions found in all patients, 45 were cytohistologically associated with the cells of condylomatous lesions. Of 36 patients in whom cervical squamous-cell carcinoma lesions were detected, 18 (50%) were staged (FIGO) as carcinoma in situ (stage 0); the remainder were in stages IA, IB, IIA and IIB, with none in stages III or IV.


Aeromonas proteolytica--a halophilic aeromonad?
Aeromonas proteolytica, a halophilic bacterium originally isolated from the intestine of a marine isopod, was compared with 93 strains of Aeromonas hydrophila and representative strains of five similar genera in a computer and serological analysis. Aeromonas proteolytica was peritrichate and non-reactive with six A. hydrohila antisera, and possessed a percentage guanine + cytosine ratio (49.5) outside the range for other aeromonads (55-62%). Moreover, in the computer analysis it shared a lower level of similarity with other aeromonads than with both strains of Vibrio anguillarum tested.


Health-related quality of life in a trial of acupuncture, sham acupuncture and conventional treatment for chronic sinusitis.
Acupuncture is commonly used to treat chronic sinusitis, though there is little documentation on the effect. This study presents the health-related quality of life (HRQoL) outcomes in a trial comparing traditional Chinese acupuncture, sham acupuncture, and conventional treatment for chronic sinusitis. In a three-armed single blind randomized controlled study, we recruited 65 patients with symptoms of sinusitis >3 months and signs of sinusitis on computed tomography (CT). Patients were randomized to one of three study arms: (1) 2-4 weeks of medication with antibiotics, corticosteroids, 0.9% sodium chloride solution, and local decongestants (n = 21), (2) ten treatments with traditional Chinese acupuncture (n = 25), or (3) ten treatments with minimal acupuncture at non-acupoints (n = 19). Change in HRQoL was assessed over 12 weeks using the Chronic Sinusitis Survey (CSS) and Short form 36 (SF-36) questionnaires.In the study, we found only a non-significant difference on the CSS symptom scale between conventional medical therapy and traditional Chinese acupuncture. On the SF-36 scale role-physical the change was larger in the conventional group than in the sham group (p = 0.02), and on the mental health scale the change in the conventional therapy arm was larger than in the traditional Chinese acupuncture group (p = 0.03). There was no difference in effect on HRQoL on any scale between the sham and traditional Chinese acupuncture groups. There was no clear evidence of the superiority of one treatment over another on short-term HRQoL outcomes, although there was a statistically non-significant advantage of conventional therapy in a few dimensions.


The oncogenic and growth-suppressive functions of the integrin-linked kinase are distinguished by JNK1 expression in human cancer cells.
While most reports detail an oncogenic function for the integrin-linked kinase (ILK) in human cancer, few describe a contradictory growth-suppressive function. We previously reported that ILK functions as either a tumor suppressor or an oncogene in rhabdomyosarcoma (RMS), in a manner linked to expression of the c-jun amino terminal kinase-1 (JNK1). However, studies in other tumors are lacking. With the advent of bioavailable small molecule inhibitors of ILK, defining both the function of ILK and biomarkers to predict its behaviour are of critical importance. Here, we studied the role of ILK in a panel of tumor cell lines. We demonstrate that ILK functions as either a growth-promoter or suppressor in numerous tumor cell lines. Further, cell lines in which ILK functioned as a growth suppressor displayed elevated JNK1 expression relative to cells in which ILK functioned as an oncogene. Comparison of endogenous JNK1 and JNK1β isoform expression levels to the cellular response to ILK overexpression demonstrated that JNK1β isoforms represent biomarkers differentiating the two functions of ILK. Moreover, RNAi and overexpression-based alteration of JNK1 expression levels was sufficient to switch the function of ILK in both transformed and untransformed cells. These results indicate widespread oncogenic and growth-suppressive functions for ILK in multiple human malignancies and suggest that JNK1 isoforms represent biomarkers for ILK neoplastic activity. These results provide a rationale for stratifying patients to receive ILK kinase inhibitors based on individualized tumor-specific ILK function.


USAC: a universal framework for random sample consensus.
A computational problem that arises frequently in computer vision is that of estimating the parameters of a model from data that have been contaminated by noise and outliers. More generally, any practical system that seeks to estimate quantities from noisy data measurements must have at its core some means of dealing with data contamination. The random sample consensus (RANSAC) algorithm is one of the most popular tools for robust estimation. Recent years have seen an explosion of activity in this area, leading to the development of a number of techniques that improve upon the efficiency and robustness of the basic RANSAC algorithm. In this paper, we present a comprehensive overview of recent research in RANSAC-based robust estimation by analyzing and comparing various approaches that have been explored over the years. We provide a common context for this analysis by introducing a new framework for robust estimation, which we call Universal RANSAC (USAC). USAC extends the simple hypothesize-and-verify structure of standard RANSAC to incorporate a number of important practical and computational considerations. In addition, we provide a general-purpose C++ software library that implements the USAC framework by leveraging state-of-the-art algorithms for the various modules. This implementation thus addresses many of the limitations of standard RANSAC within a single unified package. We benchmark the performance of the algorithm on a large collection of estimation problems. The implementation we provide can be used by researchers either as a stand-alone tool for robust estimation or as a benchmark for evaluating new techniques.


"Acupuncture anesthesia"--a clinical study.
Forty-two patients who were to undergo plastic surgical procedures were asked whether they would accept acupuncture as a substitute for local anesthesia. Eight patients agreed to acupuncture; one of these had 2 operative procedures with acupuncture. Five of the 9 procedures were successful; the remaining 4 required conversion to local anesthesia. After interviewing the patients, we felt that the success of "acupuncture anesthesia" was largely dependent on patient motivation, and that a patient may experience pain during surgical procedures without any change in facial expression or vital signs. We concluded that "acupuncture anesthesia" is of little value in our patient population at present. Its results are unpredictable; therefore, we anticipate that patient acceptance will be small.


