An online growth mindset intervention in a sample of rural adolescent girls.
Students living in rural areas of the United States exhibit lower levels of educational attainment than their suburban counterparts. Innovative interventions are needed to close this educational achievement gap. We investigated whether an online growth mindset intervention could be leveraged to promote academic outcomes. We tested the mindset intervention in a sample of 222 10th-grade adolescent girls (M age = 15.2; 38% White, 25% Black, 29% Hispanic) from four rural, low-income high schools in the Southeastern United States. We conducted a randomized controlled trial to test the efficacy of the growth mindset intervention, relative to a sexual health programme. We used random sampling and allocation procedures to assign girls to either the mindset intervention (n = 115) or an attention-matched control programme (n = 107). We assessed participants at pre-test, immediate post-test, and 4-month follow-up. Relative to the control condition, students assigned to the mindset intervention reported stronger growth mindsets at immediate post-test and 4-month follow-up. Although the intervention did not have a total effect on academic attitudes or grades, it indirectly increased motivation to learn, learning efficacy and grades via the shifts in growth mindsets. Results indicate that this intervention is a promising method to encourage growth mindsets in rural adolescent girls.


[The roles of RNA silencing in plant biotic stress].
RNA silencing is a common strategy shared by eukaryotic organisms to regulate gene expression, and also can operate as a defense mechanism against biotic stress. In plants, small RNAs play an important role in defensing against viruses, bacteria or herbivore attack, such as miRNAs and siRNAs. As a response to this defense system, both viruses and bacteria have evolved viral suppressors of RNA silencing (VSRs) or bacterial suppressors of RNA silencing (BSRs) to overcome the host silencing response, which can act at various steps of the different silencing pathways. This review highlights the current understanding and the new insights concerning of the roles of small RNAs in defensing against biotic stress and the mechanism of VSRs and BSRs in suppressing host RNA silencing in plants.


Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C.
To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus (HCV). One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin (800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed. Eighty-two patients (35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response (RVR): while the figures were 74.1% for early virologic response (EVR) and 44.4% for sustained virologic response (SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events (SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication. Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.


Dynamic and accurate assessment of acetaminophen-induced hepatotoxicity by integrated photoacoustic imaging and mechanistic biomarkers in vivo.
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention. Perturbation of liver function and cellular viability was assessed in C57BL/6J male mice by Indocyanine green (ICG) clearance (Multispectral Optoacoustic Tomography (MSOT)) and by measurement of mechanistic (miR-122, HMGB1) and established (ALT, bilirubin) circulating biomarkers in response to the acetaminophen and its treatment with acetylcysteine (NAC) in vivo. We utilised a 60% partial hepatectomy model as a situation of defined hepatic functional mass loss to compared acetaminophen-induced changes to. Integration of these mechanistic markers correlated with histological features of APAP hepatotoxicity in a time-dependent manner. They accurately reflected the onset and recovery from hepatotoxicity compared to traditional biomarkers and also reported the efficacy of NAC with high sensitivity. ICG clearance kinetics correlated with histological scores for acute liver damage for APAP (i.e. 3h timepoint; r=0.90, P<0.0001) and elevations in both of the mechanistic biomarkers, miR-122 (e.g. 6h timepoint; r=0.70, P=0.005) and HMGB1 (e.g. 6h timepoint; r=0.56, P=0.04). For the first time we report the utility of this non-invasive longitudinal imaging approach to provide direct visualisation of the liver function coupled with mechanistic biomarkers, in the same animal, allowing the investigation of the toxicological and pharmacological aspects of APAP-ILI and hepatic regeneration.


Post-ERCP Pancreatitis: Risk factors and role of NSAIDs in primary prophylaxis.
To determine efficacy of diclofenac suppository in reducing post-ERCP pancreatitis (PEP) and identify risk factors for PEP. This is a placebo-based prospective study at Department of Medicine & Gastroenterology, Services Institute of Medical Sciences / Services Hospital, Lahore performed from January 2018 to June 2019. Patients were randomized to receive diclofenac suppository or glycerine suppository before ERCP. Both groups were compared for PEP using chi square x2 test while risk factors for PEP were determined using binary logistic regression. Total of 165 patients with mean age 49.1(±15.2) and male to female ratio 1/1.6 (63/102) were included. Among 82 (49.7%) patients in diclofenac group, 8 (9.7%) developed pancreatitis while 19(22.9%) of 83(50.3%) in placebo group had PEP (p value 0.02). After multivariate analysis, age>45 years (p value 0.014, OR 3.2), Bilirubin >3 mg/dl (p value 0.004 OR 3.58), time to cannulation> 5 minutes (p value<0.000 OR 9.2), use of precut (p value< 0.000 OR 4.9), pancreatic duct cannulation (p value 0.000 OR 5.46) and total procedure time >30 minutes (p value 0.01 OR 3.92) were risk factors for PEP. Pre-procedure Diclofenac suppository reduces post-ERCP pancreatitis. Age > 45 years, serum bilirubin > 3 mg/dl, cannulation time > 5 minutes, use of precut, pancreatic duct cannulation and procedure time > 30 minutes are risk factors for post-ERCP pancreatitis.


Genetic engineering of avian pathogenic E. coli to study the functions of FimH adhesin.
Adhesion of pathogen to host cells is an important prerequisite for successful colonization and establishment of the pathogenesis. The aim of this study is to examine the function of FimH adhesin in the adherence of avian pathogenic E. coli to porcine intestinal epithelial cell lines (IPEC-J2) and human lung epithelial cell line (A549) in an in vitro infection model. Three strains of avian pathogenic Escherichia coli (APEC) and one strain of non-pathogenic E coli were used. The isogenic FimH mutants were constructed by lambda Red-mediated recombination system. The wild types and mutants strains were adhered to the host cells with different adherence patterns in certain incubation time. The results demonstrated that the adherence of the isogenic FimH mutants to the porcine intestinal epithelial cells (IPEC-J2) were similar to those of wild types. However, the adherences of isogenic FimH mutants to human lung epithelial cells (A549) were significantly different from the wild types. A549 cell can be used as a type of cell model for colonization of the chicken extraintestinal. FimH offers a unique opportunity to investigate the role of the strength of adhesion independently from the many other factors that may affect surface colonization.


Role of uncoupled endothelial nitric oxide synthase in abdominal aortic aneurysm formation: treatment with folic acid.
It has been shown that endothelial NO synthase (eNOS) uncoupling occurs in hypertension and atherosclerosis. However, its causal role in vascular pathogenesis has not been characterized previously. Here, we challenged eNOS preuncoupled hyperphenylalaninemia (hph)-1 mice (deficient in eNOS cofactor tetrahydrobiopterin biosynthetic enzyme GTPCHI) with angiotensin II (Ang II; 0.7 mg/kg per day, 14 days). Both wild-type and hph-1 groups developed hypertension similarly up to day 6 to 7. Thereafter, ≈14% of Ang II-infused (0.7 mg/kg per day) hph-1 mice (n=72) started to die suddenly of ruptured abdominal aortic aneurysm (AAA). Among the survivors, 65% developed AAA, resulting in a total morbidity rate of 79%. In contrast, none of the Ang II-infused wild-type mice died or developed AAA. Ang II progressively deteriorated eNOS uncoupling in hph-1 mice while augmenting tetrahydrobiopterin and nitric oxide (NO(·)) deficiencies. The abundance of the tetrahydrobiopterin salvage enzyme dihydrofolate reductase in the endothelium was decreased in hph-1 mice and further diminished by Ang II infusion. Intriguingly, restoration of dihydrofolate reductase expression by oral administration of folic acid or overexpression of dihydrofolate reductase completely prevented AAA formation in Ang II-infused hph-1 mice while attenuating progressive uncoupling of eNOS. Folic acid also attenuated vascular remodeling and inflammation characterized by medial elastin breakdown and augmented matrix metalloproteinase 2 activity and activation of matrix metalloproteinase 9, as well as macrophage infiltration. In conclusion, these data innovatively suggest a causal role of eNOS uncoupling/tetrahydrobiopterin deficiency in AAA formation. Therefore, oral folic acid administration, endothelium-targeted dihydrofolate reductase gene therapy, and perhaps other countermeasures directed against eNOS uncoupling could be used as new therapeutics for AAA.


Isolation, culture optimization and physico-chemical characterization of laccase enzyme from Pleurotus fossulatus.
Pleurotus fossulatus (Cooke) Sace is member of oyster mushroom can produced extracellular laccase (benzenediol: oxygen oxidoreductase; EC 22.214.171.124) in submerged fermentation. To analyze the optimum production for laccase P. fossulatus was cultured both in stationary and shaking condition in different media. Partial purification of laccase was done after 0-80% ammonium sulphate precipitation, followed by DEAE (Diethylaminoethyl) Sephadex (A-50) anion exchange chromatography. Potato-sucrose peptone (PSP) medium and Potato-dextrose (PD) medium showed highest laccase production in shaking and stationary conditions, respectively. Though the time required for optimum laccase production in stationary condition was much more than the shaking condition but the amount of laccase was about 2.75t greater in former condition. The laccase produced in stationary condition was more stable than the enzyme produced in shaking condition. The partially purified enzyme showed highest affinity towards o-dianisidine than guaiacol and ABTS (2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) as evidenced by their K(m). The physico-chemical properties of the laccase suggested the significance of this enzyme in industrial applications.


