Relationship between various functional impression techniques and different operators.
The purpose of the present investigation was to determine the relationship between the reproducibility of soft tissue contours by three different functional impression techniques and four dentists for mandibular distal-extension removable partial dentures. The selected functional impression methods were Lejoyeux, Rouot and McLean techniques. A mucostatic impression technique was used for the control group. To compare and measure the degree of tissue displacement, a three-dimensional coordinate measuring system was used. The differences in vertical displacement of soft tissue among the operators were statistically determined for each impression technique used. Lejoyeux technique produced the least variation in tissue displacement followed respectively by McLean, mucostatic and Rouot methods.


Stereotactic radiotherapy for ocular melanoma: initial experience using closed eyes for ocular target immobilization.
To assess the reliability and target positioning reproducibility with eyes closed in uveal melanoma patients treated with a micromultileaf-based linear accelerator dedicated for stereotactic radiotherapy. Five consecutive patients treated with curative radiotherapy for uveal melanoma were monitored for positioning reproducibility with resimulation CT scans performed every two days while on treatment (23 resimulation CTs available). All patients underwent MRIs of the orbits before simulation to help to define the target and organs at risk (e.g., lenses, optic nerves, ciliary bodies, and lacrimal glands) in the simulation CT (MRI-to-CT bone registration). Patients were simulated, resimulated, and treated with eyes closed. Patient #1 was treated with 5 daily fractions while patients #2 to #5, were treated with 10 daily fractions. We chose the lens of the tumor-bearing eye as the structure to be controlled, assuming that correct repositioning of the lens should be a valid surrogate for correctness of target repositioning. Displacements (mean and standard deviations, SD) of the lens in the three axes were measured for each patient. Systematic and standard errors were calculated. Planning target volume (PTV) margins were estimated according to McKenzie et al. [Phys Med Biol 45, 3331-3342 (2000)]. For both AP-PA and left-right shifts calculated SD were always below 1 mm, except for patient #4, who was treated with a non-customized bolus that pushed the globe backwards in a random fashion. In ideal set-up conditions PTV margins around the target were estimated to be 3 mm. Asking patients to close their eyes is a simple and reliable immobilization procedure when treating ocular tumors with stereotactic radiotherapy. Margins of 3 mm around the target may be necessary to safely treat these tumors under ideal set-up conditions.


[The usefulness of computerized axial tomography (CT) in establishing the composition of calculi].
Determining stone composition before extracorporeal lithotripsy can be potentially useful. A total of 90 calculi of 6 different chemical composition (calcium oxalate monohydrate, calcium oxalate dihydrate, magnesium ammonium phosphate, phosphate carbonate, uric acid and phosphate oxalate) were analyzed in vitro using computed tomography (CT). The mean, central, peripheral, maximum, minimum stone density and stone morphology were determined. At least in vitro, the serial analyses of the mean, minimum, central stone density and stone morphology permitted distinguishing these 6 types of calculi, although 53% of the calcium oxalate dihydrate calculi could not be distinguished from the phosphate oxalate stones.


The Review of Insulin Pens-Past, Present, and Look to the Future.
Currently, there are about 150-200 million diabetic patients treated with insulin globally. The year 2021 is special because the 100th anniversary of the insulin discovery is being celebrated. It is a good occasion to sum up the insulin pen technology invention and improvement which are nowadays the leading mode of an insulin delivery. Even though so many years have passed, insulin is still administered subcutaneously, that is why devices to deliver it are of great importance. Insulin pens have evolved only through the last decades (the reusable, durable pens, and the disposable, prefilled pens) and modern smart insulin pens have been developed in the last few years, and both types of the devices compared to traditional syringes and vials are more convenient, discrete in use, have better dosing accuracy, and improve adherence. In this review, we will focus on the history of insulin pens and their improvement over the previous decades.


Bioactive compounds and antioxidant activities in the agro-industrial residues of acerola (Malpighia emarginata L.), guava (Psidium guajava L.), genipap (Genipa americana L.) and umbu (Spondias tuberosa L.) fruits assisted by ultrasonic or shaker extraction.
The aim of this study was to analyze the residue powders of Malpighia emarginata L., Psidium guajava L., Genipa americana L. and Spondias tuberosa L. regarding their total phenolic compounds contents, antioxidant activity (ABTS, DPPH and FRAP), soluble sugars, carotenoids, organic acids by HPLC-DAD/RID and individual phenolic compounds by the UPLC-QDa-MS system. The genipap residue had a high content of soluble sugars (422.72 ± 19.15 mg.g-1 DW), with a higher content of sucrose (170.83 ± 10.89 mg.g-1 DW). Nystose was found in the residues of guava (6.59 ± 0.56 mg.g-1 DW) and umbu (65.61 ± 2.31 mg.g-1 DW). The residues of acerola and umbu showed contents of β-carotene of 5.84 ± 0.01 mg.g-1 DW and 0.10 ± 0.05 mg.g-1 DW, respectively while high concentration (1116.00 ± 2.00 mg.100 g-1 DW) of tartaric acid was found in acerola residue and quinic acid (6340 ± 104.00 mg.100 g-1 DW) in umbu residue. Acetone (80%) and ultrasonic extraction were the best conditions for the residues of acerola, guava and genipap, however, for the umbu residue, extraction with shaker showed better results. The acerola and umbu residues showed higher yields of total phenolics, the values being 378.69-444.05 mg GAE.100 g-1 DW and 326.14-404.36 mg GAE.100 g-1 DW, respectively, as well as antioxidant activity. Naringenin was the individual phenolic compound with the highest concentration in the residue of acerola and genipap, vanillin in guava and rutin in umbu. Thus, residues powders from acerola, guava, genipap and umbu constitute potential sources of bioactive compounds, which could be used in the food, pharmaceutical and cosmetic industries.


Phase-cycling coherent anti-Stokes Raman scattering using shaped femtosecond laser pulses.
We demonstrate a homodyne coherent anti-Stokes Raman scattering (CARS) technique based on femtosecond laser pulse shaping. This technique utilizes fast phase cycling to extract nonlinear Raman signatures with a self-generated reference signal acting as a local oscillator. The local oscillator is generated at the focus and is intrinsically stable relative to the Raman signal even in highly scattering samples. We can therefore retrieve phase information from the Raman signal and can suppress the ubiquitous non-resonant background.


The organization of microtubules during anaphase and telophase spindle elongation in the rust fungus Puccinia.
The entire framework of microtubules (MTs) in the meiotic spindle of the rust fungus Puccinia has been reconstructed during the later stages of meiosis I, by tracking MTs through transverse serial sections. This spindle is of special interest because it elongates considerably during anaphase spindle elongation, from 5 microns at metaphase to 15 microns at telophase. The spindle is composed mainly of MTs from opposite poles which interdigitate or overlap in the middle of the spindle. In the overlap region, MTs from one pole seek out as near neighbors, MTs from the opposite pole at a preferred spacing of 43 to 55 nm. During anaphase elongation three changes in spindle structure occur: 1) the region of overlap decreases, but this reduction in overlap cannot account for all the increase in spindle length; 2) interdigitated MTs (MTs from one pole that are within 80 nm of a MT from the opposite pole) dramatically increase in length by MT polymerization and; 3) kinetochore MTs, free MTs (those unattached to the poles) and non-interdigitated polar MTs shorten and disappear. The mechanism of anaphase elongation and the control over MT polymerization and depolymerization during anaphase are discussed.


Atypical maternal cradling laterality in an impoverished South African population.
Human studies consistently report a 60%-80% maternal left cradling preference. The dominant explanation points to an engagement of the emotionally more-attuned right brain. In contrast, we found equal incidences of left (31.3%), right (34.3%) and no-preference (34.3%) cradling in an impoverished South African population living under adverse conditions characterized by extreme dangers. We found striking differences on the Parenting Stress Index (PSI) between mothers with no cradling laterality preference and mothers with either a left or right preference. In several mammals a homologous left preference becomes stronger when acute threats prevail, rendering the rightwards shift we observed under dangerous conditions seemingly paradoxical. We propose this paradox can be resolved in terms of life-history strategy theory which predicts reduced parental investment in chronically dangerous environments. We interpret our high PSI score findings in no-preference cradlers as indicative of poorer, or at least ambivalent, maternal coping which many studies show is typically associated with reduced emotional sensitivity and responsiveness. We suggest that the latter may be a psychological mechanism mediating a partial withdrawal of parental investment in response to an enduringly adverse environment. To the best of our knowledge, this is the first study investigating cradling laterality preferences in an adverse socioeconomic environment.


The role of bile acids in regulating glucose and lipid metabolism.
In recent years, bile acids (BAs) are increasingly being appreciated as signaling molecules beyond their involvement in bile formation and fat absorption. The farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) are two dominating receptors through which BAs modulate glucose and lipid metabolism. FXR is highly expressed in the intestine and liver. GPBAR1 is highly expressed in the intestine. The present study reviews the metabolism and regulation of BAs, especially the effects of BAs on glucose and lipid metabolism by acting on FXR in the liver and intestine, and GPBAR1 in the intestine. Furthermore, it explains that fibroblast growth factor 15/19 (FGF15/19), ceramide, and glucagon like peptide-1 (GLP-1) are all involved in the signaling pathways by which BAs regulate glucose and lipid metabolism. This article aims to provide an overview of the molecular mechanisms by which BAs regulate glucose and lipid metabolism, and promote further scientific and clinical research on BAs.


