Directly Formed Alucone on Lithium Metal for High-Performance Li Batteries and Li-S Batteries with High Sulfur Mass Loading.
Lithium metal is considered the "holy grail" of next-generation battery anodes. However, severe parasitic reactions at the lithium-electrolyte interface deplete the liquid electrolyte and the uncontrolled formation of high surface area and dendritic lithium during cycling causes rapid capacity fading and battery failure. Engineering a dendrite-free lithium metal anode is therefore critical for the development of long-life batteries using lithium anodes. In this study, we deposit a conformal, organic/inorganic hybrid coating, for the first time, directly on lithium metal using molecular layer deposition (MLD) to alleviate these problems. This hybrid organic/inorganic film with high cross-linking structure can stabilize lithium against dendrite growth and minimize side reactions, as indicated by scanning electron microscopy. We discovered that the alucone coating yielded several times longer cycle life at high current rates compared to the uncoated lithium and achieved a steady Coulombic efficiency of 99.5%, demonstrating that the highly cross-linking structured material with great mechanical properties and good flexibility can effectively suppress dendrite formation. The protected Li was further evaluated in lithium-sulfur (Li-S) batteries with a high sulfur mass loading of ∼5 mg/cm2. After 140 cycles at a high current rate of ∼1 mA/cm2, alucone-coated Li-S batteries delivered a capacity of 657.7 mAh/g, 39.5% better than that of a bare lithium-sulfur battery. These findings suggest that flexible coating with high cross-linking structure by MLD is effective to enable lithium protection and offers a very promising avenue for improved performance in the real applications of Li-S batteries.


Evaluation of neonatal streptozotocin induced diabetic rat model for the development of cataract.
Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.


[Related inflammation markers among different types of coronary heart disease].
To study the relationship between levels of activity of NF-kappaB p65, plasma soluble inter-cellular adhesion molecule-1, C-reactive protein on plaque stability, and different types of coronary heart disease. We measured the levels of plasma soluble inter-cellular adhesion molecule-1 and C-reactive protein by enzyme-linked immunosorbant assay and the activity of NF-kappaB p65 in peripheral blood lymocytes immunohistochemically. Compared with the stable angina and the control group, the baseline activity of NF-kappaB p65, sICAM-1 and C-reactive protein was significantly elevated in the acute myocardial infarction and the unstable angina (P <0.01). After 3 month follow-up, the levels of activity of NF-kappaB p65 and sICAM-1 were unchanged (P > 0.05). In all groups, C-reactive proteins were lowered at the review (P <0.01). The levels of activity of NF-kappaB p65, sICAM-1 and C-reactive protein are related to the plaque stability among different types of coronary heart disease. NF-kappaB p65, and sICAM-1 are not affected by the acute event. These plasma markers may be important risk factors for the development of the acute coronary syndrome.


Previous Ischemic Stroke Significantly Alters Stroke Risk in Newly Diagnosed Cancer Patients.
Previous ischemic stroke (IS) is a risk factor for subsequent IS in the general population; it is unclear if this relationship remains true in patients with cancer. Our objective was to examine the association between previous IS and risk for future IS in individuals newly diagnosed with cancer. We conducted a retrospective population-based matched cohort study of newly diagnosed adult cancer patients (excluding nonmelanoma skin cancers and primary central nervous system tumors) in Ontario, Canada from 2010 to 2020; those with prior IS were matched (1:4) by age, sex, year of cancer diagnosis, cancer stage, and cancer site to those without a history of stroke. Cumulative incidence function curves were created to estimate the incidence of IS. Subdistribution adjusted hazard ratios (aHRs) and 95% CIs were calculated, where death was treated as a competing event. Multivariable analysis was adjusted for imbalanced baseline characteristics. We examined 65 525 individuals with cancer, including 13 070 with a history of IS. The median follow-up duration was 743 days (interquartile range, 177-1729 days). The incidence of IS following cancer diagnosis was 261.3/10 000 person-years in the cohort with prior IS and 75.3/10 000 person-years in those without prior IS. Individuals with prior IS had an increased risk for IS after cancer diagnosis compared with those without a history (aHR, 2.68 [95% CI, 2.41-2.98]); they also had more prevalent cardiovascular risk factors. The highest risk for stroke compared with those without a history of IS was observed in the gynecologic cancer (aHR, 3.84 [95% CI, 2.15-6.85]) and lung cancer (aHR, 3.18 [95% CI, 2.52-4.02]) subgroups. The risk of IS was inversely correlated with lag time of previous stroke; those with IS 1 year before their cancer diagnosis had the highest risk (aHR, 3.68 [95% CI, 3.22-4.22]). Among individuals with newly diagnosed cancer, those with IS history were almost 3× more likely to experience a stroke after cancer diagnosis, especially if the prediagnosis stroke occurred within 1 year preceding cancer diagnosis.


Quality of life and pain multidimensional aspects in individuals with HTLV-1.
HTLV-1 creates a chronic health condition that involves moderate to severe pain with a negative impact on quality of life (QoL). There is no consensus on which attitudes to pain are more related to the worsening of QoL in HTLV-1 infected patients. The aim of this study was to investigate the correlation between QoL and multidimensional aspects of pain in patients with HTLV-1. A cross-sectional study was conducted in Salvador, Bahia, Brazil. The study included individuals diagnosed with HTLV-1. The Short Form 36 Questionnaire was used to analyze QoL, and the Brief Pain Inventory was used to assess multidimensional aspects of pain. The mean pain intensity was 4.88±3.06 on the visual pain scale, and the average impact on QoL corresponded to a loss of approximately 40%. Moderate to high correlations between pain intensity and all domains of QoL were observed and compared reaction attitudes for general activity, mood, ability to walk, ability to work, relationships, sleep, and ability to enjoy life (r>0.40; p<0.05). Moderate correlations were found between all domains of QoL, pain intensity, and reactive attitudes to pain. The greatest pain intensity impacts involved difficulty to walk and to work, and interpersonal relationships in the emotional aspect of QoL.


[Liver transplantation for hepatocellular carcinoma: experience at an Australian transplantation unit].
The author experienced 11 cases of orthotopic liver transplantation (LTx) for hepatocellular carcinoma (HCC) in Sydney, Australia, series. LTx was selected in 5 cases for the treatment of HCC and in 6 for terminal liver failure. Three patients had new lesions, which were not detected on preoperative imaging, and 5 had vascular or extrahepatic infiltrations. Two patients with hepatitis C had recurrence of hepatitis at an early stage. Two had tumor recurrence, one of which had 7 lesions with invasion to the vessels and bare area. Thus some problems remain in LTx for HCC, including the recurrence of hepatitis in hepatitis C and tumor recurrence in cases with high-risk factors based on the pathologic findings.


Interaction of purified precipitating and non-precipitating (coprecipitating) antibodies with hapten and with haptenated protein. Evidence of an asymmetric antibody molecule.
The interaction of monovalent hapten dinitrophenyl epsilon-amino caproic acid (DNP-EACA) with purified IgG1 sheep anti-DNP precipitating and non-precipitating antibodies, and their F(ab')2, F(ab') and Fab fragments, was studied by fluorescence quenching and by a radioimmunoassay. The Scatchard plots of whole non-precipitating antibody and its F(ab')2 fragment showed a bi-modal curve that could be interpreted as due to the existence of two populations of sites with very different affinity for the ligand, each population representing 50% of the total number of sites. The F(ab) fragments of the non-precipitating antibody could be fractionated by immunoadsorption into two populations of high and low affinity whose association constants differed by more than 2 logs. The study of the interaction of whole antibodies with DNP-bovine serum albumin (BSA) demonstrated that each molecule of precipitating antibody can combine with two molecules of antigen but non-precipitating antibody cannot combine with more than one molecule of antigen. It is concluded that the molecule of non-precipitating antibody is asymmetric and has a site of high affinity and another of low affinity. As a consequence of this structure the non-precipitating antibody behaves functionally as univalent and is unable to form precipitates with the multivalent antigen and to activate effector mechanisms.


[Health demands in adolescence. The results of 2 epidemiological studies in the Padua area in 1990-1992].
In order to make a detailed analysis of the specific requirements of adolescent health in this country, local health unit n. 19 in Padua performed an epidemiological survey with the collaboration of 15 general physicians who were asked to record all ambulatory visits by 13-24 year olds on a special form. The survey, which lasted two years, revealed that of a total of 4748 records, 2112 (44.48%) were male and 2636 (55.51%) were female. The age at which the greatest number of visits was recorded was 18. The majority of adolescents attended alone (68.48%) and this pattern tended to increase with age. The frequency of annual attendance was 86.64%. In order of frequency, diagnoses included: requests for certificates and prescriptions (21.76%); respiratory disease and influenza (21.61%); obstetric and gynecological problems (8.61% of the total and 15.52% of female attendance) which together with auxoendocrinological problems amounted to a frequency of 10.55%; psychological problems (6.53%); dermatological diseases (6.324%); problems involving the osteomuscular structure, problem of the digestive tract (4.93%); nervous disorders and diseases of the sense organs (4.87%); medication and requests for information (3.60%); nephro-uro-andrological problems (3.26%). the high rate of attendance at medical clinics does not show that adolescents are an often ill population but that the doctor has been selected as the prime interlocutor for all health-related problems. It should also be pointed out that the majority of problems tend to be reported as somatic, whereas only a minimum part (6.53%) are classified as psychological. This analysis confirms, however, that the health requirements presented as somatic often involve a psychological component.


Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.
The ubiquitin-proteasome pathway plays a pivotal role in tumor progression. Rpn10 is the major ubiquitin (Ub) receptor of the 26S proteasome. Mounting evidence shows that Rpn10 is associated with the progression of several tumor types. However, little is known regarding the mechanistic role of Rpn10 in hepatocellular carcinoma (HCC). In this study, we found that the upregulation of Rpn10 in HCC was associated with poor prognosis. The ectopic overexpression of Rpn10 increased HCC cell proliferation, whereas silencing Rpn10 expression resulted in decreased cell proliferation. Furthermore, we demonstrated that knockdown of Rpn10 induced cell cycle arrest at G1 phase in HCC cells. In addition, we found that Rpn10 increased cell proliferation via regulation of the PTEN/Akt pathways. Knockdown of Rpn10 induced suppression of cell proliferation could be reversed by overexpressing active Akt in HCC cells. Rpn10 directly promoted PTEN degradation through the ubiquitin-proteasome system. The transcription factor HIF1α directly bound to the Rpn10 promoter and increased its expression in HCC tissue. Moreover, we observed a significant correlation between HIF1α expression and Rpn10 levels in HCC patients and found that the combination of these two parameters was a more powerful predictor of poor prognosis than either parameter alone. Collectively, these findings highlight the molecular mechanism of Rpn10 expression in HCC and provide valuable information for cancer prognosis and treatment.


Fine aspiration versus fine cutting needle, and comparison between smear cytology, inclusion cytology and microhistology in abdominal lesions.
Two hundred patients underwent ultrasound guided percutaneous fine needle biopsy of focal solid abdominal lesions using 22 gauge aspiration and cutting needles. The material obtained by aspiration needle was treated by smear cytology and by inclusion cytology, and that obtained by cutting needle by microhistology. The retrieval rate was 89% for aspiration needle (smear cytology = 89%, inclusion cytology = 83.5%) and was 83% for cutting needle; the combined diagnostic accuracy was 98%. The typing accuracy was 76% for smear cytology, and was 84% for inclusion cytology and microhistology. We conclude that: 1. to obtain the highest retrieval rate (98%) both aspiration and cutting needles are necessary, because the aspiration needle is more likely to secure necrotic or soft tissue, and the cutting needle, fibrous or hard tissue; 2. histologic treatment of the samples yields a higher typing accuracy: 84% vs 76%; however, smear cytology remains essential because it permits a much faster evaluation of the adequacy of the sample and because it may avoid histologic methods in 76% of cases; 3. the smear cytology + microhistology combination seems to be the best solution (retrieval rate = 97.5%), but the costs are much higher because the cutting needle is somewhat expensive. The best solution would be to use the combination smear + inclusion cytology (retrieval rate = 89%) and to reserve the cutting needle for when aspiration needle material proves to be inadequate.


Differences in the predicted nasoseptal flap length among races: A propensity score matching analysis.
We compared the lengths of a nasoseptal flap (NSF) and skull base according to race, age, and sex. We performed paranasal sinus computed tomography in 19,961 adult patients between 2003 and 2022. The race of the patients was East Asian (n = 71), Caucasian (n = 71), or Middle Eastern (n = 71). The expected lengths of the NSF and anterior skull base defect were measured and analyzed according to race, age, and sex. Compared with Caucasians and Middle Easterners, East Asians had a shorter NSF length (p < 0.001) and lower ratio of the expected NSF length to the expected defect length (p < 0.001). There was no difference in the values among age groups. The expected NSF length was longer, and the ratio of the expected NSF length to the expected defect length was higher, in males than females (p < 0.001 for both). East Asians and females had a shorter NSF length and lower ratio of expected NSF to surgical defect lengths after anterior skull base reconstruction compared with the other races and with males, respectively. Anatomical differences should be considered when long NSF lengths are required, such as for anterior skull base reconstruction.


Research advances in major cereal crops for adaptation to abiotic stresses.
With devastating increase in population there is a great necessity to increase crop productivity of staple crops but the productivity is greatly affected by various abiotic stress factors such as drought, salinity. An attempt has been made a brief account on abiotic stress resistance of major cereal crops viz. In spite of good successes obtained on physiological and use molecular biology, the benefits of this high cost technology are beyond the reach of developing countries. This review discusses several morphological, anatomical, physiological, biochemical and molecular mechanisms of major cereal crops related to the adaptation of these crop to abiotic stress factors. It discusses the effect of abiotic stresses on physiological processes such as flowering, grain filling and maturation and plant metabolisms viz. photosynthesis, enzyme activity, mineral nutrition, and respiration. Though significant progress has been attained on the physiological, biochemical basis of resistance to abiotic stress factors, very little progress has been achieved to increase productivity under sustainable agriculture. Therefore, there is a great necessity of inter-disciplinary research to address this issue and to evolve efficient technology and its transfer to the farmers' fields.


A deep-blue emitter with electron transporting property to improve charge balance for organic light-emitting device.
Highly efficient deep-blue organic light-emitting devices (OLEDs) have been fabricated using 2,7-di(2,2':6',2″-terpyridin-4-yl)-9,9-dioctyl-9H-fluorene (DTPF) as the emitter, which has a wide energy gap, high emission quantum yield (Φf = 0.88), and high electron transporting property to improve the charge balance. A high efficiency of 2.55 cd/A and 2.67 lm/W are obtained in OLED. The device also exhibits a low turn-on voltage of 3.0 V and Commission Internationale de l'Éclairage (CIE) coordinates of (0.16, 0.09).


Cellular Reprogramming Using Protein and Cell-Penetrating Peptides.
Recently, stem cells have been suggested as invaluable tools for cell therapy because of their self-renewal and multilineage differentiation potential. Thus, scientists have developed a variety of methods to generate pluripotent stem cells, from nuclear transfer technology to direct reprogramming using defined factors, or induced pluripotent stem cells (iPSCs). Considering the ethical issues and efficiency, iPSCs are thought to be one of the most promising stem cells for cell therapy. Induced pluripotent stem cells can be generated by transduction with a virus, plasmid, RNA, or protein. Herein, we provide an overview of the current technology for iPSC generation and describe protein-based transduction technology in detail.


Substance P immunoreactivity in Alzheimer disease: a study in cases presenting symmetric or asymmetric cortical atrophy.
Substance P-like immunoreactivity was visualized by immunohistochemical methods in 20 postmortem brains: 6 senile, 4 presenile Alzheimer dementia (AD), 3 AD with interhemispheric asymmetric cortical atrophy, and 7 control cases. For all pathological cases, the SP-like immunoreactivity was significantly reduced in the neocortical areas and in the hippocampus. This contrasted with an enhanced SP-like immunoreactivity in the pallidum and the substantia nigra in AD brains and a more pronounced SP-like immunoreactivity in the more atrophic side in the asymmetrically atrophied brains.


Transition strategies from cangrelor to oral platelet P2Y12 receptor antagonists.
Cangrelor is the first parenteral antagonist of the platelet P2Y12 receptor. This direct-acting antagonist of the platelet P2Y12 receptor should be considered an adjunct to a percutaneous coronary intervention in patients who have not been adequately pretreated with platelet P2Y12 receptor antagonists at the time of the procedure. The use of cangrelor requires transition to an oral platelet P2Y12 receptor antagonist. Transition strategies have been developed on the basis of pharmacologic characteristics of platelet P2Y12 receptor antagonists, results of pharmacodynamic studies, and results from clinical trials. Cangrelor blocks the binding to the platelet P2Y12 receptor of the active metabolite of the thienopyridines, clopidogrel and prasugrel. The active metabolite of thienopyridines is present in blood for a short interval after administration. For this reason, clopidogrel should be administered after cangrelor is stopped. Prasugrel can be administered at the end of the cangrelor infusion or up to 30 min before cangrelor is stopped. Ticagrelor is also a reversible direct-acting antagonist of the platelet P2Y12 receptor. Because there is no interaction between ticagrelor and cangrelor, ticagrelor can be administered before or during the infusion of cangrelor.


Interleukin 4 gene-defective mice reconstituted with wild-type bone marrow fail to produce normal immunoglobulin E levels.
The ability to reconstitute interleukin (IL)-4-/- mice with bone marrow of IL-4+/+ mice was investigated. The absence of the IL-4-/- gene in donor or recipient cells did not impair the reconstitution. All immunoglobulin (Ig) subsets occurred at normal serum levels except for IgE and to some extent IgG1. IgE production did not recover in the reconstituted mice over prolonged time. However, these mice were competent for IgE production, because a single intrasplenic injection of IL-4 restored IgE levels, which then remained constant. Wild-type mice reconstituted with wild-type bone marrow constantly had IgE serum levels comparable to untreated animals. In wild-type mice reconstituted with IL-4-/- bone marrow, IgE levels dropped gradually and disappeared by week 12. We make three unrelated but nonetheless important conclusions: (a) (immunoregulation) the tightly regulated IL-4 gene should be expressed constantly in low amounts (and with apparent absence of antigen stimulation) to keep the normal threshold of IgE; (b) (ontogeny of the immune system) an early unidentified source of IL-4 must be postulated which is lost in adult mice; and (c) (bone marrow transfer/gene therapy) under certain circumstances, the genotype of the recipient influences the reconstitution.


Coagulation parameters for the differential diagnosis of pancreatic cancer in the early stage: a retrospective study.
In recent years, conventional coagulation (CC) and thromboelastography (TEG) parameters have been reported to be closely related to the progression of pancreatic cancer (PC). However, the potential utility of these parameters in differentiating benign and malignant pancreatic diseases is still unclear. A retrospective study was conducted to evaluate the efficacy of coagulation parameters in differentiating pancreatic cancer/early stage pancreatic cancer (EPC, TNM stages I and II) from benign control conditions, and to further explore whether coagulation parameters could improve the differential value of CA199. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to identify the diagnostic value of each coagulation parameter or combination of parameters. Compared with benign pancreatic disease (BPD), patients with pancreatic malignant tumors had significant coagulation disorders, specifically manifested as abnormal increases or decreases in several CC and TEG parameters (such as activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (DD2), K time, R time, Angle, maximum amplitude (MA), coagulation index (CI), and Ly30). In the training group, ROC curve showed that FIB, DD2, Angle, MA, and CI had favorable efficacy at differentiating PC or EPC from BPD (for PC, AUC = 0.737, 0.654, 0.627, 0.602, 0.648; for EPC, AUC = 0.723, 0.635, 0.630, 0.614, 0.648). However, several combined diagnostic indicators based on FIB, DD2 and CI failed to outperform the individual coagulation indexes in diagnostic efficiency. Combinations of certain coagulation indexes with CA199 outperformed CA199 alone at identifying PC or EPC, especially FIB + CA199 (for PC, AUC = 0.904; for EPC, AUC = 0.905), FIB + DD2 + CA199 (for PC, AUC = 0.902; for EPC, AUC = 0.900), FIB + CI + CA199 (for PC, AUC = 0.906; for EPC, AUC = 0.906), and FIB + DD2 + CI + CA199 (for PC, AUC = 0.905; for EPC, AUC = 0.900). The results from a validation set also confirmed that these combinations have advantageous diagnostic value for PC and EPC. A significant hypercoagulable state was common in PC. Some CC and TEG parameters are valuable in the differential diagnosis of benign and malignant pancreatic diseases. In addition, coagulation indexes combined with CA199 can further enhance the differential diagnosis efficacy of CA199 in PC and EPC.


