Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening.
This study sought to determine the prevalence of hypertrophic cardiomyopathy (HCM) in elite athletes. Hypertrophic cardiomyopathy is considered to be the most common cause of exercise-related sudden death in young athletes. The prevalence of HCM in elite athletes has never been reported but has important implications with regard to pre-participation screening for the disorder. Between 1996 and 2006, 3,500 asymptomatic elite athletes (75% male) with a mean age of 20.5 +/- 5.8 years (range 14 to 35 years) underwent 12-lead electrocardiography and 2-dimensional echocardiography. None had a known family history of HCM. Of the 3,500 athletes, 53 (1.5%) had left ventricular hypertrophy (mean 13.6 +/- 0.9, range 13 to 16), and of these 50 had a dilated left ventricular cavity with normal diastolic function to indicate physiological left ventricular hypertrophy. Three (0.08%) athletes with left ventricular hypertrophy had a nondilated left ventricular cavity and associated deep T-wave inversion that could have been consistent with HCM. However, none of the 3 athletes had any other phenotypic features of HCM on further noninvasive testing and none had first-degree relatives with features of HCM. One of the 3 athletes agreed to detrain for 12 weeks, which showed resolution of electrocardiography and echocardiographic changes confirming physiologic left ventricular hypertrophy. The prevalence of HCM in highly trained athletes is extremely rare. Structural and functional changes associated with HCM naturally select out most individuals from competitive sports. Screening athletes with echocardiography is not cost effective. However, electrocardiography is useful in selecting out those individuals who may have pathological left ventricular hypertrophy for subsequent echocardiography.


Ecophysiological and antioxidant traits of Salvia officinalis under ozone stress.
Ecophysiological and antioxidant traits were evaluated in sage (Salvia officinalis) plants exposed to 120 ppb of ozone for 90 consecutive days (5 h day(-1)). At the end of fumigation, plants showed slight leaf yellowing that could be considered the first visual symptom of leaf senescence. Ozone-stressed leaves showed (1) reduced photosynthetic activity (-70 % at the end of exposure), (2) chlorophyll loss (-59 and -56 % of chlorophyll a and b concentrations, starting from 30 days from the beginning of exposure), and (3) cellular water deficit (-12 % of the relative water content at the end of the fumigation). These phenomena are indicative of oxidative stress in the chloroplasts (as confirmed by the strong degradation of β-carotene) despite the photoprotection conferred by xanthophyll cycle [as demonstrated by the significant rise of de-epoxidation index, reaching the maximum value at the end of the treatment (+69 %)], antioxidant compounds [as confirmed by the increase of phenols (in particular caffeic acid and rosmarinic acid)], and water-soluble carbohydrates (especially monosaccharides). By means of combined ecophysiological and biochemical approaches, this study demonstrates that S. officinalis is able to activate an adaptive survival mechanism allowing the plant to complete its life cycle even under oxidative stressful conditions.


Predicting high risk adolescents' substance use over time: the role of parental monitoring.
We examined whether parental monitoring at baseline predicted subsequent substance use in a high-risk youth population. Students in 14 alternative high schools in Washington State completed self-report surveys at three time points over the course of 2 years. Primary analyses included 1,423 students aged 14-20 who lived with at least one parent or step-parent at baseline. Using hierarchical linear modeling, we found that high parental monitoring at baseline predicted significantly less use of alcohol, marijuana, downers, cocaine, PCP, LSD, and prescription drugs and drinking to intoxication at the first posttest. Approximately 1 year later, high parental monitoring at baseline predicted significantly less use of alcohol, cocaine, prescription drugs, uppers, and ecstasy and drinking to intoxication. Study results suggest that parental monitoring serves as a protective factor, even for high-risk alternative high school students. Including a parental monitoring component may increase the effectiveness of traditional drug prevention programs.


Endoscopic evaluation of the gastro-duodenal tolerance of short-term analgesic treatment with 25 mg diclofenac-K liquid capsules.
Diclofenac-potassium (diclofenac--K) 25 mg liquid capsule is absorbed more quickly than the tablet formulation. It offers potential for rapid pain relief, but may alter gastro-duodenal tolerability. To evaluate the gastro-duodenal tolerance of diclofenac-K 25 mg liquid capsules vs. diclofenac-K 12.5 mg tablets, acetylsalicylic acid (ASA) 500 mg tablets and ibuprofen 200 mg liquid capsules. In an endoscopist-blinded, randomised, parallel-group study, volunteers received 15 doses of diclofenac-K 25 mg liquid capsules (n = 36), diclofenac-K 2 × 12.5 mg tablets (n = 36), ibuprofen 2 × 200 mg liquid capsules (n = 24) or ASA 2 × 500 mg tablets (n = 36) over 5 days. The primary outcome was the incidence of erosive gastro-duodenal lesions at Day 6. Secondary outcomes included modified Lanza score and change in gastric mucosal prostaglandin synthesis. The lowest incidence of erosive gastro-duodenal lesions was with diclofenac-K liquid capsules (53%), compared to 61% with diclofenac-K tablets (P = 0.52), 75% with ibuprofen (P = 0.08) and 94% with ASA (P = 0.001). Results were similar for the Lanza scores, although diclofenac-K liquid capsules were significantly superior to ibuprofen liquid capsules (P = 0.04). Diclofenac-K liquid capsules inhibited prostaglandin synthesis by 52% compared to 64% for diclofenac-K tablets (P = 0.10), 50% for ibuprofen (P = 0.85) and 79% for ASA (P = 0.002). With respect to safety, adverse events were most frequent in the ASA group, predominantly gastrointestinal events. Mucosal injury with diclofenac-K liquid 25 mg liquid capsules was similar to diclofenac-K 25 mg tablets, significantly lower than ASA 1 g tablets and showed some superiority over ibuprofen 400 mg liquid capsules (EudraCT Number 2009-011278-14).


[Cardiac electrostimulation in childhood (author's transl)].
The AA. relate on two cases of pacemaker implantation in childhood, and they outline the causes that make necessary a cardiac pacemaker in such an age and the troubles can possibly occur.


Histidinaemia. Part I: Reconciling retrospective and prospective findings.
We reach the conclusion that histidinaemia in the typical form (autosomal recessive impairment of L-histidine ammonia lyase activity (EC22.214.171.124)) is not a 'disease' in man. Retrospective and prospective studies (Rosenmann et al., 1983; Coulombe et al., 1983) together indicate that the prevalence of disadaptive phenotypes (e.g. impaired intellectual or speech development, seizures, behavioural or learning disorder) in the histidinaemia population, is not higher than the frequency of these functional disorders in the non-histidinaemia population. However, one cannot exclude the possibility that histidinaemia is a risk factor for development of an unfavourable CNS phenotype, in particular individuals under specific circumstances (e.g. abnormal perinatal events). From this viewpoint, we propose that newborn screening for early diagnosis and treatment of histidinaemia does not meet the criteria for a public health service. Screening for continuing research on histidinaemia remains justifiable, for example, to discern whether there are atypical forms of the biochemical and enzymatic phenotypes.


Coronal oblique imaging of the knee: can it increase radiologists' confidence in diagnosing posterior root meniscal tears?
To investigate the utility of the coronal oblique sequence in the interrogation of posterior root meniscal lesions. Following international review board approval, 62 consecutive knee arthroscopy cases were referred to the musculoskeletal (MSK) radiologists from the same orthopaedic surgeon for imaging/surgical correlation of the posterior meniscal roots. Of 62 cases, 45 lateral and 46 medial menisci met the inclusion criteria. Imaging evaluation was performed with standard magnetic resonance imaging (MRI) sequences, including a coronal oblique proton density sequence. Two blinded fellowship-trained MSK radiologists independently evaluated the menisci on standard sequences indicating whether a tear was identified and then specifying a confidence score using a scale of 1-3 on each study interpreted. Immediately thereafter, the coronal oblique sequence was evaluated using the same method. Statistics were performed on meniscal lesions involving the posterior horn/root junction or isolated root tears comparing confidence scores. Reader A identified nine posterior horn/root junction tears and 14 isolated root tears. Following the addition of the coronal oblique sequence, confidence scores increased in three of 14 (21.4%) isolated root tears. All three final reads were concordant with arthroscopy. Reader B identified 10 posterior horn/root junction tears and 19 isolated root tears. The confidence score increased in six cases: five of 19 (26.3%) isolated root tears and one of 10 (10%) posterior horn/root junction tears. All six final reads were concordant with arthroscopy. Kappa coefficients indicated near perfect agreement. The coronal oblique sequence increased reader confidence in nearly 24% of the posterior root cases identified in this series.


Bioactive delivery systems based on starch and its derivatives: Assembly and application at different structural levels.
Starch and modified starch, spanning various structural levels, are comprehensively reviewed, with a special emphasis on the advancement of starch and its derivative-based delivery systems for bioactive substances. The pivotal aspect highlighted is the controlled release of active ingredients by starch-based delivery systems with distinct hierarchical structures. At the molecular level, diverse categories of starch degradation products, such as dextrin and highly branched starch, serve as versatile amphiphilic carriers for encapsulating active ingredients. At the level of helical structure, the distinctive configuration of the starch-guest complex partly determines the mechanism of controlled release for diverse active components. At the crystal and particle structural level, starch assumes the role of a carrier, effectively modulating the release of active substances, and enhances the innate physiological activity of different active components. As a natural polymer molecule, starch can also generate hydrogel materials in polymer form, expanding its utility in the fields of food, materials, and even medicine.


Gastric conduit resection and jejunal interposition for recurrent esophageal cancer.
We describe the case of a 58-year-old man with recurrent adenocarcinoma at the site of an esophagogastrostomy that we treated by radical surgical resection and jejunal interposition. Oral intake was started on the 6th postoperative day and the patient was discharged on the 11th postoperative day. Seven months after the surgical procedure no signs of tumor recurrence were detected. Resection of localized (recurrent) esophageal cancer may well be a valuable treatment option and is therefore an interesting therapeutic option in patients with recurrent disease. However this needs to be investigated in a randomized controlled trial.