Deep vein thrombosis and serum D-dimer after pelvic lymphadenectomy in gynecological cancer.
Venous thromboembolism prevention during the perioperative period requires comprehensive risk-level assessment. The aim of this study was to evaluate the incidence of deep vein thrombosis and to assess the cut-off levels of serum D-dimer as a screening strategy for deep vein thrombosis during the perioperative period. A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were enrolled. We retrospectively analyzed the data on the cut-off value of D-dimer assessed using area under the receiver operating characteristic curve preoperatively, and 2 or 3 months, postoperatively. All patients underwent leg vein ultrasonography regardless of the serum D-dimer level. Furthermore, CT scans were performed to evaluate both disease status and venous thromboembolism, including pulmonary thromboembolism. Statistical analyzes were performed using the Mann-Whitney U-test (D-dimer values of each cancer), Chi-square test, Fisher's exact test (incidence of deep vein thrombosis), and one-way analysis of variance (patient characteristics). A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were included in the analysis. Deep vein thrombosis rates were significantly higher in patients with ovarian cancer (P<0.001). The postoperative D-dimer value was significantly higher than the preoperative value. Postoperative D-dimer values were also significantly higher in patients who received adjuvant chemotherapy (P=0.001). The cut-off value of D-dimer was 1.55 µg/mL preoperatively (sensitivity, 48.0%; specificity, 94.1%), and this value was higher postoperatively, at 1.95 µg/mL (sensitivity, 37.0%; specificity, 90.9%). Postoperative D-dimer values are higher not only after surgery but also in patients who received adjuvant chemotherapy. The cut-off value of D-dimer at 2 or 3 months postoperatively was higher than preoperative value.


Nucleotide sequence of streptococcal pyrogenic exotoxin type C.
The nucleotide sequence of the gene speC, encoding streptococcal pyrogenic exotoxin type C (SPE C), was determined. The gene encoded a mature protein of 208 amino acids, with a calculated molecular weight of 24,354. The mature amino acid sequence of SPE C was analyzed for homology with the amino acid sequences of streptococcal pyrogenic exotoxin type A, the staphylococcal enterotoxins, and toxic shock syndrome toxin-1. Of these, SPE C shared the greatest amount of homology with streptococcal exotoxin type A.


A Cuff Lead for Delivering Ionic Direct Current (iDC) to Block Neural Activities of Sciatic Nerve.
Direct current (DC) applied extracellularly can block action potential (AP) propagation in a neuron. This suppression paradigm has been proposed as a possible treatment for blocking nociceptive pain. However, the application of DC is limited in duration due to the charge injection constraint imposed by the evolution of electrochemical reactions at the metal electrode. To prolong the application of DC, a microfluidic lead filled with conductive electrolyte can be used to separate the metal electrode from the target nerve. Here, we describe a tripolar nerve cuff lead fabricated with biocompatible silicone to block the APs in the rat sciatic nerve. This lead has a self-curling silicone membrane to wrap around sciatic nerve for secured mechanical attachment and electrical isolation between the nerve and the surrounding muscle. In-vivo testing showed that delivering 1.4mA DC via the cuff lead blocked the nerve activity and reduced the evoked compound action potential (eCAP) to 30% of its unblocked response.


Amino acids for amyotrophic lateral sclerosis / motor neuron disease.
Amyotrophic lateral sclerosis, also known as motor neuron disease, is a progressive neuromuscular disease that causes disability and eventual death. Various amino acid preparations, the three branched-chain amino acids (L-leucine, L-valine and L-isoleucine) or, alternatively, L-threonine have been used as experimental therapy. To examine the efficacy of amino acid therapies in prolonging survival and/or slowing the progression of amyotrophic lateral sclerosis/motor neuron disease. We searched the Cochrane Neuromuscular Disease Group trials register (searched February 2003), MEDLINE (from January 1966 to December 2002) and EMBASE (from January 1980 to December 2002) databases and reports of specialist conferences. Authors of known studies were contacted. We included randomised or quasi-randomised trials of participants with a clinical diagnosis of amyotrophic lateral sclerosis/motor neuron disease treated with all combinations of amino acids. Our primary outcome measure was survival determined by a pooled hazard ratio of all studies. Our secondary outcome measures were (in order of priority): survival at six and 12 months, muscle strength, any validated rating scale of physical function, quality of life, proportion of patients completing therapy and proportion of patients reporting adverse events attributable to treatment. We identified six eligible trials and rejected a further seven because of incomplete data or inadequate duration. Eligible studies were rated for methodological quality and missing data sought from the authors. After this examination two studies were excluded from analysis. Our pooled survival analysis was performed by the Parmar method, other statistical calculations were done using the Review Manager 4.2 software package. No benefit could be demonstrated for either branched-chain amino acids or L-threonine in improving survival in amyotrophic lateral sclerosis/motor neuron disease. Neither could we find evidence of an effect of either treatment on muscle strength or disability as measured by functional rating scales. No study assessed quality of life. Both branched-chain amino acids and L-threonine appeared well tolerated and caused a degree of adverse events comparable to that of the control medication. There is no evidence to support a beneficial effect of either branched-chain amino acids or L-threonine in amyotrophic lateral sclerosis/motor neuron disease.


Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial.
To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. Double-blind placebo-controlled intervention study. Outpatient clinic. A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.


Adult acute non-lymphoblastic leukaemia: reliability and prognostic significance of pretreatment bone marrow S-phase size determined by flow cytofluorometry.
46 adult patients with non-lymphoblastic acute leukaemia (AnLL) had pretreatment proliferative activity of bone marrow (BM) blasts determined simultaneously with propidium iodide DNA flow cytofluorometry (as the percentage of cells with DNA content intermediate between the diploid and the tetraploid values, 2n-4n cell %) and in vitro tritiated thymidine cytoautoradiography (as the labelling index, LI). They were then treated with the same chemotherapy regimen, including 2-3 courses of sequential vincristine, arabinosylcytosine and adriamycin, for response induction, and monthly courses of different cytostatics for maintenance. Median 2n-4n cell % was 9.9 and median LI was 5.9. A close linear relationship (r = 0.913, p less than 0.001) between the two parameters was found. Patients having a 2n-4n cell % greater than 15.6 responded more often to chemotherapy than patients having a lower percentage (p less than 0.05) but also experienced a shorter duration of first response (p less than 0.05). Overall survival was longer in patients with 2n-4n cell % greater than 15.6 (p less than 0.02). Multiple regression analysis indicates that 2n-4n cell % is a statistically significant (p less than 0.05) independent factor correlating with duration of response in adult AnLL.


Probing the oligomeric assemblies of pea porphobilinogen synthase by analytical ultracentrifugation.
The enzyme porphobilinogen synthase (PBGS) can exist in different nonadditive homooligomeric assemblies, and under appropriate conditions, the distribution of these assemblies can respond to ligands such as metals or substrate. PBGS from most organisms was believed to be octameric until work on a rare allele of human PBGS revealed an alternate hexameric assembly, which is also available to the wild-type enzyme at elevated pH [Breinig, S., et al. (2003) Nat. Struct. Biol. 10, 757-763]. Herein, we establish that the distribution of pea PBGS quaternary structures also contains octamers and hexamers, using both sedimentation velocity and sedimentation equilibrium experiments. We report results in which the octamer dominates under purification conditions and discuss conditions that influence the octamer:hexamer ratio. As predicted by PBGS crystal structures from related organisms, in the absence of magnesium, the octameric assembly is significantly destabilized, and the oligomeric distribution is dominated largely by the hexameric assembly. Although the PBGS hexamer-to-octamer oligomeric rearrangement is well documented under some conditions, both assemblies are very stable (under AU conditions) in the time frame of our ultracentrifuge experiments.


Relational aspects of identity: late adolescents' perceptions of their relationships with parents.
This study examines the relationship between late adolescents' identity status and their memories of their relationships to their parents. One hundred male and female undergraduates completed two questionnaires. The first assessed subjects' retrospective perceptions of their affective relationships with parents across five age periods: 1 to 5 years, 5 to 10 years, 10 to 15 years, 15 to 20 years, and the present. The second questionnaire, the Extended Objective Measure of Ego Identity Status, assessed subjects' current identity status. Trend analyses revealed: (1) a significant quadratic trend in identity committed subjects' ratings of the amount of love they felt for mother across the five age periods, and (2) a significant linear trend of increasing love from mother. In contrast, uncommitted subjects showed significant linear trends of decreasing love both for and from their mothers. Results are interpreted as evidence of the importance of resolution of identity issues to the establishment of feelings of intimacy between late adolescents and their parents.


Affinity interactions between phenylboronic acid-carrying self-assembled monolayers and flavin adenine dinucleotide or horseradish peroxidase.
A method is provided for the recognition of glycated molecules based on their binding affinities to boronate-carrying monolayers. The affinity interaction of flavin adenine dinucleotide (FAD) and horseradish peroxidase (HRP) with phenylboronic acid monolayers on gold was investigated by using voltammetric and microgravimetric methods. Conjugates of 3-aminophenylboronic acid and 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) or 11-mercaptoundecanoic acid were prepared and self-assembled on gold surfaces to generate monolayers. FAD is bound to this modified surface and recognized by a pair of redox peaks with a formal potential of -0.433 V in a 0.1 M phosphate buffer solution, pH 6.5. Upon addition of a sugar to the buffer, the bound FAD could be replaced, indicating that the binding is reversible. Voltammetric, mass measurements, and photometric activity assays show that the HRP can also be bound to the interface. This binding is reversible, and HRP can be replaced by sorbitol or removed in acidic solution. The effects of pH, incubation time, and concentration of H(2)O(2) were studied by comparing the catalytic reduction of H(2)O(2) in the presence of the electron-donor thionine. The catalytic current of the HRP-loaded electrode was proportional to HRP concentrations in the incubation solution in the range between 5 microg mL(-1) and 0.1 mg mL(-1) with a linear slope of 3.34 microA mL mg(-1) and a correlation coefficient of 0.9945.


