Effect of lifestyle weight loss intervention on disease severity in patients with psoriasis: a systematic review and meta-analysis.
Psoriasis is a chronic inflammatory disease of the skin with joint manifestations. Greater psoriasis severity and lower response to treatment have been linked to obesity. However, the effect of weight reduction by non-pharmacologic intervention on disease severity is still questionable. This is a systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of dietary and lifestyle weight loss interventions on psoriasis severity. We comprehensively searched PubMed/MEDLINE, EMBASE and CENTRAL from their inception to August 2014. Inclusion criteria were RCTs that examined lifestyle intervention by diet or exercise in overweight or obese patients with psoriasis and measured the severity of psoriasis as an outcome compared with controls. Two authors independently assessed article quality and extracted the data. Out of 12 full-text articles, 7 RCTs involving 878 participants met our inclusion criteria. Five of these RCTs were included in the meta-analysis, which was based on the random-effects model. There was a greater reduction in the Psoriasis Area Severity Index (PASI) score in patients receiving weight loss intervention than in controls, with a pooled mean difference of -2.49 (95% confidence interval (CI), -3.90 to -1.08; P=0.004). More participants in the intervention group than in the control group achieved a 75% reduction in the PASI score, with a pooled odds ratio of 2.92 (95% CI, 1.39-6.13; P=0.005). Nonpharmacologic, nonsurgical weight loss intervention is associated with reduction in the severity of psoriasis in overweight or obese patients. However, more RCTs with more participants are needed to provide better quality of evidence.


ACP5, a direct transcriptional target of FoxM1, promotes tumor metastasis and indicates poor prognosis in hepatocellular carcinoma.
Tartrate-resistant acid phosphatase 5 (ACP5), which is essential for bone resorption and osteoclast differentiation, promotes cell motility through the modulation of focal adhesion kinase phosphorylation. However, whether ACP5 contributes to the metastasis and progression of hepatocellular carcinoma (HCC) remains unknown. In this paper, a complementary DNA microarray, serial deletion, site-directed mutagenesis and a chromatin immunoprecipitation assays confirmed that ACP5 is a direct transcriptional target of Forkhead box M1 (FoxM1). ACP5 expression was markedly higher in HCC tissues compared with adjacent noncancerous tissues. ACP5 overexpression was correlated with microvascular invasion, poor differentiation and higher tumor-node-metastasis stage. HCC patients with positive ACP5 expression had poorer prognoses than those with negative ACP5 expression. A multivariate analysis revealed that ACP5 expression was an independent and significant risk factor for disease recurrence and reduced-patient survival following curative resection. Transwell assays and an orthotopic metastatic model showed that the upregulation of ACP5 promoted HCC invasion and lung metastasis, whereas ACP5 knockdown inhibited these processes. The knockdown of ACP5 significantly attenuated FoxM1-enhanced invasion and lung metastasis. Immunohistochemistry revealed that ACP5 expression was positively correlated with FoxM1 expression in human HCC tissues, and their coexpression was associated with poor prognoses. In summary, ACP5 is a direct transcriptional and functional target of FoxM1. This novel FoxM1/ACP5 signaling pathway promotes HCC metastasis and may be a candidate biomarker for prognosis and a target for new therapies.


Widespread transcript shortening through alternative polyadenylation in secretory cell differentiation.
Most eukaryotic genes produce alternative polyadenylation (APA) isoforms. Here we report that, unlike previously characterized cell lineages, differentiation of syncytiotrophoblast (SCT), a cell type critical for hormone production and secretion during pregnancy, elicits widespread transcript shortening through APA in 3'UTRs and in introns. This global APA change is observed in multiple in vitro trophoblast differentiation models, and in single cells from placentas at different stages of pregnancy. Strikingly, the transcript shortening is unrelated to cell proliferation, a feature previously associated with APA control, but instead accompanies increased secretory functions. We show that 3'UTR shortening leads to transcripts with higher mRNA stability, which augments transcriptional activation, especially for genes involved in secretion. Moreover, this mechanism, named secretion-coupled APA (SCAP), is also executed in B cell differentiation to plasma cells. Together, our data indicate that SCAP tailors the transcriptome during formation of secretory cells, boosting their protein production and secretion capacity.


Corneoscleral locally aggressive fibrous histiocytoma in Xeroderma Pigmentosum patient: A case report.
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that has been found in all continents and racial groups in relation to faulty repair of DNA with sun exposure. Several cutaneous and ocular tumors have been described in relation to XP including fibrous histiocytoma (FH). The diagnosis of conjunctival FH is challenging owing to the rarity of this tumor and the diversity of its classification into benign, locally aggressive and malignant. We are describing a recurrent FH exhibiting a locally aggressive behavior in a child with history of XP. Detailed histopathological features are presented with literature review.


Structure and molecular orbital study of ergoline derivatives. 1-(6-Methyl-8 beta-ergolinylmethyl)imidazolidine-2,4-dione (I) and 2-(10-methoxy-1,6-dimethyl-8 beta-ergolinyl)ethyl 3,5-dimethyl-1H-2-pyrrolecarboxylate toluene hemisolvate (II) and comparison with nicergoline (III).
(I): C19H22N4O2 (Registry No. 95688-34-9), m.p. greater than 573 K, Mr = 338.4, orthorhombic, P2(1)2(1)2(1), a = 8.392 (2), b = 13.004 (2), c = 15.676 (5) A, V = 1710.7 (7) A3, Z = 4, Dx = 1.31 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.08 mm-1, F(000) = 720, T = 293 K, final R = 0.051 for 990 independent reflexions. (II): C26H33N3O3.1/2C7H8 (Registry No. 54370-23-9), m.p. 427-429 K, Mr = 481.64, monoclinic, P2(1), a = 11.595 (4), b = 14.274 (2), c = 16.103 (4) A, beta = 100.19 (3) degrees, V = 2623 (1) A3, Z = 4, Dx = 1.22 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.07 mm-1, F(000) = 1036, T = 293 K, final R = 0.064 for 2738 independent reflexions. Two independent molecules constitute the asymmetric unit, together with a toluene molecule. Parallel investigations of the title compounds by single-crystal X-ray analysis and theoretical calculations have converged in showing an extended configuration of the side chain attached at the C8 atom of the ergoline nucleus.


Predator detection and avoidance by lotic mayfly nymphs of different size.
We studied antipredatory responses of lotic mayfly (Baetis) nymphs in a factorial experiment with four levels of fish presence: (1) a freely foraging fish (the European minnow,Phoxinus phoxinus), (2) a constrained fish, (3) water from a fish stream, (4) water from a fishless stream. LargeBaetis nymphs drifted mainly during night-time in treatments involving either the chemical or actual presence of fish, whereas no diel periodicity was observed when the water was not conditioned with fish odour. The response was strongest when the fish was uncaged, which suggests that visual or hydrodynamic cues are needed in addition to chemical ones for an accurate assessment of predation risk. Fish presence had no effect on the drift rates of small nymphs. Instead, they increased their refuge use in the presence of a live fish. Chemical cues alone did not have any effect on the refuge use of any of theBaetis size classes. Our results indicate active drift entry by mayfly nymphs. Because predation pressure is spatially and temporally variable, nymphs must sample the environment in order to locate predator-free areas or areas with low predation risk. Drifting should be the most energy-saving way to do this. To avoid the risk from visually feeding fish, large individuals can sample safely (i.e. enter drift) only at night-time, while the small ones can also do this safely during the day. We suggest that, contrary to some earlier assumptions, mayfly drift is not a fixed prey response. Instead,Baetis nymphs are able to assess the prevailing predation pressure, and they adjust their foraging behaviour accordingly.


Sex-based differences in the response to dexamethasone in bacterial meningitis: Analysis of the European dexamethasone in adulthood bacterial meningitis study.
Inflammatory markers have been found at higher concentrations in women than men with bacterial meningitis. To investigate sex-based differences in the response to dexamethasone, we performed a post hoc analysis of a double-blind, randomised multicentre trial of dexamethasone (10 mg, 4 times daily for 4 days) vs placebo in adults with bacterial meningitis. The primary outcome measure was the Glasgow outcome scale score at 8 weeks and interaction tests were used to examine subgroup differences. Between June 1993 and December 2001, 301 patients (56% male) were randomly assigned to a treatment group: 157 received dexamethasone and 144 placebo. Although dexamethasone reduced the risk of unfavourable outcome to a greater extent in women (relative risk [RR] 0.42, 95% confidence interval [CI] 0.21-0.86, P = .02) than men (RR 0.79, 95% CI 0.41-1.51, P = .55), on interaction testing (ratio of RR women:men 0.53, 95% CI 0.20-1.39, P = .19) patient sex was not a significant modifier of the effect of dexamethasone.


Assessing the health of an urban stream: a case study of Suzhou Creek in Shanghai, China.
Restoration of urban streams and rivers has increased rapidly in developing countries in recent years. Estimating river health provides a new perspective on evaluating the ecological conditions of streams and rivers. The Suzhou Creek restoration project in Shanghai, China is a milestone for environmental protection. Based on the environmental and ecological data, including 17 indicators in five categories, collected from March 11 to April 20, 2007, the river health index (RHI) for Suzhou Creek was constructed and analysed to quantify the ecosystem of this urban river after a restoration project. The RHI scores of 34 sites ranged from 19.24 to 33.36, i.e. from poor to good. There were no significant RHI differences among stream orders, while differences in land use resulted in significant differences in channel flow status (B12), channel alteration (B21), channel sinuosity (B22), bank stability (B23), bank profile type (B25) and riparian vegetative zone width (B31). River restoration led to improved hydrological condition and channel physical form, while ammonia nitrogen (B44) and indicator scores of the presence of macro-invertebrate families (B51) were the lowest of any indicator. This case study supports the use of river health assessment as a supplement to water quality analysis in China.