Adverse reactions and immunogenicity in adults to regular and increased dosage of diphtheria vaccine.
Booster doses of 3 Lf or 7.5 Lf of a regular diphtheria vaccine were given to 200 previously immunized adult volunteers. The toxoid was prepared from toxin with a purity of 2100 Lf/mg protein nitrogen and adsorbed to aluminium phosphate. Systemic reactions were rare and no severe symptoms were observed. Local reactions occurred in 40-50% of the vaccinees, but in only 7.5% were they of clinical significance, i.e. an area of redness/swelling greater than 5 cm. The two doses did not cause significant differences in reaction rates, and the 7.5 Lf dose elicited a better antitoxin response. Thus, a dose of 7.5 Lf diphtheria toxoid of similar purity can safely be given to adults in vaccines.


Enhancement by hyperthermia of the effect of BCNU against the EMT6 mouse tumor.
The combination of moderate hyperthermia (43 degrees C water bath for 1 hour) and BCNU against the EMT6 mouse tumor has been studied. The effect was found to be much greater than could have been predicted from the effects of the single modalities and this is true whether the endpoint is tumor cure, growth delay, or in vitro assay of clonogenic fraction. The results indicate that inhibition of "recovery from potentially lethal drug damage" is not the mechanism by which heating potentiates the action of BCNU.


Spatial and non-spatial aspects of visual attention: Interactive cognitive mechanisms and neural underpinnings.
In humans and non-human primates, the parietal lobe plays a key role in spatial attention - the ability to extract information from regions of space. This role is thought to be mediated by "priority" maps that highlight attention-worthy locations, and provide top-down feedback for motor orienting and attentional allocation. Traditionally, priority signals within the parietal cortex have been characterized as being purely spatial, i.e., encoding the desired locus of gaze or attention regardless of the context in which the brain generates that selection. Here, we highlight evidence from human behavior and neuroimaging as well as monkey physiology, to argue that non-spatial responses are critical to the establishment of priority maps in parietal cortex. This review offers an integrative view of the role that parietal cortex plays in attentional selection, providing evidence that priority maps reflect spatial and non-spatial priorities that ultimately act on sensory information in a spatial way.


Abeta peptide conformation determines uptake and interleukin-1alpha expression by primary microglial cells.
Microglia clear amyloid beta (Abeta) after immunization. The interaction of Abeta with the microglial cell surface also results in cytokine expression. Soluble oligomers and protofibrils of Abeta may be more neurotoxic than Abeta fibrils. We investigated the effects of oligomeric, protofibrillar and fibrillar Abeta40 and Abeta42 peptides on uptake and IL-1alpha expression by primary microglia. Abeta peptide assemblies were extensively characterized. Primary microglial cells were exposed to different Abeta40 and Abeta42 assemblies and IL-1alpha expression was quantified. To study uptake, microglial cells were exposed to different assemblies of Cy3-labeled Abeta. We found that Abeta42 and Abeta40 oligomers and fibrils induced IL-1alpha expression, but protofibrils did not. We also observed that all forms of Abeta42 (oligomer, protofibril and fibril) and Abeta40 fibrils were taken up by the microglial cells. These results demonstrate that microglial cells can take up non-fibrillar Abeta and that oligomeric peptide induces an inflammatory response. The uptake of oligomeric and protofibrillar Abeta by microglia merits further investigation as a potential means for removing these neurotoxic species from the brain.


Effects of SV40 transformation on the cytoskeleton and behavioural properties of human keratinocytes.
A cloned cell line (SVK14) with apparently unlimited growth potential was isolated from simian virus 40 (SV40)-infected human foreskin keratinocytes which did not appear to pass through any obvious 'crisis' (Girardi et al., J. Cell. Comp. Physiol., 1965, 65, 69-84). Indirect immunofluorescence microscopy showed that the transformed cells have the SV40 large T antigen in their nuclei and stain positively with LE61, a monoclonal antibody that reacts with a tonofilament determinant normally only found in non-keratinizing simple epithelia. SVK14 cells can be grown in the absence of 3T3 feeders and show an impaired ability to differentiate into squames, and this impairment becomes more marked with passage. At later passages the cells acquire the ability to form colonies in agar and to produce a factor with mitogenic activity which stimulates DNA synthesis in quiescent 3T3 cells. Concomitantly, the SVK14 cells become less sensitive to the growth inhibitory effect of human alpha interferons.


Omitting 50 μg of intracoronary acetylcholine injection in the left coronary artery during spasm provocation test.
Although guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 μg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 μg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 μg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 μg according to the vasoreactivity by 20 μg of ACh in the LCA. A total of 556 patients undergoing ACh provocation test with 20 μg followed by 50 and/or 100 μg were retrospectively included. Injection of 50 μg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 μg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. Positive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 μg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 μg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 μg (2.3 % vs. 0 %, p = 0.009). Omitting 50 μg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 μg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 μg of ACh should not be omitted when 20 μg of ACh induced LCA constriction ≥25 %.


Surgical Safety Checklist compliance: a job done poorly!
The Surgical Safety Checklist (SSC) has been introduced as an effective tool for reducing perioperative mortality and complications. Although reported completion rates are high, objective compliance is not well defined. The purpose of this retrospective analysis is to determine SSC compliance as measured by accuracy and completion, and factors that can affect compliance. In September 2010, our institution implemented an adaptation of the World Health Organization's SSC in an effort to improve patient safety and outcomes. A tool was developed for objective evaluation of overall compliance (maximum score 40) that was an aggregate score of completion and accuracy (20 each). Random samples of SSCs were analyzed at specific, predefined, time points throughout the first year after implementation. Procedure start time, operative time, and case complexity were assessed to determine association with compliance. A total of 671 SSCs were analyzed. The participation rate improved from 33% (95 of 285) at week 1 to 94% (249 of 265) at 1 year (p < 0.0001, chi-square test). Mean overall compliance score was 27.7 (± 5.4 SD) of 40 possible points (69.3% ± 13.5% of total possible score; n = 671) and did not change over time. Although completion scores were high (16.9 ± 2.7 out of 20 [84.5% ± 13.6%]), accuracy was poor (10.8 ± 3.4 out of 20 [54.1% ± 16.9%]). Overall compliance score was significantly associated with case start-time (p < 0.05), and operative time and case complexity showed no association. Our data indicate that although implementation of an SSC results in a high level of overall participation and completion, accuracy remained poor. Identification of barriers to effective use is needed, as improper checklist use can adversely affect patient safety.


Inadequate subendocardial oxygen delivery during perfluorocarbon perfusion in a canine model of ischemia.
Perfusion of the coronary artery distal to an occlusion was performed in 16 canine preparations to compare the mechanical perfusion of autologous blood to the perfluorocarbon fluosol DA, 20% emulsion (FDA-20). Both substances were perfused under similar conditions (30, 60, and 80 ml/min) and regional electrograms, contractility, and coronary perfusion were measured relative to native coronary perfusion. Autologous blood (60 and 80 ml/min) produced a significant increase in regional (epicardial, midmyocardial, and endocardial) and transmural flow, but not in the endocardial/epicardial perfusion ratio. No other significant changes were observed during autologous blood perfusion. In contrast, FDA-20 perfusion resulted in significant ST depression (-1.8 +/- 0.2, -1.7 +/- 0.2, and -1.3 +/- 0.3 mm) at 30, 60, and 80 ml/min, respectively. FDA-20 also induced a significant decrease in distal diastolic coronary pressure and resistance, a significant decrease in the endocardial/epicardial perfusion ratio at all three perfusion rates, and a significant reduction in delivery of O2 to the subendocardium. These results indicate that autologous blood perfusion of the distal coronary artery during occlusion preserves myocardial function to a better degree than does FDA-20.


In vitro effect of cyclosporine-A on angiotensins secretion by glomerular cells.
Cyclosporine-A (CyA) is used to control transplant rejections and to treat autoimmune diseases. We investigated the possibility that changes induced by CyA on endothelin 1 (ET), angiotensin I (AI) and angiotensin II (AII) concentrations recognize a common pathway through which different mechanisms operate. We measured ET, AI and AII concentrations, before and after either ET or CyA addition to the incubation medium of glomeruli of pig kidneys, isolated in vitro. The measurements were carried out with or without selective (ET(A) and ET(B)) or unselective ET(A)-ET(B) receptor inhibitors. In the presence of CyA, AI and ET are positively correlated either when ET(B) receptors are blocked, or when both receptors are free, while this correlation becomes negative when ET(A) receptors alone are blocked. Adding ET to the medium, the correlations between AI and ET are negative when either ET(A), or ET(B) or both are blocked. The effects of CyA and ET are significant only during the first 2 h of incubation. Cyclosporine-A recruits angiotensins and ET through ET(A) receptors, a mechanism possibly responsible of glomerular damage. This stimulation is time-dependent. Prevention of the renal damage from CyA should require selective ET(A) receptor blockade.


Coronary artery bypass grafting: the Society of Thoracic Surgeons National Database experience.
The need for accurate risk assessment has become an indispensable element in the practice of cardiac surgery. The Society of Thoracic Surgeons National Cardiac Surgery Database allows subscribing institutions to perform sophisticated patient risk assessment using traditional statistical tools and a newly developed risk model of operative mortality. The database experience with isolated coronary artery bypass grafting has been studied most closely at this point and serves as the basis for this report. The approach to operative risk assessment is presented along with an analysis of important risk factors in the practice of coronary artery surgery from 1980 through 1990. The database contains records of 80,881 patients undergoing coronary artery bypass grafting in numerous institutions from 1980 through 1990. These records were used to conduct a detailed analysis of risk factors associated with coronary operations in this time interval and to present statistical methods used to formulate a risk equation that allows one to predict the probability of operative death. In the course of this decade, there were clearly defined trends showing a statistically significant increase in adverse patient risk factors. The risk model has proven to be a reliable tool for predicting the probability of operative death in an individual patient and may be valuable in both patient counseling and medical decision making. Large multi-institutional databases of this type are key ingredients of modern operative risk assessment. A database containing a broad national experience of this type can represent an aggregate experience that may well approximate a universally accepted standard of care.