Factors associated with infant death after apparent life-threatening event (ALTE).
To detect factors associated with greater risk of death in infants after an apparent life-threatening event (ALTE). This cross-sectional, retrospective, descriptive and analytic study evaluated infants younger than 12 months who had a sudden event of cyanosis, pallor, hypotonia or apnea and were seen in the emergency department of a tertiary university hospital. Forward stepwise logistic regression (Wald) was used to calculate and adjust odds ratios to evaluate associations. Mean age of the 145 patients included in the study was 105 days (median = 65 days). Eleven (7.6%) died, and their mean age was 189 days (median = 218 days). Mean age of survivors was 98 days (median = 62 days) (p = 0.003). Activity before the event, prematurity and number of events were not associated with death. A significant association was found with pallor. Of the 11 infants, 3 had spontaneous resolution of ALTE, whereas 8 patients [27.6%; p < 0.001; OR = 14.3 (95%CI 3.51-58.3)] did not. The associations with respiratory or cardiovascular disease were also significant. In multivariate analysis, immediate spontaneous resolution [p = 0.015; OR = 6.06 (95%CI 1.02-35.94)] and diagnosis of cardiovascular disease [p = 0.047; OR = 164.27 (95%CI 7.34-3.673.78)] remained statistically significant. Infants who experienced an ALTE had a higher risk of subsequent death when their age was greater than 6 months and the event had a long duration, particularly when ALTE was associated with cardiovascular disease.


Management of perianal fistulae in five dogs using azathioprine and metronidazole prior to surgery.
To evaluate combination therapy with azathioprine and metronidazole in German Shepherd Dogs with perianal fistulae. Prospective study. Five dogs (31.5 to 36.0 kg) with perianal fistulae were treated with azathioprine (50 mg per dog orally every 24 h) and metronidazole (400 mg per dog orally every 24 h). Patients were re-evaluated at 2 week intervals by inspection, palpation, photographs of the perineal region and assessment of white blood cell counts where possible. Treatment was continued until improvement in lesions reached a plateau. Surgical excision of residual fistulae and anal sac remnants was then performed, with medical therapy continued for an additional 3 to 6 weeks. Signs attributable to anal irritation were reduced or eliminated in all dogs within 2 weeks, although visible healing of lesions progressed more slowly. Ulcerated lesions reduced in surface area and depth, and some fistulae healed completely. Non-healing areas were usually associated with anal sac rupture or chronic fibrosis. Visible improvement typically reached a plateau 4 to 6 weeks after commencing treatment. Immunosuppressive therapy continued for 5 to 24 weeks before surgical intervention to remove anal sacs (four dogs) and/or residual fistulae (five dogs). All dogs remain disease free 7 to 10 months postoperatively. No important complications of treatment were encountered. Azathioprine with metronidazole effectively reduced perianal irritation, and the severity and extent of lesions prior to surgery. Treatment was economical even in large dogs and associated with few untoward sequelae. The combined use of immunosuppressive and antimicrobial therapy followed by surgery minimised potential morbidity associated with aggressive use of either medical of surgical treatment alone.


In-plasma analysis of plasma-surface interactions.
During deposition, modification, and etching of thin films and nanomaterials in reactive plasmas, many active species can interact with the sample simultaneously. This includes reactive neutrals formed by fragmentation of the feed gas, positive ions, and electrons generated by electron-impact ionization of the feed gas and fragments, excited states (in particular, long-lived metastable species), and photons produced by spontaneous de-excitation of excited atoms and molecules. Notably, some of these species can be transiently present during the different phases of plasma processing, such as etching of thin layer deposition. To monitor plasma-surface interactions during materials processing, a new system combining beams of neutral atoms, positive ions, UV photons, and a magnetron plasma source has been developed. This system is equipped with a unique ensemble of in-plasma surface characterization tools, including (1) a Rutherford Backscattering Spectrometer (RBS), (2) an Elastic Recoil Detector (ERD), and (3) a Raman spectroscopy system. RBS and ERD analyses are carried out using a differentially pumped 1.7 MV ion beam line Tandetron accelerator generating a beam at grazing incidence. The ERD system is equipped with an absorber and is specifically used to detect H initially bonded to the surface; higher resolution of surface H is also available through nuclear reaction analysis. In parallel, an optical port facing the substrate is used to perform Raman spectroscopy analysis of the samples during plasma processing. This system enables fast monitoring of a few Raman peaks over nine points scattered on a 1.6 × 1.6 mm2 surface without interference from the inherent light emitted by the plasma. Coupled to the various plasma and beam sources, the unique set of in-plasma surface characterization tools detailed in this study can provide unique time-resolved information on the modification induced by plasma. By using the ion beam analysis capability, the atomic concentrations of various elements in the near-surface (e.g., stoichiometry and impurity content) can be monitored in real-time during plasma deposition or etching. On the other hand, the evolution of Raman peaks as a function of plasma processing time can contribute to a better understanding of the role of low-energy ions in defect generation in irradiation-sensitive materials, such as monolayer graphene.


Celiac disease and bone fractures: a systematic review and meta-analysis.
Celiac disease, an autoimmune disease induced by dietary gluten, is associated with metabolic bone disorders, such as low bone mineral density. However, it is unclear whether this translates into an association between celiac disease and such hard clinical outcomes as bone fractures. To systematically review and pool the evidence for the relationship of celiac disease with prevalence and incidence of bone fractures. We systematically searched Pubmed, Scopus, Web of Science, and Cochrane Library in January 2014 for studies of celiac disease and bone fractures. Observational studies of any design, in which bone fracture outcomes were compared in individuals with and without celiac disease were included. Two investigators independently extracted results from eligible studies. In the meta-analyses of case-control and cross-sectional studies, bone fractures were almost twice as common in individuals with a clinically diagnosed celiac disease as in those without the disease. In the meta-analyses of prospective studies, celiac disease at baseline was associated with a 30% increase (95% confidence interval [CI]: 1.14, 1.50) in the risk of any fracture and a 69% increase in the risk of hip fracture (95% CI: 1.10, 2.59). The two studies of unrecognized celiac disease (elevated circulating concentrations of celiac disease-specific autoantibodies but no celiac disease diagnosis) had contradicting findings. Our findings suggest that clinically diagnosed celiac disease and bone fractures co-occur and that celiac disease was associated with an increased risk of hip fractures as well as fractures in general. Further research would be needed to determine whether unrecognized celiac disease is associated with the risk of bone fractures.


Primary cultures of embryonic chick lens cells as a model system to study lens gap junctions and fiber cell differentiation.
A major limitation in lens gap junction research has been the lack of experimentally tractable ex vivo systems to study the formation and regulation of fiber-type gap junctions. Although immortalized lens-derived cell lines are amenable to both gene transfection and siRNA-mediated knockdown, to our knowledge none are capable of undergoing appreciable epithelial-to-fiber differentiation. Lens central epithelial explants have the converse limitation. A key advance in the field was the development of a primary embryonic chick lens cell culture system by Drs. Sue Menko and Ross Johnson. Unlike central epithelial explants, these cultures also include cells from the peripheral (preequatorial and equatorial) epithelium, which is the most physiologically relevant population for the study of fiber-type gap junction formation. We have modified the Menko/Johnson system and refer to our cultures as dissociated cell-derived monolayer cultures (DCDMLs). We culture DCDMLs without serum to mimic the avascular lens environment and on laminin, the major matrix component of the lens capsule. Here, I review the features of the DCDML system and how we have used it to study lens gap junctions and fiber cell differentiation. Our results demonstrate the power of DCDMLs to generate new findings germane to the mammalian lens and how these cultures can be exploited to conduct experiments that would be impossible, prohibitively expensive and/or difficult to interpret using transgenic animals in vivo.


EGFR-PKM2 signaling promotes the metastatic potential of nasopharyngeal carcinoma through induction of FOSL1 and ANTXR2.
Nasopharyngeal carcinoma (NPC) is notorious for its aggressiveness and high metastatic potential. NPC patients with distant metastasis have a particularly poor prognosis; however, evaluating metastatic potential by expression profiles of primary tumors is challenging. This study aimed to investigate the association between activation of epidermal growth factor receptor (EGFR) signaling and NPC metastasis and the underlying mechanisms. We found an association between EGFR protein overexpression and intense EGFR immunostaining in NPC samples with advanced tumor node metastasis stage, clinical stage, and distant metastasis in NPC patients. Exogenous EGF stimulates NPC mobility and invasiveness in vitro. Activation of EGFR signaling prompted PKM2 translocation to the nucleus. Silencing either EGFR or PKM2 attenuates NPC cell aggressiveness in vitro and in vivo. Blocking EGFR signaling with cetuximab suppressed NPC cell invasiveness in vitro and metastatic potential in vivo. Comprehensive analyses of transcriptome profiles indicated that the EGFR-PKM2 axis activates a number of novel metastasis promoters, including F3, FOSL1, EPHA2, ANTXR2, and AKR1C2. Finally, we found that the metastasis-promoting function of the EGFR-PKM2 axis is dependent on nuclear PKM2 regulation of the transcription of metastasis-related genes, including FOSL1 and ANTXR2. Our study indicates that EGFR-PKM2 signaling promotes NPC cell invasion and metastasis through induction of FOSL1 and ANTXR2 and identifies EGFR as a promising biomarker for predicting the risk of distant metastasis.