68Ga-PSMA PET/CT in Osteosarcoma in Fibrous Dysplasia.
Fibrous dysplasia (FD) is a benign bone lesion with a rare but potential for malignant transformation. Neither Tc-MDP nor F-FDG PET/CT can differentiate between FD and areas of malignant transformation in FD. We described a case of osteosarcoma developing in FD with selective uptake of tracer in malignant transformation areas demonstrated on a Ga-PSMA PET/CT scan. Our case highlights the ability of Ga-PSMA PET/CT to map tumor neoangiogenesis in osteosarcoma arising in FD, which can have potential implications in prognostication, possibility of antiangiogenesis-based therapeutic options, and in response assessment following chemotherapy.


Inhibition of the phosphorylation of the regulatory non-structural protein of vesicular stomatitis virus by an antiviral xanthate compound.
The growth of vesicular stomatitis virus (VSV) can be inhibited by the antiviral compound tricyclo-decane-9-yl-xanthogenate (D609). On analysing the antiviral mechanism we found no effect on the primary transcription of infecting VSV genomes. In contrast, the processes of replication and transcription during late stages of infection were inhibited. Despite the synthesis of all five virus-coded proteins (41% to 56% of the uninhibited control), as shown by labelling with [35S]methionine, the phosphorylation of the non-structural (NS) protein was reduced in the presence of the xanthate by a factor of at least 17. The pattern of phosphorylation of the bulk of cellular proteins remained unaltered under the same conditions. A relation between a possible loss of biological activity of the NS protein owing to the lack of phosphorylation and the decreased VSV RNA synthesis is suggested.


Partially purified Toxoplasma gondii antigens by immunoaffinity chromatography.
Tachyzoite antigens of Toxoplasma gondii (RH) were partially purified by immunoaffinity chromatography. The cultivated Toxoplasma in vivo (mouse) and in vitro (Hep-2 cell) and peritoneal fluid of T. gondii infected mice were collected for antigen analysis. Tachyzoite antigens collected from infected mouse showed positive bands of 76 kDa, 70 kDa, 64 kDa, 53 kDa, 46 kDa, 44 kDa, 41 kDa, 35 kDa, 25 kDa, 18 kDa, and 13 kDa on immunoblot with anti-Toxoplasma rabbit sera, and those from infected Hep-2 cells revealed reactive bands of 70 kDa, 64 kDa, 53 kDa, 35 kDa 28 kDa, and 13-10 kDa. After applying to an IgG-Sepharose column, two elution peaks, E-1 and E-2 fractions, were obtained from both soluble antigen of T. gondii and the peritoneal fluid of infected mice, respectively. Immunoblots of soluble antigen with immunized rabbit sera revealed positive bands of 97 kDa, 63 kDa, 53 kDa, and 35 kDa from E-1 fraction and 53 kDa and 35 kDa from E-2. In the case of the eluted peaks from mice peritoneal fluid, E-1 showed protein bands of 84 kDa, 76 kDa, 53 kDa, and 29 kDa bands and 53 kDa and 45 kDa from E-2 on immunoblots. Serum IgG antibody titer of mice immunized with T. gondii tachyzoites was increased on 1 week after booster immunization when analysed by ELISA using crude antigen, while it was elevated on 3 weeks after booster immunization by ELISA using purified antigen.


[Functional status of the left side of the heart in patients with ischemic heart disease during isometric exercise].
Hemodynamic parameters of left-ventricular and left-atrial contractility and pumping function were examined in 47 males with postinfarction cardiosclerosis and no clinical signs of circulatory insufficiency and in 30 normal male subjects, exposed to isometric leg exercise with the highest possible compression force. At the height of exercise, normal subjects showed increased left-ventricular myocardial contractility along with the initiation of the Frank-Starling mechanism, spreading to the left atrium as well, while coronary patients responded to increased stress by growing left-atrial reservoir function during the first minutes of exercise, and activated left-atrial transport and pumping functions afterwards. Isometric leg exercise is capable of detecting left-atrial and left-ventricular pumping and contractility disorders in coronary patients.


Occurrence and environmental behavior of the bactericide triclosan and its methyl derivative in surface waters and in wastewater.
The bactericide triclosan and methyl triclosan, an environmental transformation product thereof, were detected in lakes and in a river in Switzerland at concentrations of up to 74 and 2 ng L(-1), respectively. Both compounds were emitted via wastewater treatment plants (WWTPs), with methyl triclosan probably being formed by biological methylation. A regional mass balance for a lake (Greifensee) indicated significant removal of triclosan by processes other than flushing. Laboratory experiments showed that triclosan in the dissociated form was rapidly decomposed in lake water when exposed to sunlight (half-life less than 1 h in August at 47 degrees latitude). Methyl triclosan and nondissociated triclosan, however, were relatively stable toward photodegradation. Modeling these experimental data for the situation of lake Greifensee indicated that photodegradation can account for the elimination of triclosan from the lake and suggested a seasonal dependence of the concentrations (lower in summer, higher in winter), consistent with observed concentrations. Although emissions of methyl triclosan from WWTPs were only approximately 2% relative to those of triclosan, its predicted concentration relative to triclosan in the epilimnion of the lake increases to 30% in summer. Passive sampling with semipermeable membrane devices (SPMDs) indicated the presence of methyl triclosan in lakes with inputs from anthropogenic sources but not in a remote mountain lake. Surprisingly, no parent triclosan was observed in the SPMDs from these lakes. Methyl triclosan appears to be preferentially accumulated in SPMDs under the conditions in these lakes, leading to concentrations comparable to those of persistent chlorinated organic pollutants.


