Low-level laser therapy modulates demyelination in mice.
There are no effective therapies for remyelination. Low-level laser therapy (LLLT) has been found advantageous in neurogenesis promotion, cell death prevention, and modulation of inflammation in central and peripheral nervous system models. The purpose of this study was to analyse LLLT effects on cuprizone-induced demyelination. Mice were randomly distributed into three groups: Control Laser (CTL), Cuprizone (CPZ), and Cuprizone Laser (CPZL). Mice from CPZ and CPZL groups were exposed to a 0.2% cuprizone oral diet for four complete weeks. Six sessions of transcranial laser irradiation were applied on three consecutive days, during the third and fourth weeks, with parameters of 36 J/cm2, 50 mW, 0.028 cm2 spot area, continuous wave, 1 J, 20 s, 1.78 W/cm2 in a single point equidistant between the eyes and ears of CTL and CPZL mice. Motor coordination was assessed by the rotarod test. Twenty-four hours after the last laser session, all animals were euthanized, and brains were extracted. Serum was obtained for lactate dehydrogenase toxicity testing. Histomorphological analyses consisted of Luxol Fast Blue staining and immunohistochemistry. The results showed that laser-treated animals presented motor performance improvement, attenuation of demyelination, increased number of oligodendrocyte precursor cells, modulated microglial and astrocytes activation, and a milder toxicity by cuprizone. Although further studies are required, it is suggested that LLLT represents a feasible therapy for demyelinating diseases.


Polyphenols in Eucalyptus leaves improved the egg and meat qualities and protected against ethanol-induced oxidative damage in laying hens.
Polyphenols in Eucalyptus leaves (PE) were value resources due to various pharmacological activities, but data on the effect on laying hens are very scare. This study was conducted to determine the effect of PE on the laying performance, egg traits, meat quality, antioxidant status and liver tissues of laying hens. One hundred and twenty 256-day-old Yueqinhuang laying hens were randomly assigned to four treatment groups (different levels of PE at 0, 0.5, 0.8 and 1.2 g/kg diet) for 63 days with 15 replicates per group. Addition of 0.8 g/kg PE not only improved the egg trait by increasing the eggshell thickness and decreasing MDA production and cholesterol content in the egg yolk, but also significantly enhanced meat quality of hens, as suggested by the increase pH45 min (p < .01) and a* value, and decrease drip loss rate (p < .01). Meanwhile, under acute ethanol-induced oxidative damage condition, supplementation of 0.8 g/kg PE enhanced the serum antioxidant status by increasing enzymatic activities (GSH-PX, T-SOD, T-AOC), inhibited oxidative damage and provided protective effect to liver tissue. In conclusion, addition of 0.8 g/kg PE not only improved the egg traits and meat quality without obvious adverse effects, but also increased the serum antioxidant status of the hens and protected their liver tissue from ethanol-induced oxidative damage. This study indicated that PE could be utilized as an effective feed additive for laying hens to improve health performance and egg traits.


Impact of high fat/high salt diet on myocardial oxidative stress.
High fat high salt diet contributes to oxidative stress and cardiac diseases. To determine the impact of moderately high fat diet (HFD), high salt (HS) or their combination on blood pressure (Bp) and myocardial oxidants/antioxidants. Sprague Dawley rats were assigned into four groups; conventional diet (control, 5% fat, 0.5% NaCl), HFD (25% fat, 0.5% NaCl), HS (5% fat, 8% NaCl), or combined diet (HFD+HS) for 10 weeks. Bp and cardiac oxidants and antioxidants were measured. HFD, HS, and their combination didn't cause obesity or dyslipidemia. Both HS and combined diets resulted in an increase in the heart/body weight ratio accompanied by an increase in Bp. No changes were observed in levels of the glutathione (GSH) system or superoxide dismutase (SOD) activities. However, a significant decrease in TBARS levels was observed in the HFD and the combined diet with a parallel increase in catalase activity in all groups. Relative to HFD, the combined diet was associated with increases in GSH reductase/peroxidase and SOD activities. The lack of changes in the GSH system, the decrease in TBARS, and the increase in catalase activity suggest that normal hearts adapt compensatory mechanisms to prevent oxidative damage in response to HFD/and or HS.


Investigating the Vital Role of the Identified Abietic Acid from Helianthus annuus L. Calathide Extract against Hyperuricemia via Human Embryonic Kidney 293T Cell Model.
To explore the anti-hyperuricemia components in sunflower (Helianthus annuus L.) calathide extract (SCE), we identified abietic acid (AA) via liquid chromatography-mass spectrometry and found an excellent inhibitor of xanthine oxidase (IC50 = 10.60 µM, Ki = 193.65 nM) without cytotoxicity. Based on the transcriptomics analysis of the human embryonic kidney 293T cell model established using 1 mM uric acid, we evaluated that AA showed opposite modulation of purine metabolism to the UA group and markedly suppressed the intensity of purine nucleoside phosphorylase, ribose phosphate pyrophosphokinase 2, and ribose 5-phosphate isomerase A. Molecular docking also reveals the inhibition of purine nucleoside phosphorylase and ribose phosphate pyrophosphokinase 1. The SCE exhibits similar regulation of these genes, so we conclude that AA was a promising component in SCE against hyperuricemia. This present study provided a novel cell model for screening anti-hyperuricemia natural drugs in vitro and illustrated that AA, a natural diterpenoid, is a potential inhibitor of purine biosynthesis or metabolism.


Transvaginal sonographic assessment of cervix in prediction of admission to delivery interval in preterm premature rupture of membranes.
To assess the usefulness of cervical parameters measured by transvaginal sonography, that is, cervical length and posterior cervical angle, in predicting the admission to delivery interval in women with preterm rupture of membranes. This prospective study was conducted in a tertiary care centre in South India. Women with preterm premature rupture of membranes at 28-34 weeks, confirmed clinically, not in labour and presenting within 24 hours to hospital were included. We evaluated the relationship between latency interval and transvaginal sonographic parameters (cervical length and posterior cervical angle), parity, age, Amniotic Fluid Index (AFI), total leucocyte count at admission using Cox proportional hazards model. Mean time interval between the membrane rupture and delivery was 96.9 h. Majority of the women (63.8% (n = 51)) delivered within 48 hours. Transvaginal sonographic cervical length was not shown to be associated with latency interval (p = .559), whereas. Posterior cervical angle was shown to be significantly associated with the interval (hazard ratio 1.03, 95%CI: 1.01-1.06; p = .003) Conclusions: Posterior cervical angle assessment using transvaginal sonography is an useful tool in the assessing the latency interval in women with preterm premature rupture of membranes (PPROM). This could help in counselling and planning timely referral to centres with neonatal facilities.


Impact of lymph node metastasis on outcome after extrapleural pneumonectomy for malignant pleural mesothelioma.
Extrapleural pneumonectomy is a therapeutic option for selected patients with malignant pleural mesothelioma. The impact of lymph node metastasis on the site of recurrence and the role of mediastinoscopy in the selection of patients for extrapleural pneumonectomy, however, remain unclear. We reviewed 50 consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma in our institution between January 1993 and March 2005. The median survival was 11 months, with a 3-year survival of 24%. Survival was significantly worse for patients with N2 disease than for those with no lymph node metastasis (median survival 10 months vs 29 months, respectively, P = .005). Patient sex, histologic cell type, stage, and N2 disease, but not mediastinoscopy, had significant impacts on survival according to univariate analysis. In a multivariate analysis, however, only the presence of N2 disease remained a significant predictor of poor outcome. The proportion of patients with N2 disease and the long-term survival was similar regardless of whether preoperative mediastinoscopy yielded a negative result. The initial site of recurrence was determined in 28 patients (locoregional in 10 and distant in 18). The presence of N2 disease had no impact on the site of recurrence. Adjuvant hemithoracic radiation therapy, however, significantly decreased the risk of locoregional recurrence. The presence of N2 disease negatively affects the prognosis of patients with malignant pleural mesothelioma. Mediastinoscopy, however, seems to have a limited role in patient selection for extrapleural pneumonectomy. Adjuvant hemithoracic radiation therapy but not N2 disease affects the risk of locoregional recurrence.


Q fever prosthetic joint infection.
Coxiella burnetii is the causative pathogen of the zoonotic infection Q fever. Most patients with Q fever experience a non-specific febrile illness, hepatitis or pneumonia. Q fever has recently been described as a cause of prosthetic joint septic arthritis, but remains very uncommonly reported. We present a case of Q fever prosthetic joint septic arthritis that has responded to a combination of two-stage surgical exchange and prolonged medical treatment with doxycycline and hydroxychloroquine.


Polyhydroxylated Fullerene C60(OH)40 Nanofilms Promote the Mesenchymal-Epithelial Transition of Human Liver Cancer Cells via the TGF-β1/Smad Pathway.
The various growth factors change the phenotype of neoplastic cells from sedentary (epithelial) to invasive (mesenchymal), which weaken intercellular connections and promote chemotaxis. It can be assumed that the use of anti-inflammatory polyhydroxyfull nanofilms will restore the sedentary phenotype of neoplastic cells in the primary site of the tumor and, consequently, increase the effectiveness of the therapy. The studies were carried out on liver cancer cells HepG2, C3A and SNU-449, and non-cancer hepatic cell line THLE-3. Transforming growth factor (TGF), epidermal growth factor and tumor necrosis factor were used to induce the epithelial-mesenchymal transition. C60(OH)40 nanofilm was used to induce the mesenchymal-epithelial transition. Obtaining an invasive phenotype was confirmed on the basis of changes in the morphology using inverted light microscopy. RT-PCR was used to confirm mesenchymal or epithelial phenotype based on e-cadherin, snail, vimentin expression or others. Water colloids at a concentration of 100 mg/L were used to create nanofilms of fullerene, fullerenol, diamond and graphene oxide. The ELISA test for the determination of TGF expression and growth factor antibody array were used to select the most anti-inflammatory carbon nanofilm. Mitochondrial activity and proliferation of cells were measured by XTT and BrdU tests. Cells lost their natural morphology of cells growing in clusters and resembled fibroblast cells after adding a cocktail of factors. Among the four allotropic forms of carbon tested, only the C60(OH)40 nanofilm inhibited the secretion of TGF in all the cell lines used and inhibited the secretion of other factors, including insulin-like growth factor system. Nanofilm C60(OH)40 was non-toxic to liver cells and inhibited the TGF-β1/Smad pathway of invasive cells treated with the growth factor cocktail. The introduction of an anti-inflammatory, nontoxic component that can induce the mesenchymal-epithelial transition of cancer cells may represent a future adjuvant therapy after tumor resection.


