Association of fetal and maternal carboxyhemoglobin levels in normal and Rh-alloimmune pregnancies.
To compare paired antepartum fetal/maternal COHb ratios in whole blood from control and alloimmunized pregnancies and to examine the relationships between fetal and maternal COHb. COHb levels were measured in paired fetal and maternal blood samples obtained at cordocentesis in 47 control and 16 Rh-alloimmunized pregnancies. COHb was determined by gas chromatography. Results were analyzed by t-test, regression and analysis of covariance. Although fetal/maternal COHb ratios for control and alloimmunized pregnancies were not statistically significantly different, i.e. 1. 11+/-0.04 and 1.26+/-0.09, respectively (P=0.09), fetal COHb levels were higher in Rh-alloimmunized fetuses (P=0.0002). Fetal COHb levels were also higher than paired maternal levels among the alloimmunized group (P=0.011), but not among the control group (1. 04+/-0.04, P=ns). In univariate regression analysis, fetal and maternal COHb levels were significantly correlated with one another in both control (r=0.52, P=0.0002) and alloimmunized pregnancy groups (r=0.52, P=0.05). Comparison of the slopes of the fetal versus maternal COHb plots for the two groups showed a significant difference (P=0.02), with the alloimmunized group having the steeper slope. Differences in the antepartum fetal-maternal COHb relationships in control and alloimmunized groups likely reflect increased endogenous CO production among alloimmunized fetuses as a result of pathologic hemolysis.


Ambient NO2 exposure induced cardiotoxicity associated with gut microbiome dysregulation and glycerophospholipid metabolism disruption.
An average daily increase of 10 μg/m3 in NO2 concentrations could lead to an increased mortality in cardiovascular, cerebrovascular of 1.89%, 2.07%, but the mechanism by which NO2 contributes to cardiotoxicity is rarely reported. In order to assess the cardiotoxicity of NO2 inhalation (5 ppm), we firstly investigate the change of gut microbiota, serum metabonomics and cardiac proteome. Non-targeted LC-MS/MS metabonomics showed that NO2 stress could perturb the glycerophospholipid metabolism in the serum, which might destabilize the bilayer configuration of cardiac lipid membranes. Furthermore, we observed that NO2 inhalation caused augmented intercellular gap and inflammatory infiltration in the heart. Although 16 S rRNA gene amplification sequencing demonstrated that NO2 exposure did not influence the intestinal microbial abundance and diversity, but glycerophospholipid metabolism disruption might be finally reflected in gut microbiom dysregulation, such as Sphingomonas, Koribacter, Actinomarina and Bradyrhizobium Turicibacter, Rothia, Globicatella and Aerococcus. Proteome mining revealed that differentially expressed genes (DEGs) in the heart after NO2 stress were involved in necroptosis, mitophagy and ferroptosis. We further revealed that NO2 increased the number of cardiac mitochondria with depletion of cristae by regulating the expression of Mfn2 and Hsp70. This study indicating Mfn2-meidcated imbalanced mitochondrial dynamics as a potential mechanism after NO2-induced heart injury and suggesting microbiome dysregulation/glycerophospholipid metabolism exerts critical roles in cardiotoxicity caused by NO2.


Associations between perinatal factors and adiponectin and leptin in 9-year-old Mexican-American children.
Mexican-American children are at particularly high risk of obesity. Features of the perinatal environment, including maternal nutrition, anthropometry, glucose tolerance and growth rate during infancy are implicated in programming of obesity in the offspring. Greater rate of weight or length gain in the first 6 months of life is associated with lower 9-year child adiponectin levels, adjusting for 9-year child BMI. Nine-year-old child adipokine levels are strongly related to those of their mothers'. To (i) determine whether perinatal factors (including maternal anthropometry and nutrition and early life growth measures) are associated with adiponectin and leptin levels in 9-year-old children, and (ii) assess relationships between adiponectin, leptin and concurrent lipid profile in these children. We measured plasma adiponectin and leptin for 146 mothers-9-year-old child pairs from the ongoing longitudinal birth cohort followed by the Center for the Health Assessment of Mothers and Children of Salinas. Data on perinatal factors, including sociodemographics, maternal anthropometry and nutrition, and early life child growth were collected during pregnancy, birth and 6-month visits. Greater rate of weight and length gain during the first 6 months of life were associated with lower adiponectin in 9-year-olds (β = -2.0, P = 0.04; β = -8.2, P = 0.02, respectively) adjusting for child body mass index (BMI). We found no associations between child adipokine levels and either maternal calorie, protein, total fat, saturated fat, fibre, sugar-sweetened beverage consumption during pregnancy or children's concurrent sugar-sweetened beverage and fast food intake. Lipid profile in 9-year-old children closely reflected adiponectin but not leptin levels after adjustment for child BMI. Additionally, we report that child adipokine levels were closely related to their mothers' levels at the 9-year visit. Overall, our results support the hypothesis that early life factors may contribute to altered adipokine levels in children.


Correction to: Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.
Following publication of the original article [1], the authors reported errors in the presentation of Tables 2, 4 and 5.


Tumor blood flow: the principal modulator of oxidative and glycolytic metabolism, and of the metabolic micromilieu of human tumor xenografts in vivo.
We have investigated therapeutically relevant pathophysiological parameters of human breast and lung cancer xenografts in nude rats. All lung cancers and one breast cancer exhibited rapid growth and high blood flow values paralleled by high metabolic rates. The tissue of these tumors was well oxygenated up to very advanced growth stages. Xenografts from other breast cancer cell lines grew much more slowly, were poorly perfused, and exhibited low metabolic rates. Here, tumor hypoxia and tissue acidosis were evident. These results indicate that significant differences in the metabolic micromilieu can be detected in human tumors; these are due to varying perfusion rates and may be partly responsible for failure to obtain tumor control in individual patients.


Prone positioning to treat acute severe pulmonary edema in the post-cardiac surgical patient: a case report.
Noncardiogenic pulmonary edema can be fatal without adequate resuscitation. We report, for the first time, the use of prone positioning in the immediate post-cardiac surgical period to treat a patient with profound hypoxemia secondary to massive (noncardiogenic) pulmonary edema. Prone positioning corrects ventilation-perfusion mismatch and allows gravity-dependent drainage of capillary leak-mediated endobronchial pulmonary fluid.


Driver training interests of a Spanish sample of young drivers and its relationship with their self-assessment skills concerning risky driving behavior.
Poor driving self-assessment skills (e.g., over-confidence) have been pointed out as an important explanatory factor behind young drivers' accident involvement. This paper explores (1) what young drivers miss in their training as drivers in order to analyze whether an assessment of one's own driving skills plays an important role in their desire to improve as drivers, and (2) how these training interests are related to an estimate of their self-assessment skills concerning risky driving behavior. For this purpose, a study was conducted using a survey with a blocked sampling design of novice drivers. The survey solicited respondents' self-report about (1) the contents of training courses that they feel would improve their driving, (2) their risky driving behavior, and (3) their likelihood of being involved in a risky driving situation. From the initial sample invited to participate, of nearly 1300 people, we finally obtained complete data from 321 young Spanish drivers. Two main results were apparent from our data analysis: (1) the novice drivers were mainly interested in improving their ability to recognize their strengths and weaknesses as drivers (i.e., self-assessment skills); (2) a significant relationship was found between novice drivers' interests and their current self-assessment skills concerning risky driving behavior. Specifically, there was greater general interest expressed in post-license training by the under-confident self-assessors than the over-confident ones. These results provide a relevant input which should be taken into account when designing driver training programs for novice drivers. Moreover, the relationship between their training interests and their risky driving self-assessment skills introduces an additional factor to be considered in the implementation of these training programs.


Marginal gap formation of light-activated restorative materials: effects of immediate setting shrinkage and bond strength.
The purpose of this study was to explore multiple correlations between shrinkage, bonding and marginal gap parameters, immediately after light-activation, for three classes of restorative materials. The correlations of interest were between: (a) their marginal gap formation in tooth cavities, (b) their free setting shrinkage-strain determined by two different measurement methods ((i) the marginal gap-width in a non-bonding Teflon cavity and (ii) a linear (diametral) measure of shrinkage-strain), and (c) their shear bond strengths to enamel and to dentin. The maximum marginal gap width and the opposing width (if any) in the tooth cavity were measured immediately (3 min) after light-activation. Two factors for the setting shrinkage-strain and the shear bond strength to enamel and to dentin were measured concomitantly. Out of the set of restorative materials investigated, those that produced a smaller marginal gap in the tooth cavity had a smaller marginal gap in the Teflon cavity. There was a highly significant correlation between the two parameters (r=0.914, p<0.001). However, no relationship was observed between the marginal gap in the tooth cavity and the immediate diametral shrinkage-strain (p>0.05). Thus the restorative materials that produced a smaller marginal gap in the tooth cavity did not generally have a smaller diametral setting shrinkage-strain. Furthermore, no relationship was observed between the marginal gap in the tooth cavity and the shear bond strength to enamel or to dentin (p>0.50). For light-activated restorative materials during the early stage of setting (<5 min), the free shrinkage-strain, measured by marginal-gaps in Teflon cavities, had a greater correlation with immediate marginal-gaps in tooth cavities than either the immediate diametral shrinkage-strain or the bond strengths to the tooth structure.


Dihydropteridine reductase activity in eluates from dried blood spots: automation of an assay for a national screening service.
We describe the automation, using a Cobas Bio centrifugal analyser, of a method for dihydropteridine reductase (DHPR) assay in eluates from dried blood spots. This is used as part of a routine screening service of neonates with hyperphenylalaninaemia in the United Kingdom. Automation reduced reagent volumes and analysis time by about 80% and improved the precision of the assay. Relating DHPR activity to haemoglobin concentration of the eluate further improved the precision of the assay and removed some differences in 'apparent' DHPR activity between samples from different countries and different age groups.


