Isolated dissecting aneurysm of the renal artery.
We report two cases of an unusual cause of the acute onset of hypertension, a spontaneous dissecting aneurysm localized to the renal artery. Also reviewed are 16 reported cases from the literature. The mean age of the 18 patients was 52 years. The majority of these patients were males (78%). Hypertension was a presenting sign in 14 (78%), but was not usually a pre-existing feature. Loin pain, often severe, occurred in eleven patients (61%), whereas gross hematuria was recorded only in two (11%). The right renal artery was involved in ten cases (55%), the left in three (17%), and both in five cases (28%). Atherosclerosis of the renal arteries and the aorta was absent in 69%, and mild in 23%. There has been no report of renal artery rupture; however, vascular occlusion occurs frequently. Medical and surgical approaches to the management of this phenomenon have been reported and are reviewed.


Influence of Seidel distortion on combining beams from a phased telescope array.
When beams from an array of a focal telescopes are presented to a beam-combining telescope, tilt errors of the beam wave fronts with respect to the combined wave front place limits on the achievable field of view (FOV); these limits, to the best of our knowledge, have not previously been correctly described in the literature. We show that if the front-end telescopes have just the right Seidel distortion coefficient, then tilt error does not limit the FOV. If this is not the case, at least small FOV's can still be obtained, even if the FOV is not centered on the on-axis direction.


A computerized quantitative food frequency analysis for the clinical setting: use in documentation and counseling.
Documentation of nutrition counseling effectiveness is essential to reinforce its value in an era of escalating health care costs. Counseling effectiveness can be determined definitively only if dietary assessment is made both before and after intervention. Unfortunately, methods currently available have drawbacks that limit feasibility of routine use. A directly computer-readable Quantitative Food Frequency Analysis method, which eliminates the need for manual data entry, has been developed and instituted at the University of Southern California School of Medicine, Los Angeles, for outpatient counseling. A 1-hour interview, focusing upon "usual" intake, is conducted using pictorial menus for food items. Feedback is available to the patient and health care team immediately. The data base is derived from the National Heart, Lung, and Blood Institute Food Table; the intake of 61 nutrients, including 23 fatty acids, is computed. The computer printout consists of four components: a summary; an alert for foods high in fat, cholesterol, sucrose, alcohol, and/or sodium; a listing of all foods consumed by frequency, accompanied by their nutrient contribution to daily intake; and a bar graph relating current nutrient intake to recommended levels. This document serves as a counseling tool and can support claims for third-party payment.


Peroxisome proliferator-activated receptor gamma agonism modifies the effects of growth hormone on lipolysis and insulin sensitivity.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists such as thiazolidinediones (TZDs) improve insulin sensitivity in type 2 diabetes mellitus (T2DM) through effects on fat metabolism whereas GH stimulates lipolysis and induces insulin resistance. To evaluate the impact of TZDs on fat metabolism and insulin sensitivity in subjects exposed to stable GH levels. A randomized, placebo-controlled, double-blind parallel-group study including 20 GH-deficient patients on continued GH replacement therapy. The patients were studied before and after 12 weeks. Patients received either pioglitazone 30 mg (N = 10) or placebo (N = 10) once daily for 12 weeks. Adiponectin levels almost doubled during pioglitazone treatment (P = 0.0001). Pioglitazone significantly decreased basal free fatty acid (FFA) levels (P = 0.02) and lipid oxidation (P = 0.02). Basal glucose oxidation rate (P = 0.004) and insulin sensitivity (P = 0.03) improved in the patients who received pioglitazone treatment. The change in insulin-stimulated adiponectin level after pioglitazone treatment was positively correlated to the change in insulin-stimulated total glucose disposal (R = 0.69, P = 0.04). The impact of GH on lipolysis and insulin sensitivity can be modified by administration of TZDs.


Young children's online learning during COVID-19 pandemic: Chinese parents' beliefs and attitudes.
Online learning has been widely promoted to replace traditional face-to-face learning during the COVID-19 pandemic to maintain young children's learning and play at home. This study surveyed 3275 Chinese parents' beliefs and attitudes around young children's online learning during the lockdown of the COVID-19 pandemic. Most parents (92.7%) in the study reported that their children had online learning experiences during the pandemic, and many (84.6%) spent less than a half-hour each time. The parents generally had negative beliefs about the values and benefits of online learning and preferred traditional learning in early childhood settings. They tended to resist and even reject online learning for three key reasons: the shortcomings of online learning, young children's inadequate self-regulation, and their lack of time and professional knowledge in supporting children's online learning. Also, the hardship caused by the COVID-19 pandemic has made them suffering, thus more resistant to online learning at home. The results suggested that the implementation of online learning during the pandemic has been problematic and challenging for families. The Chinese parents were neither trained nor ready to embrace online learning. The paper concluded with implications for policymakers and teacher education.


Detection of circaseptan rhythm and the "Monday effect" from long-term pulse rate dynamics.
This study proposes a methodology to detect circaseptan (CS) rhythm in pulse rate (PR) data and to investigate the "Monday effect" in CS rhythm. Daily PR was collected from a middle-aged healthy working woman over one year. PR, SDNN index and sample entropy (SampEn) were chosen as the indexes of PR dynamics. In order to avoid interference from other biorhythms, ensemble empirical mode decomposition (EEMD) method was used to decompose the original PR series into multiple components. And the single cosinor method was applied to fit the detrended component signal. An optimal 7-day period was found in all indexes (P = 0.0103, P = 0.0133, P = 0.0122 for PR, SDNN index and SampEn, separately) that demonstrated an underlying CS rhythm. In the following study, a statistical Monday decrease in PR dynamics was observed especially significant in the detrended signal. The results suggested a direct relationship between the "Monday effect" and the CS variation, and also indicated a cardiac susceptibility to the social activities. The findings in CS periodicity and the "Monday effect" may help understand the human's biorhythm, provide evidence for preventive and optimized timing treatment, and also serve to daily health management.


Morphological and smooth muscle cell phenotypic changes in fetal rabbit aorta during early development.
Previous studies from our laboratory noted a) high aortic cholesterol esterification activity in the fetal rabbit, and b) increased susceptibility of fetal aortic explants to smooth muscle cell proliferation in culture, two features commonly associated with atherogenesis. This prompted us to examine in detail morphological development of fetal aorta and its relationship to fetal plasma cholesterol levels. Our studies made three important observations: 1) plasma cholesterol levels were high in early fetus which decreased at term; 2) in early fetus aortic endothelial cells appear to protrude into the lumen, whereas at birth the cells become flat, forming a continuous endothelium sheet; 3) in early fetus, smooth muscle cells exist predominantly in synthetic phenotype, while at birth the cells appear contractile. Despite the presence of synthetic smooth muscle cells and hypercholesterolemia in early fetal life, no accumulation of lipids was evident under transmission electron microscopy.


Surgical management of maxillectomy defects based on the concept of buttress reconstruction.
Few published large series have described a surgical approach to maxillary skeletal reconstruction on the basis of the extent of maxillectomy. We have reviewed a 10-year experience with 38 consecutive maxillary reconstructions with respect to maxillectomy defects, reconstructive procedures, reconstructed buttresses, and functional and aesthetic outcomes. Maxillectomy defects were classified into three categories on the basis of the buttress concept. Buttress reconstruction was most frequently performed in category III maxillary defects (56%), followed by category I (50%) and category II (20%). The vascularized composite autograft included the rectus abdominis myocutaneous free flap combined with costal cartilage, and the latissimus dorsi myocutaneous free flap combined with the V-shaped scapula is an effective method for reliable reconstruction of both skeletal and soft tissues. A critical assessment for skeletal defects and associated soft tissue defects is essential for an adequate approach to solve complex problems in maxillary reconstruction. On the basis of retrospective analysis of this series, a reconstructive algorithm for surgical management of maxillectomy defects is proposed.


Use of salicylate to estimate the "threshold" inducer level for de novo synthesis of the phenol-degrading enzymes in Pseudomonas putida strain H.
A special approach was used to elucidate the "threshold" inducer concentration for coordinative de novo synthesis of phenol hydroxylase(s), catechol 2,3-dioxygenase and the 2-hydroxymuconic semialdehyde-metabolizing enzymes which initiate phenol catabolism in Pseudomonas putida strain H. It is based on cell-precultivation with glucose (as the carbon and energy source) in the presence of different concentrations of sodium salicylate which proved to be a potent non-metabolizable inducer in strain H of these enzymes. Subsequent estimation of the activity status of resting cell suspensions and cell-free extracts, respectively, prepared from those strain H cultures clearly revealed failing de novo synthesis of the mentioned phenol-degrading enzymes at salicylate concentrations lower than 0.2 mg/l.


Precision-porous polyurethane elastomers engineered for application in pro-healing vascular grafts: Synthesis, fabrication and detailed biocompatibility assessment.
Unmet needs for small diameter, non-biologic vascular grafts and the less-than-ideal performance of medium diameter grafts suggest opportunities for major improvements. Biomaterials that are mechanically matched to native blood vessels, reduce the foreign body capsule (FBC) and demonstrate improved integration and healing are expected to improve graft performance. In this study, we developed biostable, crosslinked polyurethane formulations and used them to fabricate scaffolds with precision-engineered 40 μm pores. We matched the scaffold mechanical properties with those of native blood vessels by optimizing the polyurethane compositions. We hypothesized that such scaffolds promote healing and mitigate the FBC. To test our hypothesis, polyurethanes with 40 μm pores, 100 μm pores, and non-porous slabs were implanted subcutaneously in mice for 3 weeks, and then were examined histologically. Our results show that 40 μm porous scaffolds elicit the highest level of angiogenesis, cellularization, and the least severe foreign body capsule (based on a refined assessment method). This study presents the first biomaterial with tuned mechanical properties and a precision engineered porous structure optimized for healing, thus can be ideal for pro-healing vascular grafts and in situ vascular engineering. In addition, these scaffolds may have wide applications in tissue engineering, drug delivery, and implantable device.


Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice TgTauP301L.
The aim of this study is to clarify the relationship of microglia to phosphorylated tau accumulation and the characteristics of microglial activation in brain lesions of human tauopathies in comparison to mutant tau transgenic (TG) mice. We performed immunocytochemical analyses of brains from six patients with tauopathies, and 24 mice (18 TG mice expressing mutant tau P301L and six non-TG control mice, 11 to 27 months of age) using anti-tau antibodies and various microglial markers. In the tau TG, both semiquantitative severity ratings of microglial activation and an ultrastructural study were performed. In human tauopathies, Iba1- and major histocompatibility complex (MHC) class II-positive activated microglia increased in regions of phosphorylated tau (AT8) accumulation. The immunoreactivity of scavenger receptor class A (SRA) was present in some activated microglia, including phagocytic microglia in Alzheimer's disease (AD). Double-immunofluorescent analysis under a confocal microscope showed activated microglia at the vicinity of AT8-positive cells. Semiquantitative data of the TG and control mice indicated that the immunopositivity of AT8 was closely associated with the number of Iba1-positive microglia in the cortical area. Tau-associated microglia showed rare immunoreactivity for MHC class II antigen and SRA in the TG mice. Ultrastructurally, activated microglia with enlarged cytoplasm were located near neurons containing abnormal cytoskeletons. This comparative study of human tauopathies and tau TG mice indicated that microglial activation was closely related to phosphorylated tau accumulation, and that activated microglia of the TG mice may have the low expression of MHC class II and SRA compared with those of human tauopathies.


Effects of endogenous progesterone during ovarian follicle superstimulation on embryo quality and quantity in beef cows.
Despite modifications in techniques and protocols used for multiple ovulation embryo transfer in recent decades, transferrable quality embryos (TQE) has remained relatively unchanged. The objective of this study was to evaluate the effects of endogenous progesterone during beef cow superstimulation on embryo quality and quantity. Thirty non-pregnant beef cows were sorted into 1 of 5 replicates and randomly assigned to one of two groups: High Progesterone (HP) or Low Progesterone (LP). All cows, were pre-synchronized utilizing a 5-d CO-Synch + CIDR protocol. Nine days after estrus (d 0) with a corpus luteum present, all cows received ultrasound-guided dominant follicle ablation (DFA) and were administered a CIDR with LP cows also being administered PGF2α. All cows began a timed, 13-d, superovulation CIDR-based protocol and were artificially inseminated (AI) twice. Embryo were recovered and evaluated on each replicate 7 days after first AI. Blood samples were collected to evaluate progesterone (P4) and estradiol concentrations daily when cows were handled. Greater number of total embryos were recovered from the HP than the LP cows (19.26 vs. 10.74, P = 0.01). The HP cows also had greater number Stage 4 embryos along with more Quality Grade 3 and 4 embryos than the LP group (5.76 vs 2.20 P = 0.002; 1.87 vs 0.61, P = 0.01; 8.22 vs 2.89, P = 0.01, respectively). However, LP cows had a greater percentage overall of freezable embryos with a higher percentage of Grade 1 embryos (58.22 vs 37.32, P = 0.03) and a greater percentage of Stage 7 and 6 TQEs (18.47 vs 1.22, P = 0.01; 10.37 vs 3.19, P = 0.03). Serum P4 concentrations were greater on d 2-3 in the HP cows (P = 0.002). In addition, HP cows had greater concentrations of estradiol (P < 0.0001) on d 6. Comparatively, estradiol was greater in concentration in the LP cows (P ≤ 0.04) on d 2-4. In conclusion, removal of endogenous progesterone during superovulation may decrease the total number of embryos but increase the percentage of Grade 1 embryos and percentage of Stage 6 and 7 TQE in a single recovery.


The effect of conductivity on ST-segment epicardial potentials arising from subendocardial ischemia.
We quantify and provide biophysical explanations for some aspects of the relationship between the bidomain conductivities and ST-segment epicardial potentials that result from subendocardial ischemia. We performed computer simulations of ischemia with a realistic whole heart model. The model included a patch of subendocardial ischemic tissue of variable transmural thickness with reduced action potential amplitude. We also varied both intracellular and extracellular conductivities of the heart and the conductivity of ventricular blood in the simulations. At medium or high thicknesses of transmural ischemia (i.e., at least 40% thickness through the heart wall), a consistent pattern of two minima of the epicardial potential over opposite sides of the boundary between healthy and ischemic tissue appeared on the epicardium over a wide range of conductivity values. The magnitude of the net epicardial potential difference, the epicardial maximum minus the epicardial minimum, was strongly correlated to the intracellular to extracellular conductivity ratios both along and across fibers. Anisotropy of the ischemic source region was critical in predicting epicardial potentials, whereas anisotropy of the heart away from the ischemic region had a less significant impact on epicardial potentials. Subendocardial ischemia that extends through at least 40% of the heart wall is manifest on the epicardium by at least one area of ST-segment depression located over a boundary between ischemic and healthy tissue. The magnitude of the depression is a function of the bidomain conductivity values.


The influence of estradiol and diet on small intestinal glucose transport in ovariectomized rats.
Although gender differences exist for intestinal absorption of nutrients and drugs, the possible role estradiol may play in modulating nutrient transport has not been established. Therefore, small intestine glucose transport was measured 1 week after administering estradiol to ovariectomized rats fed diets high in carbohydrate (C) or protein (P). Rats treated with estradiol ate 21% less (P<0.05) and lost body mass (7%; P<0.05) but did not have smaller intestines. Administration of estradiol increased rates of glucose transport, but only when the rats were fed the C diet. These findings indicate that estradiol causes a disconnect between food intake and the dimensions and nutrient transport capacities of the small intestine. Furthermore, the responses to estradiol are influenced by diet composition, are not of the same magnitude for rats and dogs, and can be predicted to affect systemic availability of nutrients and drugs.


Operando Direct Observation of Filament Formation in Resistive Switching Devices Enabled by a Topological Transformation Molecule.
Conductive filaments (CFs) play a critical role in the mechanism of resistive random-access memory (ReRAM) devices. However, in situ detection and visualization of the precise location of CFs are still key challenges. We demonstrate for the first time the use of a π-conjugated molecule which can transform between its twisted and planar states upon localized Joule heating generated within filament regions, thus reflecting the locations of the underlying CFs. Customized patterns of CFs were induced and observed by the π-conjugated molecule layer, which confirmed the hypothesis. Additionally, statistical studies on filaments distribution were conducted to study the effect of device sizes and bottom electrode heights, which serves to enhance the understanding of switching behavior and their variability at device level. Therefore, this approach has great potential in aiding the development of ReRAM technology.


Simultaneous determination of deuterated and non-deuterated alpha-tocopherol in human plasma by high-performance liquid chromatography.
Labelled tocopherol is used to evaluate its absorption by biodiscriminating the dietary intake from the endogenous tocopherol pool of subject. A normal-phase high-performance liquid chromatographic method is described for the easy separation and quantification of deuterated (d(6)) and non-deuterated alpha-tocopherol. The alpha-tocopherol isotopomers were extracted from plasma triacylglycerol-rich lipoproteins in hexane, separated by two EC Nucleosil columns in series with a mobile phase of hexane-isopropanol (659.34:0.786, w/w) running isocratically. The detection of d(6)-alpha-tocopherol was performed by its UV absorbance at 297 nm with a limit of detection of 34 pmol/ml, a limit of quantification of 83 pmol/ml and a range of determination of 34-9905 pmol/ml. Between- and within-assay RSDs were 2.4% (n=10) and 2.7% (n=5), respectively.


Fos proteins are not prerequisite for osmotic induction of vasopressin transcription in supraoptic nucleus of rats.
While it is well known that osmotic stimulation induces the expression of Fos family members in the supraoptic nucleus (SON), it is unclear whether the induced protein products are involved in the regulation of the gene transcription of arginine vasopressin (AVP). In the present study, we examined the in vivo correlation between changes in AVP gene transcription and expression of the various Fos family members in the SON after acute osmotic stimuli. The data demonstrated that the peak of AVP transcription (measured by intronic in situ hybridization) observed 15min after an injection of hypertonic saline preceded the expression of Fos proteins, which became detectable at 30min and peaked at 120min. Electrophoretic mobility shift assay showed that the expressed Fos proteins bound to the composite AP-1/CRE-like site in the AVP promoter. These data suggest that Fos proteins in the SON induced by acute osmotic stimuli could affect AVP gene transcription by binding to the AVP promoter, but they are not prerequisite for the induction of AVP gene transcription.


[Significance of Helicopter Emergency Medical Service in Prehospital Trauma Care].
In the late 1960s, the helicopter emergency medical service (HEMS) was established in Germany because of an increasing number of severe injuries in traffic accidents. To get a doctor quickly on scene was the initial intention, rather than transporting the patient. Today, rescue helicopters cover the entire field of emergency medicine and are an important transportation device for polytrauma patients. The importance of the HEMS for the treatment of severely injured patients was examined by an analysis of the databases of the leading air rescue organisations ADAC and DRF Luftrettung (2005-2011). Traumatological cases, albeit with large regional differences, make up 35 % of all uses of the helicopter emergency services. For the multiply injured patient in particular, in over 40 % of the cases there is a joint patient care involving both helicopter- and ambulance-based emergency services. The HEMS undertakes especially the rapid, if necessary, even transregional transport to specialised trauma centres.


Evaluation of the change in sphingolipids in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 treated with arsenic trioxide.
Arsenic trioxide (As2O3) has been found to display anticancer activity against many types of tumors and has been developed into an anticancer drug in clinical treatments. Sphingolipids are membrane lipids that participate in many signal transduction pathways. In this paper, the changes in sphingolipids of the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803 treated with arsenic trioxide were investigated using an HPLC-ESI-MS/MS method. Analytes were separated by an XBridge BEH C8 column used for Cer, HexCer, LacCer and SM chromatographic separation, and a Capcell PAK MG II C18 column was used for Sph, dhSph, S1P and dhS1P chromatographic separation and gradient elution with acetonitrile-water containing 0.1% formic acid as a mobile phase. A tandem mass spectrometer QTrap in SRM mode was employed in combination with RPLC as a detector for quantitative analysis. The ceramide/sphingolipid internal standard (IS) mixture was used to quantify the levels of sphingolipids. The distributions of sphingolipids were found to be different in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803. Ceramide (Cer), hexosylceramide (HexCer) and dihexosylceramide (Hex2Cer) levels in U266 cell line are higher than those in MGC-803 cell line. Additionally, sphingomyelin (SM), sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (dhS1P) levels in the MGC-803 cell line are higher than those in the U266 cell line. When treated with arsenic trioxide (1-5μM iAs(III)(As(III) ions)), the levels of Hex2Cer in the human multiple myeloma cell line U266 decreased, and the levels of S1P and dhS1P in the human gastric cancer cell line MGC-803 decreased. The decrease of Hex2Cer, S1P and dhS1P in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 were observed when the concentration of iAs(III) is 1.0μM. Therefore, arsenic trioxide exhibits anti-cancer activity by altering the sphingolipid pathway in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803.