Why am I unsure? Internal and external attributions of uncertainty dissociated by fMRI.
Behavioral evidence suggests that the perceived reason of uncertainty causes different coping strategies to be implemented, particularly frequency ratings with externally attributed uncertainty and memory search with internally attributed uncertainty. We used functional magnetic resonance imaging (fMRI) to investigate whether processes related to these different attributions of uncertainty differ also in their neural substrates. Participants had to predict events that were uncertain due to internal factors, that is, insufficient knowledge. Data were compared with a preceding study in which event prediction was uncertain due to external factors, that is, event probabilities. Parametric analyses revealed the posterior frontomedian cortex, that is, mesial Brodmann Area 8 (BA 8) as the common cortical substrate mediating processes related to uncertainty no matter what the cause of uncertainty. However, processes related to the two differently attributed types of uncertainty differed significantly in relation to the brain network that was coactivated. Only processes related to internally attributed uncertainty elicited activation within the mid-dorsolateral and posterior parietal areas known to underlie working memory (WM) functions. Together, findings from both experiments suggest that there is a common cerebral correlate for uncertain predictions but different correlates for coping strategies of uncertainty. Concluding, BA 8 reflects that we are uncertain, coactivated networks what we do to resolve uncertainty.


In vitro development of imipenem/relebactam resistance in KPC-producing Klebsiella pneumoniae involves multiple mutations including OmpK36 disruption and KPC modification.
In order to inform and anticipate potential strategies aimed at combating KPC-producing Klebsiella pneumoniae infections, we analysed imipenem/relebactam and ceftazidime/avibactam single-step mutant frequencies, resistance development trajectories, differentially selected resistance mechanisms and their associated fitness cost using four representative high-risk K. pneumoniae clones. Mutant frequencies and mutant preventive concentrations were determined using agar plates containing incremental concentrations of β-lactam/β-lactamase inhibitor. Resistance dynamics were determined through incubation for 7 days in 10 mL MH tubes containing incremental concentrations of each antibiotic combination up to their 64 × baseline MIC. Two colonies per strain from each experiment were characterized by antimicrobial susceptibility testing, whole genome sequencing and competitive growth assays (to determine in vitro fitness). KPC variants associated with imipenem/relebactam resistance were characterized by cloning and biochemical experiments, atomic models and molecular dynamics simulation studies. Imipenem/relebactam prevented the emergence of single-step resistance mutants at lower concentrations than ceftazidime/avibactam. In three of the four strains evaluated, imipenem/relebactam resistance development emerged more rapidly, and in the ST512/KPC-3 clone reached higher levels compared to baseline MICs than for ceftazidime/avibactam. Lineages evolved in the presence of ceftazidime/avibactam showed KPC substitutions associated with high-level ceftazidime/avibactam resistance, increased imipenem/relebactam susceptibility and low fitness costs. Lineages that evolved in the presence of imipenem/relebactam showed OmpK36 disruption, KPC modifications (S106L, N132S, L167R) and strain-specific substitutions associated with imipenem/relebactam resistance and high fitness costs. Imipenem/relebactam-selected KPC derivatives demonstrated enhanced relebactam resistance through important changes affecting relebactam recognition and positioning. Our findings anticipate potential resistance mechanisms affecting imipenem/relebactam during treatment of KPC-producing K. pneumoniae infections.


Management of pterygium with surgery and radiation therapy. The North Florida Pterygium Study Group.
To compare our results in the management of pterygium using a higher total dose with other reported results. Between 1971 and 1991, 690 patients were treated with complete surgical excision followed by beta irradiation for primary or recurrent pterygium. Of these patients, 129 had two or more areas involving both eyes for a total of 825 lesions treated. Only 17 patients (2%) had temporal lesions with the rest of the patients having nasal pterygia. All patients underwent complete surgical resection of the pterygium before undergoing radiation therapy. One hundred forty-nine patients had undergone previous surgical resection alone but developed recurrence. After surgical excision, all patients were treated with Strontium-90 applicators starting immediately within 24 hr of surgery. Our standard policy was six weekly applications, each delivering a surface dose of 1000 cGy. The total dose delivered was 6000 cGy. Minimum follow-up was 1 year with a median of greater than 8 years. There were only fourteen recurrences (1.7%) out of a total of 825 lesions treated. Nine of the fourteen patients received suboptimal therapy undergoing less than five applications of Strontium-90. There were no major complications. The combination of surgical excision followed by adequate Strontium-90 applications is highly effective in the management of pterygium. The optimal total dose appears to be in the range of 2000 cGy to 6000 cGy.


Establishment and characterization of six human gastric carcinoma cell lines, including one naturally infected with Epstein-Barr virus.
We report the characterization of six new gastric carcinoma cell lines (designated NCC-19, NCC-20, NCC-24, NCC-59, SNU-1750 and SNU-1967) established from primary tumor samples of Korean patients. Four cell lines grew as adherent monolayers, one as both adherent and floating cell clumps and one as floating cell aggregates. The cell phenotypes, including the histopathology of the primary tumors and in vitro growth characteristics, were determined. We also performed molecular characterization, including DNA fingerprinting analysis and abnormalities of K-ras, p53, β-catenin, and TGF-βRII genes by PCR-SSCP and sequencing analyses. Population doubling times varied from 47-135 h. All cell lines showed relatively high viability, absence of mycoplasma or bacteria contamination and genetic heterogeneity by DNA fingerprinting analysis. Three lines had p53 mutations; one line had mutations in codon 13 (Gly13Asp) in K-ras and no line had a β-catenin mutation. NCC-59 cell line had a -1-bp mutation in 10-bp poly deoxy adenine repeat tract of the TGF-βRII gene. Moreover, NCC-24 gastric cancer cell line was found to be infected with Epstein-Barr virus (EBV). EBV infection was also shown in the original carcinoma tissue of the NCC-24 cell line. These well-characterized six gastric cancer cell lines should serve as useful tools for investigating the biological characteristics of gastric cancer and, in particular, NCC-24 may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis.


Contractile proteins in epidermis. Isolation and properties of guinea-pig epidermal myosin.
Proteins of apparent molecular weights between 10 000 and 250 000 could be solubilized from guinea pig epidermis using a Tris/sucrose/ATP buffer. When the ionic concentration of the solubilized extract was made 75 mM with respect to KCl and 2 mM with respect to MgCl2, a protein complex precipitated which on SDS-polyacrylamide gel electrophoresis resolved into bands corresponding in migration to myosin, actin and a number of low molecular weight proteins. Myosin was dissociated from the complex with 0.6 M KI and purified by gel filtration chromatography on an agarose column. The purified epidermal myosin fraction contained a polypeptide of 200 000 molecular weight andtwo low molecular weight polypeptides of 16 500 and 13 000. The amino acid composition of the epidermal myosin heavy chain was similar to that of muscle myosin. At high ionic strength epidermal myosin had high specific (K+ + Ca2+)- and (K+ + EDTA)-ATPase activities and low specific (K+ + Mg2+)-ATPase activity. The pH activity curves of the (K+ + Ca2+)- and (K+ + EDTA)-ATPase were different. ATP was hydrolyzed faster than other nucleoside triphosphates. At low ionic strength, the (K+ + Mg2+)-ATPase activity of epidermal myosin was stimulated two fold by skeletal muscle actin. The myosin formed bipolar filaments in 50 mM KCl in the presence of 5 mM Mg2+.


Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation.
To address current regulatory expectations on immunotoxicity testing of new chemicals, we describe an animal model that measures the primary antibody response to the T-cell dependent antigen, keyhole limpet hemocyanin (KLH). Single immunization with KLH by either footpad (300microg/rat) or intravenous (300microg/kg) route in Sprague Dawley rats resulted in increased germinal center formation in the spleen and a robust anti-KLH IgM (70-388microg/ml) and IgG (230-470microg/ml) antibody response with peak detection on Days 5 and 14 post-immunization, respectively. Subcutaneous immunization with KLH (300microg/kg) resulted in a much weaker anti-KLH IgM and IgG (< or =20microg/ml) antibody response with no detectable increase in splenic germinal center formation. The utility of a rat KLH immunization model in detecting immunosuppression was evaluated with the known immunosuppressive drugs: cyclosporin, azathioprine and prednisolone. Rats, treated with drug at a maximum tolerated dose, were immunized with KLH by footpad or intravenous injection and serum samples were collected at various intervals up to 2 weeks post-immunization. Additional study parameters included terminal body weight, hematology and/or histopathology. All three drugs inhibited the IgM (60%) and IgG (> or =90%) antibody responses in the absence of overt toxicity based on evaluation of the standard toxicology parameters. In conclusion, measurement of a rat primary antibody response to KLH by ELISA is a reliable and readily standardized method for assessing immunotoxicity of pharmaceuticals.


Aortocoronary vein graft flow in response to peripheral venous administration of sodium nitroprusside or diazepam.
Vein graft flow (VGF) in response to peripheral venous administration of sodium nitroprusside (SNP) or diazepam was studied in 13 anesthetized patients following cardiopulmonary bypass for aortocoronary vein bypass graft operations. SNP (0.5 microgram/kg/min) significantly reduced mean arterial pressure (p less than 0.05). VGF paralleled the decreased blood pressure, but the reduction was not significant (p greater than 0.05). Diazepam (0.1 mg/kg) did not significantly alter blood pressure or VGF. We conclude that peripheral venous administration of SNP or diazepam is not a pharmacologically reliable method by which to increase VGF in the period immediately following a graft operation.