Differential pharmacologic sensitivities of phosphodiesterase-3 inhibitors among human isolated gastroepiploic, internal mammary, and radial arteries.
Systematic investigations of the actions of phosphodiesterase (PDE)-3 inhibitors on different human vascular tissues have not been performed. We investigated the effects of specific PDE-3 inhibitors (olprinone, milrinone, and amrinone) on contracted human gastroepiploic arteries (n = 70), internal mammary arteries (n = 72), and radial arteries (n = 70) harvested from a total of 134 patients, all of whom were undergoing coronary artery bypass surgery. Each of these PDE-3 inhibitors dose-dependently diminished the contractile responses to 10(-6) mol/L norepinephrine and to either 10(-9) or 10(-8) mol/L of the thromboxane A2 analog U46619. In inducing vasorelaxations, these inhibitors were significantly more potent in norepinephrine-contracted rings than in those contracted with U46619. Further, at concentrations similar to the maximum therapeutic plasma concentrations (10(-7) mol/L olprinone; 10(-6) mol/L milrinone; 10(-5) mol/L amrinone) olprinone and milrinone were more potent at inducing relaxations than amrinone in gastroepiploic arteries and radial arteries, whereas in internal mammary arteries milrinone was more potent than the others. These results suggest different activities for the three PDE-3 inhibitors among human arteries located in different regions and may be informative about the effectiveness of these inhibitors in preventing spasms in the various arterial grafts used in revascularization. Because three phosphodiesterase-3 inhibitors (milrinone, olprinone, and amrinone) differed in their vasodilator potencies (against the contractile response to either norepinephrine or a thromboxane A2 analog) among human arteries removed from different parts of the body, their vascular relaxation profiles should be considered before they are used clinically.


[Study of complex lipids. Synthesis of diphosphatidylglycerol (cardiolipin) with unsaturated fatty acid residues].
Diphosphatidylglycerol (cardiolipin) with different fatty acid residues has been synthesised by condensation of 1,2-diacyl-sn-glycero-3-phosphoric acid (obtained, e.g., by the cabbage phospholipase D cleavage of 1,2-dioleyl-sn-glycero-3-phosphocholine or egg phosphatidylcholine) with 2-O-tert-butyldimethylsilylglycerol in the presence of 2,4,6-triisopropylbenzenesulphonylchloride. The synthetic cardiolipins as unsonicated aqueous calcium-free dispersions were shown, by means of 31P NMR spectroscopy, to form aggregates of the bilayer structure.


An Ultrathin Inorganic Molecular Crystal Interfacial Layer for Stable Zn Anode.
Zn metal anode suffers from dendrite growth and side reactions during cycling, significantly deteriorating the lifespan of aqueous Zn metal batteries. Herein, we introduced an ultrathin and ultra-flat Sb2 O3 molecular crystal layer to stabilize Zn anode. The in situ optical and atomic force microscopes observations show that such a 10 nm Sb2 O3 thin layer could ensure uniform under-layer Zn deposition with suppressed tip growth effect, while the traditional WO3 layer undergoes an uncontrolled up-layer Zn deposition. The superior regulation capability is attributed to the good electronic-blocking ability and low Zn affinity of the molecular crystal layer, free of dangling bonds. Electrochemical tests exhibit Sb2 O3 layer can significantly improve the cycle life of Zn anode from 72 h to 2800 h, in contrast to the 900 h of much thicker WO3 even in 100 nm. This research opens up the application of inorganic molecular crystals as the interfacial layer of Zn anode.


The impact of robotic surgery in urology.
More than a decade ago, robotic surgery was introduced into urology. Since then, the urological community started to look at surgery from a different angle. The present, the future hopes, and the way we looked at our past experience have all changed. Between 2000 and 2011, the published literature was reviewed using the National Library of Medicine database and the following key words: robotic surgery, robot-assisted, and radical prostatectomy. Special emphasis was given to the impact of the robotic surgery in urology. We analyzed the most representative series (finished learning curve) in each one of the robotic approaches regarding perioperative morbidity and oncological outcomes. This article looks into the impact of robotics in urology, starting from its background applications before urology, the way it was introduced into urology, its first steps, current status, and future expectations. By narrating this journey, we tried to highlight important modifications that helped robotic surgery make its way to its position today. We looked as well into the dramatic changes that robotic surgery introduced to the field of surgical training and its consequence on its learning curve. Basic surgical principles still apply in Robotics: experience counts, and prolonged practice provides knowledge and skills. In this way, the potential advantages delivered by technology will be better exploited, and this will be reflected in better outcomes for patients.


Synthesis and Crystal Structure of Diaqua(1,10-Phenanthroline-N,N')(Thiosulfato-O,S)Manganese(II). Biological Properties.
The synthesis of diaqua(1,10-phenanthroline-N,N')(thiosulfato-O,S)manganese(ll) [Mn(phen)(S(2)O(3))(H(2)O)(2)] was investigated. Its structure was determined by single crystal X-ray diffraction from 2418 reflections (I > 3 sigma(I)) to a final value of R = 0.047 and Rw = 0.054. Crystal data are as follows : space group P(2) (1); a = 10.356(3), b = 7.097(3), c = 20.316(2) A, beta = 94.29(2) degrees , V = 1489.1(8) , A(3), Z = 2. There are two independent title compounds in the asymetric unit. Each manganese atom has a distorted octahedral Mn(SO)N(2)O(2) geometry with the S and O atoms (from two neighbouring thiosulfate ligands) mutually trans, two N atoms from the 1,10-phenanthroline ligand and two water oxygen. The thiosulfate group behaves as a bridging ligand, connecting, through sulfur and oxygen, Mn atoms related by the binary b translation, thus forming infinite chains running parallel to this axis. Infrared and electronic spectra are reported.


Evolving Practice Patterns Over Two Decades (1993-2013) in the Management of Desmoid-type Fibromatosis in British Columbia.
Due to the rarity and varied natural history of desmoid-type fibromatosis, evidence-based treatment standards for this disease remain lacking. This study evaluated outcomes in patients with desmoid-type fibromatosis managed at a Canadian institution over two decades. Records of 227 patients with desmoid-type fibromatosis referred from 1990 to 2013 were retrospectively reviewed to investigate management strategies including active surveillance, surgery, radiation therapy, cryoablation, and systemic therapy, including tamoxifen and chemotherapy. Thirty-two per cent of cases were men, median age 40 years, median tumour size 5.4 cm. Initial treatments were surgery (79%), tamoxifen (13%), radiation therapy (5.0%), chemotherapy (1.8%) and cryoablation (1.2%). Active surveillance was used upfront in 26% of cases, most after 2005. At a median follow-up of 77 months, one patient died of disease, 13 died of unrelated causes and the remainder were alive with no evidence of disease (56%), stable/responding disease (33%) or progressive disease (4%). The recurrence rate was 25% after upfront surgery. Response rates and disease control rates were 40% and 76% for active surveillance; 68% and 96% for radiation therapy; 31% and 67% for tamoxifen; and 53% and 80% for chemotherapy. On univariable analysis, factors associated with a higher recurrence after initial surgery were young age (P = 0.012), male gender (P = 0.012) and extremity location (P = 0.005). On multivariable analysis, only young age was significantly associated with recurrence risk (P = 0.010). Active surveillance was associated with spontaneous regression and long-term disease control consistent with other studies. Primary radiation therapy appeared to provide a similar response and disease control compared with systemic treatments and may be a viable option for patients who are not candidates for surgery or active surveillance.


Recent advances in pretreating technology for recycling valuable metals from spent lithium-ion batteries.
In recent years, the amount of spent lithium-ion batteries (LIBs) increase sharply due to the promotion of new energy vehicles and the limited service life. Recycling of spent LIBs has attracted much attention because of the serious environmental pollution and high economic value. Although some established techniques have been presented in spent LIBs recycling process, but most of them focus on cathode material recycling due to its high economic value. Therefore, preparation of high purity cathode material by a proper pretreating technology is an important procedure. In this paper, the technologies used in the pretreating process of spent LIBs are summarized systematically from three main points of discharging procedure, liberation, and separation. The collaborative application of multi-technologies is the key to realize efficient pretreating process, which can lay the foundation for the subsequent metallurgical process. In addition, an alternative pretreating flowchart of spent LIBs is proposed based on the multi-process collaboration. Pretreating procedures in this process are mainly based on the physical property difference, and they include "Discharging-Shredding-Crushing-Sieving-Separation".


Evaluation of a Panel of MicroRNAs that Predicts Fragility Fracture Risk: A Pilot Study.
The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post-transcriptional gene expression. Many studies have already shown that microRNAs are involved in bone homeostasis by modulating osteoblast and osteoclast gene expression. In this pilot study, we investigated the ability of an miRNA panel (namely, the OsteomiR° score) to predict fragility fracture risk in older people. miRNAs were extracted from the sera of 17 persons who developed a fracture within 3 years of collecting the serum and 16 persons who did not experience fractures in the same period. Nineteen miRNAs known to be involved in bone homeostasis were assessed, and 10 miRNAs were employed to calculate the OsteomiR° score. We found a trend towards higher OsteomiR° scores in individuals who experienced fractures compared to control subjects. The most suitable cut-off that maximized sensitivity and specificity was determined by ROC curve analysis, and a positive predictive value of 68% and a sensitivity of 76% were obtained. The OsteomiR° score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR° score predicted more fracture events than the recommended "need-to-treat" thresholds based on FRAX° 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR° score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX°. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR° score.


Relationship between CD4 Regulatory T Cells and Anergy In Vivo.
Selective suppression of effector CD4+ T cell functions is necessary to prevent immune cell-mediated damage to healthy tissues. This appears especially true during pregnancy or in individuals predisposed to autoimmunity. Foxp3+ regulatory T (Treg) cells and induction of anergy, an acquired state of T cell functional unresponsiveness in Foxp3- cells, have both been implicated as mechanisms to suppress dangerous immune responses to tissue-restricted self-Ags. Anergic CD4+ T cells and Treg cells share a number of phenotypic and mechanistic traits-including the expression of CD73 and folate receptor 4, and the epigenetic modification of Treg cell signature genes-and an interesting relationship between these two subsets has recently emerged. In this review, we will compare and contrast these two subsets, as well as explore the role of anergy in the generation of peripheral Treg cells.