Endothelial tubuloreticular structures in intracranial germinomas.
In studying three human intracranial germinomas tubuloreticular structures were observed within the cisterns of granular endoplasmic reticulum (RER), as well as occasionally within dilated perinuclear spaces of capillary endothelial cells. These tubuloreticular structures seen as a network of branching, convoluted, tubular profiles appear to originate from amorphous material. The development of these structures could be classified into three stages. In Stage I, the precursor substance appears as dense amorphous material within the cisterns of RER. Stage II is marked by the transformation of the amorphous material to coarse particulate material which aggregates to form tubular units. During the first and second stages, the distended RER that participates in the formation of these structures is accompanied by numerous attached ribosomes and is closely associated with mitochondria. In Stage III, the tubular units fuse with one another to form the tubuloreticular structure. In this third stage both ribosomes and mitochondria are almost absent. As a result of the almost complete disappearance of these organelles at this time, both the attached ribosomes and mitochondria may play an important role in the synthesis of the precursor substance as well as in its transformation to the tubuloreticular structure.


Trumpet laminectomy for lumbar degenerative spinal stenosis.
The clinical and radiologic results of trumpet laminectomy, an improved method of extensive laminectomy preserving the facet joints (n = 35), and extensive laminectomy (n = 15) were compared in patients with degenerative lumbar spinal stenosis. The results were evaluated using a rating system and serial radiographs and a follow-up of 2 to 10 1/2 years (mean, 5.2 years). The overall results corroborate the advantage of the trumpet laminectomy, demonstrating a lower incidence and lower grade of postoperative lumbar scoliosis as well as less symptom recurrence in the trumpet laminectomy group than in the extensive laminectomy group. Risk factors for postoperative spinal instability and scoliosis appear to be facet joint destruction and elderly females with a high level of physical activity.


Potential Energy Surface of Group 11 Trimers (Cu, Ag, Au): Bond Angle Isomerism in Au3.
Potential energy surfaces for the group 11 trimers were generated at various levels of coupled-cluster theory to examine the effects of Jahn-Teller distortions. Our calculations show that the lowest-energy conformer for Cu3, Ag3, and Au3 is the 2B2 (∼65° isomer) without spin-orbit corrections. Spin-orbit corrections have negligible contributions to the relative energies for the angle dependence of the potential energy surfaces for Cu3 and Ag3. The inclusion of spin-orbit corrections for Au3 makes the 2B2 (∼65°) and 2A1 (∼55°) states approximately degenerate. A novel 2B2 isomer of Au3 at an obtuse angle of ∼125° was also characterized, providing evidence for bond angle isomerism on the same 2B2 potential energy surface. Spin-orbit corrections increase the barrier height between the 2B2 (65°) and 2B2 (125°) bond angle isomers of Au3. The calculated symmetric stretch vibrational frequencies are in good agreement with the available experimental values. All frequencies calculated for the Au3 2B2 (∼125°) state are real, and there is at least one bound bending vibration for this state. Jahn-Teller parameters are also derived for each trimer.


[A case of duodenal gangliocytic paraganglioma with lymph node metastasis].
A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.


Lateral violence in nursing: a review of the past three decades.
The author of this article reviews the literature on lateral violence in nursing. This concept was first discussed over three decades ago. Bullying and incivility are concepts similar to lateral violence that have become increasingly utilized in nursing research and scholarly writing. The research on these concepts suggests that the behavior still exists in the nursing workplace, and that few interventions have been developed to change the behaviors or the power dynamics that cause them. Suggestions are included to change practice and scholarship in this area.


Current recommendations for anterior cruciate ligament bracing: when to use.
Braces are often used during various stages of recovery from an anterior cruciate ligament tear despite there being sparse definitive research supporting their use. This article reviews the literature on brace use for patients with anterior cruciate ligament tears in order to provide a guide for clinicians. There is evidence to support immediate postoperative bracing, with the goals of maintaining full extension and decreasing effusion. There may be a psychological benefit for its use in return to sport; however, this should be weighed against decreased performance. In the context of modern graft-fixation techniques and early mobilization protocols, empiric functional brace prescription is not required for successful long-term clinical outcomes and return to sport.


Detection of methicillin-resistant Staphylococcus aureus: the evaluation of rapid agglutination methods.
The laboratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) is now commonplace. Part of the screening procedure to detect MRSA rapidly is a reliable particle agglutination test for the presence of S. aureus. Forty clinical isolates of MRSA and 12 of coagulase-negative staphylococci were grown on the three culture media most likely to be used for the isolation of MRSA. Seven particle agglutination kits were evaluated for reliability. Their accuracy and speed of agglutination varied, with four kits, Staphaurex Plus, Pastorex Staph-plus, Slidex and Staphylase, giving better results with the isolates investigated.


[Possibilities of magnetic resonance tomography in pancreatic cancer diagnosis].
There was conducted examination of 27 patients with pancreatic cancer using clinico-laboratory and instrumental methods: ultrasonic investigation, computeric tomography (CT), magnetic-resonance tomography (MRT). MRT was uninformative when pancreatic tumor was up to 3 cm in diameter. In diagnosis of cystadenocarcinoma, affection of common biliary duct and vessels and in small focal metastatic hepatic affection the results of MRT showed enhanced precision in comparison with CT. Informativity of MRT and CT in diagnosis of metastases in lymph nodes was equal.


Focused Update of 2016 Korean Society of Heart Failure Guidelines for the Management of Chronic Heart Failure.
The incidence of heart failure (HF) is increasing in South Korea and devising the optimal care plan is crucial to promote appropriate and effective treatment of HF. To this end, the first Korean guideline for management of chronic HF was published in 2016 by the HF research group under the Korean Society of Cardiology (KSC). After this publication, considerable data have been accumulated and a new guideline for the management of HF was published in Europe, and an update regarding pharmacological therapy was published in the United States, which made it warrant to update the Korean guideline. Under this premise, The Clinical Practice Guidelines Committee under the Korean Society of Heart Failure (KSHF) founded in 2018 decided to publish a focused update management guideline for chronic HF and selected 15 topics that need an update regarding the diagnosis, definition, diagnostic algorithm, monitoring, novel biomarkers, drug therapy related to non-vitamin K antagonist oral anticoagulants and angiotensin receptor neprilysin inhibitors, and with respect to comorbidities changes in the guidelines of relevant institutions, such as new guidelines for the management of hypertension, a procedure used to treat severe aortic stenosis, information on sodium glucose co-transporter-2 inhibitor, and that about sleep apnea. Among nonpharmacological therapies, changes to the recommendations for implantable cardioverter defibrillator, cardiac resynchronization therapy, and cardiac rehabilitation were updated. Subsequent and continuous updates based on additional clinical research findings, with continual supervision by the KSHF will be needed.


The investigation of guided wave propagation around a pipe bend using an analytical modeling approach.
Guided wave inspection has the advantage of providing full volumetric coverage of tens of meters of pipe from a single test location. However, guided wave behavior is complex and there are many factors to consider such as the numerous possible vibrational modes and multiple reflections. The guided wave inspection technique is potentially valuable for pipelines that cannot be inspected with internal "pigs." However, in situations such as this, there are often bends in the pipe and the presence of the bend is known to distort the received signals. In order to address this issue, a study has been carried out that uses a combination of finite element analysis and experimentation to understand the behavior of guided waves in pipe bends. In addition to this, an analytical modeling methodology is put forward that uses basic information from finite element models of pipe bends to create a computationally fast solution to a potentially infinite number of scenarios. The analytical model can be used to both predict the effects of pipe bends on a range of signals and undo the distortion caused by pipe bends. Examples of this are given and compared to finite element results for flaws beyond pipe bends.


Electrostatic guidelines and molecular tailoring for density functional investigation of structures and energetics of (Li)n clusters.
A molecular electrostatic potential (MESP)-guided method for building metal aggregates is proposed and tested on prototype lithium (Li)(n) clusters from n=4 to 58. The smaller clusters are subsequently subjected to direct density functional theory based geometry optimization, while the larger ones are optimized via molecular tailoring approach (MTA). The calculations are performed using PW91-PW91 as well as B3LYP functionals, and the trends in the interaction energies are found to be similar. The MESP-guided model for building metal clusters is validated by comparing the resulting cluster geometries with the ones reported in the literature up to n=20. A comparison of the ionization potential and polarizability (up to n=22) with their experimental counterparts shows a fairly good agreement. A new MTA-based scheme for calculating the ionization potential and polarizability values of large metal clusters is proposed and tested on Li(40) and Li(58) clusters. Further, the existence of "magic numbered clusters" up to n=22 is justified in terms of "maximum hardness principle" as well based on molecular electron density topography and distance descriptors.


Mathematical Modeling Links Pregnancy-Associated Changes and Breast Cancer Risk.
Recent debate has concentrated on the contribution of bad luck to cancer development. The tight correlation between the number of tissue-specific stem cell divisions and cancer risk of the same tissue suggests that bad luck has an important role to play in tumor development, but the full extent of this contribution remains an open question. Improved understanding of the interplay between extrinsic and intrinsic factors at the molecular level is one promising route to identifying the limits on extrinsic control of tumor initiation, which is highly relevant to cancer prevention. Here, we use a simple mathematical model to show that recent data on the variation in numbers of breast epithelial cells with progenitor features due to pregnancy are sufficient to explain the known protective effect of full-term pregnancy in early adulthood for estrogen receptor-positive (ER+) breast cancer later in life. Our work provides a mechanism for this previously ill-understood effect and illuminates the complex influence of extrinsic factors at the molecular level in breast cancer. These findings represent an important contribution to the ongoing research into the role of bad luck in human tumorigenesis. Cancer Res; 77(11); 2800-9. ©2017 AACR.