Electrocardiographic changes in dermatomyositis and polymyositis.
Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described. Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group. This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010-2013. The ECG findings between DM and PM were also compared. Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p>0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p=0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One-third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p=0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p<0.05 for all), especially the left anterior fascicular block. We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases.


Prune-belly syndrome associated with omphalocele in a female newborn.
The authors report on a female newborn with prune-belly syndrome (PBS) in association with omphalocele. This case raises the total of omphalocele associated with PBS to seven. The authors suggest that this case lends support to the concept of PBS being caused by an early disturbance of mesodermal development in both the abdominal wall and the urinary tract.


Identification of membrane-associated proteins in Trypanosoma brucei encoding an internal, EARLRAEE amino acid repeat.
Differential screening of expression libraries with nonimmune and day 4-6 immune serum from naive rats infected with the protozoan Trypanosoma lewisi was used to identify potential cell surface protein coding genes. Several T. lewisi cDNAs that resulted were partially characterized and used to clone the homologues from Trypanosoma brucei. The nucleotide sequence of the cDNAs encoding the Tb-29 genes of the parasitic protozoan T. brucei obtained by this method (3557 nucleotides for Tb-291 and 8729 nucleotides for Tb-292) encoded predicted open reading frames of 1070 and 2550 amino acids, respectively. The Tb-29 proteins encoded a large domain with an octapeptide (EARLRAEE) repeat (79 repeats in Tb-291 and 60 in Tb-292), which shared significant similarity with the octapeptide repeat of the S-antigen of isolate NF7 of Plasmodium falciparum. The predicted amino acid sequence of the Tb-292 protein encoded potential transmembrane domains (eight in total). Indirect immunofluorescence using confocal image analysis and immunoelectron microscopy located the EARLRAEE proteins to a membranous network. The Tb-29 proteins were most abundantly distributed to the area surrounding the nucleus, the region between the nucleus and the flagellar pocket, and the region immediately underneath the flagellar pocket membrane. The subcellular distribution of Tb-29 proteins suggests that these proteins may provide a constituent associated with the cell's vesicular transport system.


Transition-Metal-Free Synthesis of Heterobiaryls through 1,2-Migration of Boronate Complex.
The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp2 -sp2 cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl-heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive 11 B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.


The effect of low dose intravenous alcohol on human information processing.
A model of multiple-stage information processing predicts alcohol to have a selective effect on mechanisms involving central processing rather than sensory input. However, behavioral effects at low alcohol doses administered orally can be overshadowed by fluctuations in gastrointestinal absorption and metabolism rate. Paid volunteers, who therefore received intravenous doses of alcohol and a barbiturate, were tested on tasks varying in sensory discriminability and in central processing difficulty. The low drug doses did not affect errors of stimulus encoding but increased error rate in memory comparison tasks. These results confirmed the predictions based on the mutiple-stage model.


Infection, antibiotic exposure, and risk of celiac disease: A systematic review and meta-analysis.
There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship. To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001). Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.


The molecular landscape of the normal human breast--defining normal.
A key approach in understanding how breast cancer can occur is to determine the regulatory pathways at play in the normal breast and to identify precisely the normal developmental mechanisms subverted during early breast cancer progression. Using normal human breast tissue samples, Pardo and colleagues have identified the gene targets and pathways displaying fluctuating expression as a consequence of the menstrual cycle. Detailed characterization of how the human breast functions in its normal state, and how this may be perturbed at its earliest point, will provide a critical step toward the prevention of breast cancer.


Combined application of biochar and nitrogen fertilizer improves rice yield, microbial activity and N-metabolism in a pot experiment.
The excessive use of synthetic nitrogen (N) fertilizers in rice (Oryza sativa L.) has resulted in high N loss, soil degradation, and environmental pollution in a changing climate. Soil biochar amendment is proposed as a climate change mitigation tool that supports carbon sequestration and reduces N losses and greenhouse gas (GHG) emissions from the soil. The current study evaluated the impact of four different rates of biochar (B) (C/B0-0 t ha-1, B1-20 t ha-1, B2-40 t ha-1, and B3-60 t ha-1) and two N levels (N1; low (270 kg N ha-1) and N2; high (360 kg N ha-1)), on rice (cultivar Zhenguiai) grown in pots. Significant increases in the average soil microbial biomass N (SMBN) (88%) and carbon (87%) were recorded at the highest rate of 60-ton ha-1B and 360 kg N ha-1 compared to the control (N1C) during both seasons (S1 and S2). The photochemical efficiency (Fv/Fm), quantum yield of the photosystem (PS) II (ΦPS II), electron transport rate (ETR), and photochemical quenching (qP) were enhanced at low rates of biochar applications (20 to 40 t B ha-1) for high and low N rates across the seasons. Nitrate reductase (NR), glutamine synthetase (GS), and glutamine 2-oxoglutarate aminotransferase (GOGAT) activity were, on average, 39%, 55%, and 63% higher in the N1B3, N2B2, and N2B3 treatments, respectively than the N1C. The grain quality was higher in the N1B3 treatment than the N1C, i.e., the protein content (PC), amylose content (AC), percent brown rice (BRP), and percent milled rice (MRP) were, on average, 16%, 28%, 4.6%, and 5% higher, respectively in both seasons. The results of this study indicated that biochar addition to the soil in combination with N fertilizers increased the dry matter (DM) content, N uptake, and grain yield of rice by 24%, 27%, and 64%, respectively, compared to the N1C.


Access to global wheat reserves determines country-level vulnerability to conflict-induced Ukrainian wheat supply disruption.
The Russia-Ukraine conflict reduced global wheat supplies, yet the food security implications vary across countries. We identify a 39% decrease in Ukrainian wheat exports in 2022 resulting in >70% import losses in some of the countries most vulnerable to these disruptions, with substantial impacts felt in Egypt, Oman, Saudi Arabia, Libya, Mauritania, Yemen and Lebanon. Differential impacts are a function of access to capital and international trade, suggesting the need for policy measures to defuse the impending food crisis.


One-stage debulking procedure after flap reconstruction for degloving injury of the hand.
The aim of this study is to evaluate the use of one-stage debulking procedure to separate the fingers after flap reconstruction for degloving injury of the hand. From January 2009 to June 2014, 15 patients with degloving injuries of the hand were treated at the Kaohsiung Chang Gung Memorial Hospital. Among the 15 patients, 11 sustained degloving injury of the fingers; free flap reconstruction was performed in three patients, and a pedicle flap was used in eight. Four patients sustained complete degloving injuries of the hand; reconstruction was performed with an anterolateral thigh pocketing procedure. One-stage debulking procedure was performed for debulking of the flap and interdigitation from the flap envelope. After the 12-month follow-up and rehabilitation, the fingers could move independently and perform in opposition with the thumb. Protective sensation was also regained. The patients with degloving injury of the fingers could return to daily activity and work after 1-year follow-up, while those with complete degloving injury of the hand could return to daily activities and work after 18-month follow-up. The use of ALT pocketing procedure is simple for salvage of complete degloving injury of the hand. One-stage debulking procedure provides thin and durable skin coverage for hand after reconstruction. The fingers can also be separated from the envelope of a bulky flap for independent movement to fulfill functional and aesthetic requirements.


Increasing acid rain frequency promotes the microbial community dissimilarities of forest soil rather than agricultural soil in southern China.
Soil microbial community drives the terrestrial carbon (C) cycling by C sources metabolism (i.e., organic C decomposition), however, the microbial response to changing acid rain frequency remains less studied, thus hampering global warming projection. Here, we manipulated a simulated experiment to decipher the impact of acid rain frequency (0, 30%, and 100%) on microbial community and C sources metabolism in the agricultural and forest soils of southern China, based on the phospholipid fatty acids (PLFAs) analysis and BIOLOG method, respectively. We found that changing acid rain frequency did not affect the microbial biomass and community structure of agricultural soil during the whole experiment period, while the 30% and 100% acid rain frequencies significantly decreased the microbial biomass, and altered the microbial community structure of forest soil at the early stage. However, changing acid rain frequency did not influence the microbial C sources metabolism in the agricultural soil, but 30% acid rain frequency significantly reduced the microbial utilization of carboxylic acids in the forest soil. Moreover, increasing acid rain frequency promoted the microbial community dissimilarities of forest soil. The microbial community structure and C sources utilization of agricultural soil were significantly related to soil available phosphorus content, while that of forest soil correlated with the soil available potassium content and temperature. Changes in soil environmental condition, soil acidification parameters and soil nutrients explained most of the variance of microbial community and C sources utilization (81% and 57%, respectively) in the forest soil, whereas great uncertainties of microbial community and C sources utilization existed in the agricultural soil with the explanatory proportion being 20% and 10%, respectively. Our findings suggest that the microbial community of forest soil is more sensitive to changing acid rain frequency than that of agricultural soil in a short term. These results support the prediction of microbes-driven C cycling dynamics in specific soil ecosystems in the context of changing acid rain frequency.


Morphology of human suprarenal glands: a parameter for comparison.
Forty suprarenal glands were studied, 20 being dissected from aborted fetuses of 9 to 36 weeks' gestation and 20 obtained from human cadavers of ages 1 day to 60 years. All the specimens were from a Northern India population. The side and shape of each suprarenal gland was noted and documented. The length, breadth, thickness and volume of each gland were measured and tabulated in terms of age. The mean length, breadth and thickness in fetuses of 9-36 weeks were found to be 1.4 cm, 1 cm and 0.45 cm respectively. In the postnatal age group the measurements were 4.5 cm, 2.08 cm and 0.66 cm respectively. The commonest shape of the suprarenal glands on left side was semilunar but on the right side it was highly variable: triangular, tetrahedral, inverted Y or V shaped. On comparison of the gross measurements with available ultrasound and CT scan data it was found that both the length and thickness in the population studied were greater than reported in the literature. A knowledge of these variations is very important in diagnosis of abnormalities of the suprarenal gland, of which tumoral enlargement is rather common.