Changes in Behavior Management and Treatment Modalities in Pediatric Dentistry during COVID-19 Pandemic.
This study aims to assess the knowledge and confidence of dentists related to behavior management with extra personal protective equipment (PPE), non-aerosol-generating dental procedures in the course of the coronavirus disease-2019 (COVID-19) pandemic. A cross-sectional online survey was conducted among a sample of dentists who worked in Jordan and India in June 2020 during the COVID-19 pandemic. This study included a total of 177 dentists in Jordan and India that were practicing during the early months of the pandemic. Most dentists were seeing <6 patients per day. The most common emergency treatments during the pandemic by Jordanian dentists were abscesses (51.8%) and cellulitis (44.6%) vs (44.6%) abscesses and (35.5%) pulpitis in India. There was a high adoption of all elements of the PPE protocol. Most participants never or rarely used N2O sedation to manage their patients in Jordan and India (80.4 and 71.1%), respectively. Participants in Jordan and India that considered treatment non-aerosol-generating procedures (non-AGP) were (82.1 vs 97.5%, p = 0.000), respectively. Most of the surveyed dentists believe the extra PPE acts as a barrier to patient communication and child behavior management and would consider modifying the PPE to be more child-friendly. Most dentists consider non-AGP procedures and silver diamine fluoride (SDF) to be practical ways to practice safer dentistry, yet more training and information is needed for dentists treating children to provide a more confident safe environment for both dentists and their patients. Alsaleh MM, Sabbarini JM, Al-Batayneh OB, et al. Changes in Behavior Management and Treatment Modalities in Pediatric Dentistry during COVID-19 Pandemic. Int J Clin Pediatr Dent 2020;13(S-1):S125-S131.


Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls.
Pain threshold was measured using a pressure algometer in 126 subjects, of whom 54 were females and 72 males. These subjects included 18 males and 18 females with rheumatoid arthritis, 18 males and 18 females with osteoarthritis, 18 males with ankylosing spondylitis, and 18 male and 18 female healthy control volunteers. Six points were studied on each side of the body: 2 cm above the eyebrow on the forehead, lateral aspect of the arm at the insertion of the deltoid muscle, midpoint of the ulna, hypothenar eminence in the palm, midpoint of the quadriceps muscle, and midpoint of the antero-medial aspect of the tibia. None of these points corresponded to the "trigger" points in fibromyalgia. The pain threshold was statistically significantly higher in patients with ankylosing spondylitis than in patients with osteoarthritis, and these in turn were statistically higher than in the normal subjects. Patients with rheumatoid arthritis had significantly lower pain thresholds than the normal subjects. No laterality in pain threshold was identified, but females had in general a lower pain threshold.


In vitro and in vivo 2',5'-oligoadenylate synthetase activity induced by recombinant DNA-derived bovine interferon alpha I1 in bovine alveolar macrophages and blood mononuclear cells.
Biological responses to recombinant DNA-derived bovine interferon alpha (rBoIFN-alpha I1) by bovine alveolar macrophages were examined by measuring viral yield reduction and 2',5'-oligoadenylate synthetase (2',5'-OAS) production by IFN-treated cells. In vitro IFN pretreatment of alveolar macrophages reduced viral yield in cultures challenged exposed with parainfluenza-3 virus, compared with control cultures. In vitro treatment of alveolar macrophages with IFN also resulted in increased 2',5'-OAS activity. The 2',5'-OAS activity was measured in alveolar macrophages and blood mononuclear leukocytes of calves injected IM with 3.6 x 10(6) U of rBoIFN-alpha I1/kg of body weight. The IFN action was monitored by measuring 2',5'-OAS activity of blood mononuclear leukocytes beginning 6 days before and ending 24 hours after IFN treatment. The 2',5'-OAS activity in the blood mononuclear leukocytes sharply increased 24 hours after IFN treatment, indicating response to IFN. The alveolar macrophages collected from the same calves 24 hours after IFN administration also had increased 2',5'-OAS activity, compared with alveolar macrophages from the same calves collected 6 days before treatment. Increased 2',5'-OAS activity indicates: a possible mechanism of IFN action in cattle that may be responsible for viral yield reduction; potential use of high enzyme activity as a marker for IFN induction; and potential use of 2',5'-OAS activity as a marker for determining effects of IFN on bovine macrophages and other cells of the bovine immune system.


Cooperative gene regulation by microRNA pairs and their identification using a computational workflow.
MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/.


An unusual cause of gastric outlet obstruction during percutaneous endogastric feeding: a case report.
The differential diagnoses of acute abdomen in children include common and rare pathologies. Within this list, different types of bezoars causing gastrointestinal obstruction have been reported in the literature and different methods of management have been described. The aim of this article is to highlight a rare presentation of lactobezoars following prolonged percutaneous endoscopic gastrostomy feeding and its successful surgical management. A 16-year-old boy was admitted to a paediatric ward with abdominal distension and high output from his permanent gastrostomy feeding tube, with drainage of bilious fluids. The clinical, radiological and endoscopical examinations were suggestive of partial duodenal obstruction with multiple bezoars in the stomach and duodenum. Gastrojejunostomy was performed after the removal of 14 bezoars. The child had an uneventful postoperative course and was discharged on the sixth postoperative day in a stable condition. Lactobezoars should be included in the differential diagnosis of acute abdominal pain in patients with percutaneous endogastric feeding. Endoscopy is important in making the diagnosis of this surgical condition of the upper gastrointestinal tract in a child.


Women prisoners and HIV/AIDS.
In the last decade, both the number of female inmates and the average length of their sentences have increased dramatically. A by-product of the recent "confinement era" within criminal justice is the influx of ill and generally unhealthy female offenders into this nation's correctional institutions. As women in prison have different treatment needs and problems than their male counterparts, there is a need for gender-appropriate programs. The impact of such inmates on correctional health care services represents a potentially critical issue confronting correctional managers and correctional health service administrators. This article highlights the need for correctional policy to address the health care needs of women prisoners with HIV/AIDS.


What's ahead on quality: the managed care perspective.
Without question, the most important processes occurring in managed care that can be expected to affect quality are accreditation and the effort to obtain and compare uniform information on quality of care across health care organizations, in short, to create "report cards." For both processes, 1993 was an extremely productive year, and 1994 promises to be even more so. These two processes fit hand-in-glove--one is designed to determine that managed care organizations are equipped to serve the public and to implement better health care programs, while the other is designed to help them understand and improve their own performance. Although, in the short run, managed care organizations may view both these efforts as additional costs, in the long run, both should lead to a better industry and to better care for the public.


Mean ± Standard Deviation Intake Values for 1-<10-Year-Old South African Children for Application in the Assessment of the Inflammatory Potential of Their Diets Using the DII® Method: Developmental Research.
This study aimed to develop a set of mean ± standard deviation (SD) intake values for South African (SA) children for 36 of the 45 food parameters included in the original Dietary Inflammatory Index (DII®) tool. The SA food composition database contains 30 of the 45 food parameters included in the original DII®, and a supplementary database was developed for six of the food parameters not included in the SA database. The SA child mean ± SD intake of macronutrients, micronutrients and select flavonoids was calculated by age in years, using eight data sets from dietary surveys conducted in SA in the last three decades. A total sample of 5412 children was included in the calculation of the mean ± SD. The current study sample was determined to be representative of 1-<10-year-old children in SA, and the plausibility of the mean intake values was confirmed by being in line with age-appropriate recommendations. Furthermore, an increase in energy, macronutrient, and most micronutrient intakes with increase in age was evident. The generated mean ± SD values for SA children can be used for calculation of the inflammatory potential of the dietary intake of SA children in the age range of 1-<10-year-old children.


Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor.
Early growth responsive gene 3 (EGR3) is a zinc-finger transcription factor and plays important roles in cellular growth and differentiation. We recently demonstrated estrogen-mediated induction of EGR3 in breast carcinoma cells. However, EGR3 has not yet been examined in breast carcinoma tissues and its significance remains unknown. Therefore, in this study, we examined biological functions of EGR3 in the breast carcinoma by immunohistochemistry, in vitro study, and nude mouse xenograft model. EGR3 immunoreactivity was detected in carcinoma cells in 99 (52%) out of 190 breast carcinoma tissues and was associated with the mRNA level. EGR3 immunoreactivity was positively associated with lymph node status, distant metastasis into other organs, estrogen receptor alpha, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negatively correlated with tubule formation. EGR3 immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- and multivariate analyses. Egr3-expressing transformant cell lines derived from MCF-7 Tet-Off cells (Eg-10 and Eg-11) significantly enhanced the migration and invasion properties according to the treatment of doxycyclin, but did not significantly change the cell proliferation. Moreover, Eg-11 cells injected into athymic mice irregularly invaded into the adjacent peritumoral tissues, although Clt-7, which was stably transfected with empty vector as a control, demonstrated a well-circumscribed tumor. Eg-11 cells were significantly associated with invasive components and less tubule formation in the xenograft model. These results suggest that EGR3 plays an important role in estrogen-meditated invasion and is an independent prognostic factor in breast carcinoma.


In vitro pharmacological effects of Astragalus eremophilus and Melilotus parviflora.
Traditional medicines are composed of herbal formulations and their active ingredients and constituents which play a crucial role in the treatment of various human ailments. Astragalus eremophilus and Melilotus indicus (L.) All. (syn. Melilotus parviflora Desf.) are used traditionally as antiperspirant, tonic, diuretic, laxative and narcotic agents. The current study was designed to investigate the Astragalus eremophilus and Melilotus indicus (L.) All. (syn. Melilotus parviflora Desf.) methanol extracts for their antioxidant, antibacterial and antifungal activities. Fine powder of A. eremophilus and M. parviflora was extracted with 70% methanol to get crude methanol extract. Extract was characterized for antioxidant, antibacterial and antifungal activities. Antioxidant activity of various concentrations (3 mg/ml, 1.5 mg/ ml, 0.75 mg/ml, and 0.38 mg/ml) of both plant extracts was analyzed using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical. Salmonella typhemorium, Klebsiella pneumoniae (gram-negative) and Staphylococcus aureus, Enterococcus faecalis (gram-positive) bacterial strains were used for assessment of antibacterial activities. Antifungal activities of 7.5 mg/ml, 5.0 mg/ml, 2.5 mg/ml (A. eremophilus and M. parviflora) were conducted using Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus and Candida albicons. At high concentration (3 mg/ml), all the tested fractions of A. eremophilus and M. parviflora methanol extracts showed potent antioxidant activities, ranging between 83.8 and 63.33%. Antibacterial activities revealed that A. eremophilus showed a maximum zone of inhibition (8.1 ± 0.1) on Salmonella typhenorium followed by Enterococcus faecalis (7.2 ± 0.1), Klebsellesa pneumonia (6.1 ± 0.6), and Staphylococcus aureus (5.1 ± 0.4), and at highest concentration (7.5 mg/ml), however, maximum zone of inhibition of Melilotus parviflora was at 7.5 mg/ml followed by 5.0 mg/ml and 2.5 mg/ml against Klebsiella pneumonia, Staphylococcus aureus, Salmonella typhemorium and Enterococcus faecalis. Antifungal assessment of both plant extracts showed that the higher concentration (7.5 mg/ml) has significant inhibitory effect as compared to control. The results can lead to the conclusion that A. eremophilus and M. parviflora methanol extracts are indeed sources of potential therapeutic compounds against antibacterial, antifungal and free radical associated disorders.