Hemodialysis graft salvage with endoluminal stents.
The most common cause of failure of hemodialysis access sites is stenosis within the site. The stenoses have traditionally been corrected surgically, but endovascular techniques may be an alternative method to treat these flow-limiting lesions and maintain graft patency. Over a recent 17-month period, endoluminal stents to relieve stenoses resistant to balloon dilatation alone were placed in 14 access sites. All sites were located on the upper extremity (13 PTFE bridge grafts and 1 A-V fistula). A total of 20 stents were placed: seven at the venous anastomosis, 12 in the venous outflow tract (including 3 in the subclavian vein), and one within the graft. Nine patients had placement of a single stent, four patients had two stents placed, and one patient had three. An additional eight stenotic lesions within these 14 sites were successfully dilated without need of a stent. After stent placement, these 14 sites have remained functional for a mean of 6.2 months. Four were functioning without further intervention at a mean of 8.5 months. Nine sites occluded at a mean of 4.7 months. The remaining site remained functional until death of the patient 10 months after stent placement. Of the nine failed sites, four developed restenosis at the site of stent placement, four developed stenoses at other sites, and the other site was abandoned. Three stents were placed in subclavian vein stenoses, and none of these has failed. Further study is necessary to determine whether endovascular stenting of dialysis access site stenoses will prove to be a durable, cost-effective alternative to surgical revision.


Additive activation of yeast LEU4 transcription by multiple cis elements.
The LEU4 gene of Saccharomyces cerevisiae and the enzyme encoded by LEU4, alpha-isopropylmalate synthase, occupy a special position in amino acid metabolism. alpha-Isopropylmalate synthase catalyzes the first committed step in leucine biosynthesis. However, the reaction product alpha-isopropylmalate is not only an intermediate in the leucine biosynthetic pathway, but also functions as co-activator of at least six genes, both within and outside of the leucine pathway. The metabolic importance of alpha-isopropylmalate appears to be reflected in the surprisingly multifaceted regulation of LEU4 expression. This report describes an analysis of functional cis elements in the LEU4 promoter. Five such elements were identified. Three distal elements, designated UASLEU, GCE-A, and GCE-B, are responsible for regulation by the regulatory proteins Leu3p and Gen4p, respectively. The incremental activation of LEU4 by these elements is additive and independent. In addition, two proximal elements were localized. One of these conforms to the TATA consensus sequence and exhibits high affinity for TATA binding protein. The other element shows strong sequence identity with the Bas2p binding site and appears to be involved in basal and phosphate-mediated regulation of LEU4.


Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone Formation.
Perfusion bioreactors have been an effective tool in bone tissue engineering. Improved nutrient delivery and the application of shear forces have stimulated osteoblast differentiation and matrix production, allowing for generation of large, clinically sized constructs. Differentiation of hypertrophic chondrocytes has been considered an alternative strategy for bone tissue engineering. We studied the effects of perfusion on hypertrophic chondrocyte differentiation, matrix production, and subsequent bone formation. Hypertrophic constructs were created by differentiation in chondrogenic medium (2 weeks) and maturation in hypertrophic medium (3 weeks). Bioreactors were customized to study a range of flow rates (0-1200 μm/s). During chondrogenic differentiation, increased flow rates correlated with cartilage matrix deposition and the presence of collagen type X. During induced hypertrophic maturation, increased flow rates correlated with bone template deposition and the increased secretion of chondroprotective cytokines. Following an 8-week implantation into the critical-size femoral defect in nude rats, nonperfused constructs displayed larger bone volume, more compact mineralized matrix, and better integration with the adjacent native bone. Therefore, although medium perfusion stimulated the formation of bone template in vitro, it failed to enhance bone regeneration in vivo. However, the promising results of the less developed template in the critical-sized defect warrant further investigation, beyond interstitial flow, into the specific environment needed to optimize hypertrophic chondrocyte-based constructs for bone repair.


[A case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis caused by chronic hepatitis C].
Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in im-munocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.


Serum S-100beta as a possible marker of blood-brain barrier disruption.
Two brain-specific proteins, S-100beta and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100beta levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100beta is a marker of blood-brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100beta increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100beta is an early marker of BBB opening that is not necessarily related to neuronal damage.


Processing of heme and heme-containing proteins by bacteria.
An extensive amount of new knowledge on bacterial systems involved in heme processing has been accumulated in the last 10 years. We discuss common themes in heme transport across bacterial outer and inner membranes, emphasizing proteins and mechanisms involved. The processing of heme in the bacterial cytoplasm is extensively covered, and a new hypothesis about the fate of heme in the bacterial cell is presented. Auxiliary genes involved in heme utilization, i.e., TonB, proteases, proteins involved in heme storage and pigmentation, as well as genes involved in regulation of heme assimilation are reviewed.


Qualitative and quantitative pharmacophore-similarity assessment of anthranilamide-based factor Xa inhibitors: applications on similar molecules with identical biological endpoints.
It is a conventional practice to exclude molecules with identical biological endpoints to avoid bias in the resulting hypothesis model. Despite the diverse chemical functionalities, the receptor interactions of such molecules are often unexplored. The present study motivates the selection of these molecules diversified by single atom or functional group compared to internal molecules as external set and helps in the understanding of corresponding effects toward receptor interactions and biological endpoints. Applied on anthranilamide-series of factor Xa analogs, the inhibitory activities were correlated (r(2) = 0.99) and validated (q(2) = 0.68) with distance-based pharmacophore descriptors using support vector machine. The selected external set molecules exhibited better prediction accuracy by securing activities less than one residual threshold. The effect on inhibitory activity was assessed by the examination of pharmacophore-similarity and its interactions with key residues of Human factor Xa enzyme using molecular docking approach. Furthermore, qualitative pharmacophore models were developed on the subset of molecular dataset divided as most actives, moderately actives and least actives, to recognize crucial activity governing pharmacophore features. The outcome of this study will bring new insights about the requirements of pharmacophore features and prioritizes its selection in the design and optimization of potent Xa inhibitors.


Meta-analysis on the therapeutic state of hypertensive population in Japan: focusing on the impact of new diagnostic criteria of Japanese Guideline for the Management of Hypertension 2000.
A Meta-analysis on the therapeutic state of hypertensive population in Japan is performed by the three nation-wide governmental surveys focusing on the impact of new diagnostic criteria described in the Guidelines for the Management of Hypertension in Japan 2000. These surveys are the National Survey of Circulatory Disorders, National Nutrition Survey and Patient Survey in 1990. The meta-analysis approach is used to evaluate the validity and reliability of these three national data sets, particularly the National Nutrition Survey. The population with history of hypertensive treatment and without previous diagnosis was calculated using the old and new diagnostic criteria. The results of three national surveys are fairly consistent. National Nutrition survey can be used to monitor the overall therapeutic status of Japanese population if the definition is considered judiciously. The impact of new diagnostic criteria is extensive as demonstrated by the results of the analysis on the National Nutrition Survey of 1999. The hypertensive population doubled and one half of the Japanese population over the age of 30 is now defined as hypertensive. A policy to manage this newly diagnosed hypertensive population is urgently needed to lessen the burden on Japanese health care system.


Thin films in hydrodynamic lubrication regime: The Osiris friction setup.
A model hydrodynamic lubrication tribometer consisting of two hydrodynamic journal bearings working under thin film conditions was developed to investigate the mechanisms of hydrodynamic friction with low-viscosity fluids and the role of surface effects. A small nominal radial clearance of about 5 µm was considered between the two surfaces. This fully instrumented setup provides in situ information on the sheared fluid film in terms of simultaneous measurements of film thickness; localization and extension of the cavitation zone, with a resolution of 30°; nominal friction torques up to 0.5 N m, with an accuracy of 0.05 mN m; temperature; and the position of the shaft for velocities up to 12 000 rpm. To illustrate the capability of the Osiris tribometer, thin hydrodynamic film measurements were performed on smooth surfaces. The results are presented here, and the thermal effects, acceleration, and inertia contributions are discussed. Finally, the influence of the surface topography using textured surfaces was demonstrated and the role of adsorbed layers on the surface due to fluid formulation was highlighted.


A quantitative study of mast cells in Hodgkin's disease.
Mast cells were counted in 45 specimens from patients with Hodgkin's disease and in five lymph nodes showing follicular hyperplasia. A consistent finding was that of few mast cells in the lymphocyte depleted and lymphocyte predominant Rye subtypes of Hodgkin's disease and in the mixed cellularity variant; however, mast cells were much more prevalent in nodular sclerosing Hodgkin's disease and in the hyperplastic nodes. The mast cells were selectively stained by means of the astra blue technique.


Catalysis of Michael Additions by Covalently Modified G-Quadruplex DNA.
Enantioselective catalysis utilizing G-quadruplex DNA-based artificial metalloenzymes has emerged as a new approach in the field of aqueous-phase homogeneous catalysis. Recently, a catalytic asymmetric Michael addition employing a covalently modified G-quadruplex in combination with CuII ions has been reported. Here we assess, by systematic chemical variation and using various spectrometric techniques, a variety of parameters that govern rate acceleration and stereoselectivity of the reaction, such as the position of modification, the topology of the quadruplex, the nature of the ligand, the length of the linker between ligand and DNA, the chemical identity of monovalent ions and transition metal complexes. The DNA quadruplex modified at position 10 (dU10) with hexynyl-linked bpy ligand showed twice the initial reaction rate as compared with the DNA strand derivatized at position 12 (dU12). The strikingly different dependence of the stereoselectivity on the linker length, and their different spectroscopic properties indicate large differences in the architecture of the catalytic centers between the dU10-derivatized and the dU12-modified quadruplexes. Upon addition of CuII , both types of bpy-derivatized DNA strands form defined 1:1 Cu-DNA complexes stable enough for mass spectrometric analysis, while the underivatized strands exhibit weak and unspecific binding, correlated with much lower catalytic rate acceleration. Both dU10- and dU12-derivatized quadruplexes could be reused ten times without reduction of stereoselectivity.


The role of intraspecific variation in the ecological and evolutionary success of diatoms in changing environments.
Intraspecific variation in diatoms has been shown to play a key role in species' responses to several important environmental factors such as light, salinity, temperature and nutrients. Furthermore, modelling efforts indicate that this variation within species extends bloom periods, and likely provides sufficient variability in competitive interactions between species under hydrographically variable conditions. The intraspecific variation most likely corresponds to optimal fitness in temporary microhabitats and may help to explain the paradox of the plankton. Here, we examine the implications of intraspecific variation for the ecology and success of diatoms in general and emphasize the potential implications for our understanding of carbon metabolism in these important organisms. Additionally, data from palaeoecological studies have the potential for evaluating genetic variation through past climate changes, going thousands of years back in time. We suggest pathways for future research including the adoption of multiple strains of individual species into studies of diatom carbon metabolism, to refine our understanding of the variation within and between species, and the inclusion of experimental evolution as a tool for understanding potential evolutionary responses of diatom carbon metabolism to climate change.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'.