Population pharmacokinetics of tazobactam/piperacillin in Japanese patients with community-acquired pneumonia.
The population pharmacokinetics on tazobactam/piperacillin (TAZ/PIPC; 1:8, 4.5 g x 3) was analyzed in Japanese patients with community-acquired pneumonia using the Nonlinear Mixed Effect Model version VI. Analysis by the one-compartment model yielded the following results for PIPC: total clearance (CL) = 8.22+(Ccr-71.4) x 0.0561 (L/hr), distribution volume (Vd) = 13.7 (L). The pharmacokinetic parameters for TAZ were: CL = 8.67 + (Ccr-71.4) x 0.0682 (L/hr), Vd = 14.4 (L). Of the pharmacokinetic parameters of PIPC, CL included Ccr as a variation factor, whereas the Vd included no variation factor. Because PIPC is excreted into the urine in the unchanged form, its pharmacokinetic factors seem to reflect the renal function status. In this study of patients with community-acquired pneumonia, the mean Vd per body weight was 0.26 L/kg, and the results suggested an increase of the Vd in patients with community-acquired pneumonia as compared with the value in healthy adults.


The bright homunculus in our head: Individual differences in intuitive sensitivity to logical validity.
Classic dual process theories of human reasoning attribute explicit reasoning to effortful, deliberative thinking. According to these models, intuitive processes lack any access to the formal rules of logic and probability and hence rely exclusively on superficial problem features to determine a response. However, in recent years, researchers have demonstrated that reasoners are able to solve simple logical or probabilistic problems relatively automatically, a capability which has been called "logical intuition." In four experiments, we instructed participants to judge the validity (Experiments 1 and 4), likeability (Experiments 1, 2, and 3), and physical brightness (Experiments 2, 3, and 4) of the conclusion to several reasoning problems. Brightness judgements were made by evaluating the font shade brightness of the argument's conclusion. Participants were also asked to complete a range of individual differences measures, drawing on cognitive ability and cognitive style, to evaluate the extent to which "logical intuitions" were linked to measures of deliberative reasoning. The results showed that participants judged the conclusion of logically valid statements to be more valid, more likable, and more physically bright than invalid statements. Participants with higher cognitive ability and unlimited processing time showed greater effects of logical validity in their liking judgements (varied across experiments). However, these effects were absent in the brightness tasks, suggesting that logic effects observed under instructions to judge conclusion brightness are a purer measure of "logical intuition." We discuss the implications of our findings for recent dual process theories of human reasoning.


Initiation of simian virus 40 DNA replication in vitro: large-tumor-antigen- and origin-dependent unwinding of the template.
Analysis of the kinetics of simian virus 40 (SV40) DNA replication in vitro demonstrated the existence of a slow presynthesis reaction that occurs prior to onset of extensive chain elongation and is dependent on a subset of the cellular proteins required for the complete replication reaction. When the presynthesis reaction is carried out in the presence of topoisomerase I, it is possible to detect extensive unwinding of the template DNA. This unwinding reaction is specific for templates that contain the wild-type SV40 origin of DNA replication and requires SV40 large tumor antigen (T antigen), ATP, and a protein fraction derived from HeLa cells. The required cellular protein may be a eukaryotic single-stranded-DNA-binding protein (SSB), since unwinding of the template is also observed when Escherichia coli SSB is substituted for the HeLa protein fraction. These observations suggest that during the initial stages of SV40 DNA replication, T antigen binds specifically to the viral origin and locally unwinds the DNA. This origin-dependent unwinding reaction is presumably a prerequisite for subsequent priming and elongation steps.


Double-blind placebo-controlled trial with flunarizine in therapy-resistant epileptic patients.
The anticonvulsant efficacy and side-effect liability of flunarizine (15 mg/day) was investigated in a randomized, double-blind, placebo-controlled, crossover design in 30 outpatients with drug-resistant complex partial seizures. Flunarizine or placebo was added to the preexisting medication and each patient was followed up for 10 months. At the end of the study data from 22 patients were available for evaluation. In patients taking first flunarizine and then placebo, plasma levels of flunarizine were still detectable at the end of the 4 months' placebo phase. In the group of 13 patients starting therapy with placebo, a significant seizure frequency reduction was observed during the flunarizine period in 11 patients, whereas one patient showed no change and seizure frequency increased in another patient. Two patients had a 50% reduction in seizure frequency. Flunarizine was well tolerated and few side effects were noted.


Life's Essential 8 and Life's Simple 7 in Relation to Coronary Atherosclerosis: Results From the Population-Based SCAPIS Project.
To examine the associations between the American Heart Association scores ("Life's Essential 8" [LE8] and "Life's Simple 7" [LS7]) and 2 subclinical coronary atherosclerosis indicators: coronary computed tomographic angiography (CCTA)-stenosis and coronary artery calcium (CAC). We included a population-based sample, aged 50 to 64 years, recruited between 2013 and 2018 from the Swedish Cardiopulmonary Bioimage Study (n=24,819, 50.3% women). CCTA-stenosis was graded as no stenosis, stenosis (1%-49%) or severe stenosis (≥50%), whereas CAC was graded as 0, 1 to 99, 100 to 399, or ≥400 Agatston units. Multinomial logistic regression and receiver operating characteristic (ROC) curves were used to study the associations between cardiovascular health scores and subclinical coronary atherosclerosis. Odds ratios (ORs) for CCTA-stenosis and severe CCTA-stenosis between the lowest (<50 points) vs the highest (≥80 points) LE8 group were 4.18 (95% CI, 3.56 to 4.91) and 11.17 (95% CI, 8.36 to 14.93), respectively. For corresponding CAC results, ORs were 3.36 (95% CI, 2.84 to 3.98), 7.72 (95% CI, 6.03 to 9.89), and 14.94 (95% CI, 10.47 to 21.31) for CAC scores of 1 to 99, 100 to 399, and ≥400, respectively. Area under ROC curves for predicting any stenosis were 0.642 (95% CI, 0.635 to 0.649) and 0.631 (95% CI, 0.624 to 0.638, P<.001) for LE8 and LS7, respectively. Our data indicate that LE8 showed a strong, graded, and inverse association with CCTA-stenosis and CAC score. The capacity to predict CCTA-stenosis was comparable between LE8 and LS7, although LE8 had slightly higher prediction capacity of any stenosis. This study provides novel evidence that the LE8 score may be a useful tool for monitoring cardiovascular health.


Analysis of chromosome 6q deletion in EBV-associated NK cell leukaemia/lymphoma.
Deletions involving chromosome 6q have been reported in a number of human cancers such as ovarian and breast tumours as well as haematopoietic malignancies. It seems that this region might contain tumour-suppressor genes. Putative natural killer cell lymphomas/leukaemias (NKLL) represent a group of recently characterized haematolymphoid malignancies sharing an immunophenotype of CD3/Leu4- CD3epsilon+ CD56+, a genotype of germline T-cell receptor genes, and have a close association with Epstein-Barr virus (EBV). Deletion at 6q21-q25 was demonstrated in three recently reported cases of NKLL. Here we investigated the possible involvement of 6q deletions in the pathogenesis, and especially the tumorigenesis of NKLL. The regions of D6S1574 (6p25), DS276 (6p12), D6S257 (6q11), D6S434 (6q14), D6S287 (6q15), D6S292 (6q21), D6S308 (6q22), D6S264 (6q25), and D6S446 (6q26) were analysed by PCR in 25 cases of NKLL, including seven cases with chronic NK leukaemia, six with acute NK leukaemia and 12 with NK lymphoma. 6q deletions, especially 6q15-25, were frequently detected, but 6p deletions were not detected in any cases. Analysis of 6q21 showed possible deletion in two of seven cases (29%) with chronic NK leukaemia, three of six (50%) with acute leukaemia, and 12 of 12 (100%) with NK lymphoma. The frequency of deletion increased in clinical phases. In three cases with lymphoma, fluorescence in situ hybridisation was performed, which confirmed 6q21 deletion in two cases, although 6q telomeric and centromeric regions were preserved. The other case failed to show deletion. Our results suggest that 6q deletion, especially 6q21-25, might be involved in NKLL tumorigenesis, and support the presence of the tumour suppressor genes associated with the development of NKLL.


Manifestations of blood coagulation and its relation to clinical outcomes in severe COVID-19 patients: Retrospective analysis.
Characteristics of blood coagulation and its relation to clinical outcomes in COVID-19 patients are still rarely reported. We aimed to investigate the blood coagulation function and its influences on clinical outcomes of patients with syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 71 severe patients with confirmed SARS-CoV-2 infection who were treated in Wuhan First Hospital from February 12 to March 20, 2020, were enrolled. The blood coagulation data in these patients and in 61 healthy controls were collected. The patients with COVID-19 were divided into two groups: the aggravated group and the nonaggravated group, respectively, basing on whether the patients' conditions turned to critically ill or not after admission. Compared with healthy controls, patients with COVID-19 had significant performances with coagulation dysfunction, including dramatically elevated values of FIB, PT, APTT, INR, FDP, and D-Dimers but markedly reduced AT value (P < .05). Importantly, more noteworthy coagulation disorders similar to the differences between patients and controls were found in the aggravated patients with conditions deterioration after admission than those in the nonaggravated patients without conditions deterioration (P < .05). Moreover, the aggravated patients possessed a longer hospital stay and a higher mortality compared with the nonaggravated patients (P < .001). The coagulation parameters of COVID-19 patients were widely and closely related to the indexes of liver function and inflammation (P < .05), indicating the coagulation dysfunction of these patients may be caused by liver injury and inflammatory storm. Severe patients with SARS-CoV-2 infection often possess coagulation dysfunction on admission. A certain correlation exists in coagulation disorder and adverse clinical outcome among severe COVID-19 patients.