Knowledge and beliefs about dietary inorganic nitrate among UK-based nutrition professionals: Development and application of the KINDS online questionnaire
To examine knowledge and beliefs about the biological roles of dietary inorganic nitrate in UK-based nutrition professionals, and to explore potential differences by participants' education level. An online questionnaire was administered to UK-based nutrition professionals, exploring knowledge and/or beliefs across five areas: (1) health and performance effects of nitrate; (2) current and recommended intake values for nitrate; (3) dietary sources of nitrate; (4) methods of evaluating nitrate intake and (5) nitrate metabolism. One hundred and twenty-five nutrition professionals. Knowledge and beliefs about inorganic nitrate. Most nutrition professionals taking part in the survey had previously heard of inorganic nitrate (71%) and perceived it to be primarily beneficial (51%). The majority believed that nitrate consumption can improve sports performance (59%) and reduce blood pressure (54%), but were unsure about effects on cognitive function (71%), kidney function (80%) and cancer risk (70%). Knowledge of dietary sources of nitrate and factors affecting its content in food were generally good (41%-79% of participants providing correct answers). However, most participants were unsure of the average population intake (65%) and the acceptable daily intake (64%) of nitrate. Most participants (65%) recognised at least one compound (ie, nitric oxide or nitrosamines) that is derived from dietary nitrate in the body. Knowledge of nitrate, quantified by a 23-point index created by summing correct responses, was greater in individuals with a PhD (p=0.01; median (IQR)=13 (9-17)) and tended to be better in respondents with a masters degree (p=0.054; 13 (8-15)) compared with undergraduate-level qualifications (10 (2-14)). UK-based nutrition professionals demonstrated mixed knowledge about the physiology of dietary nitrate, which was better in participants with higher education. More efficient dissemination of current knowledge about inorganic nitrate and its effects on health to nutrition professionals will support them to make more informed recommendations about consumption of this compound.


Short report: sedation for upper gastrointestinal endoscopy--diazepam versus midazolam.
Intravenously injected midazolam was associated with a greater degree of sedation, as assessed by 24-h retrograde amnesia, than the longer acting benzodiazepine, diazepam. No differences in the frequency of pain on injection or the occurrence of venous sequelae were noted between the two preparations.


Whole-exome sequencing identified novel compound heterozygous variants in a Chinese neonate with liver failure and review of literature.
Liver failure caused by TRMU is a rare hereditary disorder and clinically manifests into metabolic acidosis, hyperlactatemia, and hypoglycemia. Limited spectrum of TRMU pathogenic variants has been reported. Whole-exome sequencing was employed for the diagnosis of a 5-day-old female who suffered from severe neonatal hyperlactatemia and hypoglycemia since birth. Sanger sequencing was performed to confirm the origin of the variants subsequently. Variants classification was followed to ACMG guideline. A compound heterozygosity of a frameshiftc.34_35dupTC (p.Gly13fs) and a missense c.244T>G (p.Phe82Val) in TRMU was detected, both variants are novel and pathogenic. Analysis of clinical and genetic information including patients reported previously indicated that there is no significant correlation between the genotype and the phenotype of TRMU-caused liver failure. To the best of our knowledge, this is the first case report of TRMU-caused liver failure in China. Whole-exome sequencing is effective for conclusive diagnosis of this disorder and beneficial for its clinical management.


Relationship between burnout and PTSD symptoms in firefighters: the moderating effects of a sense of calling to firefighting.
Firefighting has been reported to lead to burnout and posttraumatic stress disorder (PTSD). However, burnout and PTSD symptoms may vary depending on personal characteristics, such as having a sense of calling. This study examined the role of calling in the association between burnout and PTSD symptoms. We hypothesized that burnout would be associated with more severe PTSD symptoms and calling would buffer the relationship between burnout and PTSD symptoms. The Korean version of the Maslach Burnout Inventory-General Survey, Sense of Calling Subscale of the Professionalism Scale, and the Impact of Event Scale-Revised-Korean version were used to measure burnout, calling, and PTSD symptoms. Data from 109 of 127 firefighters from Gyeonggi-do, South Korea were analyzed using hierarchical linear regression. Burnout was a significant predictor of PTSD symptoms. Furthermore, the interaction term between burnout and calling accounted for a significant variance in PTSD symptoms. Higher burnout was associated with severe PTSD symptoms, but this relationship differed by the level of calling. The increase in PTSD symptoms due to increased burnout in the high calling group was relatively higher than in the low and average calling groups. Calling, though perceived as a positive variable, can be hazardous to exhausted people. A sense of calling as part of one's job identity should not be encouraged until personal circumstances and characteristics, such burnout symptoms, are evaluated. Identifying context and variables associated with PTSD for interventions with firefighters and persons in other dangerous occupations should aid in their recovery from trauma exposure.


Actin polymerization induced by pulsed electric stimulation of bone cells in vitro.
Electric field pulses, capacitively applied to tissue cultures of embryonic bone cells, were shown to induce changes in the state of cellular actin. Three actin states could be defined by DNAase I inhibition. A rapidly (20-30 s) inhibiting fraction, attributed to monomeric G-actin, amounts to 55% of total actin in nonstimulated cells. An additional fraction of 8% required approx. 20 min to reach full inhibition and was tentatively defined as polymeric 'F'-actin. The remaining 37% could be detected only after treatment of the cells with 0.75 M guanidine hydrochloride, which dissociates actin from all its protein interactions. This fraction, N-actin (network actin) is believed to represent F-actin integrated into some supramolecular structure, where it is not accessible to DNAase I. Upon short electric stimulation the distribution changed to 40% G-actin, 12% F-actin and 48% N-actin. 3-Isobutyl-1-methylxanthine (IBMX; an inhibitor of cAMP phosphodiesterase), depletion of extracellular calcium, and calmodulin inhibitors abolished this field effect.


Adenosine A2a receptor antagonists attenuate striatal adaptations following dopamine depletion.
The motor symptoms of Parkinson's disease (PD) are widely thought to arise from an imbalance in the activity of the two major striatal efferent pathways following the loss of dopamine (DA) signaling. In striatopallidal, indirect pathway spiny projection neurons (iSPNs), intrinsic excitability rises following the loss of inhibitory D2 receptor signaling. Because these receptors are normally counterbalanced by adenosine A2a adenosine receptors, antagonists of these receptors are being examined as an adjunct to conventional pharmacological therapies. However, little is known about the effects of sustained A2a receptor antagonism on striatal adaptations in PD models. To address this issue, the A2a receptor antagonist SCH58261 was systemically administered to DA-depleted mice. After 5 days of treatment, the effects of SCH58261 on iSPNs were examined in brain slices using electrophysiological and optical approaches. SCH58261 treatment did not prevent spine loss in iSPNs following depletion, but did significantly attenuate alterations in synaptic currents, spine morphology and dendritic excitability. In part, these effects were attributable to the ability of SCH58261 to blunt the effects of DA depletion on cholinergic interneurons, another striatal cell type that co-expresses A2a and D(2) receptors. Collectively, these results suggest that A2a receptor antagonism improves striatal function in PD models by attenuating iSPN adaptations to DA depletion.


The biogenesis of the immunopeptidome.
The immunopeptidome is the repertoire of peptides bound and presented by the MHC class I, class II, and non-classical molecules. The peptides are produced by the degradation of most cellular proteins, and in some cases, peptides are produced from extracellular proteins taken up by the cells. This review attempts to first describe some of its known and well-accepted concepts, and next, raise some questions about a few of the established dogmas in this field: The production of novel peptides by splicing is questioned, suggesting here that spliced peptides are extremely rare, if existent at all. The degree of the contribution to the immunopeptidome by degradation of cellular protein by the proteasome is doubted, therefore this review attempts to explain why it is likely that this contribution to the immunopeptidome is possibly overstated. The contribution of defective ribosome products (DRiPs) and non-canonical peptides to the immunopeptidome is noted and methods are suggested to quantify them. In addition, the common misconception that the MHC class II peptidome is mostly derived from extracellular proteins is noted, and corrected. It is stressed that the confirmation of sequence assignments of non-canonical and spliced peptides should rely on targeted mass spectrometry using spiking-in of heavy isotope-labeled peptides. Finally, the new methodologies and modern instrumentation currently available for high throughput kinetics and quantitative immunopeptidomics are described. These advanced methods open up new possibilities for utilizing the big data generated and taking a fresh look at the established dogmas and reevaluating them critically.


Exploring interpretable graph convolutional networks for autism spectrum disorder diagnosis.
Finding the biomarkers associated with autism spectrum disorder (ASD) is helpful for understanding the underlying roots of the disorder and can lead to earlier diagnosis and more targeted treatments. In essence, we are faced with two challenges (i) how to learn a node representation and a clean graph structure from original graph data with high dimensionality and (ii) how to jointly model the procedure of node representation learning, structure learning and graph classification. We propose FSL-BrainNet, an interpretable graph convolution network (GCN) model for jointly Learning of node Features and clean Structures in brain networks for automatic brain network classification and interpretation. We formulate an end-to-end trainable and interpretable framework for graph classification and biomarkers (salient brain regions and potential subnetworks) identification. The experimental results on the ABIDE dataset show that our proposed methods not only achieve improved prediction performance compared with the state-of-the-art methods, but also find a compact set of highly suggestive biomarkers including relevant brain regions and subnetworks to ASD. Through node feature learning and structure learning, our model can simultaneously select important brain regions and identify subnetworks.