Physiotherapy interventions encouraging frequent changes of the body position and physical activity for infants hospitalised with bronchiolitis: an internal feasibility study of a randomised control trial.
The effect of a treatment that includes frequent changes of the body position for infants with bronchiolitis has not been evaluated, although it is often used in Swedish hospitals. Because of this, a randomised control trial (RCT) has begun with the aim to evaluate this treatment, comparing the effect of an individualised physiotherapy intervention, a non-individualised intervention, and standard care in a control group. The objective of this internal pilot study was to address uncertainties concerning the ongoing RCT and to determine whether the trial is feasible or not, possibly with adjustments to the protocol. Descriptive analyses of the recruitment, retention, data supply for the primary end point, and the usability of the primary outcome measure in the full RCT were performed. A safety analysis was conducted by an independent analysis group. Ninety-one infants were included, 33 (36.3%), 28 (30.8%), and 30 (33.0%) in the respective allocation groups. Fifty-nine (64.8%) were boys. The median age was 2.5 (min-max 0.2-23.7) months. They remained in the study for a median of 46 hours (min-max 2-159). The recruitment rate was 19%. The data supply for the primary end point and for the primary outcome measure was lower than anticipated in the original sample size calculation. Difficulties concerning utilising the primary outcome measure were identified. The safety analysis detected no risks of harm related to participation in the study. It is feasible to continue the RCT with modifications of the analysis plan. Participation in the study was not associated with any safety risks. ClinicalTrials.gov NCT03575091 . Registered 2 July 2018. Retrospectively registered.


A Model of Mercury Distribution in Tuna from the Western and Central Pacific Ocean: Influence of Physiology, Ecology and Environmental Factors.
Information on ocean scale drivers of methylmercury levels and variability in tuna is scarce, yet crucial in the context of anthropogenic mercury (Hg) inputs and potential threats to human health. Here we assess Hg concentrations in three commercial tuna species (bigeye, yellowfin, and albacore, n = 1000) from the Western and Central Pacific Ocean (WCPO). Models were developed to map regional Hg variance and understand the main drivers. Mercury concentrations are enriched in southern latitudes (10°S-20°S) relative to the equator (0°-10°S) for each species, with bigeye exhibiting the strongest spatial gradients. Fish size is the primary factor explaining Hg variance but physical oceanography also contributes, with higher Hg concentrations in regions exhibiting deeper thermoclines. Tuna trophic position and oceanic primary productivity were of weaker importance. Predictive models perform well in the Central Equatorial Pacific and Hawaii, but underestimate Hg concentrations in the Eastern Pacific. A literature review from the global ocean indicates that size tends to govern tuna Hg concentrations, however regional information on vertical habitats, methylmercury production, and/or Hg inputs are needed to understand Hg distribution at a broader scale. Finally, this study establishes a geographical context of Hg levels to weigh the risks and benefits of tuna consumption in the WCPO.


Analyses of RNA Polymerase II genes from free-living protists: phylogeny, long branch attraction, and the eukaryotic big bang.
The phylogenetic relationships among major eukaryotic protist lineages are largely uncertain. Two significant obstacles in reconstructing eukaryotic phylogeny are long-branch attraction (LBA) effects and poor taxon sampling of free-living protists. We have obtained and analyzed gene sequences encoding the largest subunit of RNA Polymerase II (RPB1) from Naegleria gruberi (a heterolobosean), Cercomonas ATCC 50319 (a cercozoan), and Ochromonas danica (a heterokont); we have also analyzed the RPB1 gene from the nucleomorph (nm) genome of Guillardia theta (a cryptomonad). Using a variety of phylogenetic methods our analysis shows that RPB1s from Giardia intestinalis and Trichomonas vaginalis are probably subject to intense LBA effects. Thus, the deep branching of these taxa on RPB1 trees is questionable and should not be interpreted as evidence favoring their early divergence. Similar effects are discernable, to a lesser extent, with the Mastigamoeba invertens RPB1 sequence. Upon removal of the outgroup and these problematic sequences, analyses of the remaining RPB1s indicate some resolution among major eukaryotic groups. The most robustly supported higher-level clades are the opisthokonts (animals plus fungi) and the red algae plus the cryptomonad nm-the latter result gives added support to the red algal origin of cryptomonad chloroplasts. Clades comprising Dictyostelium discoideum plus Acanthamoeba castellanii (Amoebozoa) and Ochromonas plus Plasmodium falciparum (chromalveolates) are consistently observed and moderately supported. The clades supported by our RPB1 analyses are congruent with other data, suggesting that bona fide phylogenetic relationships are being resolved. Thus, the RPB1 gene has apparently retained some phylogenetically meaningful signal, making it worthwhile to obtain sequences from more diverse protist taxa. Additional RPB1 data, especially in combination with other genes, should provide further resolution of branching orders among protist groups within the apparently rapid early divergence of eukaryotes.


Quantificational exposure, sources, and health risks posed by heavy metals in indoor and outdoor household dust in a typical smelting area in China.
Contamination of metals in household dust remains a concern for human health. However, few studies to date have been conducted on the contribution of both indoor and outdoor environments to the health risks posed by metals. This study was carried out to assess the potential health risks from both indoor and outdoor household dust and the respective contribution to the health risks for children. The results showed that household dusts were heavily polluted by metal(loid)s, which were up to 30 times higher than the relative background level, and were attributed to smelting activity. However, there are other pollution sources in indoor environments, since the I/O ratio values of Pb, Cd, and As were significantly higher than 1. HI values of Pb and As exceeded the threshold of (1) and accounted for approximately 60% and 24% to the HIt, respectively. The HIts of Zn, Cr, Mn, Hg, and Cu were mainly attributable to indoor dust exposure, particularly for Hg (73.44%), indicating non-carcinogenic health risks could be attributed more to the indoor dust exposure. This study highlights the potential risks of metal contamination in household environment, particularly indoor environment, on the health of children who live in the vicinity of smelting activity.


MTR recovery in brain lesions in the BECOME study of glatiramer acetate vs interferon β-1b.
To compare magnetization transfer changes in new brain MRI lesions identified during monthly imaging in patients with multiple sclerosis (MS) randomized to treatment with 250 μg subcutaneous interferon-β-1b (IFN-β-1b) every other day or daily 20 mg glatiramer acetate (GA) in a post hoc study using data from the Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI (BECOME) trial. T1-weighted images acquired with and without fat saturation pulses in the BECOME study were evaluated and found to exhibit magnetization transfer ratio (MTR) effects, and were used to compute MTR images (FSMTR). Forty-three participants who had the required imaging and new lesions, from the 75 originally randomized into the BECOME study, were included in this post hoc analysis and evaluated longitudinally during treatment to determine FSMTRDrop, an experimental measure of the completeness of FSMTR recovery in new lesions. Two sets of new brain MRI lesions were defined, one based on the appearance of gadolinium contrast enhancement (Gd lesions) and the other based on FSMTR decreases (ΔFSMTR lesions). A total of 887 Gd lesions were identified in 43 participants (19 GA, 24 IFN-β-1b) and 321 ΔFSMTR lesions in 32 participants (16 GA, 16 IFN-β-1b). Participants randomized to GA exhibited greater average postlesion FSMTR recovery than did those randomized to IFN-β-1b in both Gd (p < 0.0001) and ΔFSMTR (p < 0.0001) lesions. New brain lesions that developed during treatment with GA exhibited evidence of greater FSMTR recovery than during treatment with IFN-β-1b. This study provides Class III evidence that MTR recovery in patients with MS with new MRI brain lesions is greater with GA than with IFN-β-1b.


Customer Service in Radiology: Satisfying Your Patients and Referrers.
Radiology has long been a service-oriented specialty. Although physicians in other specialties have direct interactions with patients, radiologists' interactions with patients are often indirect, most often occurring as a direct result of another provider's order. As such, radiology practices have had to focus on two distinct groups, patients and ordering providers, to grow their businesses and retain their patients. One could argue that during the past 2 decades, many of the most visible customer service initiatives in radiology practices have been directed toward the ordering provider. These initiatives have included implementing picture archiving and communication systems to improve image distribution and availability, voice dictation systems to decrease report turnaround time, computerized order entry to ease the ordering process, and structured reporting to improve the readability of the radiology report. As the practice of radiology is evolving to become more patient oriented, it is clear that the specialty needs to pivot and implement more initiatives that directly benefit patients. In this article, the concepts of customer service and a radiology department's primary customer are defined and discussed, and the concept of service quality is introduced. In addition, the author highlights the five dimensions of service quality: reliability, assurance, tangibles, empathy, and responsiveness. Each dimension is described in detail, first by using an archetypal business example and then by using an example of a project that has been successfully implemented in the author's radiology department. ©RSNA, 2018.


Relationship between the populations of Streptococcus mutans in the mouth and feces of conventional Sprague-Dawley rats.
The relationship between oral and fecal S mutans populations has been studied in rats fed high sucrose or glucose diet. All molar teeth were extracted either prior to or following oral challenge with strain 6715. In certain instances this procedure was supplemented with amputation of the incisors and disinfection of the remaining incisor surface area with iodine solution. The results suggest that in rats the colonization of S mutans on the teeth is required for its presence in the intestinal canal as well as the mouth. The significance of the observations has been discussed.


Clinical approach to rapidly progressive renal failure.
Rapidly progressive renal failure (RPRF) is an initial clinical diagnosis in patients who present with progressive renal impairment of short duration. The underlying etiology may be a primary renal disease or a systemic disorder. Important differential diagnoses include vasculitis (systemic or renal-limited), systemic lupus erythematosus, multiple myeloma, thrombotic microangiopathy and acute interstitial nephritis. Good history taking, clinical examination and relevant investigations including serology and ultimately kidney biopsy are helpful in clinching the diagnosis. Early definitive diagnosis of RPRF is essential to reverse the otherwise relentless progression to end-stage kidney disease.


