Intracellular segregation of asialo-transferrin and asialo-fetuin following uptake by the same receptor system in suspended hepatocytes.
Asialo-transferrin and asialo-fetuin are both taken up into suspended hepatocytes by the asialo-glycoprotein receptor and with similar kinetics (Tolleshaug, H., Chindemi, P. and Regoeczi, E. (1981) J. Biol. Chem. 265, 6526-6528). However, the intracellular fate of the two ligands differ. Asialo-fetuin is carried to the lysosomes and degraded. Internalized asialo-transferrin is recycled with the receptors back to the cell surface, from which it may be released by calcium chelators. In the current studies, we fractionated cell homogenates in sucrose density gradients in order to trace the pathways taken by asialo-transferrin and asialo-fetuin within the cells. More than one-half of the intracellular asialo-transferrin sedimented within a novel kind of 'light' endosomes which were recovered at 1.11 g/ml in sucrose gradients. When cells were fractionated 6 min after the addition of trace concentrations of 125I-asialo-fetuin and 131I-asialo-transferrin, their intracellular distributions were found to be roughly similar. After 24 min their distributions were clearly disparate, relatively more asialo-fetuin being recovered in a peak of heavy endosomes at 1.15 g/ml. The ligand molecules in this part of the gradient (e.g., asialo-fetuin) were delivered to the lysosomes to be degraded, while the material in the lighter peak was degraded much more slowly. The data indicate that asialo-fetuin and asialo-transferrin enter a light endosome fraction immediately after receptor-mediated endocytosis. Subsequently, they are separated; the asialo-transferrin remains receptor-bound and is returned to the cell surface, while the asialo-fetuin is transferred to endosomes of density 1.15 g/ml and is eventually degraded in the lysosomes.


[Hemophagocytic lymphohistiocytosis associated with a lymphohistiocytic pattern anaplastic large cell lymphoma: a case report].
We report the case of a 16-year-old girl with an anaplastic large cell lymphoma of lymphohistiocytic pattern revealed by a hemophagocytic syndrome. Histologically, the lymphomatous population was concealed by clusters of histiocytes. Immunohistochemical study allowed the diagnosis. The combination of these two entities is rarely described and may be a source of delay in diagnosis of a life-threatening condition.


A short-term high-dose administration of sodium pivalate impairs pyruvate metabolism without affecting cardiac function.
The pivalate moiety of some oral antibiotics enhances their intestinal absorption, but liberated pivalic acid decreases tissue carnitine concentration and could lead to impaired energy metabolism. The present study investigated the effects of short-term sodium pivalate administration on cardiac functionality and mitochondrial energy metabolism. Wistar rats received sodium pivalate (40 mM) in their drinking water for 14 days, and the carnitine content was measured in heart tissues. The activities of carnitine-dependent enzymes, including carnitine acetyltransferase (CrAT) and carnitine palmitoyltransferase I (CPT I), and the mitochondrial respiration rate were also measured. The isolated rat heart ischemia-reperfusion injury assay was performed based on the Langendorff technique through the reversible occlusion of the left anterior descending coronary artery. The administration of sodium pivalate decreased carnitine concentration in the myocardium by 37 %. Sodium pivalate significantly decreased mitochondrial respiration on pyruvate/malate by 28 %. The activities of CrAT and CPT I in sodium pivalate-treated animals were decreased by 34 and 30 %, respectively. No differences were observed in the infarct size or in the heart functional parameters between the groups. Together, these results indicate that the short-term administration of a high dose of sodium pivalate impairs cardiac mitochondrial energy metabolism without depressing cardiac function during ischemia-reperfusion injury.


Dual roles of TGF-β signaling in the regulation of dental epithelial cell proliferation.
The purpose of this study is to investigate the molecular mechanisms and biological function of TGF-β-activated Smad1/5 in dental epithelium. Immunohistochemistry was used to detect the expressions of TGF-β signaling-related gene in mice molar germ. Primary dental epithelial cells were cultured and treated with TGF-β1 at a concentration of 0.5 or 5 ng/mL. Small molecular inhibitors, SB431542 and ML347, was used to inhibite ALK5 and ALK1/2, respectively. Small interfering RNA was used to knock down Smad1/5 or Smad2/3. The proliferation rate of cells was evaluated by EdU assay. In the basal layer of dental epithelial bud TGF-β1 and p-Smad1/5 were highly expressed, and in the interior of the epithelial bud TGF-β1 was lowly expressed, whereas p-Smad2/3 was highly expressed. In primary cultured dental epithelial cells, low concentration of TGF-β1 activated Smad2/3 but not Smad1/5, while high concentration of TGF-β1 was able to activate both Smad2/3 and Smad1/5. SB431542 but not ML347 was able to block the phosphorylation of Smad2/3 by TGF-β1. Either SB431542 or ML347 was able to block the phosphorylation of Smad1/5 by TGF-β1. EdU staining showed that high concentration of TGF-β1 promoted dental epithelial cell proliferation, which was reversed by silencing Smad1/5, whereas low concentration of TGF-β1 inhibited cell proliferation, which was reversed by silencing Smad2/3. In conclusions, TGF-β exhibits dual roles in the regulation of dental epithelial cell proliferation through two pathways. On the one hand, TGF-β activates canonical Smad2/3 signaling through ALK5, inhibiting the proliferation of internal dental epithelial cells. On the other hand, TGF-β activates noncanonical Smad1/5 signaling through ALK1/2-ALK5, promoting the proliferation of basal cells in the dental epithelial bud.


Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation.
Psyllium is widely used in the symptomatic therapy of constipation. Its effects on colonic function and their correlation with symptomatic response have not been defined. After a 4-week baseline, placebo, run-in phase, 22 subjects with idiopathic constipation confirmed by prospectively administered stool diaries were randomly assigned to receive either psyllium (5 g b.d., 11 patients) or placebo (11 patients) for 8 weeks, followed by another 4-week wash-out, placebo phase. A colon transit study and anorectal manometry were performed at the beginning and at the end of each study phase. Subjects recorded, in diaries, their daily stool frequency, difficulty with defecation and weekly stool weight. Stool frequency increased significantly after 8 weeks of psyllium treatment (3.8 +/- 0.4 vs. 2.9 +/- 0.1 stools/week, P < 0.05) as did stool weight (665.3 +/- 95.8 g vs. 405.2 +/- 75.9 g, P < 0.05). Subjects also reported an improvement in stool consistency (stool consistency score: 3.2 +/- 0.2 vs. 3.8 +/- 0.2, P < 0.05) and pain on defecation (pain score: 2.0 +/- 0.4 vs. 2.6 +/- 0.5, P < 0.05) on psyllium. Colon transit and anorectal manometry parameters were unchanged on psyllium. Subjects treated with placebo did not show any change in either subjective or objective measures of constipation. Psyllium increases stool frequency and weight and improves stool consistency in idiopathic constipation. These effects are not associated with significant changes in either colonic or rectal motor function. We suggest that the beneficial effects of psyllium in constipation are primarily related to a facilitation of the defecatory process.


Cell Surface N-Glycans Influence Electrophysiological Properties and Fate Potential of Neural Stem Cells.
Understanding the cellular properties controlling neural stem and progenitor cell (NSPC) fate choice will improve their therapeutic potential. The electrophysiological measure whole-cell membrane capacitance reflects fate bias in the neural lineage but the cellular properties underlying membrane capacitance are poorly understood. We tested the hypothesis that cell surface carbohydrates contribute to NSPC membrane capacitance and fate. We found NSPCs differing in fate potential express distinct patterns of glycosylation enzymes. Screening several glycosylation pathways revealed that the one forming highly branched N-glycans differs between neurogenic and astrogenic populations of cells in vitro and in vivo. Enhancing highly branched N-glycans on NSPCs significantly increases membrane capacitance and leads to the generation of more astrocytes at the expense of neurons with no effect on cell size, viability, or proliferation. These data identify the N-glycan branching pathway as a significant regulator of membrane capacitance and fate choice in the neural lineage.


Radial tunnel syndrome: a spectrum of clinical presentations.
A variety of symptoms associated with 15 cases of resistant tennis elbow and resistant radial tunnel pain are described. These included sensations of popping, paresthesias, and paresis. The duration of symptoms averaged 2.3 years before a definitive diagnosis of radial tunnel syndrome was made. Two unique anomalies were contributing factors in the radial nerve entrapment; one case demonstrated a completely tendinous proximal border of the extensor carpi radialis brevis and the other a bifid extensor carpi radialis brevis origin. Excellent pain relief, elimination of popping, and improvement of the paresthesias and paresis was achieved by release of the radial tunnel in cases unresponsive to conservative treatment.


The Effect of Blood Transfusion in Lung Donors on Recipient Survival.
Blood transfusion can have detrimental effects on the pulmonary system, leading to lung injury and respiratory decompensation with subsequent increased morbidity and mortality in surgical and critically ill patients. How much of this effect is carried from a lung donor to transplant recipient is not fully understood, raising questions regarding transplant suitability of lungs from transfused donors. United Network for Organ Sharing data were reviewed. Lung transplants from adult donors and known donor transfusion status were included; multiorgan transplants and retransplants were excluded. Recipient mortality was evaluated based on donor and recipient characteristics using a Kaplan-Meier survival estimate, Cox proportional hazards, and logistic regression models. We further assessed whether recipient mortality risk modified the donor transfusion effect. From March 1996 to June 2017, 20,294 transplants were identified. Outcome analysis based on transfusion status showed nonsignificant difference in 1-year mortality (P = .214). Ninety-day recipient mortality was significantly higher with transfusion of >10 units (U) vs 1-10 U or no transfusion (8.5%, 6.1%, and 6.0%, respectively, P = .005). Multivariable analysis showed increased 90-day mortality with transfusion of >10 U compared to no transfusion (odds ratio 1.62, P < .001), whereas 1-10 U showed no difference (odds ratio 1.07, P = .390). When stratified by recipient transplant risk, transfusion of >10 U was associated with increased mortality even with the lowest-risk recipients, while transfusion of 1-10 U showed no mortality increase even in the highest-risk recipients. Donor transfusion of >10 U of blood was associated with increased 90-day recipient mortality even in low-risk transplants. This risk should be considered when evaluating donor lungs.


