Doxorubicin inhibits osteosarcoma progression by regulating circ_0000006/miR-646/ BDNF axis.
Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression. The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay. Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo. Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.


Elephantiasis nostras--a case report.
Elephantiasis nostras, the result of chronic lymphedema, is characterized by marked edema of the affected extremity with a thickened, verrucous, pebbly appearance of the skin. The pathogenesis is thought to be related to fibroblast proliferation following impaired lymphatic drainage, leading to fibrosis and further restriction of lymph drainage with progressive edema. A case report of a patient with massive chronic lymphedema of her feet is presented.


[Autologous composite grafts from the cavum conchae for reconstruction of multilayer nasal defects].
Autologous transplants comprising skin and cartilage, so-called composite grafts (cgs), are an important reconstructive tool for multilayered defects of the nose. A cg from the auricular cavum conchae needs to fulfill both functional and esthetic demands. This article illustrates the indications for and requirements of cgs, and also investigates graft healing and functional-aesthetic results. The current publication is a review article; the original data were published with the award of the 2014 APKO prize under the title "The auricle's cavum conchae composite graft in nasal reconstruction". At the ENT department of Ulm University Medical School, multilayered defects of different nasal esthetic subunits are reconstructed with cgs. Based on these experiences, the authors report on long-term functional and esthetic results in the areas of the donor and recipient sites. Auricular cgs are versatile and reliable autologous transplants. The ease of harvesting, minimal donor site morbidity, and stable convex shape of these grafts render them ideal for reconstruction of multilayered nasal defects. Septal splints and custom-made prosthesis promote healing and prevent stenotic scarring.


Effect of keratinocyte growth factor and activin on cell growth in the human prostatic cancer cell line LNCaP.
Keratinocyte growth factor (KGF) has paracrine properties in the human prostate which stimulate epithelial cell growth. Activins have profound effects on cell growth and function in the human prostate, and are expressed in LNCaP, DU 145 and PC3 cells. LNCaP cells were characterized by immuncytochemistry, an immunoassay and polymerase chain reaction. A 3[H]thymidine assay was used with 0.01-10 nM dihydrotestosterone, 10 micro M flutamide, 1-100 ng/ml KGF and 3 nM activin. LNCaP cells expressed Ki67, PSA, cytokeratins (8, 18, 19, 14, 15) androgenreceptor but no KGF protein. LNCaP cells showed telomerase activity. Furthermore, ARmRNA (365 bp), but no KGF or KGFRmRNA were expressed. KGF ELISA detected no intracellular or secreted KGF. DHT (1, 10 and 100 nM) and KGF (10 and 100 ng/ml) significantly stimulated LNCaP cell proliferation. However, flutamide and 3 nM activin A significantly decreased cell proliferation in the presence and absence of KGF. The results of our experiments support the hypothesis that cell growth and proliferative characteristics of LNCaP cells are modulated by KGF and activin A.


Emergency department safety assessment and follow-up evaluation 2: An implementation trial to improve suicide prevention.
Emergency departments (EDs) are important for preventing suicide. Historically, many patients with suicide risk are not detected during routine clinical care, and those who are often do not receive suicide-specific intervention. The original Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE 1) study examined the implementation of universal suicide risk screening and a multi-component ED-initiated suicide prevention intervention. The ED-SAFE 2 aims to study the impact of using a continuous quality improvement approach (CQI) to improve suicide related care, with a focus on improving universal suicide risk screening in adult ED patients and evaluating implementation of a new brief intervention called the Safety Planning Intervention (SPI) into routine clinical practice. CQI is a quality management process that uses data and collaboration to drive incremental, iterative improvements. The SPI is a personalized approach that focuses on early identification of warning signs and execution of systematic steps to manage suicidal thoughts. ED-SAFE 2 will provide data on the effectiveness of CQI procedures in improving suicide-related care processes, as well as the impact of these improvements on reducing suicide-related outcomes. Using a stepped wedge design, eight EDs collected data cross three study phases: Baseline (retrospective), Implementation (12 months), and Maintenance (12 months). Lean methods, a specific approach to pursuing CQI which focuses on increasing value and eliminating waste, were used to evaluate and improve suicide-related care. The results will build upon the success of the ED-SAFE 1 and will have a broad public health impact through promoting better suicide-related care processes and improved suicide prevention.


DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is an incurable and progressive neurodegenerative senile disorder associated with the brain accumulation of Aβ plaques. Although vaccines that reduce Aβ plaques can control AD, the rationale for their use at the onset of the disease remains debatable. Old humans and mice usually respond poorly to vaccines due to presumably age-related immunological impairments. Here, we report that by modifying vaccines, the poor responsiveness of old mice can be reversed. Unlike the Aβ peptide vaccine, DNA immunizations with the amino-terminal Aβ(1-11) fragment exposed on the surface of HBsAg particles elicit high levels of anti-Aβ antibody both in young and old mice. Importantly, in AD model 3xTgAD mice, the vaccine reduced Aβ plaques, ameliorated cognitive impairments and, surprisingly, significantly increased life span. Hence, we propose that vaccines targeting Aβ(1-11) can efficiently combat AD-induced pathological alterations and provide survival benefit in patients with AD.


Neuro-epithelial bodies in organ cultures of fetal rabbit lungs. Ultrastructural characteristics and effects of drugs.
Lung explants from fetal rabbit at the late glandular stage of development (20 days' gestation) and near term (31 days' gestation) were maintained in organ culture for up to 22 days. They were studied by light and electron microscopy to determine whether neuro-epithelial bodies (NEB) of the lung retain structural integrity in vitro. Cultured NEB retained argyrophilia and specific amine fluorescence after formaldehyde condensation. Their ultrastructural morphology showed some differences from that of uncultured NEB: the terminal axons had degenerated and the secretory granules (dense-core vesicles, DCV) were slightly larger, more pleomorphic, more electron-dense, and redistributed throughout the cytoplasm rather than being confined chiefly to the basal regions. These changes, together with hypertrophy of Golgi zones, suggest increased synthesis and storage of secretory products in the DCV during culture. In NEB from near-term explants cultured for 7 days and incubated with reserpine, the core of DCV decreased in size and electron-density and became finely granular, a sign of amine release. Ca++ ionophore No. A-23187, also, induced changes in the ultrastructure of DCV, suggesting that the secretory process in lung neuro-endocrine cells, as in other secretory cells, is Ca++-dependent.


Quantitative and Functional Analysis of PD-1+ NK Cells in Patients With Autoimmune Thyroid Disease.
Natural killer (NK) cells have an important role in innate immunity and in the regulation of immune response. The role of NK cells expressing the programmed cell death protein-1 (PD-1) regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD). To analyze the levels and function of PD-1+ NK cells in samples from AITD patients. Cases and controls, observational study. Hospital Universitario la Princesa, Spain. Forty patients with AITD, 16 with Hashimoto thyroiditis (HT), 24 with Graves' disease (GD), and 15 healthy controls. Multiparametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines. Levels and function of PD-1+ NK cells in blood samples from AITD patients and controls. Increased levels of NK cells and the CD56dimPD-1+ subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56brightPD-1+ NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56brightPD-1- NK cells, whereas CD56dimPD-1+ cells from GD patients exhibited an enhanced production of interferon-γ. PD-1+ NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1+ NK cells and clinical laboratory parameters. The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients' further support the complex role of these cells in this pathogenesis.


Impact of the preoperative body composition indexes on intraoperative blood loss in patients undergoing pancreatoduodenectomy.
This study sought to identify any significant predictors of blood loss during pancreatoduodenectomy (PD) among preoperative variables, including the body composition indexes. The preoperative data of patients undergoing PD were retrospectively reviewed. The objective variable was the percentage of blood loss during PD to the estimated circulating blood volume (proportional blood loss: PBL). The circulating blood volume was estimated using Nadler's formula. The total psoas area, average Hounsfield units of psoas area (psoas muscle density: PMD), and visceral to subcutaneous adipose tissue area ratio (VSR) were measured at the third vertebra using preoperative plain computed tomography images. A univariate analysis and multiple linear regression analysis for PBL were conducted using the preoperative variables. A total of 415 patients were analyzed. The median PBL was 24.5%. The PMD (coefficient - 0.267; 95% CI - 0.518, - 0.015), VSR (coefficient 2.719; 95% CI 0.238, 5.201), serum albumin level (coefficient - 8.458; 95% CI - 13.02, - 3.898), neoadjuvant therapy (coefficient 9.605; 95% CI 1.722, 17.49), and prothrombin time-international normalized ratio (PT-INR, coefficient 38.63; 95% CI 10.94, 66.31) were independently associated with PBL. The preoperative PMD, VSR, serum albumin level, neoadjuvant therapy, and PT-INR independently affected PBL. These factors could therefore be potential targets to reduce blood loss during PD.


[Bicyclic piperazine homologues XIV (1). Synthesis and analgesic activity of 3,8-diaza-bicyclo[3.2.1.] octane derivatives].
The synthesis of two new series of 3,8-diazabicyclo [3.2.1] octane derivatives is described. The first series includes some 3-(or 8)-allyl and 3-(or 8)-(3,3-dimethylallyl) derivatives of 3,8-diazabicyclo [3.2.1] octane and 3,8-diazabicyclo [3.2.1] octane-2-one. The second series includes some esters and carbamates of 3-(3-hydroxy-3-methyl)butyl-3,8-diazabicyclo [3.2.1] octane. Two new 3,8-diazabicyclo [3.2.1] octane derivatives structurally related to propoxyphene are also described. Some pharmacological data of these compounds are reported.