Virtual Reality Treatment Displaying the Missing Leg Improves Phantom Limb Pain: A Small Clinical Trial.
Phantom limb pain (PLP) is a common and in some cases debilitating consequence of upper- or lower-limb amputation for which current treatments are inadequate. This small clinical trial tested whether game-like interactions with immersive VR activities can reduce PLP in subjects with transtibial lower-limb amputation. Seven participants attended 5-7 sessions in which they engaged in a visually immersive virtual reality experience that did not require leg movements (Cool! TM), followed by 10-12 sessions of targeted lower-limb VR treatment consisting of custom games requiring leg movement. In the latter condition, they controlled an avatar with 2 intact legs viewed in a head-mounted display (HTC Vive TM). A motion-tracking system mounted on the intact and residual limbs controlled the movements of both virtual extremities independently. All participants except one experienced a reduction of pain immediately after VR sessions, and their pre session pain levels also decreased over the course of the study. At a group level, PLP decreased by 28% after the treatment that did not include leg movements and 39.6% after the games requiring leg motions. Both treatments were successful in reducing PLP. This VR intervention appears to be an efficacious treatment for PLP in subjects with lower-limb amputation.


Bronchial thermoplasty reduces ventilation heterogeneity measured by multiple breath nitrogen washout.
Despite demonstrated symptomatic benefit from bronchial thermoplasty (BT), the underlying pathophysiological benefits have been uncertain. The purpose of the present study was to relate clinical benefit after BT to changes in lung physiology, focusing on ventilation homogeneity assessed using multiple breath nitrogen washout (MBNW), and how this may be affected by changes in airway volume and resistance. Consecutive patients (n = 21) with severe asthma scheduled for BT, were evaluated at baseline, 6 weeks and 6 months after completion of treatment. Assessments included the Asthma Control Questionnaire (ACQ), medication usage, exacerbation frequency, spirometry, plethysmography and MBNW. Eighteen of these patients underwent detailed CT evaluation for the estimation of airway volume at baseline and then after the left lung had received BT treatment but prior to right lung treatment. Data are mean ± STDEV. Patients responded to BT with an improvement in ACQ from 3.4 ± 0.8 at baseline to 2.0 ± 1.1 at 6 months (p < 0.001). Steroid requiring exacerbations fell from 3.1 ± 2.9 in the 6 months prior to BT to 1.4 ± 1.7 following BT (p < 0.001). Significant reductions in maintenance oral steroid dosing and short acting beta agonist use were observed. Airway volume measured by CT scanning significantly increased after treatment. The FEV1 improved from 1.34 ± 0.65 l to 1.52 ± 0.76 l (p = 0.024). The Residual Volume fell from 2.87 ± 0.89 l to 2.71 ± 0.93 l (p = 0.008) and Total Airway Resistance (Raw) from 10.58 ± 6.56 to 7.64 ± 3.74 cmH2O.s.l-1 (p = 0.020). The Lung Clearance Index (LCI) was 187 ± 63% predicted at baseline and improved after treatment from 12.7 ± 3.3 to 11.8 ± 2.4 (p = 0.049). The improvement in LCI correlated with the improvement in Raw (r = 0.463, p = 0.035). Clinical benefit after BT is accompanied by improvements in lung physiology, including normalisation of lung homogeneity that seems to be driven by airway dilation and reduced resistance.


Localization and some properties of skin sulfhydryl oxidase.
Skin sulfhydryl oxidase (SSO) was prepared from cow snout skin. Dithiothreitol was the thiol substrate most efficiently utilized, with 2-mercaptoethanol, glutathione, and cysteine having less than 23% the relative efficiency of dithiothreitol. In the presence of SSO reductively denatured ribonuclease A was reoxidized and reactivated. The degree of reactivation was proportional to the incubation time and dependent on the amount of enzyme added. The oxidation of thiols by SSO required molecular oxygen as an oxidant. The oxygen consumption increased linearly with the increasing concentration of SSO during the increasing formation of disulfide from sulfhydryl groups. The activity of SSO was detected in differing amounts in each of the four layers--stratum corneum, stratum granulosum, stratum spinosum with basal cell layer, and dermis--of cow snout skin, while showing the highest specific activity in the stratum granulosum.


Liposome oligomannose-coated with neoglycolipid, a new candidate for a safe adjuvant for induction of CD8+ cytotoxic T lymphocytes.
The cytotoxic T lymphocyte (CTL) response has recently been shown to play a role in protection against human immunodeficiency virus (HIV) and it is therefore thought that a vaccine against HIV must be able to elicit a CTL response. The development of a safe, effective adjuvant is very important because alum, the only adjuvant available for use in humans at present, can barely induce a response of this type. We demonstrate here that liposomes that contain an immunodominant peptide (15 amino acids) of the envelope glycoprotein gp120 of HIV-1 and that are coated with mannopentaose-dipalmitoylphosphatidylethanolamine conjugate induce a major histocompatibility complex class I-restricted CD8+ CTL response in mice with a single subcutaneous immunization, whereas non-coated liposomes do not. Since no damage to the skin at the injection site was caused by the liposomes, and since the oligomannose-coated liposomes consist of innocuous materials ubiquitously distributed throughout the human body, they may be highly suitable for use as a safe adjuvant in vaccines inducing a CTL response against HIV.


Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium.
Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems.


Phenotype profiling of primary testicular diffuse large B-cell lymphomas.
Primary testicular diffuse large B-cell lymphomas (tDLBCL) are rare neoplasms with few comprehensive studies conducted so far. We aimed to systematically characterize the phenotype of tDLBCL. Forty-five patients from three Swiss hospitals diagnosed with tDLBCL between 1972 and 2009 were reviewed and included in this study. A tissue microarray was assembled, and the protein expression profiles were assessed by immunohistochemistry and fluorescence in situ hybridization for the C-MYC locus. All tDLBCL expressed CD79a, followed by CD20 (98% of cases) and CD19 (93%). One case expressed the germ cell marker OCT4 and showed a rearrangement of C-MYC. Eighty-two per cent of cases showed active STAT signalling by expression of either pSTAT1 or pSTAT3 or both, but not pSTAT5. The p53 was overexpressed in 10% of cases, but p21 staining (∆p21/p53) did not suggest the presence of TP53 mutations. tDLBCL had a median MIB1 labelling index of 40%, and only 6% of cases appeared to have C-MYC rearrangements. Most cases were of the non-germinal centre type (77%), and showed as expected for this cell of origin B-cell lymphoma 2 (BCL2) rearrangements only in 4% and amplifications in 15% of cases, whereas BCL6 was rearranged in 48% of cases. CXCR4 was expressed in 52% of cases, and high CXCR4 expression was of prognostic significance for progression-free survival (p = 0.003). Because 84% of cases expressed nuclear p50, the canonical NF-κB signalling pathway seems to be active. Multimarker phenotyping is important for lineage determination of tDLBCL. Occasionally, tDLBCL can express germ cell markers like OCT4, and they have active STAT signalling mediated through pSTAT1 and pSTAT3 and active canonical NF-κB signalling. tDLBCL are of non-germinal centre/post-germinal centre cell origin and not hyperproliferative. TP53 mutations are unlikely, and C-MYC as well as BCL2 rearrangements are rare, whereas BCL6 is commonly rearranged. CXCR4 might prove to be the first protein-based prognostic marker for tDLBCL, inciting studies in larger cohorts corroborating these findings.


Degree of root resorption after root canal treatment with iodoform-containing filling material in primary molars.
To compare the degree of root resorption in endodontically treated primary molars with that of homologous teeth without root canal treatment. A retrospective study was carried out comprising 105 records of children who had received root canal treatment in a primary molar. Mean age at the time of treatment was 7.0 ± 1.4 years. Inclusion criteria included one endodontically treated primary molar and a homologous primary molar with no root canal treatment on the other side of the mouth. All teeth were treated by the same operator in the same way using the same iodoform-containing root canal filling material. The degree of root resorption was compared by radiographic evaluation 12 or more months posttreatment. The degree of root resorption on the final follow-up radiograph in the endodontically treated primary molars was significantly higher (P < .05) than the degree of root resorption in the homologous teeth. The degree of root resorption was higher in boys than in girls. No statistical significance was found between the degree of root resorption and the age at the time of treatment in either the root canal-treated teeth or the homologous teeth. Follow-up radiographs demonstrated a higher degree of root resorption in the root canal treated teeth than in the homologous teeth, regardless of the type of treatment performed on the homologous side. Root canal treatment performed with iodoform-containing root canal filling material accelerates root resorption in root canal-treated primary molars compared with homologous teeth without endodontic treatment. Clinicians should be aware that endodontically treated teeth will probably shed before homologous ones that are not root canal treated.


Simultaneous determination of three alternative flame retardants (dechlorane plus, 1,2-bis(2,4,6-tribromophenoxy) ethane, and decabromodiphenyl ethane) in soils by gas chromatography-high resolution mass spectrometry.
A gas chromatography-high resolution mass spectrometry (GC-HRMS) method has been developed for the simultaneous determination of three alternative flame retardants, dechlorane plus (DP), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), and decabromodiphenyl ethane (DBDPE) in soils. The soil samples were extracted by accelerated solvent extraction, followed by purification with concentrated sulfuric acid partitioning combined with acid-base silica gel column separation. The gas chromatography featured with a thermostable capillary column of short length and a thin stationary phase was operated in pulse injection mode. A double-focusing magnetic sector high resolution mass spectrometer with electron impact ionization was used for quantification of the analytes. The method detection limits were 0.27-0.33 pg for DPs, 0.41 pg for BTBPE, and 36 pg for DBDPE. The mean recoveries for DPs, BTBPE, and DBDPE in spiked soils were 88-107%, 78-97%, and 74-113%, respectively, with relative standard deviations ranging from 5.2% to 18%. The recoveries of (13)C-labeled standards for DPs, BTBPE, and DBDPE in soil samples were 45-110%, 67-118%, and 27-82%, respectively. These results met the acceptable range of labeled standards for analysis of polybrominated diphenyl ethers as specified by the USEPA 1614 method.


