Diagnosis of ectopic pancreas by endoscopic ultrasound with fine-needle aspiration.
To study the clinical, endoscopic, sonographic, and cytologic features of ectopic pancreas (EP). This was a retrospective study performed at an academic referral center including two hospitals. Institutional review board approval was obtained. Patients referred to the University Hospital or Denver Health Medical Center Gastrointestinal Endoscopy Lab for gastroduodenal subepithelial lesions (SEL) with a final diagnosis of EP between January 2009 and December 2013 were identified. Patients in this group were selected for the study if they underwent endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or deep biopsy. A review of the medical record was performed specifically to review the following information: presenting symptoms, endoscopic and EUS findings, computed tomography or magnetic resonance imaging findings, pathology results, procedure-related adverse events, and subsequent treatments after EUS-FNA. EUS with FNA or deep submucosal biopsy was performed in all patients on an outpatient basais by one of two physicians (Attwell A, Fukami N). Review of all subsequent clinic notes and operative reports was performed in order to determine follow-up and final diagnoses. Between July 2009 and December 2013, 10 patients [3 males, 7 females, median age 52 (26-64) years] underwent EUS for a gastroduodenal SEL and were diagnosed with EP. One patient was symptomatic. Six (60%) lesions were in the antrum, 3 (30%) in the body, and 1 (10%) in the duodenum. A mucosal dimple was noted in 6 (60%). Mean lesion size was 17 (8-25) mm. Gastrointestinal wall involvement: muscularis mucosae, 10%; submucosa, 70%; muscularis propria, 60%; and serosa, 10%. Nine (90%) lesions were hypoechoic and 5 (50%) were homogenous. A duct was seen in 5 (50%). FNA was attempted in 9 (90%) and successful in 8 (80%) patients after 4 (2-6) passes. Cytology showed acini or ducts in 7 of 8 (88%). Superficial biopsies in 7 patients (70%) showed normal gastric mucosa. Deep endoscopic biopsies were taken in 2 patients and diagnostic in one. One patient (10%) developed pancreatitis after EUS-FNA. Two patients (20%) underwent surgery to relieve symptoms or confirm the diagnosis. The main limitation of the study was the fact that it was retrospective and performed at a single medical center. EUS features of EP include antral location, mucosal dimple, location in layers 3-4, and lesional duct, and FNA or biopsy is accurate and effective.


Ovarian cancer cells cisplatin sensitization agents selected by mass cytometry target ABCC2 inhibition.
Cisplatin resistance in ovarian cancer remains a complex problem as tumors frequently develop resistance against drugs, a mechanism sometimes mediated by ATP-Binding Cassette transporters. Our goal was to find compounds restricting their inhibition capacity to the cisplatin efflux mediated by ABCC2 pump, among previously identified inhibitors, derived from the 2- indolylmethylenebenzofuranones. Methodology & results: An original method setup allows direct quantitation of platinum by employing cyTOF mass cytometry. Among tested derivatives, some led to a full platinum accumulation and efficiently resensitized cisplatin-resistant A2780 cells to cisplatin while preserving most of the calcein efflux activity. CyTOF is therefore a powerful and promising method to quantify cisplatin accumulation that may be used in the clinical setting to improve and personalize cancer treatment.


The role of temporal cue-target overlap in backward inhibition under task switching.
One of the proposed mechanisms for sequential control in task-shift conditions is backward inhibition (BI), which is usually measured in terms of lag-2 task repetition costs in A-B-A task sequences relative to C-B-A task sequences. By considering the so far existing experiments it seems that these lag-2 repetition costsoccur only with temporally overlapping cues and targets. In the present study this issue was further examined in two experiments, in which temporal cue-target overlap was varied blockwise (Experiment 1) and from trial-to-trial (Experiment 2). Experiment 1 shows that lag-2 repetition effects can only be observed with temporally overlapping cues and targets, indicating that there was no BI with temporally separated cues and targets. However, the results of Experiment 2 suggest that both irrelevant task sets are inhibited in this case, and that with temporally overlapping cues and targets only the previously relevant task set is inhibited.


Evaluation of the enantiomeric composition of amino acids in tobacco.
Despite the fact that several studies have reported the concentrations of various free amino acids in tobacco, their enantiomeric composition is unknown. Both the absolute and enantiomeric compositions of proline, alanine, asparagine, aspartic acid, valine, methionine, leucine,and phenylalanine were determined for three strains of tobacco leaf, three types of smokeless tobacco, and six different blended filtered and nonfiltered reference cigarettes. Some of the highest levels of D-amino acids ever found in agricultural products were observed. Possible mechanisms for the production of these D-amino acids are considered. The relevance of D-amino acids in tobacco is discussed.


Comparison of paradoxical salivatory responses to chlorosyle and atropine in a denervated human parotid gland.
In the case of the denervated human parotid gland, atropine is a cholinopositive agent that causes an extremely intense and prolonged (up to 3-5 h) salivation. An attempt was made to find out the extent to which the "weight increase" principle had an effect on such a gland, i.e. whether larger analogues of atropine which has a relative molecular mass of 289.4 would stimulate or inhibit the paradoxical salivation. The studies involving chlorosyle of a mass of 355.89 were carried out in seven subjects during the last three years. The cholinopositive activity of chlorosyle, as a ligand with increased weight on both poles, on a denervated gland, was several times lower than that of atropine. With the increase of the ligand's dosage, the cholinoexciting activity of chlorosyle decreased sharply and was just restricted by the initial cholinomimetic excitement transforming into a blockade, which may be compared with the action of depolarizing myorelaxants. The data obtained may provide a foundation for conceptualization of the expansion of a response-active cholinopositive zone in a cholinoreceptor deprived of nervous control, which, probably, results from relocation of hydrophobic segments to the macromolecular periphery or, more precisely, to the synthesis of receptors with another part of the zone. The chlorosyle radicals with increased length and weight, while contacting the hydrophobic segments, conditioned the occurrence of cholinoblocking activity and inhibition of the cholinoexciting effect.(ABSTRACT TRUNCATED AT 250 WORDS)


RNA secondary structure regulates the translation of sxy and competence development in Haemophilus influenzae.
The sxy (tfoX) gene product is the central regulator of DNA uptake by naturally competent gamma-proteobacteria such as Haemophilus influenzae, Vibrio cholerae and probably Escherichia coli. However, the mechanisms regulating sxy gene expression are not understood despite being key to understanding the physiological role of DNA uptake. We have isolated mutations in H. influenzae sxy that greatly elevate translation and thus cause competence to develop in otherwise non-inducing conditions (hypercompetence). In vitro nuclease analysis confirmed the existence of an extensive secondary structure at the 5' end of sxy mRNA that sequesters the ribosome-binding site and start codon in a stem-loop. All of the hypercompetence mutations reduced mRNA base pairing, and one was shown to cause a global destabilization that increased translational efficiency. Conversely, mutations engineered to add mRNA base pairs strengthened the secondary structure, resulting in reduced translational efficiency and greatly reduced competence for genetic transformation. Transfer of wild-type cells to starvation medium improved translational efficiency of sxy while independently triggering the sugar starvation regulator (CRP) to stimulate transcription at the sxy promoter. Thus, mRNA secondary structure is responsive to conditions where DNA uptake will be favorable, and transcription of sxy is simultaneously enhanced if CRP activation signals that energy supplies are limited.


Cationic gemini lipids containing polyoxyethylene spacers as improved transfecting agents of plasmid DNA in cancer cells.
Lipoplex nano-aggregates have been analyzed through biophysical characterization (electrostatics, structure, size and morphology), and biological studies (transfection efficiency and cell viability) in five cancer cell lines. Lipoplexes were prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed liposomes, constituted by a zwitterionic lipid (DOPE) and a gemini cationic lipid (GCL) synthesized in this work, [bis(hexadecyl dimethyl ammonium) oxyethylene], referred to as (C16Am)2(C2O)n, (where n is the oxyethylene spacer length, n = 1, 2 or 3, between the ammonium heads). Cryo-TEM micrographs show nano-aggregates with two multilamellar structures, a cluster-type (at low-to-medium GCL composition) and a fingerprint-type that coexists with the cluster-type at medium GCL composition and appears alone at high GCL composition. SAXS diffractograms show that these lipoplexes present three lamellar structures, two of them coexisting at low and high GCL composition. The optimized transfection efficiency (TE) of pDNA was higher for lipoplexes containing GCLs with a longer (n = 3) or shorter (n = 1) polyoxyethylene spacer, at high GCL composition (α = 0.7) with low charge ratio (ρeff = 2). In the all cancer cell lines studied, the TE of the optimized formulations was much better than those of both lipofectamine 2000 and lipoplexes with GCLs of the bis(hexadecyl dimethyl ammonium) alkane series recently reported. Probably, (a) the coexistence of two lamellar structures at high GCL composition synergizes the TE of these lipid vectors, (b) the orientation of the polyoxyethylene region in (C16Am)2(C2O)3/DOPE may occur in such a way that the spacing between two cationic heads becomes smaller than that in (C16Am)2(C2O)2/DOPE which is poor in terms of TE, and (c) the synergistic interactions between serum proteins and (C16Am)2(C2O)n/DOPE-pDNA lipoplexes containing a polyoxyethylene spacer improve TE, especially at high GCL content. Lipoplexes studied here show very low levels of toxicity, which confirm them as improved vectors of pDNA in gene therapy.


Combining in vivo reflectance with fluorescence confocal microscopy provides additive information on skin morphology.
Within the last decade, confocal microscopy has become a valuable non-invasive diagnostic tool in imaging human skin in vivo. Of the two different methods that exist, reflectance confocal microscopy (RCM) displays the backscattering signal of naturally occurring skin components, whereas fluorescence confocal microscopy (FCM) provides contrast by using an exogenously applied fluorescent dye. A newly developed multilaser device, in which both techniques are implemented, has been used to combine both methods and allows to highlight different information in one image. In our study, we applied the fluorophore sodium fluorescein (SFL) intradermally on forearm skin of 10 healthy volunteers followed by fluorescence and reflectance imaging. In fluorescence mode the intercellular distribution of SFL clearly outlines every single cell in the epidermis, whereas in reflectance mode keratin and melanin-rich cells and structures provide additional information. The combination of both methods enables a clear delineation between the cell border, the cytoplasm and the nucleus. Imaging immediately, 20, 40 and 60 minutes after SFL injection, represents the dynamic distribution pattern of the dye. The synergism of RCM and FCM in one device delivering accurate information on skin architecture and pigmentation will have a great impact on in vivo diagnosis of human skin in the future.