Rapid Formation of Peptide/Lipid Coaggregates by the Amyloidogenic Seminal Peptide PAP248-286.
Protein/lipid coassembly is an understudied phenomenon that is important to the function of antimicrobial peptides as well as the pathological effects of amyloid. Here, we study the coassembly process of PAP248-286, a seminal peptide that displays both amyloid-forming and antimicrobial activity. PAP248-286 is a peptide fragment of prostatic acid phosphatase and has been reported to form amyloid fibrils, known as semen-derived enhancer of viral infection (SEVI), that enhance the viral infectivity of human immunodeficiency virus. We find that in addition to forming amyloid, PAP248-286 much more readily assembles with lipid vesicles into peptide/lipid coaggregates that resemble amyloid fibrils in some important ways but are a distinct species. The formation of these PAP248-286/lipid coaggregates, which we term "messicles," is controlled by the peptide:lipid (P:L) ratio and by the lipid composition. The optimal P:L ratio is around 1:10, and at least 70% anionic lipid is required for coaggregate formation. Once formed, messicles are not disrupted by subsequent changes in P:L ratio. We propose that messicles form through a polyvalent assembly mechanism, in which a critical surface density of PAP248-286 on liposomes enables peptide-mediated particle bridging into larger species. Even at ∼50-fold lower PAP248-286 concentrations, messicles form at least 10-fold faster than amyloid fibrils. It is therefore possible that some or all of the biological activities assigned to SEVI, the amyloid form of PAP248-286, could instead be attributed to a PAP248-286/lipid coaggregate. More broadly speaking, this work could provide a potential framework for the discovery and characterization of nonamyloid peptide/lipid coaggregates by other amyloid-forming proteins and antimicrobial peptides.


Experimental evidence of incomplete fluorescence quenching of pyrene bound to humic substances: implications for Koc measurements.
Fluorescence quenching (FQ) is extensively used for quantitative assessment of partition coefficients (KOC) of polycyclic aromatic hydrocarbons (PAHs) to natural organic materials - humic substances (HS). The presence of bound PAHs with incompletely quenched fluorescence would lead to underestimation of the KOC values measured by this technique. The goal of this work was to prove the validity of this assumption using an original experimental setup, which implied FQ measurements upon excitation into two distinct vibronically coupled electronic states. Pyrene was used as a fluorescent probe, and aquatic fulvic acid (SRFA) and leonardite humic acid (CHP) were used as the humic materials with low and high binding affinity for pyrene, respectively. Excitation of pyrene into the forbidden (S0-S1) and allowed (S0-S2) electronic states yielded two pairs of nonidentical FQ curves. This was indicative of incomplete quenching of the bound pyrene, and the divergence of the two FQ curves was much more pronounced for CHP as compared to SRFA. The two component model of fluorescence response formation was proposed to estimate the KOC values from the data obtained. The resulting pyrene KOC value for CHP (220 ± 20) g L(-1) was a factor 3 higher compared to the KOC value determined with the use of the Stern-Volmer formalism (68 ± 2) g L(-1). At the same time for aquatic FA the difference in FQ curves was almost negligible, which enables the use of the Stern-Volmer formalism for weakly interacting HS and PAHs.


Bidirectional associations between valued activities and adolescent positive adjustment in a longitudinal study: positive mood as a mediator.
Although activity involvement has been linked to positive youth development, the value that adolescents place on these activities (i.e., how much they enjoy the activities, find them important, and spend time on them) has received less attention. The purpose of the present study was to examine the bidirectional longitudinal association between engagement in valued activities and adolescent positive adjustment (optimism, purpose in life, and self-esteem), as well as investigate a possible underlying mechanism for this link. High school students (N = 2,270, 48.7% female) from Ontario, Canada completed questionnaires annually in grades 10, 11, and 12. Auto-regressive cross-lagged path analyses were conducted over time, controlling for gender, parental education, and academic grades. Greater engagement in valued activities predicted higher optimism, purpose, and self-esteem over time. Importantly, the results did not support an alternate hypothesis of selection effects, in that adolescents who were better adjusted were not more likely than their peers to engage in valued activities over time. We also found that the longitudinal associations between valued activities and positive adjustment may be due partly to an underlying effect of increased positive mood. Thus, engagement in valued activities appears to be important for adolescent positive adjustment, and may help to foster thriving. Communities, educators, and parents should actively support and encourage adolescents to develop valued activities, and seek to ensure that there are ample opportunities and resources available for them to do so.


Novel adaptive zeroing neural dynamics schemes for temporally-varying linear equation handling applied to arm path following and target motion positioning.
While the handling for temporally-varying linear equation (TVLE) has received extensive attention, most methods focused on trading off the conflict between computational precision and convergence rate. Different from previous studies, this paper proposes two complete adaptive zeroing neural dynamics (ZND) schemes, including a novel adaptive continuous ZND (ACZND) model, two general variable time discretization techniques, and two resultant adaptive discrete ZND (ADZND) algorithms, to essentially eliminate the conflict. Specifically, an error-related varying-parameter ACZND model with global and exponential convergence is first designed and proposed. To further adapt to the digital hardware, two novel variable time discretization techniques are proposed to discretize the ACZND model into two ADZND algorithms. The convergence properties with respect to the convergence rate and precision of ADZND algorithms are proved via rigorous mathematical analyses. By comparing with the traditional discrete ZND (TDZND) algorithms, the superiority of ADZND algorithms in convergence rate and computational precision is shown theoretically and experimentally. Finally, simulative experiments, including numerical experiments on a specific TVLE solving as well as four application experiments on arm path following and target motion positioning are successfully conducted to substantiate the efficacy, superiority, and practicability of ADZND algorithms.


T-cell fate and function: PKC-theta and beyond.
The serine/threonine-specific protein kinase C-theta (PKC-theta) is a core component of the immunological synapse that was shown in vitro to play a central role in the activation of T cells after T cell receptor (TCR) and co-stimulatory molecule engagement. In recent years, a series of in vivo studies have shown that the situation is far more complex; specifically, PKC-theta signaling is differentially required for Th1, Th2, Th17 and CD8+ cytotoxic T-cell responses. These studies highlight the combination of signals that directly regulate T-cell differentiation and effector responses. In this review, we highlight recent in vivo studies investigating PKC-theta function and discuss this in the context of how the integration of extrinsic signals determines T cell fate and function.


Correction to: Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy.
The article "Expected Budget Impact and Health Outcomes of Expanded Use of Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy", written by Molly F. Purser, Deirdre M. Mladsi, Alan Beckman, Francesca Barion, John Forsey was originally published electronically on the publisher's internet portal (currently SpringerLink) on August 24, 2018 without open access.


Isolation and characterization of cancer stem cells from a human glioblastoma cell line U87.
A variety of malignant cancers have been found to contain a subpopulation of stem cell-like tumor cells, or cancer stem cells (CSCs). However, the existence of CSCs in U87, a most commonly used glioma cell line, is still controversial. In this study, we demonstrate that U87 cell line contained a fraction of tumor cells that could form tumor spheres and were enriched by progressively increasing the concentration of serum-free neural stem cell medium with or without low dose vincristine. These cells possessed the ability of self-renewal and multipotency, the defined characteristics of CSCs. Moreover, the tumors formed by the secondary spheres displayed typical histological features of human glioblastoma, including cellular pleomorphism, pseudopalisades surrounding necrosis, hyperchromatic nuclei, high density of microvessels and invasion to the brain parenchyma. These results indicate that gradually increasing the concentration of serum-free neural stem cell culture medium with or without vincristine is a simple and effective method for isolation of CSCs to study the initiation and progression of human glioblastoma.


Do as I do, not as I say: Actions speak louder than words in preschoolers learning from others.
To date, no research has examined children's imitative abilities in the context of learning self-regulatory strategies from adults-especially when there is a conflict between communicative intent and later behavior. A sample of 84 4- and 5-year-olds performed a delay-of-gratification task after observing an adult perform the same task. Across four between-participants conditions, the model either did or did not state her intention to complete the task (positive vs. negative communication), modeled self-regulatory strategies, and then either did or did not complete the task successfully (positive vs. negative outcome). Children in the positive outcome conditions were more likely to imitate the novel strategies and successfully wait in both familiar and unfamiliar self-regulation tasks irrespective of the model's communicated intent. We discuss implications for practice and interventions.


Esterification of xanthophylls by human intestinal Caco-2 cells.
We recently found that peridinin, which is uniquely present in dinoflagellates, reduced cell viability by inducing apoptosis in human colon cancer cells. Peridinin is also found in edible clams and oysters because the major food sources of those shellfish are phytoplanktons such as dinoflagellates. Little is known, however, about the fate of dietary peridinin and its biological activities in mammals. The aim of the present study was to investigate the enzymatic esterification of xanthophylls, especially peridinin which is uniquely present in dinoflagellates, using differentiated cultures of Caco-2 human intestinal cells. We found that peridinin is converted to peridininol and its fatty acid esters in differentiated Caco-2 cells treated with 5mumol/L peridinin solubilized with mixed micelles. The cell homogenate was also able to deacetylate peridinin and to esterify peridininol. Other xanthophylls, such as fucoxanthin, astaxanthin and zeaxanthin, were also esterified, but at relatively lower rates than peridinin. In this study, we found the enzymatic esterification of xanthophylls in mammalian intestinal cells for the first time. Our results suggest that the esterification of xanthophylls in intestinal cells is dependent on their polarity.


Granulomatous myocarditis secondary to cornstarch.
A 44-year-old white female with chronic rheumatic heart disease and mitral insufficiency was admitted to the hospital for cardiac catheterization and mitral valve replacement. On the ninth postoperative day the patient experienced a sudden onset of chest pain, hypotension, and died shortly therafter. Autopsy revealed multiple mural thrombi of the left atrium, one of which occluded the mitral orifice. Histologic examination showed a granulomatous and non-specific interstitial myocarditis involving all chambers of the heart. In the granulomas, both inside and outside giant cells, rounded foreign bodies were noted which stained light blue with hematoxylin and eosin, red with the periodic acid Schiff reagent, dark bluish-black with Gram's iodine, and showed Maltese cross birefringence under polarized light. These particles were identical with starch granules from surgical glove powder. The cause of death was acute mitral occlusion form a flapping mural thrombus.


Correlation Between Mucosal IL-6 mRNA Expression Level and Virulence Factors of Helicobacter pylori in Iranian Adult Patients With Chronic Gastritis.
Helicobacter pylori infection is associated with gastritis and marked infiltration of the gastric mucosa by several cytokines secreting inflammatory cells that contribute to sustained local inflammation. In this study, we sought to examine IL-6 expression in H. pylori-infected and uninfected gastric mucosa and elucidate the implication in the pathogenesis of H. pylori-associated gastritis in human. The current study aimed to determine mucosal IL-6 mRNA expression level and their correlation with virulence factors and the grade of chronic gastritis among H. pylori infected patients with chronic gastritis from Shahrekord, Iran. Mucosal IL-6 mRNA levels was measured by real-time PCR using endoscopic biopsies taken from the gastric antrum of 58 subjects infected with H. pylori and 44 uninfected subjects. Presence of vacA and cagA virulence factors was evaluated using PCR. The IL-6 mRNA expression levels were significantly more elevated in H. pylori-positive patients than uninfected individuals and expression of this cytokine was independent from the virulence factors. There was a correlation between IL-6 expression level and the grade of chronic gastritis. Enhanced induction of IL-6 may be involved in the pathogenesis of H. pylori-associated gastritis.