A heptamethine cyanine-based colorimetric and ratiometric fluorescent chemosensor for the selective detection of Ag+ in an aqueous medium.
A highly selective and sensitive ratiometric fluorescent chemosensor for Ag(+) in aqueous solution was developed, in a linear range of 0.6 × 10(-7) to 50 × 10(-7) mol L(-1), based on a A-Ag(+)-A binding mode with a heptamethine cyanine motif containing one adenine moiety.


Amniotic Membrane Grafts to Reduce Pterygium Recurrence.
To demonstrate the long-term outcome of pterygium surgery with adjunctive amniotic membrane transplantation (AMT) and intraoperative mitomycin C (MMC) in a large case series. Medical records were retrieved for this noncomparative retrospective study of all patients who had pterygium excision with adjunctive AMT and intraoperative MMC, from October 2010 to June 2016 with at least 6 months of follow-up. There were a total of 556 eyes of 535 patients (291 males and 244 females) with average age of 51.9 ± 13 years who had pterygium excision (527 primary and 29 recurrent). For an average follow-up period of 17.3 ± 0.8 months (range 6-74 months), corneal recurrence occurred in 20 eyes (3.6%) and conjunctival recurrence in 12 (2.2%) in a total of 32 eyes (5.8%). Eleven eyes (2%) underwent reoperation. Other complications included granuloma (0.5%), diplopia (1.1%), and steroid-induced ocular hypertension (4.3%). Adjunctive use of AMT and short exposure of MMC can reduce recurrence after pterygium surgery. The procedure is less tedious and less time consuming, resulting in early recovery while saving the conjunctiva for future surgeries.


Predicted functional and taxonomic analysis of subgingival biofilm of Grade C periodontitis in young patients under maintenance therapy.
In Grade C periodontitis in young patients (PerioC-Y), the functional roles of the subgingival community after years of periodontal treatment are still underexplored. This study evaluated the taxonomic and predicted functional content of the subgingival microbiome of PerioC-Y patients under supportive periodontal therapy (SPT). Clinical and microbiological data from subgingival biofilm were assessed from 10 PerioC-Y patients at two time points: at baseline and after 5.7 ± 1.3 years of SPT. This was compared with 15 patients without a history of periodontitis. The V1-V3 and V4-V5 regions of the 16S rRNA were sequenced using the Illumina Miseq. Microbial composition was evaluated by the core microbiome, and alpha- and beta-diversity. The microbiome functional content was predicted using Picrust2, and the gene differential abundance was analyzed with DESeq2. Clinical improvements were seen in PerioC-Y-SPT. Differences in β-diversity between PerioC-Y and health were observed (health x PerioC-Y-baseline, P = 0.02; health x PerioC-Y-SPT, P = 0.05). Moreover, although β-diversity did not statistically change between baseline and SPT in PerioC-Y, the microbial correlation evidenced increased Streptococcus and decreased Treponema network contributions during SPT. Based on predicted functional data, treatment induced a reduction in genes related to flagellar protein and signal transduction in PerioC-Y. However, compared with healthy individuals, some genes remained more highly abundant in PerioC-Y-SPT, such as quorum sensing and efflux pump transporters. Despite clinical improvements and a shift in taxonomic composition, the PerioC-Y patients' periodontal treatment was not enough to reach a similar microbiome to patients without disease experience. Some functional content in this biofilm remained altered in PerioC-Y regardless of disease control.


[A new case of associated sarcoidosis and tuberculosis, or the close relationship between 2 granulomatous diseases...].
The case reported here concerns a 30-year old male patient who had both very severe, multivisceral tuberculosis and equally severe sarcoidosis, with repercussions on the respiratory function that required corticosteroid therapy. Prolonged anti-tuberculous therapy and corticosteroids gave favourable results. This case is remindful of an old debate which opposed the two diseases on account of their histological lesions. It offers a new example of the severity of tuberculosis in "immunocompromised" patients, and it raises anew the still unresolved problem of the individuality of sarcoidosis in pulmonary pathology.


Roles of psychiatrists and other professionals in mental healthcare: results of a formal group judgement method among mental health professionals.
Professional boundaries between psychiatrists and other mental health professionals are difficult to set. Empirical evidence for the distribution of diagnostic and treatment tasks among professionals is lacking. This study examines the 'collective sense of the profession' about the relationship between patient characteristics and the contribution of tasks by disciplines. An adapted RAND appropriateness method was used. Eighty-six professionals judged 77 case descriptions of psychiatric patients on the contribution to diagnostic and treatment tasks of eight selected disciplines. In two multi-level models the variance explained by the judges' characteristics was 3.7% for diagnostic tasks and 4.5% for treatment tasks. The variance explained by the patient characteristics was zero for diagnostic and 0.5% for treatment tasks. The variance explained by the indicated disciplines was 36.8% for diagnostic and 12.6% for treatment tasks. The collective sense of the profession on the contribution of psychiatrists to mental healthcare is unambiguous but not related to patient characteristics. It seems to be based on an a priori ranking order of disciplines.


Anatomic Anterior Cruciate Ligament Reconstruction.
Anterior cruciate ligament reconstruction (ACLR) techniques have substantially evolved over the past several decades, driven by evidence that nonanatomic techniques increase the risk for instability, loss of motion, surgical failure, and posttraumatic osteoarthritis. Early techniques used transtibial femoral tunnel drilling, although improved understanding of the anatomy and biomechanics has led to independent femoral tunnel. Anatomic ACLR requires careful consideration of the native ACL dimensions and orientation. Although there is significant variation between patients, understanding of anatomic patterns allows for reliable identification of the ACL footprints and appropriate tunnel positioning, particularly in chronic injuries where the remanent ACL stump is degraded or absent. The femoral tunnel should be placed low and posterior on the lateral femoral condyle using the lateral intercondylar and bifurcate ridges as landmarks. The center of the tibial footprint can be determined by referencing the medial tibial spine and posterior border of anterior horn of lateral meniscus. Measurement of the dimensions of the native ACL and intercondylar notch is also critical for determining graft size and minimizing the risk of impingement, with a goal of reconstructing 50% to 80% of the tibial footprint area. Clinical outcome studies have demonstrated superior anteroposterior and rotatory knee stability with low surgical revision rates (reported between 3% and 5%). By adhering to the principles of anatomic ACLR, surgeons can produce an appropriately sized and located graft for the individual patient, thereby best restoring native knee kinematics and maximizing function. The aim of this infographic is to highlight essential features of anatomic ACLR techniques, which a focus on the native anatomy and surgical planning to achieve an anatomic ACLR.


Inter-joint coordination variability during a sit-to-stand fatiguing protocol.
A repetitive sit-to-stand (STS) task is often used as a fatiguing protocol. Although post-fatigue reductions in muscle strength have been frequently used to indicate fatigue, little is known about changes in body movement during the fatiguing process. This study examined changes in variability of hip-knee and knee-ankle coordination during the STS fatiguing course in 15 young (age: 26.7 ± 5.8 years; 9 females, 6 males) and 15 older adults (age: 69.3 ± 5.7 years; 9 females, 6 males). Participants were asked to perform repetitive STS movements until exhaustion or for 30 min at a self-selected pace. Motion data from 3 consecutive STS cycles were extracted from every minute during the entire fatiguing course and time normalized to STS duration and dummy coded as five stages: 0-20, 20-40, 40-60, 60-80, and 80-100% of the course. Outcome variables were hip-knee and knee-ankle inter-joint coordination variabilities. A 2*5 mixed-effect ANOVA was used to examine changes in variability during different stages of the course in young and older adults. No Age × Time interactions were found in either hip-knee or knee-ankle coordination variability. The hip-knee coordinative variability significantly increased along the STS fatiguing course regardless of age, and the knee-ankle variability from standing to sitting was also higher at the ending, when compared to the beginning, of the fatiguing protocol. The impact of fatigue during repetitive STS protocol is not only limited to a force production decline but also manifested as increased coordinative variability, which could be considered as a fatigue indicator.


Associations of sodium and potassium intake with chronic kidney disease in a prospective cohort study: findings from the Hispanic Community Health Study/Study of Latinos, 2008-2017.
According to dietary recommendations, reduction of sodium intake has potential to reduce Chronic Kidney Disease (CKD) risk; however the role of dietary potassium and the sodium -to- potassium ratio in the development of CKD is unclear. We studied 9778 participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from four US urban communities. Participants were aged 18-74 yrs., free from CKD at baseline in 2008-2011 and re-examined between 2014 and - 2017. Dietary intake of sodium, potassium and the ratio of dietary sodium -to- potassium were measured from two baseline 24-h dietary recalls. Incident CKD was defined as: 1) estimated glomerular filtration rate (eGFR) decline of 1 unit per year and eGFR < 60 ml/min/1.73m2 or 2) albumin to creatinine ratio ≥ 30 mg/g at the follow-up visit. We used multivariable survey weighted Poisson regression to estimate adjusted incident rates of incident CKD. At baseline, mean age was 41 years. Average follow up time was 6.2 years. From fully adjusted Poisson regression analyses, self-reported sodium intake was not associated with incident CKD. However, for each 500 mg decrement in potassium intake, there was an 11% increase risk of incident CKD (IRR = 1.11, 95% CI = 1.00, 1.24). Additionally, every 1 M ratio increment of sodium -to -potassium ratio was associated with a 21% increased risk of incident CKD (IRR = 1.21, 95% CI = 1.02, 1.45), p < 0.05). We conclude that diets low in potassium and high in sodium are associated with increased risk of developing chronic kidney disease among healthy US Hispanic/Latino adults.