Early gastric cancer: a morphological study of 144 cases.
Within 144 early gastric cancers (EGC), the ulcerated type was most frequent (54.2%), followed by the superfical (29.9%) and protruded types (16%). 10.4% of EGC originated from adenomatous polyps of gastric mucosa. No positive correlation between hyperplastic polyps and occurrence of EGC could be stated. Antrum and corpus regions were preferred localization of EGC, harboring about 90% of the tumors. Histologic classification according to Laurén (1965) proved to be very reliable, revealing an intestinal type of EGC in 53.1% and a diffuse type in 32.4%. Primary anaplastic tumors seem to be very rare. Intestinal types were predominant in males, especially in the elderly patient. In about 50% the tumor was still limited to the mucosa with the exception of Type I, since those tumors originating from polyp infiltrated submucosa above and those without evidence of a preceding polyp, below average. Regional metastases were found in 4.2% with one primary tumor still limited to the mucosa. In the pure intestinal type of EGC metastases did not occur at all. Multicentricity of EGC was, with 2.8%, remarkably low, compared with the findings of others. Excluding malignancies, the only other noteworthy concurrent lesions were ulcer scars or chronic ulcers with 6.9% and B II resection for benign disease with 2.8%.


On the stochastic dependence between photomultipliers in the TDCR method.
The TDCR method (Triple to Double Coincidence Ratio) is widely implemented in National Metrology Institutes for activity primary measurements based on liquid scintillation counting. The detection efficiency and thereby the activity are determined using a statistical and physical model. In this article, we propose to revisit the application of the classical TDCR model and its validity by introducing a prerequisite of stochastic independence between photomultiplier counting. In order to support the need for this condition, the demonstration is carried out by considering the simple case of a monoenergetic deposition in the scintillation cocktail. Simulations of triple and double coincidence counting are presented in order to point out the existence of stochastic dependence between photomultipliers that can be significant in the case of low-energy deposition in the scintillator. It is demonstrated that a problem of time dependence arises when the coincidence resolving time is shorter than the time distribution of scintillation photons; in addition, it is shown that this effect is at the origin of a bias in the detection efficiency calculation encountered for the standardization of (3)H. This investigation is extended to the study of geometric dependence between photomultipliers related to the position of light emission inside the scintillation vial (the volume of the vial is not considered in the classical TDCR model). In that case, triple and double coincidences are calculated using a stochastic TDCR model based on the Monte-Carlo simulation code Geant4. This stochastic approach is also applied to the standardization of (51)Cr by liquid scintillation; the difference observed in detection efficiencies calculated using the standard and stochastic models can be explained by such an effect of geometric dependence between photomultiplier channels.


Combination chemotherapy for extracranial metastases of a primary malignant cerebral neoplasm.
A patient with a mixed malignant glioma metastatic to the bones and lungs failed to respond to two different broad-spectrum combination chemotherapy regimens which included Adriamycin, methotrexate, cyclophosphamide, CCNU and cis-dichlorodiammineplatinum(II).


Outcomes of graft failure after umbilical cord blood transplantation in acute leukemia: a study from Eurocord and the Acute Leukemia Working Party of the EBMT.
Graft failure has remained a limitation of umbilical cord blood transplantation (CBT). Here, we assessed the outcomes of patients who experienced graft failure after CBT. Inclusion criteria were patients (age ≥ 18 years) experiencing graft failure after unrelated CBT (single or double) between 2005 and 2016, for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), no prior allogeneic or autologous transplantation, no other stem cell product. The study included 87 patients. At 1-year, cumulative incidence of relapse and nonrelapse mortality (NRM) was 35% and 37%, respectively. One-year overall survival (OS) and progression-free survival (PFS) was 40% and 29%, respectively. Forty-six patients underwent a salvage second transplantation with 1-year and 2-year OS and PFS from second transplantation 41% and 34% for OS, and 37% and 34% for PFS, respectively. In multivariate analysis, complete remission (CR) at CBT (HR = 0.45, 95% CI 0.25-0.83, P = 0.01) and reduced-intensity conditioning (HR = 0.51, 95% CI 0.29-0.91, P = 0.023) were associated with better OS. In conclusion, in this retrospective study, we observed that approximately one-quarter of patients experiencing graft failure after CBT remained alive without relapse 2 years later.


Supramolecular biofunctional materials.
This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.


In vivo quantification of receptor-mediated uptake of asialoglycoproteins by rat liver.
The in vivo kinetics of hepatic clearance of 125I-asialo-orosomucoid and 125I-asialofetuin was determined with a portal vein injection technique in barbiturate-anesthetized rats. Nonlinear regression analyses of saturation data gave the following parameters for asialo-orosomucoid, Km = 0.26 +/- 0.06 mg/ml, Vmax = 320 +/- 70 micrograms/min/g, and for asialofetuin, Km = 0.32 +/- 0.07 mg/ml, Vmax = 240 +/- 40 micrograms/min/g. Unlabeled asialofetuin inhibited the clearance of 125I-asialo-orosomucoid with a Ki = 0.25 +/- 0.04 mg/ml. Based on a model assuming that in vivo receptor concentration much greater than receptor KD, then the maximal binding capacity of the external surface of liver cells in vivo for asialo-orosomucoid is 2Km or 520 micrograms/ml or 52 micrograms/g of liver, assuming the liver interstitial space is 0.1 ml/g. Our estimate of in vivo binding capacity approximates in vitro estimates of total hepatic binding capacity, but is 10-fold greater than in vitro estimates of binding capacity on the external surface of liver cells. These results suggest the large majority of asialoglycoprotein receptors are located on the external surface of liver cells. The saturability of 125I-asialo-orosomucoid clearance was also demonstrated with a portal vein double bolus technique, wherein the portal injection of 20-1000 micrograms of unlabeled asialo-orosomucoid was followed 30 s later by the portal injection of tracer. Maximal inhibition of uptake was obtained with a portal vein injection of greater than or equal to 500 micrograms of asialo-orosomucoid. The specific extraction of the 125I-asialo-orosomucoid, which was near zero shortly after a 400-micrograms loading dose, gradually increased toward normal levels with a t1/2 of 21 min. This t1/2 may represent the in vivo rate of receptor recycling, since the gradual increase in unoccupied receptor sites is consistent with the model of receptor binding, internalization, and recycling.


Mineral nutrition and leaf longevity in Ledum palustre: the role of individual nutrients and the timing of leaf mortality.
The effects of fertilization on leaf longevity and leaf mortality in the Alaskan evergreen shrub, Ledum palustre (Ait.) Hult., were investigated in a field experiment. The fertilization treatments included N alone, P alone, N plus P, and N plus P plus K. After 5 years all treatments had the same effect on leaf longevity, decreasing life expectancy from about 2 years in controls to 1-1.5 years in the fertilized plants. In the NPK-fertilized plants, most of the decrease in leaf longevity was due to increased winter leaf mortality; fertilization actually decreased leaf losses during the growing season. The results are consistent with previous research suggesting that one function of overwintering evergreen leaves is to serve as nutrient storage organs, a function that is superfluous when nutrient supplies for new growth can be obtained from current uptake.


Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.
The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.


Failure to awaken from general anesthesia due to infratentorial hemorrhage after cervical spine surgery: A case report.
Emergence is not simply the reverse process of induction. Many dynamic situations could occur in this period by distinct neurobiology as recent studies indicated. Herein we report a rare case of failure of emergence from general anesthesia after cervical spine surgery. Despite the perioperative vital signs and laboratory results were unremarkable, the patient could not recover his mental status and spontaneous breathing during emergence. 20 minutes after cessation of anesthetic drug administration, his blood pressure suddenly began to decrease requiring transfusion and vasopressor. After thorough inspection of intraoperative alterations of hemodynamic and metabolic values, which showed no significant changes except possible signs of delayed volume loss, cerebrovascular bleeding was most suspected as the cause of the event. Computed tomography was performed and infratentorial hemorrhage after cervical spine surgery was checked. Decompression operation was required for removing the hemorrhage. However, the patient's family refused further management considering his limited life expectancy. The patient expired on postoperative day 5. Failure to awaken is a relatively rare event. It could be confused with simple delayed emergence, which is often caused by residual drug effect. However, when it occurs, the result could be devastating. Therefore, appropriate recognition and prompt response are required to decrease the mortality and morbidity of the patient.


Unique Abnormalities in Right Ventricular Longitudinal Strain in Systemic Sclerosis Patients.
Cardiac involvement in systemic sclerosis (scleroderma [SSc]) adversely affects long-term prognosis, often remaining undetectable despite close clinical examination and 2-dimensional echocardiographic monitoring. Speckle-derived strain of the right ventricle (RV) was utilized to detect occult abnormalities in regional and global contractility in SSc patients. A total of 138 SSc patients with technically adequate echocardiograms was studied and compared with 40 age- and sex-matched healthy non-SSc controls. Standard assessment of RV chamber function included tricuspid annular plane systolic excursion and fractional area change. RV longitudinal systolic speckle-derived strain was assessed in the basal, mid, and apical free wall. Tricuspid annular plane systolic excursion was not different between groups (P=0.307). Although fractional area change was lower in SSc patients than in controls (mean, 48.9 versus 55; P=0.002), the mean fractional area change was still within the normal range (>35). In contrast, RV longitudinal systolic speckle-derived strain measures were significantly different between groups, both globally (-20.4% versus -17.7%; P=0.005) and regionally: they were decreased in the apex (-8.5% versus -17.1%; P<0.0001) and mid segments (-12.4% versus -20.9%; P<0.0001), and increased in the base (-32.2% versus -23.3%; P=0.0001) for the SSc group. The regional difference in the base compared with the apex was significantly greater for SSc than for controls (P<0.0001 for interaction). The differences observed in regional strain between SSc and control were unchanged after adjusting for RV systolic pressure. Speckle-derived strain reveals a heterogenous pattern of regional heart strain in SSc that is not detected by conventional measures of function, suggestive of occult RV myocardial disease.


Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia.
In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.


Nonmetric Cranial Trait Variation and Ancestry Estimation in Asian and Asian-Derived Groups.
Traditionally, precontact Native Americans and Asian groups have been conflated for aspects of the biological profile due to their distantly shared genetic history, although this grouping remains largely unexplored. This study examines craniomorphic variability to ascertain whether Asian groups can be differentiated from each other and from Asian-derived groups using more fine-tuned models. Cranial and mandibular data for 35 nonmetric traits were recorded on precontact Native Americans (n = 150) and modern Japanese (n = 150) and Thai (n = 150) individuals. Chi-square analyses indicate that all groups exhibit statistically significant differences in most traits. Additionally, cross-validated binary logistic regression equations resulted in correct classification rates in the range of 65.0-93.3% and demonstrate that sex does not contribute to statistical models. Therefore, numerous traits provide discriminatory resolution that detects differences between the samples, thus highlighting the potential utility of nonmetric traits in identifying individuals beyond the traditional African, European, and Asian forensic ancestry groupings.


Mating motives are neither necessary nor sufficient to create the beauty premium.
Mating motives lead decision makers to favor attractive people, but this favoritism is not sufficient to create a beauty premium in competitive settings. Further, economic approaches to discrimination, when correctly characterized, could neatly accommodate the experimental and field evidence of a beauty premium. Connecting labor economics and evolutionary psychology is laudable, but mating motives do not explain the beauty premium.


Duodenal pH in cystic fibrosis and its relationship to fat malabsorption.
To investigate the relationship between duodenal pH levels and supplemental pancreatic enzyme function in cystic fibrosis, 18 children with this condition had pH recordings performed from the second and fourth part of the duodenum. Compared to age-matched controls, patients with cystic fibrosis had significantly longer periods below a pH of 4.0 in the postprandial period and significantly less time above pH 5.8. These values correspond to the pH levels at which lipase is irreversibly destroyed (pH 4.0) and enteric coating of enzyme supplements dissolves (pH 5.8). A significant relationship was found between the pH recordings from the fourth part of the duodenum and the degree of residual fat malabsorption while taking enteric-coated enzyme supplements. Four patients with an excessively acidic duodenum and residual fat malabsorption despite high-dose enzyme supplementation were treated with misoprostol (Searle), a known acid-reducing agent. There were significant improvements in both duodenal pH values and fat absorption. We conclude that there is a wide range of duodenal pH values found in patients with cystic fibrosis and that the efficiency with which enzyme supplements work is closely related to these pH levels. Administration of misoprostol to those patients with excessively acidic duodenal pH levels as well as residual malabsorption appears to be of benefit in improving both the excessively acidic pH levels and the fat malabsorption.


Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial.
and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo. This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes. There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001). Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding.


Risk factors for early-onset corneal haze after photorefractive keratectomy in an Asian population: Outcomes from the Singapore Armed Forces Corneal Refractive Surgery Programme 2006 to 2013.
To assess the incidence and risk factors for early corneal haze after myopic photorefractive keratectomy (PRK). Tertiary eye center, Singapore. Retrospective case series. The refractive results and corneal haze severity 3 months after PRK were analyzed. Eyes were categorized into 4 groups based on haze severity. Multivariate ordinal logistic regression analysis adjusting for age, ethnicity, sex, use of intraoperative mitomycin-C (MMC), preoperative sphere, and preoperative cylinder was performed. The study reviewed data from 177 patients (347 eyes) with a mean age of 22.6 years ± 4.1 (SD). The majority of the patients were Chinese (98.3%) and men (98.3%). The mean preoperative spherical equivalent (SE) was -3.34 ± 1.19 diopters (D). One hundred thirty-five eyes (38.9%) had PRK with MMC. Ten eyes (2.9%) had enhancement surgery. The overall efficacy index was 0.88 and the safety index was 1.07. At 3 months, 187 eyes (53.9%) had no haze, 76 eyes (21.9%) had a haze grade of more than 0 and less than 1, 76 eyes (21.9%) had a haze grade of 1 or more and less than 2, and 8 eyes (2.3%) had grade 2 haze. Higher degrees of myopia (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.13-1.63; P = .001) and astigmatism (OR, 1.56; 95% CI, 1.09-2.24; P = .014) were associated with increased severity of corneal haze, whereas older age (OR, 0.94; 95% CI, 0.88-0.99; P = .023) had a protective effect. Myopia and astigmatism were associated with increased severity of haze, and older age was protective against early corneal haze development after PRK in an Asian population. None of the authors has a financial or proprietary interest in any material or method mentioned.


First Detection of SARS-CoV-2 in White Rhinoceros during a Small-Scale Coronavirus Surveillance in the Bandia Reserve, Senegal.
The SARS-CoV-2 pandemic has heightened interest in the monitoring and surveillance of coronaviruses in wildlife. Testing for the virus in animals can provide valuable insights into viral reservoirs, transmission, and pathogenesis. In this study, we present the results of the molecular surveillance project focused on coronaviruses in Senegalese wildlife. During the project, we screened fecal samples of the wild animals living in the Bandia Reserve (ten non-human primates, one giraffe, and two white rhinoceros) and the free-living urban population of African four-toed hedgehogs in Ngaparou. The results showed the absence of coronaviruses in hedgehogs, non-human primates, and a giraffe. A single positive sample was obtained from a white rhinoceros. The sequencing results of amplified RdRp gene confirmed that the detected virus was SARS-CoV-2. This study represents the first documented instance of molecular detection of SARS-CoV-2 in white rhinoceros and, therefore, extends our knowledge of possible SARS-CoV-2 hosts.


Can caterpillar density or host-plant quality explain host-plant-related parasitism of a generalist forest caterpillar assemblage?
Herbivore-carnivore interactions are influenced by the plants on which herbivores feed. Accordingly, dietary generalist herbivores have been shown to experience differential risk of mortality from carnivores on different host-plant species. Here, we investigate whether caterpillar density and host-plant quality play a role in driving variation in generalist forest caterpillar mortality from insect parasitoids using a large-scale, multi-year observational study. A total of 4,500 polyphagous caterpillars were collected from eight host-tree species in Connecticut deciduous forests over 5 years, and frequencies of mortality from insect parasitoids (flies and wasps) were compared across the eight host-plant species for the entire generalist caterpillar assemblage (76 species). Separate comparisons were made using seven numerically dominant generalist species, allowing us to account for variation in caterpillar species-specific parasitism risk. We find significant variation in parasitism frequencies of generalist caterpillars across the eight host-plant species when accounting for variation in caterpillar density. We find no support for an influence of caterpillar density on parasitism and no clear evidence for an effect of host-plant quality on parasitism. Therefore, the results of this study discount the hypotheses that variation in caterpillar density and host-plant quality are responsible for variation in parasitism frequencies across host-plant species. Instead, our findings point to other plant-related characteristics, such as plant-derived parasitoid attractants, which may have robust, community-wide effects.


Signal-averaged electrocardiograms in patients with atrial fibrillation or flutter.
The signal-averaged QRS complex that is prolonged because of low amplitude late potentials predicts ventricular tachycardia. This study investigated if signal-averaged low amplitude atrial potentials predict atrial fibrillation or flutter (AFF). Low amplitude potentials were considered to be high-frequency, high amplitude P (HiFP) duration recorded between 50 and 250 Hz at 1.0 mm/microV amplitude minus unfiltered P (UnFP) duration at 0.1 mm/microV. In nine normals, HiFP averaged 115.6 msec +/- 9.8 SD. HiFP were wider in 26 control patients (133.5 msec +/- 15.7, p less than 0.005) but HiFP-UnFP (11.2 msec +/- 8.5) and signals less than 10 microV terminating HiFP inscription (21.7 msec +/- 23.4) were similar to normal values. Seventeen patients with paroxysmal or recently cardioverted AFF did not have significantly longer intervals than controls (HiFP averaged 138.8 msec +/- 23.0, HiFP-UnFP 13.2 msec +/- 9.3, and signals less than 10 microV 32.4 msec +/- 19.5). Therefore, signal-averaged P waves do not identify patients with AFF.


COVID-19 and diarrhea: putative mechanisms and management.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has recently posed a threat to global health by spreading at a high rate and taking millions of lives worldwide. Along with the respiratory symptoms, there are gastrointestinal manifestations and one of the most common gastrointestinal symptoms is diarrhea which is seen in a significant percentage of COVID-19 patients. Several studies have shown the plausible correlation between overexpressed angiotensin converting enzyme 2 (ACE2) in enterocytes and SARS-CoV-2, as ACE2 is the only known receptor for the virus entry. Along with the dysregulated ACE2, there are other contributing factors such as gut microbiome dysbiosis, adverse effects of antiviral and antibiotics for treating infections and inflammatory response to SARS-CoV-2 which bring about increased permeability of gut cells and subsequent occurrence of diarrhea. Few studies found that the SARS-CoV-2 is capable of damaging liver cells too. No single effective treatment option is available. Confirmed pathophysiology is still unavailable. Studies regarding global population are also insufficient. In this review, based on the previous works and literature, we summarized the putative molecular pathophysiology of COVID-19 associated diarrhea, concomitant complications and the standard practices of management of diarrhea and hepatic manifestations in international setups.