Acyl-CoA synthetase activity in Plasmodium knowlesi-infected erythrocytes displays peculiar substrate specificities.
In its blood stages the malaria parasite, Plasmodium, displays very high lipid metabolism. We present evidence for an abundant long-chain acyl-CoA synthetase (EC 18.104.22.168) activity in Plasmodium knowlesi-infected simian erythrocytes. The activity was found to be 20-fold higher in the schizont-infected (the last parasite stage) than in control erythrocytes. The cosubstrate requirements of the enzyme were similar to those previously reported for acyl-CoA synthetases from other sources. Among the separated reaction products of oleyl-CoA synthetase, only PPi and oleyl-CoA were inhibitory, with Ki over 350 microM. The fatty acid specificity of the parasite acyl-CoA synthetase activity was fairly marked and depended on the unsaturation state of the substrate. The tested fatty acids displayed similar Vmax, whereas their Km ranged from 11 (palmitate) to 59 microM (arachidonate). Finally, experiments involving heat inactivation and separation on hydroxyapatite excluded the presence of a specific arachidonyl-CoA synthetase identical to those present in other cells. On the other hand, fatty acid competition experiments evidenced the existence of at least two distinct enzymatic sites for fatty acid activation in P. knowlesi-infected simian erythrocytes: one is specific for saturated fatty acids and the other for polyunsaturated species, whereas oleate could be activated at both sites.


Purification of human erythrocyte glucose 6-phosphate dehydrogenase and glutathione reductase enzymes using 2',5'-ADP Sepharose 4B affinity column material in single chromatographic step.
The enzymes of glucose 6-phosphate dehydrogenase and glutathione reductase were purified from human erythrocytes in one chromatographic step consisting of the use of the commercially available resin 2',5'-ADP Sepharose 4B by using different washing buffers. Ammonium sulfate (30-70%) precipitation was performed on the hemolysate before applying to the affinity column. Using this procedure, G6PG, having the specific activity of 22.9 EU/mg proteins, was purified with a yield of 43% and 9150-fold; GR, having the specific activity of 20.7 EU/mg proteins, was purified with a yield of 26% and 8600-fold. The purity of the enzymes was checked on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and each purified enzyme showed a single band on the gel. This procedure has advantages of preventing of enzyme denaturation, short experimental duration, and use of less chemical materials for purification of the enzymes.


Daily consensus interferon (CIFN) monotherapy in non-responders or relapsers to a previous interferon regime: one year follow-up after 48 weeks of treatment.
Data suggests on the basis of thrice a week therapy, efficacy of mono consensus interferon is comparable to other alpha interferons. One-year follow-up after 12-month daily consensus interferon monotherapy for chronic hepatitis C among non-responders or relapsers to previous consensus interferon monotherapy is investigated. Between February and August 1998, 11 non-cirrhotic patients with previous consensus interferon failure were treated. Six were relapsers and five non-responders. Serum HCV-RNA was tested at the 12th and 48th weeks of treatment and followed for one year thereafter. Eight (72%) were HCV-RNA negative at both 12th and 48th weeks. Of these, 60% (3/5) were among previous non-responders and 83% (5/6) were among previous relapsers. One year sustained virological response was 55%. Of this, 40% (2/5) were among non-responders and 66% (4/6) previous relapsers. These findings suggest that daily consensus interferon needs to be further investigated as an alternative to pegylated formulations, especially with the addition of ribavirin.


Maintenance repetitive transcranial magnetic stimulation can inhibit the return of tinnitus.
A single patient was tested to examine the safety and feasibility of using maintenance sessions of low-frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) to reduce tinnitus loudness and prevent its return over time. Interrupted time series with multiple replications. Tinnitus loudness was assessed using a visual analogue rating (VAR) with 0 = no tinnitus, and 100 = loudest tinnitus experienced; 1,800 TMS pulses delivered at 1 Hz and 110% of motor threshold were administered over the posterior, superior lateral temporal gyrus of the subject's right hemisphere until subjective tinnitus fell to a VAR of 25. TMS was reapplied as tinnitus returned to a VAR of 25 or higher. Cerebral metabolism was measured using positron emission tomography before and after treatment. In this patient, tinnitus could be reduced to a VAR of 6 or lower each time it reoccurred using one to three maintenance sessions of rTMS. Tinnitus loudness remained at or below a VAR of 25 and was reported to be unobtrusive in daily life when last assessed 4 months after the third and final round of maintenance treatment. Asymmetric increased cerebral metabolism in the right hemisphere reduced following treatment and as tinnitus improved. Maintenance treatment was well tolerated with no side effects. Although a case study cannot establish treatment efficacy, this study demonstrates for the first time that it is feasible to use maintenance rTMS to manage chronic tinnitus. Maintenance rTMS might impede cortical expansion of the tinnitus frequency into adjacent cortical areas, but group studies are necessary to confirm this speculation.


Cell surface antigens of Trypanosoma cruzi: possible correlation with the interiorization process in mammalian cells.
Differences were observed in the pattern of the cell surface proteins of evolutive stages of Trypanosoma cruzi after radioiodination of the cells and subsequent analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Affinity chromatography revealed that surface glycoproteins also vary in the epimastigote and trypomastigote forms of the parasite. The cell surface antigens of the two forms were identified after radioiodination or biosynthetic labeling with [35S]methionine and incubation with different antisera. Both epimastigotes and trypomastigotes share two main antigens, possibly glycoproteins, of apparent molecular weight 95 000 and 80 000, respectively, which are recognized by all antisera tested. On the other hand, the trypomastigote form possesses somewhat more cell surface antigens recognized both by rabbit anti-trypomastigote and by human Chagasic sera. Sequential immunoprecipitations with heterologous and homologous antisera established that an 85 000 and some higher molecular weight antigens are specific to the trypomastigote form. Preincubation of the trypomastigotes with sera from Chagasic patients elicits a 60% inhibition of the parasite interiorization into mammalian cells in culture when compared with normal human serum or anti-epimastigote serum. This result suggests that the antigens specific to the trypomastigote form are involved in the interiorization process.


Mutagenicity testing on chinese hamster V79 cells treated in the in vitro liver perfusion system. Comparative investigation of different in vitro metabolising systems with dimethylnitrosamine and benzo[a]pyrene.
A comparative study of three in vitro metabolising systems was performed in combination with Chinese hamster V79 cells, at which point mutation to 6-thioguanine resistance was scored. The three metabolising systems used were: (1) rat liver microsomal fraction (S9-mix); (2) feeder layer of primary embryonic golden hamster cells, according to Hubermann's system; (3) in vitro perfusion of rat liver according to the system of Beije et al. As model substances dimethylnitrosamine (DMN) and benzo[a]pyrene (BP) was used. The liver perfusion was more efficient than S9-mix as an activating system of DMN, while the feeder layer of embryonic cells was unable to activate this compound. The activation of DMN with S9-mix was dependent on the presence of NADP. By exposing the target cells in the liver perfusion at different distances from the liver the biological half life of the active metabolite of DMN could be estimated to less than 5 s. With BP the three metabolising systems showed reversed results as compared with DMN--both the feeder layer cells and S9-mix activated BP, the feeder layer cells being most efficient. With liver perfusion, the perfusate itself was totally negative. Only the bile showed a week mutagenic effect. These results are in accordance with the notion that intact liver cells perform both an activation and a subsequent deactivation of BP. Because of the importance of hepatic bio-transformation in chemical mutagenesis and carcinogenesis it is emphasied that a liver perfusion system could be used in a testing protocol for genotoxic effects as a valuable tool in order to analyse the mechanism of action of mutagenic and carcinogenic compounds detected in other test systems, for instance bacterial/microsomal tests.


Vigilin and enzyme expression in isolated pancreatic acini after mellitin and gamma-interferon treatment.
Pancreatitis goes along with changes in exocrine enzyme synthesis and secretion in pancreatic acini. The multi-KH domain protein vigilin is supposed to play an important role in t-RNA trafficking especially in cells with high protein synthesis rates and may reflect the degree of stimulation of translational machinery during pathological processes. In relation to these phenomena we explored in this connection the impact of two different inflammation mediators in a system of isolated rat pancreatic acini. Acini were prepared from male Sprague-Dawley rats by collagenase digestion and incubated with mellitin or gamma interferon. Secretion and cytosolic cell content of pancreatic trypsin and amylase as well as the expression of vigilin were determined. The phospholipase A(2) activator mellitin caused morphological alterations and increased release of trypsin and amylase, while vigilin expression and the intracellular content of these enzymes decreased. Gamma-interferon, a cytokine which is involved at different steps in inflammation processes, selectively inhibits the release of trypsin(ogen) while not affecting amylase secretion and vigilin expression. Mellitin as well as gamma interferon causes alterations in pancreatic enzyme secretion. Additionally, mellitin seems to influence the expressed gene pattern of pancreatic acini while interferon-gamma has no effect on protein synthesis but enzyme secretion.


The relationship between cell and population growth.
A steady-state model of cell volume frequency distribution using the method of Williams (1971) is derived. Results are compared to a Monte Carlo simulation of cell growth and division. It is suggested that the Monte Carlo method might be of value for investigating cell and population properties for which analytic methods are not currently available.


Perfusion computed tomography-guided subacute endovascular reperfusion in a patient with carotid occlusion.
Most patients with symptomatic internal carotid artery occlusion have a single minor or major hemispheric stroke. A minority of patients have ipsilateral retinal ischemia, recurrent strokes, or transient ischemic attacks. Whereas spontaneous carotid recanalization is rare, acute surgical recanalization has been attempted, with mixed results. Recently, acute endovascular recanalization has been performed and described as feasible and relatively safe. We describe a patient with symptom recurrence related to hemodynamic factors after occlusion of the carotid artery who was successfully treated 14 days after symptom onset.