Sequential extraction of metals from mixed and digested sludge from aerobic WWTPs sited in the south of Spain.
The content of heavy metals is the major limitation to the application of sewage sludge in soil. However, assessment of the pollution by total metal determination does not reveal the true environmental impact. It is necessary to apply sequential extraction techniques to obtain suitable information about their bioavailability or toxicity. In this paper, sequential extraction of metals from sludge before and after aerobic digestion was applied to sludge from five WWTPs in southern Spain to obtain information about the influence of the digestion treatment in the concentration of the metals. The percentage of each metal as residual, oxidizable, reducible and exchangeable form was calculated. For this purpose, sludge samples were collected from two different points of the plants, namely, sludge from the mixture (primary and secondary sludge) tank (mixed sludge, MS) and the digested-dewatered sludge (final sludge, FS). Heavy metals, Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Ti and Zn, were extracted following the sequential extraction scheme proposed by the Standards, Measurements and Testing Programme of the European Commission and determined by inductively-coupled plasma atomic emission spectrometry. The total concentration of heavy metals in the measured sludge samples did not exceed the limits set out by European legislation and were mainly associated with the two less-available fractions (27-28% as oxidizable metal and 44-50% as residual metal). However, metals as Co (64% in MS and 52% in FS samples), Mn (82% in MS and 79% in FS), Ni (32% in MS and 26% in FS) and Zn (79% in MS and 62% in FS) were present at important percentages as available forms. In addition, results showed a clear increase of the concentration of metals after sludge treatment in the proportion of two less-available fractions (oxidizable and residual metal).


Intranuclear rodlets in woodchuck thyroid follicular cells.
Intranuclear rodlets are seen in thyroid follicular cells of woodchucks fixed during summer and fall. They are not observed in winter and spring animals. A functional significance of these structures is suggested.


Familial Hemophagocytic Lymphohistiocytosis secondary to UNC13D mutation: a report of two cases.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by some clinical signs (e.g., non-remitting fever, hepatosplenomegaly) and laboratory findings (e.g., cytopenia, increased ferritin level, hypofibrinogenemia, lipid disorders, coagulopathy, and multiple organ failure). Depending on the etiology, HLH is divided into familial (i.e., primary) and acquired (i.e., secondary) forms. Familial HLH (FHL), an autosomal recessive condition, is classified into five subtypes based on underlying genetic defects. The PRF1, STX11, UNC13D, HPLH1, and STXBP2 are the most well-known genes of this type which are related to granule-mediated cytotoxic T and Natural killer (NK) cells. The treatment is based on the HLH-2004 protocol. The current report presents two cases of HLH with presentations different from each other and previously reported cases. Case 1 was a 15-month-old boy with fever, skin rash, splenomegaly, and bicytopenia, raised triglyceride levels, AST (aspartate transaminase), and ALT (alanine aminotransferase), normal ferritin, and abundant hemophagocytic cell in bone marrow aspiration. He was diagnosed with HLH and received HLH protocol as treatment. The patient had a homozygous intronic mutation; NM_199242: c.2448-13G > A in UNC13D. The associated disease was Familial Hemophagocytic Lymphohistiocytosis 3 (FHL3). Case 2, a 37-day-old female presented with fever, a history of neonatal cholestasis, and huge hepatosplenomegaly. Her whole-exome sequencing report manifested that the patient had the same mutation as case 1. Unfortunately, both patients passed away. The sequencing of the entire UNC13D gene (coding and non-coding regions) is an applicable and valuable diagnostic procedure for the detection of deep intronic splicing variants and large inversions in patients with atypical manifestations of HLH (such as normal ferritin or triglyceride and cholesterol).


Endovascular Thrombolysis in the Management of Iliofemoral Thrombosis in Children: A Multi-Institutional Experience.
To evaluate technical feasibility, complications, and clinical outcomes of endovascular thrombolysis for iliofemoral thrombosis at two tertiary-care children's hospitals. Institutional review board-approved retrospective review from March 2003 through June 2013 showed that venous thrombolysis for iliofemoral thrombosis was performed in 57 children (64 limbs) with a median age of 16.1 years (mean age, 14.5 y; range, 1.0-17.8 y). Techniques included catheter-directed thrombolysis (CDT), percutaneous mechanical thrombectomy (PMT), and pharmacomechanical catheter-directed thrombolysis (PCDT) with adjunctive angioplasty and/or stent placement. Villalta and modified Villalta scales were applied retrospectively to follow-up data to assess postthrombotic syndrome (PTS). Technical success (≥ 50% thrombolysis) rate was 93.7%: grade III (100%) in 19 limbs, grade II (50%-99%) in 41 limbs, and grade I (< 50%) in four limbs. Techniques included CDT with PCDT (32.8%) or PMT (35.9%), CDT alone (26.6%), PCDT alone (4.7%) or with adjunctive angioplasty (54.7%), and stent placement (6.3%). Mean duration of CDT was 36.5 hours (range, 2.9-89.6 h). There was one major complication (1.8%) of bleeding requiring transfusion. Minor complications (ie, bleeding) occurred in seven patients (12.2%). Median follow-up was 1.5 years (range, 30 d to 7 y). Seven patients underwent repeat thrombolysis for recurrent thrombosis. The PTS rate was 59.3% per modified Villalta scale but only 2.1% per Villalta scale. Endovascular thrombolysis is technically feasible and safe for iliofemoral thrombosis in children. Variable results were seen with two scales to assess PTS, suggesting an acute need for standardization of outcome measurement in children.


Trends and variations of pH and hardness in a typical semi-arid river in a monsoon climate region during 1985-2009.
The rapid growth of urbanization and industrialization, along with dramatic climate change, has strongly influenced hydrochemical characteristics in recent decades in China and thus could cause the variation of pH and general total hardness of a river. To explore such variations and their potential influencing factors in a river of the monsoon climate region, we analyzed a long-term monitoring dataset of pH, SO4 (2-), NOx, general total hardness (GH), Mg(2+), Ca(2+), and Cl(-) in surface water and groundwater in the Luan River basin from 1985 to 2009. The nonparametric Seasonal Kendall trend test was used to test the long-term trends of pH and GH. Relationship between the affecting factors, pH and GH were discussed. Results showed that pH showed a decreasing trend and that GH had an increasing trend in the long-term. Seasonal variation of pH and GH was mainly due to the typical monsoon climate. Results of correlation analysis showed that the unit area usage amounts of chemical fertilizer, NO3 (-), and SO4 (2-) were negatively correlated with pH in groundwater. In addition, mining activity affected GH spatial variation. Acid deposition, drought, and increasing the use of chemical fertilizers would contribute to the acidification trend, and mining activities would affect the spatial variation of GH. Variations of precipitation and runoff in semi-arid monsoon climate areas had significant influences on the pH and GH. Our findings implied that human activities played a critical role in river acidification in the semi-arid monsoon climate region of northern China.


Inversion vs retention of configuration in gas-phase ammonium ion/alcohol reactions.
The potential energy surface for gas-phase reactions of ammonium ion with alcohols was examined by ab initio and DFT methods. Transition structures for inversion (S(N)2) and retention (S(N)F) mechanisms were located for 2-propanol and exo-2-norbornanol. The S(N)F (retention) process was found to be 6-8 kcal/mol higher in energy than the inversion S(N)2 counterpart for the 2-propanol system. The retention process in the 2-exo-norbornanol/ammonium ion system was favored by 1.3 kcal/mol.


Synthesis and expression of laminin during human foetal lung development.
The lung develops by epithelial tubes budding and branching into a flexible mesenchyme. This growth is associated with the remodelling of the epithelial basement membrane, of which laminin is a major component. Both the synthesis and expression of laminin were studied in the human lung between 10 and 31 weeks of gestation, using in situ hybridization and immunohistochemistry. The synthesis of the beta chain was active in the epithelial and surrounding mesenchymal cells. The mRNAs coding for the gamma chain were less abundant and mainly found in the epithelium. The synthesis of these two chains continued throughout gestation, and no significant difference in the density of hybridization grains could be detected between the tips of the expanding buds and the proximal portions. Immunohistochemical localization of laminin showed important modifications of the basement membrane during gestation. In the first part of the pseudoglandular stage the epithelial basement membrane stained continuously for laminin. Later, the basement membrane was labelled in a graded fashion: at the apex of the growing buds the staining became weak with focal disruptions. Both epithelial and mesenchymal synthesis of laminin remained active, while the polypeptide was undetectable using immunohistochemistry. These findings suggest that the remodelling of the basement membrane during human lung morphogenesis is probably not related to a decreasing synthesis of laminin, but to either a proteolytic degradation or the assembly of an inadequate complex undetectable with the polyclonal antibody antilaminin.


The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.
Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.


NR4A3 induces endothelial dysfunction through up-regulation of endothelial 1 expression in adipose tissue-derived stromal cells.
Hypertension is one of the most prevalent diseases worldwide. Increased synthesis of the vasoconstrictor peptide endothelin 1 (encoded by EDN1) might be responsible for high blood pressure. The present study further confirmed the abnormal EDN1 upregulation within adipose tissue-derived stromal cells (ADSCs) derived from morbidly obese subjects. The overexpression of EDN1 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by human umbilical vein endothelial cell (HUVEC). Transcription factor NR4A3 was positively correlated with EDN1, binding to EDN1 promoter region to upregulate EDN1 expression. Similarly, the overexpression of NR4A3 in ADSCs derived from non-obese subjects significantly promoted the proliferation and migration of HUVECs and tube formation by HUVECs, as well as EDN1 protein levels in ADSCs. However, the effects of NR4A3 overexpression on EDN1 protein levels in ADSCs and the proliferation and migration of HUVECs and tube formation by HUVECs were significantly reversed by EDN1 silencing in ADSCs. In conclusion, NR4A3 is abnormally upregulated in ADSCs derived from morbidly obese subjects; NR4A3 could promote HUVEC angiogenesis through binding to EDN1 promoter and upregulating EDN1 expression.