The risk of eye splash in burn surgery.
Although the incidence of eye splash injury has been assessed for a number of surgical specialities, such risks posed to the burn surgeon have not been previously quantified. During 100 consecutive procedures the operating burns team wore a clean set of goggles, counting the number of blood splashes on the goggles after each procedure. During this study there were 47 cases of potential eye splash injury, although the individual was only aware of 2 of these intra-operatively. Seven of the splashes involved more than 6 blood droplets on the goggles. The consultant burn surgeon was the most likely to be splashed, sustaining a potential injury in over half cases operated upon. Procedures greater than 45 min in length were more likely to result in a splash than those shorter than 45 min. We recommend that eye protection should be used either in the form of goggles or a visor and should encompass all burn theatre cases as a matter of policy.


Analysis of alpha-1-acid glycoprotein isoforms using CE-LIF with fluorescent thiol derivatization.
The analysis of glycoprotein isoforms is of high interest in the biomedical field and clinical chemistry. Many studies have demonstrated that some glycoprotein isoforms could serve as biomarkers for several major diseases, such as cancers and vascular diseases, among others. Capillary zone electrophoresis (CZE) is a well-established technique to separate glycoprotein isoforms, however, it suffers from limited sensitivity when UV-Vis detection is used. On the other hand, with laser-induced fluorescence (LIF) detection, derivatization reaction to render the proteins fluorescent can destroy the resolution of the isoforms. In this work, a derivatization procedure through the thiol groups of glycoproteins using either 5-(iodoacetamide) fluorescein (5-IAF) or BODIPY iodoacetamide is presented with the model protein of alpha-1-acid glycoprotein (AGP). The derivatization process presented enabled high-resolution analysis of AGP isoforms by CZE-LIF. The derivatization procedure was successfully applied to label AGP from samples of serum and secretome of artery tissue, enabling the separation of the AGP isoforms by CE-LIF in natural samples at different concentration levels.


Identification and targeting of protein tyrosine kinase 7 (PTK7) as an immunotherapy candidate for neuroblastoma.
GD2-targeting immunotherapies have improved survival in children with neuroblastoma, yet on-target, off-tumor toxicities can occur and a subset of patients cease to respond. The majority of neuroblastoma patients who receive immunotherapy have been previously treated with cytotoxic chemotherapy, making it paramount to identify neuroblastoma-specific antigens that remain stable throughout standard treatment. Cell surface glycoproteomics performed on human-derived neuroblastoma tumors in mice following chemotherapy treatment identified protein tyrosine kinase 7 (PTK7) to be abundantly expressed. Furthermore, PTK7 shows minimal expression on pediatric-specific normal tissues. We developed an anti-PTK7 chimeric antigen receptor (CAR) and find PTK7 CAR T cells specifically target and kill PTK7-expressing neuroblastoma in vitro. In vivo, human/murine binding PTK7 CAR T cells regress aggressive neuroblastoma metastatic mouse models and prolong survival with no toxicity. Together, these data demonstrate preclinical efficacy and tolerability for targeting PTK7 and support ongoing investigations to optimize PTK7-targeting CAR T cells for neuroblastoma.


Pelvic congestion syndrome (pelvic venous incompetence): impact of ovarian and internal iliac vein embolotherapy on menstrual cycle and chronic pelvic pain.
The purpose of this study was to analyze the impact of transcatheter embolotherapy on pain perception and menstrual cycle in women with chronic pelvic pain caused by the presence of ovarian and pelvic varices (ie, women with pelvic congestion syndrome or pelvic venous incompetence). From July 1998 to August 2000, 56 patients (mean age, 32.3 y) were treated for chronic pelvic pain. Diagnostic venography of the ovarian veins was followed by transcatheter embolotherapy with a sclerosing agent and coils. A second session was completed to embolize the internal iliac veins in 43 of 56 patients. Visual analog scales (VAS) used to measure pain were administered before embolization and at 3-, 6-, and 12-month follow-up. Questionnaires regarding menstrual history were used as part of the postprocedural analysis. Percutaneous transcatheter embolotherapy of ovarian and pelvic varices was technically successful in 56 of 56 patients (100%); three patients developed recurrent varices, two of whom were treated with repeat transcatheter embolotherapy. Two patients, early in the experience, had complications in which coils placed in the internal iliac veins embolized to the pulmonary circulation; the coils were snared without clinical sequelae. On the VAS, the mean baseline pain level was 7.8 (range, 3.2-9.8; n = 56); at 3-month follow-up, it was 4.2 (range, 0.0-7.2; n = 56); at 6 months, 3.8 (range, 0.0-6.7; n = 41); and at 12 months, 2.7 (range, 0.0-6.9; n = 32). Differences were significant (P <.001) between baseline pain levels and those at all follow-up intervals (ie, 3, 6, and 12 months). The mean decrease in VAS was 5.1 (65% decrease). The clinical follow-up in this series ranged between 6 and 38 months; the mean was 22.1 months. Regarding the impact of embolization on menstruation, all 24 patients responding to questionnaires indicated no change in menstrual cycle. For patients with ovarian/internal iliac varices, transcatheter embolotherapy provides a nonsurgical treatment option. There is a significant decrease in pain based on VAS without any notable impact on menstrual cycle.


Update on viral hepatitis in pregnancy.
Pregnant women with acute viral hepatitis are at higher risk of morbidity and death than pregnant women with chronic viral hepatitis. The risk of death is highest with acute viral hepatitis E, and the rate of transmission to the baby may be highest with hepatitis B virus (HBV) infection. Managing viral hepatitis in pregnancy requires assessing the risk of transmission to the baby, determining the gestational age at the time of infection and the mother's risk of decompensation, and understanding the side effects of antiviral drugs.


Catalytic Synthesis of Formamides by Integrating CO2 Capture and Morpholine Formylation on Supported Iridium Catalyst.
Herein we report an efficient and recyclable catalytic system for tandem CO2 capture and N-formylation to value-added chemicals. CO2 is apt to be captured by morpholine solution, while a highly efficient heterogeneous catalyst, isolated iridium atoms supported over nanadiamond/graphene, is discovered to be highly reactive for the formylation of morpholine, leading to the formation of N-formylmorpholine with excellent productivity (with a turnover number of 5 120 000 in a single batch reaction) and selectivity (>99 %). In addition, the CO2 captured by morpholine under atmospheric conditions can be converted to N-formylmorpholine with decent conversion (51 %), which realizes the integration of CO2 capture and conversion to value-added chemicals.


Miniature mass spectrometer signal processing based on ensemble empirical mode decomposition feature enhancement.
The high sensitivity of the miniature mass spectrometer plays an irreplaceable role in rapid on-site detection. However, its analysis accuracy and stability should be improved due to the influence of sample pretreatment and use environment. The present study investigates the processing effects of ensemble empirical mode decomposition (EEMD) feature enhancement methods on the determination coefficient (R2 ) and relative standard deviation (RSD) of caffeine mass spectrometry (MS) signals. This paper employs the EEMD method combined with polynomial curve fitting to enhance the characteristics of seven caffeine mass spectrum signals with different concentrations and 15 groups of caffeine mass spectrum signals with the same concentration, and the wavelet analysis method was used for comparative verification. The determination coefficient and RSD of the two methods were compared. We found the EEMD method's capability in adaptively decomposing caffeine mass spectrum signals is better than wavelet analysis method. The determination coefficient of the EEMD enhanced feature is better than 0.999, and the RSD is better than 2%, and both are better than wavelet analysis methods. The feature enhancement processing using the EEMD method has significantly improved the determination coefficient and RSD of the sample curve, improving the accuracy and stability of the data and providing a new way for miniature mass spectrometer signal processing.


Density-dependent resistance of the gypsy moth Lymantria dispar to its nucleopolyhedrovirus, and the consequences for population dynamics.
The processes controlling disease resistance can strongly influence the population dynamics of insect outbreaks. Evidence that disease resistance is density-dependent is accumulating, but the exact form of this relationship is highly variable from species to species. It has been hypothesized that insects experiencing high population densities might allocate more energy to disease resistance than those at lower densities, because they are more likely to encounter density-dependent pathogens. In contrast, the increased stress of high-density conditions might leave insects more vulnerable to disease. Both scenarios have been reported for various outbreak Lepidoptera in the literature. We tested the relationship between larval density and disease resistance with the gypsy moth (Lymantria dispar) and one of its most important density-dependent mortality factors, the nucleopolyhedrovirus (NPV) LdMNPV, in a series of bioassays. Larvae were reared in groups at different densities, fed the virus individually, and then reared individually to evaluate response to infection. In this system, resistance to the virus decreased with increasing larval density. Similarly, time to death was faster at high densities than at lower densities. Implications of density-resistance relationships for insect-pathogen population dynamics were explored in a mathematical model. In general, an inverse relationship between rearing density and disease resistance has a stabilizing effect on population dynamics.