Recent advances in microfluidic chip integrated electronic biosensors for multiplexed detection.
Utilizing biosensors for multiplexed detection can greatly increase analysis throughput and thus, the amount of information obtained in a single assay. The microfluidic chip, a type of micro-total analysis system (µTAS), has provided a necessary platform for portable and high-throughput biosensors. Biosensors and microfluidic chips are powerful individually, and their super combination is very meaningful for analytical especially for biological applications. In this paper, every kind of microfluidic-chip-integrated electronic biosensors including some emerging technologies for simultaneous detection of multiple analytes are reviewed. Different ways to reduce or avoid cross-talking and more efforts to achieve lab on chip multisensors were also introduced to help readers form a general idea of current developments in different angles.


Snoring assessment: do home studies and hospital studies give different results?
We have developed a device (Glan Clwyd Snore Box) suitable for the objective measurement of the loudness and duration of snoring. The device is simple for the patient to operate, portable, battery powered, and able to produce objective results. We have used the Snore Box to record the snoring at home and during sleep studies in the hospital. Twenty-nine patients were studied. Overall the Snore Index recorded in the home was greater than in the hospital (P < 0.001), the average difference being 67 snores/h. We conclude that snoring is more appropriately assessed at home than in the hospital. We suggest the deficit arises from sleeping in an unfamiliar environment and the presence of several wires connecting the patient to the recording monitor which interfere with natural sleep in the hospital setting.


Prevalence of medication adherence and glycemic control among patients with type 2 diabetes and influencing factors: A cross-sectional study.
This study aimed to assess medication adherence, glycemic control, and their influencing factors among outpatients at an Indonesian clinic with type 2 diabetes. A cross-sectional study was conducted among patients with type 2 diabetes at a hospital-based clinic in Surabaya, Indonesia, from September to December 2018. A purposive sampling was used; patients aged 18 years and older, had diabetes and any comorbidity, received hypoglycemic agents, and provided written informed consent were included. The previously validated Brief Medication Questionnaire was used to measure medication adherence, while glycosylated hemoglobin (A1C) levels were used to evaluate glycemic control. Binary logistic regression was used to identify factors associated with medication adherence and glycemic control. Of 321 patients enrolled in the study, 268 (83.5%) patients were medication nonadherent. Patients who did not engage regularly in physical activity (aOR: 0.49, 95% CI: 0.26-0.93) was more likely to be medication adherent. Poor glycemic control (A1C: >7%) was observed in 106 (33.0%) of the patients. Patients who used a combination of oral hypoglycemic agents and insulin (aOR: 2.74, 95% CI: 1.09-6.86), did not take biguanide (aOR: 2.73, 95% CI: 1.16-6.43), reported hyperglycemia (aOR: 4.24, 95% CI: 1.53-11.81), and had comorbid diseases (aOR: 4.33, 95% CI: 1.08-17.34) increased the risk of having poor glycemic control. Patients who were more likely to achieve good glycemic control were male (aOR: 0.39, 95% CI: 0.20-0.74) and aged older (aOR: 0.95, 95% CI: 0.92-0.99). The proportion of patients who were medication nonadherent was much higher than those with poor glycemic control. Whereas regular exercise was a predictor of nonadherence, age, sex, diabetes medication, not taking biguanide, acute complications, and comorbidity were predictors of poor glycemic control. Therefore, strategies are needed to improve medication adherence and glycemic control.


Different calcification patterns of tricuspid and bicuspid aortic valves and their clinical impact.
Mechanical strain plays a major role in the development of aortic calcification. We hypothesized that (i) valvular calcifications are most pronounced at the localizations subjected to the highest mechanical strain and (ii) calcification patterns are different in patients with bicuspid and tricuspid aortic valves. Multislice computed tomography scans of 101 patients with severe aortic stenosis were analysed using a 3-dimensional post-processing software to quantify calcification of tricuspid aortic valves (n = 51) and bicuspid aortic valves (n = 50) after matching. Bicuspid aortic valves exhibited higher calcification volumes and increased calcification of the non-coronary cusp with significantly higher calcification of the free leaflet edge. The non-coronary cusp showed the highest calcium load compared to the other leaflets. Patients with annular calcification above the median had an impaired survival compared to patients with low annular calcification, whereas patients with calcification of the free leaflet edge above the median did not (P = 0.53). Calcification patterns are different in patients with aortic stenosis with bicuspid and tricuspid aortic valves. Patients with high annular calcification might have an impaired prognosis.


Modulation of PPARalpha expression and inflammatory interleukin-6 production by chronic glucose increases monocyte/endothelial adhesion.
We have previously reported increased monocyte adhesion to human aortic endothelial cells (HAECs) cultured in 25 mmol/L glucose (HG) compared with normal glucose (NG) (5.5 mmol/L). In this study, we explored mechanisms that contribute to increased monocyte adhesion by elevated glucose. We found that HAECs cultured in HG have increased production of the chemokine interleukin-6 (IL-6). We examined whether IL-6 directly modulated monocyte adhesion to EC. Inhibition of IL-6 using a neutralizing antibody significantly reduced glucose-mediated monocyte adhesion by 50%, and addition of IL-6 directly to human EC stimulated monocyte adhesion. PPARalpha has been reported to negatively regulate expression of IL-6 in vascular cells, so we examined PPARalpha-associated signaling in EC. A known PPARalpha agonist, Wy14,643, prevented glucose-mediated IL-6 production by EC and reduced glucose-mediated monocyte adhesion by 40%. HG-cultured HAEC had a 50% reduction in expression of PPARalpha compared with control EC. Primary aortic EC isolated from PPARalpha knockout (KO) mice showed increased monocyte adhesion compared with EC isolated from control mice. PPARalpha KO EC also had increased production of IL-6. Finally, we measured IL-6 levels in diabetic db/db mice and found significant 6-fold elevations in IL-6 levels in db/db EC. These data indicate that IL-6 production is increased in diabetes and contributes to early vascular inflammatory changes. PPARalpha protects EC from glucose-mediated monocyte adhesion, in part through regulation of IL-6 production.


Effect of two types of environmental enrichment for singly housed mice on food intake and weight gain.
For animals that cannot be housed socially for scientific reasons, such as rodents on food intake-energy expenditure studies, the provision of environmental enrichment may alleviate stress. However, the influence of environmental enrichment on food intake and energy expenditure is unresolved. The authors tested the effects of two environmental enrichment options on food intake and weight gain in singly housed mice. Their results may be helpful in developing rodent enrichment programs.


Quantitative MRCP assessment of pancreatic exocrine reserve and its correlation with faecal elastase-1 in patients with chronic pancreatitis.
This retrospective study was done to correlate a quantitative assessment of the pancreatic exocrine reserve by dynamic secretin magnetic resonance cholangiopancreatography (MRCPQ) with the faecal elastase-1 (FE-1) test in patients with chronic pancreatitis. Thirty-five patients with a clinical diagnosis of chronic (CP) or acute recurrent (ARP) pancreatitis were enrolled. FE-1 was indicative of the pancreatic exocrine reserve. Subsequently, the patient population was subdivided into two groups according to a clinical threshold value of 200 μg/g. All patients underwent MRCP examination during secretin administration. Duodenal filling volume was calculated on T2-weigthed rapid acquisition with relaxation enhancement (RARE) MRCP images obtained 10 min after secretin injection. Duodenal filling volumes were compared with FE-1 values. Scatter plots, Pearson correlation coefficient and the Mann-Whitney U test were performed. Thirty-five paired MRCPQ-FE1 data sets were analysed. MRCPQ was significantly different (p=0.007) between patients with impaired and preserved pancreatic function; median and interquartile range (IQR) were 150.7 ml (137.3-205.5 ml; n=9) and 332.4 ml (190.6-506.9 ml; n=26). Both Pearson correlation coefficient (p<0.001) and the Mann-Whitney U test (p=0.007) were significant. MRCPQ significantly correlates with FE-1 values. It is possible to discriminate impaired and preserved pancreatic exocrine function using MRCPQ.


Transforming the blood glucose meter into a general healthcare meter for in vitro diagnostics in mobile health.
Recent advances in mobile network and smartphones have provided an enormous opportunity for transforming in vitro diagnostics (IVD) from central labs to home or other points of care (POC). A major challenge to achieving the goal is a long time and high costs associated with developing POC IVD devices in mobile Health (mHealth). Instead of developing a new POC device for every new IVD target, we and others are taking advantage of decades of research, development, engineering and continuous improvement of the blood glucose meter (BGM), including those already integrated with smartphones, and transforming the BGM into a general healthcare meter for POC IVDs of a wide range of biomarkers, therapeutic drugs and other analytical targets. In this review, we summarize methods to transduce and amplify selective binding of targets by antibodies, DNA/RNA aptamers, DNAzyme/ribozymes and protein enzymes into signals such as glucose or NADH that can be measured by commercially available BGM, making it possible to adapt many clinical assays performed in central labs, such as immunoassays, aptamer/DNAzyme assays, molecular diagnostic assays, and enzymatic activity assays onto BGM platform for quantification of non-glucose targets for a wide variety of IVDs in mHealth.


Intestinal Ultrasound for Differentiating Fibrotic or Inflammatory Stenosis in Crohn's Disease: A Systematic Review and Meta-analysis.
Intestinal ultrasound [IUS] has been increasingly reported to distinguish inflammatory or fibrotic intestinal stenosis in Crohn's disease [CD] patients. However, the diagnostic value is unclear. This systematic review and meta-analysis aimed to assess the diagnostic role of different modes of IUS parameters. We searched PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2021. Regarding effect sizes, weighted mean differences [WMDs] or standardised mean differences [SMDs] were used. We pooled data using a random-effects or fixed-effects model according to heterogeneity. The diagnostic accuracy of IUS for distinguishing fibrosis was pooled. A total of 19 studies were retained for qualitative analysis, and 14 were included in the meta-analysis [with 511 total subjects and 635 bowel segments]. In patients with fibrotic stenosis, the pooled WMDs for bowel wall thickness were 1.30 mm (95% confidence interval [CI]: 0.69-1.91) thicker than in patients with inflammatory stenosis, and the pooled SMDs for strain value and strain ratio were 0.80 [95% CI: 0.41-1.20] and 1.08 [95% CI: 0.55-1.60] harder than in patients with inflammatory stenosis, respectively. The percentage of maximal enhancement of fibrotic stenosis was lower than that of inflammatory stenosis [WMD -10.03; 95% CI: -17.91- -2.16]. The diagnostic accuracy of IUS was not performed because only a few studies provided relevant diagnostic indicators, and these studies used different modes and parameters. IUS currently is inaccurate to differentiate fibrotic or inflammatory stenosis in CD patients, and more studies assessing the significance of each parameter and its cut-off value in different modes of IUS are needed to be conducted in the future.