Spaceflight induces specific alterations in the proteomes of Arabidopsis.
Life in spaceflight demonstrates remarkable acclimation processes within the specialized habitats of vehicles subjected to the myriad of unique environmental issues associated with orbital trajectories. To examine the response processes that occur in plants in space, leaves and roots from Arabidopsis (Arabidopsis thaliana) seedlings from three GFP reporter lines that were grown from seed for 12 days on the International Space Station and preserved on orbit in RNAlater were returned to Earth and analyzed by using iTRAQ broad-scale proteomics procedures. Using stringent criteria, we identified over 1500 proteins, which included 1167 leaf proteins and 1150 root proteins we were able to accurately quantify. Quantification revealed 256 leaf proteins and 358 root proteins that showed statistically significant differential abundance in the spaceflight samples compared to ground controls, with few proteins differentially regulated in common between leaves and roots. This indicates that there are measurable proteomics responses to spaceflight and that the responses are organ-specific. These proteomics data were compared with transcriptome data from similar spaceflight samples, showing that there is a positive but limited relationship between transcriptome and proteome regulation of the overall spaceflight responses of plants. These results are discussed in terms of emergence understanding of plant responses to spaceflight particularly with regard to cell wall remodeling, as well as in the context of deriving multiple omics data sets from a single on-orbit preservation and operations approach.


Personnel administration: the case method of teaching.
Only recently are case materials being used in the area of personnel administration, general library administration, and reference services. These permit more intellectual involvement on the part of the student than do the generalizations which result from the traditional lecture-discussion techniques. The medical library field has a professional character quite particular to itself. This is illustrated by its highly specialized clienteles, the quite special nature of the materials involved and their control, and the aura of special ethical considerations involved in any aspect of medicine. The development of a body of case materials would seem to have merit as a teaching vehicle for the medical library course, for in-service training in larger medical libraries, for workshops and institutes, and as a learning vehicle for the individual medical librarian.


Effects of hypoxia on platelet activation in pilots.
In order to evaluate the effect of hypoxia on platelet activation, 53 pilots were chosen for this study. Thirty were selected as the hypoxic group, and the other 23 as a control group. The plasma concentration of thromboxane B2(TXB2), 6-keto-prostaglandin f1 alpha (6-keto-PGF1 alpha), beta-thrombo-globulin (BTG) and platelet factor 4 (PF4) were measured during altitude chamber tests. After staying at 5000 m for 15 min, the plasma level of TXB2, BTG and PF4 increased significantly over pre-test levels (p < 0.01), but 6-keto-PGF1 alpha had no distinct change (p > 0.05). These changes indicate that moderate acute hypoxia causes increases in platelet activation, but has less effects on the endothelial cells.


Protein kinase G type Ialpha activity in human ovarian cancer cells significantly contributes to enhanced Src activation and DNA synthesis/cell proliferation.
Previously, we showed that basal activity of nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) signaling pathway protects against spontaneous apoptosis and confers resistance to cisplatin-induced apoptosis in human ovarian cancer cells. The present study determines whether basal PKG kinase activity regulates Src family kinase (SFK) activity and proliferation in these cells. PKG-Ialpha was identified as predominant isoform in both OV2008 (cisplatin-sensitive, wild-type p53) and A2780cp (cisplatin-resistant, mutated p53) ovarian cancer cells. In both cell lines, ODQ (inhibitor of endogenous NO-induced cGMP biosynthesis), DT-2 (highly specific inhibitor of PKG-Ialpha kinase activity), and PKG-Ialpha knockdown (using small interfering RNA) caused concentration-dependent inhibition of DNA synthesis (assessed by bromodeoxyuridine incorporation), indicating an important role of basal cGMP/PKG-Ialpha kinase activity in promoting cell proliferation. DNA synthesis in OV2008 cells was dependent on SFK activity, determined using highly selective SFK inhibitor, 4-(4'-phenoxyanilino)-6,7-dimethoxyquinazoline (SKI-1). Studies using DT-2 and PKG-Ialpha small interfering RNA revealed that SFK activity was dependent on PKG-Ialpha kinase activity. Furthermore, SFK activity contributed to endogenous tyrosine phosphorylation of PKG-Ialpha in OV2008 and A2780cp cells. In vitro coincubation of recombinant human c-Src and PKG-Ialpha resulted in c-Src-mediated tyrosine phosphorylation of PKG-Ialpha and enhanced c-Src autophosphorylation/activation, suggesting that human c-Src directly tyrosine phosphorylates PKG-Ialpha and the c-Src/PKG-Ialpha interaction enhances Src kinase activity. Epidermal growth factor-induced stimulation of SFK activity in OV2008 cells increased PKG-Ialpha kinase activity (indicated by Ser(239) phosphorylation of the PKG substrate vasodilator-stimulated phosphoprotein), which was blocked by both SKI-1 and SU6656. The data suggest an important role of Src/PKG-Ialpha interaction in promoting DNA synthesis/cell proliferation in human ovarian cancer cells. The NO/cGMP/PKG-Ialpha signaling pathway may provide a novel therapeutic target for disrupting ovarian cancer cell proliferation.


Particle-Catalyst-Free Vapor-Liquid-Solid Growth of Millimeter-Scale Crystalline Compound Semiconductors on Nonepitaxial Substrates.
Direct growth of single-crystal compound semiconductors on nonepitaxial substrates is a promising route for device processing simplification in electronic and optoelectronic applications. However, the nonepitaxial growth technique for 2D single crystals is still a fundamental challenge. Here, we demonstrate that the macroscopic 2D interface of liquid metals and nonepitaxial solid substrates could be universally designed for the chemical vapor deposition growth of crystalline compound semiconductors. By adopting a sandwiched solid metal/liquid metal/solid substrate environment, millimeter-scale 2D GaS, 2D GaSe, and 1D GaTe single crystals of high quality were synthesized at the interface of liquid gallium and nonepitaxial substrates. Evidence shows that the particle-catalyst-free vapor-liquid-solid growth is driven by screw dislocations. Furthermore, we successfully extend the growth strategy to various metal chalcogenides (Sn, In, Cu, and Ag) and pnictides (Sb). Our work opens up a new route for the direct growth of single-crystalline compound semiconductors on nonepitaxial substrates.


Guiding Brain-Tumor Surgery via Blood-Brain-Barrier-Permeable Gold Nanoprobes with Acid-Triggered MRI/SERRS Signals.
Surgical resection is a mainstay in the treatment of malignant brain tumors. Surgeons, however, face great challenges in distinguishing tumor margins due to their infiltrated nature. Here, a pair of gold nanoprobes that enter a brain tumor by crossing the blood-brain barrier is developed. The acidic tumor environment triggers their assembly with the concomitant activation of both magnetic resonance (MR) and surface-enhanced resonance Raman spectroscopy (SERRS) signals. While the bulky aggregates continuously trap into the tumor interstitium, the intact nanoprobes in normal brain tissue can be transported back into the blood stream in a timely manner. Experimental results show that physiological acidity triggers nanoparticle assembly by forming 3D spherical nanoclusters with remarkable MR and SERRS signal enhancements. The nanoprobes not only preoperatively define orthotopic glioblastoma xenografts by magnetic resonance imaging (MRI) with high sensitivity and durability in vivo, but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner. Microscopy studies verify the precisely demarcated tumor margin marked by the assembled nanoprobes. Taking advantage of the nanoprobes' rapid excretion rate and the extracellular acidification as a hallmark of solid tumors, these nanoprobes are promising in improving brain-tumor surgical outcome with high specificity, safety, and universality.


[Pharmaconutrition: pharmacological approach to nutrition therapy].
Reviewing the literature of nutrition therapy one can conclude that during the last decade the pharmacological action of several nutrients has been demonstrated. However, research activity is still at the beginning and it could be verified in a restricted number of nutrients only that in which conditions (illnesses), dose and duration we can expect therapeutic effect in addition to nutrition. The examples of glutamine, arginine, taurine, leucine, ω-3 fatty acids, however, support the possibility that complex reactions and treatment results observed in certain patients are not purely due to nutritional support but the consequence of additional pharmacological action as well. Evaluation of results of therapeutic intervention is especially difficult because in the everyday practice physicians try to use several therapeutic modalities that can be beneficial for the patient. Therefore, retrospective separation of beneficial components of the therapeutic agents is almost impossible. Only well designed, randomized and multicentric studies can verify specific therapeutic action of certain ingredients ie. nutrients.


[Cervicothoracic angiomyolipoma: an unusual tumor located at a site difficult to reach for surgery].
Angiomyolipoma is an uncommon hamartomatous renal tumor very prone to spontaneous bleeding. However it is possible to find it in extrarenal sites, being the liver the most frequent one. The rest of sites recorded in literature are exceptional. In fact, to our knowledge, this is the first case reported of cervicothoracic settlement of an angiomyolipoma. This rare location, together with its marked tendency to bleed bleeding determinate a complicated diagnoses a difficult surgical approach.


Harvesting Broad Frequency Band Blue Energy by a Triboelectric-Electromagnetic Hybrid Nanogenerator.
Ocean wave associated energy is huge, but it has little use toward world energy. Although such blue energy is capable of meeting all of our energy needs, there is no effective way to harvest it due to its low frequency and irregular amplitude, which may restrict the application of traditional power generators. In this work, we report a hybrid nanogenerator that consists of a spiral-interdigitated-electrode triboelectric nanogenerator (S-TENG) and a wrap-around electromagnetic generator (W-EMG) for harvesting ocean energy. In this design, the S-TENG can be fully isolated from the external environment through packaging and indirectly driven by the noncontact attractive forces between pairs of magnets, and W-EMG can be easily hybridized. Notably, the hybrid nanogenerator could generate electricity under either rotation mode or fluctuation mode to collect energy in ocean tide, current, and wave energy due to the unique structural design. In addition, the characteristics and advantages of outputs indicate that the S-TENG is irreplaceable for harvesting low rotation speeds (<100 rpm) or motion frequencies (<2 Hz) energy, which fits the frequency range for most of the water wave based blue energy, while W-EMG is able to produce larger output at high frequencies (>10 Hz). The complementary output can be maximized and hybridized for harvesting energy in a broad frequency range. Finally, a single hybrid nanogenerator unit was demonstrated to harvest blue energy as a practical power source to drive several LEDs under different simulated water wave conditions. We also proposed a blue energy harvesting system floating on the ocean surface that could simultaneously harvest wind, solar, and wave energy. The proposed hybrid nanogenerator renders an effective and sustainable progress in practical applications of the hybrid nanogenerator toward harvesting water wave energy offered by nature.