Enantioselective total synthesis of (+)-azimine and (+)-carpaine.
[reaction: see text] The enantioselective total syntheses of (+)-azimine and (+)-carpaine have been developed, starting with (S)-1,2,4-butanetriol as a single source of chirality. The key common feature in these syntheses involves stereoselective intramolecular hetero-Diels-Alder reaction of an acylnitroso compound. The critical macrocyclic dilactonization of the N-Cbz derivatives of azimic acid and carpamic acid was efficiently achieved by using the Yamguchi macrocyclization conditions.


Endogenous reverse transcriptase: a mediator of cell proliferation and differentiation.
Endogenous, non-telomeric Reverse Transcriptase (RT) is encoded by two classes of repeated genomic elements, retrotransposons and endogenous retroviruses, and is an essential component of the retrotransposition machinery of both types of elements. Expression of RT-coding genes is generally repressed in non-pathological, terminally differentiated cells, but is active in early embryos, germ cells, embryo and tumor tissues, all of which have a high proliferative potential. To clarify whether reverse transcription is functionally implicated in control of cell growth, differentiation and in embryogenesis, recent experiments have been undertaken to inactivate the endogenous RT activity. RT was inhibited in normal and transformed cell lines by exposure to nevirapine, a non-nucleosidic RT inhibitor. The endogenous RT was also blocked in murine embryos by microinjection of an anti-RT antibody. Both experimental approaches yielded a dramatic inhibition of proliferation. Murine embryos arrested at pre-implantation stages. Transformed cell lines underwent a significant reduction in the rate of cell growth, concomitant with the induction of differentiation. In addition, RT inhibition induced an extensive reprogramming of the gene expression profile both in cultured cell lines and in preimplantation embryos. From these studies, endogenous RT begins to emerge as a key function with a driving role in normal and pathological developmental processes.


Temporal cortex dopamine D2/3 receptor binding in major depression.
The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [(123)I]epidepride to image D(2/3) receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D(2/3) receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives.


Does size matter in platelet production?
Platelet (PLT) production represents the final stage of megakaryocyte (MK) development. During differentiation, bone marrow MKs extend and release long, branched proPLTs into sinusoidal blood vessels, which undergo repeated abscissions to yield circulating PLTs. Circular-prePLTs are dynamic intermediate structures in this sequence that have the capacity to reversibly convert into barbell-proPLTs and may be related to "young PLTs" and "large PLTs" of both inherited and acquired macrothrombocytopenias. Conversion is regulated by the diameter and thickness of the peripheral microtubule coil, and PLTs are capable of enlarging in culture to generate barbell-proPLTs that divide to yield 2 smaller PLT products. Because PLT number and size are inversely proportional, this raises the question: do macrothrombocytopenias represent a failure in the intermediate stages of PLT production? This review aims to bring together and contextualize our current understanding of terminal PLT production against the backdrop of human macrothrombocytopenias to establish how "large PLTs" observed in both conditions are similar, how they are different, and what they can teach us about PLT formation. A better understanding of the cytoskeletal mechanisms that regulate PLT formation and determine PLT size offers the promise of improved therapies for clinical disorders of PLT production and an important source of PLTs for infusion.


High-temperature stability of silicon carbide nanowires.
The paper reports morphology and structure transitions of silicon carbide (SiC) nanowires during high temperature annealing; the as-prepared nanowires are in the form of SiC core and SiO2 shell. The transition temperature is about 1200 degrees C, 600 degrees C lower than that of SiC microfibers, and it starts with the formation of junctions of individual nanowires. The junctions grow into webs while the crystalline SiC cores of the nanowires oxidize. The growth and the oxidation eventually lead to the formation of an oxide film, when the transition completes. The thermal stability and the transition mechanisms of SiC nanowires are critical to their applications in high temperature environments.


Optimizing pain management to facilitate Enhanced Recovery After Surgery pathways.
The optimal management of postoperative pain using multimodal analgesia is a key component of Enhanced Recovery After Surgery (ERAS). Pain has adverse clinical implications on postoperative recovery, including prolonging the time to recovery milestones and length of hospital stay. Moreover, the ubiquity of opioids in postoperative analgesic regimens results in adverse effects, such as sedation, postoperative nausea and vomiting, urinary retention, ileus, and respiratory depression, which can delay discharge. Thus, multimodal analgesia, i.e., the use of more than one analgesic modality to achieve effective pain control while reducing opioid-related side effects, has become the cornerstone of enhanced recovery. The purpose of this review is to address the analgesic techniques used as part of multimodal analgesic regimens to optimize postoperative pain control and to summarize the evidence for their use in reducing opioid requirements and side effects. There is a wide variety of analgesic techniques available for multimodal postoperative analgesia. These modalities are divided into pharmacological and non-pharmacological techniques. Systemic pharmacological modalities involve opioids and non-opioids such as acetaminophen, non-steroidal anti-inflammatory drugs, N-methyl-D-aspartate receptor antagonists, anticonvulsants (e.g., gamma-aminobutyric acid analogues), beta-blockers, alpha-2 agonists, transient receptor potential vanilloid receptor agonists (capsaicin), and glucocorticoids. Other pharmacological modalities include central neuraxial techniques, surgical-site infiltration, and regional anesthesia. Evidence supports the use of these pharmacological techniques as part of multimodal analgesia, but each has its own advantages and specific safety profile, which highlights the importance of selecting the appropriate analgesics for each patient. Adjunctive non-pharmacological techniques include acupuncture, music therapy, transcutaneous electrical nerve stimulation, and hypnosis. There is mixed evidence regarding such techniques, although a lack of harm is associated with their use. There are continuing advancements in multimodal analgesic techniques; however, postoperative pain in general continues to be undermanaged. Furthermore, a continuing challenge in multimodal pain research related to ERAS is the difficulty in carrying out randomized trials to determine the relative importance of any one component, including analgesia.


[Megaesophagus microbiota and carcinogenesis].
The risk of development of spin cell carcinoma of the esophagus is 33 times higher in patients with chagasic achalasia. It is possible that the production of N-nitroso compounds in the esophageal lumen by of bacterial action in the stasis liquid that reduce nitrates from diet into nitrites may play a role in this process. To analyze qualitatively and quantitatively the microbiota in chagasic megaesophagus with special attention to bacteria capable of transforming nitto reduction. Fifteen patients (six men and nine women) were prospectively studied, with ages varying from 28 to 73 years. Patients were divided into three sub-groups according to Rezende et al. classification of esophageal dilation (grade I, grade II and grade III). The sample collection was performed using a method specially developed to avoid contamination with microorganisms of the oral cavity and oropharynx, using a Levine catheter n 14 and a 7,5 oro-traqueal tube. Ninety three point three percent of the cultures were positive, with great bacterial variability and predominance of a variety of aerobic Gram-positive and anaerobic bacteria. The bacterial concentrations were generally more elevated in grade III in comparison to grade I and grade II. Among the microorganisms found, Staphylococcus sp, Corynebacterium sp, Peptostreptococcus sp e a Veillonella sp were those with the capability of nitrate reduction. It was concluded that patients with megaesophagus present some bacteria in the esophageal lumen that are able to reduce nitrates intro nitrites, an important step in the formation of N-nitroso compounds.


Allowing more time to ILCOR Step A of neonatal resuscitation leads to better residents' task completion in simulated scenarios. A problem of time pressure?
Roughly 10% of newborns need help to complete the transition of birth. For these infants, international guidelines recommend supporting them using a 4-step procedure (A to D). Step A is an assessment time, which includes eight tasks and finishes by starting the positive pressure ventilation (PPV), if necessary (step B). The guidelines changed in 2015 and the allotted time was raised from 30 to 60 seconds for step A completion. This study aimed to assess if the reduced time constraint in step A could have an impact on 1st-year pediatric residents' performance to complete step A and if could lead to later initiation of step A. Using video recordings of standardized neonatal scenarios over 6 years (3 before the change and 3 after), we assessed the ability of 1st-year pediatric residents of the Paris region to complete step A and initiate PPV in the allotted time in each period. Among the sessions, including at least five scenarios we evaluated all the PPV required scenarios executed for the first time by a dyad of 1st-year pediatric residents. Among 52 sessions, we included 104 scenarios (25 sessions and 50 scenarios before the change and 27 sessions and 54 scenarios after). PPV started roughly at 1-minute resuscitation in both periods, but completion of the tasks before PPV-start was significant. Only 12% of the dyad of residents executed the eight tasks before PPV initiation in the first period versus 54% in the second period (p < 0.0001). Additionally, the completion of the eight tasks of step A was significantly better during the second period (6 [6-7] vs. 8 [7-8] p < 0.001). These results could suggest that a reduced time constraint for step A imposed by the new Guidelines was associated with better performance.


The importance of enteral nutrition to prevent or treat undernutrition in children undergoing treatment for cancer.
Nutrition therapy is a therapeutic approach to treating medical conditions and symptoms via diet, which can be done by oral, enteral or parenteral routes. It is desirable to include nutritional interventions as a standard of care in pediatric cancer units (PCUs) at all levels of care. The interventions are dependent on available resources and personnel across all clinical settings. Enteral nutrition is easy, inexpensive, uses the gastrointestinal tract, maintains gut mucosal integrity, and allows for individualized nutritional strategies. This narrative review describes enteral nutritional interventions for children undergoing cancer treatment and is aimed at PCUs of all levels of care located in a low- and middle-income country.