An Integrative Analysis of the InR/PI3K/Akt Network Identifies the Dynamic Response to Insulin Signaling.
Insulin regulates an essential conserved signaling pathway affecting growth, proliferation, and metabolism. To expand our understanding of the insulin pathway, we combine biochemical, genetic, and computational approaches to build a comprehensive Drosophila InR/PI3K/Akt network. First, we map the dynamic protein-protein interaction network surrounding the insulin core pathway using bait-prey interactions connecting 566 proteins. Combining RNAi screening and phospho-specific antibodies, we find that 47% of interacting proteins affect pathway activity, and, using quantitative phosphoproteomics, we demonstrate that ∼10% of interacting proteins are regulated by insulin stimulation at the level of phosphorylation. Next, we integrate these orthogonal datasets to characterize the structure and dynamics of the insulin network at the level of protein complexes and validate our method by identifying regulatory roles for the Protein Phosphatase 2A (PP2A) and Reptin-Pontin chromatin-remodeling complexes as negative and positive regulators of ribosome biogenesis, respectively. Altogether, our study represents a comprehensive resource for the study of the evolutionary conserved insulin network.


Genomic divergence across ecological gradients in the Central African rainforest songbird (Andropadus virens).
The little greenbul, a common rainforest passerine from sub-Saharan Africa, has been the subject of long-term evolutionary studies to understand the mechanisms leading to rainforest speciation. Previous research found morphological and behavioural divergence across rainforest-savannah transition zones (ecotones), and a pattern of divergence with gene flow suggesting divergent natural selection has contributed to adaptive divergence and ecotones could be important areas for rainforests speciation. Recent advances in genomics and environmental modelling make it possible to examine patterns of genetic divergence in a more comprehensive fashion. To assess the extent to which natural selection may drive patterns of differentiation, here we investigate patterns of genomic differentiation among populations across environmental gradients and regions. We find compelling evidence that individuals form discrete genetic clusters corresponding to distinctive environmental characteristics and habitat types. Pairwise FST between populations in different habitats is significantly higher than within habitats, and this differentiation is greater than what is expected from geographic distance alone. Moreover, we identified 140 SNPs that showed extreme differentiation among populations through a genomewide selection scan. These outliers were significantly enriched in exonic and coding regions, suggesting their functional importance. Environmental association analysis of SNP variation indicates that several environmental variables, including temperature and elevation, play important roles in driving the pattern of genomic diversification. Results lend important new genomic evidence for environmental gradients being important in population differentiation.


Maternal cannabis use in the sudden death syndrome.
The smoking of cannabis and tobacco is common in many countries. In contrast to tobacco, which is an established risk factor for the sudden infant death syndrome (SIDS), nothing is known about cannabis and its effects on SIDS risk. We analysed data collected in a nation-wide case control study in New Zealand (393 cases, 1592 controls) to determine if there is any association between maternal cannabis use and SIDS risk. Adjusting for ethnicity and maternal tobacco use, the SIDS odds ratio for >weekly maternal cannabis use since the infant's birth was 2.23 (95% CI = 1.39, 3.57) compared to non-users; and the multivariate odds ratio was 1.55 (95% CI = 0.87, 2.75). We conclude that frequent maternal cannabis use may be a weak risk factor for SIDS, but this finding requires further research.


Uterine structural anomalies and arthrogryposis-death of an urban legend.
In a review of 2,300 cases of arthrogryposis collected over the last 35 years, 33 cases of maternal uterine structural anomalies were identified (1.3%). These cases of arthrogryposis represent a very heterogeneous group of types of arthrogryposis. Over half of individuals affected with arthrogryposis demonstrated asymmetry and some responded to removal of constraint, 29 of the 33 cases of arthrogryposis whose mother had a uterine structural anomaly could be identified as having a specific recognizable type of arthrogryposis. Only two cases (0.08%) had primarily proximal contractures that returned to almost normal function within 1 year. Craniofacial asymmetry was the most striking finding in these two cases. A quarter of cases had ruptured membranes between 32 and 36 weeks and either oligohydramnios or prematurity. The pregnancy histories of the mothers with uterine structural anomalies were typical in having infertility, multiple miscarriages, and stillbirths. The finding of only two cases which are likely to have multiple congenital contractures on the basis of uterine constraint suggests that it is a very rare primary cause of arthrogryposis.


Association of Fatigue Intensification with Cognitive Impairment during Radiation Therapy for Prostate Cancer.
Cancer-related fatigue is a common complaint during cancer treatment and is often associated with cognitive impairment. This study examined cognitive deficits that were associated with fatigue symptoms during external-beam radiation therapy (EBRT) in men with localized prostate cancer. A total of 36 participants were enrolled and followed up at baseline, 24 h, 7 days, 14 days after EBRT initiation, at midpoint, and at completion of EBRT. Fatigue was measured by self-report using the Functional Assessment of Cancer Therapy - Fatigue (FACT-F), and cognitive impairment by the Computer Assessment of Mild Cognitive Impairment (CAMCI®). Subjects with increased fatigue during EBRT reported a significant decline in cognitive function and had difficulties with CAMCI®'s route finding and item recall tasks during EBRT. Increased fatigue during EBRT was associated with perceived cognitive difficulties in executive function and recognition memory, but not with attention or verbal memory. Our results suggest that there might be specific cognitive domains that are associated with increased fatigue during EBRT. These findings will provide important information for targeting specific cognitive domains using pharmacotherapy or behavioral interventions. CAMCI® is a valuable tool for psycho social providers to detect subtle cognitive impairment in fatigued cancer patients in a clinical setting.


Epidemiology, drug resistance, and pathophysiology of Plasmodium vivax malaria.
Malaria, caused by the protozoan parasites of the genus Plasmodium, is a major health problem in many countries of the world. Five parasite species namely, Plasmodium falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi, cause malaria in humans. Of these, P. falciparum and P. vivax are the most prevalent and account for the majority of the global malaria cases. In most areas of Africa, P. vivax infection is essentially absent because of the inherited lack of Duffy antigen receptor for chemokines on the surface of red blood cells that is involved in the parasite invasion of erythrocytes. Therefore, in Africa, most malaria infections are by P. falciparum and the highest burden of P. vivax infection is in Southeast Asia and South America. Plasmodium falciparum is the most virulent and as such, it is responsible for the majority of malarial mortality, particularly in Africa. Although, P. vivax infection has long been considered to be benign, recent studies have reported life-threatening consequences, including acute respiratory distress syndrome, cerebral malaria, multi-organ failure, dyserythropoiesis and anaemia. Despite exhibiting low parasite biomass in infected people due to parasite's specificity to infect only reticulocytes, P. vivax infection triggers higher inflammatory responses and exacerbated clinical symptoms than P. falciparum, such as fever and chills. Another characteristic feature of P. vivax infection, compared to P. falciparum infection, is persistence of the parasite as dormant liver-stage hypnozoites, causing recurrent episodes of malaria. This review article summarizes the published information on P. vivax epidemiology, drug resistance and pathophysiology.


Macrophage subpopulations and their impact on chronic allograft rejection versus graft acceptance in a mouse heart transplant model.
Macrophages infiltrating the allografts are heterogeneous, consisting of proinflammatory (M1 cells) as well as antiinflammatory and fibrogenic phenotypes (M2 cells); they affect transplantation outcomes via diverse mechanisms. Here we found that macrophage polarization into M1 and M2 subsets was critically dependent on tumor necrosis factor receptor-associated factor 6 (TRAF6) and mammalian target of rapamycin (mTOR), respectively. In a heart transplant model we showed that macrophage-specific deletion of TRAF6 (LysMCre Traf6 fl/fl ) or mTOR (LysMCre Mtorfl/fl ) did not affect acute allograft rejection. However, treatment of LysMCre Mtorfl/fl recipients with CTLA4-Ig induced long-term allograft survival (>100 days) without histological signs of chronic rejection, whereas the similarly treated LysMCre Traf6 fl/fl recipients developed severe transplant vasculopathy (chronic rejection). The presentation of chronic rejection in CTLA4-Ig-treated LysMCre Traf6 fl/fl mice was similar to that of CTLA4-Ig-treated wild-type B6 recipients. Mechanistically, we found that the graft-infiltrating macrophages in LysMCre Mtorfl/fl recipients expressed high levels of PD-L1, and that PD-L1 blockade readily induced rejection of otherwise survival grafts in the LysMCre Mtorfl/fl recipients. Our findings demonstrate that targeting mTOR-dependent M2 cells is critical for preventing chronic allograft rejection, and that graft survival under such conditions is dependent on the PD-1/PD-L1 coinhibitory pathway.


BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway.
The process of vascular calcification shares many similarities with that of physiological skeletal mineralization, and involves the deposition of hydroxyapatite crystals in arteries. However, the cellular mechanisms responsible have yet to be fully explained. Bone morphogenetic protein (BMP-9) has been shown to exert direct effects on both bone development and vascular function. In the present study, we have investigated the role of BMP-9 in vascular smooth muscle cell (VSMC) calcification. Vessel calcification in chronic kidney disease (CKD) begins pre-dialysis, with factors specific to the dialysis milieu triggering accelerated calcification. Intriguingly, BMP-9 was markedly elevated in serum from CKD children on dialysis. Furthermore, in vitro studies revealed that BMP-9 treatment causes a significant increase in VSMC calcium content, alkaline phosphatase (ALP) activity and mRNA expression of osteogenic markers. BMP-9-induced calcium deposition was significantly reduced following treatment with the ALP inhibitor 2,5-Dimethoxy-N-(quinolin-3-yl) benzenesulfonamide confirming the mediatory role of ALP in this process. The inhibition of ALK1 signalling using a soluble chimeric protein significantly reduced calcium deposition and ALP activity, confirming that BMP-9 is a physiological ALK1 ligand. Signal transduction studies revealed that BMP-9 induced Smad2, Smad3 and Smad1/5/8 phosphorylation. As these Smad proteins directly bind to Smad4 to activate target genes, siRNA studies were subsequently undertaken to examine the functional role of Smad4 in VSMC calcification. Smad4-siRNA transfection induced a significant reduction in ALP activity and calcium deposition. These novel data demonstrate that BMP-9 induces VSMC osteogenic differentiation and calcification via ALK1, Smad and ALP dependent mechanisms. This may identify new potential therapeutic strategies for clinical intervention.