The 18-kDa form of cat allergen Felis domesticus 1 (Fel d 1) is associated with gelatin- and fibronectin-degrading activity.
Fel d 1, an important allergen from domestic cats, is a significant cause of asthma. In addition to directly promoting IgE synthesis, other biological activities of allergens may contribute to either allergic sensitization or the magnitude of allergic effector responses. For example, allergens that degrade proteins have been suggested to facilitate allergen presentation by increasing parallelular permeability of airways epithelium. However, little information exists to indicate whether Fel d 1 has other activities relevant to allergic responses. To study whether Fel d 1 is associated with enzyme activity. Fel d 1 was obtained by a rigorous purification strategy and its identity confirmed by laser desorption mass spectrometry, cleavage and sequencing. The ability of Fel d 1 to degrade gelatin, fibronectin and the artificial substrate N-benzoyl-FVR-p-nitroanilide was studied. The effect of Fel d 1 on the morphology of tight junctions in epithelial cell monolayers was also investigated. The 18-kDa form of Fel d 1 caused degradation of denatured collagens (gelatin) and cleaved a 20-kDa fragment from the A chain of plasma fibronectin. Catalytic activity was not altered by inhibitors of cysteine peptidases, matrix metallopeptidases or by removal of divalent cations. In contrast, aprotinin and TLCK were inhibitors of Fel d 1. The absence of a serine peptidase catalytic triad in Fel d 1, together with the stoichiometry of the inhibition of TLCK and aprotinin, suggest that their inhibitory action may be due to noncatalytic site interactions. Alternatively, highly purified Fel d 1 may be associated with an active contaminant, although none were found. These results suggest that Fel d 1 is another example of a domestic allergen which is associated with enzyme activity. It remains to be established whether the activity resides in Fel d 1 itself or in an unresolved, and possibly related, protein.


Protein quantification by selective isolation and fragmentation of isotopic pairs using FT-ICR MS.
Isolation of tryptic peptide ions, along with their differentially labeled analogs derived from an artificial QconCAT protein, is performed using multiple correlated harmonic excitation fields in an FT-ICR cell. Simultaneous fragmentation of the isolated unlabeled and labeled peptide pairs using IRMPD yields specific y-series fragment ions useful for quantification. The mass increment attributed to stable isotope labeling at the C-terminus is maintained in the C-terminal fragment ions, providing multiple measurements of labeled/unlabeled intensity ratios during highly selective detection. The utility of this approach has been demonstrated in the absolute quantification of components of an unfractionated chicken muscle protein mixture.


Irradiated Tree Nut Flours for Use in Oral Immunotherapy.
Tree nut allergies affect an estimated 1% of the US population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products. Food products used in OIT are considered drugs by the Food and Drug Administration (FDA) because they are intended to modulate the individuals' immune responses to the food allergens. As such, OIT drug products must meet FDA standards for acceptable levels of microbes and undergo testing for allergenic proteins. We aimed to determine the suitability of walnut, cashew, hazelnut, and almond flours for use in OIT trials. We employed gamma irradiation on commercially available walnut, cashew, hazelnut, and almond flours and tested their levels of microbial contamination, total protein, and allergen content, along with stability of these parameters over time. Our results demonstrate that irradiation of tree nut flours greatly diminishes the levels of total aerobic bacteria, mold, yeast, Escherichia coli, and Salmonella, whereas there are no substantial changes in total protein or allergen content. Importantly, the microbial levels, protein, and allergen content remained stable over a 24-month period. Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.


Isolation and characterization of a novel mouse lymphatic endothelial cell line: SV-LEC.
The lymphatic system regulates interstitial fluid and protein balance and modulates immune responses by regulating leukocyte and antigen traffic to lymph nodes. The present article describes a stable mouse lymphatic endothelial cell line from mesenteric adventitial tissue (SV-LEC) which is distinct from blood aortic (AEC) and venous (VEC) endothelial cells, based on expression of several lymphatic markers (e.g., Prox-1, LYVE-1, Flt-4). SV-LEC also expresses MAdCAM-1 in response to TNF-alpha, an effect seen in VEC, but not AEC. Lymphatic endothelial cells (SV-LEC) were isolated from mesenteric adventitia from mice expressing temperature-sensitive SV40 large T ('Immortomouse', H-2K(b)tsA58) selected with hypoxia culture in D-valine-substituted MEM supplemented with VEGFC in a low oxygen atmosphere (0% O2, 5% CO2, and 95% N2) with 5 mM thioglycolate. Expression of lymphatic-specific markers (Flt-4, LYVE-1, Prox-1) and the tight junction proteins (ZO-1) were examined by RT-PCR, immunoblotting, and fluorescent microscopy. MAdCAM-1 (a high endothelial venular marker) expression was also examined in response to TNF-alpha IL-1beta and IFN-gamma. Message for Flt-4 and LYVE-1 was detected on SV-LEC. Immunoblotting for LYVE-1 and Prox-1 showed strong expression on SV-LEC and VEC, but not AEC. Occludin expression was seen in all cell types, junctional ZO-1 was detected at SV-LEC and VEC junctions, not AEC. SV-LEC expresses several lymphatic endothelial markers, some of which are shared with VEC, but not AEC, and may represent a useful system for modeling lymphatic function in vitro.


Keep the bounce in your step. One perspective of health education for the aged in Australia.
Recognising the need to design, promote, market and manage health education programmes for the elderly people, the Department of Health of New South Wales (NSW), Australia, set in 1982, the infrastructure to foster a healthier aged population through the formation of the Senior Adult Unit.


Distinguishing the relative contributions of landscape composition and configuration change on ecosystem health from a geospatial perspective.
Understanding the impact mechanisms of landscape composition and configuration change on ecosystem health (EH) is critical to ecosystem conservation and human well-being. However, existing studies mainly focused on EH changes due to combined effects of landscape composition and configuration change, while the individual impacts and spatial heterogeneity of these factors on EH remain unclear. Thus, taking Chongqing as an example, this study distinguished the relative contributions of landscape configuration and composition on EH based on scenario analysis method, and further explored how these impacts change between and within different topographic, geological and urbanization zones. The results showed that EH displayed an improving trend during 2000-2020, with the increasing areas distributed in the mountainous of southeast and northeast in Chongqing, largely influenced by increased forest landscape cohesion and their synergistic effects with forest expansion, accounting for 91.05 % and 87.86 % of the study area respectively, while the decreasing areas were mostly located in urban cores, dominated by changes in landscape composition (e.g. farmland reclamation and urban sprawl), accounting for 50.95 % of area proportion. The scenario analysis of EH showed that the areas dominated by landscape configuration were 5.39 times greater than the landscape composition under the same climate scenario. In terms of zoning comparison, the influence of landscape composition change on EH displayed the greatest difference within urbanization zones, while topographic zones for landscape configuration change. This paper provides a novel perspective to explore the impact of landscape pattern on EH, which is important to regional ecosystem conservation and land use management.


HPV infection and intraepithelial lesions from the anal region: how to diagnose?
In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN) and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.


Clinical Profile and Long-Term Follow-Up of Children with Brugada Syndrome.
Brugada syndrome (BrS) is a rare channelopathy associated with sudden cardiac death (SCD). Although outcome data of adult cohorts are well known, information on children are lacking. The aim of the present study was to analyze the clinical profile, treatment approach and long-term outcome of children affected with BrS. After a systematic review of the literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Libary, Cinahl), data from a total of 4 studies which included 262 BrS patients were identified. The mean age of patients was 12.1 ± 5.5, 53.8% males and 19.8% spontaneous BrS type I. 80.2% of patients presented BrS ECG I after receiving sodium channel blockers. 76% of these patients were asymptomatic while only 17.9% suffered from recurrent syncope. Around 1.5% of the patients were admitted due to aborted SCD, and 3% suffered from atrial arrhythmias. Electrophysiological work-up was performed in 132 patients. Induction of ventricular tachycardia/ventricular fibrillation using programmed ventricular stimulation was inducible in 16 patients. 56 children received an ICD. 11 patients received quinidine. An electrical storm was documented in 1 patient. Appropriate shocks occured in 16% of the patients over a median follow-up period of 62.2 (54-64). ICD-related complications were observed in 11 patients (19.6%) with a predominance of inappropriate shocks and lead failure and/or fracture. Although BrS in the childhood is rare, diagnosis and management continues to be challenging. ICD therapy is an effective therapy in high-risk children with BrS, however, with relevant ICD-related complications.


[Secondary limb lymphedema].
Lymphedema is related to congenital lymphatic abnormality (primary forms) or acquired (secondary forms) after lesions of lymphatic system. Upper to limb secondary lymphedema after breast cancer treatment is the most frequent in France. The first worldwide cause is lymphatic filariosis. Secondary lymphedema is related to adverse effects after cancer treatment including surgery with lymph nodes excision associated with radiotherapy: breast, melanoma for upper limb, cervical, uterine, prostate, bladder cancer, melanoma for lower limb. At lymphedema onset, deep venous thrombosis and recurrent cancer should be investigated. Rare causes of lymphedema are also reported: rheumatic diseases (rheumatoid arthritis), Kaposi sarcoma, retroperitoneal fibrosis, immunosuppressive agent (sirolimus).


Irradiation induces homing of donor endothelial progenitor cells in allogeneic hematopoietic stem cell transplantation.
Functional abnormalities of the endothelial system may be caused by allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study is to explore the possibility that endothelial progenitor cells (EPCs) can be used in endothelial repair post-HSCT. EPCs were isolated from mouse bone marrow by density centrifugation and differential adherence. Numbers of endothelial cells (ECs) (CD31(+)CD133(-)CD45(-)), EPCs (CD31(+)CD133(+)-CD45(low/-)) and carboxyfluorescein succinimidyl ester (CFSE)-positive cells in peripheral blood, spleen and bone marrow were determined at various time points by flow cytometry. The distribution of labeled EPCs was observed by fluorescence microscopy; morphological alterations of tissues were assessed by light microscopy and transmission electron microscopy. In the irradiated group, the numbers of circulating ECs and EPCs were elevated after pre-conditioning, reaching peaks at days 3 and 5; the counts remained high for about 5 days. In addition, CFSE-labeled cells were visualized in tissue and bone marrow. In conclusion, these results suggest the following: (a) the EPCs derived from mouse bone marrow mononuclear cells express phenotypes characteristic of normal EPCs, (b) irradiation during preconditioning damaged the endothelium, which initiated mobilization of EPCs, and (c) injury to the endothelium also caused extrinsic EPCs home to the damaged tissue.