Prevalence of the metabolic syndrome in kidney transplant recipients: A single-center study.
Metabolic syndrome (MS) is characterized by a combination of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and alterations in glucose homeostasis). Insulin resistance is suggested to be the common pathogenic background. This syndrome is also a risk factor for diabetes and chronic kidney disease. In renal transplant recipients, MS has been shown to be an independent risk factor for chronic allograft dysfunction, graft failure, new-onset diabetes, and CV disease. We performed a cross-sectional study on 106 stable renal transplant recipients to detect MS between January 2013 and August 2013. This syndrome was diagnosed according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Patients with history of diabetes mellitus were excluded from the study. In this group of patients, 56 (52.8%) had MS. There were 32 males (57.1%) and 24 females (42.9%). The mean age of the MS group was significantly higher than the non-MS group. The mean serum creatinine was higher in the MS group than the non-MS group, but there was no significant difference between them (P >0.05). The calculated glomerular filtration rate was also similar in the two groups (P >0.05). The patients with MS had higher body weight (64.61 ± 14.17 kg vs. 58.76 ± 11.70 kg, P <0.05) and also higher body mass index (BMI) (P <0.05). The prevalence of BMI >25 kg/m2 in the MS group was 75% versus 25% in the non-MS group (P <0.05). Since MS is an important and common risk factor in renal transplant recipients, we have to try to prevent it by educating the patients to control it by modifying their lifestyle. Efforts toward promoting healthy diets, physical activity, and blood pressure control must be undertaken.


Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: from basic to clinic.
The lipid metabolism in sperm cells is important both for energy production and for cell structure. A special composition of membrane phospholipids, rich in polyunsaturated fatty acids (PUFA), and the different composition of sperm and immature germ cell membrane are described and discussed. Testis germ cells as well as epididymal maturing spermatozoa are endowed with enzymatic and non-enzymatic scavenger systems to prevent lipoperoxidative damage. Catalase, superoxide dismutase, and glutathione-dependent oxidoreductases are present in variable amounts in the different developmental stages. Phospholipid hydroperoxide glutathione peroxidase (PHGPx) activity and roles in caput and cauda epididymal sperm cells are discussed. Also seminal plasma has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation and the degree of PUFA insaturation acts to achieve the same goal. Systemic predisposition and a number of pathologies can lead to an anti-oxidant/pro-oxidant disequilibrium. Scavengers, such as glutathione can be used to treat these cases as they can restore the physiological constitution of PUFA in the cell membrane.


HNRNPH1 is required for rhabdomyosarcoma cell growth and survival.
Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-y survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in three cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction of tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data contribute to understanding the role of HNRNPH1 in RMS development.


Resistance to biofilm formation on otologic implant materials.
New materials and coatings are now being developed to resist permanent bacterial contamination of implanted medical devices. This study exposed several styles of middle ear ventilation tube materials and coatings to high concentrations of Pseudomonas and Staphylococcus. Electron microscopy was then used to evaluate these tubes' resistance to bacterial biofilm formations. Ionized, processed silicone tubes were the only tubes resistant to Pseudomonas adhesion. Tubes that were made of fluoroplastic or that were ionized processed were very resistant to Staphylococcus contamination when compared with untreated silicone or silver oxide-treated silicone. This study suggests that ionized, coated fluoroplastic would be a highly effective tube material in preventing bacterial biofilm contamination of implanted ventilation tubes.


Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy.
Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation. We also focus on the influence of immunosuppressive drugs on MDSCs as well as future obstacles and research directions in this field.


The herbicide glyphosate is a weak inhibitor of acetylcholinesterase in rats.
The current work evaluated the inhibitory potency of the herbicide glyphosate (GLP) on acetylcholinesterase (AChE) activity in male and female rat tissues. The AChE activity in brain was higher (p<0.05) than those observed in kidney (females: 2.2-fold; males: 1.9-fold), liver (females: 6-fold; males: 6.9-fold) and plasma (females: 14.7-fold; males: 25.3-fold). Enzyme activities were higher in presence of 10mM GLP compared to those measured at an equimolar concentration of the potent AChE inhibitor dichlorvos (DDVP). Moreover, IC50s for GLP resulted between 6×10(4)- and 6.8×10(5)-fold higher than those observed for DDVP. In conclusion, GLP is a weak inhibitor of AChE in rats.


Studying electron transfer through alkanethiol self-assembled monolayers on a hanging mercury drop electrode using potentiometric measurements.
A new approach based on measuring the change of the open-circuit potential (OCP) of a hanging mercury drop electrode (HMDE), modified with alkanethiols of different chain length conducted in a solution containing a mixture of Ru(NH3)6(2+) and Ru(NH3)6(3+) is used for studying electron transfer across the monolayer. Following the time dependence of the OCP allowed the extraction of the kinetic parameters, such as the charge transfer resistance (R(ct)) and the electron transfer rate constant (k(et)), for different alkanethiol monolayers. An electron tunneling coefficient, beta, of 0.9 A(-1) was calculated for the monolayers on Hg.


Age-area scaling of extinction debt within isolated terrestrial vertebrate assemblages.
A new model of delayed species loss (extinction debt) within isolated communities is applied to a large data set of terrestrial vertebrate assemblages (n = 188) occupying habitat fragments or islands varying greatly in size and age. The model encapsulates previous approaches based on diversity-dependent (DD) extinction rates while allowing for a more flexible treatment of temporal dynamics. Three important results emerge. First, species loss rate slows down with the age of the isolate, a strong and general pattern largely unnoticed so far. Secondly, while being good candidates in the light of previous works, DD models fail to account for this pattern, a result that necessitates a search for other mechanisms. Thirdly, a simple diversity-independent model based on area (converted into population size) and age explains 97% of the variability in species loss rate and appears to be a promising predictive tool to handle extinction debt following habitat loss.


Comparison of diphtheria intoxication in human and nonhuman cell lines and their resistant variants.
Differences in sensitivity to diphtheria toxin of several toxin-sensitive and toxin-resistant human and non-human cell lines were compared. A method is described whereby it is possible to compare the sensitivity of one cell line with another and obtain meaningful quantitative results. Based on the concentration of toxin required to produce 50% inhibition of protein synthesis after 24 h of exposure the ID50 (24) value toxin-resistant cells were found to be 105 to 106 times more resistant to toxin than toxin-sensitive cells. There was little variation in the ID50 (24) values for cells in each of the two groups. The toxin-resistant cells used in this study, naturally resistant as well as selected variants, possess elongation factor 2 which is susceptible to inactivation by toxin. It is suggested that they are capable of activation of toxin but either cannot bind toxin or are unable to transport toxin across the plasma membrane. Protein synthesis is inhibited when these resistant cells are exposed to high concentrations of toxin. Under these conditions it is likely that enough toxin is able to bypass the block in toxin-specific entry and reach the cytosol by a second, less efficient, nonspecific mechanism to catalyze the inactivation of elongation factor 2 and inhibit protein synthesis.


Variation of antioxidant activity and the levels of bioactive compounds in lipophilic and hydrophilic extracts from hot pepper (Capsicum spp.) cultivars.
Peppers (Capsicum spp.) are a rich source of diverse bioactive compounds with potential health-promoting properties. This study investigated the extraction efficiency of five solvents on antioxidant activities from cayenne (CA408 and Mesilla), jalapeño (Ixtapa) and serrano (Tuxtlas) pepper cultivars. Freeze-dried peppers were extracted using a Soxhlet extractor with five solvents: hexane, ethyl acetate, acetone, methanol, and methanol:water (80:20). The levels of specific bioactive compounds (phenolics, capsaicinoids, carotenoids and flavonoids) were determined by HPLC and antioxidant activities were assayed by three methods. For all pepper cultivars tested, hexane extracts had the highest levels of capsaicinoids and carotenoids, but methanol extracts had the maximum levels of flavonoids. Hexane extracts showed higher 2,2-diphenyl-1-pricrylhydrozyl (DPPH) radical-scavenging activity and higher reducing power, and acetone extracts (from Mesilla pepper) had a high reducing power. All pepper extracts, except hexane, were effective in preventing deoxyribose degradation, and the inhibition was increased by high concentrations of extracts. The results of the present study indicated that, among the different measures of antioxidant activity, DPPH radical-scavenging activity was strongly correlated with total bioactive compounds (capsaicinoids, carotenoids, flavonoids and total phenolics) in pepper cultivars.


Insulin and a putative insulin metabolic mediator fraction from liver and muscle stimulate p33 messenger ribonucleic acid accumulation by apparently different mechanisms.
We have previously shown that in rat H4 hepatoma cells insulin enhances the nuclear transcription of p33 mRNA in a dose- and time-dependent manner, with no alteration in mRNA half-time (t1/2). Presumably, this effect is mediated by the cell surface receptor. In this report, we have investigated the effect of putative insulin mediator fractions which act to control metabolic events on p33 mRNA accumulation in these cells. Initial experiments originally demonstrated an insulin-like effect of an added putative metabolic fraction to enhance p33 mRNA concentrations. However, when the fetal calf serum supply was changed, the effect of insulin remained, but that of added mediator was no longer observed. After a series of experimental approaches designed to alter the permeability of the cell membrane, it was found that in the presence of increased Ca2+, the effect of mediator could again be observed. The present data demonstrate that the partially purified cAMP-dependent protein kinase/adenylate cyclase inhibitory putative mediator fractions from liver and muscle enhance p33 mRNA accumulation in intact H4 hepatoma cells by a mechanism that is differentiated from that of insulin. The action of the putative mediator is inhibited by cycloheximide, while the action of insulin itself is not. These results suggest that insulin may control nuclear transcription by multiple signaling mechanisms. Alternatively, the added putative metabolic mediator may not enter the cell in the presence of cycloheximide or is inactive as such within the cell and must first be converted to an active species by a step requiring protein synthesis.