Linear DNA introduced into carrot protoplasts by electroporation undergoes ligation and recircularization.
The integrated DNA in stable transformants formed by direct gene transfer often shows complex restriction patterns. One cause of these complex restriction patterns could be the ligation of plasmid fragments prior to their integration. This paper provides evidence for the ligation of plasmid fragments by plant cells. Carrot protoplasts were electroporated in the presence of pCaMVCATM and assayed for chloramphenicol actyltransferase (CAT) activity 24 h later. Linear and supercoiled forms of pCaMVCATM supported similar levels of CAT expression. Surprisingly, digestion of the plasmid at a site between the CaMV 35S promoter and the CAT coding region reduced expression by only 40-50%. Electroporation carried out in the presence of isolated plasmid fragments suggested that this result was due to ligation of the linearized plasmid by the protoplasts. CAT expression was obtained with a mixture of isolated CaMV 35S promoter and the CAT coding region; neither fragment alone supported expression. Further evidence of ligation was provided by electroporation of protoplasts in the presence of a mixture of linearized pGEM and the 1.5-kb Hind III fragment of pCaMVCATM. DNA isolated from nuclei of the protoplasts was used to transform competent cells of Escherichia coli, and colonies were recovered that carried pGEM with Hind III-CaMVCAT inserts. Electroporation of protoplasts in the presence of linear and supercoiled pGEM and use of DNA isolated from nuclei to transform E. coli yielded an estimate of the frequency of plasmid ligation. A maximum of only 4% of the input linear DNA was recovered as circular molecules. This result suggests the frequency of ligation is low, but examination of the plasmid DNA in the plant nuclei by electrophoresis indicates extensive degradation of the plasmid and preferential loss of the circular forms. Thus, the ligated plasmids may be converted to the linear form and hence rendered unrecoverable by cloning into E. coli.


Differential effects of butylated hydroxytoluene analogs on bull sperm subjected to cold-induced membrane stress.
Previous reports established that butylated hydroxy toluene (BHT) minimized cold-induced membrane rupture in sperm from several species. No data regarding the specificity of its effect is available. In this study 25 BHT analogs were tested for their effect on bovine sperm membrane stability. Fourteen were membrane lytic at 25 degrees C and 6 were neither membrane lytic nor membrane stabilizing. The remaining 5 compounds, a family of 2,6-tert-butyl phenols with substitutions at position 4 of hydrogen, methyl (BHT), ethyl, butyl, hexyl, or octyl, afforded effective membrane protection to cold shock. Since membrane protection is a function of both the ability of a compound to partition into the membrane and a molecule's effectiveness once there, an analysis of each analog's membrane partitioning, assessed by measuring the cellular analog/cholesterol ratio, showed the following extents of transfer for the analogs: ethyl = butyl greater than methyl = hydrogen greater than hexyl greater than octyl. Thus, an optimum chain length exists for partitioning from micellar donors into cells. A separate experiment established that all analogs, when incorporated in equivalent amounts, protect equally plasma and mitochondrial membranes from cold shock. No effect on acrosomal membrane stability was noted. BHT, but not the other analogs, reduced sperm motility. Addition of egg yolk to extender containing BHT analog protected sperm motility from cold shock but had little effect on membrane stabilization. Analysis of sperm membrane compartments revealed that little to no analog was partitioned into the outer acrosomal membrane or the plasma membrane overlying the acrosome, but rather was localized in other portions of the sperm. We conclude that (a) the effective BHT analogs, if partitioned into the membrane, are indistinguishable with regard to their capacity to eliminate cold-induced membrane lysis; (b) membrane-linked events (e.g., motility) are uniquely disrupted by a subset of this analog family; and (c) when concentrations of egg yolk and BHT analogs are carefully controlled, unique synergistic effects are noted.


Object-centered encoding by face-selective neurons in the cortex in the superior temporal sulcus of the monkey.
Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and in the inferior temporal cortex respond to faces. To determine if some face responsive neurons encode stimuli in an object-centered coordinate system rather than a viewer-centered coordinate system, a large number of neurons were tested for sensitivity to head movement in 3 macaque monkeys. Ten neurons responded only when a head undergoing rotatory movements was shown. All of these responded to a particular movement independently of the orientation of the moving head in relation to the viewer, maintaining specificity even when the moving head was inverted or shown from the back, thereby reversing viewer-centered movement vectors. This was taken as evidence that the movement was encoded in object-centered coordinates. In tests of whether there are neurons in this area which respond differently to the faces of different individuals relatively independently of viewing angle, it was found that a further 18 neurons responded more to one static face than another across different views. However, for 16 of these 18 cells there was still some modulation of the neuronal response with viewing angle. These 16 neurons thus did not respond perfectly in relation to the object shown independently of viewing angle, and may represent an intermediate stage between a viewer-centered and an object-centered representation. In the same area as these neurons, other cells were found which responded on the basis of viewer-centered coordinates. These neurophysiological findings provide evidence that some neurons in the inferior temporal visual cortex respond to faces (or heads) on the basis of object-centered coordinates, and that others have responses which are intermediate between object-centered and viewer-centered representations. The results are consistent with the hypothesis that object-centered representations are built in the inferior temporal visual cortex.


[Study on multiple aldosterone-producing adenomas].
To investigate the experience on diagnosis and treatment of multiple adrenal aldosterone-producing adenomas (APA). Eighteen cases of multiple adrenal APA were analyzed retrospectively, which were admitted from October 1992 to April 2006. Adrenalectomy was performed for 4 cases of unilateral synchronous multiple APA, which were discovered with three adenomas by 3D-CT; bilateral tumor resection was performed for 6 cases of bilateral synchronous multiple APA. There were 8 cases of bilateral metachronous multiple APA, including 2 cases of ipsilateral recurrent adrenal APA after adrenal tumor removal, which underwent tumor resection. Another 6 cases were contralateral APA following adrenalectomy due to adrenal APA, and underwent tumor resection. After operation, the adrenal function seemed to be normal, and no recurrence had been found on follow-up. Unilateral multiple synchronous APA require adrenalectomy. Tumor resection should be performed for bilateral or asynchronous APA, and it is very important to preserve healthy adrenal tissue as much as possible. 3D-CT has much value on diagnosis of small APA, unilateral multiple synchronous APA and ipsilateral recurrent adrenal APA.


Tris[N,N-bis-(3,5-di-tert-butyl-benz-yl)di-thio-carbamato-κ2 S,S']-μ3-sulfido-tris-μ2-disulfido-triangulo-trimolybdenum(IV) iodide.
The title compound, [Mo3(C31H46NS2)3S7]I, crystallizes on a threefold rotational axis in P31c (space group No. 159). The [Mo3S7(S2CN(CH2C6H3-3,5- t Bu2)2)3]+ cations are arrayed in sheets in the ab plane with inter-ligand hydro-phobic inter-actions between tert-butyl groups guiding the packing arrangement. These cations form stacks parallel to the c axis with a separating distance of 10.9815 (6) Å (the c axis length) between the Mo3 centroids. On the underside of the cluster, opposite the μ3-S2- ligand, the iodide counteranion forms close contacts of 3.166 (2) Å with the sulfur atoms of the μ2-S2 2- ligands. These contacts are less than the sum of the van der Waals radii of the atoms (1.8 and 2.1 Å for S and I, respectively), thus indicating an appreciable degree of covalency to the [Mo3S7(S2CN(CH2C6H3-3,5- t Bu2)2)3]+⋯I- inter-actions.


2F1 antigen, the mouse homolog of the rat "mast cell function-associated antigen", is a lectin-like type II transmembrane receptor expressed by natural killer cells.
Inhibitory lectin-like receptors expressed on the surface of hematopoietic cells are critically involved in regulation of their effector functions. Here we report that a novel mAb specific for mouse NK cells, 2F1, recognizes the mouse homolog of the mast cell function-associated antigen (MAFA), an inhibitory lectin-like transmembrane receptor expressed on rat mast cells. The 2F1 antigen (2F1-Ag) and rat MAFA are structurally highly conserved and contain a cytoplasmic motif similar to the immunoreceptor tyrosine-based inhibitory motif that is presumably utilized for inhibitory signaling. We also identified a human homolog that is closely related to the rodent MAFA/2F1-Ag proteins. Like rat MAFA, 2F1-Ag is probably encoded by a single gene, which exhibits relatively little polymorphism. Strikingly, while rat MAFA is considered a mast cell antigen, we have been unable to detect cell surface expression of 2F1-Ag by mouse mast cell lines, bone marrow-derived mast cells, or peritoneal mast cells. Furthermore, mouse bone marrow-derived mast cells were devoid of 2F1-Ag mRNA. Instead, we find that approximately 40% of mouse NK cells express 2F1-Ag. Thus, MAFA/2F1-Ag may modulate immunological responses on at least two different cell types bridging the specific and innate immune system.


Analysis of human T lymphocyte activation in a T cell tumor model system.
The human T leukemia line Jurkat maintains functional characteristics of normal T cells in responding to inducing stimuli by the release of interleukin 2 (IL 2). Presence of a phorbol ester during stimulation eliminated the requirement for specialized accessory cells in the response to cell mitogenic agents such as the lectin concanavalin A or treatment with neuraminidase and galactose oxidase. Antibodies directed against the T cell receptor-associated antigen T3 served as efficient stimuli, especially if aided by agents that cross-link immunoglobulin, indicating that a triggering signal is received by a T cell via aggregation of its antigen receptor complex. A Burkitt lymphoma cell line, Raji, was found to selectively trigger Jurkat cells, suggesting the ability of those cells to respond to certain foreign stimuli. The Jurkat cell line has been instrumental in the purification of IL 2 and cloning of the corresponding gene. Our data suggest it can also serve as a useful model for induction of T cell responses.