Naphthazarin derivatives: synthesis, cytotoxic mechanism and evaluation of antitumor activity.
The rate of the GSH conjugate formation, the inhibition of DNA topoisomerase-I and the cytotoxic activity against L1210 cells of the naphthoquinones showed the same order; 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) > 6-(1-hydroxyethyl)-DMNQ > 2-(1-hydroxyethyl)-DMNQ; the steric hindrance of the substituents, particularly 2-substutuent, in reacting with cellular nucleophiles must be the main cause for lowering the bioactivities. Acetylation of 2-(1-hydroxyethyl)-DMNQ producing 2-(acetyloxyethyl)-DMNQ potentiated the bioactivities; 2-(1-hydroxyethyl)-DMNQ did not react with GSH and the enzyme, and showed ED50 of 0.680 microgram/ml, whereas the values of 2-(1-acetyloxyethyl)-DMNQ were the conjugate formation of 0.14 microM, IC50 value of 81 microM for the enzyme inhibition and ED50 of 0.146 microgram/ml for the cytotoxcity. Furthermore, the acetylation 2-(1-hydroxyethyl)-DMNQ (T/C, 119%) enhanced the T/C values for the mice bearing S-180 tumor [T/C of 2-(1-acetyloxyethyl)-DMNQ, 276%]. It was assumed that the difference in bioactivities ensued by acetylation was based on the mechanism of the so-called bioreductive alkylation.


Toxic retrobulbar neuritis due to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-based chronic sinusitis in the left sphenoid sinus: a case report.
Abrupt visual impairment constitutes a medical urgency, necessitating an interdisciplinary diagnostic and therapeutic approach owing to the broad spectrum of potential etiologies, thereby engaging numerous medical specialties. A 21-year-old Mixed White and Asian female patient, with medical history of nonsteroidal antiinflammatory drug-exacerbated respiratory disease necessitating previous sinus surgery, reported sudden monocular vision loss. Unremarkable ophthalmological examination of the fellow eye and hematological parameters, save for a slight elevation in lymphocytes and eosinophils, were observed. Imaging studies indicated recurrence of bilateral chronic rhinosinusitis with nasal polyps and a mucocele in the left sphenoid sinus, accompanied by bony structural deficits. Emergency revision sinus surgery, guided by navigation, was promptly performed. The patient received treatment with methylprednisolone, ceftriaxone, cyanocobalamin, pyridoxine, thiamine, and acetylsalicylic acid. During the hospital stay, she developed steroid-induced glaucoma, which was subsequently managed successfully. Negative microbiological swabs, along with pathohistological evidence of increased tissue eosinophilia and the patient's clinical history, led to the diagnosis of toxic retrobulbar neuritis secondary to recurrent nonsteroidal antiinflammatory drug-exacerbated respiratory disease-associated chronic rhinosinusitis of the left sphenoid sinus. In cases of acute unilateral vision loss, optic neuritis is a highly probable differential diagnosis and may be induced by pathologies of the paranasal sinuses. Nonsteroidal antiinflammatory drug-exacerbated respiratory disease, a subtype of chronic rhinosinusitis, is associated with type 2 inflammation, which is increasingly recognized for its role in the pathogenesis of bronchial asthma, eosinophilic esophagitis, and atopic eczema. Clinicians should consider chronic rhinosinusitis as a potential differential diagnosis in unilateral visual loss and be cognizant of the rising significance of type 2 inflammations, which are relevant to a variety of diseases.


Modelling changes in the determinants of PHI utilisation in Western Australia across five health care policy eras between 1981 and 2001.
In this study of the Western Australian population we analysed changes in the demographic determinants of PHI use across health policy eras. Specifically, we aimed to predict the probability that an individual, defined by a pre-determined set of characteristics, would utilise PHI for in-patient hospitalisation in WA in each of five health policy eras spanning 1981-2001. The WA Data Linkage System was used to extract hospital morbidity data from 1 January 1981 to 31 December 2001. Random effects logistic regression analysis was used to estimate the likelihood of utilising private health insurance in each of five health policy eras based on the timing and composition of changes in federal health care policy. The use of PHI for in-patient hospitalisation fell significantly from 1981 to 1997 (61% above to 53% below the odds of being a public patient). From 1999, however, the odds of using PHI substantially increased to 16% above that of being a public patient. The likelihood of using PHI in all age fell approximately exponentially across successive health policy eras compared with that in the oldest (70+ years) age group. From 1997 onwards, the relative probabilities of average and disadvantaged individuals using PHI substantially increased compared with extremely advantaged individuals. Our study found that the overall likelihood of utilising PHI versus utilising Medicare for in-patient hospitalisation, adjusted for all demographic characteristics, decreased between 1981 and 1998 but increased precipitously after 1999. We also found that the determinants of using PHI have changed significantly across health policy eras. The most significant changes occurred with respect to age (the probability of PHI use by older individuals increased) and socio-economic status (the probability of PHI use by average and disadvantaged individuals increased). This shift in the effects of determinants of PHI suggests that the introduction of the recent health policies were associated with a change in both the age and socio-economic profile of individuals who utilise PHI.


Contribution of local area deprivation to cultural-linguistic inequalities in foetal growth restriction: trends over time in a Canadian metropolitan centre.
This study investigated temporal trends in heterogeneity of foetal growth restriction across neighbourhood deprivation levels for two culturally distinct communities (Anglophones and Francophones) in a North American metropolitan centre. Inequalities in foetal growth restriction related to deprivation fell from 1989 to 2008 for Francophones, but initial improvements for Anglophones later reversed with a rise in poor foetal growth in the most materially disadvantaged and, unexpectedly, advantaged areas as well. Inequalities in foetal growth restriction related to neighbourhood material deprivation may be emerging in this minority Anglophone population. Potential mechanisms underlying these trends are discussed, as well as implications for perinatal health policy.


Plasma serotonin contents in cerebrovascular disease.
The plasma serotonin contents of fourty-three cerebrovascular patients were examined. 1. Abnormal serotonin contents were found in 72 per cent of fourty-three cerebrovascular patients. 2. In cerebral hemorrhage, serotonin contents were significantly low in the acute period. 3. Serotonin contents in cerebral hemorrhage and subarachnoid hemorrhage, had an increasing tendency from the fourth week to the eigth week, but after the eighth week, they returned to normal.


Pervenous retrieval of embolized catheters from the right heart and pulmonary arteries.
Successful removal of embolized or retained catheter fragments from the right heart was achieved in two out of four patients using pervenous catheter techniques. For the first time a fragment, radiolucent on image intensification, was retrieved from the right pulmonary artery using a wire snare. In a second case a hook-loop was made in the right ventricle with a Judkins left femoral coronary angiographic catheter, which has advantages over previously described hooking devices, to withdraw a fragment to the iliac vein for subsequent snaring. Failure of retrieval occurred only in specially difficult circumstances; when a catheter embolized to the pulmonary artery of a Tetralogy of Fallot, and when in spite of successful ensnarement, a fractured electrode was firmly adherent to the right ventricular apex. Successful pervenous retrieval may require a combination of techniques which move or dislodge, such as a hook or balloon combined with those which ensnare, such as a wire loop or bioptome. Using such techniques, with minimal additions to standard equipment, retrieval procedures can be offered as a routine cardiac catheterization service with a high rate of success.


A Case of 45,X/46,XY Mosaicism Presenting as Swyer Syndrome.
Swyer syndrome is a difference of sex development that is typically associated with mutations in genes responsible for testicular development. It is speculated that some cases may result from cryptic 45,X/46,XY mosaicism leading to abnormal gonadal development. The presence or absence of a 45,X lineage is important for prognosis and management. We present a case of apparent Swyer syndrome associated with a 46,XY chromosomal complement in lymphocytes and 45,X/46,XY mosaicism on analysis of her noncancerous gonad. Gonadal histology was consistent with a 45,X phenotype. This case demonstrates the clinical variability in the presentation of 45,X/46,XY mosaicism and highlights the importance of thorough genetic testing that includes consideration of chromosomal mosaicism. We will discuss the implications of this diagnosis for management.


Influence of stage of cycle, corpus luteum location, follicle size, and number of large follicles on estradiol-17 beta concentrations in bovine follicles.
Concentrations of estradiol-17 beta in follicular fluid were correlated to follicular size, stage of estrous cycle, location of corpus luteum, and presence of large follicles. Paired ovaries were obtained from 481 nonpregnant cows at slaughter and follicles were classified as ipsilateral or contralateral to the corpus luteum. Follicular fluid estradiol-17 beta concentrations from 2494 small, 1485 medium, and 396 large follicles were quantified by radioimmunoassay. Stage of estrous cycle was estimated by visual examination of the corpus luteum. Follicles in stage 1 of the estrous cycle (d 1 to 4) had the highest estradiol-17 beta concentration and the smallest mean follicular diameter. Location of follicles relative to the corpus luteum had no influence on estradiol-17 beta concentrations. As follicular size increased, concentration of estradiol-17 beta also increased. The presence of a single large follicle did not affect the concentration of estradiol-17 beta in medium or small follicles. In contrast, if multiple large follicles occurred in the same cow, concentrations of estradiol-17 beta were significantly lower in medium but not small follicles.


Density distribution, characterization and comparative aspects of plasma lipoproteins in the salamander, Pleurodeles waltii.
Blood plasma from a Urodele amphibian, Pleurodeles waltii, has been found to contain very-low density, low-density and high-density lipoproteins (VLDL, LDL and HDL, respectively). HDL and LDL predominated (concentration range 72-114 and 51-101 mg/dl) with lesser quantities of VLDL (23-51 mg/dl). Following isolation by density gradient ultracentrifugation, the physicochemical properties (morphology, particle size, hydrated density, electrophoretic mobility, and chemical composition) of the three major classes resembled, but were not identical with, those of the corresponding fractions in normal human plasma. The protein moieties of VLDL and LDL consisted mainly of polypeptides of high molecular weight (Mr greater than 60,000), which in their solubility were akin to human apo-B; smaller amounts of another protein migrated to the position of human apo-C-III in basic polyacrylamide gels. The major HDL apolipoproteins were of Mr 31,000 and 27,000, with minor amounts of 13,000, 61,000 and 76,000 components; in alkaline, urea-containing polyacrylamide gels, these major proteins migrated faster than the major components (apo-AI and apo-AII) of human HDL. Immunochemically, lipoproteins with pre-beta-, beta- and alpha-mobility were detected in the VLDL, LDL and HDL, respectively. Salamander VLDL and LDL were found to share an antigenic site(s) with the LDL of trout, chicken and guinea-pig, suggesting the presence of an apo-B-like protein. The chemical compositions and immunochemical reactions of salamander lipoproteins indicate that their structure and metabolism resemble that of other amphibia, reptiles and fish rather more closely than that of most mammals and birds.