Effect of cell type on the subcellular localization of the thyrotropin-releasing hormone receptor.
The localization of an epitope-tagged receptor for thyrotropin-releasing hormone (TRH) expressed in different cell contexts was studied with immunofluorescence microscopy. In pituitary lactotrophs, which normally express TRH receptors, and in AtT20 pituitary corticotrophs, TRH receptor immunoreactivity was primarily confined to the plasma membrane. In HEK 293 and COS7 cells, TRH receptors were predominantly intracellular. In transiently transfected COS7 cells, the TRH receptor colocalized with endoplasmic reticulum and Golgi markers. The pattern of TRH receptor immunofluorescence was the same over a wide range of receptor expression in transiently transfected COS7 cells, and all cell lines bound similar amounts of 3H- and rhodamine-labeled TRH analogs, suggesting that cell-specific differences in TRH receptor localization were not simply the result of overexpression. In all cell contexts, TRH receptors on the plasma membrane underwent extensive ligand-driven endocytosis. Inhibitors of glycosylation did not alter the subcellular distribution of receptors. In HEK 293 cells expressing the transfected TRH receptor, protein synthesis inhibitors caused translocation of intracellular receptors to the cell surface, as shown by a marked increase in cell surface immunofluorescence and [3H][N3-methyl-His2]TRH binding. These results demonstrate that the subcellular localization of the TRH receptor depends on the cell context in which it is expressed and that intracellular receptors are capable of translocation to the plasma membrane.


Regulation of the angiotensinogen gene by estrogens in rat liver and different brain regions.
Estrogens regulate the production of angiotensinogen (AOG) in liver and other tissues. However, evidence suggests that the effect is tissue specific and that it may depend on a variety of factors. We have tested the effects of ethynylestradiol (EE) on liver AOG mRNA and plasma AOG in intact male and ovariectomized female rats, as well as in hypophysectomized male rats. EE stimulated both variables to a comparable extent and in a dose-dependent manner. However, its effect on plasma AOG was significantly higher in female than in male rats. In addition, there was no response in hypophysectomized male rats; however, responsiveness was restored by pretreatment of the animals with prolactin. AOG mRNA concentration was also affected by EE in brain, but there were striking time- and region-specific differences. These results indicate that cell-specific factors also modulate the response of the AOG gene to EE in extrahepatic tissues.


Influence of a Commercial Synbiotic Administered In Ovo and In-Water on Broiler Chicken Performance and Meat Quality.
The present study aimed to test the synbiotic PoultryStar® solUS delivered in ovo to evaluate its effect on hatchability, productive performance and meat quality, compared to its post-hatch administration in water. On the twelfth day of embryonic incubation, 1200 fertile eggs were divided into synbiotic groups injected with 2 mg/embryo (T1) and 3 mg/embryo (T2), a saline group injected with physiological saline and an uninjected control group (C). After hatching, 120 male chicks/group were reared and chicks from the saline group were supplemented with the synbiotic via drinking water (T3). Hatchability was low in both T1 and T2 groups. Growth performance was not affected by the treatments. However, in the second rearing phase (15-36 days), birds from the C and T3 groups were heavier than T1 birds, due to a higher feed intake and daily weight gain. Neither route of synbiotic administration influenced final body weight (at 56 days), weight and yield of the carcass or commercial cuts. Physico-chemical properties, total lipid, cholesterol and fatty acid composition of breast muscle were not affected by the treatments. Considering its exploratory nature, this study has raised many questions that need further investigation, such as the bioactive combination and the effect on embryonic development.


VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd.
Regulation of vascular endothelial (VE) growth factor (VEGF)-induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell-specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase Cγ, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE-cadherin-positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad(-/-) mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.


DM-GRASP/ALCAM/CD166 is required for cardiac morphogenesis and maintenance of cardiac identity in first heart field derived cells.
Vertebrate heart development requires specification of cardiac precursor cells, migration of cardiac progenitors as well as coordinated cell movements during looping and septation. DM-GRASP/ALCAM/CD166 is a member of the neuronal immunoglobulin domain superfamily of cell adhesion molecules and was recently suggested to be a target gene of non-canonical Wnt signalling. Loss of DM-GRASP function did not affect specification of cardiac progenitor cells. Later during development, expression of cardiac marker genes in the first heart field of Xenopus laevis such as Tbx20 and TnIc was reduced, whereas expression of the second heart field marker genes Isl-1 and BMP-4 was unaffected. Furthermore, loss of DM-GRASP function resulted in defective cell adhesion and cardiac morphogenesis. Additionally, expression of DM-GRASP can rescue the phenotype that results from the loss of non-canonical Wnt11-R signalling suggesting that DM-GRASP and non-canonical Wnt signalling are functionally coupled during cardiac development.


Simultaneous determination of refractive index, extinction coefficient, and void distribution of titanium dioxide thin film by optical methods.
The refractive index n(λ) and the extinction coefficient k(λ) of a TiO(2) film prepared by electron-beam evaporation are determined in the spectral region 1.5-5.5 eV. The transmission spectrum of the TiO(2) film on a vitreous silica specimen is inverted to get the k(λ) of TiO(2) in its interband transition region. Above 3.5 eV, k(λ) is used to get the coefficients of the quantum mechanically derived dispersion relation of an amorphous TiO(2). These coefficients and n(∞) are used to determine n(λ). The modeling procedure is applied to spectroscopic ellipsometry data of a TiO(2) film on a c-Si specimen, and the void distribution of the film is revealed. With spectroscopic ellipsometry data above the fundamental band gap, valuable information about surface roughness is obtained. The effective thickness of this rough surface layer is confirmed by an atomic force microscopy measurement.


KDR Kinase Inhibitor Isolated from the Mushroom Boletopsis leucomelas.
Three novel p-terphenyl compounds, named boletopsins A (1), B (2), and C (3), and four known analogues (4-7) were isolated from fruiting bodies of the mushroom Boletopsis leucomelas. Compounds 1-7 were tested for KDR kinase inhibitory activity, and boletopsin C (3) was found to have an IC(50) value of 70.7 microM. Compound 3 also showed inhibition of proliferation of human umbilical vein endothelial cells, with an IC(50) value of 9.04 microM.


Psoriasis and inflammatory bowel disease: links and risks.
Psoriasis and the spectrum of inflammatory bowel diseases (IBD) are chronic, inflammatory, organotropic conditions. The epidemiologic coexistence of these diseases is corroborated by findings at the level of disease, biogeography, and intrafamilial and intrapatient coincidence. The identification of shared susceptibility loci and DNA polymorphisms has confirmed this correlation at a genetic level. The pathogenesis of both diseases implicates the innate and adaptive segments of the immune system. Increased permeability of the epidermal barrier in skin and intestine underlies the augmented interaction of allergens and pathogens with inflammatory receptors of immune cells. The immune response between psoriasis and IBD is similar and comprises phagocytic, dendritic, and natural killer cell, along with a milieu of cytokines and antimicrobial peptides that stimulate T-cells. The interplay between dendritic cells and Th17 cells appears to be the core dysregulated immune pathway in all these conditions. The distinct similarities in the pathogenesis are also reflected in the wide overlapping of their therapeutic approaches. Small-molecule pharmacologic immunomodulators have been applied, and more recently, biologic treatments that target proinflammatory interleukins have been introduced or are currently being evaluated. However, the fact that some treatments are quite selective for either skin or gut conditions also highlights their crucial pathophysiologic differences. In the present review, a comprehensive comparison of risk factors, pathogenesis links, and therapeutic strategies for psoriasis and IBD is presented. Specific emphasis is placed on the role of the immune cell species and inflammatory mediators participating in the pathogenesis of these diseases.


Proteomic analysis of rat soleus muscle undergoing hindlimb suspension-induced atrophy and reweighting hypertrophy.
A proteomic analysis was performed comparing normal rat soleus muscle to soleus muscle that had undergone either 0.5, 1, 2, 4, 7, 10 and 14 days of hindlimb suspension-induced atrophy or hindlimb suspension-induced atrophied soleus muscle that had undergone 1 hour, 8 hour, 1 day, 2 day, 4 day and 7 days of reweighting-induced hypertrophy. Muscle mass measurements demonstrated continual loss of soleus mass occurred throughout the 21 days of hindlimb suspension; following reweighting, atrophied soleus muscle mass increased dramatically between 8 hours and 1 day post reweighting. Proteomic analysis of normal and atrophied soleus muscle demonstrated statistically significant changes in the relative levels of 29 soleus proteins. Reweighting following atrophy demonstrated statistically significant changes in the relative levels of 15 soleus proteins. Protein identification using mass spectrometry was attempted for all differentially regulated proteins from both atrophied and hypertrophied soleus muscle. Five differentially regulated proteins from the hindlimb suspended atrophied soleus muscle were identified while five proteins were identified in the reweighting-induced hypertrophied soleus muscles. The identified proteins could be generally grouped together as metabolic proteins, chaperone proteins and contractile apparatus proteins. Together these data demonstrate that coordinated temporally regulated changes in the skeletal muscle proteome occur during disuse-induced soleus muscle atrophy and reweighting hypertrophy.


Congenital vascular anomalies causing tracheoesophageal compression.
Congenital vascular anomalies of the great vessels causing marked tracheoesophageal compression are rare. Notable symptoms usually manifest in the neonatal period and include stridor, repeated cyanotic attacks, recurrent pneumonia, and dysphagia. Although the diagnosis can often be made from barium swallow studies, the preoperative examination should nevertheless include an endoscopy. This is essential if the degree of tracheomalacia is to be adequately assessed and other tracheobronchial abnormalities are to be identified. Possible airway problems can then be anticipated, thus minimizing postoperative respiratory difficulties.


Systems of Oppression: The Impact of Discrimination on Latinx Immigrant Adolescents' Well-Being and Development.
With over 400 harmful immigration policy changes in the past 4 years, Latinx adolescents and families nationwide are developing within a context of extreme anti-immigrant sentiment (Dismantling and reconstructing the U.S. immigration system: A catalog of changes under the Trump presidency, Migration Policy Institute, 2020). This paper introduces the Multitiered Model of Oppression and Discrimination (MMOD), a conceptual model for understanding the impacts of multiple levels of discrimination on the well-being and development of Latinx immigrant adolescents. Interpersonal discrimination (Hispanic Journal of Behavioral Sciences, 2010, 32, 259), community-held stereotypes (Social Psychology of Education, 2001, 5, 201), institutional policies (Children and Youth Services Review, 2018, 87, 192), and structural practices (Journal of Criminal Justice, 2020, 66, 1) can negatively impact well-being and development among these adolescents. Culturally sustaining interventions, civic engagement and mobilization, and policies targeting inequitable policies and practices will provide healing and an avenue for liberation.