Transitions in histone variants during sea urchin spermatogenesis.
Transitions in the histone complement of nuclei during sea urchin spermatogenesis were investigated by two-dimensional gel electrophoresis. Nuclei were isolated from male gonads of individuals differing in degree of maturity. Unlike protamines, the sea urchin sperm-specific histone variants Sp H1 and Sp H2B appear early in spermatogenesis, well before spermatid differentiation, as the predominant representatives of their classes. Both proteins are phosphorylated from their first appearance until the last steps of spermiogenesis, when the highly condensed late spermatid nuclei become spermatozoan nuclei. Phosphorylation of serine occurs mostly (Sp H1) or entirely (Sp H2B) on the N-terminal portions of these molecules. We conclude that phosphorylated sperm-specific histone variants in the sea urchin function in spermatocytes during meiosis and are the major histones present during replication and transcription in some spermatogonia as well. We propose that the dephosphorylation of Sp H1 and Sp H2B in late spermatids is not primarily responsible for spermatid chromatin condensation but instead may act to stabilize the chromatin of the spermatozoon or aid in the final shaping of the sperm nucleus.


Additively manufactured flexible on-package phased array antennas for 5G/mmWave wearable and conformal digital twin and massive MIMO applications.
This paper thoroughly investigates material characterization, reliability evaluation, fabrication, and assembly processes of additively manufactured flexible packaging and reconfigurable on-package antenna arrays for next-generation 5G/mmWave wearable and conformal applications. The objective is to bridge the technology gap in current Flexible Hybrid Electronics (FHE) designs at mmWave frequencies and address the challenges of establishing future design standards for additively manufactured flexible packages and System-on-Package (SoP) integrated modules. Multiple 3D printed flexible materials have been characterized for their electrical and mechanical properties over the 5G/mmW frequency band (26-40 GHz), and the inkjet printed interconnects on 3D printed Polypropylene (PP) substrates demonstrated excellent electrical and mechanical performance during a 10,000-time cyclic bending test over typical wearable flexible radii down to 1 inch. A proof-of-concept flexible on-package phased array with an integrated microfluidic cooling channel on 3D printed substrates was fabricated and measured, demonstrating [Formula: see text] beam steering capability with efficient cooling. The proposed reconfigurable design and low-temperature fabrication approach using additive manufacturing can be widely applied to next-generation highly-complex on-demand FHE, flexible multi-chip-module integration, and on-package phased-array modules for 5G/mmWave wearable and conformal smart skin, digital twin and massive MIMO applications.


Case report of testicular failure and azoospermia after antegrade embolization of varicocele: A rare complication.
Varicocele is a common condition affecting males of reproductive age and accounting for the most frequent cause of secondary infertility in males. A young male presented with second infertility and bilateral varicoceles and underwent antegrade angioembolization. He developed testicular ischemia and testicular failure with new onset hypogonadism and cryptozoospermia. Antegrade embolization is a valid option in patients with varicoceles but has its own unique risks of complications.


Immune checkpoint blockade in the treatment of malignant tumor: current statue and future strategies.
After being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves non-stop activation of the PD-1 pathway in the tumor microenvironment. PD-1/PD-L1 inhibitors can block the combination of PD-1 and PD-L1, inhibit hostile to regulatory signals, and restore the activity of T cells, thereby bettering immune response. The current researchers assume that the efficacy of these drugs is related to PD-L1 expression in tumor tissue, tumor mutation burden (TMB), and other emerging biomarkers. Although malignant tumors can benefit from the immunotherapy of PD-1/PD-L1 inhibitors, formulating a customized medication model and discovering biomarkers that can predict efficacy are the new trend in the new era of malignant tumor immunotherapy. This review summarizes the mechanism of action of PD-1/PD-L1 inhibitors, their clinical outcomes on various malignant tumors, their efficacy biomarkers, as well as predictive markers of irAEs.


Hospital surgical volume and perioperative mortality of pelvic exenteration for gynecologic malignancies.
To examine the association between hospital surgical volume and perioperative mortality of pelvic exenteration performed for gynecologic malignancies. A population-based retrospective study utilizing the Nationwide Inpatient Sample was conducted to examine pelvic exenteration for gynecologic malignancies from 2001 to 2011. Annualized hospital surgical volume was defined as the average number of procedures a hospital performed per year in which at least one case was performed, and this was correlated to perioperative mortality. A total 1912 exenterations performed at 181 centers were included. Nearly two thirds of exenteration-performing centers had a minimum surgical volume of one case per year (121 centers, 66.9%). Perioperative mortality rate was 1.8%. In multivariable analysis surgical volume remained an independent factor for perioperative mortality (adjusted-odds ratio 0.21; 95% confidence interval, 0.09-0.49; P < .001). Perioperative mortality rates were 3.7% for the centers with minimum surgical volume (1 exenteration a year), 1.4% for the centers performing more than one but two or less exenterations a year, and 0% for the top decile centers (>2 exenterations a year), respectively (P < .001). Pelvic exenteration for gynecologic malignancy is a rare surgical procedure with most hospitals performing few cases annually. A higher surgical volume of pelvic exenteration was associated with lower perioperative mortality.


The synthesis and evaluation of cyclic ureas as HIV protease inhibitors: modifications of the P1/P1' residues.
Two series of cyclic ureas modified at the P1/P1' residue were prepared and evaluated for HIV protease inhibition and whole cell antiviral activity. Compounds 8b, 10 (3- and 4-pyridylmethyl analogs) and 6b (4-methoxy analog) showed significant improvement in antiviral activity relative to lead compounds DMP323 and DMP 450.


Atmospheric deposition levels of chosen elements in the Czech Republic determined in the framework of the International Bryomonitoring Program 1995.
In order to determine the atmospheric loads of 13 elements (Al, As, Cd, Co, Cr, Cu, Fe, Mo, Ni, Pb, S, V, Zn), samples of Pleurozium schreberi (81.1%), Hypnum cupressiforme (11.2%) and Pseudoscleropodium purum (7.7%) bryophytes (mosses) were taken and analysed from an approx. 20 x 20-km grid extending over the entire territory (78,864 km2) of the Czech Republic (abbreviated 'the CZ' in this study). The level of the elements found in the bryophytes reflects the relative atmospheric deposition loads of the elements at the investigated sites. Five hot spots indicating relatively high deposition levels were identified in the CZ. The marginal hot spots are the following: the CZ part of the so-called Black Triangle I territory in northwestern CZ; the CZ part of the Black Triangle II territory in northeastern CZ; and the CZ part of the Sudeten mountains (Jizerské Mts and Giant Mts) and their foothills in northern CZ. Inland hot spots were found in the southwestern industrial part of central Bohemia and in the southern Moravian industrial district. The average element contents in CZ bryophytes were comparable with the respective average values obtained in Germany and Poland. However, the CZ average bryophyte values were higher and lower in comparison to the average Austrian and Slovak values, respectively. The CZ average relative atmospheric deposition loads of the elements were found to be 2-3 times higher than the respective loads in the cleanest parts of Europe (e.g. clean parts of Nordic countries). A comparison of the analytical results obtained repeatedly at 20 identical localities in the CZ showed a significant decrease in the relative deposition loads of all of the investigated elements in 1995 as compared to 1991. This decrease has been caused by the dramatic restriction of the industrial production, mainly that of the metallurgical and chemical industries, in the CZ. Desulphurisation programs and the effective trapping of flying dust particles in CZ power plants has also had a positive influence on the deposition climate in the CZ. The average values for the absolute atmospheric deposition of the investigated elements in the CZ in 1994-1995 as found from bryomonitoring are presented in this paper.


A collection of idioms for modeling activity level evaluations in forensic science.
This paper presents a collection of idioms that is useful for modeling activity level evaluations in forensic science using Bayesian networks. The idioms are categorized into five groups: cause-consequence idioms, narrative idioms, synthesis idioms, hypothesis-conditioning idioms, and evidence-conditioning idioms. Each category represents a specific modeling objective. Furthermore, we support the use of an idiom-based approach and emphasize the relevance of our collection by combining several of the presented idioms to create a more comprehensive template model. This model can be used in cases involving transfer evidence and disputes over the actor and/or activity. Additionally, we cite literature that employs idioms in template models or case-specific models, providing the reader with examples of their use in forensic casework.


Facial perception of infants with cleft lip and palate with/without the NAM appliance.
This study aimed to assess adults' subjective perception of infants with a unilateral cleft lip and palate (UCLP) with and without a nasoalveolar molding (NAM) appliance compared to those of controls concerning (1) adult gaze patterns and (2) emotional valence. This interdisciplinary study was performed by (1) the Department of Orthodontics and (2) the Department for Psychiatry and Psychotherapy, University Medical Center Goettingen, using eye tracking and a 10-point Likert scale questionnaire. Eye movements and valence rating of 30 unaffected adults (15 women, 15 men; mean age: 25.5 years, standard deviation [SD] = 7.5) were recorded while presenting them infants in three picture categories (1) infant with UCLP, (2) infant with UCLP and inserted NAM appliance and (3) infant without UCLP. Total fixation time in two main areas of interest (AOI upper/lower face) was measured according to picture category as well as participants' valence rating regarding infants' appearance. In pictures of infants with UCLP or UCLP and NAM appliance participants had longer fixation times on AOI lower face compared to reconstructed pictures of infants without UCLP. No significant effect of a NAM appliance on gaze patterns could be detected. The valence of pictures of infants with UCLP was rated more negative compared to pictures of unaffected infants. An inserted NAM appliance improved this rating. The results bolster the assumption that facial disruptions like UCLP alter adults' perception of infants. Even though the NAM appliance is not able to re-establish usual adult gaze patterns, it can help to improve adults' emotional assessment.