[Lactate dehydrogenase activity in the presence of certain structural analogs of the nicotinamide fragment of NAD].
The activity of lactate dehydrogenase from the cattle myocardium extract as well as of this enzyme crystalline form was studied in the presence of structural analogues of the nicotinamide fragment NAD-amide, diethyl amide and N-oxymethyl amide of nicotinic acid. It is shown that the rate of the reaction catalyzed with lactate dehydrogenase under the effect of amide and N-oxymethyl amide of nicotinic acid decreases to a different extent depending on their concentration. Nicotinic diethyl amide practically has no effect on the activity of lactate dehydrogenase. Ki for crystalline lactate dehydrogenase and myocardium lactate dehydrogenase in the presence of nicotinic amide is 0.23.10-3 and 1.13.10-3 M. respectively, in the presence of nicotinic N-oxymethyl amide-0.30.10-3 and 0.10.10-3 M.


Death and lysis of leptospirae when cultured in asbestos-filtered growth media.
Death and lysis of leptospirae, when cultured in asbestos-filtered bovine albumin polysorbate 80 media, was quantitated. The pathogens (virulent and avirulent) required 2 x 10(6) cells/ml to initiate growth in such media, whereas inocula of 2 to 20 cells/ml grew in control medium. Saprophytic leptospirae initiated growth from 2 cells/ml in asbestos-filtered medium as well as control medium. The adverse action of asbestos-filtered medium was not removed by storage of medium for 2 years at 25 C and was not diminished when such medium was frozen at -80 C. Washing with water, HCl and NaHCO(3)-NaCl, citric acid, and medium components did not remove the lytic activity associated with asbestos-filtered culture medium. Continuous subculture in asbestos-filtered medium was possible from large inocula; however, upon subsequent dilution and reinoculation into asbestos-filtered media, there was no evidence of acquired resistance, and all pathogens failed to grow.


Persistent Organic Chlorinated Compound Residues in the Breast Milk of Female Seasonal Agricultural Workers.
This retrospective descriptive study aimed to investigate organochlorine compounds in women who breastfeed and work as a seasonal agricultural worker (SAW). It was carried out on 100 woman working as SAW. Data were collected with a questionnaire by face-to-face interview and analyzed the residues of 27 items of organochlorine pesticides, dichlorodiphenyltrichloroethane (DDT) metabolites and polychlorinated biphenyls, from persistent organic pollutants in mothers' 50 mL breast milk. Descriptive statistics, Chi-square test, and correlation analysis were used to evaluate data. Polychlorinated biphenyl (PCB)28 component was determined in almost all women's milk and more than half of collected milk contained beta-hexachlorocyclohexane (HCH), PCB52, pp'-dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), PCB70, pp'- dichlorodiphenyltrichloroethane (DDT) ve Gamma HCH, respectively. It was recommended that necessary legal regulations and public information policy about that subject should exist.


Investing in mental health and well-being: findings from the DataPrev project.
A systematic review was conducted to determine the extent to which an economic case has been made in high-income countries for investment in interventions to promote mental health and well-being. We focused on areas of interest to the DataPrev project: early years and parenting interventions, actions set in schools and workplaces and measures targeted at older people. Economic evaluations had to have some focus on promotion of mental health and well-being and/or primary prevention of poor mental health through health-related means. Studies preventing exacerbations in existing mental health problems were excluded, with the exception of support for parents with mental health problems, which might indirectly affect the mental health of their children. Overall 47 studies were identified. There was considerable variability in their quality, with a variety of outcome measures and different perspectives: societal, public purse, employer or health system used, making policy comparisons difficult. Caution must therefore be exercised in interpreting results, but the case for investment in parenting and health visitor-related programmes appears most strong, especially when impacts beyond the health sector are taken into account. In the workplace an economic return on investment in a number of comprehensive workplace health promotion programmes and stress management projects (largely in the USA) was reported, while group-based exercise and psychosocial interventions are of potential benefit to older people. Many gaps remain; a key first step would be to make more use of the existence evidence base on effectiveness and model mid- to long-term costs and benefits of action in different contexts and settings.


Identification of injured elements in computational models of spinal cord injury using machine learning.
The purpose of this study was to use machine learning (ML) algorithms to identify tissue damage based on the mechanical outputs of computational models of spinal cord injury (SCI). Three datasets corresponding to gray matter, white matter, and the combination of gray and white matter tissues were used to train the models. These datasets were built from the comparison of histological images taken from SCI experiments in non-human primates and corresponding subject-specific finite element (FE) models. Four ML algorithms were evaluated and compared using cross-validation and the area under the receiver operating characteristic curve (AUC). After hyperparameter tuning, the AUC mean values for the algorithms ranged between 0.79 and 0.82, with a standard deviation no greater than 0.02. The findings of this study also showed that k-nearest neighbors and logistic regression algorithms were better at identifying injured elements than support vector machines and decision trees. Additionally, depending on the evaluated dataset, the mean values of other performance metrics, such as precision and recall, varied between algorithms. These initial results suggest that different algorithms might be more sensitive to the skewed distribution of classes in the studied datasets, and that identifying damage independently or simultaneously in the gray and white matter tissues might require a better definition of relevant features and the use of different ML algorithms. These approaches will contribute to improving the current understanding of the relationship between mechanical loading and tissue damage during SCI and will have implications for the development of prevention strategies for this condition.Clinical Relevance- Linking FE model predictions of mechanical loading to tissue damage is an essential step for FE models to provide clinically relevant information. Combined with imaging technologies, these models can provide useful insights to predict the extent of damage in animal subjects and guide the decision-making process during treatment planning.