A new approach to the determination of airway resistance: interrupter technique vs. plethysmography.
To determine the agreement between interrupter resistance (Rint) and airway resistance (Raw) by plethysmography in order to verify the clinical applicability of the interrupter technique. The Rint technique was performed with the patients in a sitting position, during exhalation, with a nose clip and cheek support. Plethysmography was carried out in accordance with standard protocols. All measurements were taken prior to and after the administration of an inhaled bronchodilator via a metered dose inhaler with a spacer. The study comprised 99 consecutive patients referred to the Porto Alegre Hospital de Clínicas, located in the city of Porto Alegre, Brazil, for pulmonary function testing. Patient ages ranged from 18 to 82 years, and 52 of the patients were women. In the patients with FEV1 ≥ 60% of predicted, there was good agreement between the methods (r = 0.8; intraclass correlation coefficient = 0.8). The Rint values were lower than were those of Raw by plethysmography in the patients with more severe disease. However, there was good agreement between Rint ≥ 4 cmH2O L(-1) s(-1) and Raw by plethysmography > 2.5 cmH2O L(-1) s(-1) (likelihood ratio > 8; kappa coefficient = 0.73). In the patients with less severe disease, there was good agreement between Rint and Raw by plethysmography. The agreement between the two methods was also strong regarding the detection of an increase in Raw. The Rint technique is a potentially useful method for the evaluation of adult patients.


Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study.
Amisulpride (AMS), a second generation antipsychotic, suffers from low oral bioavailability (48%). This might be due to its pH-dependent solubility or being a substrate of P-glycoprotein efflux pump. Nanostructured lipid carriers (NLCs) were proposed in this study to enhance the oral absorption of AMS. AMS-NLCs were prepared by solvent evaporation technique according to (21.41.31) factorial design, whereas the type of solid lipid (tripalmitin or Gelucire® 43/1), lipid to drug ratio (7:1, 10:1, or 13:1) and type of external suspending medium (double distilled water, 0.5% TSP pH 12, 1% HPMC or 2.5% glycerin) were the independent variables. The average entrapment efficiency, particle size, polydispersity index, and zeta potential of the prepared formulations ranged from 29.01 to 69.06%, 184.9 to 708.75 nm, 0.21 to 0.59, and - 21 to - 33.55 mV, respectively. AMS-NLCs were optimized according to the desirability function to maximize the entrapment efficiency and minimize the particle size. Formulae G12, G10, and G7 with the highest desirability values of 0.915, 0.84, and 0.768, respectively, were chosen for further investigations. Novel AMS-NLCs capsules were prepared from the lyophilized formulations (TG7 and MG10) to enhance stability and increase patient compliance. The capsules were evaluated in terms of weight variation, content uniformity, and in vitro release pattern. The pharmacokinetics of AMS-NLCs capsules (formula TG7) were tested in rabbits compared to the commercial Amipride® tablets. The relative bioavailability of AMS-NLCs capsules was found to be 252.78%. In conclusion, the NLC-based capsules show potential to improve the oral bioavailability of AMS.


Dominican Children with HIV not Receiving Antiretrovirals: Massage Therapy Influences their Behavior and Development.
Forty-eight children (M age = 4.8 years) infected with HIV/AIDS and living in the Dominican Republic were randomly assigned to a massage therapy or a play session control group. The children in the massage therapy group received two weekly 20-min massages for 12 weeks; the children in the control group participated in a play session (coloring, playing with blocks) for the same duration and length as the massage therapy group. Overall, the children in the massage therapy group improved in self-help abilities and communication, suggesting that massage therapy may enhance daily functioning for children with HIV/AIDS. Moreover, the HIV infected children who were six or older also showed a decrease in internalizing behaviors; specifically depressive/anxious behaviors and negative thoughts were reduced. Additionally, baseline assessments revealed IQ equivalence below normal functioning for 70% of the HIV infected children and very high incidences of mood problems (depression, withdrawn) for 40% of the children and anxiety problems for 20% of the children, suggesting the need for better monitoring and alternative interventions in countries with limited resources to improve cognition and the mental health status of children infected with HIV/AIDS.


Modulation of type I interferon signaling by African swine fever virus (ASFV) of different virulence L60 and NHV in macrophage host cells.
ASFV causes an important disease of domestic swine and wild boar. Currently no vaccine is available, highlighting the necessity to understand ASFV modulation of innate immune responses in natural host cells. With this aim, macrophage cultures enriched in SWC9 and CD163 differentiation markers were infected in parallel with high virulent ASFV/L60 and low virulent ASFV/NHV, the latter lacking MGF 360 and 505/530 genes associated with type I interferon (IFN I) control. IFN I production and signaling were studied after completion of the viral cycles. None of the viruses increased IFN I production in host cells, and accordingly, didn't cause activation of the central mediator of the pathway IRF3. However, upon stimulation by poly:IC treatment during infections, L60 and NHV similarly inhibited IFN I production. This didn't seem to depend on IRF3 modulation since its activation levels were not significantly decreased in L60 infection and were even increased in NHV's, in comparison to stimulated mock infections. The infections didn't evidently activate JAK-STAT pathway mediators STAT1 and STAT2, but did increase expression of interferon stimulated genes (ISGs), to higher levels in NHV than L60 infection. Interestingly, in presence of IFN-α, L60 but not NHV was able to decrease significantly the expression of some of the ISGs tested. Overall, both L60 and NHV were able to inhibit IFN I production in macrophages, through a mechanism not dependent on IRF3 modulation. The high virulent isolate showed however a more effective control of the downstream ISGs expression pathway.


[Treatment of papillary microcarcinoma of the thyroid].
We retrospectively analyzed the recurrence, distant metastases and mortality of 78 patients with papillary microcarcinoma during a mean period of 6.8 years. None of the 56 patients with unifocal tumors without metastases relapsed, irrespective of the type of treatment (22 submitted to lobectomy, 11 to total thyroidectomy without ablation and 23 with ablation). The same occurred for the 15 cases of multicentric tumors restricted to the thyroid and treated with total thyroidectomy and radioiodine. Of the 7 patients with metastases in the initial presentation and treated with extensive surgery and ablative therapy, cervical recurrence was observed in 1 case. Detectable anti-thyroglobulin antibodies were more common after lobectomy (22.7% vs. 9%) and the specificity of thyroglobulin was compromised by this procedure, but not in patients submitted to total thyroidectomy without ablation. Two cases of definitive hypoparathyroidism were observed in the group submitted to total thyroidectomy (3.5%) and no cases with lobectomy. The present study agrees that lobectomy can be sufficient for the treatment of single microcarcinoma restricted to the thyroid. However, the Tg specificity is compromised. Total thyroidectomy is recommended for multicentric tumors or with lymph nodes metastases, but the routine use of radioiodine is a matter of controversy.


A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.
Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.


Hard metal lung disease in an oil industry worker.
Hard metal lung disease, which manifests as giant cell interstitial pneumonia, is caused by exposure to hard metal dust. We report the case of an oil industry worker diagnosed with hard metal lung disease. The diagnosis was based on the clinical, radiological and anatomopathological analysis, as well as on pulmonary function testing.


[Lung resection: predictive value of respiratory function].
The most important preoperative cardiopulmonary variables for identifying patients at increased risk prior to lung resection are: FEV1, FEV1-ppo, DLCO, MVO2, and SO2. The aim of this study was to evaluate the ability and usefulness of predictive postoperative FEV1 (FEV1-ppo) in 80 patients undergoing lung resection. Spirometry was performed before and 6 months after operation; residual respiratory function was calculated using Nakahara's formula, and data analysis calculations were performed using the chi 2 test. It was observed that the resulting predictive values were almost comparable to the values observed 6 months postoperatively in 63.75% of patients and the correlation proved statistically significant (P < 0.005). In view of its simple and rapid execution, we conclude that Nakahara's formula, compared with the others, remains a reliable standard method of assessing high-risk patients and planning appropriate surgery.


Stable mode sorting by two-dimensional parity of photonic transverse spatial states.
We describe a mode sorter for two-dimensional parity of transverse spatial states of light based on an out-of-plane Sagnac interferometer. Both Hermite-Gauss (HG) and Laguerre-Gauss (LG) modes can be guided into one of two output ports according to the two-dimensional parity of the mode in question. Our interferometer sorts HG(nm) input modes depending upon whether they have even or odd order n+m; it equivalently sorts LG(l)(p) modes depending upon whether they have an even or odd value of their orbital angular momentum l. It functions efficiently at the single-photon level, and therefore can be used to sort single-photon states. Due to the inherent phase stability of this type of interferometer as compared to those of the Mach-Zehnder type, it provides a promising tool for the manipulation and filtering of higher order transverse spatial modes for the purposes of quantum information processing. For example, several similar Sagnacs cascaded together may allow, for the first time, a stable measurement of the orbital angular momentum of a true single-photon state. Furthermore, as an alternative to well-known holographic techniques, one can use the Sagnac in conjunction with a multi-mode fiber as a spatial mode filter, which can be used to produce spatial-mode entangled Bell states and heralded single photons in arbitrary first-order (n+m = 1) spatial states, covering the entire Poincar e sphere of first-order transverse modes.