Memantine partly rescues behavioral and cognitive deficits in an animal model of neurodegeneration.
Memantine, a non-competitive NMDA receptor antagonist, is used for the treatment of Alzheimer's disease (AD) and off-label as an anti-depressant. Here we investigated possible anti-depressant, cognitive enhancing and neuroprotective effects of memantine in the olfactory bulbectomized (OBX) rat. OBX is used as a screening model for antidepressants and shows cognitive disturbances. In Experiment I, memantine treatment started 14 days after OBX surgery (this setup is similar to what we use for screening of potential antidepressants) and 2 days before surgery in experiment II. In both experiments, memantine (20 mg/kg, p.o) was administered once daily for 28 days. Animals were tested in the open field (locomotor activity), passive avoidance (fear learning and memory), and holeboard (spatial acquisition and memory) before and after the bulbectomy. Memantine, when administered before surgery, prevented OBX-induced hyperactivity and partly fear memory loss. These behavioral effects were present for at least 3 weeks after cessation of treatment. Memantine, however did not improve spatial memory. When administered 2 weeks after OBX surgery, memantine was ineffective in normalizing open field hyperactivity and improving cognitive deficits. Interestingly, after the animals were retrained in passive avoidance, memantine- treated OBX rats (both in experiment I and II) showed improved fear learning and memory. Our findings suggest that memantine has both neuroprotective and cognitive enhancing effects without antidepressant-like properties in the OBX rat. Based on our results, we propose that memantine may be more beneficial to AD patients when administered early in the disease process.


Climate warming negatively affects plant water-use efficiency in a seasonal hydroperiod wetland.
Climate warming has substantial influences on plant water-use efficiency (PWUE), which is defined as the ratio of plant CO2 uptake to water loss and is central to the cycles of carbon and water in ecosystems. However, it remains uncertain how does climate warming affect PWUE in wetland ecosystems, especially those with seasonally alternating water availability during the growing season. In this study, we used a continuous 10-year (2011-2020) eddy covariance (EC) dataset from a seasonal hydroperiod wetland coupled with a 15-year (2003-2017) satellite-based dataset (called PML-V2) and an in situ warming experiment to examine the climate warming impacts on wetland PWUE. The 10-year EC observational results revealed that rising temperatures had significant negative impacts on the interannual variations in wetland PWUE, and increased transpiration (Et) rather than changes in gross primary productivity (GPP) dominated these negative impacts. Furthermore, the 15-year satellite-based evidence confirmed that, in the study region, climate warming had significant negative consequences for the interannual variations in wetland PWUE by enhancing wetland Et. Lastly, at the leaf-scale, the light response curves of leaf photosynthesis, leaf Et, and leaf-scale PWUE indicated that wetland plants need to consume more water during the photosynthesis process under warmer conditions. These findings provide a fresh perspective on how climate warming influences carbon and water cycles in wetland ecosystems.


Granulocyte isolation from whole blood of goat, sheep, cattle, horse, dog, pig, and man.
A simple two step procedure for the isolation of caprine, ovine, bovine, equine, canine, porcine and human peripheral blood granulocytes is described. After enrichment of granulocytes by centrifugation, contaminating erythrocytes are lysed hypotonically. Recovery, purity, and viability of the granulocyte suspensions are determined. FACScan analysis of the cell suspensions measuring cellular size by forward and sideward light scatter is compared with the corresponding analysis of whole blood leukocytes. Constituencies of the isolated cell suspensions and loss of granulocyte subpopulations through isolation procedure is discussed with regard to granulocyte function assays.


The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.
Graves' orbitopathy (GO) is an orbital manifestation of autoimmune Graves' disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves' orbital fibroblasts. The messenger RNA (mRNA) expression of multiple adipokines was investigated in adipose tissues harvested from GO and healthy subjects. Adipsin protein production was analyzed in primary cultured orbital fibroblasts under insulin growth factor (IGF)-1, CD40 ligand (CD40L) stimulation, and adipogenesis. The effect of blocking adipsin with small interfering RNA (siRNA) on pro-inflammatory cytokine production and adipogenesis was evaluated using quantitative real-time PCR, Western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining. Adipsin gene expression was significantly elevated in GO tissue and increased after the stimulation of IGF-1 and CD40L, as well as adipocyte differentiation in GO cells. Silencing of adipsin suppressed IGF-1-induced IL-6, IL-8, COX2, ICAM-1, CCL2 gene expression, and IL-6 protein secretion. Adipsin suppression also attenuated adipocyte differentiation. Exogenous treatment of recombinant adipsin resulted in the activation of the Akt, ERK, p-38, and JNK signaling pathways. Adipsin, secreted by orbital fibroblasts, may play a distinct role in the pathogenesis of GO. Inhibition of adipsin ameliorated the production of pro-inflammatory cytokines and adipogenesis in orbital fibroblasts. Our study provides an in vitro basis suggesting adipsin as a potential therapeutic target for GO treatment.


Susceptibility and Pathogenesis of Eurasian Tree Sparrows Experimentally Inoculated with Velogenic Newcastle Disease Virus.
Wild-caught Eurasian tree sparrows (Passer montanus) were experimentally inoculated with genotype VII velogenic Newcastle disease virus (NDV) APMV1/chicken/Japan/Fukuoka-1/2004 to investigate the susceptibility and pathogenesis of infected sparrows. Intranasal inoculation of two groups with high or low doses of the virus resulted in the mortality of some birds in both groups on days 7-15 postinoculation. Neurologic signs, ruffled feathers, labored breathing, emaciation, diarrhea, depression, and ataxia were observed in a few birds that eventually succumbed to death. The inoculation of the higher viral load resulted in higher mortality and hemagglutination inhibition antibody detection rates. Tree sparrows that survived the 18-day observation period after inoculation exhibited no apparent clinical signs. Histologic lesions in dead birds were observed in the nasal mucosa, orbital ganglion, and central nervous system, accompanied by NDV antigens detected by immunohistochemistry. Viral inclusion bodies were rarely observed in the cytoplasm of neurons. NDV was isolated from the oral swab and brain of dead birds but not from other organs, including the lung, heart, muscle, colon, and liver. In another experimental group, tree sparrows were intranasally inoculated with the virus and then examined 1-3 days later to examine the early pathogenesis of the disease. Inoculated birds exhibited inflammation of the nasal mucosa with viral antigens, and virus was isolated from some oral swab samples on days 2 and 3 postinoculation. The results of the present study suggest that tree sparrows are susceptible to velogenic NDV, and the infection could be fatal, although some birds can exhibit asymptomatic or mild infection. The unique pathogenesis regarding the neurologic signs and viral neurotropism of velogenic NDV was characteristic in infected tree sparrows.


The platelet receptor for type III collagen (TIIICBP) is present in platelet membrane lipid microdomains (rafts).
Platelet interactions with collagen are orchestrated by the presence or the migration of platelet receptor(s) for collagen into lipid rafts, which are specialized lipid microdomains from the platelet plasma membrane enriched in signalling proteins. Electron microscopy shows that in resting platelets, TIIICBP, a receptor specific for type III collagen, is present on the platelet membrane and associated with the open canalicular system, and redistributes to the platelet membrane upon platelet activation. After platelet lysis by 1% Triton X-100 and the separation of lipid rafts on a discontinuous sucrose gradient, TIIICBP is recovered in lipid raft-containing fractions and Triton X-100 insoluble fractions enriched in cytoskeleton proteins. Platelet aggregation, induced by type III collagen, was inhibited after disruption of the lipid rafts by cholesterol depletion, whereas platelet adhesion under static conditions did not require lipid raft integrity. These results indicate that TIIICBP, a platelet receptor involved in platelet interaction with type III collagen, is localized within platelet lipid rafts where it could interact with other platelet receptors for collagen (GP VI and alpha2beta1 integrin) for efficient platelet activation.


Demographic Features and Clinical Course of Patients With Pediatric-Onset Multiple Sclerosis on Newer Disease-Modifying Treatments.
Treatment of pediatric-onset multiple sclerosis (POMS) is challenging given the lack of safety and efficacy data in the pediatric population for many of the disease-modifying treatments (DMTs) approved for use in adults with MS. Our objective was to describe the demographic features and clinical and radiologic course of patients with POMS treated with the commonly used newer DMTs within the US Network of Pediatric MS Centers (NPMSC). This is an analysis of prospectively collected data from patients who initiated treatment before age 18 with the DMTs listed below at the 12 regional pediatric MS referral centers participating in the NPMSC. One hundred sixty-eight patients on dimethyl fumarate, 96 on fingolimod, 151 on natalizumab, 166 on rituximab, and 37 on ocrelizumab met criteria for analysis. Mean age at DMT initiation ranged from 15.2 to 16.5 years. Disease duration at the time of initiation of index DMT ranged from 1.1 to 1.6 years with treatment duration of 0.9-2.0 years. Mean annualized relapse rate (ARR) in the year prior to initiating index DMT ranged from 0.4 to 1.0. Mean ARR while on index DMT ranged from 0.05 to 0.20. New T2 and enhancing lesions occurred in 75%-88% and 55%-73% of the patients, respectively, during the year prior to initiating index DMT. After initiating index DMT, new T2 and enhancing lesions occurred in 0%-46% and 11%-34% patients, respectively. Rates of NEDA-2 (no evidence of disease activity) ranged from 76% to 91% at 6 months of treatment with index DMTs and 66% to 84% at 12 months of treatment with index DMTs. Though limited by relatively short treatment duration with the index DMTs, our data suggest clinical and MRI benefit, as well as high rates of NEDA-2, in a large number of POMS patients, which can be used to guide future studies in this population.