Towards competitive instead of biased testing of heuristics: a reply to hilbig and richter (2011).
Our programmatic article on Homo heuristicus (Gigerenzer & Brighton, 2009) included a methodological section specifying three minimum criteria for testing heuristics: competitive tests, individual-level tests, and tests of adaptive selection of heuristics. Using Richter and Späth's (2006) study on the recognition heuristic, we illustrated how violations of these criteria can lead to unsupported conclusions. In their comment, Hilbig and Richter conduct a reanalysis, but again without competitive testing. They neither test nor specify the compensatory model of inference they argue for. Instead, they test whether participants use the recognition heuristic in an unrealistic 100% (or 96%) of cases, report that only some people exhibit this level of consistency, and conclude that most people would follow a compensatory strategy. We know of no model of judgment that predicts 96% correctly. The curious methodological practice of adopting an unrealistic measure of success to argue against a competing model, and to interpret such a finding as a triumph for a preferred but unspecified model, can only hinder progress. Marewski, Gaissmaier, Schooler, Goldstein, and Gigerenzer (2010), in contrast, specified five compensatory models, compared them with the recognition heuristic, and found that the recognition heuristic predicted inferences most accurately.


Draft Whole-Genome Sequences of Salmonella enterica subsp. enterica Serovars Enteritidis, Veneziana, and Salford, Isolated from Herbs.
Salmonellais a foodborne pathogen found in a wide variety of sources. Here, we report draft genome sequences of threeSalmonella entericasubsp.entericaserovars found in herbs: Enteritidis, Veneziana, and Salford, with the latter two being extremely rare in California.


Enhancement of ciliary action by a beta-adrenergic stimulant.
It is known that beta-adrenergic stimulants enhance mucociliary transport in the respiratory tract. The present study clearly indicated that such an enhancement resulted from not only the alteration in secretory function but also the direct stimulation of ciliated cells. However, the enhancement of ciliary beating depended on the morphological changes in ciliated cells. On the other hand, the effect of terbutaline aerosol, a beta-adrenergic stimulant, on patients with chronic sinusitis was evaluated by paranasal sinus radiography. Consequently, marked improvements in shadows were achieved after 4 weeks in 40% of the cases examined.


Relationship of feeder lamb frame size to feedlot gain and carcass yield and quality grades.
Small-(S), medium-(M), and large-(L) framed feeder lambs (n = 243 S, 247 M, and 245 L) were finished on five diets differing in amount of concentrate (C) and crude protein (CP): 1) 30% C, 12.5% CP; 2) 55% C, 12.5% CP; 3) 55% C, 14.5% CP; 4) 80% C, 12.5% CP; and 5) 80% C, 14.5% CP. Lambs were sampled over a wide weight range to establish relationships of frame size to daily gain and live weight at specific carcass grade end points. Increased frame size (F) was associated with more rapid gains during finishing, although differences in daily gain among L, M, and S lambs were not expressed consistently across all dietary treatments (D), as reflected by a significant F x D interaction for ADG. The rate at which external fat thickness increased as the lambs became heavier was not affected by frame size, sex, or diet. However, increased frame size was associated with lower (P < .05) values for fat thickness (FT), body wall thickness (BWT), yield grade (YG), and quality grade (QG) when comparisons were made at a constant slaughter weight. Similarly, later-maturing wether lambs were leaner and had lower YG and QG than ewes of the same weight. Dietary treatment had no effect on FT, BWT, and YG when treatment groups were compared at a constant live weight. Subclass regressions of YG on live weight were used to project the weights at which lambs of various frame sizes would be expected to produce YG-2 carcasses. Projected final weights for wethers were less than 50 kg for S, 50 to 55 kg for M, and greater than 55 kg for L. Projected final weights for ewe lambs were approximately 2.5 kg lower. Dietary treatment did not affect relationships among frame size, live weight, and YG. A grading/classification system for feeder lambs based on frame size could be developed to predict carcass grade end point.


Microbial degradation of fluometuron is influenced by roundup weatherMAX.
Laboratory experiments were conducted to describe the influence of glyphosate and fluometuron on soil microbial activity and to determine the effect of glyphosate on fluometuron degradation in soil and by Rhizoctonia solani. Soil and liquid medium were amended with formulated fluometuron alone or with two rates of formulated glyphosate. The soil carbon mineralization was measured hourly for 33 days. The fluometuron remaining in the soil was quantified following 3, 6, 10, 15, 20, 30, and 40 days of incubation. The fluometuron remaining in medium and fungal biomass was measured after 1, 3, 6, 10, 15, and 20 days of incubation. The addition of glyphosate with fluometuron increased C-mineralization and increased the rate of fluometuron degradation relative to fluometuron applied alone. However, more fluometuron remained in the media and less fungal biomass was produced when glyphosate was included.


Periodicity of sleep states is altered in infants at risk for the sudden infant death syndrome.
The normal succession of sleep and waking states through a night is disturbed in infants at risk for the sudden infant death syndrome. Compared with normal infants, siblings of the sudden infant death syndrome victims have longer intervals between active sleep epochs at particular times during the night in the newborn period and a decreased tendency to enter short waking periods at 2 and 3 months of age. The latter finding is interpreted as an increased tendency to remain asleep, or a relative failure to arouse from sleep in infants at risk.


When the sun never sets: diverse activity rhythms under continuous daylight in free-living arctic-breeding birds.
Circadian clocks are centrally involved in the regulation of daily behavioural and physiological processes. These clocks are synchronized to the 24 h day by external cues (Zeitgeber), the most important of which is the light-dark cycle. In polar environments, however, the strength of the Zeitgeber is greatly reduced around the summer and winter solstices (continuous daylight or continuous darkness). How animals time their behaviour under such conditions has rarely been studied in the wild. Using a radio-telemetry-based system, we investigated daily activity rhythms under continuous daylight in Barrow, Alaska, throughout the breeding season in four bird species that differ in mating system and parental behaviour. We found substantial diversity in daily activity rhythms depending on species, sex and breeding stage. Individuals exhibited either robust, entrained 24 h activity cycles, were continuously active (arrhythmic) or showed 'free-running' activity cycles. In semipalmated sandpipers, a shorebird with biparental incubation, we show that the free-running rhythm is synchronized between pair mates. The diversity of diel time-keeping under continuous daylight emphasizes the plasticity of the circadian system, and the importance of the social and life-history context. Our results support the idea that circadian behaviour can be adaptively modified to enable species-specific time-keeping under polar conditions.


Impact of HIV and a history of marijuana dependence on procedural learning among individuals with a history of substance dependence.
Marijuana (MJ) use and HIV infection are both associated with neurocognitive deficits, yet there is little research to date examining their interactions, specifically how they pertain to procedural learning (PL). We examined a sample of 86 individuals with a history of dependence for multiple substances who underwent a comprehensive evaluation including measures of mental health, substance use history, and three measures of PL: the photoelectric Rotary Pursuit Task (RPT), the Star Mirror Tracing Task (SMT), and the Weather Prediction Task (WPT). We found that a positive HIV serostatus and a history of marijuana dependence were both independently associated with overall poorer performance on the SMT and RPT in this sample of individuals with a history of dependence for multiple substances. Rate of improvement across trial blocks did not differ as a function of HIV serostatus or history of marijuana dependence. Although we found no significant HIV × MJ interaction for any of the PL tasks, we did observe evidence of additive negative effects from HIV and a history of marijuana dependence on overall performance on the SMT and RPT, but not the WPT. The findings suggest that complex motor skills are adversely affected among abstinent polysubstance users with a history of marijuana dependence and that such deficits are compounded by HIV.


The Quality of Reporting of Intervention Studies in the Korean Journal of Women Health Nursing (KJWHN): Based on the TREND Guidelines.
This study was done to evaluate quality of reports of non-randomized controlled quasi-experimental study articles published in the Korean Journal of Women Health Nursing (KJWHN). A search was done for experimental studies assessing intervention effects among all articles published in the KJWHNfrom 2008 to 2013. Original articles were reviewed and analyzed according to the 22 checklist items of the guidelines for Transparent Reporting for Evaluations with Non-randomized Designs (TREND). Thirty-five articles on experimental studies were identified. The evaluation of the quality of reporting in these experimental studies found that there was a wide variety in the level of satisfying the TREND checklist. In particular, according to TREND topics, low levels of reporting quality were found for "title & abstract (only for information on how units were allocated to the intervention)", "outcomes in methods", "assignment in methods", "blinding in methods", "recruitment in results", "baseline data in results", "interpretation in discussion (especially intervention mechanism and success or barriers), "generalizability in discussion". Results indicate that adherence to TREND guidelines varied in experimental studies published in the KJWHN suggesting the recommendation that for higher levels of complete reporting, TREND guidelines be used in reports on experimental studies.


Involvement of the histaminergic system in the resuscitating effect of centrally acting leptin in haemorrhagic shock in rats.
Leptin, acting centrally as a neuromodulator, induces the activation of the sympathetic nervous system, which may lead to a pressor action in normotensive animals. In haemorrhagic shock, leptin administered intracerebroventricularly (icv.) evokes the resuscitating effect, with long-lasting rises in mean arterial pressure (MAP) and heart rate (HR), subsequent increase in peripheral blood flows, and a 100% survival at 2 h. Since leptin is able to activate histaminergic neurons, and centrally acting histamine also induces the resuscitating effect with the activation of the sympathetic nervous system, in the present study, we investigated an involvement of the histaminergic system in leptin-evoked cardiovascular effects in haemorrhagic shock. The model of irreversible haemorrhagic shock, with MAP decreased to and stabilised at 20 - 25 mmHg, has been used. Leptin (20 μg) given icv. at 5 min of critical hypotension evoked 181.5% increase in extracellular hypothalamic histamine concentration during the first 10 min after injection. Rises in MAP, HR and renal, mesenteric and hindquarters blood flows induced by leptin were inhibited by icv. pre-treatment with histamine H1 receptor antagonist chlorpheniramine (50 nmol). In contrast, there was no effect of H2, H3 and H4 receptor antagonists ranitidine (25 nmol), VUF 5681 (25 nmol) and JNJ 10191584 (25 nmol), respectively. In conclusion, the histaminergic system is involved in centrally-acting leptin-induced resuscitating effect in haemorrhagic shock in rats.