V1-Cal hydrogelation enhances its effects on ventricular remodeling reduction and cardiac function improvement post myocardial infarction.
Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1-Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.


Voltage-operated calcium channel heterogeneity in pancreatic beta cells: physiopathological implications.
Voltage-operated calcium channels play crucial roles in stimulus-secretion coupling in pancreatic beta cells. A growing body of evidence indicates that these channels in beta cells are heterogeneous. In particular, not all the high-threshold calcium channels expressed belong to the best known L-type. In rat insulinoma cells, for example, L, N, and P/Q-type channels are present, while in human beta cells L-type and P/Q-type dominate. Where present, N-type and P/Q-type channels participate, alongside with the dominant L-type, in the control of sugar- or depolarization-induced hormone release. Distinct biophysical properties and selective modulation of the channel subtypes are likely to play important physiological roles. T-type channels are involved in beta cell apoptosis, while calcium channel autoantibodies recognizing high-threshold channels in beta cells, have been described both in neurological and diabetic patients. Subtype-selective calcium channel drugs have the potential for being beneficial in beta cell pathological states.


Highly photothermal and biodegradable nanotags-embedded immunochromatographic assay for the rapid monitoring of nitrofurazone.
Immunochromatographic assay platforms are up-and-coming detection tools for disease diagnosis and harmful substances monitoring in food. Herein, by combining photothermal imaging and immunochromatographic analysis, a photothermal immunoassay is developed for the rapid and ultrasensitive detection of nitrofurazone. The nickel disulfide nanosphere with excellent biocompatibility, biodegradability, and high photothermal conversion efficiency, is introduced to offer straightforward readout by color and temperature based on the nature of the crystal, without advanced equipment. It is demonstrated that the nitrofurazone metabolite of semicarbazide can be qualitatively detected by colorimetric signals with a visual limit of 2 μg kg-1. And the quantitative detection limit of photothermal signals is 0.01 μg kg-1, improving the detection sensitivity by about 200 times. Furthermore, recovery rates of the proposed method in food samples were 93 %-120 %. This photothermal immunoassay not merely provides straightforward, rapid, simultaneous qualitative/quantitative detection tactics but may also be valuable in automated and portable diagnostic applications.


Characterization of extracellular vesicles by flow cytometry: Challenges and promises.
The International Society for Extracellular Vesicles (ISEV) defines the extracellular vesicle (EV) as "the particles naturally released from the cell that are delimited by a lipid bilayer and cannot replicate, i.e. do not contain a functional nucleus". The size (diameter) of EVs ranges in ~30-1000 nm, with peak population at ~ 100 nm. Flow cytometry (FCM) is the most commonly used technique for analysis of EVs. However, accurate characterization, procedure standardization, instrument calibration and results interpretation/validation of EVs is confounded by their complex and variable composition, small size and substantial differences in physiological concentrations. Here, the challenges to and promises of FCM for characterization of EVs are discussed. Specifically, we systematically reviewed the pitfalls of FCM in the detection of (small) EVs and the corresponding strategies for enhancing the sensitivity and resolution of the instrument. The shortcomings and improvement in the overall FCM system are described in terms of reference material for calibration, the collection optics for fluorescence (FL), side scatter (SSC) and forward scatter (FSC) signals and fluidics. This study may provide a comprehensive reference for a brief overview pertaining to the challenges and promises of a modern FCM system for analysis of EVs.


The evolution and summary results of the Stanford randomized clinical trials of the management of Hodgkin's disease: 1962-1984.
This is a summary report of the Stanford randomized clinical trials of the management of Hodgkin's disease, initiated in 1962. There have been four major changes in the treatment protocols during this 22 year period. Between 1962-67, 132 patients with CS I, II and III disease were enrolled on various radiation trials. Between 1968-74, 367 patients were enrolled on studies primarily evaluating the role of adjuvant MOPP chemotherapy. Between 1974-80, variations in the chemotherapy regimen and the sequences of the combined modality programs were studied. The current studies, initiated in 1980, have enrolled 102 patients, and test a new mild adjuvant chemotherapy, VBM, (vinblastine, bleomycin and methotrexate) and utilizes ABVD in combined modality and alternating regimens. During the two decades of these studies, involving more than 800 patients, the initial remission rate and duration and the survival of all patients treated have progressively improved.


Peanut lectin and anti-Ii antibodies reveal structural differences among human gastrointestinal glycoproteins.
Human gastrointestinal glycoproteins (mucins), isolated by pepsin digestion from foetal stomachs and meconia, and from paired tumour and non-neoplastic mucosal samples of patients with gastric and colorectal carcinomas, were tested for precipitating reactions with peanut lectin (PNL) and four anti-carbohydrate antibodies (two anti-I, Ma and Low, and two anti-i, Den and Galli). There was remarkable correlation between reactivities with PNL and anti-I (Ma): both reagents reacted with non-neoplastic gastric glycoproteins of "non-secretors", but not with those of "secretors", and also with the majority of gastric tumour and meconium extracts regardless of secretor status. Colorectal tissue extracts (with the exception of one tumour extract) reacted with neither reagent. The various precipitating activities, and results of mild acid hydrolysis and affinity chromatography experiments, enable certain inferences to be made regarding the oligosaccharide moieties of gastrointestinal glycoproteins: (a) expression of PNL and anti-I (Ma) determinants in gastric glycoproteins is dependent on secretor status; (b) extracts reacting with PNL and anti-I (Ma) are mixtures of macromolecules: minor populations react with both reagents, or with PNL only; the major population lacks both determinants, or they are masked by other substitutions; (c) determinants reactive with anti-Ii sera other than anti-I (Ma) are less frequently expressed; and (d) colonic glycoproteins in their lack of PNL and Ii determinants. This suggests that there are structural differences in the oligosaccharide backbones of the two types of glycoprotein.


The relationship between end-plate size and transmitter release in normal and dystrophic muscles of the mouse.
1. The morphology of nerve terminals and sub-neural apparatuses was examined in the muscles of normal and dystrophic adult mice of the Bar Harbor 129 ReJ strain. Nerve terminals were larger in dystrophic muscles than in normal muscles and nerve terminal sprouting was evident in about 50% of the dystrophic muscles fibres. End-plate area was positively correlated with muscle fibre diameter in both normal and dystrophic muscles. 2. Polynueronal innervation was found in only 1% of dystrophic muscle fibres impaled with micro-electrodes. 3. Miniature end-plate potential amplitude was positively correlated with muscle fibre input resistance in both normal and dystrophic muscles. There was however, a greater than normal variation in the amplitudes of m.e.p.p.s recorded from individual dystrophic muscle fibres. 4. Quantum contents of end-plate potentials were estimated in normal and dystrophic mouse nerve-muscle preparations partially blocked with D-tubocurarine. The quantum content of e.p.p.s seemed to be related to muscle fibre diameter, and in dystrophic muscles the characteristics of evoked release were indistinguishable from normal. 5. It was concluded that the nerve terminal sprouting and the expansion of end-plate area which were observed in dystrophic muscles are not a consequence of any form of denervation, but represent an attempt by the axon to expand the area of synaptic contact in hypertrophied muscle fibres.


Functional MRS with J-edited lactate in human motor cortex at 4 T.
While functional MRI (fMRI) localizes regions of brain activation, functional MRS (fMRS) provides insights into metabolic underpinnings. Previous fMRS studies detected task-induced lactate increase using short echo-time non-edited 1H-MRS protocols, where lactate changes depended on accurate exclusion of overlapping lactate and lipid/macromolecule signals. Because long echo-time J-difference 1H-MRS detection of lactate is less susceptible to this shortcoming, we posited if J-edited fMRS protocol could reliably detect metabolic changes in the human motor cortex during a finger-tapping paradigm in relation to a reliable measure of basal lactate. Our J-edited fMRS protocol at 4T was guided by an fMRI pre-scan to determine the 1H-MRS voxel placement in the motor cortex. Because lactate and β-hydroxybutyrate (BHB) follow similar J-evolution profiles we observed both metabolites in all spectra, but only lactate showed reproducible task-induced modulation by 0.07 mM from a basal value of 0.82 mM. These J-edited fMRS results demonstrate good sensitivity and specificity for task-induced lactate modulation, suggesting that J-edited fMRS studies can be used to investigate the metabolic underpinning of human cognition by measuring lactate dynamics associated with activation and deactivation fMRI paradigms across brain regions at magnetic field lower than 7T.


Continuing improvement in cadaver donor graft survival in North American children: the 1998 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).
This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) covers the years 1987-1997, and analyses data on 3,133 cadaver donor (CD) transplants performed in 2,736 patients. There has been a steady decline in the number of CD transplants in children since 1996. Kidneys recovered from donors under 10 years of age accounted for 35% of all transplants in 1987, whereas by 1996 they comprised less than 20%. Caucasian children received 54% of CD transplants, whereas African-American children received 21%. Children under 6 years of age received 17% of CD transplants. Approximately half (46%) of the patients were induced with a T-cell antibody, and at 7 years post-transplant triple therapy is used in 70% of those with a functioning graft. Cyclosporin A is the primary immunosuppressant, with 92% of the patients being maintained on it at 5 years post-transplant. Among patients receiving a transplant in 1997, 11% were initiated with another calcineurin inhibitor, tacrolimus. At 15 days post-transplant 20% of the patients have had a rejection episode and by day 45, 46% have had an acute rejection. The probability of developing a rejection within the first year was reduced from 71% in 1987-1988 to 47% in 1995-1996.