Thermal management analyses of induction motor through the combination of air-cooling and an integrated water-cooling system.
The correct strategy of heat management in electric machines is extremely important due to their operating costs and length of operation. In this paper, the thermal management element strategies of the induction motors are developed to assure better endurance and boost efficiency. Additionally, an extensive review of the literature was carried out in terms of cooling methods for electrical machines. As the main result, the thermal analysis of an air-cooled and large-capacity induction motor is given, considering well-known heat distribution problems. Moreover, this study also presents an integrated approach with two or more cooling strategies to be the need of the hour. A model of a 100-kW air-cooled induction motor and an improved thermal management model of the same motor were both numerically investigated, using a combination of air cooling and integrated water cooling systems to achieve a significant improvement in motor efficiency. The integrated system comprising air- and water-cooled systems are investigated using SolidWorks 2017 and ANSYS Fluent version 2021. Three different flow rates of water 5 LPM, 10 LPM and 15 LPM are analyzed and compared with a conventional air-cooled induction motor, which was validated with the available published resources. Performed analyses indicate that for different flow rates of 5 LPM, 10 LPM and 15 LPM respectively, we have obtained a reduction of temperature accordingly of 2.94%, 4.79% and 7.69%. Hence, the results indicated that an integrated induction motor is efficient in bringing down the temperature compared to air cooled induction motor.


[Oxoprenolol and plasmatic renin activity in essential hypertension: preliminary data].
We have studied PRA levels in 10 healthy subjects compared with 10 patients affected with essential hypertension (with low PRA) on venous blood samples collected after 8 hours of rest and after 15-20 minutes of slow plain walk and 15 minutes after intravenous administration of oxoprenolol (mg 2). Contemporarely we have taken up arterious pression levels in each class of subjects of these studies. Postural changes produces significant rise of PRA in subjects affected with essential hypertension, that is significantly inhibited by pharmacologic interference produced by beta-blocking agents. This occurrence is independent of arterial pressure changes.


Use of RNA interference to validate Brk as a novel therapeutic target in breast cancer: Brk promotes breast carcinoma cell proliferation.
Brk (PTK6) is a nonreceptor protein tyrosine kinase, which is expressed in over 60% of breast carcinoma tissue samples and breast tumour cell lines, but not normal mammary tissue or benign lesions. Since experimental Brk expression in nontransformed mammary epithelial cells enhances their mitogenic response to epidermal growth factor, it was important to determine the role Brk plays in the proliferation of breast carcinoma cells and validate it as a therapeutic target. We have used RNA interference to efficiently and specifically downregulate Brk protein levels in breast carcinoma cells, and determined that this results in a significant suppression of their proliferation. Additionally, through the expression of a kinase-inactive mutant, we have determined that Brk can mediate promotion of proliferation via a kinase-independent mechanism, potentially functioning as an 'adapter'. These data identify Brk as a novel target for antiproliferative therapy in the majority of breast cancers, and illustrate the power of RNA interference for rapidly validating candidate therapeutic targets.


Associations between Pretend Play, Psychological Functioning and Coping Strategies in Pediatric Chronic Diseases: A Cross-Illness Study.
Children with chronic illnesses are called to undertake complicated processes of adjustment and re-organization in their daily lives; as a result, they could experience several internalizing problems. Symbolic play could be a useful way to cope with these difficulties. The main aim of this paper is to assess pretend play, coping, and psychological symptoms in three groups of school-aged children with pediatric chronic diseases. The study involved 44 Italian school-aged, chronically ill children: 16 with type 1 diabetes mellitus (T1DM), 12 with cystic fibrosis (CF), and 15 with Leukemia. All patients were assessed by the Affect in Play Scale-Brief version (APS-Br), and the Children's Coping Strategies Checklist-Revision1 (CCSC-R1). Children with T1DM and CF also completed the Separation Anxiety Symptom Inventory for Children (SASI-C) and the Strengths and Difficulties Questionnaire (SDQ)-children's version. Cohen's d (effect size) was applied between clinical and normative samples, and it showed a more organized play (APS-BR), but a more negative affect tone, comfort, and frequency of affect expression. Comparing APS-BR and CCSC-R1 rates between the three groups, significant differences were found for all the APS-BR dimensions, except for tone, and for CCSC-R1 seeking understanding. Comparing SASI-C score between T1DM and CF, higher scores were found for children with CF. In the end, correlations between all dimensions highlighted several relationships between play, coping, and adjustment problems for children with T1DM, and relationship between affect play and all variables for children with CF. Symbolic play helps chronically ill children to express emotions; helping them, as well as clinicians, to understand the difficulties caused by chronic conditions, and to cope with them.


Computer-aided detection of small pulmonary nodules in chest radiographs: an observer study.
To evaluate the impact of computer-aided detection (CAD, IQQA-Chest; EDDA Technology, Princeton Junction, NJ) used as second reader on the detection of small pulmonary nodules in chest radiography (CXR). A total of 113 patients (mean age 62 years) with CT and CXR within 6 weeks were selected. Fifty-nine patients showed 101 pulmonary nodules (diameter 5-15mm); the remaining 54 patients served as negative controls. Six readers of varying experience individually evaluated the CXR without and with CAD as second reader in two separate reading sessions. The sensitivity per lesion, figure of merit (FOM), and mean false positive per image (mFP) were calculated. Institutional review board approval was waived. With CAD, the sensitivity increased for inexperienced readers (39% vs. 45%, P < .05) and remained unchanged for experienced readers (50% vs. 51%). The mFP nonsignificantly increased for both inexperienced and experienced readers (0.27 vs. 0.34 and 0.16 vs. 0.21). The mean FOM did not significantly differ for readings without and with CAD irrespective of reader experience (0.71 vs. 0.71 and 0.84 vs. 0.87). All readers together dismissed 33% of true-positive CAD candidates. False-positive candidates by CAD provoked 40% of all false-positive marks made by the readers. CAD improves the sensitivity of inexperienced readers for the detection of small nodules at the expense of loss of specificity. Overall performance by means of FOM was therefore not affected. To use CAD more beneficial, readers need to improve their ability to differentiate true from false-positive CAD candidates.


Adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle inhibits neointimal hyperplasia in a rat aortic wire injury model.
Neointimal hyperplasia is a persistent complication after vascular interventions, and it is also the leading cause of vascular graft restenosis and failure after arterial interventions, so novel treatment methods are needed to treat this complication. We hypothesized that adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle (hydrogel-PLGA-rapamycin) could inhibit neointimal hyperplasia in a rat aortic wire injury model. The HA/SA hydrogel was fabricated by the interaction of hyaluronic acid (HA), sodium alginate (SA), and CaCO3; and loaded with PLGA rapamycin nanoparticle or rhodamine uniformly. A SD rat aortic wire injury induced neointimal hyperplasia model was developed, the control group only received wire injury, the adventitial application group received 10 μL hydrogel-PLGA-rapamycin after wire injury, and the adventitial injection group received 10 μL hydrogel-PLGA-rapamycin injected into the aortic adventitia after wire injury. Tissues were harvested at day 21 and analyzed by histology and immunohistochemical staining. Hydrogel loaded with rhodamine can be successfully injected into the aortic adventitia and was encapsuled by the adventitia. The hydrogel could be seen beneath the adventitia after adventitial injection but was almost degraded at day 21. There was a significantly thinner neointima in the adventitial application group and adventitial injection group compared to the control group (p = 0.0009). There were also significantly fewer CD68+ (macrophages) cells (p = 0.0012), CD3+ (lymphocytes) cells (p = 0.0011), p-mTOR+ cells (p = 0.0019), PCNA+ cells (p = 0.0028) in the adventitial application and adventitial injection groups compared to the control group. The endothelial cells expressed arterial identity markers (Ephrin-B2 and dll-4) in all these three groups. Adventitial injection of hydrogel-PLGA-rapamycin can effectively inhibit neointimal hyperplasia after rat aortic wire injury. This may be a promising drug delivery method and therapeutic choice to inhibit neointimal hyperplasia after vascular interventions.


Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients.
Heart rate variability (HRV) has been linked to mortality in maintenance hemodialysis (HD) patients, but it is less clear whether HRV is associated with major adverse cardiovascular events (MACEs) and hospitalization. This study enrolled 179 maintenance HD patients. HRV was measured to assess its prognostic significance in relation to MACEs and hospitalization. During the follow-up period of 33.3 ± 6.7 months, 36 (20.1%) patients had a MACE, and 98 (54.7%) experienced hospitalization. In multivariate adjusted Cox regression analysis, low very low frequency (VLF) power (hazard ratio [HR], 0.727; 95% confidence interval [CI], 0.624-0.848; p < 0.001), a history of coronary artery disease, high ultrafiltration rate, the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and the use of beta-blockers were all significantly associated with MACEs. Low VLF power (HR, 0.873; 95% CI, 0.785-0.971; p = 0.012), low serum albumin, low serum creatinine, low Kt/V levels, and high serum calcium-phosphorus product levels significantly predicted hospitalization in maintenance HD patients. Reduced VLF power is linked to an increased risk of MACEs and hospitalization in maintenance HD patients. Assessing cardiac autonomic function through HRV is of pivotal prognostic significance for this patient population.


Pneumomyelia Secondary to Interlaminar Cervical Epidural Injection Causing Acute Cord Injury with Transient Quadriparesis.
Cervical radiculopathy and cervicalgia are commonly managed with spinal epidural steroid injections in the outpatient setting. Although cervical epidural injections are routinely performed, there is potential for significant complications if proper technique and safety measures are not followed. Spinal cord infarction and stroke following transforaminal injection have been described in the literature, whereas interlaminar injections have been associated with both epidural hematomas and direct cord injury. Here we describe a case of pneumomyelia after cervical interlaminar epidural steroid injection resulting in acute quadriparesis. The patient's symptoms were caused by an inadvertent puncture of the cervical cord and injection of air present in the needle or syringe via an interlaminar approach. The initial computed tomography imaging showed a slit-like lesion at C7-T2 with density consistent with air that migrated rostrally on a follow-up scan. Epidural steroid injections are often the treatment of choice in management of neck pain and cervical radiculopathy. Devastating complications can ensue if proper safety measures and technique are not used during the procedure regardless of the approach used.