Wheat Bread Fortification by Grape Pomace Powder: Nutritional, Technological, Antioxidant, and Sensory Properties.
Grape pomace powder (GPP), a by-product from the winemaking process, was used to substitute flour for wheat bread fortification within 0, 5, and 10 g/100 g. Rheological properties of control and fortified doughs, along with physicochemical and nutritional characteristics, antioxidant activity, and the sensory analysis of the obtained bread were considered. The GPP addition influenced the doughs' rheological properties by generating more tenacious and less extensible products. Concerning bread, pH values and volume of fortified products decreased as the GPP inclusion level increased in the recipe. Total phenolic compounds and the antioxidant capacity of bread samples, evaluated by FRAP (ferric reducing ability of plasma) and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) assays, increased with GPP addition. Moreover, the GPP inclusion level raised the total dietary fiber content of bread. Regarding sensory evaluation, GPP fortification had a major impact on the acidity, the global flavor, the astringency, and the wine smell of bread samples without affecting the overall bread acceptability. The current results suggest that GPP could be an attractive ingredient used to obtain fortified bread, as it is a source of fiber and polyphenols with potentially positive effects on human health.


Fast atom bombardment mass spectrometry.
Fast atom bombardment mass spectrometry has become a powerful structural tool since the first reports of its use in 1981. Samples are ionized in the condensed state, usually in a glycerol matrix, by bombarding the matrix with xenon or argon atoms with energies of 5000 to 10,000 electron volts. This yields both positive and negative secondary ions, which are sputtered from the surface. The technique has been used to detect inorganic ion clusters to mass 25,800 and biologically active peptides to mass 5700, and it gives molecular ions of such highly polar or labile organic compounds as glycosphingolipids and polyene antibiotics. It can be especially valuable in determining the sequences of amino acids in polypeptides.


Pathotypes Detected Among Populations of Pratylenchus neglectus Collected From Montana.
The root lesion nematode, Pratylenchus neglectus, is one of the most damaging nematodes to affect wheat worldwide. The nematode is widely distributed in Montana, primarily affecting winter wheat within the state. Managing the nematode primarily involves rotation to resistant and moderately resistant crops (peas, lentils, and barley). A nematode survey was conducted across the state nearly 10 years after an initial survey, to reassess the nematode threat and assess the impact of changing trends in crop rotations. To assess the broad applicability of rotation crops to control P. neglectus across Montana, greenhouse trials were conducted to challenge rotational crops using eight populations of P. neglectus collected from geographically diverse locations across the state. In the trials, conducted with four Montana crops, a significant interaction was detected between crop and nematode population (analysis of variance P < 0.001). Populations from Hill, Dawson, and Chouteau counties were found to be pathogenic on barley. Male nematodes were detected in seven of the eight pot culture populations, and these were confirmed to be P. neglectus by morphological and molecular methods. These results suggest a re-evaluation of barley and lentils as a management option for P. neglectus in Montana, as pathotypes for each exist within the state.


Newborn metabolic screening: a search for "nature's experiments".
The rationale for metabolic screening includes discovery of new diseases, development of treatment methods, determination of the true incidence of disease in order to provide genetic counseling, and relief to the taxpayer when retardation is preventable. The number of diseases for which we can now screen is large and growing and must be periodically reviewed. Physical, cultural, and religious factors affect gene pool mixing, making it impossible to predict a priori what the incidence of a given disorder will be within the population screened. This paper reviews the rationale for establishing neonatal metabolic screening programs and the significance of the information gained.


Tumor and stromal-based contributions to head and neck squamous cell carcinoma invasion.
Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.


[The 80th anniversary of the organization of phthisiatric services in Russia].
The paper outlines the history of foundation of a state phthisiologic service in Russia. In Russia, there was no state antituberculous service before the Soviet power. The date of foundation of a phthisiologic service should be considered October 25, 1918, when the Meeting of the Board of the People's Commissariat of Health of Russia approved the point "On a Tuberculosis Control Section of the People's Commissariat of Health". The Section comprised authoritative scientists and practitioners who had experience in controlling tuberculosis. The section solved problems promptly and on a collective basis. It analyzed and introduced locally adjusted foreign experience in controlling tuberculosis. The decisions made by the Section were sent for their implementation in situ. Antituberculous dispensaries and sanatoria were founded in each administrative unit in a short period. The Section founded the State Tuberculosis Institute in 1921, the Department of Tuberculosis in 1922, began to issue the periodical "Voprosy Tuberkulyoza", or Problems of Tuberculosis, in 1923, and to hold Congresses of Phthisiologists in 1922. The Section was greatly supported by the government and financed by the state. Surveys and treatment are free of charge. The Section tackles both social and medical problems.


CD271 promotes proliferation and migration in bladder cancer.
Bladder cancer is a urothelial cancer and effective therapeutic strategies for its advanced stages are limited. Here, we report that CD271, a neurotrophin receptor, promotes the proliferation and migration of bladder cancer cells. CD271 knockdown decreased proliferation in both adherent and spheroid cultures, and vice versa when CD271 was overexpressed in bladder cancer cell lines. CD271 depletion impaired tumorigenicity in vivo. Migration activity was reduced by CD271 knockdown and TAT-Pep5, a known CD271-Rho GDI-binding inhibitor. Apoptosis was induced by CD271 knockdown. Comprehensive gene expression analysis revealed alterations in E2F- and Myc-related pathways upon CD271 expression. In clinical cases, patients with high CD271 expression showed significantly shortened overall survival. In surgically resected specimens, pERK, a known player in proliferation signaling, colocalizes with CD271. These data indicate that CD271 is involved in bladder cancer malignancy by promoting cell proliferation and migration, resulting in poor prognosis.


Solitary metastatic carcinoma of the spleen.
A care is reported in which an isolated metastatic lesion of the spleen was discovered one year after a modified radical mastectomy for carcinoma of the breast, and seven years following total hysterectomy and bilateral salpingo-oophorectomy for carcinoma of the left ovary. Splenectomy was followed by significant clinical improvement of the patient who remains alive and well four years after operation. Regular physical and roentgen examinations have revealed no evidence of recurrent disease. The factors relating to the occurrence of solitary splenic metastasis are discussed briefly. This case is apparently the fifth reported in the literature.


[Materno-fetal transmission of hepatitis B virus in Ivory Coast. Plea for mass vaccination].
Hepatitis B is a major public health problem in the developing countries of Africa and Asia because the prevalence of HBs antigen carriers is high. In Ivory Coast, the prevalence of HBs antigen carriers is more than 8% (6 to 29%). In these countries, in which hepatitis B is highly endemic, most infections with hepatitis B virus (HBV) occur during early childhood. The chronic carriage of HBV was found to be common in children, who played a key role in maintaining the high level of endemicity in these areas. Vaccines against HBV are effective and their introduction as part of the Expanded Program of Immunization (EPI), as recommended by the WHO, is feasible. The aim of this study was to evaluate the prevalence of HBs antigen in pregnant women and to determine the rate of maternal transmission of HBV to the fetus, to demonstrate the importance of HBs antigen screening during pregnancy and the immunization of babies in the Ivory Coast. Between August 1995 and February 1996, 395 women in the last three months of pregnancy (age 25 +/- 6.9 years) were screened for HBs antigen. Those testing positive were also screened for HBe antigen. Transmission of HBV in utero was studied with 322 mothers and their offspring. HBs antigen was assayed in the cord blood of the offspring of HBs antigen-positive mothers. If the test for HBs antigen was positive, HBe antigen was also assayed. Second-generation ELISA tests (MONOLISA HBs Ag and MONOLISA HBe Ag from Sanofi Pasteur) were used. Babies from HBs antigen-positive mothers were vaccinated at birth with three doses of GenHevac B.


Recommendations for choosing an analysis method that controls Type I error for unbalanced cluster sample designs with Gaussian outcomes.
We used theoretical and simulation-based approaches to study Type I error rates for one-stage and two-stage analytic methods for cluster-randomized designs. The one-stage approach uses the observed data as outcomes and accounts for within-cluster correlation using a general linear mixed model. The two-stage model uses the cluster specific means as the outcomes in a general linear univariate model. We demonstrate analytically that both one-stage and two-stage models achieve exact Type I error rates when cluster sizes are equal. With unbalanced data, an exact size α test does not exist, and Type I error inflation may occur. Via simulation, we compare the Type I error rates for four one-stage and six two-stage hypothesis testing approaches for unbalanced data. With unbalanced data, the two-stage model, weighted by the inverse of the estimated theoretical variance of the cluster means, and with variance constrained to be positive, provided the best Type I error control for studies having at least six clusters per arm. The one-stage model with Kenward-Roger degrees of freedom and unconstrained variance performed well for studies having at least 14 clusters per arm. The popular analytic method of using a one-stage model with denominator degrees of freedom appropriate for balanced data performed poorly for small sample sizes and low intracluster correlation. Because small sample sizes and low intracluster correlation are common features of cluster-randomized trials, the Kenward-Roger method is the preferred one-stage approach.


Intestinal hyperabsorption of oxalate in calcium oxalate stone formers: application of a new test with [13C2]oxalate.
In up to one-third of patients with calcium oxalate stones, a hyperoxaluria can be detected. Hyperoxaluria can result from increased endogenous production, from excessive oxalate content of the food, or from intestinal hyperabsorption. For a causal therapy, it is important to discriminate between metabolic and hyperabsorptive hyperoxaluria. Our new 13C-oxalate test allows this differentiation. Under standardized conditions, 50 mg of disodium salt of [13C2]oxalic acid was applied. From the amount of labeled oxalate excreted in urine as measured by a gas chromatographic-mass spectrometric assay, the intestinal absorption was calculated. Seventy patients with recurrent calcium oxalate urolithiasis who had no signs of inflammatory bowel disease were tested. Their mean intestinal oxalate absorption was 9.2+/-5.1%. This was significantly higher than the mean absorption of 50 healthy volunteers (6.7+/-3.9%). There was no difference in oxalate absorption between male (n = 25) and female volunteers. Oxalate absorption correlated with the oxalate excretion in the 24-h urine (volunteers: r = 0.46, P < 0.01; patients: r = 0.62, P < 0.001). Oxalate hyperabsorption was defined as an absorption exceeding 10%. According to this definition, 34% of the patients had oxalate hyperabsorption; 20% of the volunteers showed a hyperabsorption, too. The 13C-oxalate absorption test allows reliable determination of intestinal oxalate absorption. Because of the use of a stable isotope, this test may be repeated as often as required. It will allow the control of therapeutic regimens and also help to unravel genetic influences in stone formation.