Genetic analyses of the in vivo function of LolA, a periplasmic chaperone involved in the outer membrane localization of Escherichia coli lipoproteins.
The major outer membrane lipoprotein (Lpp) of Escherichia coli is released from the cytoplasmic membrane into the periplasm as a complex with LolA, a periplasmic chaperone, prior to the localization in the outer membrane. To determine whether or not LolA is generally involved in the outer membrane localization of lipoproteins in vivo, the chromosomal lolA gene was manipulated so as to be controlled by the lac promoter-operator. Depletion of LolA caused a severe growth defect, and impaired the outer membrane localization of Lpp and Pal, another outer membrane lipoprotein. Although LolA depletion did not immediately arrest the growth of cells lacking Lpp, disruption of the chromosomal lolA gene was lethal to the lpp strain, indicating that LolA is generally required for the outer membrane localization of lipoproteins, and therefore essential irrespective of the presence or absence of Lpp.


Invited Discussion on: "Complications and Disasters After Minimal Invasive Tissue Augmentation with Different Types of Fillers: A Retrospective Analysis".
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Symptomatic myoma treated with laparoscopic uterine vessel occlusion and subsequent immediate myomectomy: which is the optimal surgical approach?
To determine the optimal surgical approach when patients are treated with laparoscopic uterine vessel occlusion (LUVO) combined with myomectomy in the management of women with symptomatic uterine fibroids. An observational study. Medical centers. One hundred thirty-one patients with symptomatic myomas underwent LUVO plus laparoscopic myomectomy (LM; LUVO+LM) (n = 49) or LUVO plus ultra-mini laparotomy UMLT-M (LUVO+UMLT-M) (n = 82). Myomectomy through laparoscopy or UMLT access. The outcome was measured by comparing surgical techniques, and 3-year follow-up, including symptom control and reintervention (hysterectomy or myomectomy), in both groups. General characteristics of the patients were similar in both groups, except the number of myomas. Surgical techniques seemed to be easier in the LUVO+UMLT-M group than in LUVO+LM group, because of less operation time (56.1 +/- 16.9 minutes vs. 73.4 +/- 26.9 minutes; P=.009) and a higher success rate (100% vs. 91.8%; P=.018). There were no differences in the 3-year follow-up of the therapeutic outcomes of the LUVO+UMLT-M and LUVO+LM groups, with low reintervention rates (1.2% vs. 0) and good symptom control rates in both groups. The LUVO+LM, either through laparoscopy or UMLT, was acceptable in the management of symptomatic uterine fibroids. However, the LUVO+UMLT-M technique might be more feasible, as it required less operative time and had a higher success rate.


Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements.
Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p<0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.


Analysis of systematic effects on congenital sensorineural deafness in German Dalmatian dogs.
We have analysed the systematic influences, phenotypic colour markers and the additive genetic variation for congenital sensorineural deafness (CSD) in German Dalmatian dogs in order to help elucidate the importance of phenotypic breed characteristics for genetic differences of CSD. Linear animal models using restricted maximum likelihood methods were employed to estimate variance components. Data were obtained from all three German Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was recorded by standardized protocols for brainstem auditory-evoked response (BAER). The material included 1899 German Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The animal model regarded the fixed effects of sex, coat colour, eye colour, presence of patches, litter size, percentage of examined puppies per litter, kennel club, and inbreeding coefficient. The common environment of the litter and kennel as well as the additive genetic effect of the animal were taken into account as randomly distributed effects. The fixed effects of eye colour, percentage of puppies examined per litter and kennel club were significant in the mixed model analysis. A significant proportion of additive genetic variation could be shown despite corrections for phenotypic colour variants. The heritability estimate for CSD in German Dalmatian dogs was h(2)=0.27+/-0.07. The additive genetic correlation of CSD with presence of blue eyes was r(g)=0.53+/-0.41 and with presence of patches r(g)=-0.36+/-0.24. We concluded that additional genes other than those associated with phenotypic colour markers in German Dalmatian dogs significantly contribute to the occurrence of CSD.


Juvenile rheumatoid arthritis with myelofibrosis with myeloid metaplasia.
Myelofibrosis with myeloid metaplasia is defined as a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extramedullary hematopoesis and varying degree of myelofibrosis. It may be idiopathic or secondary to a large number of conditions. Here is a rare case of myelofibrosis occurring in a patient with juvenile rheumatoid arthritis.


In vitro cytotoxicity in adult Xenopus generated against larval targets and minor histocompatibility antigens.
Our experiments reveal that application of several minor H antigen-disparate skin grafts to adult Xenopus over an 18-month period can lead to in vitro generation of CML reactivity toward these minor antigens. Furthermore, we demonstrate that, following MHC-disparate skin graft rejection, adult effectors can efficiently kill both adult and larval donor-strain targets; this killing is MHC-specific and requires MLC restimulation with cells syngeneic to the skin graft donor. The ability to kill larval lymphoblasts, which have been shown elsewhere to be MHC class I-negative but class II-positive, suggests the probable importance of class II-restricted killing in this species.


Display of Oligo-α-1,6-Glycosidase from Exiguobacterium sibiricum on the Surface of Escherichia coli Cells.
Cell-surface display using anchor motifs of outer membrane proteins allows exposure of target peptides and proteins on the surface of microbial cells. Previously, we obtained and characterized highly catalytically active recombinant oligo-α-1,6-glycosidase from the psychrotrophic bacterium Exiguobacterium sibiricum (EsOgl). It was also shown that the autotransporter AT877 from Psychrobacter cryohalolentis and its deletion variants efficiently displayed type III fibronectin (10Fn3) domain 10 on the surface of Escherichia coli cells. The aim of the work was to obtain an AT877-based system for displaying EsOgl on the surface of bacterial cells. The genes for the hybrid autotransporter EsOgl877 and its deletion mutants EsOgl877Δ239 and EsOgl877Δ310 were constructed, and the enzymatic activity of EsOgl877 was investigated. Cells expressing this protein retained ~90% of the enzyme maximum activity within a temperature range of 15-35°C. The activity of cells expressing EsOgl877Δ239 and EsOgl877Δ310 was 2.7 and 2.4 times higher, respectively, than of the cells expressing the full-size AT. Treatment of cells expressing EsOgl877 deletion variants with proteinase K showed that the passenger domain localized to the cell surface. These results can be used for further optimization of display systems expressing oligo-α-1,6-glycosidase and other heterologous proteins on the surface of E. coli cells.


Sensory substance P-innervation of the urinary bladder: possible site of action of capsaicin in causing urine retention in rats.
In rats treated neonatally with capsaicin there is, in later life, a tendency tendency towards urine retention. Since capsaicin is known to cause irreversible loss of certain primary sensory neurons, notably those containing substance P, we have studied the sensory innervation of the bladder in capsaicin-treated and control rats using retrograde tracing methods and immunohistochemistry; in addition, the motor function of the bladder was assessed in in vitro experiments, using electrical field stimulation. Five days after injection of the fluorescent tracer True Blue into the wall of the bladder, numerous labelled cells were identified in dorsal root ganglia T13, L1, L2, L6, and S1 and smaller numbers of cells were found in T12 and L3. In capsaicin-treated rats the numbers of labelled cells were reduced by over 50% in L1, L6 and S1. In control rats, 10-16% of True Blue labelled cells also contained substance P as demonstrated by indirect immunofluorescence, but in capsaicin-treated rats substance P cells were virtually absent. In in vitro studies, contractions of the detrusor muscle to electrical field stimulation, both before and after atropine, were similar in control and capsaicin-treated rats. We suggest that capsaicin causes urine retention in rats due to an impairment of sensory transmission from the bladder (that could involve substance P) and a consequent failure in the normal micturition reflexes.


Poly (lactic-co-glycolic acid) nanospheres allow for high l-asparaginase encapsulation yield and activity.
l-Asparaginase (ASNase) is an amidohydrolase used as a chemotherapeutic agent for the treatment of acute lymphoblastic leukemia (ALL). The nanoencapsulation of this enzyme is strategic to avoid its immediate immunogenic effects that lead to a decrease in the enzyme half-life. In this work, ASNase-containing nanoparticles (NPs) were prepared by double emulsification, through an ultrasonic sonicator or an Ultra-Turrax, using two copolymers of 50:50 (w/w) poly (lactic-co-glycolic acid) (PLGA) with different ranges of molecular weight (24-38 kDa and 30-60 kDa) and varying the concentration of polyvinyl alcohol (PVA) as a stabilizer (0.5, 1.0, 1.5 and 2.0%) as well as the emulsification time (30 and 60 s). Using 24-38 kDa PLGA and 1.0% PVA, we obtained by cavitation NPs with hydrodynamic diameter of 384 nm, polydispersity index of 0.143 and Zeta potential of -16.4 mV, whose ASNase encapsulation efficiency was as high as 87 ± 2%. The encapsulated enzyme showed an activity 22% higher than that of the free enzyme, and no conformational changes were detected by circular dichroism. The enzyme release from NPs entrapped in dialysis bags (500 kDa molecular weight cut-off) allowed selecting a controlled system able to release about 60% of the enzyme within 14 days, for which the Korsmeyer-Peppas model provided the best correlation (R2 = 0.966).


Cultivation of mammalian cells in heat-sealable pouches that are permeable to carbon dioxide.
Petri plates, 96-well plates, and other unsealed culture vessels are the chief cause of air-borne contamination of cell cultures. In this study, heat-sealable plastic pouches that are permeable to CO2 and other gases are used as a means to avoid contamination. Several applications of heat-sealable pouches are described. First, petri plates can simply be sealed in a wide variety of plastic films that are permeable to CO2. Second, a few CO2-permeable plastic films can be used directly as substrata for mammalian cell growth and can also be cut with a simple hole punch for the isolation of clones. Third, one can grow cells in chemically sterilized carbonic acid solutions and thereby avoid the use of a CO2 incubator entirely.