Experimental sleep fragmentation impairs attentional set-shifting in rats.
To evaluate the effect of experimental sleep fragmentation (sleep interruption; SI) on complex learning in an intradimensional-extradimensional (ID/ED) set-shifting task in rats. A sleep fragmentation paradigm of intermittent forced locomotion was validated in adult rats by examining electrographic effects. Discrimination task performances were assessed in rats following sleep fragmentation or 2 control conditions. 41 young adult male Fischer-Norway rats. A treadmill was used to produce 30 awakenings/h for the 24-h period prior to testing. Exercise control rats received an equivalent amount of treadmill-induced locomotion that permitted 30-minute pauses to allow consolidated sleep. SI rats were selectively impaired on the extradimensional-shift phase of the task, taking significantly more trials to achieve criterion performance (15.4 +/- 2.0) than either control group (cage control = 10.4 +/- 0.9; exercise control = 6.3 +/- 0.2). The SI schedule reduced the average duration of nonREM sleep (NREMS) episodes to 56 s (baseline = 182 s), while the exercise control group increased average NREMS episode duration to 223 s. Total (24-h) NREMS time declined from 50% during baseline to 33% during SI, whereas rapid eye movement sleep (REMS) was absent in SI animals (7% during baseline and 0% during SI), and time spent awake increased proportionally (from 43% during baseline to 67% during SI). 24-hour SI produced impairment in an attentional set-shifting that is comparable to the executive function and cognitive deficits observed in humans with sleep apnea or after a night of experimental sleep fragmentation.


Organ procurement from executed prisoners in China.
Organ procurement from executed prisoners in China is internationally condemned, yet this practice continues unabated in 2014. This is despite repeated announcements from Chinese authorities that constructive measures have been undertaken to conform to accepted ethical standards. While there is unanimous agreement on the unethical nature of using organs from executed prisoners, due to its limitations on voluntary and informed consent, there is insufficient coverage of forced organ procurement from prisoners of conscience without consent. Strategies to influence positive change in China over the last few decades have failed to bring this practice to an end. While organ donation and transplantation services in China have undergone considerable structural changes in the last few years, fundamental attempts to shift practice to ethically sourced organs have floundered. In this article, we discuss the organ trade in China, reflect upon organ procurement from executed prisoners (including both capital prisoners and prisoners of conscience) and provide an overview of contradictory Chinese efforts to halt forced organ procurement from executed prisoners. Finally, we highlight current actions being taken to address this issue and offer comprehensive recommendations to bring this ethically indefensible practice to an immediate end.


[Dynamics of vowel acoustic space indicators in patients with long-term hearing loss].
New procedure of vowel acoustic space (VAS) (of vowel acoustic triangles) transformation for the purpose of characterization of vowel production in individuals with long-term hearing loss (HL) was developed. To characterize VAS of adult Russian speakers with long-term HL using newly developed acoustic indicators. Recordings of sustained Russian cardinal vowels /a/, /i/, /u/ of 10 women and 10 men with long-term HL were acoustically analyzed. For each participant, two first formants of each vowel were measured and log-transformed (logF1, logF2). VAS was transformed into right triangles, their /u/ corners were moved to the origin, and their legs were aligned with axes. VAS was almost symmetrical, equal and have a maximum size in the control group consisted of subjects without hearing impairment while these of long-term HL group VAS size tended to have reduced and VAS stretched along one axis. Our study showed that a new VAS normalization approach can distinguish at least three groups of people with long-term HL. There are those with vowel triangles stretched along logF1-axis, with vowel triangles stretched along logF2-axis, and with symmetrical vowel triangles. Causes of the VAS differences require further investigation.


[THE ADVERSE EFFECTS OF SMOKING ON THE HANDS].
Cigarette smoking is known to cause a multitude of harmful effects throughout the body. There are only a few accounts in the literature of these effects as related to the hands. This is a review of the literature, demonstrating the collected knowledge of decreased hand vascularity due to tobacco use and assessing the evidence connecting smoking and supposed resultant maladies, including Raynaud's phenomenon, hand-arm vibration syndrome, Buerger's disease, Dupuytren's contracture, carpal tunnel syndrome, effects on skin and fingernails, decreased skin and bone healing, complications of digit replantation and complex regional pain syndrome. Also presented is the possible increased risk of congenital hand malformations as related to maternal smoking.


[Positron emitters for the study of tumor metabolism].
Positron emission tomography with metabolically active substances is a noninvasive imaging modality to determine tumor metabolism. Quantification of tumor metabolism provides valuable information, e.g., for the differential diagnosis of malignancies. Radiolabeled therapeutic substances can be traced with PET. Measurement of fluorouracil metabolite concentrations provides data about the accumulation pattern of the cytostatic agent and allows assessment of the therapeutic outcome.


Efficient immersion imaging of components with nonplanar surfaces.
Ultrasonic array inspection of a component with a nonplanar surface can be achieved in immersion using a liquid layer to couple ultrasonic waves from an array probe into a solid structure. This paper presents an efficient way to compute the appropriate element time delays in immersion without compromising the measurement accuracy. In the proposed imaging process, the surface geometry is first measured ultrasonically by forming an image of the component surface in the couplant. This leads to a set of discrete points that define the surface profile of the component. The propagation time from an array element to a point in the component is then determined by a grid search of candidate ray-paths through each surface point to identify the one that yields the shortest traveling time. Propagation times in the component are first generated on a coarse mesh of points and then these values are linearly interpolated to find the propagation time to each image pixel. The computed propagation times are finally used to reconstruct an image of the component interior. An analytical model is developed to determine a relationship between estimated propagation time errors and their effect on the array inspection in terms of signal amplitude from a reflector. For nominally normal incidence inspection of a metallic component with a minimum surface radius of 30 wavelengths immersed in water, it is found that the surface of the component can be adequately described by points spaced by one wavelength and that delays can be computed on a coarse grid of points spaced at 3 wavelengths. With these parameters, the reduction in amplitude of a point target in the component is shown to be less than 1 dB.