[Cytogenetic consequences of hyperbaric oxygenation in the sequence of cell cycles of human peripheral blood lymphocytes].
High pressure of oxygen induces chromosomal rearrangements in metaphases of human peripherical blood cells treated in vitro. An increase in the percentage of rearrangements was detected in the third mitosis, due mainly to chromatid breaks. The data of cytogenetical analysis of lymphocytes of human blood treated in vivo at 3 ata for 30 min are presented. A differential character of distribution spectrum of chromosomal aberrations induced after in vivo and in vitro treatment was noted. Some unusual alterations in chromosome morphology are described, namely, solid, not stained clear lense-like bodies surrounded by chromatin and localised in the long arm of chromatids.


Rhythmic E-box binding by CLK-CYC controls daily cycles in per and tim transcription and chromatin modifications.
The Drosophila melanogaster circadian oscillator comprises interlocked per/tim and Clk transcriptional feedback loops. In the per/tim loop, CLK-CYC-dependent transcriptional activation is rhythmically repressed by PER or PER-TIM to control circadian gene expression that peaks around dusk. Here we show that rhythmic transcription of per and tim involves time-of-day-specific binding of CLK-CYC and associated cycles in chromatin modifications. Activation of per and tim transcription occurs in concert with CLK-CYC binding to upstream and/or intronic E-boxes, acetylation of histone H3-K9, and trimethylation of histone H3-K4. These events are associated with RNA polymerase II (Pol II) binding to the tim promoter and transcriptional elongation by Pol II that is constitutively bound to the per promoter. Repression of per and tim transcription is associated with PER-dependent reversal of these events. Rhythms in H3-K9 acetylation and H3-K4 trimethylation are also associated with CLOCK-BMAL1-dependent transcription in mammals, indicating that the mechanism that controls rhythmic transcription is a conserved feature of the circadian clock even though feedback repression is mediated by different proteins.


Emergent Medical Illnesses Related to Cannabis Use.
As more states rush to legalize the use of cannabis products, both medically and recreationally, there are more medical harms being seen in emergency departments (ED). The tetrahydrocannabinol (THC) concentration today is much stronger than the concentration from the 90s. In the 1990s most typical "joints" contained 1-3 mg of THC. Today, plants are being raised and modified to produce a higher concentration of THC. In turn, the amount of cannabidiol (CBD) is decreasing. Previously, people would smoke 1-3 mg of THC. The typical joint in Colorado contains 18 mg of THC or more. Currently, in the ED, we see patients who self-report smoking 2,000 mg or more of THC in a day. In 2015, 2.6 million individuals started cannabis use, 45% were 12-17 years of age.3 This brief report includes some of the more common illnesses that have been seen over the last four years of legalization in Colorado, and is by no means inclusive of all the potential problems that can occur. Among the many untoward effects being seen, illnesses that will be discussed are: cannabinoid associated hyperemesis, acute psychosis, cannabinoid catatonia syndrome, acute myo-pericarditis and ingestions.


Shape up: An eye-tracking study of preschoolers' shape name processing and spatial development.
Learning the names of geometric shapes is at the intersection of early spatial, mathematical, and language skills, all important for school-readiness and predictors of later abilities in science, technology, engineering, and mathematics (STEM). We investigated whether socioeconomic status (SES) influenced children's processing of shape names and whether differences in processing were predictive of later spatial skills. Three-year-olds (N = 79) with mothers of varying education levels participated in an eye-tracking task that required them to look at named shapes. Lower SES children took longer to fixate target shapes and spent less time looking at them than higher SES children. Gaze variables measured at age 3 were predictive of spatial skills measured at age 5 even though the spatial measures did not require shape-related vocabulary. Early efficiency in the processing of shape names may contribute to the development of a foundation for spatial learning in the preschool years. (PsycINFO Database Record


Determination, mechanism and monitoring of knockdown resistance in permethrin-resistant human head lice, Pediculus humanus capitis.
Permethrin resistance has been reported worldwide and clinical failures to commercial pediculicides containing permethrin have likewise occurred. Permethrin resistance in head lice populations from the U.S. is widespread but is not yet uniform and the level of resistance is relatively low (~4-8 fold). Permethrin-resistant lice are cross-resistant to pyrethrins, PBO-synergized pyrethrins and to DDT. Nix((R)), when applied to human hair tufts following manufacture's instructions, did not provide 100% control when assessed by the hair tuft bioassay in conjunction with the in vitro rearing system. Resistance to permethrin is due to knockdown resistance (kdr), which is the result of three point mutations within the alpha-subunit gene of the voltage-gated sodium channel that causes amino acid substitutions, leading to nerve insensitivity.A three-tiered resistance monitoring system has been established based on molecular resistance detection techniques. Quantitative sequencing (QS) has been developed to predict the kdr allele frequency in head lice at a population level. The speed, simplicity and accuracy of QS made it an ideal candidate for a routine primary resistance monitoring tool to screen a large number of louse populations as an alternative to conventional bioassay. As a secondary monitoring method, real-time PASA (rtPASA) has been devised for a more precise determination of low resistance allele frequencies. To obtain more detailed information on resistance allele zygosity, as well as allele frequency, serial invasive signal amplification reaction (SISAR) has been developed as an individual genotyping method. Our approach of using three tiers of molecular resistance detection should facilitate large-scale routine resistance monitoring of permethrin resistance in head lice using field-collected samples.


[A case report of Bochdalek's hernia with volvulus of the stomach in an adult].
We report a rare case of Bochdalekhs hernia, congenital posterolateral diaphragmatic hernia with mesenterioaxia volvulus of the stomach, in an adult. A 23-year-old man suddenly felt severe pain in his left chest after drinking beer. Roentgenologic examination of the chest showed air above the left diaphragm, and the mediastinum was displaced to the right. Upper gastrointestinal series revealed mesenterioaxial volvulus of the stomach in which the pylorus was displaced to the left. Thoracotomy through the left seventh intercostal space was performed. The stomach, colon, spleen and greater omentum were displaced into the left thoracic cavity. After reduction of the herniated viscera, a defect measuring 10 X 4 cm, in the posterolateral part of the diaphragm, was closed with double interrupted Tevdek sutures. Three months later, he was asymptomatic and his chest roentgenogram was normal.


The dynamics of trust: comparing humans to automation.
Complex industrial environments involve cooperation between operators and automation. The strategies used to allocate tasks to automation are a crucial component of that cooperation and are known to be affected by the operators' trust in the automation. In 2 simulated process control experiments, the authors compared trust in automation with trust in human partners in equivalent situations. Experiment 1 found the relationship between trust and task allocation to be qualitatively identical, but quantitatively attenuated, for human partners as compared with automation. Experiment 2 additionally identified the operators' trustworthiness, as they thought it would be perceived by a human partner, as crucial to task allocation under human collaboration but not under automation. The results imply that human collaboration benefits from calibration of people's assessment of how others perceive them.


Can practice guidelines reduce the number and costs of malpractice claims?
Practice guidelines have the potential to reduce the number of malpractice cases and the costs of settling them. However, for practice guidelines to exert any influence, they must be assumed to be (1) developed for conditions or procedures that frequently lead to events for which negligence claims are filed; (2) widely accepted in the medical profession; (3) fully integrated into clinical practice; and (4) straightforward and readily interpreted in a litigation setting. Because the validity of each of these assumptions can be questioned, the idea that inserting practice guidelines into the existing litigation process will generate large savings in the near future is overly optimistic.


Dynamic regulation of CD45 lateral mobility by the spectrin-ankyrin cytoskeleton of T cells.
The leukocyte common antigen, CD45, is a critical immune regulator whose activity is modulated by cytoskeletal interactions. Components of the spectrin-ankyrin cytoskeleton have been implicated in the trafficking and signaling of CD45. We have examined the lateral mobility of CD45 in resting and activated T lymphocytes using single-particle tracking and found that the receptor has decreased mobility caused by increased cytoskeletal contacts in activated cells. Experiments with cells that have disrupted betaI spectrin interactions show decreased cytoskeletal contacts in resting cells and attenuation of receptor immobilization in activated cells. Applying two types of population analyses to single-particle tracking trajectories, we find good agreement between the diffusion coefficients obtained using either a mean squared displacement analysis or a hidden Markov model analysis. Hidden Markov model analysis also reveals the rate of association and dissociation of CD45-cytoskeleton contacts, demonstrating the importance of this analysis for measuring cytoskeleton binding events in live cells. Our findings are consistent with a model in which multiple cytoskeletal contacts, including those with spectrin and ankyrin, participate in the regulation of CD45 lateral mobility. These interactions are a major factor in CD45 immobilization in activated cells. Furthermore, cellular activation leads to CD45 immobilization by reduction of the CD45-cytoskeleton dissociation rate. Short peptides that mimic spectrin repeat domains alter the association rate of CD45 to the cytoskeleton and cause an apparent decrease in dissociation rates. We propose a model for CD45-cytoskeleton interactions and conclude that the spectrin-ankyrin-actin network is an essential determinant of immunoreceptor mobility.