Generation of new transforming viruses from SIRC cells "phenotypically transformed" in the medium with low concentrations of serum or calcium ions.
The work reported here demonstrates the possibility of rapid generation of highly transforming viruses from rabbit epithelial corneal cells (SIRC) originated from simian sarcoma associated virus (SSAV). The results of the experiments indicate a possible association of the phenomenon of "phenotypic transformation" with the expression of cellular genes with a potential transforming activity. SIRC/SSAV phenotypic transformation was induced by cultivation of these cells in the medium with a low concentration of serum or calcium ions. During subsequent infection of mink lung fibroblasts the authors succeeded in obtaining two new transforming SSAV isolates which induced transformation foci of various morphological types in cellular lines permissive for SSAV replication.


The population and landscape genetics of the European badger (Meles meles) in Ireland.
The population genetic structure of free-ranging species is expected to reflect landscape-level effects. Quantifying the role of these factors and their relative contribution often has important implications for wildlife management. The population genetics of the European badger (Meles meles) have received considerable attention, not least because the species acts as a potential wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland. Herein, we detail the most comprehensive population and landscape genetic study of the badger in Ireland to date-comprised of 454 Irish badger samples, genotyped at 14 microsatellite loci. Bayesian and multivariate clustering methods demonstrated continuous clinal variation across the island, with potentially distinct differentiation observed in Northern Ireland. Landscape genetic analyses identified geographic distance and elevation as the primary drivers of genetic differentiation, in keeping with badgers exhibiting high levels of philopatry. Other factors hypothesized to affect gene flow, including earth worm habitat suitability, land cover type, and the River Shannon, had little to no detectable effect. By providing a more accurate picture of badger population structure and the factors effecting it, these data can guide current efforts to manage the species in Ireland and to better understand its role in bTB.


X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile Aquifex aeolicus at 1.6 A resolution: determinants of thermostability revealed from structural comparisons.
An open reading frame optimized for expression of 6,7-dimethyl-8-ribityl-lumazine synthase of the hyperthermophilic bacterium Aquifex aeolicus in Escherichia coli was synthesized and expressed in a recombinant E. coli strain to a level of around 15 %. The recombinant protein was purified by heat-treatment and gel-filtration. The protein was crystallized in the cubic space group I23 with the cell dimensions a = b = c = 180.8 A, and diffraction data were collected to 1.6 A resolution. The structure was solved by molecular replacement using lumazine synthase from Bacillus subtilis as search model. The structure of the A. aeolicus enzyme was refined to a resolution of 1.6 A. The spherical protein consists of 60 identical subunits with strict icosahedral 532 symmetry. The subunit fold is closely related to that of the B. subtilis enzyme (rmsd 0.80 A). The extremely thermostable lumazine synthase from A. aeolicus has a melting temperature of 119.9 degrees C. Compared to other icosahedral and pentameric lumazine synthases, the A. aeolicus enzyme has the largest accessible surface presented by charged residues and the smallest surface presented by hydrophobic residues. It also has the largest number of ion-pairs per subunit. Two ion-pair networks involving two, respectively three, stacking arginine residues assume a distinct role in linking adjacent subunits. The findings indicate the influence of the optimization of hydrophobic and ionic contacts in gaining thermostability.


An update on the prone position: Continuing Professional Development.
The purpose of this Continuing Professional Development module is to provide information needed to prepare for and clinically manage a patient in the prone position. Prone positioning is required for surgical procedures that involve the posterior aspect of a patient. We searched MEDLINE(®) and EMBASE™ from January 2000 to January 2015 for literature related to the prone position and retrieved only original articles in English. We reviewed the advantages and disadvantages of various equipment used in prone positioning, the physiological changes associated with prone positioning, and the complications that can occur. We also reviewed strategies for the safe conduct and management of position-related complications. Increased age, elevated body mass index, the presence of comorbidities, and long duration of surgery appear to be the most important risk factors for complications associated with prone positioning. We recommend a structured team approach and careful selection of equipment tailored to the patient and surgery. The systematic use of checklists is recommended to guide operating room teams and to reduce prone position-related complications. Anesthesiologists should be prepared to manage major intraoperative emergencies (e.g., accidental extubation) and anticipate postoperative complications (e.g., airway edema and visual loss).


[The efficacy of using enzymes in treating toxic-allergic reactions after cataract extraction with intraocular lens implantation].
Physiotherapy was administered to 84 patients aged 59-78 years with toxic allergic reaction in the eye after extracapsular cataract extraction with implantation of intraocular lenses (IOL). The patients were divided into 4 groups. Group 1 (n = 15) were treated by fibrinolysin magnetophoresis, group 2 (n = 17) lidase magnetophoresis, group 3 (n = 28) lecozyme magnetophoresis, and group 4 (n = 24) collalysin magnetophoresis. Treatment started on days 3-5 after surgery. Magnetophoresis was carried out using Russian Gradient-1 device, generating a low-frequency magnetic field of 10-12 mT, 10-12 min exposure. For patients with pronounced iridocyclitis and uveitis, enzyme magnetophoresis was supplemented with atropine, adrenalin, and calcium chloride electrophoresis (with monitoring the pupil size). Comprehensive treatment resulted in complete resolution of exudation in the anterior and posterior segments of the eye, hypopyon, loosening and resorption of anterior and posterior synechiae, the vitreous body grew more transparent, visual acuity improved in 91.1% patients (coarse dystrophic changes in the central zone of the fundus oculi were detected in 8.9%). Magnetophoresis with fibrinolysin and lidase is most effective in patients with toxic allergic reaction during the early periods after cataract extraction with IOL implantation, while in later periods magnetophoresis with lecozyme and collalysin should be preferred. The efficacy of collalysin is not inferior to that of lecozyme, but its effect is more mild and the drug causes no allergic reactions. Magnetophoresis with mydriatics (with monitoring the pupil size) and calcium chloride is recommended for all cases.


Physiologic concentrations of homocysteine inhibit the human plasma GSH peroxidase that reduces organic hydroperoxides.
The plasma reduced glutathione (GSH) selenoperoxidase is a highly conserved enzyme. Furthermore, a small clinical study reported that patients with severe atherosclerosis had low peroxidase activities. Together these observations suggest that the peroxidase is important in preventing atherosclerosis. Yet others have reported that when the assay was run in Tris buffer, it was inactive with the concentrations of GSH found in the plasma. Second, it is known that hyperhomocysteinemia increases the rate of atherogenesis. Because there is some homology between homocysteine and the cysteine in GSH, the question is whether the hyperhomocysteinemia effect may be due to inhibition of the peroxidase. We purified the peroxidase from human plasma and determined its activity by a coupled spectrophotometric assay and a substrate disappearance chemiluminescence assay. When the peroxidase activity was determined in phosphate-buffered saline solution (PBS), there was significant activity with the reported plasma GSH concentrations (5 to 20 micromol/L). The peroxidase was exclusively in the HDL fraction. There was no correlation between the peroxidase activity and the HDL or LDL cholesterol concentrations. Finally, at physiologic concentrations of GSH (9 micromol/L), the peroxidase was inhibited by physiologic, free homocysteine concentrations (1 to 5 micromol/L). These data suggest that the peroxidase is active in vivo and may be important in protecting the endothelium from atherosclerosis by preventing oxidant injury. The homocysteine inhibition of the peroxidase suggests a possible biochemical basis for the observed association between hyperhomocysteinemia and cardiovascular disease. Our studies imply that low concentrations of this peroxidase may be an independent risk factor for atherosclerosis.


Disruption of imprinting by mutator transposon insertions in the 5' proximal regions of the Zea mays Mez1 locus.
Imprinting is a form of epigenetic gene regulation in which alleles are differentially regulated according to the parent of origin. The Mez1 gene in maize is imprinted such that the maternal allele is expressed in the endosperm while the paternal allele is not expressed. Three novel Mez1 alleles containing Mutator transposon insertions within the promoter were identified. These mez1-mu alleles do not affect vegetative expression levels or result in morphological phenotypes. However, these alleles can disrupt imprinted expression of Mez1. Maternal inheritance of the mez-m1 or mez1-m4 alleles results in activation of the normally silenced paternal allele of Mez1. Paternal inheritance of the mez1-m2 or mez1-m4 alleles can also result in a loss of silencing of the paternal Mez1 allele. The paternal disruption of imprinting by transposon insertions may reflect a requirement for sequence elements involved in targeting silencing of the paternal allele. The maternal disruption of imprinting by transposon insertions within the Mez1 promoter suggests that maternally produced MEZ1 protein may be involved in silencing of the paternal Mez1 allele. The endosperms with impaired imprinting did not exhibit phenotypic consequences associated with bi-allelic Mez1 expression.


A Man With Distal Asymmetric Leg Weakness.
To discuss a case of adult-onset asymmetric distal leg weakness in a patient who presented with weakness and atrophy of the posterior compartment of the left leg. 1. What is the differential diagnosis of asymmetric distal leg weakness?2. How would a clinician approach diagnostic testing for such a patient?3. What is the final diagnosis for this patient?4. How to treat this patient?


Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells.
CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME areas of pancreatic ductal adenocarcinoma (PDA) populated by CD8+ T cells infiltrating both murine and human tumors. In this lipid-rich but otherwise nutrient-poor TME, access to using lipid metabolism becomes particularly valuable for sustaining cell functions. Here, we found that intrapancreatic CD8+ T cells progressively accumulate specific long-chain fatty acids (LCFAs), which, rather than provide a fuel source, impair their mitochondrial function and trigger major transcriptional reprogramming of pathways involved in lipid metabolism, with the subsequent reduction of fatty acid catabolism. In particular, intrapancreatic CD8+ T cells specifically exhibit down-regulation of the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity. Metabolic reprogramming of tumor-specific T cells through enforced expression of ACADVL enabled enhanced intratumoral T cell survival and persistence in an engineered mouse model of PDA, overcoming one of the major hurdles to immunotherapy for PDA.