Randomized double-blind placebo-controlled crossover study of efficacy of pollen blocker cream for perennial allergic rhinitis.
This study evaluates the efficacy and safety of a pollen blocker cream in treatment of perennial allergic rhinitis (PAR) in a Chinese population. A randomized double-blind placebo-controlled, crossover trial was conducted in the Outpatient Department of the Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China. Patients diagnosed with PAR were randomly assigned to receive pollen blocker cream or placebo, which was applied and evenly distributed to the lower internal nose region three times daily for a total of 30 days. The primary outcome measures for efficacy were nasal symptom scores (NSSs) and quality of life scores (QoLSs). Medication scores and adverse events were also monitored. After application of pollen blocker, the mean NSS fell from 23.1 to 12.4 points, and the QoLSs fell from 83.9 to 53.2 points (p < 0.001). The decrease in NSSs of pollen blocker (10.7) was highly significant compared with the placebo (3.6; p < 0.001). The decrease in QoLSs of pollen blocker was 30.7 compared with 7.1 in the placebo group, and the difference was also significant (p < 0.05). Interestingly, the mean NSS of the placebo group also decreased from 23.7 to 20.1 (p < 0.05). Additionally, the efficacy of pollen blocker was superior to the placebo both in adults and in children. However, there was no significant difference for individual symptoms of rhinorrhea, nasal itching, sneezing, and nasal congestion between the pollen blocker group and placebo group (p > 0.05). Only one mild epistaxis was reported. The pollen blocker was significantly more effective than the placebo in relieving allergy symptoms and improving life quality of PAR in 30 Chinese people.


Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing anti-glioma efficacy by modulating glioma microenvironment.
Glioma, one of the most common brain tumors, remains a challenge worldwide. Due to the specific biological barriers such as blood-brain barrier (BBB), cancer stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then, these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which showed near-spherical morphology with an average size of 155.8 nm and uniform distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor, which is over-expressed on the surface of tumor cells, other associated cells (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy could attribute to the accumulation in glioma site and the regulation of tumor microenvironment with depletion of TAMs, inhibition of VMs, and elimination of CSCs.


Generating Data Visualizations of Longitudinal Cohort Ambient Air Pollution Exposure: Report-Back Intervention Development in Participatory Action Research.
A civic engagement and data science design was used to develop a report-back intervention to address stakeholder concerns related to air emissions surrounding a coke oven factory near Buffalo, NY. This factory had historically emitted high levels of benzene pollution and ceased operation in October 2018 because of violations of the US Clean Air Act and US Resource Conservation and Recovery Act. Using publicly available air pollution and weather data, descriptive time series and wind-rose data visualizations were developed using open-source software as part of a two-page report-back brief. Data from two air toxics monitoring sites in this direction suggest that industrial sources were likely the major contributor to the benzene in the air at these locations prior to May 2018, after which traffic emissions became the likely major contributor. Wind-rose visualizations demonstrated that the wind typically blew toward the northeast, which was qualitatively consistent with locations of stakeholder concerns. With the factory closed, collective efforts subsequently shifted to address traffic emission air pollution sources, factory site cleanup, and ground and water pollution mitigation. Because this intervention utilized open-source software and publicly available data, it can serve as a blueprint for future data-driven nursing interventions and community-led environmental justice efforts.


A colloidal route to semiconducting tungsten disulfide nanosheets with monolayer thickness.
Transition metal dichalcogenides (TMDs) are a class of materials that have been extensively studied in the last decade, with molybdenum disulfide (MoS2) being the main protagonist. Typically, the interesting TMD properties, e.g. a direct band gap transition, or broken inversion symmetry, are only present in monolayer thick TMDs, and in the absence of strong lateral confinement, we require different materials or alloys thereof when we want to obtain TMDs with varying (direct) band gap energies. With this in mind, tungsten disulfide (WS2) is emerging as a direct competitor of MoS2 due to its similar properties but larger band gap energy. While several colloidal strategies have been reported for the synthesis of WS2, the synthesis of monolayer WS2 and detailed studies on the effect of synthesis parameters on the synthesis outcome have remained elusive. In this work we therefore focused on a colloidal synthesis method for monolayer WS2 using a design of experiment (DOE) approach. After optimization, we obtained nanosheets with a band gap transition consistent with the expected value for a monolayer. The thickness was further confirmed by Raman spectroscopy. While we could identify two temperature ranges where we could obtain a monolayer, sample characterization by XPS spectroscopy revealed the presence of different ratios of the metallic phase, with the sample synthesized at lower temperature displaying a lower concentration of the metallic phase.


How to study the prevalence and mechanisms of racial differences in coronary vasomotor response.
The rapid progress of therapeutic modalities of cardiovascular diseases have led to the development of clinical practice guidelines on the basis of large scale clinical trials. However, an individual response of each patient may not match the mean effect of an intervention in these trials. Therefore, recommendations based on clinical trials performed in a given patient population may not be applicable to the other races. Here, we assessed epidemiological and pathophysiological differences in cardiovascular diseases across racial groups. The incidence of coronary artery disease is the lowest in Japan of all the industrialized nations. Our previous study that compared post-hospital course of acute myocardial infarction in Japanese and Caucasians in North America demonstrated that cardiac events were significantly less in Japanese even when the initial infarct size was similar. Ischemic heart disease constitutes the most common cause of heart failure in the United States but nonischemic cardiomyopathy occurs more frequently in Japan. On the other hand, vasospastic angina is by far more common in the Japanese population. The first comparative study we carried out in Japanese and Italian patients with acute myocardial infarction also showed that percentage of vasospasm in the infarct-related arteries is 3 times higher in Japanese. Thus, coronary spasm appears to be more important as well as the pathogenesis of myocardial infarction in Japan. This fact was reflected by the more frequent use of calcium antagonists in Japan during the acute phase of myocardial infarction. On the other hand, the use of inotropic agents has now been contraindicated for the treatment of patients with chronic heart failure, however it may not be the case in the Japanese population in whom mortality is relatively low. Cardiotonic therapy could be justified in Japanese as it allows optimal care in the context of relief of symptoms and an improved quality of life. Therefore, each racial group should obtain specific evidence aimed at developing its own guidelines for therapy rather than translating major guidelines developed for other populations.


A prospective study of marital quality and body weight in midlife.
Few studies have gone beyond studying marital status to examine effects of marital quality on body weight. This study examined the association of marital quality with weight change and incident obesity in midlife. It differentiated positive and negative components of marital quality considering overall marital quality, marital support, and marital strain. Data are from 2,636 adults from the Midlife in the United States study who participated in 2 waves of data collection 10 years apart. Marital quality was self-reported. Body weight was assessed with self-reported height and weight. Generalized estimating equations examined primary associations also considering potential confounders and mediating factors including sociodemographics, baseline health conditions, and health behaviors. Overall marital quality was inversely associated with weight gain (β = -0.70, 95% confidence interval [CI] [-1.38, -0.01]). Marital support was inversely related to both weight gain (β = -1.48, 95% CI [-2.80, -0.16]) and incident obesity (risk ratio = 0.79, 95% CI [0.65, 0.96]). Marital strain was not associated with either weight change or incident obesity. The association between marital support and incident obesity remained when marital strain was simultaneously included in the model. There was evidence that the associations of marital support and marital strain with incident obesity might differ by gender, and were evident only in men. This study shows a supportive marital relationship is associated with healthier body weight in midlife. It also indicates marital support may have effects over and beyond the mere absence of marital strain. Findings suggest the potential utility of involving spouses/partners in obesity prevention and treatment. (PsycINFO Database Record


INFECTIVITY, MULTIPLE INFECTIONS, AND THE GENETIC CORRELATION BETWEEN WITHIN-HOST GROWTH AND PARASITE VIRULENCE: A REPLY TO HOCHBERG.
Two experimental studies, Ebert (1994) and Ebert and Mangin (1997), described a genetic correlation between parasite virulence and the number of transmission stages found in the hosts. It was concluded that this correlation is evidence that within-host growth rate of the parasite is positively correlated with virulence. Hochberg (1998) has criticized this interpretation, arguing that differential infectivity and density-dependent parasite growth could confound the results. Here I point out that density dependence is unlikely to have confounded the results, but, at least for Ebert (1994), differential infectivity is likely to have been a confounding factor. However, Ebert and Mangin (1997) measured infectivity and showed that strains with higher infectivity had lower virulence, which is contrary to Hochberg's hypothesis. In summary, I conclude that differential infectivity played a role in the assessment of the correlation between parasite reproduction and virulence, but that differential within-host growth remains the most likely explanation for the correlation observed in Ebert and Mangin (1997).