Single and Combined Salinity and Heat Stresses Impact Yield and Dead Pericarp Priming Activity.
In the face of climate change and the predicted increase in the frequency and severity of abiotic stresses (e.g., hot spell, salinity), we sought to investigate the effect of salinity (S), short episodes of high temperature (HS) and combination of salinity and high temperature (SHS), at the reproductive phase, on yield with a special focus on the properties of dead pericarps of Brassica juncea. Three interval exposures to HS resulted in massive seed abortion, and seeds from salt-treated plants germinated poorly. Germination rate and final germination of B. juncea seeds were slightly reduced in the presence of salt and SHS pericarp extracts. All pericarp extracts completely inhibited seed germination of tomato and Arabidopsis, but removal of pericarp extracts almost fully restored seed germination. Heat and salinity profoundly affected the accumulation of phytohormones in dead pericarps. Combined stresses highly reduced IAA and ABA levels compared with salt, and enhanced the accumulation of GA1, but abolished the positive effect of salt on the accumulation of GA4, JA and SA. Interestingly, pericarp extracts displayed priming activity and significantly affected seedling performance in a manner dependent on the species and on the origin of the pericarp. While control pericarps improved and reduced the seedlings' performance of autologous and heterologous species, respectively, pericarps from salt-treated plants were harmless or improved heterologous seedling performance. Thus, the strategy employed by the germinating seed for securing resources is set up, at least partly, by the mother plant in conjunction with the maternal environment whose components are stored in the dead maternal organs enclosing the embryo.


Consumption of fruit and vegetable and risk of coronary heart disease: a meta-analysis of prospective cohort studies.
Observational studies suggest that an association between fruit and vegetable consumption and coronary heart disease (CHD). However, the results are inconsistent. We conducted a meta-analysis to evaluate the relationship of fruit and vegetable consumption with CHD risk and quality the dose-response relationship between them. Relevant prospective studies were identified by a search of PubMed, Embase and Web of Science databases to July 2014. A random-effects model was used to calculate the pooled relative risk (RR) and 95% confidence intervals (CI). Twenty-three studies involving 937,665 participants and 18,047 patients with CHD were included. Compared with the lowest consumption levels of total fruit and vegetable, fruit and vegetable, the RR of CHD was 0.84 (95% CI, 0.79-0.90), 0.86 (95% CI, 0.82-0.91), 0.87 (95% CI, 0.81-0.93), respectively. The dose-response analysis indicated that, the RR of CHD was 0.88 (95% CI: 0.85-0.91) per 477 g/day of total fruit and vegetable consumption, 0.84 (95% CI: 0.75-0.93) per 300 g/day of fruit intake and 0.82 (95% CI: 0.73-0.92) per 400 g/day of vegetable consumption. A nonlinear association of CHD risk with fruit or vegetable consumption separately was found (P for nonlinearity <0.001). In the subgroup analysis of location, a significant inverse association was observed in Western populations, but not in Asian populations. This meta-analysis indicates that total fruit and vegetable, fruit and vegetable consumption, are significantly associated with a lower risk of CHD. The significant inverse association was found in Western populations, but not in Asian populations, which warrants further research.


Exploring the uncommon: A case report on localized peritonitis caused by ingested toothpick.
Bowel perforation is a serious emergency. Occasionally, sharp objects like toothpicks can get stuck in narrow parts of the small intestine, potentially resulting in impaction, obstruction, or perforation. A 20-year-old male arrived at our hospital's emergency department with sudden, severe abdominal pain persisting for 24 h. On examination, his abdomen showed tenderness, and bowel sounds were reduced. Contrast-enhanced computed tomography (CECT) indicated possible small intestine inflammation due to a foreign object and a diagnostic laparoscopy revealed a hyperemic terminal ileum. This case involves ileal perforation from an unnoticed toothpick ingestion. Detecting foreign object perforations is challenging, often leading to misdiagnoses and CT scans are the most effective for toothpick detection. Definitive diagnosis is through laparoscopy, and treatment varies between laparoscopic suturing to intestinal resection. Healthcare providers must consider toothpick ingestion in cases of acute abdominal symptoms to avert treatment delays and potential life-threatening outcomes.


Renal function during reflexly activated catecholamine flow through an adrenorenal rete.
Reflex vasoconstriction that occurs in the kidney of the dog can be the result of either of two mechanisms. The first is by activation of the renal sympathetic nerves and the second by reflex activation of catecholamine flow through an adrenorenal rete. Both reflex mechanisms can be activated by transient hypotension caused by experimentally induced atrial fibrillation in the sodium-replete pentobarbital-anesthetized dog. This study was undertaken to measure and compare the magnitude of changes in renal function that occur when these reflex mechanisms are activated and to evaluate the possible role of intrarenal angiotensin II in these two reflex effects. Reflex activation of catecholamine flow through an adrenorenal rete in intact or denervated kidneys produced a 26 +/- 3% decrease in renal plasma flow, a 23 +/- 4% decrease in glomerular filtration rate, a 58 +/- 7% decrease in urinary sodium excretion, and a 4 +/- 1% increase in filtration fraction, but no change in the fractional distribution of intrarenal blood flow. Changes of a similar direction and magnitude were seen in the same animals during reflex activation of the renal sympathetic nerves in the kidneys with intact or ligated adrenorenal rete. The same studies were performed after the intrarenal action of angiotensin II was blocked with [Sar1,Ala8]angiotensin II and similar responses were seen. Both of these reflexes appear to be important mechanisms by which the kidney can maintain vascular volume, and neither depends on intrarenal angiotensin II activity.


Early irradiation of matter in the solar system: magnesium (proton, neutron) scheme.
The occurrence of positive and negative (26)Mg anomalies in inclusions of the Allende meteorite is explained in terms of proton bombardment of a gas of solar composition. A significant fraction of (26)Mg in the irradiated gas is stored temporarily in the form of radioactive (26)Al by the reaction (26)Mg(p,n) (26)Al. Proton fluxes of 10(17) to 10(19) protons per square centimeter per year at l million electron volts are inferred. Aluminum-rich materials condensing from the gas phase have positive (26)Mg anomalies, whereas magnesium-rich materials have negative (26)Mg anomalies. The proton flux required to account for the observed magnesium anomalies is used to investigate possible isotopic anomalies in the elements from oxygen to argon. Detectable isotopic anomalies are predicted only for neon. The anomalous neon is virtually pure (22)Ne from (22)Na decay. The predicted amount of anomalous (22)Ne is about 10(-8) cubic centimeter (at standard temperature and pressure) per milligram of sodium.


Professionals' perspectives on relevant approaches to psychological care in moral injury: A qualitative study.
Despite the increasing consensus that moral injury (MI) is a unique type of psychological stressor, there is an ongoing debate about best practices for psychological care. This qualitative study explored the perceptions of UK and US professionals in the field of MI investigating advances and challenges in treatment or support delivery and issues relating to treatment/support feasibility and acceptability. 15 professionals were recruited. Semi-structured, telephone/online interviews were carried out, and transcripts were analyzed using thematic analysis. Two interconnected themes emerged: perceived barriers to appropriate care for MI cases and recommendations for providing effective care to MI patients. Professionals highlighted the challenges that occur due to the lack of empirical experience with MI, the negligence of patients' unique individual needs and the inflexibility in existing manualised treatments. These findings illustrate the need to evaluate the effectiveness of current approaches and explore alternative pathways, which will effectively support MI patients in the long-term. Key recommendations include the use of therapeutic techniques which lead to a personalised and flexible support plan to meet patients' needs, increase self-compassion and encourage patients to reconnect with their social networks. Interdisciplinary collaborations (e.g., religious/spiritual figures), could be a valuable addition following patients' agreement.


Identification of prenylated pterocarpans and other isoflavonoids in Rhizopus spp. elicited soya bean seedlings by electrospray ionisation mass spectrometry.
Phytoalexins from soya are mainly characterised as prenylated pterocarpans, the glyceollins. Extracts of non-soaked and soaked soya beans, as well as that of soya seedlings, grown in the presence of Rhizopus microsporus var. oryzae, were screened for the presence of prenylated flavonoids with a liquid chromatography/mass spectrometry (LC/MS)-based screening method. The glyceollins I-III and glyceollidins I-II, belonging to the isoflavonoid subclass of the pterocarpans, were tentatively assigned. The formation of these prenylated pterocarpans was accompanied by that of other prenylated isoflavonoids of the subclasses of the isoflavones and the coumestans. It was estimated that approx. 40% of the total isoflavonoid content in Rhizopus-challenged soya bean seedlings were prenylated pterocarpans, whereas 7% comprised prenylated isoflavones and prenylated coumestans. The site of prenylation (A-ring or B-ring) of the prenylated isoflavones was tentatively annotated using positive-ion mode MS by comparing the (1,3) A(+) retro-Diels-Alder (RDA) fragments of prenylated and non-prenylated isoflavones. Furthermore, the fragmentation pathways of the five pterocarpans in negative-ion (NI) mode were proposed, which involved the cleavage of the C-ring and/or D-ring. The absence of the ring-closed prenyl (pyran or furan) gave exclusively -H(2) O(x,y) RDA fragments, whereas its presence gave predominantly the common RDA fragments.


Imaging of iron oxide nanoparticles by MR and light microscopy in patients with malignant brain tumours.
Ferumoxtran-10 (Combidex), a dextran-coated iron oxide nanoparticle, provides enhancement of intracranial tumours by magnetic resonance (MR) for more than 24 h and can be imaged histologically by iron staining. Our goal was to compare ferumoxtran imaging and histochemistry vs. gadolinium enhancement in malignant brain tumours on preoperative and postoperative MR. Seven patients with primary and metastatic malignant tumours underwent MR imaging with gadolinium and ferumoxtran both pre- and postoperatively. Normalized signal intensities on the ferumoxtran-enhanced scans were determined in representative regions of interest. Resected tissue from six ferumoxtran patients and from three patients who did not receive ferumoxtran was assessed for localization of iron in tumour and reactive brain. All malignant tumours (all of which enhanced by gadolinium MR) showed ferumoxtran accumulation with T1 and T2 signal changes, even using a 0.15 T intraoperative MR unit in one patient. Iron staining was predominantly in reactive cells (reactive astrocytes and macrophages) and not tumour cells. In five of the seven patients, including two patients who showed additional lesions, areas enhancing with ferumoxtran but not with gadolinium were observed. Comparison of the pre- and postoperative MR revealed residual ferumoxtran-enhancing areas in four of seven cases. In malignant tumours, ferumoxtran may show areas of enhancement, even with a 0.15 T intraoperative MR, that do not enhance with gadolinium. Ferumoxtran-enhancing lesions have persistent increased T1 signal intensity for 2-5 days, which may provide advantages over gadolinium for postoperative imaging. Histochemistry for iron shows uptake of ferumoxtran in reactive cells (astrocytes and macrophages) rather than tumour cells.