Maxillofacial Bone Grafting Materials: 2021 Update.
For successful outcomes in bone grafting, it is important to have a clear and detailed understanding of the fundamentals and basics in regenerative science. This article summarize the grafting materials and growth factors that are now in use to provide an improved understanding of the properties of each material and indications for subsequent use. The article gives an overview of the fundamentals of bone healing, including the physiology of regeneration. It is hoped that clinicians can make improved decisions that are based in literature when considering treatment options for restoring patients' functional dentition.


[Spontaneous heterotopic pregnancy. Case report].
Heterotopic pregnancy has increased in frequency due to the increasing number of assisted reproductive procedures. The diagnosis is difficult even with ultrasonography. To report the case of a patient with heterotopic pregnancy without a history of in vitro fertilization or fertility treatment. Heterotopic pregnancy is a rarity that requires a high diagnostic suspicion, specialized desk studies and early surgical care to ensure a favorable outcome to the embryo.


Interleukins 2, 6, and 8 levels in human gingival sulcus during orthodontic treatment.
The aims of this study were to determine levels of interleukins 2, 6, and 8 during tooth movement, and test whether they differ from each other with leveling and distalization forces used in various treatment stages of standard orthodontic therapy. Fifteen patients (9 female, 6 male; ages, 15-19 years; mean age, 16.7 +/- 2.3 years) participated in this study. Each underwent a session of professional oral hygiene and received oral hygiene instructions. Two months later, a fixed orthodontic appliance was placed. The patients were seen at baseline, at days 7 and 21, and as the teeth were leveled. Records of the baseline scores for the distalization forces were taken at the sixth month. Scores of days 7 and 21 after 6 months of the distalization treatment were also recorded. Increases were seen in the volume of gingival crevicular fluid and the concentrations of interleukins 2, 6, and 8. Leveling and distalization of the teeth evoke increases in interleukins 2, 6, and 8 levels in the periodontal tissues that can be detected in gingival crevicular fluid.


Quality of life of chronic heart failure patients: a systematic review and meta-analysis.
Despite various individual studies on the quality of life (QOL) in patients with CHF, a comprehensive study has not yet been conducted; therefore, this study aims to assess the QOL of CHF patients. In the present systematic review and meta-analysis, PubMed, Scopus, and the Web of science databases were searched from January 1, 2000, to December 31, 2018, using QOL and heart failure as keywords. The searches, screenings, quality assessments, and data extractions were conducted separately by two researchers. A total of 70 studies including 25,180 participants entered the final stage. The mean QOL score was 44.1 (95% confidence interval (CI) 40.6, 47.5; I2 = 99.3%) using a specific random effects method in 40 studies carried out on 12,520 patients. Moreover, according to the geographical region, heart failure patients in the Americas had higher scores. In 14 studies, in which a general SF-36 survey was implemented, the average physical component score (PCS) and mental component score (MCS) were 33.3 (95% CI 31.9, 34.7; I2 = 88.0%) and 50.6 (95% CI 43.8, 57.4; I2 = 99.3%), respectively. The general and specific tools used in this study indicated moderate and poor QOL, respectively. Therefore, it is necessary to carry out periodic QOL measurements using appropriate tools as part of the general care of CHF patients.


Research On Maize Disease Identification Methods In Complex Environments Based On Cascade Networks And Two-Stage Transfer Learning.
Achieving accurate and reliable maize disease identification in complex environments is a huge challenge. This is because disease images obtained from natural environments are often in complex contexts that may contain elements similar to disease characteristics or symptoms. Based on cascade network and two-stage transformation learning, the new method is proposed in this paper and applied the improved method to the task of identification and classification of four maize leaf types in a complex environment. The proposed method has a cascade structure which consists of a Faster R-CNN leaf detector (denoted as LS-RCNN) and a CNN disease classifier, named CENet(Complex Environment Network). The LS-RCNN detector with an attention mechanism was used to detect maize leaves from the image, and the CENet model further classified the leaf images detected in the first stage into four categories: Cercospora leaf spot, Common rust, Northern Leaf Blight, and Healthy, which allowed image features to be extracted more efficiently. The subsequent use of a two-stage transfer learning strategy to train CENet models of disease images in complex contexts allows for faster training of the models while ensuring accuracy. The experimental results show that the proposed method is used to identify four types of maize leaves with an F1-score of 99.70%, which is better than some popular CNN models and others' methods, and has a more obvious advantage in terms of training speed. The model proposed in this experiment has a positive significance for exploring other Crop variety identification and classification under complex backgrounds.


Healthcare utilization and costs associated with a diagnosis of incident atrial fibrillation.
Atrial fibrillation (AF) is the most common heart rhythm disorder among adults and leads to substantial morbidity and mortality. The purpose of the study was to provide current estimates on the incremental healthcare utilization and cost burden associated with incident AF diagnosis in the United States. Adults with an incident diagnosis of AF (2017-2020) were identified using the Optum Clinformatics database. Propensity matching was employed to match patients with incident AF to a comparator group of non-AF patients on several demographic and clinical characteristics. Outcomes including 12-month all-cause and cardiovascular (CV)-related healthcare utilization, as well as the medical cost associated with health services use, were assessed. Logistic and general linear models were used to examine study outcomes. Sub-analyses were performed to determine the incremental AF burden by specific sex and racial/ethnic categories. A total of 79,621 patients were identified in each cohort (AF and non-AF). As compared to the non-AF cohort, patients with AF had significantly higher all-cause inpatient visits (relative risk [RR] 1.77; 95% confidence interval [CI] 1.76-1.78), CV-related inpatient visits (RR 2.51; 95% CI 2:49-2:53), and CV-related emergency room visits (RR: 2.41; 95% CI 2:35-2:47). The mean total healthcare cost for patients with AF was $27,896 more (per patient per year) than the non-AF cohort ($63,031 vs $35,135, P < .001). Medical services utilization and cost were significantly higher among AF patients than non-AF patients. Early treatment is likely to be critical to addressing the considerable disease burden imposed by AF.


The effect of shoot growth stage of Pinus contorta and Pinus sylvestris on the growth and survival of Panolis flammea larvae.
Young Panolis flammea (Lepidoptera: Noctuidae) larvae were unable to survive on the mature (one-year old) needles of Pinus contorta and Pinus sylvestris. Larval growth and survival on the current year's shoots of the 2 pine host plants first incresed, and then decreased as pine shoot development progressed, the effect on survival being more marked at 10° C that 18° C. The survival of larvae on lodgepole pine on field-grown plants transferred to 10° C rose from 26% in March to 87% in mid May, and rose from 3% to 82% on Scots pine in the same period. Larval survival exceeded 70% for about 8 weeks on lodgepole pine and about 6 weeks on Scots pine, this period starting and ending earlier on lodgepole than on Scots pine. The nitrogen, water and phosphorus contents of both pines were at a maximum in May and decline gradually thereafter; the soluble tannin content showed a more complex pattern. These results are discussed in relation to the possible importance of phenological coincidence on the population dynamics of P. flammea with emphasis on its greater abundance on lodgepole pine in Scotland.


A new flavonoid regulates angiogenesis and reactive oxygen species production.
The tumor vascular system, which is critical to the survival and growth of solid tumors, has been an attractive target for anticancer research. Building on studies that show that some flavonoids have anticancer vascular effects, we developed and analyzed the flavonoid derivative R24 [3, 6-bis (2-oxiranylmethoxy)-9H-xanthen-9-one]. A CAM assay revealed that R24 disrupted neovascular formation; fewer dendrites were detected and overall dendritic length was shorter in the R24-treated chicken embryos. The antiproliferative effect of R24 was measured by MTT assay in A549 (lung cancer), AsPC-1 (pancreatic cancer), HCT-116 (colorectal cancer), and PC-3 (prostate cancer) cell lines. R24 reduced proliferation with an IC50 of 3.44, 3.59, 1.22, and 11.83 μM, respectively. Cell-cycle analysis and Annexin-V/propidium iodide staining showed that R24 induced apoptosis. In addition, R24 regulated intracellular ROS production in a dose-dependent manner. CM-H2DCFDA staining indicated that intracellular ROS production increased with the R24 dose. In summary, we found that R24 exhibits potent antiangiogenic and antiproliferative effects, induces apoptosis, and promotes ROS production.


Effects of atorvastatin on oxidized low-density lipoprotein, low-density lipoprotein subfraction distribution, and remnant lipoprotein in patients with mixed hyperlipoproteinemia.
Atorvastatin (10 to 20 mg/day) was administered for 3 months to 15 outpatients (average age 58 +/- 4 years) with hypercholesterolemia accompanied by hypertriglyceridemia without hypolipemic treatment. Changes in lipid profile, particularly oxidized low-density lipoprotein (LDL) (malondialdehyde LDL), subfractions of LDL, and remnant lipoprotein (RLP) cholesterol, were examined before and after administration. In addition, the influence of atorvastatin on lipoprotein(a) (known to be an independent risk factor for atherosclerosis), asymmetric dimethylarginine (known to be an endogenous inhibitor of nitric oxide synthase), and homocysteine (methionine metabolite) was also investigated. Administration of atorvastatin significantly decreased serum total cholesterol, LDL cholesterol, and triglycerides. Conversely, a significant increase in high-density lipoprotein cholesterol was shown. In LDL subfractions, large, buoyant LDL fractions were not influenced by treatment with atorvastatin (before administration, 99 +/- 14 mg/dl; after administration, 91 +/- 6 mg/dl, shown as a cholesterol content in each subfraction), but a marked decrease in small, dense LDL fractions (p <0.001) (before administration, 119 +/- 17 mg/dl; after administration, 43 +/- 10 mg/dl) was shown. Moreover, oxidized LDL was significantly decreased (p < 0.01) (before administration, 169 +/- 13 U/L; after administration, 119 +/- 10 U/L) and RLP cholesterol also was significantly decreased (p <0.01) (before administration, 11.9 +/- 2.0 mg/dl; after administration, 6.0 +/- 0.9 mg/dl) with atorvastatin treatment. No significant change was observed in fasting plasma glucose, hemoglobin A1c, lipoprotein(a), asymmetric dimethylarginine, homocysteine, and so on. These data suggest that administration of relatively low doses of atorvastatin to patients with hypercholesterolemia accompanied with hypertriglyceridemia results in a decrease not only in LDL cholesterol and triglycerides, but also in oxidized LDL and RLP cholesterol, with an increase in high-density lipoprotein cholesterol. Furthermore, small, dense LDL decreased with a shift in LDL subfractions to large, buoyant fractions, and these changes are considered to be involved in the inhibition of the onset and progression of atherosclerosis.