BESST: a novel LncRNA knockout strategy with less genome perturbance.
Long noncoding RNAs (lncRNAs) are >200 nt RNA transcripts without protein-coding potential. LncRNAs can be categorized into intergenic, intronic, bidirectional, sense, and antisense lncRNAs based on the genomic localization to nearby protein-coding genes. The current CRISPR-based lncRNA knockout strategy works efficiently for lncRNAs distant from the protein-coding gene, whereas it causes genomic perturbance inevitably due to technical limitations. In this study, we introduce a novel lncRNA knockout strategy, BESST, by deleting the genomic DNA fragment from the branch point to the 3' splicing site in the last intron of the target lncRNA. The BESST knockout exhibited comparable or superior repressive efficiency to RNA silencing or conventional promoter-exon1 deletion. Significantly, the BESST knockout strategy minimized the intervention of adjacent/overlap protein-coding genes by removing an average of ∼130 bp from genomic DNA. Our data also found that the BESST knockout strategy causes lncRNA nuclear retention, resulting in decapping and deadenylation of the lncRNA poly(A) tail. Further study revealed that PABPN1 is essential for the BESST-mediated decay and subsequent poly(A) deadenylation and decapping. Together, the BESST knockout strategy provides a versatile tool for investigating gene function by generating knockout cells or animals with high specificity and efficiency.


On-street parking availaibilty data in San Francisco, from stationary sensors and high-mileage probe vehicles.
This dataset contains records of the measured on-street parking availability in San Francisco, obtained from the public API of the SFpark project. In 2011, the San Francisco Municipal Transportation Agency (SFMTA) started a project on smart parking, called SFpark, whose goal was the improvement of on-street parking management in San Francisco, mostly by means of demand-responsive price adjustments [1]. One of the key points of the project was the collection of information about on-street parking availability. To this aim, about 8,000 parking spaces were equipped with specific sensors in the asphalt, periodically broadcasting availability information. The SFpark project made available a public REST API, returning the number of free parking spaces and total number of provided parking spaces per road segment, for 5,314 parking spaces on 579 road segments in the pilot area. We collected parking availability data from 2013/06/13 until 2013/07/24, by querying this API at approximately 5-min intervals. As a result, we obtained in total about 7 million observations of parking availability on the road segments. These observations represent the first dataset we are providing. In addition, we simulated the achievable sensing coverage of on-street parking availability that could be achieved by a fleet of taxis, if they were equipped with sensors able to detect free parking spaces, like side-scanning ultrasonic sensors [3], or windshield-mounted cameras [4]. In particular, by exploiting real taxi trajectories in San Francisco from the Cabspotting project [5], we first computed the frequencies of taxi visits for each road segment covered by the SFpark sensors. Then, we downsampled the first dataset, in order to have a parking availability information for a road segment at a given time only in presence of a transit of a taxi on that segment at that time. This step was replicated for 5 different sizes of taxi fleets, namely 100, 200, 300, 400, and 486. Consequently, in total six datasets are available for further research in the field of on-street parking dynamics. All these datasets can be downloaded at: https://dataverse.harvard.edu/dataset.xhtml?persistentId=doi:10.7910/DVN/YLWCSU.


Uncovering the design rules for peptide synthesis of metal nanoparticles.
Peptides are multifunctional reagents (reducing and capping agents) that can be used for the synthesis of biocompatible metal nanoparticles under relatively mild conditions. However, the progress in peptide synthesis of metal nanoparticles has been slow due to the lack of peptide design rules. It is difficult to establish sequence-reactivity relationships from peptides isolated from biological sources (e.g., biomineralizing organisms) or selected by combinatorial display libraries because of their widely varying compositions and structures. The abundance of random and inactive amino acid sequences in the peptides also increases the difficulty in knowledge extraction. In this study, a "bottom-up" approach was used to formulate a set of rudimentary rules for the size- and shape-controlled peptide synthesis of gold nanoparticles from the properties of the 20 natural alpha-amino acids for AuCl(4)(-) reduction and binding to Au(0). It was discovered that the reduction capability of a peptide depends on the presence of certain reducing amino acid residues, whose activity may be regulated by neighboring residues with different Au(0) binding strengths. Another finding is the effect of peptide net charge on the nucleation and growth of the Au nanoparticles. On the basis of these understandings, several multifunctional peptides were designed to synthesize gold nanoparticles in different morphologies (nanospheres and nanoplates) and with sizes tunable by the strategic placement of selected amino acid residues in the peptide sequence. The methodology presented here and the findings are useful for establishing the scientific basis for the rational design of peptides for the synthesis of metal nanostructures.


Cardiovascular Outcomes Following Rotational Atherectomy: A UK Multicentre Experience.
To identify factors associated with outcomes following rotational atherectomy (RA). RA is an effective way to mechanically modify heavily calcified lesions before stenting; however its outcomes are not well defined. Retrospective evaluation of all patients who underwent RA in three large UK centers (Leeds General Infirmary (LGI), Royal Infirmary of Edinburgh (RIE) and University Hospital of North Staffordshire (UHNS)) from March 2005 to January 2013. Five hundred and eighteen patients had RA with median follow-up period of 22 months. About 68.3% were male, 28.7% had DM and 34.6% were treated because of ACS. Stents were deployed in 97.3% of the patients while 30.7% of the procedures were performed transradially. Maximum burr was ≤1.75 mm in 85.5% and the mean SYNTAX score was 19.5 ± 11.6. Peri-procedural complications occurred in 6.4% and vascular access complications in 1.9%. Outcomes in the follow-up period were: MACE 17.8%, cardiac death 7.1%, MI 11.7%, TVR 7.5%, all-cause death 13.7%, definite stent thrombosis (ST) 1.4% and stroke 2.9%. Patients with intermediate and high SYNTAX scores were more likely to suffer MACE, cardiac death, MI, all-cause death and ST. Patients with a SYNTAX score >32 were also more likely to have a peri-procedural complication. Multiple logistic regression analysis showed that the presence of PVD (P = 0.026, OR = 2.0), DM (P = 0.008, OR = 2.1), ACS presentation (P = 0.011, OR = 2.1) and SYNTAX score ≥23 (P = 0.02, OR = 1.9) had a significant association with MACE. RA is safe and effective, with high rate of procedural success and relatively low incidence of MACE. PVD, DM, ACS presentation and SYNTAX score were significant predictors for MACE. © 2016 Wiley Periodicals, Inc.


Primary tracheal non-Hodgkin lymphoma: case report with an emphasis on computed tomography findings.
A 24-year-old male presented with productive cough associated with fever, dyspnea, and hoarseness. A chest radiograph showed nonhomogeneous air-space consolidations, mainly in the middle and inferior zones of both lungs, with cavitations and peribronchial thickening. The computed tomography scan demonstrated irregular, lobulated narrowing of the trachea, and parenchymal consolidations containing air bronchogram, peribronchial thickening, and cavitations. Afterward, the patient was referred for a bronchoscopy with a biopsy of the tracheal mucosa. The samples were submitted to immunohistochemical analysis and revealed a diagnosis of diffuse large B-cell non-Hodgkin lymphoma of the trachea. A culture of bronchoalveolar lavage fluid revealed Pseudomonas aeruginosa. Antibiotic treatment was proposed as a first treatment. The patient did not receive intensive chemotherapy because of his comorbid conditions and died 2 months later.


[Use of the round ligament of the liver to prevent post-pancreatectomy hemorrhage].
Rupture of a pseudoaneurysm after pancreaticoduodenectomy is a fatal complication. To prevent this, we used the round ligament of the liver to separate the hepatic artery from pancreatic anastomosis, obtaining good results. The procedure involved detaching the round ligament of the liver from the abdominal wall during laparotomy and winding it from the proper and common hepatic artery mainly on a gastroduodenal artery stump after reconstruction. Postoperative computed tomography (CT) scan revealed that a thick layer of fat separated the hepatic artery from the abdominal abscess. We retrospectively analyzed 56 patients who had undergone pancreaticoduodenectomy at Tsubame Rosai Hospital from 2003 until 2012. The round ligament was used for 22 patients( ligament group) and was not used for 34 patients( non-ligament group). There was no difference in morbidity from intra-abdominal abscess and pancreatic fistula between the ligament and non-ligament group. Intra-abdominal hemorrhage occurred in 2 patients( 5.9%) in the non-ligament group but did not occur in the ligament group. We believe that this procedure is easy and useful for the prevention of post-pancreatectomy hemorrhage.


CXCR2+ MDSCs promote breast cancer progression by inducing EMT and activated T cell exhaustion.
Although myeloid-derived suppressor cells (MDSCs) have been demonstrated to contribute to tumor initiation, progression and metastasis, however, which MDSC subsets are preferentially expanded and activated, and what's the key molecular mechanism responsible for specific MDSC subsets in promoting tumor progression need to be fully addressed. Here we identify that Ly6GmiLy6CloCD11b+CXCR2+ subpopulation (named CXCR2+ MDSCs) are predominately expanded and recruited in systemic and local tumor microenvironment during breast cancer progression and metastasis. The proportion of CXCR2+ MDSCs is inversely correlated with the infiltration of CD4+ or CD8+ T cells. Besides, CXCR2+ MDSCs promote breast cancer growth and metastasis to lung and/or lymph node in vivo. Furthermore, CXCR2+ MDSCs induce epithelial mesenchymal transition (EMT) of breast cancer cells via IL-6. Moreover, CXCR2+ MDSCs upregulate the expression of immunosuppressive molecules programmed cell death protein 1(PD1), PD1 ligand 1 (PDL1), lymphocyte activation gene 3 protein (LAG3), cytotoxic T lymphocyte antigen 4 (CTLA4), and T cell immunoglobulin domain and mucin domain protein 3 (TIM3) on CD4+ or CD8+ T cells, and induce exhaustion of the activated T cells partially via IFN-γ. These results demonstrate that CXCR2+ MDSCs accelerate breast cancer progression via directly inducing cancer cell EMT and indirectly promoting T cell exhaustion, suggesting that CXCR2+ MDSCs may be a potential therapeutic target of breast cancer.