The sentinel node biopsy in patients with breast cancer; many controversies remain.
The sentinel node procedure has increasingly been used as a diagnostic tool for staging breast cancer. Although many institutes have embraced this procedure, many issues concerning the indications and the technique itself remain unsolved. In this review, several aspects regarding these controversies are discussed from the perspective of The Netherlands Cancer Institute. These include the definitions used to identify the sentinel node, the indications and contraindications for this procedure and the injection site of the tracer and blue dye. What are the clinical implications of a micro-metastasis in the sentinel node? What is the best treatment for patients with an involved axillary node? Should non-axillary sentinel nodes be pursued, and if so, what are the implications for further management of these patients? Finally, the current TNM system is discussed in perspective of the evolving sentinel node procedure. Although many questions remain to be solved, the regional recurrence rates are low when axillary clearance is omitted because of a tumor-free sentinel node.


Honey bee (Apis mellifera) sociability and nestmate affiliation are dependent on the social environment experienced post-eclosion.
Underpinning the formation of a social group is the motivation of individuals to aggregate and interact with conspecifics, termed sociability. Here, we developed an assay, inspired by vertebrate approaches to evaluate social behaviours, to simultaneously examine the development of honey bee (Apis mellifera) sociability and nestmate affiliation. Focal bees were placed in a testing chamber which was separated from groups of nestmates and conspecific non-nestmates by single-layer mesh screens. Assessing how much time bees spent contacting the two mesh screens allowed us to quantify simultaneously how much bees sought proximity and interaction with other bees and their preference for nestmates over non-nestmates. Both sociability and nestmate affiliation could be detected soon after emergence as an adult. Isolation early in adult life impaired honey bee sociability but there was no evidence for a critical period for the development of the trait, as isolated bees exposed to their hive for 24 h when as old as 6 days still recovered high levels of sociability. Our data show that, even for advanced social insects, sociability is a developmental phenomenon and experience dependent.


The secret.
The revelation of secrets lies at the core of much psychotherapeutic method and was the seed from which early psychoanalytic theory grew. The notion of "the secret" can therefore be regarded as critical to an understanding of the psychotherapeutic process. This paper puts forward a view which contrasts, in important aspects, with traditional concepts and which emphasizes the positive or creative value of certain hidden ideas and the importance of the social arena on which they are displayed.


Orthodontic treatment with a series of removable appliances.
In the United States, the demand for straight white teeth has never been more important to patients. Crowded, poorly aligned teeth are not esthetically pleasing and are difficult to keep clean. However, until recently, the process of straightening the teeth typically has involved appliances involving bands, brackets and wires that also can be difficult to clean. The desire for a cosmetic solution to misaligned teeth has led to an increase in the number of patients seeking veneers, crowns and other laboratory-fabricated cosmetic restorations. Some clinicians are not aware that there are other ways to align teeth without either significant enamel reduction or conspicuous fixed orthodontic appliances. An alternative method of treatment, involving a series of clear removable appliances, circumvents this shortcoming and enables tooth alignment while avoiding deterioration in the cosmetics of the smile during treatment. This article describes a method of treatment, Invisalign (Align Technology, Santa Clara, Calif.), that clinicians can use in conjunction with 3-D computer models to accomplish the esthetic and oral hygiene objectives during and after treatment. The authors present three case reports, all involving a chief concern of crowding. The first case involved treatment of both arches by interproximal reduction, alignment of teeth and leveling the curve of Spee. The second case involved treatment of both arches by proclination, expansion and minor interproximal reduction. The final case shows relief of lower-arch crowding via lower-incisor extraction. In addition to satisfying the patient's chief concern of desiring straight teeth, this method of treatment satisfies additional objectives of esthetic treatment and esthetic results with significant oral hygiene benefits. Clinicians can address a patient's chief concern effectively without requiring an inventory of appliances (such as bands, brackets, wires and instruments). Furthermore, the use of 3-D computer models can give clinicians additional information to make more complete decisions regarding treatment.


Gas-phase acidities of nitrated azoles as determined by the extended kinetic method and computations.
Making use of the extended kinetic method and the alternative method for data analysis, we have experimentally determined ΔH°acid (kcal/mol) for six mononitrated azole species (2-nitropyrrole = 337.0, 3-nitropyrrole = 335.8, 3-nitropyrazole = 330.5, 4-nitropyrazole = 329.5, 2-nitroimidazole = 327.4, and 4-nitroimidazole = 325.0). We report an absolute uncertainty of ±2.2 kcal/mol that arises from the uncertainties of the reference acids; the relative values are known within 0.4 kcal/mol. Combining these experimental ΔH°acid values with ΔS°acid values calculated at the B3LYP/aug-cc-pVTZ level of theory, we report ΔG°acid (kcal/mol) for the nitroazoles (2-nitropyrrole = 329.4, 3-nitropyrrole = 328.4, 3-nitropyrazole = 323.1, 4-nitropyrazole = 322.0, 2-nitroimidazole = 319.7, and 4-nitroimidazole = 317.6); the absolute uncertainties are ±2.4 kcal/mol. In addition to the experimental studies, we have computationally investigated the gas-phase acidities and electron affinities of the azoles in this work, as well as higher-order aza- and dinitro-substituted azoles. We discuss trends in the stabilities of the deprotonated azoles based on aza substitution and nitro group placement. 4-Nitroimidazole has already found use as the anionic component in ionic liquids, and we propose that the additional nitrated azolate ions are potential candidates for the anionic component of ionic liquids.


Shechita (Kosher slaughtering) and European legislation.
Shechita is the procedure of killing or slaughtering animals for food production, according to Jewish tradition and it is performed without prior stunning. USA and European legislations conditionally allow slaughter without prior stunning in the frame of religion freedom (USA) or religious/cultural traditions (EU); nevertheless some traditional events in Europe de nitely represent a concern for animal welfare. It is possible to identify animal welfare issues in the rules for shechita: correct restrain of the animal; adequacy of the instrument (knife); technical ability of the operator. Animals restrain techniques evolved along the time in order to accomplish to less stressful immobilization of animals in course of shechita. When performed in the right way, shechita cannot be framed as negligent or intentionally painful, distressing or inducing su ering to animals. Today's stunning techniques raise concerns relative to adequacy and e ectiveness of stunning on animals, with welfare implications due to automatism of next dressing procedures. Shechita needs in Europe are in line with average meat demand by non Jewish population.


miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes.
Hyperglycemic damage to the endothelial cells (ECs) leads to increased synthesis of inflammatory cytokines. We have previously shown miR-146a downregulation in ECs and in the tissues of diabetic mice. Here we investigated the role of miR-146a, in the production of specific inflammatory cytokines and extracellular matrix (ECM) proteins in retina and kidneys in diabetes. We generated an endothelial specific miR-146a overexpressing transgenic mice (TG). We investigated these mice and wild type (WT) controls with or without streptozotocin (STZ) induced diabetes. Retinal and renal cortical tissues from the mice were examined for mRNAs for specific inflammatory markers, (ECM) proteins and inflammation inducible transcription factor by real time RT-PCR. Corresponding proteins, where possible, were examined using immunofluorescence or ELISA. In parallel, we examined ECs following incubation with various levels of glucose with or without miR-146a mimic transfection. In the retina and kidneys of WT mice with diabetes, increased expression of inflammatory markers (IL-6, TNFα, IL1β) in association augmented expression of ECM proteins (collagen 1αIV, fibronectin) and NF κB-P65 were observed, compared to WT non-diabetic controls. These changes were prevented in diabetic miR-146a TG mice along with retinal and renal functional and structural changes. In vitro studies showed similar changes in the ECs exposed to high glucose. Such changes were corrected in the cells following miR-146a mimic transfection. Further analyses of renal cortical tissues showed diabetes induced significant upregulation of two regulators of NFκB, namely Interleukin-1 associated Kinase 1 and tumour necrosis factor receptor associated factor. Such changes were prevented in diabetic TG animals. These data indicate that augmented production of inflammatory cytokines and ECM proteins in the retina and kidneys in diabetes are regulated through endothelium derived miR-146a. Identification of such novel mechanisms may potentially lead to the development of novel therapies.


Differentiating facial incongruity and flatness in schizophrenia, using structured light camera data.
Incongruity between emotional experience and its outwardly expression is one of the prominent symptoms in schizophrenia. Though widely reported and used in clinical evaluation, this symptom is inadequately defined in the literature and may be confused with mere affect flattening. In this study we used structured-light depth camera and dedicated software to automatically measure facial activity of schizophrenia patients and healthy individuals during an emotionally evocative task. We defined novel measures for the congruence of emotional experience and emotional expression and for Flat Affect, compared them between patients and controls, and examined their consistency with clinical evaluation. We found incongruity in schizophrenia to be manifested in a less specific range of facial expressions in response to similar emotional stimuli, while the emotional experience remains intact. Our study also suggests that when taking into consideration affect flatness, no contextually inappropriate facial expressions are evident.