The Hermansky-Pudlak syndrome.
Hermansky-Pudlak Syndrome (HPS) is a rare, inheritable disorder characterized by the classic triad of oculo-cutaneous albinism, platelet dysfunction, and ceroid deposition. An associated complication is pulmonary fibrosis with progressive restrictive lung disease. This report discusses the lung involvement often seen in this condition correlated with radiography, computed tomography, high-resolution computed tomography, and the underlying pathology, by means of two such afflicted siblings. The elder died of respiratory failure while awaiting lung transplantation. The younger sibling is currently undergoing evaluation for transplantation.


Coexpression of organic anion-transporting polypeptides 1B3 and multidrug-resistant proteins 2 increases the enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid on hepatocellular carcinoma in magnetic resonance imaging.
We aimed to elucidate the relationship between the contrast enhancement effect of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) on magnetic resonance imaging (MRI) of hepatocellular carcinomas (HCC) and the expressions of hepatocyte transporters (i.e. organic anion-transporting polypeptide [OATP]1B3, multidrug-resistant protein [MRP]2 and MRP3) and to clarify the characteristics of HCC with an MRI high-contrast enhancement effect. We retrospectively examined the relationship between the relative enhancement ratio (RER) of HCC, absolute and relative immunohistochemical staining scores of hepatocyte transporters, and histological differentiation of 22 HCC from 21 patients who had undergone preoperative Gd-EOB-DTPA-enhanced MRI. RER had a significant correlation with OATP1B3 expression according to the absolute and relative scores (P = 0.016 vs 0.0006). The RER of HCC with high OATP1B3 and MRP2 expression levels was higher than that of HCC with low OATP1B3 or MRP2 expression levels (P = 0.0003). The RER of HCC with higher OATP1B3 rates was greater than that of HCC with lower OATP1B3 rates (P = 0.0005). HCC histological differentiation showed a significant correlation with OATP1B3 expression and RER (P = 0.023 vs 0.0095). We found that coexpression of OATP1B3 and MRP2 influenced the high contrast enhancement of HCC on MRI.


Specifics of immunogenesis and metabolism in young hogs under biogeochemical conditions of Chuvash Center.
Combined treatment of young hogs with Trepel food supplement and Polystim immunomodulator with consideration for specific biogeochemical properties of Chuvash Center produced immunostimulating and metabolic effects and optimized the balance between free radical oxidation response and body antioxidant potential.


Evaluation of skill-acquisition process in mitral valve repair techniques: a simulation-based study.
Increased patient awareness, duty-hour restrictions, escalating costs, and time constraints in the operating room have revolutionized surgical education. A bovine heart model was designed for training in mitral valve repair procedures. In this article, we aimed to share our experience with this model and to test the validity of simulation with respect to skill acquisition during the training course. After reviewing instructional video recordings of mitral valve repair techniques, 5 junior residents (first and second year) and 5 senior residents (year 4 or higher), who had no experience in mitral valve repair surgery previously, performed mitral valve repair techniques on bovine heart model in a three-month period. Nine different internet videos demonstrating surgical techniques were watched prior to performance in each case. Different text books were studied before the study course. Following repair in each case, the left ventricle of each bovine heart was statically pressurized, the coaptation depth was measured, and the regurgitation (if any) was scored. Each performance was recorded. At the end of the study, video records were evaluated in a blind fashion by 3 different surgeons experienced in mitral valve repair techniques. The monthly scores obtained were statistically analyzed. The mean coaptation depth values measured on a monthly basis were as follows: 2.75±0.63, 4.90±0.91, and 6.55±0.88 for the junior residents and 4.30±0.65, 5.45±0.68, and 7.00±0.64mm for the senior residents. Regurgitation scores noted were 2.20±0.52, 1.65±0.58, and 0.10±0.30 for the junior residents and 1.50±0.60, 0.65±0.67, and 0.70±0.65 for the senior residents During the study period, the practice improved in terms of the aforementioned parameters in both groups (p<0.05). This simulation model of mitral valve repair helped in skill acquisition on monthly basis in both resident groups.


Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers.
The Elecsys NT-proBNP assay is based on two polyclonal antibodies directed at residues 1-21 and 39-50 of the NT-proBNP molecule. Analytical performance was assessed using NCCLS protocol EP-5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7-1.6 (1010) and 1.2-1.5 (2010) and between run CV 5.3-6.7 (1010) and 4.4-5.0 (2010). In the multicentre evaluation within run CV was 1.0-2.5% with total imprecision 1.5-2.5% and between labs imprecision 3.8-4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x-0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 degrees C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT-proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT-proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT-proBNP values increased with age and were higher in women than men.


One-stage efficacy of single tract minimally invasive ECIRS in the improved prone frog split-leg position for staghorn stones.
To explore the feasibility, safety, and effectiveness of single tract minimally invasive endoscopic combined intrarenal surgery (stmECIRS) in the improved prone frog split-leg position for staghorn stones. A total of 83 patients with staghorn stones were retrospectively reviewed between January 2018 and June 2021. According to surgical procedure and position, patients were divided into a group of single tract minimally invasive percutaneous nephroscopy (stmPNL) in the prone position and a group of stmECIRS in the improved prone frog split-leg position (turned to the prone position after preset the flexible ureteroscope sheath in lithotomy position, meanwhile, bend both hips and knees to be frog abduction). Demographic characteristics, laboratory tests, stone characters, surgical information, stone-free rate (SFR), and perioperative complications were observed and analyzed. There were no significant differences in demographic characteristics, changes level of Scr and Hb, stone size, radiation density, length of hospital stay, and operation time between the two groups. One-stage SFR in the stmECIRS group was significantly higher than that in the stmPNL group (84.4% vs. 57.9%) (P = 0.007), only 2 patients required blood transfusion after surgery (P = 0.862), and other postoperative complications were not statistically significant (P = 0.345). StmECIRS in improved prone frog split-leg position has a higher one-stage SFR than stmPNL for staghorn renal stones, and without complications increased, which is a safe, efficient and feasible treatment.


The role of intuition and deliberative thinking in experts' superior tactical decision-making.
Current theories argue that human decision making is largely based on quick, automatic, and intuitive processes that are occasionally supplemented by slow controlled deliberation. Researchers, therefore, predominantly studied the heuristics of the automatic system in everyday decision making. Our study examines the role of slow deliberation for experts who exhibit superior decision-making outcomes in tactical chess problems with clear best moves. Our study uses advanced computer software to measure the objective value of actions preferred at the start versus the conclusion of decision making. It finds that both experts and less skilled individuals benefit significantly from extra deliberation regardless of whether the problem is easy or difficult. Our findings have important implications for the role of training for increasing decision making accuracy in many domains of expertise.


Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.
The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 microM) suppressed the amplitude of delayed rectifier K+ current (I K(DR)) in a concentration-dependent manner with an IC50 value of 3.1 microM. The presence of ACO enhanced the rate and extent of I K(DR) inactivation, although it had no effect on the initial activation phase of I K(DR). It could shift the inactivation curve of I K(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for I K(DR) was also enhanced by ACO. Orphenadrine (30 microM) or methyllycaconitine (30 microM) slightly suppressed I K(DR) without modifying current decay. ACO (10 microM) had an inhibitory effect on voltage-dependent Na+ current (I Na). Under current-clamp recordings, ACO increased the firing and widening of action potentials in these cells. With the aid of the minimal binding scheme, the ACO actions on I K(DR) was quantitatively provided with a dissociation constant of 0.6 microM. A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked I K(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on I K(DR) and I Na.


Gene expression profiling in breast cancer: towards individualising patient management.
Breast cancer is a complex and clinically heterogeneous disease. The increase in knowledge of breast cancer biology has led to a number of clinical advances in the treatment of breast cancer, most notably the implementation of widespread mammography screening and advances in adjuvant treatment of early-stage disease. In the last 20 years, arrays of potential prognostic and/or predictive markers of breast cancer have been analysed. However, relatively few have proven to be clinically useful. To date, the only widely accepted markers for routine use in breast cancer are the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor, HER-2 (c-erbB2/neu). Expression microarray technology and laser capture microdissection have now been employed to further our understanding of the molecular pathogenesis of breast cancer. Recently reported advances in array technology and RNA amplification methods are having a considerable impact in this field, allowing the analysis of pre-malignant and pre-invasive lesions. A number of studies have identified prognostic and predictive gene 'signatures', whose prediction of disease outcome and response to treatment is superior to conventional prognostic indicators. Despite major technological advances, a number of confounding issues remain concerning the potential clinical utility of gene expression profiling, including differences in study design, patient selection, array technology, chemistry, and methods of analysis. It seems likely, however, that following careful 'hypothesis driven' validation studies and clinical trials, expression profiling will be applied in the future to identify patient-specific disease profiles and provide rationale for individualised treatment. This review focuses on the current use and future potential of microarray profiling in breast cancer.


