Deep localized distortion of alternating bonds and reduced transport of charged carriers in conjugated polymers under photoexcitation.
In a real bulk heterojunction polymer solar cell, after exciton separation in the heterojunction, the resulting negatively-charged carrier, a polaron, moves along the polymer chain of the acceptor, which is believed to be of significance for the charged carrier transport properties in a polymer solar cell. During the negative polaron transport, due to the external light field, the polaron, which is re-excited and induces deep localization, also forms a new local distortion of the alternating bonds. It is revealed that the excited polaron moves more slowly than the ground-state polaron. Furthermore, the velocity of the polaron moving along the polymer chain is crucially dependent on the photoexcitation. With an increase in the intensity of the optical field, the localization of the excited polaron will be deepened, with a decrease of the polaron's velocity. It is discovered that, for a charged carrier, photoexcitation is a significant factor in reducing the efficiency during the charged carrier transport in polymer solar cells. Mostly, the deep trapping effect of charged carrier in composite conjugated polymer solar cell presents an opportunity for the future application in nanoscale memory and imaging devices.


Targeting Induced Local Lesions in Genomes (TILLING): advances and opportunities for fast tracking crop breeding.
The intensification of food production via conventional crop breeding alone is inadequate to cater for global hunger. The development of precise and expeditious high throughput reverse genetics approaches has hugely benefited modern plant breeding programs. Targeting Induced Local Lesions in Genomes (TILLING) is one such reverse genetics approach which employs chemical/physical mutagenesis to create new genetic sources and identifies superior/novel alleles. Owing to technical limitations and sectional applicability of the original TILLING protocol, it has been timely modified. Successions include: EcoTILLING, Double stranded EcoTILLING (DEcoTILLING), Self-EcoTILLING, Individualized TILLING (iTILLING), Deletion-TILLING (De-TILLING), PolyTILLING, and VeggieTILLING. This has widened its application to a variety of crops and needs. They can characterize mutations in coding as well as non-coding regions and can overcome complexities associated with the large genomes. Combining next generation sequencing tools with the existing TILLING protocols has enabled screening of huge germplasm collections and mutant populations for the target genes. In silico TILLING platforms have transformed TILLING into an exciting breeding approach. The present review outlines these multifarious TILLING modifications for precise mutation detection and their application in advance breeding programmes together with relevant case studies. Appropriate use of these protocols will open up new avenues for crop improvement in the twenty first century.


Dyskinesia and impulsive compulsive behaviour in Parkinson's disease are not related: Insights from a study with a wearable sensor.
Previous studies have suggested an association between Impulsive Compulsive Behaviour (ICB) and dyskinesia in Parkinson's disease (PD). However, none of these studies have employed an objective home-based measure of dyskinesia. To evaluate in advanced PD the relationship between ICB and dyskinesia, objectively measured with a wearable device. In this cross-sectional study, ICB and other neuropsychiatric symptoms were assessed by means of structured clinical interview and specific screening instruments. Presence and severity of motor fluctuations and dyskinesia were rated with patient's and clinician's based rating instruments. Motor fluctuations and dyskinesia were also measured at home for 5-days using a validated wearable devise, the Parkinson's KinetiGraph™(PKG). We included 89 subjects with PD (29 females, 62 ± 7 years, disease duration 10.3 ± 4.5), of whom 36 (40%) had ICB. Patients with and without ICB did not differ by presence and severity of dyskinesia measured by clinical scales and PKG. There was no association between the presence of ICB and dyskinesia in the whole sample. Our data suggest that ICB and dyskinesia are common but unrelated disorders in advanced PD.


Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway.
Creatine is a nitrogenous organic acid known to function in adenosine triphosphate (ATP) metabolism. Recent evidence indicates that creatine regulates the differentiation of mesenchymal stem cells (MSCs) in processes such as osteogenesis and myogenesis. In this study, we show that creatine also has a negative regulatory effect on fat cell formation. Creatine inhibits the accumulation of cytoplasmic triglycerides in a dose-dependent manner irrespective of the adipogenic cell models used, including a C3H10T1/2 MSC line, 3T3-L1 preadipocytes, and primary human MSCs. Consistently, a dramatic reduction in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), glucose transporters, 1 and 4 (Glut1, Glut4), and adipocyte markers, aP2 and adipsin, was observed in the presence of creatine. Creatine appears to exert its inhibitory effects on adipogenesis during early differentiation, but not late differentiation, or proliferation stages through inhibition of the PI3K-Akt-PPARγ signaling pathway. In an in vivo model, administration of creatine into mice resulted in body mass increase without fat accumulation. In summary, our results indicate that creatine downregulates adipogenesis through inhibition of phosphatidylinositol 3-kinase (PI3K) activation and imply the potent therapeutic value of creatine in treating obesity and obesity-related metabolic disorders.