A critical role of endothelial cell protein C receptor in the intestinal homeostasis in experimental colitis.
Crohn's disease and ulcerative colitis are the two forms of disorders of the human inflammatory bowel disease with unknown etiologies. Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, which is expressed on the endothelium and other cell types, including epithelial cells. Here, we report that EPCR is expressed in the colon epithelial cells, CD11c+, and CD21+/CD35+ myeloid cells surrounding the crypts in the colon mucosa. EPCR expression was markedly decreased in the colon mucosa during colitis. The loss of EPCR appeared to associate with increased disease index of the experimental colitis in mice. EPCR-/- mice were more susceptible to dextran sulfate sodium (DSS)-induced colitis, manifested by increased weight loss, macrophage infiltration, and inflammatory cytokines in the colon tissue. DSS treatment of EPCR-/- mice resulted in increased bleeding, bodyweight loss, anemia, fibrin deposition, and loss of colon epithelial and goblet cells. Administration of coagulant factor VIIa significantly attenuated the DSS-induced colon length shortening, rectal bleeding, bodyweight loss, and disease activity index in the wild-type mice but not EPCR-/- mice. In summary, our data provide direct evidence that EPCR plays a crucial role in regulating the inflammation in the colon during colitis.


Infrarenal aortic occlusion: a reassessment of surgical indications.
Citing a high incidence of proximal propagation of aortic thrombosis, several authors have advocated aortic reconstruction for all patients with infrarenal aortic occlusion irrespective of their preoperative symptoms and potential operative risks. To test this thesis, the records and follow-up data of 38 patients seen at our institution between 1965 and 1982 with infrarenal aortic occlusion were analyzed. Twenty-four of the 38 patients were treated surgically (Group I); 16 (42 percent) had an aortobifemoral graft and 8 (21 percent) had an axillofemoral bypass graft. When the 14 patients who did not have surgery (Group II) and the 8 patients who had an axillofemoral graft were combined, 22 patients (58 percent) did not have aortic reconstruction (Group III), thus the aortic thrombus was left in situ. There was no significant difference in cumulative survival between the three groups at 4 year follow-up. Of 13 patients in Group III who were followed for more than 6 months (mean 48 months), none died from proximal propagation of aortic thrombosis. The decision for surgical intervention in patients with distal aortic occlusion should be arrived at, as in other patients with aortoiliac occlusive disease, by weighing preoperative symptoms and operative risks and not primarily by the level of risk of proximal propagation of thrombosis.


A comparison of Norinyl and Brevicon in three sites in Sri Lanka.
A set of 3 four-cell randomized, blind clinical trials was carried out in Sri Lanka to evaluate the impact of vitamin supplements and different oral contraceptive formulations. This paper concentrates on the comparisons of oral contraceptives. There seems to be no important difference between Norinyl, a standard-dose oral contraceptive, and Brevicon of a lower estrogen dosage--in either continuation or side effects. Continuation at one site was higher among Norinyl users, but several factors led us to the belief that this difference was due to differences in field worker performance rather than to the pharmacological properties of the drugs. Some differences in side effects were observable along predictable lines; breakthrough bleeding was more common among Brevicon users than Norinyl users, and most other side effects were more frequent among Norinyl users, although these latter differences were quite small, and there were several exceptions.


Pharmacological characterization of DPTN and other selective A3 adenosine receptor antagonists.
The A3 adenosine receptor (AR) is emerging as an attractive drug target. Antagonists are proposed for the potential treatment of glaucoma and asthma. However, currently available A3AR antagonists are potent in human and some large animals, but weak or inactive in mouse and rat. In this study, we re-synthesized a previously reported A3AR antagonist, DPTN, and evaluated its affinity and selectivity at human, mouse, and rat ARs. We showed that DPTN, indeed, is a potent A3AR antagonist for all three species tested, albeit a little less selective for mouse and rat A3AR in comparison to the human A3AR. DPTN's Ki values at respective A1, A2A, A2B, and A3 receptors were (nM) 162, 121, 230, and 1.65 (human); 411, 830, 189, and 9.61 (mouse); and 333, 1147, 163, and 8.53 (rat). Its antagonist activity at both human and mouse A3ARs was confirmed in a cyclic AMP functional assay. Considering controversial use of currently commercially available A3AR antagonists in rats and mice, we also re-examined other commonly used and selective A3AR antagonists under the same experimental conditions. The Ki values of MRS1523 were shown to be 43.9, 349, and 216 nM at human, mouse, and rat A3ARs, respectively. MRS1191 and MRS1334 showed incomplete inhibition of [125I]I-AB-MECA binding to mouse and rat A3ARs, while potent human A3AR antagonists, MRS1220, MRE3008F20, PSB10, PSB-11, and VUF5574 were largely inactive. Thus, we demonstrated that DPTN and MRS1523 are among the only validated A3AR antagonists that can be possibly used (at an appropriate concentration) in mouse or rat to confirm an A3AR-related mechanism or function.


Suppression of tumor promotion by inhibitors of poly(ADP)ribose formation.
Tumor promoters, such as phorbol esters or hormones, cause many biological effects which may contribute to the expression of cancer. The mechanism of cancer expression may have a common theme. One method of learning about this common mechanism is the identification of chemicals that interfere with tumor development. That there is actually a common theme between very different substances, such as inflammatory skin tumor promoters and estradiol causing breast cancer, was shown by the fact that both skin and breast cancers are suppressed by the same agents, e.g., protease inhibitors and retinoids. In addition to skin and breast, protease inhibitors suppress colon, bladder, and liver cancers. The substances that crossed over in suppressing many varieties of cancer were found to inhibit oxygen radical formation by tumor promoter-activated neutrophils and ras oncogene expression in NIH 3T3 cells. Poly(ADP)ribose polymerase (PADPR polymerase) may serve as the connecting link between oxygen radicals that cause its activation and oncogene expression. PADPR polymerase is inhibited by retinoids, antioxidants, and some protease inhibitors. Benzamide, an inhibitor of PADPR polymerase, is also a chymotrypsin inhibitor which suppresses oxygen radical formation by tumor promoter-activated neutrophils. The inhibition of PADPR polymerase causes the expulsion of some oncogenes from NIH 3T3 cells at definite times after oncogene transfection. Further work is required to find what are the contributions of PADPR polymerase to tumor promotion and of its inhibitors to suppression of oncogene expression.


EX-PRESS® Implant Position and Function: Comparative Evaluation with Ultrasound Biomicroscopy and Optical Coherence Tomography.
This study evaluated the feasibility of anterior segment optical coherence tomography (OCT) and ultrasound biomicroscopy (UBM) for the imaging of EX-PRESS(®) implant. This nonrandomized comparative case series was performed at the Department of Ophthalmology of the University Hospital of Heraklion, Crete, Greece. The Ellex Eye Cubed (40 MHz) UBM and the Zeiss Visante OCT systems were used. The filtering bleb morphology (BL), aqueous outflow (AS), and tube position (TB) were evaluated by two independent observers using a quality scale of 1 (worst) to 4 (best). Data were also collected on corneal and iris clearance from the tip of the tube (CC and IC, respectively). Data from both the devices were statistically analyzed. P < 0.05 was considered as statistically significant. Ten eyes of 10 patients (6 males) with EX-PRESS(®) implant were examined. TB, AS, and BL scores using UBM were 2.40 ± 0.39, 3.45 ± 0.72, and 2.45 ± 0.64, respectively. TB, AS, and BL scores for OCT were 3.35 ± 0.41, 1.55 ± 0.43, and 2.55 ± 0.55, respectively. AS was significantly higher with UBM whereas the opposite was true for TB. Differences in BL between OCT and UBM were not statistically significant (P > 0.05). Imaging of the EX-PRESS(®) implant is feasible with both UBM and OCT. Both modalities allow visualization of the position of the implant tube in relation to the iris or cornea and delineate the internal structure of the filtering bleb.


Risk factors and timing of venous thromboembolism after radical cystectomy in routine clinical practice: a population-based study.
To describe the risk factors and timing of perioperative venous thromboembolism (VTE) and its association with survival for patients undergoing radical cystectomy (RC) in routine clinical practice. The population-based Ontario Cancer Registry was linked to electronic records of treatment to identify all patients who underwent RC between 1994 and 2008; VTE events were identified from hospital diagnostic codes. Multivariate logistic regression analysis was used to determine the factors associated with perioperative VTE. A Cox proportional hazards regression model explored the associations between VTE and survival. Of the 3 879 patients included in the study, 3.6% (141 patients) were diagnosed with VTE at ≤1 month of their surgical admission date. This increased to 4.7% (181) at ≤2 months and 5.4% (211) at ≤3 months. In all, 55% of VTE events presented after hospital discharge. In multivariate analysis, factors associated with VTE included higher surgeon volume (P = 0.004) and increased length of hospital stay (LOS; P < 0.001). Lymph node yield and adjuvant chemotherapy were not associated with VTE. VTE was associated with an inferior cancer-specific survival [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13-1.62] and overall survival (HR 1.27, 95% CI 1.08-1.49). Over half of VTE events in RC patients occur after hospital discharge, with a substantial incidence up to 3 months after surgery. Limited actionable risk factors for VTE were identified other than LOS. In this population-based cohort, VTE was associated with inferior long-term survival.