Calmodulin and calcium-release channels.
Calmodulin (CaM) is a ubiquitous cytosolic protein that plays a critical role in regulating cellular functions by altering the activity of a large number of ion channels. There are many examples for CaM directly mediating the feedback effects of Ca2+ on Ca2+ channels. Recently the molecular mechanisms by which CaM interacts with voltage-gated Ca2+ channels, Ca(2+)-activated K+ channels and ryanodine receptors have been clarified. CaM plays an important role in regulating these ion channels through lobe-specific Ca2+ detection. CaM seems to behave as a channel subunit. It binds at low [Ca2+] and undergoes conformational changes upon binding of Ca2+, leading to an interaction with another part of the channel to regulate its gating. Here we focus on the mechanism by which CaM regulates the inositol 1,4,5-trisphosphate receptor (IP3R). Although the IP3R is inhibited by CaM and by other CaM-like proteins in the presence of Ca2+, we conclude that CaM does not act as the Ca2+ sensor for IP3R function. Furthermore we discuss a novel Ca(2+)-induced Ca(2+)-release mechanism found in A7r5 (embryonic rat aorta) and 16HBE14o- (human bronchial mucosa) cells for which CaM acts as a Ca2+ sensor.


Mogamulizumab versus investigator's choice of chemotherapy regimen in relapsed/refractory adult T-cell leukemia/lymphoma.
Mogamulizumab, a humanized defucosylated anti-C-C chemokine receptor 4 monoclonal antibody, has been approved in Japan for the treatment of C-C chemokine receptor 4-positive adult T-cell leukemia/lymphoma (ATL). This phase II study evaluated efficacy and safety of mogamulizumab in ATL patients with acute, lymphoma, and chronic subtypes with relapsed/refractory, aggressive disease in the US, Europe, and Latin America. With stratification by subtype, patients were randomized 2:1 to intravenous mogamulizumab 1.0 mg/kg once weekly for 4 weeks and biweekly thereafter (n=47) or investigator's choice of chemotherapy (n=24). The primary end point was confirmed overall response rate (cORR) confirmed on a subsequent assessment at 8 weeks by blinded independent review. ORR was 11% (95%CI: 4-23%) and 0% (95%CI: 0-14%) in the mogamulizumab and chemotherapy arms, respectively. Best response was 28% and 8% in the respective arms. The observed hazard ratio for progression-free survival was 0.71 (95%CI: 0.41-1.21) and, after post hoc adjustment for performance status imbalance, 0.57 (95%CI: 0.337-0.983). The most frequent treatment-related adverse (grade ≥3) events with mogamulizumab were infusion-related reaction and thrombocytopenia (each 9%). Relapsed/refractory ATL is an aggressive, poor prognosis disease with a high unmet need. Investigator's choice chemotherapy did not result in tumor response in this trial; however, mogamulizumab treatment resulted in 11% cORR, with a tolerable safety profile.


Heterozygous mutation of cysteine528 in XPO1 is sufficient for resistance to selective inhibitors of nuclear export.
Exportin-1 (CRM1/XPO1) is a crucial nuclear export protein that transports a wide variety of proteins from the nucleus to the cytoplasm. These cargo proteins include tumor suppressors and growth-regulatory factors and as such XPO1 is considered a potential anti-cancer target. From this perspective, inhibition of the XPO1-mediated nuclear export by selective inhibitor of nuclear export (SINE) compounds has shown broad-spectrum anti-cancer activity. Furthermore, the clinical candidate SINE, selinexor, is currently in multiple phase I/II/IIb trials for treatment of cancer. Resistance against selinexor has not yet been observed in the clinic, but in vitro selection of resistance did not reveal any mutations in the target protein, XPO1. However, introduction of a homozygous mutation at the drug's target site, the cysteine 528 residue inside the XPO1 cargo-binding pocket, by genetic engineering, confers resistance to selinexor. Here we investigated whether this resistance to selinexor is recessive or dominant. For this purpose we have engineered multiple leukemia cell lines containing heterozygous or homozygous C528S substitutions using CRISPR/Cas9-mediated genome editing. Our findings show that heterozygous mutation confers similar resistance against selinexor as homozygous substitution, demonstrating that SINE resistance can be obtained by a single and dominant mutation of the cysteine528 residue in XPO1.


Focused Ion Beam Milling and Cryo-electron Tomography Methods to Study the Structure of the Primary Cell Wall in Allium cepa.
Cryo-electron tomography (cryo-ET) is a formidable technique to observe the inner workings of vitrified cells at a nanometric resolution in near-native conditions and in three-dimensions. One consequent drawback of this technique is the sample thickness, for two reasons: i) achieving proper vitrification of the sample gets increasingly difficult with sample thickness, and ii) cryo-ET relies on transmission electron microscopy (TEM), requiring thin samples for proper electron transmittance (<500 nm). For samples exceeding this thickness limit, thinning methods can be used to render the sample amenable for cryo-ET. Cryo-focused ion beam (cryo-FIB) milling is one of them and despite having hugely benefitted the fields of animal cell biology, virology, microbiology, and even crystallography, plant cells are still virtually unexplored by cryo-ET, in particular because they are generally orders of magnitude bigger than bacteria, viruses, or animal cells (at least 10 μm thick) and difficult to process by cryo-FIB milling. Here, we detail a preparation method where abaxial epidermal onion cell wall peels are separated from the epidermal cells and subsequently plunge frozen, cryo-FIB milled, and screened by cryo-ET in order to acquire high resolution tomographic data for analyzing the organization of the cell wall. This protocol was validated in: Curr Biol (2022), DOI: 10.1016/j.cub.2022.04.024.


A theory on the natural history of colloid cysts of the third ventricle.
Patients with third ventricular colloid cysts typically are diagnosed when they develop symptoms related to cerebrospinal fluid (CSF) obstruction at the foramen of Monro. However, the clinical and neuroimaging characteristics related to symptom development are poorly understood. From January 1974 to June 1998, 155 patients with newly diagnosed colloid cysts were managed at our center. Eighty-seven patients (56%) were thought to have tumor-related symptoms, and they underwent surgery (resection, n = 74; ventriculoperitoneal shunting, n = 11; stereotactic aspiration, n = 2). Sixty-eight patients (44%) had colloid cysts thought to be asymptomatic, and observation with serial neuroimaging was recommended. Recursive partitioning was used to examine the association of patient and tumor characteristics with the development of cyst-related symptoms. Univariate analysis comparing symptomatic and asymptomatic patients revealed four factors associated with cyst-related symptoms: 1) younger patient age (44 yr versus 57 yr; P < 0.001); 2) cyst size (13 mm versus 8 mm; P < 0.001); 3) ventricular dilation (83% versus 31%; P < 0.001); and 4) increased signal on T2-weighted magnetic resonance images (44% versus 8%; P = 0.001). All four variables remained significant in a multivariate logistic regression model: patient age (P = 0.04; odds ratio, 1.0); cyst size (P = 0.04; odds ratio, 1.2); ventricular dilation (P = 0.02, odds ratio, 7.2); and increased signal on T2-weighted magnetic resonance images (P = 0.04; odds ratio, 2.7). The most significant variable was ventriculomegaly (yes versus no). Patients with normal-sized ventricles (n = 62) were further categorized by cyst size (< or = 10 mm versus > 10 mm). For patients with enlarged ventricles (n = 93), patient age (< or = 50 yr versus > 50 yr) was the most important variable. Patients older than 50 years also were split with respect to cyst size; patients aged 50 years or younger with enlarged ventricles were not affected by cyst size. The percentage of patients with cyst-related symptoms was 12, 50, and 85% in the three final patient classes, respectively. Multivariate analysis including the patient classes resulted in removal of the other significant variables from the model, whereas the patient classes remained significant (P < 0.0001; odds ratio, 6.3) for predicting patients with cyst-related symptoms. The patient and neuroimaging characteristics of the different patient classes support a theory on the natural history of colloid cysts. Patients with third ventricular colloid cysts become symptomatic when the tumor enlarges rapidly, causing CSF obstruction, ventriculomegaly, and increased intracranial pressure. Some cysts enlarge more gradually, however, allowing the patient to accommodate the enlarging mass without disruption of CSF flow, and the patient remains asymptomatic. In these cases, if the cyst stops growing, the patient can maintain a steady state between CSF production and absorption and may not require neurosurgical intervention.


Glucocorticosteroid status in chronic alcoholics with and without skeletal muscle myopathy.
1. Chronic alcoholism is associated with a selective atrophy of type II skeletal muscle fibres. We studied the glucocorticoid status of chronic alcoholics with and without myopathy to determine if hypercortisolism is responsible for the myopathy. 2. Twenty-four hour urinary cortisol excretion and diurnal serum cortisol measurements were not significantly different in chronic alcoholics, with and without atrophy of type II skeletal muscle fibres. 3. Diurnal serum cortisol variation was normal for both groups of alcoholics studied. None of the patients with myopathy had raised serum cortisol levels. 4. We conclude that chronic alcoholic myopathy is not due to alcohol-related pseudo-Cushing's syndrome.


[Specific changes in the phospholipid composition of seminal fluid in male infertility].
High-performance liquid chromatography was used to study the phospholipid composition of spermatozoa and sperm plasma in men with fertility disorders. The changes in the phospholipid spectrum of both germ cells and its surroundings were found to depend on the nature of changes in the spermatogram. The most pronounced shifts were common to subjects with asthenozoo-, oligozoo-, and teratozoospermia, which may be a cause of infertility.


Effect of carbenoxolone on prostaglandin synthesizing and metabolizing enzymes and correlation with gastric mucosal carbenoxolone concentrations.
Carbenoxolone in a dose dependent manner inhibits the activity of the prostaglandin (PG) metabolizing enzymes 15-hydroxy-PG-dehydrogenase and delta 13-PG-reductase in vitro, while this drug in the same dose range does not influence gastric mucosal PG synthesis by a microsomal cell fraction. Using a radioimmunoassay for carbenoxolone determination, we could show that during absorption high levels of the drug are reached within the gastric mucosa of human volunteers and gastric ulcer patients. From the tissue levels reached it seems possible that carbenoxolone inhibits PG inactivating enzymes of gastric mucosa in vivo as it does in vitro. Thus, decreased inactivation cytoprotective PG synthesized within the gastric mucosa, might contribute to the ulcer healing effect of carbenoxolone.