Autocatalytic activation of human cathepsin K.
The in vitro activation of the recombinant purified human cathepsin K (EC 188.8.131.52) was examined by mutagenesis. Cathepsin K was expressed as a secreted proenzyme using baculovirus-infected Sf21 insect cells. Spontaneous in vitro activation of procathepsin K occurred at pH 4 and was catalyzed by exogenous mature cathepsin K. Three intermediates were identified as resulting from cleavages after Glu19, Ser98, and Glu110. The mature enzyme was composed of mixture of enzymes with N termini of Gly113, Arg114, and Ala115 with varying ratios depending on the preparation. Molecular weight determinations were consistent with the absence of carbohydrate in the mature protein, while electrospray mass spectroscopy indicated that six of the eight cysteine residues were in disulfide linkage, and that the protein had Met329 as the C-terminal residue. A mutant was constructed in which the active site Cys139 was changed to Ser. [Ser139,Ala163]Procathepsin K (containing mutation C139S,S163A) failed to spontaneously process and was only partially processed in the presence of 1% exogenous wild-type mature cathepsin K forming intermediates, which were identical to those observed in the activation of wild-type. [Ser139,Ala163]Procathepsin K could be fully processed to mature enzyme by including one equivalent of wild-type procathepsin K in the activation mixture. These results indicated that in vitro activation of the procathepsin K was an autocatalytic process.


[A Case of Recurrent Rectal Cancer with Acute Lower Extremity Arterial Occlusion during Treatment with Bevacizumab].
The patient was 40s male, who underwent laparoscopic low anterior resection for his upper rectal cancer with final pathology results of tub2, pT3(SS), no lymph metastasis and fStage Ⅱ. He was followed up without adjuvant chemotherapy. Half a year after surgery, tumor marker was elevated and CT scan revealed multiple liver metastases. He was treated with oxaliplatin, irinotecan, Leucovorin and 5-fluorouracil(FOLFOXIRI)plus bevacizumab because of RAS mutant type. In the third courses, he has pain in the lower extremities and was diagnosed with acute lower extremity arterial occlusion. Subsequently, chemotherapy was resumed with the exception of bevacizumab, in combination with DOAC, which resulted in tumor shrinkage and allowed resection of the liver metastases.


Free energy of adhesion of lipid bilayers on silica surfaces.
The free energy of adhesion per unit area (hereafter referred to as the adhesion strength) of lipid arrays on surfaces is a key parameter that determines the nature of the interaction between materials and biological systems. Here we report classical molecular simulations of water and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers at model silica surfaces with a range of silanol densities and structures. We employ a novel technique that enables us to estimate the adhesion strength of supported lipid bilayers in the presence of water. We find that silanols on the silica surface form hydrogen bonds with water molecules and that the water immersion enthalpy for all surfaces varies linearly with the surface density of these hydrogen bonds. The adhesion strength of lipid bilayers is a linear function of the surface density of hydrogen bonds formed between silanols and the lipid molecules on crystalline surfaces. Approximately 20% of isolated silanols form such bonds but more than 99% of mutually interacting geminal silanols do not engage in hydrogen bonding with water. On amorphous silica, the bilayer displays much stronger adhesion than expected from the crystalline surface data. We discuss the implications of these results for nanoparticle toxicity.


Predicting flow at work: investigating the activities and job characteristics that predict flow states at work.
Flow (a state of consciousness where people become totally immersed in an activity and enjoy it intensely) has been identified as a desirable state with positive effects for employee well-being and innovation at work. Flow has been studied using both questionnaires and Experience Sampling Method (ESM). In this study, we used a newly developed 9-item flow scale in an ESM study combined with a questionnaire to examine the predictors of flow at two levels: the activities (brainstorming, planning, problem solving and evaluation) associated with transient flow states and the more stable job characteristics (role clarity, influence and cognitive demands). Participants were 58 line managers from two companies in Denmark; a private accountancy firm and a public elder care organization. We found that line managers in elder care experienced flow more often than accountancy line managers, and activities such as planning, problem solving, and evaluation predicted transient flow states. The more stable job characteristics included in this study were not, however, found to predict flow at work.


Calculation of dose in off-central axis planes using off-axis ratios.
Accuracy of dose calculation for regular fields in off-central axis planes was investigated on a RAD-8 treatment planning computer for 4- and 10-MV x-ray beams produced by Varian Clinac -4 and Clinac -18 linear accelerators. These calculations, which are based on central axis depth dose and off-axis ratios in the principal planes, can be in error by as much as 25%-30% at locations well within the irradiated volume for the 4-MV x-ray beam. These large errors for the Clinac -4 beam result from the falloff in dose beyond the peak dose along a diagonal of a large field at distances greater than 14 cm from the central axis due to the lead flattening filter. The profile data stored in the computer along the principal planes cannot be used to calculate the dose accurately in such a situation. Computed doses for the 10-MV x-ray beam agreed with the measured doses within 4%-6% at all locations.


[The Bassini-Houdard type herniorhaphy. Long-term results and factors of recurrence].
The aim of this long term study was to confirm that long term results are worsening with time and to establish the factors favourising recurrence. The study was retrospective and concerned 751 inguinal herniorraphies, performed from 1972 to 1982 according to the Bassini procedure modified by Houdard. The mean follow-up was 180.3 +/- 45.2 months (16.2-250.6). Available information was collected for 565 (75.3%) cases. The recurrence rate was 10%. The mean time between operation and recurrence was 102 +/- 65.6 months (6.1-226.3). The recurrence rate was lower for indirect hernias (4.7%) than for the group of direct, combined and sliding hernias (16%), (p < 0.00001). For recurrent hernias the recurrence rate was 22% versus 8.9% in primary herniorraphies (p > 0.01). This study suggests that recurrences can occur a long time after primary surgery because of parietal weakening with time; the low recurrence rate in indirect hernias does not justify the use of prostheses in this type of hernias, then higher rate in direct, combined, sliding and recurrent hernias warrants wider use of prostheses.


[Esophageal stenosis in a patient with primary biliary cirrhosis and mucous membrane pemphigoid].
A 77-year-old man with primary biliary cirrhosis was admitted to our hospital with a complaint of dysphagia. Upper gastrointestinal endoscopy revealed multiple ulcers in the oral cavity and pharynx, with circumferential ulceration in the cervical and upper thoracic esophagus. It was difficult to pass the endoscope through the upper thoracic esophagus, indicating stenosis. The patient was referred to the ophthalmology department for ocular lesions, where he was diagnosed with symblepharon due to ocular pemphigoid. Furthermore, direct immunofluorescence microscopy of esophageal biopsy specimens revealed linear deposits of IgG, IgA, and C3 in the epithelial basement membrane zone. On the basis of these findings, a diagnosis of mucous membranous pemphigoid was made.


The feasibility of endoscopy-CT image registration in the head and neck without prospective endoscope tracking.
Endoscopic examinations are frequently-used procedures for patients with head and neck cancer undergoing radiotherapy, but radiation treatment plans are created on computed tomography (CT) scans. Image registration between endoscopic video and CT could be used to improve treatment planning and analysis of radiation-related normal tissue toxicity. The purpose of this study was to explore the feasibility of endoscopy-CT image registration without prospective physical tracking of the endoscope during the examination. A novel registration technique called Location Search was developed. This technique uses physical constraints on the endoscope's view direction to search for the virtual endoscope coordinates that maximize the similarity between the endoscopic video frame and the virtual endoscopic image. Its performance was tested on phantom and patient images and compared to an established registration technique, Frame-To-Frame Tracking. In phantoms, Location Search had average registration errors of 0.55 ± 0.60 cm for point measurements and 0.29 ± 0.15 cm for object surface measurements. Frame-To-Frame Tracking achieved similar results on some frames, but it failed on others due to the virtual endoscope becoming lost. This weakness was more pronounced in patients, where Frame-To-Frame tracking could not make it through the nasal cavity. On successful patient video frames, Location Search was able to find endoscope positions with an average distance of 0.98 ± 0.53 cm away from the ground truth positions. However, it failed on many frames due to false similarity matches caused by anatomical structural differences between the endoscopic video and the virtual endoscopic images. Endoscopy-CT image registration without prospective physical tracking of the endoscope is possible, but more development is required to achieve an accuracy suitable for clinical translation.


How Christian ethics became medical ethics: the case of Paul Ramsey.
Over the last century Christian ethics has moved from an attempt to Christianize the social order to a quandary over whether being Christian unduly biases how medical ethics is done. This movement can be viewed as the internal development of protestant liberalism to its logical conclusion, and Paul Ramsey can be taken as one of the last great representatives of that tradition. By reducing the Christian message to the 'ethical upshot' of neighbour love, Ramsey did not have the resources to show how Christian practice might make a difference for understanding or forming the practice of medicine. Instead, medicine became the practice that exemplified the moral commitments of Christian civilization, and the goal of the ethicist was to identify the values that were constitutive of medicine. Ramsey thus prepared the way for the Christian ethicist to become a medical ethicist with a difference, and the difference simply involved vague theological presumptions that do no serious intellectual work other than explaining, perhaps, the motivations of the ethicist.