Acute, recurrent total knee dislocation: Polyethylene dislocation and malreduction.
A 62-year-old man underwent total knee arthroplasty using a mobile-bearing prosthesis. Four days post-operatively the patient experienced the first of several acute knee dislocations. Closed reduction was performed at an outside hospital a total of three times prior to presentation at this institution. A two-stage exchange of the TKA was recommended due to the clinical suspicion for an infected prosthesis. Upon surgical exploration, it was discovered that the polyethylene insert had spun out completely to 180°. Closed reduction attempts of a posterior dislocation of a mobile-bearing knee prosthesis may contribute to complete 180° spinout of the polyethylene insert.


Late intensification with high-dose melphalan and autologous bone marrow support in breast cancer patients responding to conventional chemotherapy.
Fifteen patients with advanced breast cancer who had achieved either a good partial or a complete response to conventional chemotherapy were selected to receive intensification treatment with high-dose melphalan 140-200 mg/m2 (HDM). All patients received autologous bone marrow rescue. All patients experienced marked haematological toxicity, and most experienced moderate or mild gastrointestinal side effects. There were three treatment-related deaths. Of twelve assessable patients eleven have relapsed; median time to relapse after HDM is 7 months. Nine of these eleven have died from recurrent breast cancer. Of the three patients remaining alive, only one is disease-free, at 18 months after HDM. Analysis of the pattern of metastatic relapse suggests that recurrence was due to failure of HDM to eradicate residual disease in the patient, rather than reinfusion of viable tumour cells. Treatment intensification with HDM has not succeeded in prolonging survival in patients already in good remission.


Construct validity of change scores of the Chair Stand Test versus Timed Up and Go Test, KOOS questionnaire and the isometric muscle strength test in patients with severe knee osteoarthritis undergoing total knee replacement.
The Chair Stand Test (CST) is a frequently used performance-based test in clinical studies involving individuals with knee osteoarthritis and demonstrates good reliability. To assess the construct validity of change scores of the CST compared to three other measures in patients before and after total knee replacement surgery. The construct validity of change scores of the CST compared to the Timed Up and Go (TUG) test, the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS, subscale ADL) and the isometric muscle strength test of the knee extensors (IMS sum) was measured 1-2 week before and 3 months after surgery. Change (%) CST = -4.45, TUG = -2.08, KOOS ADL = 43.90, IMS sum = -13.24. Correlations CST-TUG = 0.56 (95% confidence interval (CI) 0.29, 0.74), CST-KOOS = -0.31 (95% CI -0.57, 0.01), CST-IMS sum = -0.11 (95% CI -0.42, 0.22). Comparison of pairwise correlations: CST-KOOS versus CST-TUG (p < 0.0004), CST-TUG versus CST-IMS sum (p < 0.0068), CST-KOOS versus CST-IMS sum (p < 0.3100). For patients undergoing TKR, the CST might not be an ideal measure to assess change between pre-surgery and 3 months post-surgery. Construct validity of change scores was close to zero but the result might have been influenced by the relatively small homogeneous sample size and the chosen timespan of measurement. We ordered pairwise correlations based on the strength of correlation between the different instruments, which to our knowledge has never been done before.


Structural remodelling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: A cross-sectional and comparative ultrasound study.
With low back pain (LBP), remodelling of the lumbar soft tissues involves both trunk muscles and neighbouring passive connective tissues. The aim of the present study was to compare three quantitative measures of these tissues, using ultrasound imaging (USI), among healthy controls and individuals with LBP. USI measures from 30 healthy subjects and 34 patients with non-acute LBP were compared between groups and sexes. The measures employed were (1) lumbar multifidus echogenicity (fatty/fibrosis infiltration) at three vertebral levels; (2) posterior layer thickness of the thoracolumbar fascia, and (3) thickness of the perimuscular tissues surrounding the external oblique, internal oblique and transversus abdominis (TrA). USI measures of (1) multifidus echogenicity showed statistically significant changes between vertebral levels and sexes (females > males; p = 0.02); (2) differences in thoracolumbar fascia thickness approached statistical significance between groups (LBP > controls; p = 0.09) and sexes (females < males; p = 0.07); and (3) perimuscular tissue surrounding the TrA was significantly thinner (p ≤ 0.001) in patients with LBP compared to controls. The thinner perimuscular tissues surrounding the TrA in patients with LBP is a new finding, concurring with previous findings with regard to the lower activation of this deep muscle as well as more recent findings on other perimuscular tissue. Overall, USI measures were sensitive to different potential changes (pain status, sex, vertebral level), and this is useful in studying the remodelling of various soft tissues of the trunk.


Non-vitamin K oral anticoagulants as first-line regimen for acute ischemic stroke with non-valvular atrial fibrillation.
There are various patterns in determining the choice of the first-line antithrombotic agent for acute stroke with non-valvular atrial fibrillation. We investigated the efficacy and safety of non-vitamin K oral anticoagulants as first-line antithrombotics for patients with acute stroke and non-valvular atrial fibrillation. Patients with non-valvular atrial fibrillation and ischemic stroke or transient ischemic attack within 24 h from stroke onset were included. On the basis of the first regimen used and the regimen within 7 days after admission, the study population was divided into three groups: 1) antiplatelet switched to warfarin (A-W), 2) antiplatelet switched to NOAC (A-N), and 3) NOAC only (N only). We compared the occurrence of early neurologic deterioration, symptomatic intracranial hemorrhage, systemic bleeding, and poor functional outcome at 90 days. Of 314 included patients, 164, 53, and 97 were classified into the A-W, A-N, and N only groups, respectively. Early neurologic deterioration was most frequently observed in the A-W group (9.1%), followed by the A-N (5.7%) and N only (1.0%) groups (p = 0.017). Multivariable analysis adjusting for potential confounders demonstrated that the N only group was independently associated with a lower rate of early neurologic deterioration (odds ratio [OR] 0.104, 95% CI 0.013-0.831) or poor functional outcome at 90 days (OR 0.450, 95% CI 0.215-0.940) than the A-W group. However, the rate of symptomatic intracranial hemorrhage or any systemic bleeding event did not differ among the groups. Using non-vitamin K oral anticoagulants as the first-line regimen for acute ischemic stroke may help prevent early neurologic deterioration without increasing the bleeding risk.


Creating Virtual Models and 3D Movies Using DemoMaker for Anatomical Education.
Three-dimensional (3D) anatomy models have been used for education in health professional schools globally. Virtual technology has become more popular for online teaching since the COVID-19 pandemic. This chapter will describe a project in which a series of virtual anatomical models of organs and structures were developed for educational purposes, and it will describe in detail how to build three-dimensional (3D) movies using DemoMaker. Although setting up the 3D system was complicated and challenging, the process of reconstructing 3D models from radiographic images and the steps of creating animations and 3D movies are exponentially simpler. These efforts require minimal training, thus allowing most people to be able to engage in this modeling process and utilize the moviemaking steps. Amira® software and computed tomographic angiography (CTA) data were used to create 3D models of the lungs, heart, liver, stomach, kidney, etc. The anatomical locations of these structures within the body can be identified and visualized by recording information from multiple CTA slices using volume and surface segmentation. Ultimately, these virtual 3D models can be displayed via dual projectors onto a specialized silver screen and visualized stereoscopically by viewers as long as they wear 3D polarized glasses. Once these 3D movies are created, they can be played automatically on a computer screen, silver screen, 3D system playback screen, and video player, and they can be embedded into PowerPoint lecture slides. Both virtual models and movies are suitable for self-directed learning, face-to-face class teaching, and virtual anatomy education. Model animations and 3D movie displays offer students the opportunities to learn about anatomy and the anatomical positions of organs in the body and their 3D relationships to one another. By observing and studying these 3D models, students have the potential to be able to compartmentalize the anatomical information and retain it at a higher level than students learning corresponding anatomy without similar resources.


Ten Years of Publications: Scientometric Comparison of Major Neurosurgical Journals.
The goal of this study was to examine neurosurgical scientific publications and change in the trends in major neurosurgical journals during the last 10 years. The peer-reviewed articles published in 12 prominent neurosurgical journals over the last 10 years were analyzed. The journals were grouped into 2 groups based on the number of articles published in a journal in a year (≥500 or <500). The total number of peer-reviewed articles published in 10 years in these 12 journals was 48,957. The number of peer-reviewed articles published in a year increased from 3441 to 7316 over this time. The maximum number of peer-reviewed articles were published in 2019 in Group A (n = 7170) and in 2018 in Group B journals (n = 615). The commonest article types were Original Articles and Case Reports in both the groups, but the proportion of Original Articles published was greater in Group A journals (54.0%) as compared with Group B journals (44.5%). Review Articles were more commonly published in Group B journals. The proportion of articles published in Group A and B journals from the United States was 48.0% and 31.7%, respectively, whereas the proportion of articles from Europe was 21.4% and 36.2%, respectively. Neurosurgical publications are continuously increasing, with a parallel growth in the number of authors and citations all over the world. There are significant differences in the scientometric indices of major neurosurgical journals based on their yearly articles published.


Metabolism of adenosine analogues by Schistosoma mansoni and the effect of nucleoside transport inhibitors.
Schistosoma mansoni incorporated tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, 7,9-dideaza-7-thiaadenosine and toyocamycin but not sangivamycin, 3'-deoxy-sangivamycin, or 1-methylformycin into their nucleotide pool after a 4-hr incubation in vitro. In contrast to mammalian systems, addition of nucleoside transport inhibitors nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), dilazep, or benzylacyclouridine had no significant effect on the pattern of incorporation of these adenosine analogues. Dipyridamole, on the other hand, reduced, but did not prevent, the incorporation of these analogues into the nucleoside 5'-triphosphate pool. These results suggest that the transport of purine nucleosides in schistosomes is different from that of their mammalian hosts. Therefore, coadministration of a specific nucleoside transport inhibitor with tubercidin, nebularine, 9-deazaadenosine, 5'-deoxy-5'-iodo-2-fluoroadenosine, toyocamycin, or 7,9-dideaza-7-thiaadenosine may result in high selective toxicity against schistosomes, as was the case with the combination of tubercidin plus NBMPR-P [el Kouni et al., Proc. natn. Acad. Sci. U.S.A. 80, 6667 (1983); el Kouni et al., Biochem. Pharmac. 34, 3921 (1985)], by protecting the host but not the parasite from the toxicity of these analogues.