[Two types of "spike-wave" discharges in the electrocorticogram of WAG/Rij rats, the genetic model of absence epilepsy].
WAG/Rij rats were injected with apomorphine (0.5 mg/kg, i.p.), an agonist of D2 receptors. Two types of spike-wave discharges (generalized and local) were found in the baseline ECoG of the intact and injected rats. Injections of apomorphine led to a suppression of the generalized (type 1) for about 30 minutes and a 8-10-fold increase in the local spike-wave discharges (type 2) within 4-6 minutes. Since it has been shown earlier that haloperidol, which acts on dopamine receptors oppositely to apomorphine, enhance the generalized spike-wave activity and suppress the local discharges. Thus, the different pharmacological characteristics of the two types of spike-wave activity suggest the controlling role of the dopaminergic system in the processes of spike-wave generation.


Association between the body mass index and the risk of Barrett's esophagus in Japan.
We investigated the association between long-segment Barrett's esophagus and obesity in the Japanese population in a multicenter case-control trial. One hundred thirteen patients with endoscopically detected Barrett's esophagus with a length of more than 2 cm and the same number of sex- and age-matched controls were prospectively enrolled. Barrett's esophagus was diagnosed based on the Prague C and M criteria. The body mass index (BMI) of the subjects was categorized into the following groups: normal, BMI <22.9; overweight, BMI 23.0-24.9, and obese, BMI >25.0. To determine the association between BMI and the risk of Barrett's esophagus, multivariate logistic regression analyses were performed. The basically adjusted regression model adjusted for smoking and alcohol consumption revealed that overweight and obesity were significantly associated with an elevated risk of Barrett's esophagus (OR 2.4, 95% CI 1.2-4.7, and OR 2.5, 95% CI 1.3-4.6, respectively). The intensity of the association was not attenuated even after adjustment for gastroesophageal reflux disease-related parameters. An increased BMI was associated with an increased risk for Barrett's esophagus through a gastroesophageal reflux-independent mechanism in the Japanese population. Further, unlike in Caucasian populations, being even slightly overweight with a BMI of 23.0-24.9 was an independent risk factor in the Japanese population.


One or two low affinity penicillin-binding proteins may be responsible for the range of susceptibility of Enterococcus faecium to benzylpenicillin.
Three benzylpenicillin-resistant, clinical isolates of Enterococcus faecium (MIC values 16-64 micrograms ml-1) contained six penicillin-binding proteins (PBPs), of which PBP5 was the most abundant and had the lowest affinity for the antibiotic. Four benzylpenicillin-susceptible strains (MIC values 0.031-0.5 microgram ml-1) were obtained as spontaneous derivatives from these above organisms. There were significant decreases in the amounts of PBP5 in each of the derivatives, with the concomitant appearance of a new, higher affinity PBP (5*) in three strains. Increased amounts of PBP5, with no changes in PBP5*, were found in several mutants with intermediate-level benzylpenicillin-resistance (MIC values 1-8 micrograms ml-1) selected from two of the susceptible strains. Examination of 18 other clinical isolates, with a wide range of susceptibilities to benzylpenicillin (MIC values 0.062-128 micrograms ml-1), showed that PBP5* was present in 13 strains, and PBP5 in all of them, but in differing amounts. The results concerning the relative amounts and relative affinities of PBPs 5* and 5 allowed the categorization of the various strains into six groups, within which organisms had somewhat similar susceptibilities to benzylpenicillin.


Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep.
Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. Lactoferrin, a cationic protein released from activated neutrophils, binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor of tryptase and found that it is both a potent (Ki' is 24 nM) and selective inhibitor. Size exclusion chromatography studies revealed that lactoferrin disrupted the quaternary structure of active tryptase. Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.


Antenatal intravenous immunoglobulin in chronic immune thrombocytopenic purpura: case report and literature review.
Immune thrombocytopenic purpura (ITP) may complicate pregnancy and, uncommonly, may cause severe neonatal thrombocytopenia. However, it is difficult to predict which neonates are at risk of severe thrombocytopenia. Direct fetal sampling is not commonly done, as it poses significant risks to the fetus. Furthermore, appropriate antenatal treatment of neonates is controversial. We describe the case of a 32-year-old woman with chronic severe ITP and a previous severely affected infant, pregnant with trichorionic triplets, who was successfully managed with the use of weekly intravenous immunoglobulin 1 g/kg without recourse to direct fetal sampling.


Bridging the gap between moral reasoning and adolescent engagement in risky behavior.
Relations among moral reasoning, domain judgment and engagement in risky behaviors were assessed with 68 students attending a Just Community school and 122 comparison students from the larger high school with which the alternative school is affiliated. Risky behaviors were perceived as personal decisions, rather than as ones of morality or convention. Engagement and domain judgment of risky behavior interacted; with increasing substance involvement, students were more likely to view the decision to use drugs and alcohol as a personal decision than as either a moral or conventional decision. Domain judgments of risks appeared to moderate the relation between moral reasoning and engagement in risky behavior, suggesting that moral education interventions must encourage youth to explore their views that much of their behavior is only their own business.


Polarization change induced by a galvanometric optical scanner.
We study the optical properties of a two-axis galvanometric optical scanner constituted by a pair of rotating planar mirrors, focusing our attention on the transformation induced on the polarization state of the input beam. We obtain the matrix that defines the transformation of the propagation direction of the beam and the Jones matrix that defines the transformation of the polarization state. Both matrices are expressed in terms of the rotation angles of two mirrors. Finally, we calculate the parameters of the general rotation in the Poincaré sphere that describes the change in the polarization state for each mutual orientation of the mirrors.