Complex spatio-temporal features in meg data.
Magnetoencephalography (MEG) brain signals are studied using a method for characterizing complex nonlinear dynamics. This approach uses the value of d(infinity) (d-infinite) to characterize the system's asymptotic chaotic behavior. A novel procedure has been developed to extract this parameter from time series when the system's structure and laws are unknown. The implementation of the algorithm was proven to be general and computationally efficient. The information characterized by this parameter is furthermore independent and complementary to the signal power since it considers signals normalized with respect to their amplitude. The algorithm implemented here is applied to whole-head 148 channel MEG data during two highly structured yogic breathing meditation techniques. Results are presented for the spatio-temporal distributions of the calculated d(infinity) on the MEG channels, and they are compared for the dirrerent phases of the yogic protocol. The algorithm was applied to six MEG data sets recorded over a three-month period. This provides the opportunity of verifying the consistency of unique spatio-temporal features found in specific protocol phases and the chance to investigate the potential long term effects of these yogic techniques. Differences among the spatio-temporal patterns related to each phase were found, and they were independent of the power spatio-temporal distributions that are based on conventional analysis. This approach also provides an opportunity to compare both methods and possibly gain complementary information.


Managing Brachycaudis persicae (Homoptera: Aphididae) during peach orchard establishment.
We investigated whether preplant root dips or postplant sprays or drenches could be used to control the black peach aphid, Brachycaudus persicae (Passerini), on young peach trees. In greenhouse trials, B. persicae died after being placed on peach trees that had their roots dipped in imidacloprid before planting. All rates (0.8, 1.6, and 3.2 ml/liter of water) tested controlled this aphid. B. persicae died faster on trees dipped in imidacloprid (1.6 ml/liter of water) for 5 min before planting than on trees dipped for 2 s. Aphids eventually died on all treated trees. Approximately 50% of untreated trees died from B. persicae infestations in greenhouse studies. Results from afield experiment show that peach trees root-dipped in imidacloprid before planting or drenched with imidacloprid after planting eliminate B. persicae infestations and prevent root colonization for at least 1 yr.


Setting mental health priorities: problems and possibilities.
A recent project at the Hastings Center examined the question of priority setting in the provision of mental health services. A central issue was whether those services should be prioritized independently of other health services. The answer to that question was no: they should have full parity. Even so, priority setting can be a complex venture. At the heart of any such effort will be the relationship between empirical evidence on treatment outcomes and efficacy and the political and ethical interests that legitimately bear on interpreting and using that evidence. An argument is made that a priority should be given those whose suffering and inability to function in ordinary life is most pronounced, even if the available treatment for them is comparatively less efficacious than for other conditions.


Development and health status of Centropomus undecimalisparasitized by Rhabdosynochus rhabdosynochus (Monogenea) under different salinity and temperature conditions.
This study evaluated the correlation of hematological parameters with the mean abundance of the monogenean helminth Rhabdosynochus rhabdosynochus in Centropomus undecimalis reared at different temperatures and salinities. The experimental conditions were: 28 °C/0 ppt (parts per thousand); 28 °C/15 ppt; 28 °C/32 ppt; 25 °C/0 ppt; 25 °C/15 ppt; and 25 °C/32 ppt. The prevalence was 100.0% in fish at 28 °C/15 ppt, 28 °C/32 ppt and 25 °C/15 ppt, which was significantly different (p < 0.05) from those at 25 °C/32 ppt. The red blood cell (RBC) count, hematocrit and total leukocyte (WBC) count were significantly higher in fish at 28 °C/15 ppt and 28 °C/32 ppt. The mean abundance of R. rhabdosynochus, hematocrit and RBC showed positive correlations (P < 0.05) with temperature (ρ= 0.3908; ρ= 0.4771 and ρ = 0.2812). Mean abundance showed negative correlations with hemoglobin (ρ= -0.3567) and mean corpuscular hemoglobin concentration (MCHC) (ρ = -0.2684). No correlation between abundance and salinity was detected among the experimental conditions (ρ = -0.0204). The low numbers of monogeneans recorded (min -1 and max -33) explain the few changes to fish health. This suggests that these experimental conditions may be recommended for development of rearing of C. undecimalis in Brazil, without any influence or economic losses from R. rhabdosynochus.


Effect of chartreusin on macromolecular synthesis.
Chartreusin (CT), a natural compound derived from Streptomyces chartreusis which exhibits antitumor activity, was demonstrated to be an equally potent inhibitor of DNA and RNA synthesis in cultured human KB cells and in isolated nuclei. Polymerization of nucleic acids in nuclei prepared from adenovirus-infected KB cells responded to CT in a similar manner. In contrast, protein biosynthesis was not inhibited by up to 30 microgram/ml CT in whole KB and rabbit reticulocyte cells as well as in their cell free lysates.


[Serologic detection of hantavirus antibodies].
Within the framework of diagnosis of highly dangerous infections in the Army of the Czech Republic serological assessment of hantaviral antibodies was introduced. Because military units in the field can be in contact with sources of hantaviral infections, the authors investigated this population sample. In 1999-2000 a total of 542 healthy subjects were examined (age 20-40 years). Hantaviral antibodies were detected in 9. In three antibodies against the serotype Hantaan were found, in two antibodies against serotype Puumala and in four against serotype Seoul. The mean seropositivity was 1.66%. As compared with results which were obtained in the National Institute of Public Health in Prague in 1998 in a sample of the general population (430 subjects) where seropositivity of hantaviral antibodies was 0.93% the seropositivity in military units is higher. It is thus essential to make this laboratory diagnosis in the laboratories of the Army of the Czech Republic.


The Removal of Atrazine and Benalaxyl by the Fly Ash Released from Kosovo A Power Plant.
The development of low-cost adsorbent coal FA (Kosovo A) for pesticide removal is an important area of scientific research. With this study, we show the potential of adsorption of coal FA (Kosovo A) for the removal of benalaxyl and atrazine from water. We have found that the amount of adsorbed benalaxyl and atrazine increases with an increasing amount of coal FA (Kosovo A) in solution. The maximum capacity coal FA (Kosovo A) to adsorb benalaxyl and atrazine was found to be 0.46 and 0.45 mg/g according to the Freundlich equation and 3.48 and 3.33 mg/g according to the Langmuir equation. The Freundlich adsorption equation better explains the adsorption results of pesticides (benalaxyl and atrazine) in coal FA (Kosovo A), as the values of the recovery coefficient (R 2) were higher in Freundlich equation than the Langmuir equation. The adsorption isotherms were of type L and show that the adsorption efficiency of the coal FA (Kosovo A) depends on the initial concentration of benalaxyl and atrazine in solution and the maximum removal of benalaxyl and atrazine was achieved at concentrations less than 10 µg/ml. This study's results are expected to have implications for the use of coal FA (Kosovo A) for the removal of pesticides from water.


Microwave-Assisted Synthesis of the Red-Shifted Pentamethine Tetrahydroxanthylium Core with Absorbance within the Near Infrared-II Window.
Thirteen red-shifted pentamethine dimethyl and diethylamino tetrahydroxanthylium derivatives have been successfully synthesized via the microwave-assisted approach. The optimized conditions developed in the synthesis provided an excellent yield in expedited reaction time. These newly synthesized dyes show well-defined optical properties resulting from the diverse substitutions at the central meso positions. The majority of the compounds have a maximum wavelength of absorbance within 946-1022 nm with extinction coefficients in the range of 9700-110,680 M-1 cm-1 in various solvents such as MeOH, EtOH, DMSO, DCM, MeCN, and DMF. These fluorophores, to the best of our knowledge, are the first NIR-II small molecules synthesized using microwave chemistry. We also investigated these dyes for their NIR fluorescence imaging capabilities. Diethylamino-substituted compounds and bromination resulted in higher uptake in the adrenal gland compared to dimethylamino fluorophores. In addition, micellar structures of compounds 7 and 15 improved the targetability of the original dyes to the bone marrow, lymph nodes, and nerves. Overall, NIR-II imaging has the potential to visualize biologically targeted tissues in living organisms.


A Million Steps: Developing a Health Promotion Program at the Workplace to Enhance Physical Activity.
The workplace is a key setting for the prevention of occupational risks and for promoting healthy activities such as physical activity. Developing a physically active lifestyle results in many health benefits, improving both well-being and quality of life. This article details the experience of two Spanish companies that implemented a program to promote physical exercise in the workplace, called "A Million Steps." This program aimed to increase the physical activity of participants, challenging them to reach at least a million steps in a month through group walks. Participant workers reached the set goal and highlighted the motivational and interpersonal functions of the program.


Risk of recurrent preterm birth and placental pathology.
To estimate whether placental pathological lesions from an index preterm birth are associated with an increased risk of recurrent preterm birth and to estimate whether certain pathologic lesions recur in a woman's next delivery. We performed a retrospective cohort study of all women who delivered at less than 37 weeks and had their next delivery at our institution during a 5-year period. Women were included in the cohort if placental pathology was available from their preterm birth. Placental pathology from their subsequent birth was also collected. Placental pathology was classified into presence or absence of two classes of lesions-inflammatory and thrombotic. Variables considered as possible confounders included race, gestational age of preterm birth, interpregnancy interval, tobacco use, payor status, years of education, and maternal medical problems. Inflammatory lesions (n=173) were associated with recurrent preterm birth overall as well as recurrent spontaneous preterm birth (P<.001). Thrombotic lesions (n=158) were not associated with recurrent preterm birth or any subtypes of preterm birth. The association between inflammatory lesions and recurrent spontaneous preterm birth remained significant when controlling for gestational age of preterm birth, race, and tobacco use, with an adjusted odds ratio of 2.4 (95% confidence interval 1.2-4.7). Inflammatory placental lesions (n=194) were associated with inflammatory lesions in the subsequent delivery P=.001). Recurrent preterm birth is more likely among women with inflammatory lesions on placental pathology from a prior preterm birth. Additionally, these women are more likely to have placental inflammatory lesions with their next delivery. II.