Virtual bronchoscopic navigation for peripheral pulmonary lesions.
Virtual bronchoscopic navigation (VBN) is a method in which the bronchoscope is guided on the bronchial route to a peripheral lesion using virtual bronchoscopic images. In reports on VBN for peripheral pulmonary lesions searched in PubMed as of November 2013, the diagnostic yield by ultrathin bronchoscopy in combination with computed tomography and VBN was within the range of 65.4-81.6%. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) and VBN, it was between 63.3 and 84.4%, and using X-ray fluoroscopy and VBN, it was between 62.5 and 78.7%. The overall diagnostic yield was 73.8% [95% confidence interval (CI) 70.9-76.8%] and that for lesions ≤ 2 cm was 67.4% (95% CI 63.3-71.5%). These values indicate high diagnostic rates. In randomized comparative trials, the combination of VBN with EBUS-GS improved the diagnostic yield and shortened the examination time. The diagnostic yields for lesions in the right upper lobe, those invisible on posterior-anterior radiographs and those located in the peripheral third of the lung field were improved by VBN on ultrathin bronchoscopy in combination with X-ray fluoroscopy. The usefulness of VBN was also found on meta-analysis. Taken together, VBN is a promising navigational bronchoscopy method as it requires no specific training, has a low overall complication rate of 1.0% (95% CI 0.2-1.8%) and does not directly induce or cause severe complications. To maximize the full potential of VBN and promote its use, investigation of cases in which it is useful, determination of the optimum combination of procedures, a cost/benefit analysis and advancement of the VBN system are warranted.


From 'mad honey' to hypotensive agents, the grayanoid diterpenes.
The toxicity of Rhododendron species and other members of the Ericaceae which is due to the grayanoid diterpenes, is described. Their structures, biogenesis and biological activity is reviewed.


Histone H3 (lys-9) deacetylation is associated with transcriptional silencing of E-cadherin in colorectal cancer cell lines.
Epigenetic parameters linked to E-cadherin gene were investigated in 5 human colorectal cancer cell lines. Treatment with trichostatin A led to enhanced acetylation of histone H3-K9 with concurrent induction of E-cadherin mRNA in 3 E-cadherin low/negative cell lines that are not DNA methylated. Co-treatment with 5-aza-2'-deoxycytidine and trichostatin A resulted in additive/synergic induction of E-cadherin mRNA in all 5 cell lines with concomitant enhancement of histone H3-K9 acetylation in 4 E-cadherin low/negative cell lines. Our results suggest that histone H3-K9 deacetylation appears to play a crucial role in transcriptional repression of E-cadherin in colorectal cancers.


Physiological basis of interval training for performance enhancement.
What is the topic of this review? This review considers the physiological basis of interval training for performance enhancement, with an emphasis on the capacity for aerobic energy provision. What advances does it highlight? It highlights advances regarding the effect of interval training on primary physiological determinants of aerobic energy provision, which are associated with performance. Interval training refers to an intermittent style of exercise, in which bouts of more intense effort are interspersed with recovery periods within a given training session. Physiological responses to interval training depend on numerous factors, including the specific nature of the intervention and the initial training state of the individual. Interval training improves performance in part by enhancing the capacity for aerobic energy provision, even in those who are already trained. Two primary mechanisms in this regard are an increased whole-body maximal oxygen uptake and an enhanced capacity for oxidative metabolism in skeletal muscle owing to an increase in mitochondria. In comparison to moderate-intensity continuous exercise, interval training can elicit superior responses when total work is matched, and similar responses despite a reduced training volume and time commitment.


Lack of local suppression in orally tolerant CD8-deficient mice reveals a critical regulatory role of CD8+ T cells in the normal gut mucosa.
We found that feeding keyhole limpet hemocyanin (KLH) to CD8-deficient (CD8-/-) mice induced oral tolerance that was comparable in both magnitude and quality to that induced in wild-type (wt) mice. The tolerance was dose dependent, and only higher doses of KLH caused significant reduction in specific Ab and T cell responses. Both Th1 and Th2 CD4+ T cell functions were affected. Feeding KLH together with cholera toxin (CT) adjuvant, however, abrogated the induction of oral tolerance equally well in CD8-/- and wt mice. On the contrary, CT adjuvant was unable to abrogate already established oral tolerance in both CD8-/- and wt mice. Most importantly, whereas Ag feeding induced hyporesponsiveness in systemic as well as in local gut IgA responses in wt mice, a lack of local suppression was evident in orally tolerant CD8-/- mice following oral immunizations. Thus, contrary to the situation in wt mice, Ag feeding induces systemic, but not local, gut IgA hyporesponsiveness in CD8-/- mice, suggesting that CD8+ T cells in the normal gut mucosa exert an important down-regulatory function. In wt mice the local suppression extended to an unrelated Ag, OVA, given together with KLH and CT adjuvant, i.e., bystander suppression. Based on these results we propose that tolerance induced by feeding Ag is highly compartmentalized, requiring CD8+ T cells for local suppression of IgA responses, whereas systemic tolerance may affect CD4+ T cells of both Th1 and Th2 types independently of CD8+ T cells. Finally, the adjuvant effect of CT abrogates induction, but not established, oral tolerance through a mechanism that does not require CD8+ T cells.


Some observations on the medulla of the kidney.
Terminology of the cortex of the kidney is discussed and some new terms are suggested. Observations are described on 50 kidneys which have been injected and variously dissected. These include descriptions of the medulla, papillae and calyces. Some developmental, radiological and surgical aspects are mentioned and suggestions for further study are made.


[Improvement in the informativeness of diuretic kidney function scintigraphy by calculation of a washout index].
Diuresis renography after administration of 123I-(131I-)Hippuran of 248 patients (492 kidneys) were compared retrospectively with clinical findings, history, i.v. urography, and ultrasound examinations. A new wash-out-index was calculated. In cases with obstructive dilatation of the collecting system this index was smaller than 0.9. If it was 0.9 to 1.2 additional diagnostic procedures seem necessary. An index more then 1.4 excludes obstruction. The shape of the renogram curve after furosemide is important for the diagnosis too. A concave shape was found in non-obstructive dilatation, a convex shape in obstructive dilatation of the renal pelvis. The wash-out-index is a reliable parameter if cases with reflux, lower ureteral obstruction and shrunken kidneys are excluded.


Isolation of flavonoids from Aleurites moluccana using chitosan modified with benzaldehyde (CH-Bz) as chromatographic support.
This paper describes the preparation, characterization and use of a derivative of chitosan as a chromatographic sorbent. Chitosan modified with benzenic ring (CH-Bz) was used to separate two flavonoids, swertisin and 2"-O-rhamnosylswertisin, from ethyl acetate fraction of Aleurites moluccana. The results showed that CH-Bz can be used as a sorbent for the separation of flavonoid compounds. The studies showed that CH-Bz in column chromatography produces goods results, separation of the flavonoid compounds.


The Short Form of the Breastfeeding Self-Efficacy Scale as a Prognostic Factor of Exclusive Breastfeeding among Mandarin-Speaking Chinese Mothers.
Little is known about the effect of maternal perceived breastfeeding self-efficacy on the exclusive breastfeeding rate at 6 months postpartum in mainland China. The aim of this study was to examine the relative effect of maternal breastfeeding self-efficacy and selected relevant factors on the exclusive breastfeeding rate at 6 months postpartum. The internal consistency and construct validity of the Chinese (Mandarin) version of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) were also examined. This was a prospective cohort study conducted at a regional teaching hospital in Guangzhou, China. A total of 562 in-hospital mothers who were within 72 hours postpartum were recruited to the study and followed up by telephone for 6 months. Although all of the mothers breastfed their babies within 72 hours postpartum, only 25% of the mothers breastfed exclusively. The mean survival time of continuation of exclusive breastfeeding was 16.7 days. The proportion of mothers who breastfed exclusively after discharge was 14.8%, 2.0%, and 0.2% at 1, 4, and 6 months, respectively. Cox regression analysis revealed that the mothers who had a higher BSES-SF score at baseline, underwent cesarean section, and practiced exclusive breastfeeding within 72 hours after delivery were significantly associated with a lower hazard of discontinuation of exclusive breastfeeding before 6 months postpartum. The exclusive breastfeeding rate among Chinese women is far from satisfactory. The Chinese (Mandarin) version of the BSES-SF can help in identifying mothers who need more support for exclusive breastfeeding before 6 months postpartum.


Radioimmunoassay of sulfated lithocholates.
A sensitive, rapid radioimmunoassay for sulfated species of lithocholic acid (sulfolithocholyglycine, sulfolithocholyltaurine, and sulfolithocholic acid) was developed and used to measure the total concentration of sulfated lithocholates in serum from healthy human subjects. Sulfolithocholylglycine was conjugated to bovine serum albumin by a carbodiimide procedure, and the reaction product, emulsified in Freund's adjuvant, was injected into rabbits. The antiserum obtained was capable to binding 40% of [3H]sulfolithocholylglycine at 1:1000 dilution. The assay featured a 2-hr binding step at 42 degrees C followed by precipitation of bound tracer with polyethylene glycol at 4 degrees C. The assay can be used with 0.1 ml of serum and was reproducible. The antibody had little affinity for the 3-sulfate of cholic or chenodeoxycholic acid, a number of steroid sulfates, or unsulfated bile acids. In 50 healthy subjects, mean (+/-SE) fasting-state serum levels of immunoreactive sulfated lithocholyl conjugates (+sulfated lithocholate) was 1.6 +/- 0.1 micrometer; based on results with a separate radioimmunoassay for unsulfated lithocholyl conjugates, most of the lithocholate in serum in healthy man is present in sulfated form.


A comparison of the production of reactive oxygen species by suspended particulate matter and diesel exhaust particles with macrophages.
Oxidative stress has emerged as a pivotal mechanism that underlies the toxic pulmonary effects of suspended particulate matter (SPM). Experimental evidence shows that redox-active transition metals, redox-cycling quinoids, and polycyclic aromatic hydrocarbons (PAHs) contained in SPM act synergistically, producing reactive oxygen species (ROS). The direct production of superoxide anion and the damaging hydroxyl radical has been studied in aqueous and dimethyl sulfoxide (DMSO) suspensions of SPM both with and without H2O2; however, no study has reported on the release of ROS from ingesting macrophages with SPM. We investigated the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to SPM, carbon black particles, and diesel exhaust particles (DEP). We also examined hydroxyl radical generation from the same experimental system using the 2-deoxy-d-robse method. We found an increase of CL for SPM, but not for carbon black particles or for DEP. Hydroxyl radical generation was observed in both SPM and DEP, but the release from DEP was more frequent than that from SPM. These results suggest that certain components of SPM are important in the response of ROS from ingesting macrophages with SPM, and that those components are discharged from SPM into the atmosphere.