Comparison of Rescue Medication Prescriptions in Patients with Chronic Obstructive Pulmonary Disease Receiving Umeclidinium/Vilanterol versus Tiotropium Bromide/Olodaterol in Routine Clinical Practice in England.
Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting β2-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO. This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥80% (secondary), and time-to-initiation of triple therapy (exploratory). Inverse probability of treatment weighting (IPTW) was used to balance potential confounding baseline characteristics. Superiority of UMEC/VI versus TIO/OLO for the primary outcome of rescue medication prescriptions was assessed using an intention-to-treat analysis with a p-value < 0.05. In total, 8603 patients were eligible (UMEC/VI: n = 6536; TIO/OLO: n = 2067). Following IPTW, covariates were well balanced across groups. Patients initiating UMEC/VI had statistically significantly fewer (mean [standard deviation]; p-value) rescue medication prescriptions versus TIO/OLO in both the unweighted (4.84 [4.78] vs 5.68 [5.00]; p < 0.001) and weighted comparison (4.91 [4.81] vs 5.48 [5.02]; p = 0.0032) at 12 months; consistent results were seen at all timepoints. Adherence was numerically higher for TIO/OLO versus UMEC/VI at all timepoints. Time-to-triple therapy was similar between treatment groups. UMEC/VI was superior to TIO/OLO in reducing rescue medication prescriptions at 12 months after treatment initiation in a primary care cohort in England, potentially suggesting improvements in symptom control with UMEC/VI compared with TIO/OLO.


Relationship between Admission Electrolyte Level and Short-term Prognosis of Patients with Acute ST-segment Elevation Myocardial Infarction after Percutaneous Coronary Intervention.
The objective of this study is to analyze the relationship between the electrolyte level of patients with acute ST-segment elevation myocardial infarction (STEMI) and short-term prognosis after percutaneous coronary intervention (PCI). The clinical data of 142 patients with acute STEMI who underwent PCI in our hospital from September 2018 to September 2019 were retrospectively analyzed. According to the level of serum sodium, potassium, and chloride in patients admitted to the hospital, they were divided into the normal electrolyte group (n = 78), the mild decline group (n = 46), and the severe decline group (n = 16). Univariate and logistic regression multivariate analysis of the relationship between patient electrolyte levels and general clinical data is performed. Statistical analysis of patients' adverse events within 90 days was performed. The Kaplan-Meier survival curve analyzed the relationship between the survival period and electrolyte levels in patients with acute STEMI without major acute cardiovascular events (MACE) within 90 days. The levels of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), myocardial infarction area, and Gensini score in patients with mild decline were significantly higher than those in the normal group, left ventricle ejection fractions (LVEF) value was significantly lower than the normal group, and patients with severe decline were significantly higher in creatine kinase (CK) level than the normal group (P < 0.05). The levels of CK-MB, CK, cTnI, and myocardial infarction area of the patients in the severe decline group were significantly higher than those in the mild decline group, and the LVEF values were significantly lower than those in the mild decline group (P < 0.05). The levels of CK-MB, CK, cTnI, the area of myocardial infarction, and Gensini score in patients with acute STEMI have an independent effect on their electrolyte levels. The patients in the mild decline group and severe decline group had significantly higher rates of cardiogenic shock, heart failure, ventricular aneurysm formation, ventricular septal perforation, or death within 90 days after PCI. The median without MACE survival time of patients with mildly and severely reduced electrolyte levels was significantly lower than that of patients with normal electrolyte levels. Patients with acute STEMI are prone to electrolyte disturbances, and their CK-MB, CK, and cTnI levels; myocardial infarction area; and Gensini score have independent effects on electrolyte levels. Patients with electrolyte disturbances are prone to poor prognosis after PCI, and their survival period without MACE at 90 days is significantly lower than that of normal patients.


Streptocollin, a Type IV Lanthipeptide Produced by Streptomyces collinus Tü 365.
Lanthipeptides are ribosomally synthesized and post-translationally modified microbial secondary metabolites. Here, we report the identification and isolation of streptocollin from Streptomyces collinus Tü 365, a new member of class IV lanthipeptides. Insertion of the constitutive ermE* promoter upstream of the lanthipeptide synthetase gene stcL resulted in peptide production. The streptocollin gene cluster was heterologously expressed in S. coelicolor M1146 and M1152 with 3.5- and 5.5-fold increased yields, respectively. The structure and ring topology of streptocollin were determined by high resolution MS/MS analysis. Streptocollin contains four macrocyclic rings, with one lanthionine and three methyllanthionine residues. To the best of our knowledge, this is the first report on the isolation of a class IV lanthipeptide in preparative amounts, and on the successful heterologous expression of a class IV lanthipeptide gene cluster.


Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study.
Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.


Interactive Effects of Genotype and Molybdenum Supply on Yield and Overall Fruit Quality of Tomato.
Molybdenum (Mo) is an essential trace element for plant growth, development, and production. However, there is little known about the function and effects of molybdenum in tomato plants. The present study assessed the influences of different Mo concentrations on four tomato F1 hybrids ("Bybal" F1, "Tyty" F1, "Paride" F1, and "Ornela" F1) grown using a soilless system with different Mo levels [0.0, 0.5 (standard NS), 2.0, and 4.0 μmol L-1, respectively]. The crop yield, plant vigor, fruit skin color, TA, fruit water content as well as the accumulation of SSC, and some antioxidant compounds such as lycopene, polyphenols and ascorbic acid were evaluated. The minerals concentration, including nitrogen (N), Mo, iron (Fe), and copper (Cu), were measured in tomato fruits. Results revealed that tomato plants grown with 2.0 μmol Mo L-1 compared to plants grown with 0.5 μmol Mo L-1 incurred a significant increase of total yield by 21.7%, marketable yield by 9.1%, aboveground biomass by 16.7%, plant height at 50 DAT by 6.5%, polyphenol content by 3.5%, ascorbic acid by 1.0%, SSC by 3.5%, N fruit content by 24.8%, Mo fruit content by 20.0%, and Fe fruit content by 60.5%. However, the Mo concentration did not significantly influence the average fruit weight, b* fruit skin color coordinate and TA. Furthermore, tomato fruits from plants grown with 2.0 μmol Mo L-1 showed a lower Cu fruit content (16.1%) than fruits from plants grown with 0.5 μmol Mo L-1 (standard NS). Consequently, our study highlights the different behavior of the tomato genotypes tested when subjected to different levels of Mo concentration in the nutrient solution. Nevertheless, taking all in consideration our results clearly suggest that a Mo fertilization of 2.0 μmol Mo L-1 effectively enhance crop performance and overall fruit quality of tomato.


Virulence factor genotyping of Helicobacter pylori isolated from Costa Rican dyspeptic patients.
Costa Rica is one of the countries with the highest incidence and mortality rates for gastric cancer. Helicobacter pylori infection rates are high in the whole country. We have previously shown that H. pylori CagA+ is significantly associated with atrophic gastritis (AG) of the antrum in a dyspeptic population. The aim of this work is to determine if other H. pylori virulence factors (vacA, dupA, oipA, iceA and babA2) are associated with atrophic gastritis (AG) or duodenal ulcer (DU). The presence of virulence genes in Costa Rican H. pylori isolates was analyzed by PCR in 151 cultured strains from patients with dyspeptic symptoms. Endoscopic and histopathological diagnoses were available. Odds-ratio and 95% confidence intervals for AG patients vs. non-atrophic gastritis (NAG) or DU patients vs. no duodenal ulcer (NDU) patients were calculated. Amongst the studied isolates, 82% had the cagA+, 76.2% had the vacA s1m1, 97.0% had the oipA+, 21.0% had the icea1, 79.0% had the iceA2, 44.0% had the babA2+ and 76.0% the dupA+ genotypes. Infection with H pylori cagA+, dupA+, oipA+, iceA, babA2+, and vacA s1m1 genotypes was not associated with AG risk. The frequency of the dupA gene was 78.7 and 60.9% in isolates from patients with NDU and DU, respectively, and its presence was significantly associated with decreased risk of duodenal ulcer [odds-ratio: 0.33, p = 0.024, confidence interval 95% (0.11-0.85)]. H. pylori dupA genotype is inversely associated with DU risk in this population.


Radiation response of "clonogenic" tumor cell release from NFSA2ALM1 tumors.
A newly developed "clonogenic" tumor cell release assay was applied to a transplantable spontaneous mouse fibrosarcoma, NFSA2ALM1 , growing in the leg. The tumors 32 days after transplantation (3400 mm3) released 36 "clonogenic" tumor cells per hour into the blood circulation. After irradiation of the leg tumors, the "clonogenic" tumor cell release rate declined in 1 day to a minimum, and remained low during the following several days. The dose-response curve for the "clonogenic" tumor cell release determined 1 day after local irradiation of the tumors showed a D0 of 3.8 Gy.


The effects of prenatal ultrasound exposure on postnatal growth and acquisition of reflexes.
The examination of pregnant women using diagnostic ultrasound has increased greatly over past decades in the United States. As sonography techniques have been altered and refined, there has been renewed interest concerning possible effects on the developing fetus, since exposures in mid-gestation occur during the sensitive period of brain development. The present study is concerned with possible neonatal functional deficits due to exposure of the fetus to ultrasound. An ultrasound exposure tank was designed specifically for controlled studies of bioeffects. Thirty-six pregnant rats were anesthetized, immersed to the axilla in a water tank and exposed on the 15th, 17th and 19th days of gestation. Twelve rats were exposed to 5.0 MHz pulsed ultrasound of effective pulse duration equal to approximately 0.170 microseconds, pulse repetition rate 1 kHz, and a spatial peak, temporal peak intensity (ISPTP) of 500 W/cm2, representing a clinically relevant exposure level. The spatial peak, pulse average intensity (ISPPA), spatial peak temporal average intensity (ISPTA) and maximum intensity (Im) were determined to be 100 W/cm2, 24 mW/cm2 and 230 W/cm2, respectively. The maximum rarefaction pressure, pr, was measured as 12.5 x 10(5) Pa, and the total power was 2.5 mW. Twelve other rats were exposed to 1500 W/cm2, ISPTP (ISPPA, 350 W/cm2; ISPTA, 58 mW/cm2; Im, 600 W/cm2). Twelve additional rats were sham-exposed. Since the focal area was about 0.5 cm2, computer-controlled stepper motors moved the rats through the ultrasound field to assure uniform exposure of the abdominal/pelvic region. Total exposure time was 35 min. Additionally, a miniature thermocouple was implanted in a few rats to verify that no significant increase in body temperature took place during exposure. All neonates were subjected to five reflex tests and observed for four physiological parameters. Postnatal growth also was monitored. Analyses of the data indicate there were no significant alterations in neonatal development or postnatal growth due to exposure to 5.0 MHz ultrasound below an intensity (ISPTP) of 1500 W/cm2. Studies continue to be completed at higher exposure levels to determine the margin of safety, and the animals will continue to be monitored and evaluated through young adulthood to determine if there are long-term behavioral effects due to fetal exposure to ultrasound.