Global-Service Learning and Student-Athletes: A Model for Enhanced Academic Inclusion at the University of Washington.
The University of Washington (UW) continues to create opportunities to engage all students in transformational undergraduate educational opportunities, such as study abroad. This article describes specific efforts to increase inclusion for student-athletes in study abroad, particularly for first-generation students, including low-income students of color. Given the overrepresentation of students of color in sports vis-à-vis the larger student body at predominantly white institutions (PWIs), like UW, service-learning in communities beyond campus boundaries provides opportunities to apply international learning to a local context and to create a continuum of learning. By coupling educational theories from the classroom-particularly theories related to power and privilege-with community-based leadership in local communities, students are better prepared to actively engage in improving their own institutions. During the summers of 2013, 2014, and 2015, the author was the instructor for study abroad courses to French Polynesia with student-athletes. The courses were for 12 days (10 days on the ground and 2 days of flying), the maximum time that football players could be away from required summer workouts. This paper examines student evaluations from the French Polynesia trip in 2015. Student-athlete evaluations of a study abroad experience underscored: the transformative impact of study abroad to their academic, social, and athletic lives; the benefit of creating family-like relationships outside the confines of their sport; an appreciation for the many forms where indigenous knowledge resides, such as in navigation, dance, fishing, weaving, and cooking; intense feelings of culture shock upon return to the US, even when the trip is short in duration; a desire to engage with the diverse communities in Seattle beyond the scope of the program's structure, and; frustration, particularly for the male student-athletes, about the ways coaches, family, and friends wanted to frame the study abroad experience as a tourist experience in the South Pacific. In this regard, the student-athletes encountered stereotypes from their own communities that framed Oceania as a place for tourism, and student-athletes as uninterested in deep engagement with research and theory-stereotypes that the student-athletes resist. This paper explains how the findings, coupled with Hartman and Kiely's theories for global service learning (GSL), lead to recommendations for strengthening the future connections between global and local learning for students.


Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial.
Obesity and depression are two prevalent conditions that are costly to individuals and society. The bidirectional association of obesity with depression, in which unhealthy dietary patterns may play an important role, has been well established. Few experimental studies have been conducted to investigate whether supplementing specific nutrients or improving diet and food-related behaviors can prevent depression in overweight persons. The MooDFOOD prevention trial examines the feasibility and effectiveness of two different nutritional strategies [multi-nutrient supplementation and food-related behavioral change therapy (FBC)] to prevent depression in individuals who are overweight and have elevated depressive symptoms but who are not currently or in the last 6 months meeting criteria for an episode of major depressive disorder (MDD). The randomized controlled prevention trial has a two-by-two factorial design: participants are randomized to daily multi-nutrient supplement (omega-3 fatty acids, calcium, selenium, B-11 vitamin and D-3 vitamin) versus placebo, and/or FBC therapy sessions versus usual care. Interventions last 12 months. In total 1000 participants aged 18-75 years with body mass index between 25-40 kg/m(2) and with a Patient Health Questionnaire-9 score ≥ 5 will be recruited at four study sites in four European countries. Baseline and follow-up assessments take place at 0, 3, 6, and 12 months. Primary endpoint is the onset of an episode of MDD, assessed according to DSM-IV based criteria using the MINI 5.0 interview. Depressive symptoms, anxiety, food and eating behavior, physical activity and health related quality of life are secondary outcomes. During the intervention, compliance, adverse events and potentially mediating variables are carefully monitored. The trial aims to provide a better understanding of the causal role of specific nutrients, overall diet, and food-related behavior change with respect to the incidence of MDD episodes. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective nutritional public health strategies for the prevention of clinical depression. ClinicalTrials.gov. Number of identification: NCT02529423 . August 2015.


Topiramate for phantom limb pain in an upper limb amputee: A case report.
To increase the awareness of topiramate as a phantom limb pain treatment. Outpatient rehabilitation office in an urban academic center. 34-year-old white female who suffered a traumatic right upper limb amputation. Oral topiramate at an initial dosage of 100 milligrams per day increased to 200 milligrams per day. After failure of multiple medications traditionally used to control phantom pain, the patient described significant relief with the use of oral topiramate. The authors suggest topiramate as an alternative approach to phantom limb pain treatment.


Prenatal and perinatal environmental influences on the human fetal and placental epigenome.
Drug, hormonal, and nutritional exposures in pregnancy can cause birth defects, or have more subtle influences that may affect adult health through epigenetic developmental programming. Characterizing these epigenetic changes may provide valuable insight into the mechanism by which our health is influenced by the environment and provide biomarkers of exposure; however, currently there are few data from human studies directly addressing this. We review data on three types of exposures-nutritional, glucocorticoid, and endocrine-disrupting chemicals-and discuss how these may be associated with epigenetic changes in the fetus and the placenta, a key mediator of in utero environment. In addition, we outline some considerations for investigation of epigenetic effects in the fetus and placenta that are important to consider in the design of studies for the future.


Quantifying the Probing and Selection of Microenvironmental Pores by Motile Immune Cells.
Immune cells are constantly on the move through multicellular organisms to explore and respond to pathogens and other harmful insults. While moving, immune cells efficiently traverse microenvironments composed of tissue cells and extracellular fibers, which together form complex environments of various porosity, stiffness, topography, and chemical composition. In this protocol we describe experimental procedures to investigate immune cell migration through microenvironments of heterogeneous porosity. In particular, we describe micro-channels, micro-pillars, and collagen networks as cell migration paths with alternative pore size choices. Employing micro-channels or micro-pillars that divide at junctions into alternative paths with initially differentially sized pores allows us to precisely (1) measure the cellular translocation time through these porous path junctions, (2) quantify the cellular preference for individual pore sizes, and (3) image cellular components like the nucleus and the cytoskeleton. This reductionistic experimental setup thus can elucidate how immune cells perform decisions in complex microenvironments of various porosity like the interstitium. The setup further allows investigation of the underlying forces of cellular squeezing and the consequences of cellular deformation on the integrity of the cell and its organelles. As a complementary approach that does not require any micro-engineering expertise, we describe the usage of three-dimensional collagen networks with different pore sizes. Whereas we here focus on dendritic cells as a model for motile immune cells, the described protocols are versatile as they are also applicable for other immune cell types like neutrophils and non-immune cell types such as mesenchymal and cancer cells. In summary, we here describe protocols to identify the mechanisms and principles of cellular probing, decision making, and squeezing during cellular movement through microenvironments of heterogeneous porosity. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Immune cell migration in micro-channels and micro-pillars with defined pore sizes Support Protocol 1: Epoxy replica of generated and/or published micro-structures Support Protocol 2: Dendritic cell differentiation Basic Protocol 2: Immune cell migration in 3D collagen networks of variable pore sizes.


Solitary tuberculoma of the larynx: a case report.
A case of solitary tuberculoma of the larynx in a 56-year-old man from Calabar, Nigeria, is presented. He had upper respiratory tract obstruction severe enough to necessitate a tracheostomy. It is suggested that tuberculoma of the larynx may not be as rare as a review of the currently available medical literature would suggest. More may be discovered if all cases of polypoid masses in the larynx, however innocent they look, are histologically examined.


The advantage of reading over listening text comprehension in Down syndrome: what is the role of verbal memory?
The current study was designed to investigate the role played by verbal memory in the advantage shown by individuals with Down syndrome in reading over listening text comprehension (Roch & Levorato, 2009). Two different aspects of verbal memory were analyzed: processing load and coding modality. Participants were 20 individuals with Down syndrome, aged between 11 and 26 years who were matched for reading comprehension with a group of 20 typically developing children aged between 6;3 and 7;3 years. The two groups were presented with a listening comprehension test and four verbal memory tasks in which the degree of processing load and the coding modality were manipulated. The results of the study confirmed the advantage of reading over listening comprehension for individuals with Down syndrome. Furthermore, it emerged that different aspects of verbal memory were related respectively to reading and to listening comprehension: visual memory with low processing load was related to the former and oral memory with high processing load to the latter. Finally, it was demonstrated that verbal memory contributed to explain the advantage of reading over listening comprehension in Down syndrome. The results are discussed in light of their theoretical relevance and practical implications.


Bone resorption following weight loss surgery is associated with treatment procedure and changes in secreted Wnt antagonists.
To assess if altered bone turnover following bariatric surgery is related to metabolic consequences of the surgical procedure or weight loss. We evaluated serum markers reflecting bone turnover and metabolic pathways at baseline and after 1-year in a controlled non-randomized clinical trial comparing Roux-en-Y gastric bypass surgery (n = 74) with lifestyle intervention (n = 63) on obesity-related comorbidities. The decrease in body mass index (BMI) was larger in the surgery (-14.0 kg/m(2)) compared to lifestyle (-3.7 kg/m(2)). Markedly increased bone turnover was observed following surgery compared to lifestyle intervention and was correlated with change in BMI. Stepwise multivariable regression analysis revealed that group (β = 0.31, p < 0.01), and changes in BMI (β = -0.28, p < 0.01), dickkopf-1 (β = 0.20, p < 0.001) and sclerostin (β = 0.11, p < 0.05) were predictors of change in the bone resorption marker N-terminal telopeptide. Our data support that mechanisms related to the procedure itself and changes in secreted Wnt antagonists may contribute to increased bone turnover following bariatric surgery.


Single-molecule photoelectron tunnelling spectroscopy.
Experimental mapping of transmission is essential for understanding and controlling charge transport through molecular devices and materials. Here we developed a single-molecule photoelectron tunnelling spectroscopy approach for mapping transmission beyond the HOMO-LUMO gap of the single diketopyrrolopyrrole molecule junction using an ultrafast-laser combined scanning tunnelling microscope-based break junction set-up at room temperature. Two resonant transport channels of ultrafast photocurrent are found by our photoelectron tunnelling spectroscopy, ranging from 1.31 eV to 1.77 eV, consistent with the LUMO + 1 and LUMO + 2 in the transmission spectrum obtained by density functional theory calculations. Moreover, we observed the modulation of resonant peaks by varying bias voltages, which demonstrates the ability to quantitatively characterize the effect of the electric field on frontier molecular orbitals. Our single-molecule photoelectron tunnelling spectroscopy offers an avenue that allows us to explore the nature of energy-dependent charge transport through single-molecule junctions.