Nutrition policy critical to optimize response to climate, public health crises.
The effects of unanticipated crises on health care and first-responder systems are reflected in climate-fueled environmental emergencies, to which human resilience is diminished by our chronic disease epidemic. For example, people who depend on specialized medications, like refrigerated insulin for diabetes, will likely face additional challenges in receiving treatment and care during extreme heat, floods, disasters, and other adverse events. These circumstances may be compounded by staff and equipment shortages, lack of access to fresh food, and inadequate healthcare infrastructure in the wake of a disaster. Simply put, our health care and first-response systems struggle to meet the demands of chronic disease without such crises and may be fundamentally unable to adequately function with such crises present. However, nutrition's primacy in preventing and controlling chronic disease directly enhances individual and public resilience in the face of existential threats. Highlighting the shared diet-related etiology clearly demonstrates the need for a national policy response to reduce the disease burden and potentiate mitigation of the sequelae of climate risks and capacity limits in our food and health care systems. Accordingly, this article proposes four criteria for nutrition policy in the Anthropocene: objective government nutrition recommendations, healthy dietary patterns, adequate nutrition security, and effective nutrition education. Application of such criteria shows strong potential to improve our resiliency despite the climate and public health crises.


The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) for mood disorders: double-blind, placebo-controlled studies.
Our previous study has shown the beneficial effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as adjunctive therapy with carbamazepine (CBZ) in the 12-week treatment of bipolar disorders (Zhang ZJ, Kang WH, Tan QR, Li Q, Gao CG, Zhang FG, et al., Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res; 2005). Here, we present follow-up data obtained from a continuation of the previously reported study. Treatment and clinical evaluation of bipolar patients (n=188) who had randomly received 12-week CBZ plus placebo (n=92) or CBZ plus FEWP (n=96) were extended to 26 weeks under double-blind condition. Patients in adjunctive FEWP showed a significantly lower overall discontinuation rate (31%) at endpoint compared to placebo (51%, p=0.009), and of 15% in adjunctive FEWP discontinued due to intolerable side effects, markedly lower than those in placebo (28%, p=0.019). No difference in discontinuation for lack of efficacy and exacerbation was observed in the two groups. Patients receiving adjunctive FEWP had significantly fewer adverse side effects and lower serum levels of CBZ than those in placebo. A separate study was further conducted to evaluate the effectiveness of FEWP as monotherapy in depressed patients. A total of 87 unipolar and 62 bipolar depressed patients were randomly assigned to treatment with 36 g/day FEWP (n=86) or placebo (n=63) for 12 weeks under double-blind condition. Efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). Both unipolar and bipolar patients assigned to FEWP displayed significantly greater improvement on the three efficacy indices and significantly higher clinical response rate (74%) than those treated with placebo (42%, p<0.001) at endpoint. These results suggest that adjunctive FEWP improves tolerability of CBZ in the long-term use, which may be associated with the suppression of blood CBZ concentrations via herb-drug interactions. FEWP monotherapy may be also an effective alternative treatment for depressed conditions.


Extended Stability of Sodium Phosphate Solutions in Polyvinyl Chloride Bags.
Sodium phosphate injection is used to treat moderate to severe hypophosphatemia. There have been no published reports documenting the physical compatibility or chemical stability of sodium phosphate injection in IV solutions. To evaluate the physical compatibility and chemical stability of 30 and 150 mmol/L solutions of phosphate, prepared from sodium phosphate injection, in 5% dextrose in water (D5W) and in 0.9% sodium chloride (normal saline [NS]) and stored in polyvinyl chloride (PVC) bags at 23°C or 4°C over 63 days. On study day 0, solutions of phosphate 30 and 150 mmol/L in D5W or NS were prepared in PVC bags and stored at 4°C and 23°C. On prespecified days during the 63-day study period, the concentrations of sodium and phosphate were determined, and admixture weight was checked to assess moisture loss during storage without a plastic overwrap. Chemical stability was calculated from the intersection of the lower 95% confidence limit of the degradation rate and the lower limit of acceptability (90%) for concentration remaining. The analytical methods for both sodium and phosphate were found to be precise (coefficient of variation averaging less than 1% for pre-study validation samples). Both sodium and phosphate retained more than 94% of the initial concentration over the 63-day study period. With 95% confidence, the time to achieve 90% of the initial concentration of both sodium and phosphate approached or exceeded the 63-day study period, regardless of temperature, concentration, or base solution. Sodium phosphate solutions at a phosphate concentration of 30 or 150 mmol/L in either NS or D5W retained more than 94% of the initial concentration of both sodium and phosphate over 63 days when stored at 23°C or 4°C. In compliance with United States Pharmacopeia General Chapter <797> recommendations, a beyond-use date of 14 days (with refrigeration) or 48 h (room temperature) may be applied. Extending the beyond-use date beyond these limits may be considered, if a validated sterility test is performed.


Semaphorin 3A promotes osteogenic differentiation in human alveolar bone marrow mesenchymal stem cells.
The aim of the present study was to investigate the role of Semaphorin 3A (Sema3A) in the osteogenic differentiation of human alveolar bone marrow mesenchymal stem cells (hABMMSCs). To investigate whether Sema3A affects hABMMSC proliferation and osteogenic differentiation, a stable Sema3A-overexpression cell line was generated by infection with the pAdCMV-SEMA3A-MCS-EGFP vector. Cell counting kit-8 and clone formation assays were performed to determine the proliferation ability of hABMMSCs, while cell osteogenic differentiation was assayed using Alizarin Red S staining. In addition, reverse transcription-quantitative polymerase chain reaction was employed to detect the mRNA expression level of osteogenesis-associated genes, Runt-related transcription factor 2 (Runx2), osteopontin (Opn) and osteocalcin (Ocn), during the osteogenic differentiation. The results revealed that, compared with the normal control group, the cell morphology of the infected cells was stable and no significant alterations were observed. Overexpression of Sema3A in hABMMSCs significantly increased the cell proliferation ability compared with the control group. Furthermore, the Alizarin Red S staining assay results indicated that the ossification process of hABMMSCs overexpressing Sema3A was evidently faster in comparison with that of the control group cells. Overexpression of Sema3A by pAdCMV-SEMA3A-MCS-EGFP infection also significantly increased the mRNA expression levels of the osteogenic marker genes Runx2, Opn and Ocn. In conclusion, Sema3A was observed to be a key positive regulator in hABMMSC osteogenic differentiation.


Psychometric properties of a computerized adaptive test for assessing mobility in older adults using novel video-animation technology.
This paper reports on the psychometric properties of a computerized adaptive test (CAT) version of the Mobility Assessment Tool (MAT) for older adults (MAT-CAT). An item pool of 78 video-animation-based items for mobility was developed, and response data were collected from a sample of 234 participants aged 65-90 years. The video-animation-based instrument was designed to minimize ambiguity in the presentation of task demands. In addition to evaluating traditional psychometric properties including dimensionality, differential item functioning (DIF), and local dependence, we extensively tested the performance of several MAT-CAT measures and compared their performances with a fixed format. Operationally, the MAT-CAT was sufficiently unidimensional and had acceptable levels of local independence. One DIF item was removed. Most importantly, the CAT measures showed that even starting with a single fixed item at the mean ability, the adaptive version delivered better performance than the fixed format in terms of several criteria including the standard error of estimate. The MAT-CAT demonstrated satisfactory psychometric properties and superior performance to a fixed format. The video-animation-based adaptive instrument can be used for assessing mobility with specificity and precision.


Astigmatic optical systems with separated and prismatic or noncoaxial elements: system matrices and system vectors.
A general system of noncoaxial separated astigmatic optical elements is examined. Allowance is made for prismatic elements including decentered lenses and refracting surfaces, prisms, and plane interfaces. The directions and positions of a ray entering and emerging from the system are related by a system matrix and a system vector. Given an incident ray one can readily obtain the emergent ray. The analysis is of fundamental importance for visual optics. Two numerical examples are presented. One is a model eye with astigmatic and obliquely crossing astigmatic and decentered surfaces.


Causal Inference on Multidimensional Data Using Free Probability Theory.
In this paper, we deal with the problem of inferring causal relations for multidimensional data. Based on the postulate that the distribution of the cause and the conditional distribution of the effect given cause are generated independently, we show that the covariance matrix of the mean embedding of the cause in reproducing kernel Hilbert space (RKHS) is free independent with the covariance matrix of the conditional embedding of the effect given cause. This, called freeness condition, induces a cause-effect asymmetry that a designed measurement is 0 in the causal direction but smaller than 0 in the anticausal direction, and it uncovers the causal direction. One important novel aspect of this paper is that we interpret the independence as a freeness condition between covariance matrices of RKHS distribution embeddings, and it has a wide applicability. We show that our freeness condition-based inference method succeeds in scenarios like additive noise cases, where other methods fail, by theoretical analysis and experimental results.


Myelin basic protein in Alzheimer disease neuronal fractions and mammalian neurofilament preparations.
We previously reported a marked increase of a 20,000 molecular weight (MW) protein, P20, in some neuronal fractions and whole cortical homogenates isolated from affected cortex in Alzheimer disease; P20 comigrated electrophoretically with an unidentified, major 20,000 MW protein present in human neurofilament (NF) fractions. We now report that the 20,000 MW protein is a major constituent of rodent as well as human NF fractions and that it comigrates by one- and two-dimensional gel electrophoresis with purified myelin basic protein (MBP). Peptide mapping and staining with amido black confirmed the identity of the 20,000 MW protein of mammalian NF fractions as MBP. One- and two-dimensional gel electrophoresis of neuronal perikaryal fractions from human cortex indicated that the increased P20 protein in Alzheimer neuronal fractions comigrates with human MBP. Deliberate contamination of cortical samples with adjacent subcortical white matter (i.e., myelin) prior to neuronal separation did not result in an increase of P20 in the neuronal fraction. On the basis of these and additional experiments, we conclude that the increase of a 20,000 MW protein in neuronal fractions and whole homogenates from affected cortex in Alzheimer disease represents MBP of intracortical origin.