Nasal changes with nasoalveolar molding in Colombian patients with unilateral cleft lip and palate.
Presurgical nasoalveolar molding (PNAM) is controversial in maxillofacial orthopedics. It supposedly improves the nasal esthetics and function in unilateral cleft lip/palate (UCLP) patients. However, there is no research available in South America to support this claim. The purpose of this study was to evaluate the efficacy of presurgical nasoalveolar molding therapy on morphological changes of the noses of unilateral cleft lip/palate patients in a Colombian sample. Seventeen neonate UCLP patients using PNAM received facial impressions at the beginning of treatment; before primary rhinocheiloplasty; and before palatoplasty. A submentovertex photograph of each cast was taken and analyzed by digital photogrammetry. Wilcoxon and Friedman tests were used for within- and between-group comparisons. A statistically significant reduction of cleft nostril width, without significant changes in noncleft nostril width or total nasal width, was found after PNAM. A significant increase in cleft and noncleft nostril height, plus a nonsignificant increase in nostril area in both sides and a nonsignificant uprighting of the columella were found. These changes were maintained or further improved after rhinocheiloplasty. The presurgical nasoalveolar molding technique improved nasal tip projection and alar cartilage depression and decreased partially columella deviation before rhinocheiloplasty in South American unilateral cleft lip/palate patients.


Voluntary involuntariness: thought suppression and the regulation of the experience of will.
Participants were asked to carry out a series of simple tasks while following mental control instructions. In advance of each task, they either suppressed thoughts of their intention to perform the task, concentrated on such thoughts, or monitored their thoughts without trying to change them. Suppression resulted in reduced reports of intentionality as compared to monitoring, and as compared to concentration. There was a weak trend for suppression to enhance reported intentionality for a repetition of the action carried out after suppression instructions had been discontinued.


Crohn's disease: an update.
Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.


PARP9 is overexpressed in human breast cancer and promotes cancer cell migration.
Poly(ADP-Ribose) polymerase family member 9 (PARP9) promotes the proliferation, survival and chemotherapy resistance in lymphoma and prostate cancer. The expression and function of PARP9 in human breast cancer remains unknown. In the present study, it was demonstrated that PARP9 is frequently overexpressed in human breast cancer. In 57 normal breast tissues, the expression of PARP9 was not detected in 43 cases (75.4%), but low levels of PARP9 were detected in 13 cases (22.8%), and modest levels of PARP9 (PARP9/GAPDH ratio ~1:1) were detected in only 1 case (1.7%). In contrast, the expression of PARP9 was detected in all 57 breast cancer tissues, in which the levels of PARP9 were higher than that in paired normal breast tissues. In addition, high levels of PARP9 were detected in 43.8% of breast cancer tissues. Overexpression of PARP9 was negatively associated with estrogen receptor expression, and positively associated with axillary lymph node metastasis. However, PARP9 expression was not associated with other clinicopathological parameters, including age, HER-2 and tumor size. Furthermore, PARP9-knockdown inhibited breast cancer cell migration. These data indicate that PARP9 may promote breast cancer progression.


Characterization of the enzymatic and structural properties of human D-aspartate oxidase and comparison with those of the rat and mouse enzymes.
D-Aspartate (D-Asp), a free D-amino acid found in mammals, plays crucial roles in the neuroendocrine, endocrine, and central nervous systems. Recent studies have implicated D-Asp in the pathophysiology of infertility and N-methyl-D-Asp receptor-related diseases. D-Asp oxidase (DDO), a degradative enzyme that is stereospecific for acidic D-amino acids, is the sole catabolic enzyme acting on D-Asp in mammals. Human DDO is considered an attractive therapeutic target, and DDO inhibitors may be potential lead compounds for the development of new drugs against the aforementioned diseases. However, human DDO has not been characterized in detail and, although preclinical studies using experimental rodents are prerequisites for evaluating the in vivo effects of potential inhibitors, the existence of species-specific differences in the properties of human and rodent DDOs is still unclear. Here, the enzymatic activity and characteristics of purified recombinant human DDO were analyzed in detail. The kinetic and inhibitor-binding properties of this enzyme were also compared with those of purified recombinant rat and mouse DDOs. In addition, structural models of human, rat, and mouse DDOs were generated and compared. It was found that the differences among these DDO proteins occur in regions that appear involved in migration of the substrate/product in and out of the active site. In summary, detailed characterization of human DDO was performed and provides useful insights into the use of rats and mice as experimental models for evaluating the in vivo effects of DDO inhibitors.


Mapping a gene defect in absorptive hypercalciuria to chromosome 1q23.3-q24.
Absorptive hypercalciuria (AH), a common cause of kidney stones, is due to intestinal hyperabsorption of calcium. The presence of a family history of nephrolithiasis, in about half of the affected individuals studied indicates that an inherited genetic defect is one likely cause of AH. Although it is known that intestinal calcium absorption is regulated by a number of factors, the molecular biological basis for the increased calcium absorption in AH is unknown. This study was designed to determine the chromosomal locus of the gene defect linked to the AH phenotype in three families with a severe form of AH. Three kindreds were evaluated in a systematic autosomal genome-wide linkage analysis study. The AH phenotype, characterized by hyperabsorption of calcium and hypercalciuria, was linked to only one chromosomal locus, 1q23.3-q24. A 2-point logarithm of odds score of 3.3 was obtained with markers D1S318 and D1S196 at a recombination frequency of theta = 0. Nonparametric multipoint linkage analysis yielded a peak nonparametric linkage Z(all)-score of 12.7, P = 6 x 10(-6) Analysis of key recombinants within the families studied localized the gene to a 4.3-megabase region between markers D1S2681 (centromere) and D1S2815. A trait associated with intestinal hyperabsorption of calcium in a severe form of absorptive hypercalciuria has been mapped to chromosome 1q23.3-q24.