Genital Herpes in Marital Partners.
During 1983-86, 225 patients were clinically diagnosed to have genital herpes (GH) at our clinic. Of these, 90 men and 55 women were currently married. All the spouses were screened clinically and through standardized techniques for isolation and typing of herpes simplex virus, serological testing and Papanicolaou smear. There were 90 couples in whom at least one spouse had GH and in 38 (42%) couples both partners had GH. Clinically, 49% of wives and 75% of husbands of GH patients were diagnosed to have the disease. The spouses of recurrent GH patients had a higher frequency of the disease than spouses of primary GH patients. Among spouses who were clinically asymptomatic, 40% had high serological titres suggestive of GH. Wives generally experienced more severe symptoms, especially pain in the lesions. Majority of lesions in both the partners were vesicles and ulcers. Prodromata were more among recurrent GH patients in both the partners. The frequency of recurrences wasalso similar in spouses. Seventy percent of wives and 40% of husbands could not identify any precipitating factor. Intercourse, physical stress and rich food were cited as possible factors in the remaining. All the wives had acquired the diseases through their husbands who were promiscuous. Fifty percent of husbands had been infected before marriage. Given the fact that asymptomatic carriers exist, it is better to consider all marital partners of GH as infected. Repeated and long-term follow, - up examination, particularly of wives of GH patients is therefore essential as an important socio-preventive aspect of this disease.


Changes in salicylic acid and antioxidants during induced thermotolerance in mustard seedlings
Heat-acclimation or salicylic acid (SA) treatments were previously shown to induce thermotolerance in mustard (Sinapis alba L.) seedlings from 1.5 to 4 h after treatment. In the present study we investigated changes in endogenous SA and antioxidants in relation to induced thermotolerance. Thirty minutes into a 1-h heat-acclimation treatment glucosylated SA had increased 5.5-fold and then declined during the next 6 h. Increases in free SA were smaller (2-fold) but significant. Changes in antioxidants showed the following similarities after either heat-acclimation or SA treatment. The reduced-to-oxidized ascorbate ratio was 5-fold lower than the controls 1 h after treatment but recovered by 2 h. The glutathione pool became slightly more oxidized from 2 h after treatment. Glutathione reductase activity was more than 50% higher during the first 2 h. Activities of dehydroascorbate reductase and monodehydroascorbate reductase decreased by at least 25% during the first 2 h but were 20% to 60% higher than the control levels after 3 to 6 h. One hour after heat acclimation ascorbate peroxidase activity was increased by 30%. Young leaves appeared to be better protected by antioxidant enzymes following heat acclimation than the cotyledons or stem. Changes in endogenous SA and antioxidants may be involved in heat acclimation.


Thermostable malate synthase of Streptomyces thermovulgaris.
The gene, encoding malate synthase (MS), aceB, was cloned from the thermophilic bacterium Streptomyces thermovulgaris by homology-based PCR. The 1,626-bp cloned fragment encodes a protein consisting of 541 amino acids. S. thermovulgaris malate synthase (stMS) gene was over-expressed in Escherichia coli using a glutathione-S transferase (GST) fusion vector (pGEX-6P-1), purified by affinity chromatography, and subsequently cleaved from its GST fusion partner. The purified stMS was characterized and compared to a mesophilic malate synthase (scMS) from Streptomyces coelicolor. stMS exhibited higher temperature optima (40-60 degrees C) than those of scMS (28-37 degrees C). It was more thermostable and very resistant to the chemical denaturant urea. Amino acid sequence comparison of stMS with four mesophilic streptomycete MSs indicated that they share 70.9-91.4% amino acid identities, with stMS possessing slightly more charged residues (approximately 31%) than its mesophilic counterparts (approximately 28-29%). Seven charged residues (E85, R187, R209, H239, H364, R382 and K520) that were unique to stMS may be selectively and strategically placed to support its peculiar characteristics.


Abnormalities in urinary pterin levels in Rett syndrome.
The pterins, neopterin and biopterin, occur naturally in body fluids including urine. Increased neopterin levels are associated with activation of the cellular immune system and reduced biopterins are essential for biosynthesis of the monoamine neurotransmitters. The present study measured urinary neopterin and biopterin by high-performance liquid chromatography in 40 subjects with Rett syndrome, eight of their healthy sisters and 29 female control volunteers (age range 2-54 years). The results confirm earlier preliminary findings that urinary neopterin levels are raised in a proportion of young girls with Rett syndrome but not in the older women. In contrast urinary biopterin levels are not different from controls in the youngest children but remain low while control values increase with age. These findings may indicate immune activation during the regression phase of Rett syndrome but also raise the possibility that an inherited fault in tetrahydrobiopterin metabolism increases the risk of developing the disorder.


Electrochemical Immunosensors Developed for Amyloid-Beta and Tau Proteins, Leading Biomarkers of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common neurological disease and a serious cause of dementia, which constitutes a threat to human health. The clinical evidence has found that extracellular amyloid-beta peptides (Aβ), phosphorylated tau (p-tau), and intracellular tau proteins, which are derived from the amyloid precursor protein (APP), are the leading biomarkers for accurate and early diagnosis of AD due to their central role in disease pathology, their correlation with disease progression, their diagnostic value, and their implications for therapeutic interventions. Their detection and monitoring contribute significantly to understanding AD and advancing clinical care. Available diagnostic techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are mainly used to validate AD diagnosis. However, these methods are expensive, yield results that are difficult to interpret, and have common side effects such as headaches, nausea, and vomiting. Therefore, researchers have focused on developing cost-effective, portable, and point-of-care alternative diagnostic devices to detect specific biomarkers in cerebrospinal fluid (CSF) and other biofluids. In this review, we summarized the recent progress in developing electrochemical immunosensors for detecting AD biomarkers (Aβ and p-tau protein) and their subtypes (AβO, Aβ(1-40), Aβ(1-42), t-tau, cleaved-tau (c-tau), p-tau181, p-tau231, p-tau381, and p-tau441). We also evaluated the key characteristics and electrochemical performance of developed immunosensing platforms, including signal interfaces, nanomaterials or other signal amplifiers, biofunctionalization methods, and even primary electrochemical sensing performances (i.e., sensitivity, linear detection range, the limit of detection (LOD), and clinical application).


Longitudinal associations between hearing loss and general cognitive ability: The Lothian Birth Cohort 1936.
Hearing impairment is associated with poorer cognitive function in later life. We tested for the potential contribution of childhood cognitive ability to this relationship. Childhood cognitive ability is strongly related to cognitive function in older age, and may be related to auditory function through its association with hearing impairment risk factors. Using data from the Lothian Birth Cohort, 1936, we tested whether childhood cognitive ability predicted later-life hearing ability then whether this association was mediated by demographic or health differences. We found that childhood cognitive ability was negatively associated with hearing impairment risk at age 76 (odds ratio = .834, p = .042). However, this association was nonsignificant after subsequent adjustment for potentially mediating demographic and health factors. Next, we tested whether associations observed in older age between hearing impairment and general cognitive ability level or change were accounted for by childhood cognitive ability. At age 76, in the minimally adjusted model, hearing impairment was associated with poorer general cognitive ability level (β = -.119, p = .030) but was not related to decline in general cognitive ability. The former association became nonsignificant after additional adjustment for childhood cognitive ability (β = -.068, p = .426) suggesting that childhood cognitive ability contributes (potentially via demographic and health differences) to the association between levels of hearing and cognitive function in older age. Further work is needed to test whether early life cognitive ability also contributes to the association (documented in previous studies) between older-age hearing impairment and cognitive decline. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Designing three-dimensional transformation optical media using quasiconformal coordinate transformations.
We introduce an approach to the design of three-dimensional transformation optical (TO) media based on a generalized quasiconformal mapping approach. The generalized quasiconformal TO (QCTO) approach enables the design of media that can, in principle, be broadband and low loss, while controlling the propagation of waves with arbitrary angles of incidence and polarization. We illustrate the method in the design of a three-dimensional carpet ground plane cloak and of a flattened Luneburg lens. Ray-trace studies provide a confirmation of the performance of the QCTO media, while also revealing the limited performance of index-only versions of these devices.


Perspectives on Telemedicine from a National Study of Youth in the United States.
Introduction: Telemedicine is increasingly popular with the recent surge in use due to the COVID-19 pandemic. Despite youth status as "tech natives," limited data are available on their perspectives on telemedicine. Our study seeks to understand youth telemedicine knowledge, prior experiences, preferences for use, and the impact of COVID-19 on these perspectives. Methods: Participants in MyVoice, a national text message cohort of U.S. youth age 14-24, were sent five open-ended questions in October 2019 and October 2020. A codebook was iteratively developed by using inductive analysis. Responses were independently coded by two investigators, with discrepancies resolved by discussion or a third investigator. Results: Sixty-five percent (836/1,283) and 77% (887/1,129) of participants responded to at least 1 question in 2019 and 2020, respectively. Most youth reported awareness of telemedicine and although many have not used it, COVID-19 has increased use. Further, many are willing to try telemedicine services. Most youth noted a preference for video rather than phone visits, but they believe both to be less effective than in person. Youth also reported varied preferences on services best suited for telemedicine, with COVID-19 positively impacting their views. Discussion: Youth are aware of and willing to use telemedicine services, with many reporting use during the COVID-19 pandemic. Youth are willing to accept a wide variety of telemedicine services, though they still desire in-person options. Health systems and clinics should offer a wide range of services via telemedicine to fit the varying needs of youth both during and after the COVID-19 pandemic.