The longitudinal relationship between set-shifting at 4 years of age and eating disorder related features at 9 years of age in the general pediatric population.
Individuals with anorexia nervosa (AN) tend to have rigid thoughts and behaviors regarding their body weight, body image, and eating habits. While a diagnosis of AN implies severe levels of impairment, AN traits can vary on a continuum within the population. However, little is known about how early markers of AN relate to rigid thought patterns and to what extent cognitive rigidity is already present in early childhood. We examined the association of set-shifting abilities as a measure of cognitive flexibility in preadolescents with AN-related features. Participants included 3,987 children participating in the Generation R Study, a Dutch population-based birth cohort. Set-shifting abilities (mother report) were assessed at 4 years of age, body mass index (BMI) was determined at 4 and 9 years and restrictive eating patterns (mother report) and body image (child report) were assessed at 9 years. Lower set-shifting abilities at 4 years were associated with a lower BMI (β = -.44, p = 2.2 × 10-4 ) in girls, and more restrictive eating (β = 0.15, p = 2.7 × 10-6 ) in both boys and girls at 9 years of age. Moreover, set-shifting at age 4 was not associated with body image at age 9. These findings contribute to the idea that the association between set-shifting problems and AN-related features are present early in childhood, prior to the typical range of the onset of eating disorders (EDs). Longitudinal studies that capture the peak age for the development of EDs will be important to assess whether early cognitive inflexibility is an early marker of AN.


Liposomal encapsulation of yeast alcohol dehydrogenase with cofactor for stabilization of the enzyme structure and activity.
Yeast alcohol dehydrogenase (YADH) with its cofactor nicotinamide adenine dinucleotide (NAD+) could be stably encapsulated in liposomes composed of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine). The YADH- and NAD+-containing liposomes (YADH-NADL) were 100 nm in mean diameter. The liposomal YADH and NAD+ concentrations were 2.3 mg/mL and 3.9 mM, respectively. A synergistic effect of the liposomal encapsulation and the presence of NAD+ was examined on the thermal stability of YADH at 45 and 50 degrees C. The enzyme stability of the YADH-NADL was compared to the stabilities of the liposomal YADH (YADHL) containing 3.3 mg/mL YADH without NAD+ as well as the free YADH with and without NAD+. Free YADH was increasingly deactivated during its incubation at 45 degrees C for 2 h with decrease of the enzyme concentration from 3.3 to 0.01 mg/mL because of the dissociation of tetrameric YADH into its subunits. At that temperature, the coexistence of free NAD+ at 3.9 mM improved the stability of free YADH at 2.3 mg/mL through forming their thermostable complex, although the stabilization effect of NAD+ was lowered at 50 degrees C. The turbidity measurements for the above free YADH solution with and without NAD+ revealed that the change in the enzyme tertiary structure was much more pronounced at 50 degrees C than at 45 degrees C even in the presence of NAD+. This suggests that YADH was readily deactivated in free solution due to a decrease in the inherent affinity of YADH with NAD+. On the other hand, both liposomal enzyme systems, YADH-NADL and YADHL, showed stabilities at both 45 and 50 degrees C much higher than those of the above free enzyme systems, YADH/NAD+ and YADH. These results imply that the liposome membranes stabilized the enzyme tertiary and thus quaternary structures. Furthermore, the enzyme activity of the YADH-NADL showed a stability higher than that of the YADHL with a more remarkable effect of NAD+ at 50 degrees C than at 45 degrees C. This was considered to be because even at 50 degrees C the stabilization effect of lipid membranes on the tertiary and quaternary structures of the liposomal YADH allowed the enzyme to form its thermostable complex with NAD+ in liposomes.


[Preparation of doxorubicin-loaded stealth liposomes modified with RGD mimetic and cellular association in vitro].
To investigate the possibility of using stealth liposomes modified with arginine-glycine-aspartic acid (RGD) mimetic as the targeted carriers to achieve increased accumulation in tumor and enhanced intracellular delivery for the encapsulated anticancer drugs. RGD mimetic (RGDm) as a ligand for integrins was synthesized and covalently conjugated to the active PEGylated phospholipids (DSPE-PEG-BTC) to form RGDm conjugate (DSPE-PEG-RGDm). Then RGDm-modified SL (RGDm-SL) containing DOX (RGDm-SL-DOX) and SL containing DOX (SL-DOX) were prepared by film dispersion followed by ammonium sulfate gradient method. The pH-sensitive probe, BCECF-AM, was used to study the binding of melanoma cells to DSPE-PEG-RGDm. Flow cytometry and confocal microscopy were performed to evaluate the cellular association or DOX uptake for RGDm-SL-DOX or SL-DOX in vitro. The melanoma cells A375 and B16 showed enhanced binding to the immobilized DSPE-PEG-RGDm. The cells treated with RGDm-SL-DOX showed remarkable increase in cellular association or DOX uptake compared with SL-DOX. The RGDm-modified SL could be as the targeted carriers to facilitate the delivery of the encapsulated anti-cancer drugs into tumor cells by receptor-mediated way.


Smile esthetics from patients' perspectives for faces of varying attractiveness.
Delivering an attractive smile is a key element in orthodontic patient satisfaction. Smile characteristics can be affected by the facial context. The purpose of this study was to investigate smile esthetics related to facial attractiveness and sex of the model. Attractive, average, and unattractive model faces (2 of each; 3 male, 3 female) determined by peer ratings were combined with 10 smile variables (buccal corridor, smile arc, maxillary gingival discrepancy, gingival display, incisal-edge discrepancy, cant, overbite, central-incisor gingival margin discrepancy, and maxillary midline to face, and maxillary midline to mandibular midline). Each smile characteristic was altered digitally and presented with slider technology to allow a continuous range of choices. Raters chose the ideal and the limits of acceptability. The variables were divided into 6 separate surveys and rated 96 times. Reliability was assessed by answering each question twice. Individual smile variable reliability ranged from fair to excellent, except for the buccal corridor. Clinically significant values were defined as greater than 1.0 mm with statistical significance (P <0.05). Rater sex did not make a difference. Clinical significance was found for smile arc, gingival display, and maxillary midline to face. For females, accentuated smile arcs were preferred for the unattractive and attractive models compared with the average models. The opposite was found for male models. More gingival display was preferred for the attractive and unattractive male and female models compared with the average models. Attractive models were allowed less midline deviation. Facial attractiveness and model sex impacted smile variables with a facial context, except for occlusal cant. These smile characteristics with a facial context should be considered when diagnosing and planning treatment for an orthodontic patient.


Effect of personalized perioperative blood pressure management on postoperative complications and mortality in high-risk patients having major abdominal surgery: protocol for a multicenter randomized trial (IMPROVE-multi).
Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management-based on preoperative automated blood pressure monitoring-reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery. Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. ClinicalTrials.gov NCT05416944. Registered on June 14, 2022.


A finite element study on the effects of follower load on the continuous biomechanical responses of subaxial cervical spine.
In spine biomechanics, follower loads are used to mimic the in vivo muscle forces acting on a human spine. However, the effects of the follower load on the continuous biomechanical responses of the subaxial cervical spines (C2-T1) have not been systematically clarified. This study aims at investigating the follower load effects on the continuous biomechanical responses of C2-T1. A nonlinear finite element model is reconstructed and validated for C2-T1. Six levels follower loads are considered along the follower load path that is optimized through a novel range of motion-based method. A moment up to 2 Nm is subsequently superimposed to produce motions in three anatomical planes. The continuous biomechanical responses, including the range of motion, facet joint force, intradiscal pressure and flexibility are evaluated for each motion segment. In the sagittal plane, the change of the overall range of motion arising from the follower loads is less than 6%. In the other two anatomical planes, both the magnitude and shape of the rotation-moment curves change with follower loads. At the neutral position, over 50% decrease in flexibility occurs as the follower load increases from zero to 250 N. In all three anatomical planes, over 50% and 30% decreases in flexibility occur in the first 0.5 Nm for small (≤100 N) and large (≥150 N) follower loads, respectively. Moreover, follower loads tend to increase both the facet joint forces and the intradiscal pressures. The shape of the intradiscal pressure-moment curves changes from nonlinear to roughly linear with increased follower load, especially in the coronal and transverse planes. The results obtained in this work provide a comprehensive understanding on the effects of follower load on the continuous biomechanical responses of the C2-T1.


Stabilization of finger ulnar deviation in rheumatoid arthritis: extensor indicis proprius tenodesis.
Ulnar deviation of fingers in rheumatoid arthritis is a common deformity that can markedly compromise hand function. These deformities also result in an aesthetic impairment that is often troubling to patients. A variety of surgical procedures have been recommended to correct the ulnar deviation, either at the wrist level or at the metacarpophalangeal (MCP) joints. We present a surgical technique that uses the extensor indicis proprius as a tenodesis across the dorsum of the MCP joints of the fingers. The technique can also be used in conjunction with other surgical procedures, including prosthetic replacement arthroplasties of the MCP joints. The procedure has been used in 6 patients. Ulnar deviation averaged 62 degrees preoperatively and 15 degrees postoperatively. All patients have been satisfied with the results.


Synthesis and biological evaluation of imidazol-2-one and 2-cyanoiminoimidazole derivatives: novel series of PDE4 inhibitors.
This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.