[Dynamic changes of B7-H1 expression on mDCs and T cells in chronic hepatitis B patients treated with PEG-IFN alpha-2a].
To study the dynamic changes of B7-H1 expression on myeloid dendritic cells (mDCs) and T cells in chronic hepatitis B (CHB) patients undergoing PEG-IFN alpha-2a therapy, and to analyze the association of the changes with the efficiency of interferon-alpha therapy. Expressions of B7-H1 on mDCs and T cells in 14 patients with chronic HBV infection, including 6 responders and 8 non-responders to the antiviral therapy, were monitored by using flow cytometric analysis. Peripheral blood mononuclear cells from patients were incubated in vitro and the numbers of IFN-gamma-producing antigen-specific T cells were measured using ELISPOT assay. B7-H1 expressions by mDCs, CD4+ T cells and CD8+ T cells were all significantly upregulated at 4 weeks after starting PEG-IFN alpha-2a therapy. After this time point, B7-H1 expressions persistently decreased in the responders to the antiviral treatment, while non-responders maintained high levels of B7-H1 expression. In addition, the frequency of HBV-specific IFN-gamma-producing T cells significantly increased in the responders, but significantly decreased in the non-responders. Blocking the B7-H1 signal pathway increased the numbers of HBV-specific IFN-gamma-producing T cells in both the responders and non-responders. Dynamic changes of B7-H1 expression by mDCs and T cells in CHB patients undergoing PEG-IFN alpha-2a therapy can predict the efficiency of the therapy. Blocking the B7-H1 inhibitory pathway likely enhances the antiviral cellular T-cell responses.


L-arginine-threonine-arginine (RTR) tetramer peptide inhibits ulceration in the alkali-injured rabbit cornea.
Proline-glycine-proline (PGP) peptides have been identified as inflammatory mediators initiating neutrophil invasion into alkali-injured cornea. The complementary peptide, arginine-threonine-arginine (RTR), has been shown to bind to the PGP sequence and impede neutrophil infiltration. A prior study showed that L-RTR tetramer and D-RTR tetramer, used alternately (14 times a day), resulted in significantly reduced incidences of corneal ulceration and severity. The purpose of this experiment is to determine the effectiveness of both tetramers, used separately, compared with control. Rabbit corneas were exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly assigned to each of 3 groups: 1) phosphate-buffered saline (PBS), 2) 1.5 mM L-RTR, or 3) 800 microM D-RTR. One drop of each was administered hourly (14 times a day) for 36 days. Additional studies were done to assess neutrophil infiltration into corneas with and without RTR treatment. The severity of corneal ulceration in both RTR groups was statistically significantly different from the 21st day of the experiment to the end. As a result of ulcers healing in the L-RTR group, there was a statistically significant reduction in the number of ulcers beginning on day 22 versus control. Although there was healing in the D-RTR group, the incidence of ulcers was not significantly different from control or L-RTR. Morphometric analysis revealed decreased neutrophil (PMN) invasion with RTR treatment compared with PBS control. Binding of the PGP molecules by RTR tetramer seems to deprive the cornea of this neutrophilic chemotactic stimulus, leading to a reduction in the severity and incidence of corneal ulceration.


[Education in maternal breastfeeding and their repercussions in clinical practice].
The study aimed at understanding the aspects that the nurses makes available to mothers regarding to breastfeeding and to verify which communication skills are used in advice in breastfeeding. That was a descriptive-exploratory study with the use of an application form that was completed by 45 nurses from a post-graduate pediatrics course. The average age of the participants was 32,7 years-old, being the majority females. It was observed that after the training course the students become more aware of the maternal body posture and breast anatomy. Changes in the advices given to the mothers with the purpose of promoting better practices concerning to the positioning and way of nursing were also observed after the training, nevertheless, the communication skills used were few. It was concluded that the breastfeeding advice training course was not enough, requiring a greater development.


Positive association between ATP2B1 rs17249754 and essential hypertension: a case-control study in Burkina Faso, West Africa.
Genetic and environment play a significant role in the etiology of essential hypertension (EH). Recently STK39 rs3754777, ATP2B1 rs2681472 and rs17249754 have been associated with BP variation and hypertension. In this study we aimed to determine firstly whether index variants were associated with the risk of developing EH in Burkina Faso and secondly to characterize cardiovascular risk markers. We conducted a case-control study with 380 participants including 180 case subjects with EH and 200 control subjects with normal BP. We used TaqMan genotyping assays with probes from Applied Biosystems to genotype polymorphisms using the 7500 Real-Time PCR System. Biochemical parameters were measured using chemistry analyzer COBAS C311. T-test showed that cardiovascular risk markers such as body mass index, waist circumference, blood sugar, total cholesterol and triglycerides were significantly higher in hypertensive compared to normotensive (all p < 0.05). Binary logistic regression analysis revealed in decreasing order that overweight, family history of hypertension, central obesity and alcohol intake increased the risk of developing EH (all OR > 3.8; all p < 0.001). In genetic level we observed that individuals carrying the AA+AG genotype of ATP2B1 rs17249754 had a low risk of developing EH than those carrying the GG genotype (OR = 0.48 [95% CI: 0.31-0.75] p = 0.001) and the A allele frequency in the cases was significantly lower than that of the controls (OR = 0.56 [95% CI: 0.38-0.82] p = 0.003). We also observed that ATP2B1 rs17249754 was significantly associated with higher SBP and DPB in case and control groups (GG versus AG + AA; p < 0.05), ATP2B1 rs2681472 was significantly associated with higher SBP only in case and control group (AA versus AG + GG; p < 0.05), STK39 rs3754777 was not significantly associated with any of the BP traits (CC versus CT + TT; p > 0.05). Our results confirmed the significant association of ATP2B1 rs17249754 with the risk of developing EH in Burkinabe and showed an increase of cardiovascular risk markers levels in subjects with EH.


Generation of tunable picosecond pulses by pulse stacking in an Yb-fiber gain-assisted pulse stacker.
We report on the generation of tunable picosecond pulses of high repetition rate by pulse stacking in an Yb-fiber stacker that benefited from high optical gain, properly time delay and laser synchronization. The gain-assisted pulse stacker could be controlled for pulse shaping to produce tunable pulse duration from ps to sub-ns range by managing the intracavity dispersion and adjusting the time delay. The energy loss during the pulse shaping process was compensated by the gain of a 60-cm-long Yb-fiber pumped by a diode laser. The temporal profiles of the output pulses were measured by using a special cross-correlation technique. The duration of the stacked pulses could be tuned from 5 to 200 ps with a controllable time interval.


The role of complement in arterial hypertension and hypertensive end organ damage.
Increasing evidence indicates that hypertension and hypertensive end organ damage are not only mediated by haemodynamic injury but that inflammation also plays an important role. The complement system protects the host from a hostile microbial environment and maintains tissue and cell integrity through the elimination of altered or dead cells. As an important effector arm of innate immunity, it plays also central roles in the regulation of adaptive immunity. Thus, complement activation may drive the pathology of hypertension through its effects on innate and adaptive immune responses, aside from direct effects on the vasculature. Recent experimental data strongly support a role for complement in all stages of arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical haemolytic uraemic syndrome suggest also a role for complement in the development of malignant nephrosclerosis. Here, we review the role of complement in hypertension and hypertensive end organ damage. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.


Pre-adipocyte determination either by insulin or by 5-azacytidine.
CHEF/18 is a diploid Chinese hamster cell line of embryonic origin, which is fibroblastic in structure, but behaves like a mesenchymal stem cell line in its ability to differentiate into adipocytes, myoblasts, and chondrocytes. With these cells, adipocyte formation has been divided experimentally into two stages: (i) determination of pre-adipocytes, which have lost the ability to form other cell types while retaining their fibroblast structure; and (ii) commitment or terminal differentiation, in which lipids accumulate, adipocyte structure develops, and cells lose the ability to divide. This paper reports that the first stage can be induced by exposure to 5-azacytidine or 2'-deoxy-5-azacytidine, drugs that also induce CHEF cells to form other mesenchymal cell types, or by growth with added insulin. Pre-adipocytes are distinguished from CHEF stem cells by (i) their inability to form other mesenchymal cell types; and (ii) their rapid accumulation of lipid in response to added insulin. The possibility is discussed that both insulin and the cytidine analogs promote differentiation by the same mechanism, namely changes in the pattern of DNA methylation.


[Protein studies of viral hemorrhagic septicemia in rainbow trout].
Comparative investigations were carried out on the changes in the blood serum of normal and diseased rainbow trout with virus hemorrhagic septicaemia. Determined was the amount of the total protein and the protein fractions. The electrophoretic investigation of blood serum of rainbow trout revealed one dominating albumin fraction, 3 alfa-globulin fractions, 2 beta-globulin ones, and one gamma-globulin one. The following up of the protein fraction dynamic during the various seasons did not reveal any dependence on the temperature curve. Rainbow trout manifesting clinically virus hemorrhagic septicaemia showed lowering of the total protein amount and changes in the electrophoretic profile and the quantitative ratio of the protein fractions. There were a drop of the albumin percent and a rise of the beta- and gamma-globulin fractions. This led to a change in the coefficients alfa:beta (0.89) and albumin: globulin (0.14).


Temperature measurement error reduction for MRI-guided HIFU treatment.
We present a method to remove the temperature measurement errors due to the movement of the ultrasound applicator during MRI-guided high-intensity focused ultrasound (MRgHIFU) treatment. MR thermometry, based on proton resonance frequency (PRF) shift, can provide high accuracy and temporal resolution of MR temperature imaging for tumour treatment by MRgHIFU. However, the challenge is that the movement of the ultrasound applicator causes temperature measurement errors due to the magnetic susceptibility of the applicator. In a clinical environment the applicator has to be moved to cover the whole tumour volume, even in the case of a phased array ultrasound applicator. With conventional PRF shift-based phase mapping method, a reference image must be repetitively acquired as the ultrasound applicator is repositioned and tissue cooling down time must be inserted before a new reference scan. Therefore, the treatment workflow becomes complex and time consuming. In this paper we propose a method to reduce temperature measurement error by compensating the ultrasound applicator susceptibility through a pre-measured or calculated magnetic field distribution of the applicator. The large temperature measurement error shown around the ultrasound focal region can be significantly reduced by compensating the ultrasound applicator-induced delta magnetic field. Accurate temperature maps can be obtained when the ultrasound applicator is repositioned without repetitively acquiring new reference images. The reference image can be repetitively used for the temperature imaging when the ultrasound applicator is repositioned. Therefore, the treatment workflow is simplified resulting in a reduction in total treatment time.