Leo Doyle, master surgeon.
On 3 March 1953 Leo Doyle died at the Mercy Hospital, Melbourne. The day before he died Leo Doyle had been operating at the Mercy Hospital when he took ill. Doyle's final illness was almost certainly the result of the severe aortic stenosis that had been developing over some years. His death at the relatively young age of 61 ended the career of a man described by Sir Gordon Gordon Taylor as the greatest technical surgeon that he had ever seen. In all likelihood Australian surgery will never see the likes of Doyle, a virtuoso surgeon, again. And yet to many of the surgeons who were Doyle's contemporaries and to those who followed him he remained somewhat of an enigma. Perhaps in some way the description of the great French surgeon Baron Dupuytren may also be applicable to Leo Doyle: known to all, loved by many, understood by few. By all accounts Leo Doyle's surgical repertoire knew no bounds. He operated with equal facility on the central nervous system, the head and neck, in the thorax, abdomen and pelvis and he was more than competent in gynaecology, urology and orthopaedics. In the latter part of his career he became, par excellence, a cancer surgeon. He was, arguably, Australia's first surgical oncologist. No procedure was deemed too complicated or demanding. Like some other superb technicians his judgement at times did not match his technical ability. Doyle was one of the first surgeons in Australia to perform hindquarter amputation and he helped to pioneer the operations of total gastrectomy and oesophagogastrectomy. An avid reader of the surgical literature, he possessed an enormous library which was matched by an equally large collection of surgical instruments. Unlike Devine he published relatively little. He was not a good clinical teacher, preferring to teach by example in the operating theatre. Although interested in music and the visual arts, surgery was his life.


Ocular manifestations of Turner's syndrome.
In a series of 24 patients with Turner's syndrome, amblyopia was found to be present in ten (41.6 per cent), strabismus in nine (37.5 per cent), hypermetropia in ten (41.6 per cent), ptosis in seven (29.1 per cent), and bilateral epicanthus in eleven (45.8 per cent) cases. Turner (1938) described a syndrome of infantilism, congenital webbed neck, and cubitus valgus, which has come to be known as Turner's syndrome. Since then many cases have been reported and multiple other associated features have also been recognized. Isolated ocular features have been mentioned in some sporadic case reports (Cunningham and Harley, 1951; Laurent, Royer, and Noel, 1961; Lessell and Forbes, 1966; Khodadoust and Paton, 1967; Szymanska and Szymanski, 1976; Troupe and Troupe, 1981). So far no significant series of cases has been studied to assess the ocular defects. This report of a series of 24 patients presents classified ophthalmic features.


Continuous renal replacement therapy in children post-hematopoietic stem cell transplantation: the present and the future.
Allogeneic hematopoietic stem cell transplantation (HSCT) use has expanded markedly to treat different disorders like hematologic malignancies, immunodeficiency, and inborn errors of metabolism. However, it is commonly associated with complications that limit the benefit of this therapy. Acute renal failure occurs commonly after HSCT and results in increased risk of mortality. In many instances, children post-HSCT develop acute renal insufficiency in the context of other organ failure, necessitating intensive care unit admission for management. Recently, continuous renal replacement therapy (CRRT) has emerged as the favored modality of renal replacement therapy in the care of critically ill children who are hemodynamically unstable. Currently, CRRT is being utilized more often in the care of critically ill post- HSCT children to treat renal failure or to prevent fluid overload (FO). FO > 20% has been shown in many studies to be an independent risk of mortality in critically ill children and therefore, many clinicians will initiate this therapy due to FO even without overt renal failure. CRRT may be beneficial in disease processes as acute lung injury due to removal of fluid. CRRT results in improved oxygenation in post-HSCT children with acute lung injury and this improvement is sustained for at least 48 hours after initiation of this therapy. Survival in post-HSCT children requiring this therapy ranges from 17% to 45%, however, long term survival is still poor. This review will discuss current practice of CRRT in children post-HSCT, as well as future directions.


Cartilage turnover in embryonic chick tibial explant cultures.
Growth plate cartilage regulates the rate of growth and ultimate length of several bones in the skeleton. Chondrocytes within the growth plate proliferate, differentiate, enlarge, and die. The extracellular matrix undergoes synthesis, reorganization, and eventually degradation. The majority of research in growth plate physiology has focused on the proliferation and differentiation of chondrocytes as well as proteins they produce for the extracellular matrix. However, little is known about the transition from hypertrophic to apoptotic chondrocytes or the regulation of terminal degradation of cartilage prior to bone formation. An explant culture has been developed to study cartilage differentiation using 12-d-old embryonic chick tibiae. We have modified the explant culture and are using it to further elucidate mechanisms involved in the regulation of growth plate cartilage turnover. In our cultures, chondrocytes mature and then die, completely degrading the cartilage in approximately 16 d. The matrix undergoes a predictable pattern of degradation in which proteoglycans followed by collagen are removed. Increases in matrix metalloproteinase activity and nitric oxide production are detected in cartilage concurrently with release of proteoglycans into media. Inhibitors of nitric oxide inhibit nitric oxide production and proteoglycan degradation, suggesting that nitric oxide, at least in part, regulates growth plate cartilage turnover in the explant culture. Information gained from using this explant culture will aid in understanding the regulation of growth plate cartilage turnover in vivo and potentially help determine the cause of bone growth diseases such as tibial dyschondroplasia.


Reproductive isolation due to prezygotic isolation and postzygotic cytoplasmic incompatibility in parasitoid wasps.
The reproductive barriers that prevent gene flow between closely related species are a major topic in evolutionary research. Insect clades with parasitoid lifestyle are among the most species-rich insects and new species are constantly described, indicating that speciation occurs frequently in this group. However, there are only very few studies on speciation in parasitoids. We studied reproductive barriers in two lineages of Lariophagus distinguendus (Chalcidoidea: Hymenoptera), a parasitoid wasp of pest beetle larvae that occur in human environments. One of the two lineages occurs in households preferably attacking larvae of the drugstore beetle Stegobium paniceum ("DB-lineage"), the other in grain stores with larvae of the granary weevil Sitophilus granarius as main host ("GW-lineage"). Between two populations of the DB-lineage, we identified slight sexual isolation as intraspecific barrier. Between populations from both lineages, we found almost complete sexual isolation caused by female mate choice, and postzygotic isolation, which is partially caused by cytoplasmic incompatibility induced by so far undescribed endosymbionts which are not Wolbachia or Cardinium. Because separation between the two lineages is almost complete, they should be considered as separate species according to the biological species concept. This demonstrates that cryptic species within parasitoid Hymenoptera also occur in Central Europe in close contact to humans.


Vertical phase separation in bulk heterojunction solar cells formed by in situ polymerization of fulleride.
Vertical phase separation of the donor and the acceptor in organic bulk heterojunction solar cells is crucial to improve the exciton dissociation and charge transport efficiencies. This is because whilst the exciton diffusion length is limited, the organic film must be thick enough to absorb sufficient light. However, it is still a challenge to control the phase separation of a binary blend in a bulk heterojunction device architecture. Here we report the realization of vertical phase separation induced by in situ photo-polymerization of the acrylate-based fulleride. The power conversion efficiency of the devices with vertical phase separation increased by 20%. By optimising the device architecture, the power conversion efficiency of the single junction device reached 8.47%. We believe that in situ photo-polymerization of acrylate-based fulleride is a universal and controllable way to realise vertical phase separation in organic blends.


Thermoreversible laminin-functionalized hydrogel for neural tissue engineering.
Traumatic injury to the central nervous system (CNS) triggers cell death and deafferentation, which may activate a cascade of cellular and network disturbances. These events often result in the formation of irregularly shaped lesions comprised of necrotic tissue and/or a fluid-filled cavity. Tissue engineering represents a promising treatment strategy for the injured neural tissue. To facilitate minimally invasive delivery of a tissue engineered system, a thermoreversible polymer is an attractive scaffold candidate. We have developed a bioactive scaffold for neural tissue engineering by tethering laminin-1 (LN) to methylcellulose (MC), a thermoresponsive hydrogel. The base MC chain was oxidized via sodium m-periodate to increase MC tethering capacity. Protein immobilization was facilitated by a Schiff base reaction between primary amine groups on LN and the carbonyl groups of the oxidized MC chain. Immunoassays demonstrated tethering of LN at 1.6 +/- 0.5 ng of LN per milligram of MC. Rheological measurements for different MC-LN constructs indicated MC composition- and MC treatment-dependent effects on solution-gelation transition temperature. Cellular assays with primary rat cortical neurons demonstrated enhanced cell adhesion and viability on LN-functionalized MC when compared with base and oxidized MC. This bioadhesive thermoresponsive scaffold may provide a robust delivery vehicle to injured CNS tissue for neural cell transplantation strategies.


[Non-invasive electrophysiologic study and radiofrequency current ablation of tachycardia responsible for numerous inappropriate ICD interventions in patient with post-infarction dilated cardiomyopathy].
We present a case of 75-year-old man with numerous inappropriate interventions of an implanted cardioverter-defibrillator (ICD). In this patient with ischaemic cardiomyopathy, ICD was implanted for primary prevention of sudden cardiac death following recurrent syncope. ICD interrogation and non-invasive electrophysiologic study (NIPS) confirmed a risk of reentry-mediated tachycardia and excluded the presence of a manifest or concealed accessory pathway. Invasive electrophysiologic study revealed a wide zone that triggered atrioventricular nodal reentrant tachycardia, and ablation of the slow pathway resulted in complete remission of the arrhythmia. NIPS performed using atrial and ventricular ICD leads and subsequent ICD interrogation confirmed long-term effectiveness of the procedure. At the same time, clinical improvement of heart failure was seen, leading to a suspicion of tachycardia-induced cardiomyopathy coexisting with ischaemic cardiomyopathy.


Central and peripheral quadriceps fatigue in congestive heart failure.
The clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors. We studied 10 men with CHF and 10 healthy age-matched controls. Compared with a rest condition, 10 min after incremental maximal cycle exercise, twitch quadriceps force in response to supramaximal magnetic femoral nerve stimulation fell in both groups (CHF 14.1% ± 18.1%, p=0.037; 20.8 ± 11.0%, p<0.001; no significant difference between groups). There was no significant change in quadriceps maximum voluntary contraction voluntary force. The difference in the motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex between rest and exercise conditions at 10 min, normalised to the peripheral action potential, also fell significantly in both groups (CHF: 27.3 ± 38.7%, p=0.037; 41.1 ± 47.7%, p=0.024). However, the fall in MEP was sustained for a longer period in controls than in patients (p=0.048). The quadriceps is more susceptible to fatigue, with a similar fall in TwQ occurring in CHF patients at lower levels of exercise. This is associated with no change in voluntary activation but a lesser degree of depression of quadriceps motor evoked potential.