Silver staining of cell bodies by means of physical development.
A method for silver impregnation of cell bodies is detailed. It is based on Gallyas' physical development procedure, and adds a silver stain for cell bodies to the list of histological elements stainable with high contrast by means of physical development. Its black pigment on a clear background aids visibility, localization of cytoarchitectonic boundaries, and photographic reproduction. It also stains regions of tissue damage, such as tracks from micropipettes or electrodes. A manipulation for enhancement of dendritic staining is also described.


Atraumatic loop electrodes for electroretinography.
A simple method is described for producing inexpensive, atraumatic electrodes for electroretinography. Scleral contact is obtained by a loop of ultra-lightweight stainless steel wire placed between the eye and lower lid. Recordings obtained by this method in animals are equal to those recorded with needle electrodes from the same ophthalmologically normal dog are presented.


Novel brominated and organophosphate flame retardants in the atmosphere of Fildes Peninsula, West Antarctica: Continuous observations from 2011 to 2020.
Novel brominated flame retardants (NBFRs) and organophosphate esters (OPEs) have been widely detected in various environmental matrices worldwide and raised public concerns in recent years. However, few studies reported their occurrence and temporal trend in Antarctic air. In this study, concentrations, distribution, and temporal trends of NBFRs and OPEs in the air of Fildes Peninsula, West Antarctica, were investigated using XAD resin-based passive air sampling from January 2011 to January 2020. Air concentrations of the total OPEs (Σ7OPEs) were one to two orders of magnitude higher than those of the total NBFRs (Σ6NBFRs). Decabromodiphenyl ethane and tris(2-chloroethyl) phosphate were the most abundant NBFR and OPE congeners, respectively. Significant positive correlations were observed among hexabromobenzene, pentabromoethylbenzene, and pentabromotoluene, indicating that their occurrence in Antarctic air may be affected by similar sources. No spatial differences in any of the NBFR and OPE congeners were observed, implying minor impact from local scientific research stations. Linear regression analysis was used to evaluate the temporal trends of NBFRs and OPEs in Antarctic air, with decreasing trends observed for Σ6NBFRs and Σ7OPEs. This is one of the rare studies providing a comprehensive investigation of the temporal trends in NBFRs and OPEs in Antarctic air and highlights concern regarding the contamination of these chemicals in remote polar regions.


Cytokine/Chemokine HLDA8 Workshop panel report: analysis of receptors on lymphocytes from cord blood, normal and asthmatic subjects, and HIV positive patients.
Chemokines and cytokines are involved in many processes, both physiological and pathological, particularly the recruitment, differentiation, activation, and proliferation of immune cells taking part in ontogenesis, inflammation, and cancer. It was assumed that chemokines and cytokines receptors are expressed in a regulated manner by human lymphocytes during ontogeny and later on, under the environmental stimulation of antigens they contribute to organogenesis, angiogenesis, and tissue remodeling, as well as modulating leukocyte effector functions. Using monoclonal antibodies classified by the Cytokine/Chemokine section of the 8th International Workshop on Human Leukocyte Differentiation Antigens, we analyzed human lymphocytes in blood samples drawn from the umbilical cord, normal adults, allergic and non-allergic asthma patients, HIV infected, and AIDS positive subjects. The main differences noted between adult and cord blood lymphocytes were related to CCR7 and CXCR4 receptors, which were more strongly expressed on cord blood lymphocytes, confirming the important role of these chemokines during development of the immune system. As with the HIV, CXCR4, and CCR5 co-receptors, we found no differences in CXCR4 expression between HIV and AIDS patients. However CCR5 was more strongly expressed in AIDS patients, which is likely to be associated with the evolution of disease. Further studies are needed to gain a better understanding of the functions of these molecules in the underlying pathogenesis of many diseases and to probe the use of the chemokine receptors as targets for therapeutic intervention.


CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function.
Survival of antigen-experienced T cells is essential for the generation of adaptive immune responses. Here, we show that the genetic and antibody-mediated inactivation of CD152 (cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of nonapoptotic cells in a completely Fas/Fas ligand (FasL)-dependent manner. CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression. Apoptosis protection conferred by CD152 correlated with the up-regulation of Bcl-2 and was mediated by phosphatidylinositol 3 kinase, which prevented FasL expression through the inhibitory phosphorylation of Forkhead transcription factor FKHRL1. We show that signals induced by CD152 act directly on activated T lymphocytes and, due to its differential surface expression on activated Th1 and Th2 cells, induce resistance to AICD mainly in Th2 cells.


Plant carbohydrate limitation on nitrate reduction in wetland microcosms.
Although nitrate limitation in most natural wetlands results in pseudo-first-order reductions, large site-to-site variations in apparent denitrification rates cannot be easily explained by water quality (e.g., pH, Temp, DOC) or plant productivity. Our microcosm results show increasing nitrate removal efficiencies at higher ratios of total applied plant carbon to nitrate reduced, suggesting that denitrification rates may be limited by the rates of supply of both electron donor or acceptor, described by an applied carbon to nitrate (C(App): N(Red)) ratio. However, the observed first-order rate constants varied more strongly (r2 = 0.77, p <0.0001) with the acid-soluble carbohydrates to nitrate (CH2O(App): N(Red)) ratio than the total C(App): N(Red) ratio. Although observed rate constants for bulrush (Scirpus sp.) were significantly lower (0.01 <p<0.06) than for other plant sources (Hydrocotyle sp., Lemna sp., Typha sp.), there were no significant differences in the plant-specific rate constants when compared at the same CH2O(App): N(Red) ratio. In full-scale wetlands, this suggests that either high plant productivity or low NO3- loading (high CH2O(App): N(Red)) may contribute to a high effective denitrification rate. In contrast, low productivity or a high NO3- loading (low CH2O(App): N(Red)) would promote a lower denitrification rate. This co-limitation between plant carbon and nitrate may confound first-order rate comparisons in full scale denitrification wetlands since highly N-loaded systems may become carbon limited, requiring higher order reaction kinetics to better describe performance variations. In addition to hydraulic residence time. temperature and nitrate removal data, extending these results to compare large wetlands will require estimation of the CH2O(App): N(Red) ratio from an inventory of plant species, productivity estimates and carbon quality.


Systemic HDAC3 inhibition ameliorates impairments in synaptic plasticity caused by simulated galactic cosmic radiation exposure in male mice.
Deep space travel presents a number of measurable risks including exposure to a spectrum of radiations of varying qualities, termed galactic cosmic radiation (GCR) that are capable of penetrating the spacecraft, traversing through the body and impacting brain function. Using rodents, studies have reported that exposure to simulated GCR leads to cognitive impairments associated with changes in hippocampus function that can persist as long as one-year post exposure with no sign of recovery. Whether memory can be updated to incorporate new information in mice exposed to GCR is unknown. Further, mechanisms underlying long lasting impairments in cognitive function as a result of GCR exposure have yet to be defined. Here, we examined whether whole body exposure to simulated GCR using 6 ions and doses of 5 or 30 cGy interfered with the ability to update an existing memory or impact hippocampal synaptic plasticity, a cellular mechanism believed to underlie memory processes, by examining long term potentiation (LTP) in acute hippocampal slices from middle aged male mice 3.5-5 months after radiation exposure. Using a modified version of the hippocampus-dependent object location memory task developed by our lab termed "Objects in Updated Locations" (OUL) task we find that GCR exposure impaired hippocampus-dependent memory updating and hippocampal LTP 3.5-5 months after exposure. Further, we find that impairments in LTP are reversed through one-time systemic subcutaneous injection of the histone deacetylase 3 inhibitor RGFP 966 (10 mg/kg), suggesting that long lasting impairments in cognitive function may be mediated at least in part, through epigenetic mechanisms.


Identification of Pediatric Tumors Intraoperatively Using Indocyanine Green (ICG).
Fluorescence-guided surgery (FGS) with indocyanine green (ICG) is increasingly applied in pediatric surgical oncology. However, FGS has been mostly reported in case studies of liver or renal tumors. Applying novel technologies in pediatric surgical oncology is more challenging than in adult surgical oncology due to differences in tumor histology, biology, and fewer cases. No consensus exists on ICG-guided FGS for surgically managing pediatric solid tumors. Therefore, we reviewed the literature and discuss the limitations and prospects of FGS. Using PRISMA guidelines, we analyzed articles on ICG-guided FGS for childhood solid tumors. Case reports, opinion articles, and narrative reviews were excluded. Of the 108 articles analyzed, 17 (14 retrospective and 3 prospective) met the inclusion criteria. Most (70.6%) studies used ICG to identify liver tumors, but the timing and dose of ICG administered varied. Intraoperative outcomes, sensitivity and specificity, were reported in 23.5% of studies. Fluorescence-guided liver resections resulted in negative margins in 90-100% of cases; lung metastasis was detected in 33% of the studies. In otolaryngologic malignancies, positive margins without fluorescence signal were reported in 25% of cases. Overall, ICG appeared effective and safe for lymph node sampling and nephron-sparing procedures. Despite promising results from FGS, ICG use varies across the international pediatric surgical oncology community. Underreported intraoperative imaging outcomes and the diversity and rarity of childhood solid tumors hinder conclusive scientific evidence supporting adoption of ICG in pediatric surgical oncology. Further international collaborations are needed to study the applications and limitations of ICG in pediatric surgical oncology.


Predictive validity of subtypes of chronic affective disorders derived by cluster analysis.
This study aimed to examine the predictive validity of the cluster-analytically derived 3 subtypes of chronic affective disorders that were proposed on the basis of cross-sectional symptoms and were shown to have some external validity with regard to psychosocial characteristics. Two-year naturalistic follow-up data were available for 38 (97%) of the original 39 patients with chronic affective disorders. The 3 subtypes, which were named psychotic subtype, late-onset female subtype and depressive personality subtype in the previous analyses, did not differ in their depressive severity or social functioning upon entry. In the course of the 2-year follow-up, however, there were significant differences in the Global Assessment of Functioning scores as well as the social adaptation in the economic sphere according to the Social Adjustment Scale-Self Report. All these indices revealed the psychotic subtype to have the worst outcome, followed by the depressive personality subtype, and the late-onset female subtype fared best.