Trigonocephaly: a new familial syndrome.
Trigonocephaly was found in six relatives through three generations of one family. The propositus was ascertained at birth because of omphalocele. In addition to trigonocephaly, he had minor ear, vertebral, and genital abnormalities. His father had mild microcephaly, and both had minor eye abnormalities. None of the other four affected individuals had any other malformations. In this family, trigonocephaly is an autosomal dominant trait. The ratio of affected males to affected females was 5 to 1, and although the paucity of affected females is not statistically significant, we speculate that it may reflect variable expressivity or sex limitation of the trait. We conclude that the condition in this family represents a unique syndrome in which trigonocephaly is not associated with functional brain abnormalities and where craniosynostosis is limited to the metopic region.


Significant vomiting and weight loss in a pediatric epilepsy patient secondary to vagus nerve stimulation: A case report and review of the literature.
Vagus nerve stimulation is a neuromodulatory treatment option for individuals with drug resistant epilepsy who are not resective surgical candidates. As the vagus nerve has widespread neural connections, stimulation can lead to an array of adverse effects. While vomiting and weight loss are known side effects of vagus nerve stimulation, these are typically transient, mild, and do not limit the ability to continue treatment. We describe a 17-year-old female with drug resistant focal epilepsy secondary to tuberous sclerosis complex, who began to experience daily emesis and significant weight loss approximately 2.5 years after VNS device insertion. Her body mass index progressively fell from between the 75th-85th percentiles to less than the first percentile. She underwent extensive workup by neurology, gastroenterology, and adolescent medicine services with no obvious cause identified. Prior to the insertion of an enteral tube for feeding support and urgent weight restoration, her vagus nerve stimulator was switched off, resulting in immediate cessation of her vomiting and a dramatically rapid recovery of weight over the ensuing few months. This case emphasizes the need to consider adverse effects of vagus nerve stimulation in the differential diagnosis of patients with otherwise unexplained new medical sequelae, and provides evidence potentially linking vagal stimulation to significant malnutrition-related complications. Outside of GI-related effects, few studies have shown late-onset adverse effects from VNS, including laryngeal and facial pain as well as bradyarrhythmia. Further research is needed to elucidate the exact mechanisms of vagus nerve stimulation to better anticipate and mitigate adverse effects, and to understand the pathophysiology of late-onset adverse effects in previously tolerant VNS patients.


Age differences in attention lapses mask age differences in memory failures: a methodological note on suppression.
Although objective measures of memory performance typically indicate memory declines with age, self-reported memory failures often show no relation to age. In contrast, self-reported attention failures are reliably negatively correlated with age. This contrast suggests the possibility that age-related awareness and reporting of memory failures might be masked by a concurrent decrease in attention failures, which would reduce encoding failures with age and hence reduce perceived memory failures. Self-reported problems of attention and memory were evaluated in two samples with the ages spanning eight decades. Initial analysis indicated that attention failures significantly decreased with age, whereas memory problems did not to differ across age. The association of self-reported memory failures became significantly positive, however, when residualized on attention lapses. In contrast, the correlation between attention lapses and age was modestly affected when memory failures were controlled. These results highlight the close relation of attention lapses and memory problems and, beyond the implications of individual differences in attention for memory research, suggest the advisability of assessing attention failures for a full evaluation of memory problems.


Lipogenic stromal cells as members of the foam-cell population in human atherosclerosis: Immunocytochemical and ultrastructural assessment of 6 cases.
To identify the nature of foam cells in atherosclerosis, carotid atherosclerotic plaques (CAPs) from six patients were studied. Hematoxylin-and-eosin, Congo Red and Oil Red O staining were used to study histopathologic alterations in CAPs. CD31, α-smooth-muscle actin (α-SMA), CD68, desmin and S100 were stained immunohistochemically. The ultrastructure of foam cells was analyzed by transmission electron microscopy (TEM). CAPs were shown to be composed of a fibrous cap covering a dome-shaped mass with a peripheral, circumferential fringe merging with a basal band which itself met the tunica media, the latter consisting of smooth-muscle cells (SMCs). The interior of the dome-shaped mass exhibited fibrosis, neovascularization, hemorrhage, necrosis and calcification. Lipid droplets identified by histological stains and TEM were found in the rounded epithelioid foam cells regarded as macrophages, as well as in spindled cells interpreted here as lipoleiomyocytes (lipid-containing SMCs), lipofibroblasts and lipomyofibroblasts; and all these cells were located in different regions of the CAPs. All of these lipid-laden cells were strongly positive for CD68 but negative for desmin. Foam cells were weakly positive for α-SMA, CD31 and S100. The results indicate that the light microscopically identifiable population of foam/lipid-laden cells hide a spectrum of diverse differentiation ranging from the expected macrophage phenotype to non-macrophage phenotypes. The origin of these diverse cell phenotypes in terms of multipotential mesenchymal precursors and the origin of the intracellular lipid are discussed.


Differences in Colorectal Cancer Survival Based on Primary Tumor Location: Retrospective Study from a Single Institution.
Objective: The location of the primary tumor in colorectal cancer (CRC) could be a prognostic factor related to survival. However, its usefulness has not been sufficiently analyzed. The results in patients with tumors in initial stages are very limited, and there are descriptive parameters of survival that have not been analyzed in detail. In this study, the relationship between primary tumor location and survival in CRC patients was analyzed. Materials And Methods: This was a retrospective observational study. All patients treated consecutively for CRC between January 2005 and December 2019 in the same hospital center were included. Overall survival (OS), cancer-related survival (CRS), time to recurrence (TTR), relapse-free survival (RFS) and postrecurrence survival (PRS) were analyzed, and the results were classified by tumor stage. The results were compared among patients with right colon (RS), left colon (LS) and rectal tumors. Results: In the entire cohort, patients with RS tumors had lower OS and lower CRS at 60 months after diagnosis than did patients with LS or rectal tumors. In the regression analysis, the localization of the primary tumor was an independent prognostic indicator for OS and CRS. Analysis by tumor stage showed that patients with RS stage III tumors had lower OS and lower CRS at 60 months than did patients with LS and rectal tumors (42%, 59% and 53%, respectively, p = 0.006; and 48%, 63% and 57%, respectively, p = 0.025). Additionally, patients with RS Stage IV tumors had lower OS and lower CRS at 36 months than did patients with LS and rectal tumors (9%, 24%, 24%, respectively, p < 0.001; and 10%, 24% and 24%, respectively, p < 0.001). No differences were found in TTR and RFS among patients with stage I and II RS, LS, and rectal tumors. In contrast, patients with stage RS III tumors had significantly poorer PRS (9% for RS tumors, 13% for LS tumors, and 22% for rectal tumors) (p < 0.001). Conclusion: The location of the primary tumor in patients with CRC is related to survival. The effect of laterality is more marked in patients with stage III and IV tumors. Patients with RS tumors had lower OS and CRS due to the lower survival of patients with stage IV RS tumors and lower PRS for patients with stage III tumors.


The incidence and prognostic significance of mutations in codon 13 of the N-ras gene in acute myeloid leukemia.
To determine the incidence and prognostic significance of mutation in the N-ras gene in de novo acute myeloid leukemia (AML) we performed an analysis of bone marrow smears from 219 patients with de novo AML treated between 1984 and 1986 and followed for at least six years. DNA extracted from bone marrow smears taken at diagnosis was screened for the presence of mutations in codons 12 and 13 of exon 1 by using the polymerase chain reaction to insert an Hph1 restriction enzyme site into DNA. Presumptive mutations were confirmed by direct sequencing. Mutations were detected in a total of 26 patients (12%); in nine patients (4%) in codon 12 only, in ten patients (5%) in codon 13 only, and in seven patients (3%) in both codons. Mutations in codon 12 or codon 13 were not associated with any clinical features. Mutations in codon 12 had no prognostic significance but mutations in codon 13 were associated with an increased remission rate, a more durable remission, and a significantly prolonged survival which appeared to be independent of other prognostic factors.


Depressive symptoms, inflammation, and ischemic stroke in older adults: a prospective analysis in the cardiovascular health study.
To investigate the mediator role of inflammation in any relationship between depressive symptoms and ischemic stroke. Longitudinal prospective study. Review of medical records, death certificates, and the Medicare healthcare utilization database for hospitalizations. Total of 5,525 elderly men and women aged 65 and older who were prospectively followed from 1989 to 2000 as participants in the Cardiovascular Health Study. Depression symptom scores, inflammatory markers. Greater depressive symptoms were associated with risk of ischemic stroke (unadjusted hazard ratio (HR)=1.32, 95% confidence interval (CI)=1.09-1.59; HR=1.26, 95% CI=1.03-1.54, adjusted for traditional risk factors). When a term for inflammation (C-reactive protein (CRP)) was introduced in the model, the HRs were not appreciably altered (unadjusted HR=1.31, 95% CI=1.08-1.58; adjusted HR=1.25, 95% CI=1.02-1.53), indicating that CRP at baseline was not a mediator in this relationship. In analyses stratified according to CRP levels, a J-shaped relationship between depressive symptoms and stroke was evident in the unadjusted analyses; in the fully adjusted model, only CRP in the highest tertile was associated with a higher risk for stroke in the presence of higher depressive symptoms scores. The analyses from this prospective study provide evidence of a positive association between depressive symptoms and risk of incident stroke. Inflammation, as measured according to CRP at baseline, did not appear to mediate the relationship between depressive symptoms and stroke.