Surgical outcomes of a new affordable non-valved glaucoma drainage device and Ahmed glaucoma valve: comparison in the first year.
A new low-cost, indigenously manufactured, non-valved glaucoma drainage device (GDD) has been introduced and its design is based on the Baerveldt Glaucoma Device. We aim to demonstrate the efficacy and safety of this GDD (Aurolab aqueous drainage implant, AADI) vis-à-vis the valved device, Ahmed glaucoma valve (AGV), in the management of refractory glaucomas. Retrospective, comparative, interventional. Case review of consecutive patients who underwent GDD surgery by a single fellowship-trained surgeon at a Tertiary Centre between January 2014 and November 2016. Intraocular pressure (IOP). Antiglaucoma medication (AGM), LogMAR best-corrected visual acuity (BCVA), complications. A total of 88 eyes of 83 patients were included; 36 eyes received AGV and 52 AADI. Preoperative parameters were similar between groups. Median follow-up was 13 and 12 months for AADI and AGV, respectively. Overall success rate was higher in AADI (92.3%) vs AGV (80.5%) (p<0.001). The median IOP in mm Hg (Quartiles; IQR) (AADI 14 (10,15;5) vs AGV 16 (14,20;6)) and AGM (AADI: 0 (0,1;1) vs AGV 2 (1,2.75;1.75)) was significantly lower in the AADI group at last follow-up (p<0.001). LogMAR BCVA improved in both groups; complication rates (AADI 44.2% vs AGV 52.7%) were comparable (p=0.59). Both procedures were effective in reduction of IOP and need for AGM. Nevertheless, overall success rate was higher in the AADI group and IOP and number of AGM required was significantly lower in the AADI group; this affordable GDD could have a tremendous impact in the management of refractory glaucomas in low-income to middle-income countries.


Adult stem cell transplants for spinal cord injury repair: current state in preclinical research.
Spinal cord injury (SCI) is a traumatic disorder resulting in a functional deficit that usually leads to severe and permanent paralysis. After the initial insult to the spinal cord, additional structure and function are lost through an active and complex secondary process. Since there is not effective treatment for SCI, several strategies including cellular, pharmacological and rehabilitation therapies have been approached in animal models. Some of them have been proved in clinical trials. In this review we focus on the current state of cell therapies, particularly on cells from adult origin, assayed in preclinical research. Cell types used in SCI therapy include Schwann cells, olfactory ensheathing cells and adult stem cells, such as neural stem cells, umbilical cord blood derived cells, mesenchymal stem cells or induced pluripotent stem cells. There are not yet conclusive evidences on which types of glial or adult stem cells are most effective in SCI treatment. Their ability to incorporate into the damaged spinal cord, to differentiate into neural lineages, to exert neuroprotective effects, to promote regeneration of damaged axons, and to improve functional deficits are still discussed, before translation towards clinical use, as a single therapy or in combination with other strategies.


Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies.
Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome–associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome–associated cancers. A retrospective cohort study of individuals with Lynch syndrome–associated colorectal, endometrial, and/or ovarian cancers whose medical records were included in the clinical database of a large quaternary referral center for genomic medicine in the Northwest of England. Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncating, splicing, or large rearrangement). Age at cancer diagnosis. A total of 1063 individuals with proven Lynch syndrome were included, 495 male and 568 female (mean age 52 years; age range, 10-93 years [children were included in the database, but no children developed cancer]). There were 546 men and women with colorectal cancer, 162 women with endometrial cancer, and 49 women with ovarian cancer; mean follow-up was 68.2 months. Among MLH1 mutation carriers, mutations in MLH1 were associated with colorectal cancer in 249 (61%) of 409 men and women; endometrial cancer in 53 of 196 (27%) women; and ovarian cancer in 15 (8%) of 196 women. Among MSH2 mutation carriers, mutations in MSH2 (the most prevalent mutations overall) were most commonly associated with female-specific cancers: endometrial cancer in 83 (30%) of 279 women; ovarian cancer in 28 (10%) of 279 women; and colorectal cancer in 239 (50%) 479 men and women. Mutations in MSH6 were less prevalent, and MSH6 mutation carriers presented with colorectal and endometrial cancer at later ages than carriers of mutations in MSH2 or MLH1. When stratified by mutation type, women with truncating MLH1 mutations had later ages of onset of endometrial cancer than those with nontruncating mutations (median difference, 6.6 years; 95% CI, 2.7-10.4; P = .002). Carriers of truncating MLH1 mutations presented with colorectal cancer at later ages than those with other mutations, but the difference was not statistically significant. Individuals with known Lynch syndrome could be risk stratified by mutated gene and mutation type in tailored surveillance programs. Specifically, individuals with MSH6 mutations could be offered cancer surveillance from a later age. Furthermore, those with truncating MLH1 mutations could begin endometrial cancer surveillance later than those with nontruncating mutations.


Functional blockade of tyrosine kinase A in the rat basal forebrain by a novel antagonistic anti-receptor monoclonal antibody.
We have exploited a new monoclonal antibody against the tyrosine kinase A (TrkA) nerve growth factor (NGF) receptor to block the NGF-TrkA interaction in the rat basal forebrain. The monoclonal antibody MNAC13 is a potent antagonist that prevents the binding of NGF to TrkA in a variety of systems. This antibody was used to study the maintenance of the cholinergic phenotype in the rat basal forebrain in vivo, by the implant of antibody-secreting cells. Basal forebrain cholinergic neurons (BFCNs) are greatly affected by the antibody treatment, both in terms of cell number and of cell soma size. When antibody-secreting cells are implanted at postnatal day 2 (P2), the effects observed at P8 are as severe as those obtained with anti-NGF antibodies and, interestingly, are observed also if anti-TrkA cells are implanted at P8, when anti-NGF antibodies, delivered by the same route, are no longer effective (). The effects induced by anti-TrkA, as those induced by anti-NGF, are reversible, but the time required for recovery and the critical period in the sensitivity of BFCNs to the functional inactivation of TrkA is twice as long than that observed when NGF is intercepted. These results demonstrate that BFCNs are more sensitive to the block of TrkA activation than they are to the block of NGF. The cloning of MNAC13 variable regions and their assembly into a functional polypeptide of reduced size (single chain Fv fragment) will allow its use in gene transfer applications.


Heart Team decision making and long-term outcomes for 1000 consecutive cases of coronary artery disease.
The Heart Team has been recommended as standard care for patients with coronary artery disease (CAD). However, little is known about the real benefits, potential treatment delays and late outcomes of this approach. Our goal was to determine the safety and feasibility of multidisciplinary Heart Team decision making for patients with CAD. We retrospectively assessed 1000 consecutive cases discussed by the Heart Team between November 2010 and January 2012. We assessed (i) time intervals between different care steps involving the Heart Team; (ii) the distribution of patients according to the complexity of their CAD; and (iii) the 5-year survival as estimated from Kaplan-Meier curves. Of 1000 case discussions, 40 were repeat cases, resulting in 960 unique cases. The mean age was 65 years, 73% were men, and 29% had diabetes. Native vessel disease was present in 86.4%, of which 69% had simple 1-vessel disease (1VD) or 2-vessel disease (2VD), and 31% had complex left main (LM) or 3-vessel disease (3VD). The time interval between referral by a community hospital and final treatment was less than 6 weeks for 90% of cases. Treatment decisions were delayed in 35% of cases due to a need for additional diagnostic information. For simple 1- or 2VD with or without proximal left anterior descending artery involvement, treatment was medical therapy in 6% and 12%, respectively; percutaneous coronary intervention (PCI) in 88% and 85%, respectively; and coronary artery bypass grafting (CABG) in 6% and 3%, respectively. For 3VD disease, treatment was equally split between CABG and PCI (46% for both). PCI was preferred for isolated LM or LM with 1VD (81% vs CABG 16%), whereas CABG was preferred in LM with 2- or 3VD (71% vs PCI 19%). The 5-year mortality rate was 16% for 1- or 2VD, 17% for 3VD, 3% for isolated LM or with 1VD and 27% for LM with 2- or 3VD. In this single-centre analysis, the Heart Team approach was feasible, with decision making and treatment by the Heart Team following within a short time after referral. However, the timing of treatment could be further optimized if adequate information and imaging were available at the time of the Heart Team meeting. The final treatment recommendation by the Heart Team was largely in accordance with clinical guidelines.


Sc2(mu2-O) trapped in a fullerene cage: the isolation and structural characterization of Sc2(mu2-O)@C(s)6-C82 and the relevance of the thermal and entropic effects in fullerene isomer selection.
The new endohedral fullerene, Sc(2)(mu(2)-O)@C(s)(6)-C(82), has been isolated from the carbon soot obtained by electric arc generation of fullerenes utilizing graphite rods doped with 90% Sc(2)O(3) and 10% Cu (w/w). Sc(2)(mu(2)-O)@C(s)(6)-C(82) has been characterized by single crystal X-ray diffraction, mass spectrometry, and UV/vis spectroscopy. Computational studies have shown that, among the nine isomers that follow the isolated pentagon rule (IPR) for C(82), cage 6 with C(s) symmetry is the most favorable to encapsulate the cluster at T > 1200 K. Sc(2)(mu(2)-O)@C(s)(6)-C(82) is the first example in which the relevance of the thermal and entropic contributions to the stability of the fullerene isomer has been clearly confirmed through the characterization of the X-ray crystal structure.