Direct and regression methods do not give different estimates of digestible and metabolizable energy of wheat for pigs.
Digestible and metabolizable energy contents of feed ingredients for pigs can be determined by direct or indirect methods. There are situations when only the indirect approach is suitable and the regression method is a robust indirect approach. This study was conducted to compare the direct and regression methods for determining the energy value of wheat for pigs. Twenty-four barrows with an average initial BW of 31 kg were assigned to 4 diets in a randomized complete block design. The 4 diets consisted of 969 g wheat/kg plus minerals and vitamins (sole wheat) for the direct method, corn (Zea mays)-soybean (Glycine max) meal reference diet (RD), RD + 300 g wheat/kg, and RD + 600 g wheat/kg. The 3 corn-soybean meal diets were used for the regression method and wheat replaced the energy-yielding ingredients, corn and soybean meal, so that the same ratio of corn and soybean meal across the experimental diets was maintained. The wheat used was analyzed to contain 883 g DM, 15.2 g N, and 3.94 Mcal GE/kg. Each diet was fed to 6 barrows in individual metabolism crates for a 5-d acclimation followed by a 5-d total but separate collection of feces and urine. The DE and ME for the sole wheat diet were 3.83 and 3.77 Mcal/kg DM, respectively. Because the sole wheat diet contained 969 g wheat/kg, these translate to 3.95 Mcal DE/kg DM and 3.89 Mcal ME/kg DM. The RD used for the regression approach yielded 4.00 Mcal DE and 3.91 Mcal ME/kg DM diet. Increasing levels of wheat in the RD linearly reduced (P < 0.05) DE and ME to 3.88 and 3.79 Mcal/kg DM diet, respectively. The regressions of wheat contribution to DE and ME in megacalories against the quantity of wheat DM intake in kilograms generated 3.96 Mcal DE and 3.88 Mcal ME/kg DM. In conclusion, values obtained for the DE and ME of wheat using the direct method (3.95 and 3.89 Mcal/kg DM) did not differ (0.78 < P < 0.89) from those obtained using the regression method (3.96 and 3.88 Mcal/kg DM).


Effect of Extending the Original CROSS Criteria on Tumor Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients: A National Multicenter Cohort Analysis.
Extending the original criteria of the Chemoradiotherapy for Oesophageal Cancer followed by Surgery Study (CROSS) in daily practice may increase the treatment outcome of esophageal cancer (EC) patients. This retrospective national cohort study assessed the impact on the pathologic complete response (pCR) rate and surgical outcome. Data from EC patients treated between 2009 and 2017 were collected from the national Dutch Upper Gastrointestinal Cancer Audit database. Patients had locally advanced EC (cT1/N+ or cT2-4a/N0-3/M0) and were treated according to the CROSS regimen. CROSS (n = 1942) and the extended CROSS (e-CROSS; n = 1359) represent patients fulfilling the original or extended CROSS criteria, respectively. The primary outcome was total pCR (ypT0N0), while secondary outcomes were local esophageal pCR (ypT0), surgical radicality, and postoperative morbidity and mortality. Overall, CROSS and e-CROSS did not differ in total or local pCR rate, although a trend was observed (23.2% vs. 20.4%, p = 0.052; and 26.7% vs. 23.8%, p = 0.061). When stratifying by histology, the pCR rate was higher in the CROSS group compared with e-CROSS in squamous cell carcinomas (48.2% vs. 33.3%, p = 0.000) but not in adenocarcinomas (16.8% vs. 16.9%, p = 0.908). Surgical radicality did not differ between groups. Postoperative mortality (3.2% vs. 4.6%, p = 0.037) and morbidity (58.3% vs. 61.8%, p = 0.048) were higher in e-CROSS. Extending the CROSS inclusion criteria for neoadjuvant chemoradiotherapy in routine clinical practice of EC patients had no impact on the pCR rate and on radicality, but was associated with increased postoperative mortality and morbidity. Importantly, effects differed between histological subtypes. Hence, in future studies, we should carefully reconsider who will benefit most in the real-world setting.


Conducting nanofibers and organogels derived from the self-assembly of tetrathiafulvalene-appended dipeptides.
We demonstrate the nonaqueous self-assembly of a low-molecular-mass organic gelator based on an electroactive p-type tetrathiafulvalene (TTF)-dipeptide bioconjugate. We show that a TTF moiety appended with diphenylalanine amide derivative (TTF-FF-NH2) self-assembles into one-dimensional nanofibers that further lead to the formation of self-supporting organogels in chloroform and ethyl acetate. Upon doping of the gels with electron acceptors (TCNQ/iodine vapor), stable two-component charge transfer gels are produced in chloroform and ethyl acetate. These gels are characterized by various spectroscopy (UV-vis-NIR, FTIR, and CD), microscopy (AFM and TEM), rheology, and cyclic voltammetry techniques. Furthermore, conductivity measurements performed on TTF-FF-NH2 xerogel nanofiber networks formed between gold electrodes on a glass surface indicate that these nanofibers show a remarkable enhancement in the conductivity after doping with TCNQ.


Fluidizing effects of C-reactive protein on lung surfactant membranes: protective role of surfactant protein A.
The purpose of this study was to investigate how surfactant membranes can be perturbed by C-reactive protein (CRP) and whether surfactant protein A (SP-A) might overcome CRP-induced surfactant membrane alterations. The effect of CRP on surfactant surface adsorption was evaluated in vivo after intratracheal instillation of CRP into rat lungs. Insertion of CRP into surfactant membranes was investigated through monolayer techniques. The effect of CRP on membrane structure was studied through differential scanning calorimetry and fluorescence spectroscopy and microscopy using large and giant unilamellar vesicles. Our results indicate that CRP inserts into surfactant membranes and drastically increases membrane fluidity, resulting in surfactant inactivation. At 10% CRP/phospholipid weight ratio, CRP causes disappearance of liquid-ordered/liquid-disordered phase coexistence distinctive of surfactant membranes. SP-A, the most abundant surfactant lipoprotein structurally similar to C1q, binds to CRP (K(d)=56±8 nM), as determined by solid-phase binding assays and dynamic light scattering. This novel SP-A/CRP interaction reduces CRP insertion and blocks CRP effects on surfactant membranes. In addition, intratracheal coinstillation of SP-A+CRP into rat lungs prevents surfactant inhibition induced by CRP, indicating that SP-A/CRP interactions might be an important factor in vivo in controlling harmful CRP effects in the alveolus.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 14: brace therapy as an adjunct to or substitute for lumbar fusion.
Although conflicting reports have been presented in the literature regarding the utility of lumbar braces for the prevention of low-back pain, most Class III medical evidence suggests that these supports used prophylactically do not reduce the incidence of low-back pain or decrease the amount of time lost from work in the general working population. Among workers with a history of a back injury, their use appears to decrease the number of work days lost due to back pain. Lumbar braces appear to be an effective treatment for acute low-back pain in some populations. They do not appear to be effective in the chronic low-back pain population. If a brace is used, rigid braces offer some benefit over soft braces. There are no data to suggest that relief of low-back pain with preoperative external bracing predicts a favorable outcome following lumbar spinal fusion. No information is available on the benefit of bracing for improving fusion rates or clinical outcomes following instrumented lumbar fusion for degenerative disease.