Reliable identification of cardiac liability in drug discovery using automated patch clamp: Benchmarking best practices and calibration standards for improved proarrhythmic assessment.
Screening compounds for activity on the hERG channel using patch clamp is a crucial part of safety testing. Automated patch clamp (APC) is becoming widely accepted as an alternative to manual patch clamp in order to increase throughput whilst maintaining data quality. In order to standardize APC experiments, we have investigated the effects on IC50 values under different conditions using several devices across multiple sites. APC instruments SyncroPatch 384i, SyncroPatch 384PE and Patchliner, were used to record hERG expressed in HEK or CHO cells. Up to 27 CiPA compounds were used to investigate effects of voltage protocol, incubation time, labware and time between compound preparation and experiment on IC50 values. All IC50 values of 21 compounds recorded on the SyncroPatch 384PE correlated well with IC50 values from the literature (Kramer et al., 2013) regardless of voltage protocol or labware, when compounds were used immediately after preparation, but potency of astemizole decreased if prepared in Teflon or polypropylene (PP) compound plates 2-3 h prior to experiments. Slow acting compounds such as dofetilide, astemizole, and terfenadine required extended incubation times of at least 6 min to reach steady state and therefore, stable IC50 values. Assessing the influence of different experimental conditions on hERG assay reliability, we conclude that either the step-ramp protocol recommended by CiPA or a standard 2-s step-pulse protocol can be used to record hERG; a minimum incubation time of 5 min should be used and although glass, Teflon, PP or polystyrene (PS) compound plates can be used for experiments, caution should be taken if using Teflon, PS or PP vessels as some adsorption can occur if experiments are not performed immediately after preparation. Our recommendations are not limited to the APC devices described in this report, but could also be extended to other APC devices.


Depletion or over-expression of Sh3px1 results in dramatic changes in cell morphology.
The mammalian Sorting Nexin 9 (Snx9) family consists of three paralogs: Snx9, Snx18 and Snx33. Most of the published literature to date has centered on the role of Snx9 in clathrin-mediated endocytosis (CME). Snx9 contains an Sh3 domain at its N-terminus and has been shown to interact with Dynamin and actin nucleation factors via this domain. In addition to the Sh3 domain, Snx9 also contains a C-terminal BAR domain. BAR domains are known to sense and/or induce membrane curvature. In addition to endocytosis, recent studies have implicated the Snx9 family in diverse processes such as autophagy, macropinocytosis, phagocytosis and mitosis. The Snx9 family is encoded by a single gene in Drosophila called sh3px1. In this report, we present our initial characterization of sh3px1. We found that depletion of Sh3px1 from Drosophila Schneider 2 (S2) cells resulted in defective lamellipodia formation. A similar phenotype has been reported upon depletion of Scar, the actin nucleation factor implicated in forming lamellipodia. In addition, we demonstrate that over-expression of Sh3px1 in S2 cells results in the formation of tubules as well as long protrusions. Formation of these structures required the C-terminal BAR domain as well as the adjacent Phox homology (PX) domain of Sh3px1. Furthermore, efficient protrusion formation by Sh3px1 required the actin nucleation factor Wasp. Tubules and protrusions were also generated upon over-expressing the mammalian orthologs Snx18 and Snx33 in S2 cells. By contrast, over-expressing Snx9 mostly induced long tubules.


Nutritional characteristics of the leaves of native plants growing in adverse soils of humid tropical lowlands.
Acid sulfate, peat, sandy podzolic, and saline soils are widely distributed in the lowlands of Thailand and Malaysia. The nutrient concentrations in the leaves of plants grown in these type of soils were studied with the aim of developing a nutritional strategy for adapting to such problem soils. In sago and oil palms that were well-adapted to peat soil, the N, P, and K concentrations were the same in the mature leaves, while the Ca, Mg, Na, and Fe concentrations were higher in the mature leaves of the oil palm than of the sago palm. Melastoma malabathricum and Melaleuca cajuputi plants that were well-adapted to low pH soils, peat. and acid sulfate soils were also studied. It was observed that a high amount of Al accumulated in the M. marabathricum leaves, while Al did not accumulate in M. cajuputi leaves. M. cajuputi plants accumulated large amounts of Na in their leaves or stems regardless of the exchangeable Na concentration in the soil, while M. malabathricum that was growing in saline-affected soils excluded Na. Positive relationships between macronutrients were recognized between P and N, between K and N, and between P and K. Al showed antagonistic relationships with P, K, Ca, Mg, Fe, Zn, Cu, and Na. Na also showed antagonistic relationships with P, K, Zn, Mn, Cu, and Al. Fe showed weak antagonistic relationships with Zn, Mn, Cu, and Al.


n-3 fatty acids, γ-linolenic acid, and antioxidants in sepsis.
The usefulness of n-3 fatty acids, γ-linolenic acid and antioxidants in the critically ill is controversial. I propose that adverse outcome in the critically ill is due to excess production of proinflammatory cytokines and eicosanoids from polyunsaturated fatty acids (PUFAs), while generation of anti-inflammatory products of PUFAs may lead to a favorable outcome. Hence, I suggest that measurement of plasma levels of various cytokines, free radicals, and proinflammatory and anti-inflammatory products of PUFAs and correlating them to the clinical picture may pave the way to identify prognostic markers and develop newer therapeutic strategies to prevent and manage critical illness.


Effects of carbachol and adenosine on neurotransmitter secretion induced by potassium chloride, ionomycin, and sucrose.
We compared the effects of adenosine and cholinergic agonist carbachol on spontaneous secretion during local application of K+, ionomycin, and sucrose increasing Ca2+ concentration in the nerve terminal. Adenosine and carbachol had no effect on Ca2+ entry, but modulated later stages of exocytosis.


Evidence that glutamine is involved in neutrophil function.
Phosphate-dependent glutaminase (PDG) activity, a key enzyme of glutamine metabolism, was determined in neutrophils obtained from the intra-peritoneal cavity (PC) or bronchoalveolar space (BAS) after administration of 1 ml or 100 microl, respectively of saline, glycogen solution (1%) or lipopolysaccharide (LPS 0.1 mg (100 microl)(-1)). Neutrophils were obtained by lavage of both sites with 20 ml saline 24 h after the administration of the stimuli. Glycogen and LPS, depending on the site the cells were obtained from, differently modulated PDG activity. Cells from BAS stimulated by glycogen or LPS had raised PDG activity to 30.5 +/- 5.2 and 42.7 +/- 12.1 nmol min(-1) mg(-1) protein, respectively, when compared with saline (9.1 +/- 0.9 nmol min(-1) mg(-1) protein); mean +/- SEM. On the other hand, cells from PC showed different PDG activity: 52.0 +/- 12.6 nmol min(-1) mg(-1) for saline, 36.5 +/- 9.5 nmol min(-1) mg(-1) for glycogen, and 76.6 +/- 11.2 nmol min(-1) mg(-1) for LPS; mean +/- SEM. Therefore, PDG activity varies with the site from which neutrophils are obtained and the stimulus imposed. The effect of glutamine on nitric oxide (NO) and tumour necrosis factor (TNF) production by peritoneal neutrophils, obtained after glycogen administration, cultured in the presence of LPS (0.5 microg ml(-1)) was also examined. The addition of glutamine at concentrations varying from 2 to 20 mM did not markedly affect NO production. Glutamine alone at 2 mM did not modify the production of TNF but in the presence of LPS caused a significant decrease. So, glutamine may preserve the function of neutrophils during infections and injuries.


Functional importance of groups I and II chitinases in cuticle chitin turnover during molting in a wood-boring beetle, Monochamus alternatus.
Insects must periodically replace their old cuticle/exoskeleton with a new one in a process called molting or ecdysis to allow for continuous growth through sequential developmental stages. Many RNA interference (RNAi) studies have demonstrated that certain chitinases (CHTs) play roles in this vital physiological event because knockdown of these CHT genes resulted in developmental arrest during the ensuing molting period in several insect species. In this research we analyzed the functions of group I (MaCHT5) and group II (MaCHT10) CHT genes in molting of the Japanese pine sawyer, Monochamus alternatus, an important forest pest known as a major vector of the pinewood nematode. Real-time qPCR revealed that these two CHT genes differ in their expression patterns during late stages of development. Depletion of either MaCHT5 or MaCHT10 transcripts by RNAi resulted in lethal larval-pupal and pupal-adult molting defects depending on the double-stranded RNA (dsRNA) injection timing during development. The insects were unable to shed their old cuticle and died. Furthermore, transmission electron microscopic analysis revealed that, unlike dsEGFP-treated controls, dsMaCHT5- and dsMaCHT10-treated pharate adults exhibited a failure of degradation of the endocuticular layer of their old pupal cuticle, retaining nearly intact horizontal chitinous laminae and vertical pore canal fibers. Both enzymes were indispensable for complete turnover of the chitinous old endocuticle, which is critical for insect molting. The possible functions of two spliced variants of MaCHT10, namely, MaCHT10a and MaCHT10b, are also discussed. Our results add to the knowledge base for further functional studies of insect chitin catabolism by revealing the relative importance of both MaCHT5 and MaCHT10 in chitin turnover with subtle differences in their action. These essential genes and their encoded proteins are potential targets to manipulate for controlling populations of M. alternatus and other pest insects.


Recruitment and retention challenges and strategies in randomized controlled trials of psychosocial interventions for children with cancer and their parents: a collective case study.
In pediatric oncology there are few examples of successful recruitment and retention strategies in psychosocial care research. This study aims to summarize experiences, challenges, and strategies for conducting randomized controlled trials (RCTs) of psychosocial intervention studies among children with cancer and their parent(s). We conducted a collective case study. To identify the cases, Pubmed and two trial registries were searched for ongoing and finished RCTs of psychosocial intervention studies for children with cancer and their parents. Online semi-structured expert interviews discussing recruitment and retention challenges and strategies were performed with principal investigators and research staff members of the identified cases. Nine studies were identified. Investigators and staff from seven studies participated, highlighting challenges and strategies within three major themes: eligibility, enrollment and retention. Regarding eligibility, collaborating constructively with healthcare professionals and involving them before the start of the study were essential. Being flexible, training the research staff, enabling alignment with the participants' situation, and providing consistency in contact between the research staff member and the families were important strategies for optimizing enrollment and retention. All studies followed a stepped process in recruitment. Conclusion: Although recruitment and retention in some selected studies were successful, there is a paucity of evidence on experienced recruitment and retention challenges in pediatric psychosocial research and best practices on optimizing them. The strategies outlined in this study can help researchers optimize their protocol and trial-implementation, and contribute to better psychosocial care for children with cancer and their parents. Trial Registration: This study is not a clinical trial. What is Known: • Performing RCTs is challenging, particularly in pediatric psychosocial research when both the child and parent are targeted. Recruitment and retention are common concerns. In pediatric oncology, there are few examples of successful recruitment and retention strategies in psychosocial care research. What is New: • Key strategies to collaborate constructively with healthcare professionals were outlined. Being flexible, training the research staff, alignment with the participant's situations and providing consistency in contact between the research staff member and the families were considered as essential strategies.