Adolescent dating violence prevention programmes: a global systematic review of evaluation studies.
Adolescent dating violence negatively affects millions of young people worldwide. Through a global systematic review, we synthesised evidence from rigorous studies of prevention programmes for adolescent dating violence. Our aims were to: (1) describe the breadth of research in this area and evidence of programme effects, and (2) identify gaps in the evidence base. We included experimental and controlled quasi-experimental programme evaluations, published before Jan 1, 2020, that assessed effects on victimisation or perpetration, or both, in adolescent dating violence and in which at least half of the study population was 10-19 years old. Study design, programme elements, and outcomes were compared between evaluations implemented in high-income countries (HICs) and low-income and middle-income countries (LMICs). 52 evaluations met inclusion criteria, of which 20 (38%) were implemented in LMICs. Evaluations in HICs were more likely to assess effects on adolescent dating violence victimisation and perpetration, rather than just victimisation, than those in LMICs, and they were also more likely to include boys and girls, as opposed to just a single sex. Overall, 26 (50%) of the 52 evaluations reported a significant preventive effect on at least one outcome for adolescent dating violence, of which nine were implemented in LMICs. Across LMICs and HICs, findings suggest research is needed to shed light on how adolescent dating violence prevention programmes work and to identify whether programme effects generalise across different settings, outcomes, and subgroups. TRANSLATIONS: For the Chinese, French and Spanish translations of the abstract see Supplementary Materials section.


Long noncoding RNA TP73-AS1 in human cancers.
Long noncoding RNAs (lncRNAs) play an important role in tumor development. With the development of sequencing technology, many new lncRNAs have been discovered. lncRNA TP73-AS1 is abnormally expressed in many cancers. A summary of the current literature related to TP73-AS1 reveals that TP73-AS1 mainly regulates the occurrence and development of tumors through the mechanism of competitive endogenous RNA (ceRNA). In addition, the abnormal expression of TP73-AS1 can regulate the malignant function of tumor cells through a variety of possible mechanisms. All evidence suggests that TP73-AS1 may be a potential diagnostic biomarker or a new cancer therapeutic target.


Isoforms of MUC16 activate oncogenic signaling through EGF receptors to enhance the progression of pancreatic cancer.
Aberrant expression of CA125/MUC16 is associated with pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. However, knowledge of the contribution of MUC16 to pancreatic tumorigenesis is limited. Here, we show that MUC16 expression is associated with disease progression, basal-like and squamous tumor subtypes, increased tumor metastasis, and short-term survival of PDAC patients. MUC16 enhanced tumor malignancy through the activation of AKT and GSK3β oncogenic signaling pathways. Activation of these oncogenic signaling pathways resulted in part from increased interactions between MUC16 and epidermal growth factor (EGF)-type receptors, which were enhanced for aberrant glycoforms of MUC16. Treatment of PDAC cells with monoclonal antibody (mAb) AR9.6 significantly reduced MUC16-induced oncogenic signaling. mAb AR9.6 binds to a unique conformational epitope on MUC16, which is influenced by O-glycosylation. Additionally, treatment of PDAC tumor-bearing mice with either mAb AR9.6 alone or in combination with gemcitabine significantly reduced tumor growth and metastasis. We conclude that the aberrant expression of MUC16 enhances PDAC progression to an aggressive phenotype by modulating oncogenic signaling through ErbB receptors. Anti-MUC16 mAb AR9.6 blocks oncogenic activities and tumor growth and could be a novel immunotherapeutic agent against MUC16-mediated PDAC tumor malignancy.


Effects of Serial Sessions of Activa Mask for the Treatment of Meibomian Gland Dysfunction.
To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD). This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire. All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001). Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study.


Health care reform in Iran: Implications for nurses' moral distress, patient rights, satisfaction and turnover intention.
The aim of the present study was to assess the implications of Iran's recent health care reforms on nurses' experience of moral distress, their perceptions of the respect for patient rights and the relationship of these variables to job and income dissatisfaction and turnover intention. Health systems around the world are reforming themselves to adapt to meeting the future needs of increasing patient care to an ever-growing population. This was a cross-sectional correlational study. The participants were 276 nurses at six large private and public hospitals in Tehran, Iran. Negative correlations were reported between turnover intention and respecting patient rights (r = -0.560, p < 0.001), satisfaction with job (r = -0.710, p < 0.001) and satisfaction with income (r = -0.226, p < 0.001). The correlation between moral distress intensity (r = 0.626, p < 0.001) and frequency (r = 0.701, p < 0.001) was positive with turnover intention. Moral distress was significantly correlated to poor respect for patient rights, poor job satisfaction and income satisfaction and was a major predictor of turnover intention. Health system reform must take into account the concomitant increasing workload and its negative impact in order to ensure that reform does not lead to unintentional detrimental outcomes of increased moral distress, decreased satisfaction and increased turnover rates among nursing personnel.


Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells.
Since chronic inflammation is associated with the pathogenesis of atherosclerosis, inflammatory cytokines might contribute to the phenotypic modulation of vascular smooth muscle cells (VSMCs). Tumor necrosis factor α (TNFα) facilitated the transformation of contractile VSMCs to the synthetic phenotype, as determined by the expression of marker proteins and a collagen gel contraction assay. Western blot analysis and a cyclooxygenase-2 (COX2) promoter assay revealed that TNFα stimulation resulted in the induction of COX2. The overexpression, silencing, or pharmacological inhibition of COX2 significantly affected TNFα-induced phenotypic conversion, and of the tested prostaglandins, only PGD2 significantly induced phenotypic conversion. ERK was significantly activated by PGD2 stimulation, and the pharmacological inhibition of ERK blocked the PGD2-induced phenotypic conversion of VSMCs. However, antagonists or agonists of PGD2 receptors did not affect VSMC conversion. In contrast, spontaneously dehydrated forms of PGD2, such as PGJ2, Δ12-PGJ2, and 15-d-PGJ2, strongly induced phenotypic conversion. A reporter gene assay showed that TNFα, PGD2, and 15-d-PGJ2 significantly activated the peroxisome proliferator-responsive element (PPRE) promoter. In addition, the overexpression or silencing of peroxisome proliferator-activated receptor δ (PPARδ) significantly influenced 15-d-PGJ2-induced phenotypic conversion. Finally, atherosclerotic neointima formation was significantly suppressed in mice lacking TNFα. In addition, mice fed celecoxib exhibited complete inhibition of carotid artery ligation-induced neointima formation. This study shows that PGD2 regulates the phenotypic conversion of VSMCs by generating an endogenous ligand of PPAR, and that this leads to neointima formation in occlusive arterial disease.


Resident perception on the impact of point-of-care ultrasound in clinical care at a family medicine training program in Zambia.
Patient access to necessary medical imaging in low- and middle-income countries (LMICs) remains a major obstacle, complicating clinician decision-making and compromising patient outcomes. We implemented a longitudinal point-of-care ultrasound (POCUS) training program at a new Family Medicine residency in Zambia and subsequently evaluated residents' perceptions on the impact of POCUS in patient care. Data were documented by the scanning resident via a post-scan survey, which assessed if/how the scan assisted in medical management, and if/how the scan changed that management. The primary endpoint was frequency of scans assisting and changing management. Data were summarized using descriptive statistics. Over the 1-year study period, 366 patient encounters occurred in which POCUS was utilized, resulting in a total of 542 unique POCUS scans. POCUS assisted in decision-making in 95.6% (350/366) of patient encounters, most commonly by helping to determine a diagnosis. POCUS changed management in 65.8% (235/357) of patient encounters, most commonly leading to a medication change. Zambian resident physicians perceived POCUS to be very helpful in their clinical decision-making. These data support the need to advance POCUS education at the residency level throughout LMICs, which may be an ideal strategy to promote widespread utilization of POCUS in low-resource settings globally.


Incidence and prevalence of treated epilepsy among poor health and low-income Americans.
To determine the incidence and prevalence of treated epilepsy in an adult Medicaid population. We performed a retrospective, dynamic cohort analysis using Ohio Medicaid claims data between 1992 and 2006. Individuals aged 18-64 years were identified as prevalent cases if they had ≥2 claims of epilepsy (ICD-9-CM: 345.xx) or ≥3 claims of convulsion (ICD-9-CM: 780.3 or 780.39) and ≥2 claims of antiepileptic drugs. Incident cases were required to have no epilepsy or convulsion claims for ≥5 years before epilepsy diagnosis. Subjects were determined as having preexisting disability and/or comorbid conditions, including brain tumor, depression, developmental disorders, migraine, schizophrenia, stroke, and traumatic brain injury, when at least one of these conditions occurred before epilepsy onset. There were 9,056 prevalent cases of treated epilepsy in 1992-2006 and 1,608 incident cases in 1997-2006. The prevalence was 13.2/1,000 (95% confidence interval, 13.0-13.5/1,000). The incidence was 362/100,000 person-years (95% confidence interval, 344-379/100,000 person-years). The incidence and prevalence were significantly higher in men, in older people, in blacks, and in people with preexisting disability and/or comorbid conditions. The most common preexisting conditions in epilepsy subjects were depression, developmental disorders, and stroke, whereas people with brain tumor, traumatic brain injury, and stroke had the higher risk of developing epilepsy. The Medicaid population has a high incidence and prevalence of epilepsy, in an order of magnitude greater than that reported in the US general population. This indigent population carries a disproportionate amount of the epilepsy burden and deserves more attention for its health care needs and support services.


Hydrochemical characteristics and potential health risks of nitrate, fluoride, and uranium in Kota district, Rajasthan, India.
This study examines the uranium, fluoride, and nitrate dispositions in groundwater as well as potential health risks in Kota district, Rajasthan, India. Total 198 groundwater samples were collected in both dry and wet periods and analyzed for physicochemical parameters along with U, F-, and NO3- using standard methods. Results indicate that the electrical conductivity, total dissolved solids, total hardness, alkalinity, Ca2+, Mg2+, HCO3-, Cl-, NO3-, and F- exceed the WHO standard limits of drinking water in both periods. Uranium concentration is at the broader of drinking water permissible limit (30 μg/L) and found about 1.05 times more. Nitrate and fluoride concentrations ranged from 9.8 to 412.0 mg/L and 0.1 to 4.0 mg/L for the dry season, while in the wet period, they varied from 10.0 to 954.0 mg/L and 0.1 to 3.5 mg/L, respectively. Correlation studies show a significantly strong positive correlation between uranium and total alkalinity and carbonate. Natural background levels (NBLs) were explored to assess the source of groundwater pollution. It shows that the second inflection points of NBLs estimated for NO3-, F-, and U are about 168 mg/L, 1.2 mg/L, and 7.3 μg/L, respectively, during the experimental period. The USEPA technique was used to evaluate the non-carcinogenic health risks associated with consuming the NO3- and F--contaminated groundwater. The health risks in Kota district show that children are more at risk than adults. The risk assessment of uranium reveals that the excess cancer risk (ECR) and hazard quotient (HQ) are found to be below the standard limits, but a high concentration of uranium (31.6 μg/L) is observed at Amarpura village of Digod block. This study will provide a baseline of uranium, fluoride, and nitrate dispositions in groundwater for simulating mass transport model and safe use of drinking water.