Burden of cardiovascular disease in Japanese cancer patients and survivors: a single cancer-center study in Niigata City.
Cardiovascular disease (CVD) and cancer are major causes of death in Japan. As most CVDs are chronic and often aggravate, long-term follow-up is necessary. Although some cancer patients and survivors have CVD, its prognostic significance and prevalence are unknown. Therefore, we conducted a retrospective study at our center to determine the prevalence of cancer patients with CVD. In 2015, our 10-year (2005-2014) cancer registry was summarized. Comorbidities including left ventricular dysfunction, atrial fibrillation (AF), ischemic heart disease, aortic stenosis, venous thromboembolism (VTE), and elevation of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were examined. In total, 26,235 de novo cancer patients were registered and 16,130 survived until January 1, 2015. The 5-year survival rate was 64.0% for all cancer patients and 44.2% for cancer patients with CVD. Cox proportional hazards analysis adjusting for age, cancer stage, and body mass index revealed that AF [hazard ratio (HR) 1.219, male; P = 0.038], VTE (HR 1.517, male; P = 0.003 and HR 2.089, female; P < 0.001), and NT-proBNP elevation (HR 1.861, female; P = 0.002) were significantly associated with death. The CVD prevalence among cancer survivors in 2015 was 8.7% vs 3.5% for males vs females. AF was the most common CVD (prevalence: male, 4.0%; female, 1.0%). The prevalence of most CVD in adults increased progressively with age, with male predominance (12.1% for male and 7.5% for female patients in the 80 s age group). One in 10 elderly cancer survivors has serious CVD. AF, VTE, and heart failure were critical comorbidities. Cardiologists and cancer-care providers should recognize CVD presence and monitor patients closely, providing medications or interventions concurrently with cancer therapy.


Desegregation and the retreat of clinical psychoanalysis.
This article examines the racial politics that reshaped psychoanalytic psychotherapy and ushered in a community mental health paradigm during the U.S. Civil Rights Era. Policymakers in the 1960s adopted the language of social justice to condemn psychoanalysis for its inability to treat psychotics and its unwillingness to treat black patients; yet the community psychiatry model of treatment that replaced it compounded the denial of the black subject's clinical needs. Challenging the extant historiography that appraises psychoanalysis as a victim of neoliberalism and psychopharmacology, this paper examines how and why Freudian practitioners beat their own retreat from the specter of desegregation.


Differences in the fertility of donor insemination recipients--a study to provide prognostic guidelines as to its success and outcome.
Data on 207 couples attending for donor insemination (DI) were analyzed to determine the differences in fertility of insemination recipients and to provide prognostic guidelines as to its success. This study has shown that DI recipients with no infertility factors whose partners were azoospermic had the highest fecundability (0.178), whereas those with no infertility factors whose partners were subfertile had the lowest fecundability (0.036). Donor insemination recipients with treated endometriosis and ovulatory dysfunction have significantly higher fecundability (0.093 and 0.091, respectively) than those with other infertility factors (0.021) such as fibroids, tubal disease, or a combination of infertility factors. This study provides prognostic guidelines for DI recipients as to its success.


Prognostic value of beta-thromboglobulin in patients with transient cerebral ischaemia.
Plasma levels of beta-thromboglobulin (BTG) and fibrinopeptide A (FPA), markers of platelet alpha-granule release and thrombin generation respectively, were measured in 27 subjects with transient cerebral ischaemic attacks (TIA), 43 age-matched controls, and 32 young controls. BTG and FPA were both higher in elderly controls than in young controls. BTG was higher in TIA subjects than in age-matched controls and higher in the 12 TIA subjects who had further vascular events in the next year than in those who had no further events. FPA was not significantly associated with TIA or with further events. These results support a relationship between platelet activation and TIA and suggest that BTG levels indicate a group at higher risk of further vascular events.


Synthesis of magnetic activated carbon/α-Fe2O3 nanocomposite and its application in the removal of acid yellow 17 dye from water.
The adsorption of acid yellow 17 dye on activated carbon/α-Fe2O3 nanocomposite prepared by simple pyrolytic method using iron(II) gluconate was investigated by batch technique. The composite was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The size of iron oxide nanoparticles formed from iron(II) gluconate precursor is in the range 5-17nm. The saturation magnetization (Ms), remanence (Mr) and coercivity (Hc) of the magnetic carbon nanocomposite is 5.6emu/g, 1.14emu/g and 448Oe, respectively. The adsorption data are found to fit well with Langmuir and, fairly well with Freundlich and Tempkin isotherms at higher concentration of dye (40-100mg/L). Kinetics data indicate that the adsorption of dye follows pseudo-second order kinetics model.


[Priority of prescribed medication in patients with heart failure in an Internal Medicine Department].
Prescriptions provided to elderly patients with comorbidity on hospital discharge are usually complex. This study has aimed to know what proportion of drugs is considered essential by the prescribing doctors and the existing agreement on this qualification. Cross-sectional study. general acute care hospital. random sample of 60 hospital discharges in patients hospitalized due to heart failure between 2004 to 2006 with 540 prescribed drugs. independent review by two internal medicine specialists and qualification of each of prescribed drugs as essential, advisable or not indicated. Calculation of the proportion of prescriptions according to priority, global and by therapeutic groups, and of the agreement between reviewers. An average of 9 drugs (statistical deviation [SD] 2.4) and 13.5 daily takings (SD 4.6) by patient were prescribed on hospital discharge. The reviewers considered 68.4% of the prescriptions essential (95% confidence interval [CI], 65.5-71.2), advisable 25% (95% CI, 22.4-27.6) and not indicated 6.6% (95% CI, 5.1-8.1). An inverse relation between number of prescribed drugs and their proportion considered as essential was observed. Global agreement between reviewers in the classification of priority was relatively low: weighed Kappa 0.27 (95% CI, 0.19-0.36). More than 90% of the prescriptions were considered as essential in only 6 of the 15 therapeutic groups prescribed most, and good agreements in the qualification of their priority was only reached in 3 groups. A considerable proportion of the prescribed medication on hospital discharge in patients with heart failure was not considered essential. Agreement reached between the reviewers in this qualification was low.


Electronic spectra and photophysics of the α-carboline (1-azacarbazole) monomer.
The UV-vis electronic absorption and emission spectra of α-carboline or 1-azacarbazole, 9H-pyrido[2,3-b]indole, AC, have been investigated in aprotic solvents. Radiative, k(r), non-radiative, k(nr), rate constants and natural lifetimes, τ(N), of the AC monomer in hexane and acetonitrile, obtained from the experimentally determined fluorescence quantum yields and fluorescence lifetimes, have been compared with those theoretically estimated. The closeness between these experimental and theoretical data, the small Stokes shifts, the mirror image relationship between the absorption and fluorescence spectra and the close correspondence between the absorption and fluorescence excitation spectra, provide good evidences that the emission of AC monomer occurs directly from its lowest singlet excited state. The mono- and multi-parametric analyses of the AC solvatochromism indicate that the polarity-polarizability, the hydrogen bond donor and the hydrogen bond acceptor properties of the solvent preferentially stabilize the singlet excited over the ground state. These analyses also reveal that photoexcitation reinforces the hydrogen bond donor and acceptor properties of the AC, becoming the pyridinic nitrogen atom more basic and the pyrrolic group more acid.


Genetic determinants of lipid-lowering response to atorvastatin therapy in an Indian population.
Statins form the backbone of lipid-lowering therapy for the prevention of cardiovascular disease. However, there is large interindividual variability in clinical response to statin treatment. Several gene variants that can be aligned to either the pharmacokinetics or pharmacodynamics of statin have been proposed as potentially important determinants of statin response. We aimed to study the association of known variations in SLCO1B1, CYP3A4, ABCB1, CYP3A5, ABCG5 and CYP7A1 genes with lipid levels in response to atorvastatin therapy. Genotypes were determined using multiplex allele-specific polymerase chain reaction in 177 Indian patients, treated with 10 mg of atorvastatin for 8 weeks. Low-density lipoprotein-cholesterol (LDL-C) levels were recorded at baseline and after 8 weeks of atorvastatin treatment. A total of 177 hypercholesterolaemic patients were genotyped to study genetic determinants of atorvastatin response. The genotype distribution for all polymorphisms investigated was in Hardy-Weinberg equilibrium. In our study, patients with wild-type genotypes of CYP7A1 (rs3808607), CYP3A4 (rs2740574), SLCO1B1 (rs2306283) and variant allele-carrying genotype of ABCB1 (rs2032582, rs1045642) showed significantly greater LDL-cholesterol reductions in response to atorvastatin therapy. The variable response to atorvastatin therapy in terms of LDL-cholesterol lowering due to genetic variations in CYP7A1, CYP3A4, SLCO1B1 and ABCB1 is a promising finding. Further validation in large Indian cohorts is required before it can be assessed for clinical utility.


A cross-sectional analysis of Zika virus infection in symptomatic and asymptomatic non-pregnant travellers: Experience of a European reference center during the outbreak in the Americas.
Zika virus (ZIKV) infection a concern to travellers because of potential sexual transmission and adverse pregnancy outcomes. To describe our experience in diagnosing ZIKV in travellers returning from endemic territories. Travellers were evaluated for ZIKV at our clinic in a 12-month period during the outbreak, using ZIKV-specific RT-PCR and anti-ZIKV Immunoglobulin M/G ELISA when symptomatic, and ELISA only for asymptomatic travellers, preferably from 20 days after the last exposure. All positive ELISA results were subject to confirmation by Virus Neutralization Testing. We estimated post-test probabilities of ZIKV in asymptomatic travellers. Of 462 travellers, 227 reported symptoms and 235 did not. Asymptomatic travellers had similar baseline characteristics, but were younger (median age 31 vs. 33 years, p = 0.01) and had reproductive concerns more often (75.8% vs. 24.2%). ZIKV infection was confirmed in 49 cases: 46/227 (20.3%) were symptomatic and 3/235 (1.3%) asymptomatic. Rash (positive likelihood ratio (LRP) 5.6) and conjunctivitis (LRP 10.8) predicted ZIKV infection. The post-test probability of a negative ELISA-result at 20-25 days was below 0.1%. ZIKV infection was frequent in symptomatic, but not in asymptomatic travellers. We consider negative ELISA results at 20-25 days after exposure a safe strategy to rule out ZIKV infection. Testing for ZIKV-specific antibodies within this timeframe could be particularly valuable in the management of returning travellers who wish to conceive.