Muscle degeneration in rotator cuff tears.
Rotator cuff tears are among the most common injuries seen by orthopedic surgeons. Although small- and medium-sized tears do well after arthroscopic and open repair, large and massive tears have been shown to develop marked muscle atrophy and fatty infiltration within the rotator cuff muscles. These pathologic changes have been found to be independent predictors of failed surgical repair with poor functional outcomes. To understand the pathophysiology of rotator cuff disease, we must first develop an understanding of the changes that occur within the cuff muscles themselves. The purpose of this review is to summarize the molecular pathways behind muscular degeneration and emphasize new findings related to the clinical relevance of muscle atrophy and fatty infiltration seen with rotator cuff tears. Understanding these molecular pathways will help guide further research and treatment options that can aim to alter expression of these pathways and improve outcomes after surgical repair of massive rotator cuff tears.


Programming human pluripotent stem cells into white and brown adipocytes.
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.


Hb H Disease Results from Compound Heterozygosity of - -SEA and -αMAL3.5 in a Chinese Family.
The α+-thal deletion of 3.557 kb (NG_000006.1: g.32745_36301del, -αMAL3.5), involving the entire α2-globin gene, was identified in a Chinese family by multiplex ligation-dependent probe amplification (MLPA) followed by gap-polymerase chain reaction (gap-PCR) and sequencing. The proband, a compound heterozygote for this mutant gene and the Southeast Asian (- -SEA; NG_000006.1: g.26264_45564del19301) deletion, had a phenotype of Hb H disease [hemoglobin (Hb) 7.6 g/dL, mean corpuscular volume (MCV) 60.0 fL, Hb H (β4) 0.7%, Hb Bart's (γ4) 2.4% and Hb A2 1.1%]; one of her sisters with same genotype showed a similar phenotype. Another two family members, who were carriers of this mutant gene, had a hematological phenotype of a silent α-thal. The 5' and 3' breakpoints of this deletion are located at the Y2 and Y1 boxes, respectively, therefore, it probably originated from an unequal crossover between these two homologous boxes. This mutation constitutes an additional heterogeneous defect causing α-thal in the Chinese population and would be valuable for elucidating the arrangement in the human α-globin gene cluster.


Achievement of meiosis in XXY germ cells: study of 543 sperm karyotypes from an XY/XXY mosaic patient.
Human sperm chromosomes from a 46,XY/47,XXY male were obtained using the technique of in vitro penetration of zona-free hamster eggs. The analysis of 543 sperm complements shows a significantly increased incidence (0.9%) of hyperhaploid gonosomal 24,XY sets, with a lack of the expected corresponding gonosomal hypohaploidies, and a normal rate of autosomal non-disjunctions. These results support the suggestion that 47,XXY cells are able to go through meiosis and to form spermatozoa. Only 24,XY sperm chromosomal constitutions were observed suggesting a preferential pairing of homologous sex chromosomes in 47,XXY spermatocytes.


Phagocytosis: latex leads the way.
Phagocytosis is the process that cells have evolved to internalise large particles such as mineral debris, which they store, or apoptotic cells and pathogens, which they have the capacity to kill and degrade. However, several important pathogens can suppress these killing functions and survive and multiply within phagosomes, causing disease. Recent advances in phagosome biology have been made possible largely by a model system that uses inert latex beads. The ability to purify latex bead-containing phagosomes has opened the door to allow comprehensive biochemical analyses and functional assays to study the molecular mechanisms governing phagosome function. These approaches have led to unique insights directly relevant for the understanding of the biology of intracellular pathogens and the ways by which they subvert their hosts.


Methionine restriction enhances the chemotherapeutic sensitivity of colorectal cancer stem cells by miR-320d/c-Myc axis.
Chemotherapy resistance of colorectal cancer stem cells (CRC-SCs) has become a major challenge in clinical treatment of cancer. Methionine restriction (MR) enhances the therapeutic effect of chemotherapeutic agents. The aim of this study was to explore the molecular pathways that MR affects the chemotherapeutic sensitivity of CRC-SCs. CD133+ and CD133- SW480 or SW620 cells were isolated by magnetic-activated cell sorting (MACS). Mouse xenograft tumor model was established by subcutaneous inoculation of CD133+ SW480. MTT assay was used to detect cell viability. Phase distribution of cell cycle was detected by flow cytometry. Western blotting was used to detect drug-resistant related protein expression. miR-320d and transcription factor c-Myc expressions were detected by qRT-PCR. The interaction between miR-320d and c-Myc was verified by luciferase assay. CD133+ SW480 and SW620 cells were more resistant to 5-fluorouracil (5-FU) than CD133- cells. In vitro and in vivo experiments showed that 5-FU and MR combined therapy further inhibited CD133+ cell activity and ATP binding cassette subfamily G member 2 (ABCG2) expression, and reduced tumor volume compared with drug administration alone. Interference with miR-320d or overexpression of c-Myc reversed the increased chemotherapeutic sensitivity of CRC-SCs induced by synergistic therapy with 5-FU and MR. miR-320d can target and regulate c-Myc. Interference with c-Myc could reverse the increase in cell viability and ABCG2 expression caused by down-regulation of miR-320d. In conclusion, the combined chemotherapy with MR can enhance the chemotherapeutic sensitivity of CRC-SCs by up-regulation of miR-320d to inhibit c-Myc expression, which lays a molecular basis for MR regulation of chemotherapeutic sensitivity of CRC-SCs.


Severe tauopathy and axonopathy in the medulla oblongata in Alzheimer's disease implicate the changes in autonomic nervous function.
The autonomic dysfunctions in Alzheimer's disease (AD) have been identified from many clinical studies, however, there is still a lack of evidence directly verifying the structural abnormalities of the autonomic nervous system in AD. Human medulla oblongatas from four AD patients or five non-AD subjects were obtained and observed by using immunohistochemical staining of hyperphosphorylated tau and Aβ amyloid, and post-mortem tracing techniques. We found distinct axonal and somatic immunoreactivities for the tau markers AT8 and Tau-5 in the different areas of the medulla oblongata in AD patients, which was particularly obvious in the dorsal nucleus of the vagus nerve, the nucleus of the solitary tract and the reticular nucleus. The swollen axons, which are a typical feature of axonopathy, were not only identified in the axons with immunohistochemical labeling of AT8 and Tau-5 in the different nuclei of the medulla oblongata, but also in the tracer-labeled afferent and efferent fibres of the vagus nerve in AD patients. Such changes in tauopathy and axonopathy were only occasionally found in the non-AD aged subjects. Interestingly, we did not observe any intra- or extracellular Aβ deposits in the medulla oblongatas of the AD patients or of the non-AD subjects. These results in small samples suggest that occurrence of tauopathy and axonopathy in the parasympathetic nuclei of the medulla oblongata in AD patients may implicate the change of autonomic nervous function.


The impact of methodological and measurement factors on transdiagnostic associations with intolerance of uncertainty: A meta-analysis.
Intolerance of uncertainty is a dispositional trait associated with a range of psychological disorders, but the influence of methodological factors on theses associations remains unknown. The first aim of this meta-analysis was to quantify the strengths of the association between IU and symptoms of generalised anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, obsessive compulsive disorder, depression, and eating disorders. The second aim was to assess the influence of methodological factors on these relationships, including clinical (vs. non-clinical) status, age group, sex, IU measure, and symptom measure. We extracted 181 studies (N participants = 52,402) reporting 335 independent effect sizes (Pearson's r). Overall, there was a moderate association between IU and symptoms (r = 0.51, 95% CI = 0.50-0.52), although heterogeneity was high (I2 = 83.50, p < .001). Some small but significant moderator effects emerged between and within disorders. Effect sizes were not impacted by sample size. The results indicate that IU has robust, moderate associations with a range of disorder symptoms, providing definitive evidence for the transdiagnostic nature of IU.


Urine calcium and urine sodium concentrations are not related, after adjustment for urine magnesium.
Urine calcium correlates with urine sodium. The aims of this study were to investigate whether the urine sodium-calcium relationship persists into old age and whether it holds after adjustment for urine magnesium. Cross-sectional descriptive analysis. Residents of two aged care institutions (median age 84 years) who were not taking diuretics, calcium or vitamin D supplements. Early morning urine calcium, sodium and magnesium, plasma creatinine and serum 25-hydroxyvitamin D and parathyroid hormone. Urine calcium correlated with urine sodium (r = 0.29, P < 0.01) and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine magnesium, the relationship between urine sodium and urine calcium was no longer significant. Forty-five percent of the interindividual variation in urine calcium was explained by a linear model on the basis of urine magnesium and plasma creatinine. The data indicate that a correlation between urine sodium and calcium persists in very old age. However, this correlation no longer holds after adjustment for urine magnesium. Further studies examining urine calcium excretion should also consider urine magnesium.


What I look like: college women, body image, and spirituality.
Despite public acknowledgment of the importance of spiritual development, little has been written globally on female young adults' personal views of their spiritual values and body image. This article briefly presents the findings of a pilot study that explored female college students' reflections on body image and spirituality. Responses from participants showed that (1) many students are interested in faith and spiritual development; (2) body dissatisfaction affects those women who viewed themselves as spiritual (92%) as well as those who said they were free thinkers (49%). Nevertheless, religion and spiritual values seemed to confer some behavioral protection. Implications for educational programs that will address the spiritual dimension of learning are discussed.