A replication-selective adenoviral vector for head and neck cancers.
To test the oncolytic activity of cyclo-oxygenase 2 (COX-2) promoter-based conditional replication-selective adenovirus vector for squamous cell carcinoma cells of the head and neck. In vitro study. None. A conditional replication-selective adenovirus vector in which the expression of E1a, required for viral replication, is controlled by the COX-2 promoter, Ad-COX2-E1a, was generated. Its oncolytic activity according to the levels of COX-2 and of Coxsackie and adenovirus receptor expression was tested in a series of human head and neck squamous cell carcinoma cell lines. The respective COX-2 messenger RNA expression ratios of KB, H891, T891, T892, and L871 were 1.5, 60.0, 1.0, 14.6, and 1.3. The corresponding Coxsackie and adenovirus receptor messenger RNA expression ratios were 1, 1, 5, 3, and 1. In vitro assays showed significant growth suppression of cancer cell lines with strong expressions of COX-2. This study demonstrated the possibility of oncolytic therapy using the COX-2 promoter-based conditional replication-selective adenovirus for head and neck squamous cell carcinoma expressing COX-2.


[Retinoprotective and reparative properties of bioregulatory peptides for laser injury to eyeground].
The article desribes biologic effects of impulse nanosecond length laser in visual range. Experimental studies proved retinoprotective and reparative properties of AV-17 preparation based on synthetic bioregulatory peptides.


A new family of RSF1010-derived expression and lac-fusion broad-host-range vectors for gram-negative bacteria.
A series of broad-host-range expression and lac fusion vectors, based on RSF1010 derivatives, was constructed. The expression vectors contain various promoters (pNm, plac, ptac and pS1) for expression of foreign genes. The efficiency of the promoters was determined in Escherichia coli, Rhizobium meliloti, Rhizobium leguminosarum and Pseudomonas putida by beta-galactosidase activity measurements. Of the promoters assayed in E. coli, the most effective is the tac promoter, whereas in soil bacteria the appropriate promoter for overexpression of foreign genes is the NmR promoter. The GmR gene, serving as a selectable marker for the plasmids, was efficiently expressed in R. meliloti as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and thus, pGm was also used to construct an expression vector. The translational fusion vectors allow the identification and characterization of promoter-carrying cloned fragments on the translational level, whereas the transcriptional fusion vectors can be used to identify and to study promoters on cloned fragments. All lac fusion vectors contain the E. coli lacZ gene or the complete lac operon facilitating quantification of expression.


Public awareness of common eye diseases in Jordan.
Cataract, glaucoma, diabetic retinopathy and dry eye disease are common with high prevalence in Jordan. This study aims to assess the awareness of these ocular diseases among Jordanian population. A self-designed questionnaire was developed in Arabic and used to interview people in different provinces of Jordan. Socio-demographic data e.g. age, gender and level of education was reported. Public awareness of four ocular diseases; cataract, glaucoma, diabetic retinopathy (DR) and dry eye disease (DED) was assessed. Questions about familiarity with the diseases, familiarity with their risk factors and participants' source of knowledge were asked. Moreover, awareness of the effect of these disease on the eye whether they are blinding, preventable, treatable and/or the vision is back to normal following treatment was also assessed. A total of 802 participants (232 males and 570 females) completed the questionnaire. The average age (± standard deviation) of the study participants was 28 ± 11.6 (range 18 to 80 years old). Awareness of cataract, glaucoma, DR and DED was reported by 31%, 38%, 37% and 52% of the study population, respectively. Family/relatives/friends and mass media appeared to be the most common sources of knowledge. Age and level of education of the participants were significantly associated with the level of disease awareness. This work shows that the level of awareness of the four ocular diseases among Jordanians is good and compares with many reports in the developed and developing countries. Familiarity and knowledge about ocular diseases is essential as it would increase the chance of the subject being tested and thus diagnosed early enough if any problem occurred. Better understanding of the disease would encourage subjects to seek medical care sooner which in turn would prevent visual impairment. Therefore, awareness campaigns should be made to target unaware population.


Life history of insect parasitoids involved in successful multiparasitism.
The occurrence of multiple parasitoid emergence from individual hosts was observed on numerous occasions. Characteristically such a phenomenon is extremely rare. In the observed instances of successful multiple parasitism of Autographa californica the parasitoid life history attributes of partial host consumption, gregariousness and timing of host parasitism are suggested as traits which contributed to certain species being able to coexist within individual hosts.


Fecal calprotectin is significantly linked to azathioprine metabolite concentrations in Crohn's disease.
The value of therapeutic drug monitoring during azathioprine (AZA) therapy with respect to clinical outcomes has been convincingly demonstrated in recent meta-analyses. However, the association between AZA metabolites and the mucosal state in inflammatory bowel disease is largely unclear. We investigated the association between AZA's active metabolite 6-thioguanine nucleotides (6-TGN) and fecal calprotectin (FC) as a well-validated surrogate marker of mucosal inflammation in patients with Crohn's disease (CD) on AZA monotherapy. Of 443 6-TGN measurements, 140 values from 88 patients with CD on AZA monotherapy visiting the inflammatory bowel disease outpatient clinic between 2009 and 2016 were retrospectively analyzed. In a subcohort with serial 6-TGN measurements, longitudinal FC measurements in patients with versus without intervention (dose increase, allopurinol, and education) were assessed. In patients with 6-TGN concentrations within a predefined range (250-450 pmol/8×10 red blood cells), FC was significantly lower (median: 119.5 vs. 327.2 mg/kg, P=0.003), and hemoglobin as well as serum protein concentrations were significantly higher than in patients with 6-TGN outside of this range. C-reactive protein and transferrin saturation were not different. In the longitudinal cohort, 6-TGN increased in the intervention group, but only a minority reached the defined range; no significant change in FC was observed. This study is the first to show that in patients with CD receiving AZA monotherapy, 6-TGN concentrations within a defined range (250-450 pmol/8×10 red blood cells) are associated with significantly lower FC. A treat-to-target concept directed by 6-TGN to reach mucosal healing may thus be a promising approach (DRKS00013246).


CRISPR Correction of the GBA Mutation in Human-Induced Pluripotent Stem Cells Restores Normal Function to Gaucher Macrophages and Increases Their Susceptibility to Mycobacterium tuberculosis.
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the β-glucocerebrosidase (GCase) GBA gene, which result in macrophage dysfunction. CRISPR (clustered regularly interspaced short palindromic repeats) editing of the homozygous L444P (1448T→C) GBA mutation in type 2 GD (GBA-/-) human-induced pluripotent stem cells (hiPSCs) yielded both heterozygous (GBA+/-) and homozygous (GBA+/+) isogenic lines. Macrophages derived from GBA-/-, GBA+/- and GBA+/+ hiPSCs showed that GBA mutation correction restores normal macrophage functions: GCase activity, motility, and phagocytosis. Furthermore, infection of GBA-/-, GBA+/- and GBA+/+ macrophages with the Mycobacterium tuberculosis H37Rv strain showed that impaired mobility and phagocytic activity were correlated with reduced levels of bacterial engulfment and replication suggesting that GD may be protective against tuberculosis.


Fatty changes associated with N-Nitrosodiethylamine (DEN) induced hepatocellular carcinoma: a role of sonic hedgehog signaling pathway.
Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality across the world. Non-viral etiological factors including obesity and metabolic syndrome have now become prevalent cause of hepatocellular carcinoma. Sonic Hedgehog (SHH) pathway is activated in hepatocellular carcinoma but its role in regulation of lipogenic molecules during the hepatocarcinogenesis is not known. The aim of present study is to explore the role of SHH pathway in fatty changes associated with hepatocarcinogenesis at different stages and to further correlate the expression of SHH with lipogenic pathways. Our results demonstrated significant increase in lipidosis and fibrosis in DEN+CCl4 treated animals. It was simultaneously associated with the enhanced expression level of SHH, E2F1, adiponectin, and lipogenic molecules in DEN+CCl4 treated animals. These results were also corroborated with the similar findings in higher stage patients' biospecimens. N-Nitrosodiethylamine (DEN) and Carbon TetraChloride (CCl4) induced hepatocellular acrcinoma model in male Wistar rats were established to study the expression level of SHH pathway and associated fatty changes during different stages of hepatocarcinogenesis. The expression levels of SHH, E2F1, and lipogenic molecules were checked at different stages of hepatocellular carcinoma. These results were further compared with biospecimens of hepatocellular carcinoma patients of different stages. Our results revealed an unknown aspect of SHH pathway in hepatocarcinogenesis via its control over lipogenesis. It gives insight into the lipogenic properties of DEN+CCl4 induced rodent hepatocarcinogenesis model and how SHH pathway operate to arbitrate this response.


[Structure-functional features of peripheral nerve elements in oligochaetes].
Histological investigation of the peripheral nervous elements in the earthworm indicates that in 3-projection neurons which are found along the I and III segmentary nerves, one of the projections terminates between epithelial cells, whereas the other produces many ramifications which form multiple terminations in the longitudinal muscles. These polyvalent neurons presumably serve as a morphological basis for the peripheral axon-reflex in the earthworm.


Elevated concentrations of substance P and 5-HT in plasma in patients with carcinoid tumors.
Ten patients with metastatic carcinoid tumors in the liver showed elevated 5-hydroxytryptamine and substance P levels in plasma samples taken from hepatic or peripheral veins. Chromatographic characterization of the substance P-immunoreactivity showed that by gel permeation and high pressure liquid chromatography the substance P-immunoreactivity was indistinguishable from synthetic undecapeptide substance P. The results suggest that substance P, in addition to the 5-hydroxyinoles, may serve as a circulatory marker for some forms of carcinoid tumors.


Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome.
Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin.


Ultrasound-MRI Fusion for Targeted Biopsy of Myopathies.
OBJECTIVE. The purpose of this article is to describe the use of ultrasound-MRI fusion imaging to guide precise and targeted muscle biopsy in patients with suspected myopathies. CONCLUSION. Ultrasound-MRI fusion-guided muscle biopsy allows targeted sampling of tissues with active inflammatory changes and facilitates diagnosis of myopathies.


Mu opioid receptor activation modulates Toll like receptor 4 in murine macrophages.
Opioids have been shown to affect both innate and adaptive immunity. We previously showed that morphine affects the macrophage production of pro-inflammatory cytokines after LPS in a NFkB dependent manner. Toll like receptors (TLRs) play a crucial role in the signaling pathways which lead to NFkB activation. TLR4 is considered the Lipopolysaccaride (LPS) receptor. The data here presented show that, in murine macrophages, morphine impacts on the immune function acting on the early step of pathogen recognition. Morphine, when added to RAW 264.7 cells and when injected into mice (s.c. 20mg/kg) is in fact able to decrease TLR4 both at mRNA and protein level in RAW cells and peritoneal macrophages. In the same cells, the mu opioid receptor (MOR) antagonist Naltrexone increases TLR4 levels, thus suggesting a role of the endogenous opioid system in TLR4 regulation. The effect of the two drugs is moreover lost in case of co-administration. Experiments with MOR KO mice and with DAMGO (MOR specific agonist) confirm that the effect of morphine on TLR4 mRNA in peritoneal macrophages is due to the MOR activation. Moreover the effect on TLR4 is blocked by PTX thus indicating the involvement of a G(i) protein after MOR binding. This work unveils a clear link between MOR activation and TLR4, suggesting a new possible mechanism at the basis of the peripheral immunosuppressive effect of opioids.


Integrating feedback from a clinical data warehouse into practice organisation.
A patient oriented hospital information system (ARIANE) was inaugurated at the Sherbrooke University hospital (CHUS) in 1990 and a clinical data warehouse (CDW) completed 2004. The CDW is updated from ARIANE every 24h and includes ICD discharge diagnosis data, visit DRG and SNOMED encoding. The data is encrypted on storage. Data is accessed according to institutional approval. To facilitate data access two levels of tool have been made accessible using a web-browser. The first level consists of a 'dashboard' that has a defined design and enables a set of pre-determined dynamic queries about a patient population. This level can be operated with minimal training. The second level uses a convivial database query tool, which requires some prior training. Two prototype dashboards have been designed and evaluated for acceptability. The first for the emergency department enables analysis of patient occupancy. The second for the biochemistry department enables quality assurance evaluation. In most cases worldwide the clinical data warehouse is only beginning to be exploited, often impeded by lack of connection between different enterprise databases. Our CDW is expected rapidly to create a culture change so that clinical practice can be continuously evaluated using compiled data readily available from the electronic health record/hospital information system.


Toe resurfacing with a thin thoracodorsal artery perforator flap.
In toe reconstruction, amputation procedures are much more common than salvage procedures. However, toe resurfacing, rather than amputation, provides superior functional and aesthetic results. In this study, we report the clinical outcomes of toe resurfacing using a thin thoracodorsal artery perforator flap. Between January 2004 and June 2013, a total of 15 patients underwent toe resurfacing using thoracodorsal artery perforator flaps. Thin flaps were harvested by discarding the deep adipose layer. Twelve cases involved a great toe defect, three, a second toe defect, three, a third toe defect, and one, a fourth toe defect. Patient ages ranged from 19 to 82 years (mean, 42.9 years). The mechanism of injury varied, including crushing injury, degloving injury, and diabetic foot infection. The size of thoracodorsal artery perforator flap ranged from 4 × 3 to 20 × 8 cm2 and the thickness of the flap ranged from 4 to 9 mm (mean, 6.5 mm). All flap survived completely without complications. The mean follow-up period was 18.8 months (range, 12-60 months). Only one patient with rheumatoid arthritis had mild gait disturbance. All patients were satisfied with the aesthetic and functional results. Toe resurfacing with thin thoracodorsal artery perforator flaps appears to be a safer and more reliable option than amputation for preserving their function. © 2015 Wiley Periodicals, Inc. Microsurgery 37:312-318, 2017.


A Mössbauer spectroscopy study of cellular acquisition of iron from pyoverdine by Pseudomonas aeruginosa.
Mössbauer spectroscopy was used to investigate the cellular acquisition of iron by Pseudomonas aeruginosa which had been incubated with ferripyoverdine for 20, 40, 60, 120 or 360 min. Studies revealed that no ferripyoverdine accumulated in the cells at any of these times and that the amounts and kinds of iron complexes produced by cellular metabolism vary with time. At 20 and 40 min a ferric species, with isomer shift delta = 0.38-0.42 mm/s and quadrupole splitting delta EQ = 0.94-0.92 mm/s, was the major iron metabolite comprising approximately 80% of the iron. At later times at least three other ferric species appeared with delta = 0.54----0.72, delta EQ = 0.84----1.07 mm/s. Ferrous species, delta = 1.43----1.77 mm/s and delta EQ = 2.69----1.82 mm/s, were also seen at times as early as 20 min and comprised as much as 17% of the total iron at 20 and 40 min. The parameters of all these species identify them as being six-coordinated high-spin complexes. In addition a low-spin species, delta = 0.19 mm/s delta EQ = 0.67----0.91 mm/s, never before reported in cells, appeared at 60, 120, and 360 min as one of the major iron metabolites (50% or more). All isomer shifts are measured with respect to natural iron.


Site-directed mutagenesis of the essential arginine of the formate dehydrogenase active centre.
Sequence alignment shows that residue Arg 284 (according to the numbering of the residues in formate dehydrogenase, FDH, from the methylotrophic bacterium Pseudomonas sp. 101) is conserved in NAD-dependent FDHs and D-specific 2-hydroxyacid dehydrogenases. Mutation of Arg 284 to glutamine and alanine results in a change of the catalytic, thermodynamic and spectral properties of FDH. In comparison to wild-type, the affinity of the mutants for the substrate (K(formate)m) or the transition state analogue (K(azide)i) decreases and correlates with the ability of the side chain of residue 284 to form H-bonds. In contrast, the affinity for the coenzyme (K(NAD)d or K(NAD)m) is either not affected or increases and correlates inversely with the partial positive charge of the side chain. The temperature dependence of circular dichroism (CD) spectra of the wild-type FDH and its Ala mutant has been studied over the 5-90 degrees C temperature range. Both proteins reveal regions of enhanced conformational mobility at the predenaturing temperatures (40-55 degrees C) associated with a change of enzyme kinetic parameters and a co-operative transition around 55-70 degrees C which is followed by the loss of enzyme activity. CD spectra of the wild-type and mutant proteins were deconvoluted and contributions from various types of secondary structure estimated. It is shown that the co-operative transition at 55-70 degrees C in the FDH protein globule is triggered by a loss of alpha-helical secondary structure. The results confirm the conclusion, from the crystal structures, that Arg 284 is directly involved in substrate binding. In addition this residue seems to exert a major structural role by supporting the catalytic conformation of the enzyme active centre.


Description of a new species of Niphargus (Crustacea: Amphipoda: Niphargidae): the first record of a lake ecomorph in the Carpathian Mountains.
We describe and phylogenetically characterize a new species Niphargus mirocensis from Mt. Miroč, eastern Serbia. This species shows distinct morphology typical for a lake ecomorph of niphargid amphipod, i.e. large and stout body, elongated appendages and raptorial gnathopods and presents the first record of this ecomorph in Carpathian Mountains. Phylogenetic analyses based on Cytochrome Oxidase Subunit 1 gene (COI), Histone (H3) and 28S rRNA (28S) suggests that species is nested within a clade of lake ecomorphs spread in Italy and Central Dinaric Region. The new finding is geographic extension of clade's range, the species of which are generally narrow endemics.


From the eye to the wing: neural circuits for transforming optic flow into motor output in avian flight.
Avian flight is guided by optic flow-the movement across the retina of images of surfaces and edges in the environment due to self-motion. In all vertebrates, there is a short pathway for optic flow information to reach pre-motor areas: retinal-recipient regions in the midbrain encode optic flow, which is then sent to the cerebellum. One well-known role for optic flow pathways to the cerebellum is the control of stabilizing eye movements (the optokinetic response). However, the role of this pathway in controlling locomotion is less well understood. Electrophysiological and tract tracing studies are revealing the functional connectivity of a more elaborate circuit through the avian cerebellum, which integrates optic flow with other sensory signals. Here we review the research supporting this framework and identify the cerebellar output centres, the lateral (CbL) and medial (CbM) cerebellar nuclei, as two key nodes with potentially distinct roles in flight control. The CbM receives bilateral optic flow information and projects to sites in the brainstem that suggest a primary role for flight control over time, such as during forward flight. The CbL receives monocular optic flow and other types of visual information. This site provides feedback to sensory areas throughout the brain and has a strong projection the nucleus ruber, which is known to have a dominant role in forelimb muscle control. This arrangement suggests primary roles for the CbL in the control of wing morphing and for rapid maneuvers.


Activity of forebrain neurons during alternating movements in cats.
The firing pattern of single units in the precruciate cortex, globus pallidus, entopeduncular nucleus and ventral thalamus of cats was studied before alternating limb movements. Seventy-eight percent of the neurons in these regions of the brain changed their activity more than 500 msec before the movement. No consistent early EMG changes occurred in the proximal or axial muscles which would correlate with the early neuronal activity changes. The data suggest that the sequence of movements required for this alternation task appears to be 'set' well in advance of the activation of the muscles involved in the necessary postural adjustments or the response itself. In addition, the units which showed early activity changes may be involved in the mnemonic processing necessary to discriminate a situational context and make an appropriate response. Over 50% of the movement related units in the globus pallidus, entopeduncular nucleus and ventral thalamus were related to movement of both the contralateral and ipsilateral paws. By contrast, only 33% of cortical units showed this relationship to the movement. Therefore, this 'set' process may be a relatively non-lateralized process. The data support the concept that the basal ganglia are involved in the enabling and sequencing of movements rather than in directly causing them to occur.