Efficiency of chlorhexidine-silver sulfadiazine-impregnated venous catheters at subclavian sites.
Cost-effectiveness analyses show that chlorhexidine-silver sulfadiazine (CHSS)-impregnated catheters reduce catheter-related bloodstream infection (CRBSI) and central venous catheter (CVC)-related costs. However, no studies have reported the efficiency of CHSS-impregnated catheters for venous access when the risk of CRBSI is low; for example, at the subclavian site. This study determined the cost of a CVC, diagnosis of CRBSI, and antimicrobial agents to treat CRBSI; we did not consider the cost of increased hospital stay. This retrospective study included patients admitted to the intensive care unit at Hospital Universitario de Canarias (Tenerife, Spain) who had a subclavian venous catheter. Patients with CHSS catheters (n = 353) had a lower incidence density of CRBSI (2.12 vs 0 out of 1,000 catheter-days; P = .02) and lower CVC-related cost per catheter-day (3.35 ± 3.75 vs 3.94 ± 9.95; P = .002) than those with standard catheters (n = 518). CHSS-impregnated catheters were associated with a lower risk of CRBSI (exact logistic regression) (odds ratio, 0.10; 95% confidence interval, -∞ to 0.667; P = .008) than standard catheters when controlling for catheter duration. CHSS-impregnated catheters were also associated with a lower CVC-related cost per catheter day than standard catheters (Poisson regression) (odds ratio, 0.85; 95% confidence interval, 0.001-0.873; P < .001). CHSS-impregnated catheters may be efficient in preventing CRBSI in patients with subclavian venous access.


The influence of semantic fit on on-line sentence processing.
The interactive influence of verb complement preferences and noun phrase semantic fit on resolution of temporary syntactic ambiguity was investigated in an eye movement experiment. The present semantic fit manipulation included noun phrases that fit well as direct objects of the verbs that they followed and noun phrases that were possible but less likely direct objects of the verbs in question. This contrasted with existing research on the use of verb complement preferences and semantic fit during sentence processing, in which processing of noun phrases that are possible direct objects has been compared with processing of noun phrases that are not possible direct objects of the verbs that they follow. Verb complement preference information and noun phrase semantic fit interacted at early stages of on-line sentence processing. Implications of these results for interactive and structural models of sentence processing are discussed.


Biophysics and protein corona analysis of Janus cyclodextrin-DNA nanocomplexes. Efficient cellular transfection on cancer cells.
The self-assembling processes underlining the capabilities of facially differentiated ("Janus") polycationic amphiphilic cyclodextrins (paCDs) as non-viral gene nanocarriers have been investigated by a pluridisciplinary approach. Three representative Janus paCDs bearing a common tetradecahexanoyl multitail domain at the secondary face and differing in the topology of the cluster of amino groups at the primary side were selected for this study. All of them compact pEGFP-C3 plasmid DNA and promote transfection in HeLa and MCF-7 cells, both in absence and in presence of human serum. The electrochemical and structural characteristics of the paCD-pDNA complexes (CDplexes) have been studied by using zeta potential, DLS, SAXS, and cryo-TEM. paCDs and pDNA, when assembled in CDplexes, render effective charges that are lower than the nominal ones. The CDplexes show a self-assembling pattern corresponding to multilamellar lyotropic liquid crystal phases, characterized by a lamellar stacking of bilayers of the CD-based vectors with anionic pDNA sandwiched among them. When exposed to human serum, either in the absence or in the presence of pDNA, the surface of the cationic CD-based vector becomes coated by a protein corona (PC) whose composition has been analyzed by nanoLC-MS/MS. Some of the CDplexes herein studied showed moderate-to-high transfection levels in HeLa and MCF-7 cancer cells combined with moderate-to-high cell viabilities, as determined by FACS and MTT reduction assays. The ensemble of data provides a detail picture of the paCD-pDNA-PC association processes and a rational base to exploit the protein corona for targeted gene delivery on future in vivo applications.


Nanocube-Based Fluidic Glycan Array.
The nature of cell membrane fluidity permits glycans, which are attached to membrane proteins and lipids, to freely diffuse on cell surfaces. Through such two-dimensional motion, some weakly binding glycans can participate in lectin binding processes, eventually changing lectin binding behaviors. This chapter discusses a plasmonic nanocube sensor that allows users to detect lectin binding kinetics in a cell membrane mimicking environment. This assay only requires standard laboratory spectrometers, including microplate readers. We describe the basics of the technology in detail, including sensor fabrication, sensor calibration, data processing, a general protocol for detecting lectin-glycan interactions, and a troubleshooting guide.


Effective collection and detection of airborne species using SERS-based detection and localized electrodynamic precipitation.
Three different delivery concepts (standard diffusion, global electrodynamic precipitation, and localized nanolens-based precipitation) and three different SERS enhancement layers (a silver film, a nanolens-based localized silver nanoparticle film, and the standard AgFON) are compared. The nanolens concept is applied to increase the SERS signal: a factor of 633, when compared to a standard mechanism of diffusion, is observed.


Characteristics of IL-25 and allergen-induced airway fibrosis in a murine model of asthma.
Interleukin (IL)-25 has been implicated in the pathogenesis of human asthma by inducing a Th2 cytokine response, but its possible role in the development of airway remodelling is less clear. We developed a murine surrogate of chronic airway inflammation induced by intranasal application of IL-25 alone. Comparison was with the 'classical' surrogate of ovalbumin (OVA) intranasal instillation into previously sensitized animals. Airway fibrotic biomarkers were analysed by immunohistochemistry and enzyme-linked immunosorbent assay. Additionally, proliferation assay and real-time polymerase chain reaction analysis were performed to assess IL-25's effects on primary human bronchial fibroblasts in vitro. In Balb/c mice, intranasal instillation of IL-25 alone induced florid airway fibrosis, including increased lay down of extracellular matrix proteins such as collagen I, III, V and fibronectin, increased numbers of fibroblasts/myofibroblasts, a profibrotic imbalance in matrix metalloproteinase/tissue inhibitor of metalloproteinase production and increased expression of profibrotic mediators including connective tissue growth factor and transforming growth factor-β1. These changes broadly reproduced those seen with classical intranasal OVA challenge in OVA-sensitized animals. Furthermore, IL-25 induced proliferation and expression of collagen I and III and smooth muscle α-actin in primary human lung fibroblasts. We conclude that chronic exposure of the airways to IL-25 alone is sufficient to cause functionally relevant airway remodelling, with the corollary that targeting of IL-25 may attenuate bronchial remodelling and fibrosis in human asthmatics.


Ultrastructure, histology, and innervation of the mantle edge of the freshwater pulmonate snails Lymnaea stagnalis and Biomphalaria pfeifferi.
The mantle edge of the freshwater pulmonate snails Lymnaea stagnalis and Biomphalaria pfeifferi was investigated with histochemical and ultrastructural methods. The mantle edge gland, which is involved in shell formation, consists of the periostracal groove and the belt. This belt appears to be composed of various regions. In the area of the periostracal groove a number of subepithelial gland cell types occur; these release their products into the groove. Between the groove cells ciliated free nerve endings terminate; the corresponding perikarya occur in the subepidermal connective tissue. Also in the posterior belt region free nerve endings were observed between the epithelial cells; in addition, a particular type of subepithelial gland cell was found in this area. The epithelial cells of this part of the belt have the ultrastructural characteristics of ion and water transporting cells; they are probably involved in calcium deposition and resorption. The possible role of the free nerve endings and of the subepithelial gland cells is discussed.


Codon recognition mechanisms in plant chloroplasts.
In chloroplasts, all 61 sense codons are found in chloroplast (cp) DNA sequences coding for proteins. However among the sequenced cp tRNAs or tRNA genes, tRNAs with anticodons complementary to codons CUU/C (Leu), CCU/C (Pro), GCU/C (Ala) and CGC/A/G (Arg) [or CGC/A (Arg) in Marchantia] have not been found. In this paper we show that cp tRNA(Ala)(U*GC) cp tRNA(Pro)(U*GG) and cp tRNA(Arg)(ICG) are able to decode the corresponding four-codon family. In the case of leucine codons CUU/C, we show that 'U:U and U:C wobble' mechanisms can operate to allow the reading of these codons by cp tRNA(Leu)(UAm7G).


Airborne asbestos in Colorado public schools.
Levels of airborne asbestos for six Colorado public school facilities with sprayed-on asbestos materials were documented using three analytical techniques. Phase contrast microscopy showed levels up to the thousandths of a fiber per cubic centimeter (f/cc), scanning electron microscopy (SEM) up to the hundredths of a f/cc, and transmission electron microscopy coupled to selected area electron diffraction and energy dispersive X-ray analysis (TEM-SAED-EDXA) up to the tenths of an asbestos f/cc. Phase contrast microscopy was found to be an inadequate analytical technique for documenting the levels of airborne asbestos fibers in the schools: only large fibers which were not embedded in the filter were counted, and asbestos fibers were not distinguished from nonasbestos.


Incidence of Carpal Tunnel Syndrome Requiring Surgical Decompression: A 10.5-Year Review of 2,309 Patients.
To describe the demographics, neurophysiological grading, and incidence of patients undergoing carpal tunnel decompression (CTD) for carpal tunnel syndrome (CTS) in a single region. A retrospective review of 2,313 patients aged greater than 16 years who underwent 3,073 CTDs between January 2000 and August 2010. Crude annual and age- and sex-specific incidences were calculated for the study period. Nerve conduction study grades were recorded and compared with age and sex. Of the 2,313 patients 1,419 (61%) were female and 890 (39%) were male. Mean age at surgery was 56 years (range, 16-93 years). Females had a significantly higher CTD incidence compared with males (161 vs 108/100,000 person-years, respectively). The highest rates of CTD were seen in the 70- to 79-year age group for both men and women (307/100,000 person-years). Neurophysiological grade increased in severity with increasing age despite using an age-adjusted grading system, with higher grades in patients aged greater than 65 years. This study suggests that carpal tunnel syndrome has the highest incidence in older people who tend to have more severe neurophysiological changes. Prognostic II.