Hematogenous osteomyelitis of the wrist in children.
Wrist osteomyelitis is a rare infection, and few studies have been published about its prognosis and treatment. We retrospectively examined the medical records of 18 children older than 4 months who were diagnosed with wrist osteomyelitis. A definite diagnosis of wrist osteomyelitis required either confirmatory radiographic/bone scintigraphy changes associated with compatible clinical picture and elevated laboratory indices consistent with infection. The clinical evaluation was based on clinical and radiographic assessment at 1 week, 2 weeks, 3 months, 6 months, 1 year, and 2 years after the diagnosis. Delay between initial symptoms and treatment ranged from 1 to 45 days (mean, 7 days). The radiographs at diagnosis demonstrated a lytic zone in the distal radial or ulnar metaphysis in 5 cases. All patients were treated with 6 weeks' course of antibiotics with sequential parenteral (7 days)-oral with a third-generation cephalosporin (Cefotaxim) associated with Fosfomycin. Surgical debridement was needed in 5 cases because plain radiographs, ultrasonography, or magnetic resonance imaging (MRI) had confirmed the presence of an intraosseous or subperiosteal abscess. Seven isolated organisms were methicillin-susceptible Staphylococcus aureus, and 1 was methicillin-resistant S. aureus. The average follow-up was 2 years. Significant orthopaedic sequelae as distal radius/ulna epiphysiodesis were apparent in 2 patients. Wrist osteomyelitis is a severe infection with initial radiographic lytic zone in almost 30% of cases and with growth disturbance in 11% at the last follow-up. If we include the presence of intraosseous or subperiosteal abscess that required surgical debridement, the initial complication rate is 33%, which is superior to the 5% complication rate in the literature about general osteomyelitis. Misdiagnosis at initial clinical examination can explain this condition.


Comparison of fractional exhaled nitric oxide levels in chronic obstructive pulmonary disease, bronchial asthma and healthy subjects of Nepal.
Fractional exhaled nitric oxide levels in exhaled breath can indicate ongoing eosinophilic airway inflammation, specifically in asthma. But its utility is being explored for central airway inflammations, including chronic obstructive pulmonary disease. Normal levels of fractional exhaled nitric oxide (FENO50) have been defined in different studies but not in Nepal. This study compares FENO50 levels in normal subjects, asthma and chronic obstructive pulmonary disease. Single breath estimation of FENO50 was measured by a handheld electrochemical sensor-based device in normal non-smoking adults (n = 106), clinically controlled asthma (n = 106) and stable chronic obstructive pulmonary disease (n = 106). The geometric mean for FENO50 was 14 parts per billion (ppb) with a median of 16 ppb, first quartile at 11 ppb and third quartile at 20 ppb in normal non-smoking adults. The values were 31 ppb (geometric mean), 34 ppb (median), 17 ppb (first quartile) and 79 ppb (third quartile) in clinically controlled asthma. Similarly the values were 10 ppb (geometric mean), 11 ppb (median), 6 ppb (first quartile) and 17 ppb (third quartile) in stable chronic obstructive airway disease. The log-transformed data showed significantly higher FENO50 levels in the asthma group compared with the normal (p < 0.001) and chronic obstructive airway disease (p < 0.001). However, levels were similar between healthy and chronic obstructive airway disease groups (p = 0.08). FENO50 levels were higher in bronchial asthma (despite disease control) than in normal non-smoking adults and subjects with stable chronic obstructive pulmonary disease. Levels of FENO50 were similar between the chronic obstructive airway disease and normal groups.


Survey finds few orthopedic surgeons know the costs of the devices they implant.
Orthopedic procedures represent a large expense to the Medicare program, and costs of implantable medical devices account for a large proportion of those procedures' costs. Physicians have been encouraged to consider cost in the selection of devices, but several factors make acquiring cost information difficult. To assess physicians' levels of knowledge about costs, we asked orthopedic attending physicians and residents at seven academic medical centers to estimate the costs of thirteen commonly used orthopedic devices between December 2012 and March 2013. The actual cost of each device was determined at each institution; estimates within 20 percent of the actual cost were considered correct. Among the 503 physicians who completed our survey, attending physicians correctly estimated the cost of the device 21 percent of the time, and residents did so 17 percent of the time. Thirty-six percent of physicians and 75 percent of residents rated their knowledge of device costs "below average" or "poor." However, more than 80 percent of all respondents indicated that cost should be "moderately," "very," or "extremely" important in the device selection process. Surgeons need increased access to information on the relative prices of devices and should be incentivized to participate in cost containment efforts.


Sequence-based diversity of 23 autosomal STR loci in Koreans investigated using an in-house massively parallel sequencing panel.
As DNA databases continue to grow and international cooperation increases, forensic STR loci have expanded to increase the discriminatory power and inter-database compatibility. Current capillary electrophoresis (CE) and/or massively parallel sequencing (MPS)-based commercial STR analysis systems reflect such changing trends of expanding STR loci. Due to the general gains of larger multiplexing and the detection of sequence variation, the application of MPS technology to STR analysis has further improved discrimination and is expected to aid in mixture interpretation by increasing the effective number of alleles. However, high-throughput analysis has rarely been reported for forensic DNA databasing. In this study, we present the sequencing results from 250 Korean samples at 23 commonly used STR loci (D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045) using an in-house assay designed for MPS. All amplicons in the multiplex exhibited a size range of 77 to 217 base pairs, and the barcoded library for the MPS run was easily prepared using a PCR-based library preparation method followed by sequencing on a MiSeq System (Illumina). We compared the STR genotyping results with those obtained using CE and scrutinized the sequence variations in both the targeted STR and flanking regions. MPS results of 23 autosomal STRs were 99.97% concordant with those of CE results. D12S391 and D21S11 exhibited, respectively, the highest number of alleles and genotypes by the MPS analysis. Single nucleotide polymorphisms and insertion and deletions (Indels) were observed in the flanking regions of D1S1656, D2S441, D5S818, D7S820, D13S317, D16S539, D21S11, and Penta D. Consequently, an MPS analysis of an expanded set of STRs, as demonstrated in the population statistics of a Korean population, will be of great practical use in forensic genetics.


[Ability of the influenza viruses and their envelope proteins to stimulates endothelial cells apoptosis in vitro].
The ability of the modern epidemic strains of influenza virus type A (subtypes H5N1, H3N2, H1N1pdm) and their surface proteins, hemagglutinin (HA) and neuraminidase to cause the activation of the cellular protein caspase-3 and stimulate the emergence of phosphatidylserine on the membrane of human endothelial cell line EAhy926 has been studied. It was questioned how the viruses and their surface proteins that were studied cause the activation of caspase-3 after 0.5 h of exposure that recorded immunogistotsitohimicheski. The test viruses and neuraminidase (concentration 10 μg/ml) led to the appearance of phosphatidylserine on the cell membrane in a time interval of 2-8 h from the beginning of the treatment, which was recorded by flow cytometry. The death of endothelial cells when exposed to the HA (in a concentration of 50 μg/ml) and in the same time frame was not accompanied by the appearance of phosphatidylserine. The specific feature of apoptotic cell death during the reproduction of the virus are described, as well as the effects of viral proteins.


Intelligent Cubic-Designed Piezoelectric Node (iCUPE) with Simultaneous Sensing and Energy Harvesting Ability toward Self-Sustained Artificial Intelligence of Things (AIoT).
The evolution of artificial intelligence of things (AIoT) drastically facilitates the development of a smart city via comprehensive perception and seamless communication. As a foundation, various AIoT nodes are experiencing low integration and poor sustainability issues. Herein, a cubic-designed intelligent piezoelectric AIoT node iCUPE is presented, which integrates a high-performance energy harvesting and self-powered sensing module via a micromachined lead zirconate titanate (PZT) thick-film-based high-frequency (HF)-piezoelectric generator (PEG) and poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) nanofiber thin-film-based low-frequency (LF)-PEGs, respectively. The LF-PEG and HF-PEG with specific frequency up-conversion (FUC) mechanism ensures continuous power supply over a wide range of 10-46 Hz, with a record high power density of 17 mW/cm3 at 1 g acceleration. The cubic design allows for orthogonal placement of the three FUC-PEGs to ensure a wide range of response to vibrational energy sources from different directions. The self-powered triaxial piezoelectric sensor (TPS) combined with machine learning (ML) assisted three orthogonal piezoelectric sensing units by using three LF-PEGs to achieve high-precision multifunctional vibration recognition with resolutions of 0.01 g, 0.01 Hz, and 2° for acceleration, frequency, and tilting angle, respectively, providing a high recognition accuracy of 98%-100%. This work proves the feasibility of developing a ML-based intelligent sensor for accelerometer and gyroscope functions at resonant frequencies. The proposed sustainable iCUPE is highly scalable to explore multifunctional sensing and energy harvesting capabilities under diverse environments, which is essential for AIoT implementation.


Impact of information about obesity genomics on the stigmatization of overweight individuals: an experimental study.
Advances in genomic technologies are rapidly leading to new understandings of the roles that genetic variations play in obesity. Increasing public dissemination of information regarding the role of genetics in obesity could have beneficial, harmful, or neutral effects on the stigmatization of obese individuals. This study used an online survey and experimental design to examine the impact of genetic versus non-genetic information on obesity stigma among self-perceived non-overweight individuals. Participants (n = 396) were randomly assigned to read either genetic, non-genetic (environment), or gene-environment interaction obesity causal information. A total of 48% of participants were female; mean age was 42.7 years (range = 18-86 years); 75% were white; 45.2% had an annual household income of less than $40,000; mean BMI was 23.4 kg/m(2). Obesity stigma was measured using the Fat Phobia Scale - short form (FPS-S). After reading the experimental information, participants in the genetic and gene-environment conditions were more likely to believe that genetics increase obesity risk than participants in the non-genetic condition (both P < 0.05), but did not differ on obesity stigma. Obesity stigma was higher among whites and Asians than Hispanics and African Americans (P = 0.029), and associated with low self-esteem (P = 0.036). Obesity stigma was also negatively associated with holding 'germ or virus' (P = 0.033) and 'overwork' (P = 0.016) causal beliefs about obesity, and positively associated with 'diet or eating habits' (P = 0.001) and 'lack of exercise' (P = 0.004) causal beliefs. Dissemination of brief information about the role of genetics in obesity may have neither a beneficial nor a harmful impact on obesity stigmatization compared with non-genetic information among self-perceived non-overweight individuals.