The activity-based anorexia mouse model.
Animals housed with running wheels and subjected to daily food restriction show paradoxical reductions in food intake and increases in running wheel activity. This phenomenon, known as activity-based anorexia (ABA), leads to marked reductions in body weight that can ultimately lead to death. Recently, ABA has been proposed as a model of anorexia nervosa (AN). AN affects about 8 per 100,000 females and has the highest mortality rate among all psychiatric illnesses. Given the reductions in quality of life, high mortality rate, and the lack of pharmacological treatments for AN, a better understanding of the mechanisms underlying AN-like behavior is greatly needed. This chapter provides basic guidelines for conducting ABA experiments using mice. The ABA mouse model provides an important tool for investigating the neurobiological underpinnings of AN-like behavior and identifying novel treatments.


Telehealth spirometry for children with cystic fibrosis.
We assessed the feasibility of telehealth spirometry assessments for children with cystic fibrosis (CF) living in a regional setting. Patients with acceptable computer hardware at home were provided with a SpiroUSB (Vyaire) spirometer. Spirometry was performed during 'home admissions' or for ongoing home monitoring in children living outside metropolitan Melbourne. At the end of the session, the family forwarded the data to the Royal Children's Hospital, Melbourne. Twenty-two patients aged 7 to 17 years participated, with spirometry successful in 55 of 59 (93%) attempted sessions according to American Thoracic Society/European Respiratory Society criteria. The median distance between the subject's home and the hospital was 238 km (range 62-537 km) which equated to a travel time saving of 5 hours and 34 min per hospital visit. Home-based telehealth spirometry is feasible in children with CF and can support the CF team during home-based admissions and for ongoing outpatient monitoring.


[Low Vision Enhancement System (LVES). Initial clinical experiences with a new kind of optoelectronic rehabilitation system].
The Low-Vision-Enhancement-System (LVES) is the first binocular optoelectronic rehabilitation device with variable focus distance. LVES was attempted on 25 patients who were not adequately treatable with classic rehabilitation devices. Using the new device, short-distance vision as well as the ability to read and write were tested. In six patients, a significant improvement was achieved using LVES. In these patients, short-distance vision as measured by LVES varied from 0.63 to 1.0. All succeeded in reading fluently, and five patients, in writing. Of these patients, five suffered from large central scotomas due to macular disease, and one female patient, from post-traumatic optic nerve atrophy. In 10 patients, near-sighted vision could be improved although the ability to read and write could not be restored, while nine patients did not show any benefit. In the latter group, were four patients with retinopathia pigmentosa, who complained of the further reduction in visual field due to the system. LVES is an additional device for the rehabilitation of low-vision patients which is especially useful in cases of macular diseases.


The effect of pimecrolimus cream 1% compared with triamcinolone acetonide paste in treatment of atrophic-erosive oral lichen planus.
Oral lichen planus (OLP) is a common chronic mucocutaneous disease. Patients with atrophic and erosive types of OLP often have symptoms of soreness, and require proper treatment. The main treatment for OLP has been the administration of topical or systemic corticosteroids. The objective of this study was to compare the efficacy of adcortyl cream (triamcinolone acetonide in orabase) with topical pimecrolimus cream for the treatment of erosive OLP. Twenty-eight patients with OLP were enrolled in a single blind clinical trial and assigned to either a pimecrolimus 1% cream group or an adcortyl 0.1% cream group. The medication was applied every day for 2 months and patients were assessed every 2 weeks. The mean lesion size and mean pain and burning sensation scores did not differ between the pimecrolimus and adcortyl cream groups. The pimecrolimus cream was well tolerated. No clinical drug-related adverse events were observed. Topical pimecrolimus cream may be recommended as a safe and effective alternative therapy in the treatment of OLP. Pimecrolimus cream is as effective as adcortyl cream in managing the signs and symptoms of OLP.


Respiratory Emergencies in Geriatric Patients.
Acute dyspnea in older patients is a common presentation to the emergency department. Acute dyspnea in older adults is often the consequence of multiple overlapping disorders, such as pneumonia precipitating acute heart failure. Emergency physicians must be comfortable managing patients with acute dyspnea of uncertain cause and varying goals of care. In addition to the important role noninvasive ventilation (NIV) plays in full resuscitation, NIV can be useful as a method of providing supportive or nearly fully supportive care while more information is gathered from the patients and their loved ones.


Reversible alterations in the mitotic cycle of chick embryo cells in various states of growth regulation.
Chick embryo cells which have been kept overnight at pH 6.8 in the absence of serum multiply very slowly. Only a small fraction of cells is in the S period at any given time, and the rate of uptake of 2-deoxy-D-glucose is very low. Upon raising the pH to 7.4 and adding serum ("turn-on") the uptake of 2-deoxy-D-glucose increases immediately; the rate of DNA synthesis increases after a lag of about 4 hours, and represents an increase in the fraction of cells synthesizing DNA. the uptake of 2-deoxy-D-glucose is rapidly returned to its original low rate at any time by again lowering the pH and removing serum ("turn-off"). The synthesis of DNA in the culture remains constant or continues to rise at a markedly reduced rate following the same treatment. Lowering pH or removing serum independently of each other is less efficient at inhibiting the increase in DNA synthesis than the combined treatment but each accomplishes a similar result. Cultures which have been "turned-off" during the early stages of the rapid increase in DNA synthesis, resume their prior rate of increase immediately if "turned-on" again within 2.5 hours. If the cultures have been "turned-off" for 5.5 hours before restoring the "turn-on", there is a 2 hour delay before they resume an increased rate of DNA synthesis. The results until shortly before, or at the time of the onset of the S period. Up to 96% of the cells in post-confluent cultures growing in conventional medium become labeled upon continuous, prolonged exposure to 3H-thymidine. Seventy-eight percent of the cells in serum-deprived cultures growing at a very low rate become labeled. These and other considerations suggest that the inhibition of cell multiplication by high population density or serum deprivation is caused by a lengthening of the time cells remain in the prereplicative G1 period rather than by shifting cells into a qualitatively distinct G0 period. There may, however, be a period common to all cells regardless of growth rate, in which cells are not progressing toward the S period. The length of this variable period would then determine the growth rate of a population of cells.


The use of evoked potentials to determine sensory sub-modality contributions to acoustic and hydrodynamic sensing.
Both the lateral line and the inner ear contribute to near-field dipole source detection in fish. The precise roles these two sensory modalities provide in extracting information about the flow field remain of interest. In this study, evoked potentials (EP, 30-200 Hz) for blind Mexican cavefish were measured in response to a dipole source. Greatest sensitivity was observed at the lower and upper ends of the tested frequency range. To evaluate the relative contributions of the lateral line and inner ear, we measured the effects of neomycin on EP response characteristics at 40 Hz, and used the vital dye DASPEI to verify neuromast ablation. Neomycin increased the latency of the EP response up until 60 min post-treatment. DASPEI results confirmed that neuromast hair cell death was significant in treated fish over this timeframe. These results indicate that the inner ear, whether it is sound pressure or particle motion detection, makes a significant contribution to the dipole-induced EP in blind cavefish at near-field low frequencies where the lateral line contribution would be expected to be strongest. The results from this study imply that under some circumstances, lateral line function could be complemented by the inner ear.


Neuronal prostaglandin endoperoxide synthase 2 responses to oxygen and glucose deprivation are mediated by mitogen-activated protein kinase ERK1/2.
Prostanoids in the central nervous system define an important linkage between blood pressure and hormonal responses to hypotension/ischemia. Prostaglandin endoperoxide synthase (PGHS)-2, the inducible isoform of this enzyme, is induced by cerebral hypoperfusion/ischemia. To investigate the mechanism of the PGHS-2 gene expression in response to cerebral hypoperfusion/ischemia in neurons, we used a cell culture model (human SK-N-AS cells) to mimic the oxygen and glucose deprivation (OGD) that usually results from ischemia. Whereas OGD stimulated robust increases in PGHS-2 mRNA abundance, neither oxygen nor glucose deprivation alone was effective. Our data demonstrated that induction of both PGHS-2 mRNA and protein reached peak levels ( approximately 10 fold) after 6 h OGD. This was partially blocked by the inhibition of mitogen-activated protein kinase (MAPK) p38, and was almost completely blocked by the inhibition of extracellular signal-related kinases 1/2 (ERK1/2 or p44/42), another MAPK. These results indicate that PGHS-2 gene expression is induced by oxygen and glucose deprivation synergistically in neurons, and this induction is mediated by one or more members of the MAPK family.


Endoscopic Transfontanellar Approach of a Cyst Anterior to the Brainstem Crossing the Foramen Magnum-Part II: Success of Multiple Fenestrations: Two-Dimensional Operative Video.
Premature infants with severe germinal matrix/intraventricular hemorrhage are at high risk of posthemorrhagic ventricular dilation and hydrocephalus (Video 1). We report a 4-month-old premature infant with grade III intraventricular hemorrhage and compartmentalized hydrocephalus with an unusual craniospinal cyst. The cyst extended anteriorly from the mesencephalon to the posterior wall of C6, causing severe compression of the brainstem and spinal cord. An endoscopic procedure was performed first to achieve a unique cranial fenestration, which is detailed in "Endoscopic Transfontanellar Approach of a Cyst Anterior to the Brainstem Crossing the Foramen Magnum-Part I: Failure of Unique Fenestration." One month later the clinical picture recurred. Magnetic resonance imaging revealed hydrocephalus and cyst recurrence. A second procedure with endoscopic fenestration and shunt revision was needed. The same right transfontanellar approach was chosen, using a straight 30° endoscope. The procedure and surgical technique are explained in a step-by-step fashion. Extreme care was taken to align the head and the cervical spine. This allowed access to the extreme caudal cyst membrane posterior to C6 to create multiple transfixing fenestrations of the cyst. At 18-month follow-up, the child demonstrated almost normal neurological and psychomotor development with no cyst recurrence or hydrocephalus. Our report underlines the importance of performing multiple fenestrations of such cysts. We believe that performing a transfixing fenestration through the cyst allows cerebrospinal fluid flow and prevents recurrence, as, for instance, has been shown for suprasellar arachnoid cysts.