Preparation and culture of adrenal chromaffin cells.
Cultured chromaffin cells have been used for almost 40 years in the study of different cell functions using biochemical, electrophysiological, pharmacological, and toxicological approaches. Chromaffin cells are essentially secretory cells that are used to model sympathetic neurons or neuroendocrine cells. In this chapter, we describe the most common methods currently used to isolate and culture chromaffin cells from the animals used most commonly: cows, rats, and mice. We also provide some advice on the use of these cells in the laboratory.


Behavioural inhibition system sensitivity is no longer associated with psychotic-like experiences after controlling for depression and anxiety symptoms.
Elevated behavioural inhibition system sensitivity has been reported among schizophrenia patients. Yet, no study has investigated the relationship between behavioural inhibition system sensitivity and the occurrence of psychotic-like experiences (subthreshold psychotic symptoms considered to be less severe or impairing), despite evidence that behavioural inhibition system sensitivity is related to other forms of psychopathology known to co-occur with psychotic-like experiences, such as depression and anxiety. Thus, the aim of this study was to assess the relationship between behavioural inhibition system levels and psychotic-like experiences while controlling for depression and anxiety symptoms. We hypothesized that behavioural inhibition system sensitivity would be positively associated with the number of reported psychotic-like experiences, and that this association would be nonsignificant after accounting for depression and anxiety symptoms. Psychotic-like experiences, behavioural inhibition system sensitivity, depression symptoms, and anxiety symptoms were measured in 1162 young adults. Bivariate correlations were calculated and linear regressions performed to measure the relationship between variables of interest. Psychotic-like experiences, behavioural inhibition system sensitivity, and symptoms of depression, and anxiety were all significantly and positively correlated with one another. Behavioural inhibition system sensitivity was no longer related to the number of psychotic-like experiences reported after controlling for anxiety symptoms, with and without controlling for depression symptoms. These findings suggest that the hypersensitivity to threat observed among individuals reporting higher levels of psychotic-like experiences is likely related to co-occurring depression and anxiety symptoms. Thus, behavioural inhibition system sensitivity may be more reflective of a transdiagnostic phenotype of general psychopathology than specifically related to psychosis.


New quinoxaline 1,4-di-N-oxides. Part 1: Hypoxia-selective cytotoxins and anticancer agents derived from quinoxaline 1,4-di-N-oxides.
Hypoxic cells which are common feature of solid tumors are resistant to both anticancer drugs and radiation therapy. Thus, the identification of drugs with the selective toxicity toward hypoxic cells is an important target in anticancer chemotherapy. Tirapazamine has been shown to be an efficient and selective cytotoxin after bioreductive activation in hypoxic cells which is thought to be due to the presence of the 1,4-di-N-oxide. A new series of quinoxaline 1,4-di-N-oxides and fused quinoxaline di-N-oxides were synthesized and evaluated for hypoxic-cytotoxic activity on EAC cell line. Compound 10a was the most potent cytotoxin IC(50) 0.9 microg/mL, potency 75 microg/mL, and was approximately 15 times more selective cytotoxin (HCR>111) than 3-aminoquinoxaline-2-carbonitrile which has been used as a standard (HCR>7.5). Compounds 4 and 3a,b were more selective than the standard. In addition, antitumor activity against Hepg2 (liver) and U251 (brain) human cell lines was evaluated, compounds 9c and 8a were the most active against Hepg2 with IC(50) values 1.9 and 2.9 microg/mL, respectively, however, all the tested compounds were nontoxic against U251 cell line.


HIF-1α activation mediates resistance to anti-angiogenic therapy in neuroblastoma xenografts.
The anti-tumor activity of angiogenesis inhibitors is often limited by the development of resistance to these drugs. Here we establish HIF-1α as a major factor in the development of this resistance in neuroblastoma xenografts. Neuroblastoma xenografts were established by injecting unmodified SKNAS or NB-1691 cells (2 × 10(6) cells), or cells in which HIF-1α expression had been knocked down with shRNA, into the retroperitoneal space of SCID mice. Treatment of established tumors included bevacizumab (5mg/kg q2wk), sunitinib (40 mg/kg qd), or topotecan (0.5mg/kg qd) alone or in combination for a total of two weeks. NB-1691 xenografts showed no difference in relative growth in HIF-1α knockdowns compared to control tumors (73.33 ± 7.90 vs 79.94 ± 6.15, p=0.528). However, HIF-1α knockdowns demonstrated relative final volumes that were significantly lower than unmodified tumors when both were treated with bevacizumab (35.88 ± 4.24 vs 53.57 ± 6.61, p=0.0544) or sunitinib (12.46 ± 2.59 vs 36.36 ± 4.82, p=0.0024). Monotherapy of unmodified xenografts with bevacizumab, sunitinib, or topotecan was largely ineffective. Relative final volumes of NB-1691 xenografts were significantly less in cohorts treated with sunitinib+topotecan (4.78 ± 0.77 vs 39.17 ± 2.44 [sunitinib alone], p=0.011) and bevacizumab+topotecan (13.63 ± 1.55 vs 48.16 ± 9.94 [bevacizumab alone], p=0.014). Upregulation of HIF-1α appears to be a significant mechanism of resistance to antiangiogenic therapies in neuroblastoma. Suppressing HIF-1α with low-dose topotecan potentiates the effects of the antiangiogenic drugs in a mouse model.


On the role of competing word units in visual word recognition: the neighborhood frequency effect.
Current models of word recognition generally assume that word units orthographically similar to a stimulus word are involved in the visual recognition of this word. We refer to this set of orthographically similar words as an orthographic neighborhood. Two experiments are presented that investigate the ways in which the composition of this neighborhood can affect word recognition. The data indicate that the presence in the neighborhood of at least one unit of higher frequency than the stimulus word itself results in interference in stimulus word processing. Lexical decision latencies (Experiment 1) and gaze durations (Experiment 2) to words with one neighbor of higher frequency were significantly longer than to words without a more frequent neighbor. This neighborhood frequency effect is discussed in terms of the different types of candidate selection process postulated by contemporary models of visual word recognition.


Mucoadhesion, hydration and rheological properties of non-aqueous delivery systems (NADS) for the oral cavity.
Effective delivery of oral care actives from conventional hydrogel formulations is often compromised by poor retention associated with shear forces present in the mouth, salivary washout and over-hydration of the gel which can lead to structural breakdown and adhesive failure. Non-aqueous gels offer the opportunity to formulate rheologically acceptable vehicles with higher concentrations of bioadhesive polymer than is possible using water as the primary solvent. Accordingly, this study describes the formulation and characterisation of the rheology, hydration and bioadhesive properties of a range of non-aqueous delivery systems (NADS). The formulations were composed principally of glycerol, with varying amounts of polyethylene glycol (PEG) 400 and Carbopol 974P being incorporated in the ranges 0-31.34% and 0-4% (w/w). Work of adhesion (WOA) and maximum force of detachment (Fmax) were determined using a Dartec tensile tester after application of a normal force. Rheology was assessed using a Bohlin CS CVO rheometer. WOA and Fmax increased with increasing compression time and Carbopol concentration. Addition of 30% (w/w) PEG 400 to the formulation containing 2% Carbopol in glycerol improved bioadhesive function. Formulation rheology was largely controlled by the Carbopol concentration, and to a lesser extent by the concentration of PEG 400 and these, in turn, largely determined the bioadhesion parameters and rates of hydration. The results of this in vitro study suggest that bioadhesion, and consequently potential drug bioavailability, would be enhanced by use of a water miscible non-aqueous delivery vehicle such as glycerol containing a bioadhesive polymer such as Carbopol with the addition of controlled amounts of PEG as plasticiser.


A Review of Different Stunning Methods for Poultry-Animal Welfare Aspects (Stunning Methods for Poultry).
Electrical water bath stunning is the most commonly used method for poultry stunning prior to slaughter, but has been questioned on animal welfare and product quality grounds. Controlled atmosphere stunning (CAS) methods, involving a variety of gas mixtures, have become increasingly common, at least in Europe. CAS methods have been perceived as an improvement from an animal welfare perspective, partly because birds can be stunned without prior shackling, and are generally considered to result in improved product quality compared to water bath stunning. However, there would still be an interest in alternative stunning methods especially for small to medium size poultry slaughterhouses. This review presents an overview of the modes of action and the technical aspects of poultry stunning methods, including novel and emerging stunning technologies.


DNA value and prognosis of renal tumors. Differences between childhood and adult tumors.
In an attempt to reveal characteristic DNA ploidy patterns in primary renal tumors in children and adults, the nuclear DNA contents of 71 tumors were investigated. Nuclear DNA contents were measured by epifluorescence microscopy. The ploidy patterns of renal cell carcinomas (RCCs) and Wilm's tumors (WTs) were different. In RCCs there was no predominant DNA value, and aneuploidy indicated a poorer prognosis than diploidy. In contrast, a diploid pattern was predominant in WTs regardless of the prognosis. These results appear to reflect differences between adults and children in the mechanisms of tumorigenesis of renal tumors.


Versatile synthesis of benzothiophenes and benzoselenophenes by rapid assembly of arylzinc reagents, alkynes, and elemental chalcogens.
Rapidly aSSembled: The combination of cobalt-catalyzed migratory arylzincation and copper-mediated/catalyzed chalcogenative cyclization allows the construction of benzothiophenes and benzoselenophenes from arylzinc reagents, alkynes, and elemental chalcogens. Benzothiophenes and benzoselenophenes diversely functionalized at the benzene ring moiety can be prepared, which are not readily accessible by conventional methods.