Effect of twenty-four-week treatment with the antiestrogen EM-800 on estrogen-sensitive parameters in intact and ovariectomized mice.
Treatment with the antiestrogen EM-800, at the daily oral dose of 3 microg, 10 microg, 30 microg, or 100 microg for 24 weeks, caused a marked inhibition of uterine and vaginal weight in both intact and ovariectomized mice. Maximal 64% and 41% inhibitions of uterine weight were achieved in intact and ovariectomized animals, respectively. Similar inhibitory effects of EM-800 were observed on vaginal weight with maximal inhibitions of 71% and 35%, in intact and ovariectomized animals, respectively. The pure antiestrogenic activity of EM-800 on the hypothalamo-pituitary-ovarian axis is illustrated by the 76-91% increases in ovarian weight observed in intact animals treated with the 10-100 microg doses of the antiestrogen. Serum 17beta-estradiol was 93% increased at the 100 microg daily dose of EM-800, whereas serum androstenedione, testosterone, and dihydrotestosterone were 141-713% increased over control at the same dose of the antiestrogen. Serum LH was increased by treatment with EM-800 in intact animals, whereas no effect was observed on the elevated gonadotropin levels in ovariectomized animals. At all doses used in intact animals, the antiestrogen caused a complete disappearance of the glandular elements of the mammary gland, the atrophy being comparable with that observed in ovariectomized mice. The mammary gland of EM-800-treated animals was exclusively composed of an atrophied ductal system lined by atrophied epithelial cells with an absence of lobulo-glandular elements. No effect of the compound was observed on the histology of the mammary gland in ovariectomized animals, thus showing the pure antiestrogenic effect of EM-800 on the mammary gland, as shown also for the uterus, vagina, and hypothalamo-pituitary axis. At histopathology, all doses of EM-800 in intact animals led to a moderate to severe uterine and vaginal atrophy. The uterine atrophy affected both the myometrium and the endometrium. Interestingly, the uterine atrophy achieved in intact animals treated with EM-800 was greater than that observed after ovariectomy alone, thus clearly demonstrating the pure antiestrogenic activity of EM-800. The present data show the highly potent and pure antiestrogenic activity of EM-800 on all parameters measured after 6 months of treatment in both intact and ovariectomized mice, a maximal effect being reached at the daily 10 microg dose of the antiestrogen in intact animals.


On pseudo-values for regression analysis in competing risks models.
For regression on state and transition probabilities in multi-state models Andersen et al. (Biometrika 90:15-27, 2003) propose a technique based on jackknife pseudo-values. In this article we analyze the pseudo-values suggested for competing risks models and prove some conjectures regarding their asymptotics (Klein and Andersen, Biometrics 61:223-229, 2005). The key is a second order von Mises expansion of the Aalen-Johansen estimator which yields an appropriate representation of the pseudo-values. The method is illustrated with data from a clinical study on total joint replacement. In the application we consider for comparison the estimates obtained with the Fine and Gray approach (J Am Stat Assoc 94:496-509, 1999) and also time-dependent solutions of pseudo-value regression equations.


Effects of growth rate and promoter activity on single-cell protein expression.
Protein expression in a single cell depends on its global physiological state. Moreover, genetically-identical cells exhibit variability (noise) in protein expression, arising from the stochastic nature of biochemical processes, cell growth and division. While it is well understood how cellular growth rate influences mean protein expression, little is known about the relationship between growth rate and noise in protein expression. Here we quantify this relationship in Bacillus subtilis by a novel combination of experiments and theory. We measure the effects of promoter activity and growth rate on the expression of a fluorescent protein in single cells. We disentangle the observed protein expression noise into protein-specific and systemic contributions, using theory and variance decomposition. We find that noise in protein expression depends solely on mean expression levels, regardless of whether expression is set by promoter activity or growth rate, and that noise increases linearly with growth rate. Our results can aid studies of (synthetic) gene circuits of single cells and their condition dependence.


Pregnancy and Delivery Management With Recombinant Factor VIIa in a Glanzmann Thrombasthenia Patient: A Case Report.
The management of pregnancy and delivery in patients with Glanzmann thrombasthenia requires platelet transfusion and recombinant activated factor VII. We report two successful pregnancies in a single patient and propose a protocol for monitoring and treatment. The urgent need for controlled trials and other epidemiological studies is also underscored.


Diversity of spined loaches from Asia Minor in a phylogenetic context (Teleostei: Cobitidae).
Accurate determination of species diversity in areas of high endemicity, particularly those lacking comprehensive systematic knowledge, represents a challenge for both taxonomists and conservationists. This need is particularly evident in areas greatly affected by anthropogenic disturbances such as the Eastern Mediterranean and its freshwater environments. To improve our knowledge of Eastern Mediterranean freshwater fishes, we phylogenetically studied Western Palearctic Cobitis species, focusing on those found in Turkey. Overall, our results provide a robust framework to assess the number of species of Cobitis. Phylogenetic reconstructions based on mitochondrial (cyt b) and nuclear (RAG1) sequences show seven major clades (Clades 1-7) grouping all Western Palearctic Cobitis species, except C. melanoleuca. In general, each major clade comprises Cobitis species that inhabit geographically close areas and have similar secondary sexual characters. Multiple divergent lineages were identified in our analyses, some of which were highly divergent such as the ones inhabiting Turkish freshwaters. Moreover, in some analyses, several of the identified lineages were incongruent with a priori defined species. Furthermore, our analyses identified eight potentially new candidate species, six that had been suggested in previous studies and two that are reported here for the first time. Our results reveal Turkey as the area with the greatest diversity of spined loaches in the Mediterranean.


Intracellular redox changes during apoptosis.
In the current paradigm for apoptotic cell death, the activity of a family of proteases related to interleukin 1-beta converting enzyme (ICE) orchestrates the multiple downstream events (such as cell shrinkage and chromatin degradation) that comprise apoptosis. A variety of stimuli can induce this type of cell death. One of the most reproducible inducers is mild oxidative stress, although it is unclear how an oxidative stimulus activates ICE-like proteases. Oxidative modification of proteins and lipids have also been observed in cells undergoing apoptosis in response to non-oxidative stimuli, suggesting that intracellular oxidation may be a general feature of the effector phase of apoptosis. However, attempts to consistently detect a requirement for reactive oxygen species in apoptosis have been inconclusive. Recent experiments revealing that apoptosis is typically accompanied by a depletion of intracellular reduced glutathione (GSH) are also discussed. In JURKATT lymphocytes treated with antibodies to the Fas/APO-1 surface receptor, this depletion results from an accelerated efflux of the reduced thiol rather than any intracellular oxidation. As GSH is the most abundant cytosolic reductant, we propose that its efflux may provide a non-oxidative mechanism by which the reducing environment of apoptotic cells is lost. An increase in oxidative damage to proteins and lipids would then result even in the absence of an increase in the production of oxidants. This may explain the seemingly contradictory findings that increased oxidative stress is not required for apoptosis even though antioxidants often inhibit the process and peroxidised products accumulate in apoptotic cells.


How does stigma affect people with psoriasis?
Psoriasis is associated with a major additional psychological burden. To investigate whether the extent of skin involvement, stigmatization, and perceived social support are related to depressive symptoms in psoriasis patients. One hundred and forty-eight psoriasis patients completed in the BSA, the Beck Depression Inventory, Stigmatization Scale, and Multidimensional Scale of Perceived Social Support. Almost 13% of participants obtained a BDI total score indicating moderate depressive symptoms. The results of regression analysis revealed that greater depression severity in psoriasis patients is associated with higher levels of psoriasis-related stigma, lower perceived social support, female gender and a shorter duration of the disease, explaining 43% of the variance of depression. The stigmatization was the most powerful predictor of depressive symptoms for psoriasis patients and accounted for 33% of the variance. The extent of psoriasis does not directly lead to mood disturbance in these patients. Rather, social stigma accounted for this relationship. Strategies for reducing the stigma attached to patients with psoriasis are required.


Validation of a commercial serodiagnostic kit for diagnosing pulmonary Mycobacterium avium complex disease.
A commercial serodiagnostic kit for diagnosing pulmonary disease due to Mycobacterium avium complex (MAC-PD) was developed and launched in Japan in 2011. To evaluate the performance of this kit in routine clinical settings. In this retrospective single-centre study, data on serum levels of anti-glycopeptidolipid (GPL) core IgA antibody (U/ml) measured using the kit were analysed in patients diagnosed with MAC-PD according to American Thoracic Society criteria, in those with pulmonary tuberculosis (PTB) or pulmonary M. kansasii disease and in healthy volunteers. The anti-GPL-core IgA antibody levels of serum were significantly higher (P < 0.0001) in patients with MAC-PD (n = 485) than in those with PTB (n = 133) or pulmonary M. kansasii disease (n = 23) or in healthy subjects (n = 265). When the cut-off level was set at 0.7 U/ml, the sensitivity and specificity were respectively 78.6% and 96.9%. Higher antibody levels were observed in patients with greater extent of disease on chest computed tomography (P < 0.0001). The serodiagnostic kit revealed good sensitivity and specificity. The antibody levels may reflect disease activity. Additional work is needed to determine whether the diagnostic assay could be used in conjunction with current diagnostic criteria to improve the diagnosis of MAC-PD.