Sulfonation of raloxifene in HEK293 cells overexpressing SULT1A3: Involvement of breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4) in excretion of sulfate metabolites.
Excretion of sulfate metabolites is an essential process in disposition of raloxifene via the sulfonation pathway. However, the transporters responsible for excretion of raloxifene sulfates remain undefined. Here, sulfonation of raloxifene and excretion of its sulfate metabolites were investigated using SULT1A3-overexpressing HEK293 cells (or SULT293 cells) with significant expression of BCRP and MRP4. SULT293 cell lysate catalyzed the sulfonation of raloxifene at both 6-OH and 4'-OH groups, generating raloxifene-6-sulfate (R-6-S) and raloxifene-4'-sulfate (R-4'-S), respectively. Sulfate formation followed the Michaelis-Menten kinetics (Km = 0.49 μM and Vmax = 5.79 pmol/min/mg for R-6-S; Km = 0.33 μM and Vmax = 1.25 pmol/min/mg for R-4'-S). As expected, the recombinant SULT1A3 enzyme showed a high similarity in raloxifene sulfonation profiles with the lysate preparation. Ko143, a selective inhibitor of BCRP, significantly decreased the excretion rates of raloxifene sulfates (maximal 66.1%) while increasing the intracellular sulfates (maximal 282%). As a result, the apparent efflux clearance (CLef,app, representing the efflux efficiency of raloxifene sulfates) was substantially reduced (maximal 85.6%). Likewise, the pan-MRP inhibitor MK-571 significantly deceased the excretion rates (maximal 69.6%) and CLef,app values (maximal 96.0%) of raloxifene sulfates while increasing the intracellular sulfates (maximal 667%). Further, the short-hairpin RNA (shRNA) targeting BCRP significantly reduced (maximal 35.0%) sulfate excretion. Use of BCRP shRNA also caused significant decreases (maximal 52.5%) in the CLef,app values. Silencing of MRP4 by shRNA led to a substantial alteration in sulfate disposition (i.e., 28.6-37.8% reductions in sulfate excretion, 30.5-59.3% elevations in intracellular sulfates, and 44.8-47.7% deceases in CLef,app values). In conclusion, two sulfate metabolites R-6-S and R-4'-S were generated from raloxifene in SULT293 cells. Cellular excretion of the raloxifene sulfates was mainly mediated by BCRP and MRP4.


Celiac plexus neurolysis for abdominal cancers: going beyond pancreatic cancer pain.
Celiac plexus neurolysis (CPN) has been verified for mitigating pancreatic cancer pain. However, information regarding CPN's use beyond this remains limited. Identify which cancers benefit from CPN, which symptoms improve, and when symptoms improve. Retrospective analysis was conducted on 173 patients who received CPN for pain caused by various malignancies. Mean symptom changes on the MD Anderson Symptom Inventory (MDASI) from baseline to 2 weeks, 1 month, and 2 months after CPN were analyzed overall and then by cancer type: pancreatic (all stages and stages III-IV), hepatobiliary, and nonpancreatic, nonhepatobiliary gastrointestinal (NPNH-gastrointestinal). Eighty-two pancreatic, 43 NPNH-gastrointestinal, 14 hepatobiliary, and 34 patients with other cancers met inclusion criteria. Statistically significant changes included decrease in the pain score at 1 month by 1.01 points for all cancers, 1.65 points for all pancreatic cancers, and 1.88 points for late-stage pancreatic cancers. At 2 months, pain decreased by 1.50 points for all cancers, 1.68 points for all pancreatic cancers, 2.37 points for late-stage pancreatic cancers, and 1.50 points in NPNH-gastrointestinal cancers. At 2 months, quality of life improved by 1.07 points for all cancers and 1.53 points for all pancreatic cancers. Sleep improved at 2 months for all cancers by 0.73 points and 1.60 points in late-stage pancreatic cancers. At 2 months, pancreatic cancer patients improved in general activity by 0.93 points, walking by 1.00 points, and working by 1.12 points. Celiac plexus neurolysis can decrease cancer symptom burden beyond pain including quality of life and sleep for pancreatic and nonpancreatic cancers, as well as general activity for pancreatic cancers.


Pulmonary rehabilitation: Patient and healthcare professional perspective.
A patient and healthcare professional from The Netherlands give an overview of the pulmonary rehabilitation process http://ow.ly/R0iTI.


Developmental interneuron subtype deficits after targeted loss of Arx.
Aristaless-related homeobox (ARX) is a paired-like homeodomain transcription factor that functions primarily as a transcriptional repressor and has been implicated in neocortical interneuron specification and migration. Given the role interneurons appear to play in numerous human conditions including those associated with ARX mutations, it is essential to understand the consequences of mutations in this gene on neocortical interneurons. Previous studies have examined the effect of germline loss of Arx, or targeted mutations in Arx, on interneuron development. We now present the effect of conditional loss of Arx on interneuron development. To further elucidate the role of Arx in forebrain development we performed a series of anatomical and developmental studies to determine the effect of conditional loss of Arx specifically from developing interneurons in the neocortex and hippocampus. Analysis and cell counts were performed from mouse brains using immunohistochemical and in situ hybridization assays at 4 times points across development. Our data indicate that early in development, instead of a loss of ventral precursors, there is a shift of these precursors to more ventral locations, a deficit that persists in the adult nervous system. The result of this developmental shift is a reduced number of interneurons (all subtypes) at early postnatal and later time periods. In addition, we find that X inactivation is stochastic, and occurs at the level of the neural progenitors. These data provide further support that the role of Arx in interneuron development is to direct appropriate migration of ventral neuronal precursors into the dorsal cortex and that the loss of Arx results in a failure of interneurons to reach the cortex and thus a deficiency in interneurons.


The first analysis of Trichinella spiralis and Trichinella britovi adult worm excretory-secretory proteins by two-dimensional electrophoresis coupled with LC-MS/MS.
The two most common Trichinella species present in European countries are Trichinella spiralis and Trichinella britovi. The consumption of raw or undercooked meat with invasive larvae results in trichinellosis. Currently, the most commonly used sources for detecting specific anti-Trichinella antibodies is ELISA with the muscle larvae (ML) excretory-secretory (E-S) proteins. However, these serological methods cannot be efficiently applied at early stage of infection. The aim of the current study was to identify the common and species-specific E-S proteins of T. spiralis and T. britovi adult worms which could have potential for accurate diagnosis of Trichinella infection at an early stage of invasion. Different sets of immunoreactive proteins were identified in T. spiralis and T. britovi proteomes by a combination of two-dimensional electrophoresis (2-DE), immunoblot and LC-MS/MS analysis. Polyubiquitin-B, a possible enoyl-CoA hydratase/isomerase YngF or polyubiquitin-like protein was found to be common for both species; gene ontology analysis confirmed its involvement in proteolysis, oxidation-reduction and translation processes, as well as in molecular transport. These molecules, being secreted or excreted at an early stage of parasite development, may play a critical role in the processes occurring during the initial steps of the host invasion and hence be suitable for diagnostic test development.


Transient late-onset ischemic mitral regurgitation following Dor's procedure.
A 60-year-old man developed anteroseptal acute myocardial infarction with subsequent left hemiplegia. Echocardiography detected apical aneurysm with thrombus. Coronary artery bypass grafting with Dor's procedure were performed. Chronic heart failure (CHF) developed three months after the surgery. CHF with mitral regurgitation (MR) continued for more than two months and then disappeared. When surgical intervention is considered for late MR after Dor's procedure, it is important to consider that late-onset MR after Dor's procedure can be transient with full medication, which may require four or more months to achieve its full effects.


Adhesion-mediating molecules of human monocytes.
Adhesion of monocytes to each other and to T cells and substrates is increased by phorbol esters. In the presence of these compounds monocyte aggregation was almost completely inhibited (greater than 90%) by monoclonal antibody 60.3. This antibody recognizes GP90 (CD18), a leukocyte surface glycoprotein which is separately and noncovalently associated to either GP160 (CD11a), GP155 (CD11b), or GP130 (CD11c). Anti-LFA-1 antibody (CD11a) was only partially inhibitory (35%) while antibodies 60.1 (CD11b) and anti-Leu-M5 (CD11c) had a minimal inhibitory effect (10%). Antibody LB-2 recognizing a single glycoprotein distinct from the GP90-GP160 complex and expressed on activated B and T cells, monocytes, and vascular endothelial cells was partially inhibitory (22%). Monoclonal antibodies anti-C3bR (CD35), T29/33 (CD45, leukocyte common antigen 200). TA-1 (CD11a), OKM1 (CD11b), F10-44-2 (brain-leukocyte antigen), OKM5 (monocyte-endothelial cell antigen) and to class I or class II molecules exerted no inhibition on the monocyte aggregation. Fab fragments of antibody 60.3 efficiently inhibited not only monocyte aggregation in the absence or presence of phorbol esters but also adhesion of these cells to autologous or allogeneic T lymphocytes and, to a lesser extent, to plastic surfaces. It is thus concluded that GP90, either alone or associated to the larger glycoproteins, and LB-2 antigen mediate monocyte adhesion.


Post mortem CT of intrahepatic gas distribution in twenty-seven victims of a flood: Patterns and timing.
We reported the results of post mortem computed tomography of the liver in 27 subjects dead simultaneously during a flood. The aim of our work was to identify the different patterns of post mortem intrahepatic gas distribution and the timing of its appearance. Although post mortem CT is the method of choice for the evaluation of gas distribution, controversies exist about the first site of appearance of intrahepatic gas (portal veins versus hepatic veins) as well as the timing and steps of intrahepatic gas spreading. In each subject we performed thin slice CT scanner (Somatom Definition, Siemens) and post processing of native CT images with Minimum Intensity Projection technique. Our results show that the first site of appearance of intrahepatic gas is portal veins. Gas in hepatic veins was never seen without the presence of the gas in portal vein. Gaseous cysts in hepatic parenchyma represent a further and usually more tardive pattern of intrahepatic gas distribution. In addition, we demonstrated that differences in timing of gas spreading was statistically significative for exclusive presence of portal veins gas before 48h as well as for complete substitution of hepatic parenchyma by cysts 64h after death. In conclusion, our work shows that the CT study of postmortem intrahepatic gas distribution could be a useful complementary tool both in demonstrating the mechanism of intrahepatic gas spreading and in estimating post mortem interval.