Operative risk and preoperative hematocrit in bypass graft surgery: Role of gender and blood transfusion.
The association between lower preoperative hematocrit (Hct) and risk for morbidity/mortality after cardiac surgery is well established. We examined whether the impact of low preoperative Hct on outcome is modified by blood transfusion and operative risk in women and men undergoing nonemergent CABG surgery. Patients having nonemergent, first-time, isolated CABG were included (N=2757). Logistic regressions assessed effect of hematocrit on major perioperative morbidity/mortality separately by males (n=2232) and females (n=525). Mean age was 63.2±10.1years, preoperative hematocrit was 38.9±4.8%, and STS risk score was 1.3±1.8%. Blood transfusion was more likely in female patients (26% vs. 12%, P<0.001). Multivariate analyses revealed that lower body mass index and lower preoperative hematocrit predicted transfusion in males and females, whereas older age (OR=1.03, P=0.017) also predicted transfusion in females. Major morbidity was also more likely in female patients (12% vs. 7%, P<0.001). In multivariate analyses, blood transfusion was the only predictive factor for major morbidity in females (OR=4.56, P<0.001). In males, higher body mass index (OR=1.07, P<0.001), lower hematocrit (OR=0.94, P=0.017), interaction of STS score with hematocrit (OR=1.02, P=0.045), and blood transfusion (OR=9.22, P<0.001) were significant predictors for major morbidity. This study showed females were more likely to have blood transfusion and major morbidities after nonemergent CABG. Traditional factors that have been found to predict outcomes, such as hematocrit and STS risk, were related only to major morbidity in male patients. However, blood transfusion negatively impacted major outcome after nonemergent CABG surgery across all STS risk levels in both genders.


Anticonvulsant effects of stress: role of endogenous opioids.
Mice subjected to immobilization stress were protected against electrconvulsive shock-induced seizures in comparison to non-stressed mice. Pretreatment with naltrexone antagonized the effects of stress indicating that the protective effects of stress on seizures involved a release of endogenous opioids.


Dynamics of the systemic components of the chicken (Gallus gallus domesticus) immune system following activation by Escherichia coli; implications for the costs of immunity.
The immune response is thought to be costly and deters from growth and reproduction, but the magnitude and sources of these costs are unknown. Thus, we quantified the changes in mass of leukocytes (CD4(+) and CD8(+) T cells, Bu1(+) IgM(+) and Bu1(+) IgG(+) B cells, monocytes/macrophages, heterophils and thrombocytes) and protective plasma proteins in systemic (non-mucosal) components of adult chickens injected intravenously with dead Escherichia coli. During the first day after E. coli injection most types of blood leukocytes decreased and α-1-acid glycoprotein increased. Specific IgM, specific IgY, total IgM, Bu1(+) lymphocytes in the spleen and bone marrow and thymic CD8(+) lymphocytes increased at 5d post-injection. Quantitatively, the increases in the weight of cells and antibodies due to E. coli were dwarfed by the increase in the weight of the liver and acute phase proteins. Thus the acute phase response was markedly more costly than the subsequent adaptive response. The weight of the cells and proteins of the systemic immune system prior to challenge was 0.14% of body weight. Following E. coli injection, the additional weight of the immune components and the hypertrophy of the liver resulted in a 3.6-fold increase in weight which is equivalent to 18.5% of a large egg.


Fate, residues and dietary risk assessment of the fungicides epoxiconazole and pyraclostrobin in wheat in twelve different regions, China.
The fungicides epoxiconazole and pyraclostrobin have been widely used to control wheat fusarium head blight. This study was designed to investigate the dissipation behaviors in different climate regions and provide data for the modification of maximum residue limits of the two fungicides. Wheat samples were collected from field sites in twelve different regions, China and analyzed with an HPLC-MS/MS method for simultaneous detection of epoxiconazole and pyraclostrobin in wheat. The average recoveries of epoxiconazole and pyraclostrobin in wheat matrix were 87-112% and 85-102%, respectively, with the relative standard deviations ≤8.1%. The limits of quantification of epoxiconazole and pyraclostrobin in grain and straw were both 0.01 mg/kg. The dissipations of epoxiconazole and pyraclostrobin followed first-order kinetics, with the half-lives of 10.3 days and 7.6 days, respectively. The terminal residues of epoxiconazole and pyraclostrobin in grain were below 0.034 and 0.028 mg/kg, separately, both lower than the maximum residue limits recommended by China. Based on Chinese dietary pattern and terminal residue distributions, the risk quotients of epoxiconazole and pyraclostrobin were 13.9% and 65.9%, respectively, revealing the evaluated wheat exhibited an acceptably low dietary risk to consumers.


Exercise-induced ventricular tachycardia in a case with hypertrophic cardiomyopathy taking cibenzoline.
We report a 17-year-old woman with hypertrophic cardiomyopathy (HCM) successfully resuscitated from ventricular fibrillation while taking cibenzoline. During exercise-stress testing before implanting an implantable cardioverter-defibrillator, ventricular tachycardia was induced and thought to be a proarrhythmia due to the use-dependent effect of the Na channel blockade with cibenzoline. In patients with arrhythmogenic substrates such as HCM, it is critical to pay attention to the proarrhythmic effects of class I antiarrhythmic drugs while increasing heart rate.


Preparation and evaluation of samarium (III) phosphate [(153)Sm] colloid (SMPC) for possible therapeutic use.
A simple method of preparation of a new therapeutic colloid, samarium(III) phosphate-(153)Sm (SMPC), is reported involving the reaction of carrier-added (153)SmCl(3) with phosphoric acid. Recovery of the colloid was accomplished by dialysis leading to purification and a radiochemical (RC) yield of more than 90%. The RC purity of purified colloid formulated in isotonic phosphate buffer was more than 99% as assessed by paper chromatography. The product retained its RC purity throughout the period of stability study of 7 days. Complete retention of radioactivity instilled in the rabbit knee joint was observed over the study period of 6 days, with radioactivity in the blood being indistinguishable from the natural background activity. Ninety-six percent of colloidal particles were in the size range of 0.3-2 microm. The promising results demonstrated warrant further studies on SMPC for assessing the suitability for therapy.


The Pfizer Crystal Structure Database: An essential tool for structure-based design at Pfizer.
Pfizer's Crystal Structure Database (CSDB) is a key enabling technology that allows scientists on structure-based projects rapid access to Pfizer's vast library of in-house crystal structures, as well as a significant number of structures imported from the Protein Data Bank. In addition to capturing basic information such as the asymmetric unit coordinates, reflection data, and the like, CSDB employs a variety of automated methods to first ensure a standard level of annotations and error checking, and then to add significant value for design teams by processing the structures through a sequence of algorithms that prepares the structures for use in modeling. The structures are made available, both as the original asymmetric unit as submitted, as well as the final prepared structures, through REST-based web services that are consumed by several client desktop applications. The structures can be searched by keyword, sequence, submission date, ligand substructure and similarity search, and other common queries.


Strain-based fatigue data for Ti-6Al-4V ELI under fully-reversed and mean strain loads.
This article presents the experimental data supporting the study to obtain the mean strain/stress effects on the fatigue behavior of Ti-6Al-4V ELI. A series of strain-controlled fatigue experiments on Ti-6Al-4V ELI were performed at four strain ratios (-1, -0.5, 0, and 0.5). Two types of data are included for each specimen. These are the hysteresis stress-strain responses for the cycle in a log10 increment, and the maximum and minimum stress-strain responses for each cycle. Fatigue lives are also reported for all the experiments.


Different subtypes of tachykinin NK(1) receptor binding sites are present in the rat brain.
(2-[(125)I]iodohistidyl(1))Neurokinin A ([(125)I]NKA), which labels "septide-sensitive" but not classic NK(1) binding sites in peripheral tissues, was used to determine whether septide-sensitive binding sites are also present in the rat brain. Binding studies were performed in the presence of SR 48968 (NK(2) antagonist) and senktide (NK(3) agonist) because [(125)I]NKA also labels peripheral NK(2) binding sites and, as shown in this study, central NK(3) binding sites. [(125)I]NKA was found to label not only septide-sensitive binding sites but also a new subtype of NK(1) binding site distinct from classic NK(1) binding sites. Both subtypes of [(125)I]NKA binding sites were sensitive to tachykinin NK(1) antagonists and agonists but also to the endogenous tachykinins NKA, neuropeptide K (NPK), and neuropeptide gamma (NPgamma). However, compounds of the septide family such as substance P(6-11) [SP(6-11)] and propionyl-[Met(O(2))(11)]SP(7-11) and some NK(1) antagonists, GR 82334, RP 67580, and CP 96345, had a much lower affinity for the new NK(1)-sensitive sites than for the septide-sensitive sites. The hypothalamus and colliculi possess only this new subtype of NK(1) site, whereas both types of [(125)I]NKA binding sites were found in the amygdala and some other brain structures. These results not only explain the central effects of septide or SP(6-11), but also those of NKA, NPK, and NPgamma, which can be selectively blocked by NK(1) receptor antagonists.


Evaluation of ion release from two base-metal alloys at various pH levels.
We examined the influence of salivary pH on the corrosion of two base-metal alloys. Cobalt-chromium (Co-Cr) and nickel-chromium (Ni-Cr) alloy samples were created and submerged in artificial saliva of different pH values (pH 4, pH 5 and pH 7). The amount of each ion present in solution 1 month later was measured by flame atomic absorption spectrophotometry. Statistical analysis showed that pH significantly affected total and Co ion release, but not Ni or Cr ion release. The alloy type did not affect total ion release, but was significant for Cr ion release. Alloy-pH interaction significantly affected Cr and total ion release. To prevent metal particle release, the alloys used for dental restoration should, whenever possible, be made from noble metals and corrosion-resistant alloys.