OSM, LIF, its receptors, and its relationship with the malignance in human breast carcinoma (in situ and in infiltrative).
IL-6 cytokine family is composed by several members. IL-6, LIF, and gp130 have been associated with cancer progression. Cytokines play an important role in tumoral growth, invasion of the vessels and development of metastases. Immunoexpressions of LIF, OSM, LIFRbeta and OSMRbeta were studied in benign breast lesion, in situ and infiltrating tumors by Western blot and immunohistochemistry. Percentages of positive samples to OSM, LIF and OSMRbeta were higher in in situ carcinoma than in benign diseases and even higher in infiltrating tumors. gp130-positive samples was higher in infiltrating tumor than in benign diseases. All samples studied were LIFRbeta-positive. Infiltrating tumors showed the most intense immunostaining to LIFRbeta, OSM and OSMRbeta; comparing present results revealed an association between the expression of these proteins and increasing malignancy. In conclusions, development of breast tumor increases the expression of OSM, LIF, OSMRbeta, LIFRbeta and gp130, and this expression may be associated with the malignancy. IL-6 family exert their action through transducer receptor gp130, and gp130 expression increase with malignance, it might be a crucial point in the development of infiltrative adenocarcinoma. The secretion of OSM and LIF by both epithelial and stromal (paracrine manner) cells seems to promote tumor growth.


Pharmacists' confidence in explaining biosimilars to patients before a nationwide medicine change: A cross-sectional study.
Biosimilars can improve patient access to biological medicines. Although biosimilars have been shown to be equally effective and safe, some patients remain reluctant to transition to biosimilars. Pharmacists may support patients changing to biosimilars and are often at the frontline for dealing with queries and concerns, but their confidence and readiness for this role are unclear. This study examines pharmacists' confidence in explaining biosimilars to patients and explores the information they would provide in response to common queries. Practicing community, hospital, and primary care pharmacists (N = 142) in New Zealand completed an Internet-based survey on their experience and familiarity with bio-originators and biosimilars, attitudes and concerns towards biosimilars, confidence in explaining key concepts, and responses to common queries. A hierarchical linear regression was conducted to examine possible factors associated with confidence in explaining biosimilars, and a content synthesis was conducted to examine responses to common patient queries. Pharmacists were most confident in explaining how biosimilars are administered, their efficacy, and cost-saving, and least confident in describing manufacturing and testing. Respondents who had more positive attitudes (B = 1.64, p < .001) and more familiarity with biosimilars (B = 27.15, p < .001) were more confident in educating patients. Pharmacists' main concerns about biosimilars included reduced efficacy, safety, and a lack of knowledge and acceptance. Responses to common queries were diverse but further highlighted several gaps in knowledge. Gaps included being unable to define biosimilars, provide information on side effects, and believing that biosimilars undergo the same testing process as bio-originators. Pharmacists wanted resources (written and Internet-based) to improve their knowledge and ability to educate patients. Pharmacists reported a lack of knowledge and confidence in explaining manufacturing processes and testing of biosimilars. Additional resources are needed to support their practice and may help improve patient and companion acceptance of biosimilars.


Flow territory mapping of the cerebral arteries with regional perfusion MRI.
Conventional contrast-enhanced angiography is the gold standard for visualization of the vascular tree supplied by the major cerebral arteries and assessment of collateral flow. Thus far, however, no methods are available to assess the actual flow territories of the individual cerebral arteries. In the present study, we evaluate a noninvasive arterial spin labeling MRI method for selective mapping of the flow territories of the left and right internal carotid arteries and posterior circulation (basilar artery and vertebral arteries). A spatially selective labeling approach, regional perfusion imaging, was developed on the basis of selective slab inversion of the arterial water with a pulsed arterial spin labeling sequence. The selectivity of this method was demonstrated. Regional perfusion imaging enables assessment of the perfusion territories of the major cerebral arteries. With selective labeling of an internal carotid artery, signal is present in both the ipsilateral anterior cerebral artery and ipsilateral middle cerebral artery flow territory. With labeling of the basilar artery, perfusion-weighted signal is symmetrically present in both posterior cerebral artery flow territories. Cerebral blood flow values measured with regional perfusion imaging in the complete hemisphere (40.1 mL x min(-1) x 100 g(-1) tissue), white matter (22.1 mL x min(-1) x 100 g(-1) tissue), and gray matter (65.8 mL x min(-1) x 100 g(-1) tissue) are in agreement with data in the literature. We present the first imaging method capable of evaluating both quantitatively and qualitatively the flow territories of the individual brain-feeding arteries in vivo.


Application of cellulase for the modification of corn stalk: leading to oil sorption.
In this work, a new biotechnological procedure was developed using cellulase as a modifier to produce oil sorbent from corn stalk (CMCS). Cellulase treatment of raw corn stalk (RCS) with enzyme loading of 100 U/g at 45°C for 6h resulted in high oil sorption capacity. The sorption capacities of vegetable oil, diesel and crude oil by CMCS were 18.47, 16.15 and 27.23 g/g, respectively, which were found to be much higher than RCS. XRD, BET and SEM were applied to characterize RCS and CMCS. The effects of sorbent dose (0.1-0.5 g), initial oil amount (5-30 g), and the sorption kinetics were also studied. This work demonstrated that corn stalk modified by cellulase is an efficient and environment-friendly biosorbent for the removal of spilled oil.


Smallpox: An eradicated infection with persistent sequels - Case report and a brief on smallpox.
Sequelae of smallpox infection on the ocular surface are still seen, including corneal scars adherent leukoma and phthisical globes. This paper will report another sequel of smallpox infection causing inadvertent bleb in a 62-year-old diabetic female with no history of ocular surgery or trauma in either eye. The patient had smallpox infection during her childhood. Her follow up extended from May 1997 until August 2007 with a constant eye examinations including controlled intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked pupil.


Unintended human ingestion of nanoplastics and small microplastics through drinking water, beverages, and food sources.
The potential risks on human health from the unintentional ingestion of microplastics (MPs) and nanoplastics (NPs) is an emerging concern. Despite the mounting awareness of small-scale plastics in drinking water, beverages, and food products, little is known about potential downstream effects on human health. Furthermore, very few studies currently exist that focus on NPs and smaller sized MPs, which may be more significant for human exposure given the higher likelihood of smaller-scale particles crossing the intestinal tract. Therefore, this review summarizes the smallest NPs and MPs (NMPs) reported in the literature, focusing on a threshold size range of <50 μm detected in drinking water, beverages, and food (e.g., table salt, seafood). We show that the smallest NMPs reported currently in the literature overwhelmingly originate from drinking water, with prevalent polymer compositions including polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET). We further describe NMPs in food products and show that most studies focus on larger size ranges (e.g., <100 μm or 5-250 μm), thereby supporting the need for continued investigations to understand the breadth of contaminants in human ingestion. We cover the current methodologies for sample preparation, size characterization, and polymer identification and further discuss the potential impact of these approaches on the findings and current knowledge of NMPs. This review aims to provide a groundwork to support next steps towards better understanding the oral ingestion of NMPs and the potential impact on human health.


Functional connectivity strength and topology differences in social phobia adolescents with and without ADHD comorbidity.
Social phobia (SP) is associated with changes in functional connectivity strength and topology. However, reported changes have been heterogeneous due to small sample sizes, inconsistent methodologies, and comorbidities, such as attention-deficit/hyperactivity disorder (ADHD), which has a high comorbidity rate with SP. Furthermore, there are few studies looking at SP in an adolescent population, a critical period for the development of the social brain. This project focuses on functional connectivity strength and topological differences in social phobia patients with and without ADHD comorbidity. We examined resting-state functional MRI images from 158 subjects, including 36 SP participants without ADHD comorbidity, 60 SP participants with ADHD comorbidity, and 62 healthy controls, with an overall average age of 14.16. We used a data-driven approach to examine impaired functional connectivity in a whole-brain analysis and higher-order topological differences in functional brain networks. We identified changes in the cerebellum and default mode network in social phobia patients as a whole, with the presence of ADHD comorbidity affecting various subsystems of the default mode network. Social phobia functional connectivity networks resembled random graphs, and local connectivity patterns in the superior occipital gyrus were different due to ADHD comorbidity. These alterations may indicate impairments in self-related processing, imagery, mentalizing, and predictive processes. We then used these changes in a linear support vector machine to distinguish between each pair of groups and achieved prediction accuracy significantly above chance rates. Our study extends prior research by showing that functional connectivity changes exist at adolescence, which are affected by ADHD comorbidity. As such, these results offer a new perspective in examining neurobiological changes in SP patients.


Neodymium: YAG laser specifications for safe intravesical therapy.
The depth of penetration of a laser beam is a critical factor in determining the therapeutic potential and risks of treatment. Variable parameters of laser energy were applied endoscopically in dog bladders. Although there was a clear trend toward greater depth of necrosis with increased energy, marked variability occurred within each set of energy specifications. Full thickness injuries with penetration depths up to five mm. were observed in some animals at all energy levels above 120 joules. A number of variables affect the penetration depth of a Nd:YAG laser, some of which are difficult to control with precision in an endoscopic setting.