Slow fetal growth between first and early second trimester ultrasound scans and risk of small for gestational age (SGA) birth.
To investigate the association between fetal growth between first and early second trimester ultrasound scan and the risk of severe small for gestational age (SGA) birth. This cohort study included 69 550 singleton pregnancies with first trimester dating and an early second trimester growth scan in Stockholm and Gotland Counties, Sweden between 2008 and 2014. Exposure was difference in biparietal diameter growth between observed and expected at the second trimester scan, calculated by z-scores. Risk of birth of a severe SGA infant (birth weight for gestational age by fetal sex less than the 3rd centile) was calculated using multivariable logistic regression analysis and presented as adjusted odds ratio (aOR). Parietal growth less than 2.5 percentile between first and second trimester ultrasound examination was associated with elevated risk of being born severe SGA. (aOR 1.67; 95% Confidence Interval 1.28-2.18). The risks of preterm severe SGA (birth before 37 weeks) and term severe SGA (birth 37 weeks or later) were at similar levels, and risk of severe SGA were also elevated in the absence of preeclampsia, hypertensive diseases or gestational diabetes. Fetuses with slow growth of biparietal diameter at ultrasound examination in early second trimester exhibit increased risk of being born SGA independent of gestational age at birth and presence of maternal hypertensive diseases or diabetes mellitus.


Amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and eventual paralysis. Until recently, ALS was classified primarily within the neuromuscular domain, although new imaging and neuropathological data have indicated the involvement of the non-motor neuraxis in disease pathology. In most patients, the mechanisms underlying the development of ALS are poorly understood, although a subset of patients have familial disease and harbour mutations in genes that have various roles in neuronal function. Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria.


Influence of detergents on the function of cloned potassium channels.
The influence of detergents on cloned potassium channels expressed in Xenopus oocytes was investigated. Bath application of Triton X-100 caused a dose-dependent reduction of the peak current through the delayed rectifier channel rKv2.1 and a fast, time- and voltage-dependent, current inactivation. Onset of inactivation was observed at concentrations as low as 1 microM; at 100 microM inactivation proceeded with a time constant of about 50 ms at +50 mV. The effect of Triton did not compete with extracellular TEA and the tail current kinetics was accelerated, indicating that the molecular mechanism is not a simple open-channel block. In patch-clamp recordings the effects were readily reversible and application of detergents from the inside were most effective. Triton induced similar effects in hKv1.5 channels; for rKv1.1., d-eag, and Kir2.1 mainly a current reduction was observed. No effect of 100 microM Triton was found for the plant inward rectifier channel KAT1. Investigation of Shaker channel mutants revealed a dependence of the Triton effect upon the degree and nature of C-type inactivation. Only detergents with a long hydrophobic carbohydrate chain and a hydrophilic chain of the polyethyleneglycol type caused inactivation of rKv2.1 (e.g., Triton X-100, Thesit, Brij35 were active; CHAPS and MEGA-8 wre inactive). The presented data reveal that there are channel- and detergent-specific interactions which can result in fast inactivation leading to physiological effects similar to those exerted by local anesthetics and antiarrhythmic agents.


Vibrational Property of α-Borophene Determined by Tip-Enhanced Raman Spectroscopy.
We report a Raman characterization of the α borophene polymorph by scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy. A series of Raman peaks were discovered, which can be well related with the phonon modes calculated based on an asymmetric buckled α structure. The unusual enhancement of high-frequency Raman peaks in TERS spectra of α borophene is found and associated with its unique buckling when landed on the Ag(111) surface. Our paper demonstrates the advantages of TERS, namely high spatial resolution and selective enhancement rule, in studying the local vibrational properties of materials in nanoscale.


Effect of MK-801 and its interaction with adenosinergic agents and carbamazepine against hypoxic stress-induced convulsions and death in mice.
Effects of MK-801, adenosinergic agents and carbamazepine were investigated against hypoxic stress-induced convulsions and death in mice. MK-801, a N-methyl D-aspartate antagonist, offered a significant protective effect against hypoxic convulsions. Adenosinergic agents such as adenosine, 2-chloroadenosine, N6-cyclohexyladenosine and dipyridamole produced theophylline-sensitive protective effect as they dose-dependently prolonged the latencies for onset of convulsions and death. Pretreatment with adenosinergic agents and MK-801 markedly enhanced the protective effect of the stable analogs of adenosine namely, 2-chloroadenosine and N6-cyclohexyladenosine. However, pretreatment with combination of MK-801 and adenosine or dipyridamole did not show enhanced protective effect. Carbamazepine also exhibited dose-dependent theophylline-sensitive protective effect. The pretreatment with combination of carbamazepine and MK-801 showed significantly enhanced protective effect. The observed enhanced protective effect of MK-801 and adenosinergic agents was reversed by pretreatment with theophylline. These results indicate the possible involvement of adenosinergic mechanisms in preventing hypoxic stress-induced convulsions and the role of NMDA receptors in hypoxia-induced convulsions and death as MK-801 not only showed effect per se but also potentiated the response due to adenosinergic agents.