Localization of proteins HL29 and HL31 from Haloarcula marismortui within the 50 S ribosomal subunit by chemical crosslinking.
Isolated 50 S ribosomal subunits from the halophilic archaebacterium Haloarcula marismortui were treated in situ with the homobifunctional and cleavable crosslinking reagent dithiobis(succinimidyl propionate) (12 A). Several crosslinked complexes were obtained. Among these were the protein pairs HmaL4-HL29 and HmaL18-HL31; HL29 and HL31 are ribosomal proteins without any equivalent in eubacterial ribosomes. The crosslinked protein pairs were isolated on a preparative scale by combining conventional ion-exchange chromatography and reverse phase high-pressure liquid chromatography. The monomeric proteins involved in crosslink formation were unambiguously identified by two-dimensional gel electrophoresis and N-terminal or internal protein sequencing. Due to the homology between HmaL4 and HmaL18 and their Escherichia coli counterparts, and the roughly known location of these proteins within the 50 S subunit, our results demonstrate that HL29 is probably located in the centre of the large subunit in the vicinity of the peptidyltransferase domain, whereas HL31 must be situated within the central protuberance close to the region of the 5 S RNA.


Multiplex PCR detection of GSTM1, GSTT1, and GSTP1 gene variants: simultaneously detecting GSTM1 and GSTT1 gene copy number and the allelic status of the GSTP1 Ile105Val genetic variant.
The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 are involved in the detoxification of a broad range of toxic substances. Genetic polymorphisms in these genes have been studied intensively for their potential role in cancer susceptibility and drug response. In Caucasians, the enzyme activity of GSTM1 and GSTT1 is absent in approximately 50 and 15% of the population, respectively, due to deletions of both chromosomal copies of the genes. A trimodal phenotype pattern exists in which individuals with two, one, or no functional genes are fast, intermediate, or slow "conjugators," respectively. Most studies investigating the effect of the GSTM1 and GSTT1 deletions do not distinguish between fast and intermediate conjugators because the applied genotyping assays only detect if at least one copy of either gene is present. We present a multiplex PCR assay that detects if an individual has none, one, or two copies of the GSTM1 and GSTT1 genes and simultaneously detects the allelic status of the GSTP1 Ile105Val genetic variant. A total of 200 Danes, 100 Somalis, and 100 Greenlanders were genotyped. This multiplex PCR assay enables future large-scale studies to investigate the role of GSTs.


Effect of soil and water salinity on dry season boro rice production in the south-central coastal area of Bangladesh.
Salinity varies with location and time of the year. It can significantly impact crop production. The level of negative impacts depends on the salt concentration and time of its occurrence, which, however, has not been studied for many crops, especially for rice grown in the coastal area of Bangladesh. Our study explored the impact of spatio-temporal fluctuations in soil and water salinity on boro rice production in the south-central coast of Bangladesh. Here, we simulated the soil salinity from November 2020 to May 2021 for fourteen locations classes using the SWAP-WOFOST model. The model was calibrated and validated with measured secondary data. Next, the yield of two salt-tolerant boro rice varieties (BRRI dhan47 and BRRI dhan67) was simulated using the customized soil, weather, and crop data. We also simulated the yield by adopting agronomic management practices (i.e., changing planting time and using fresh irrigation water). Our results showed that salinity levels varied with different soil textural classes, soil depth, location, and time of the year, and that had a significant influence on boro rice production, giving spatial variability. Specifically, boro rice had a higher yield in coarse texture soil than in fine texture soil. Simulated yields in areas proximate to the sea ranged from 668 to 1239 kg ha-1, yields that are significantly lower than those simulated in moderate (2098-4843 kg ha-1) and low salinity zones (4213-4843 kg ha-1). Moreover, the simulation of yield with sowing/planting rice earlier by fifteen days provided a higher yield than the current planting practice since it could avoid salinity at later stages of growth. For a similar reason, growing rice inside the polder provided a higher yield than outside the polder. The insights gained from our study carry significant implications for contemporary crop-level adaptation strategies and policy-making in coastal districts.


Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.
Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.


COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.
To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices. This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula. The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images. Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.


Multiple myeloma with t(11;14): impact of novel agents on outcome.
Multiple myeloma (MM) patients with t(11;14) present unique biological features and their prognosis is not well established. We report a retrospective study of 591 MM patients, 17.3% of whom had t(11;14). It was designed to determine the prognostic impact of this abnormality and the effect of novel agents on the response and outcomes. Three groups were established based on their cytogenetics: (1) t(11;14); (2) high-risk chromosomal abnormalities; and (3) standard risk (SR). After 80.1 months (1.2-273.8 months) of follow-up, no differences were observed in overall survival (OS) between the t(11;14) and SR groups (75.8 vs. 87.2 months; P = 0.438). Treatment of MM t(11;14) with novel agents did not improve their overall response rate (ORR) or complete response (CR) compared with those who received conventional therapy (ORR: 87.2 vs. 79.5%, P = 0.336; CR: 23.4 vs. 12.8%, P = 0.215). This effect translated into a similar PFS (39.6 vs. 30.0 months; P = 0.450) and OS (107.6 vs. 75.7 months; P = 0.175). In summary, MM t(11;14) patients did not benefit from the introduction of novel agents as much as SR patients did, indicating that other therapies are needed to improve their outcomes.


Health related quality of life in survivors of pneumococcal meningitis.
To estimate the overall long-term health related quality of life implications of an episode of pneumococcal meningitis in childhood. Cases were identified through two regional UK surveillance studies and traced via their general practitioners (GPs) or local hospital paediatrician. Siblings were used as controls where available. Health related quality of life was assessed using the health utilities index (HUI). Mean utility scores were compared between cases and controls and univariate linear regression was used to identify factors that influenced the overall utility scores. HUI data were available for 71 cases and 66 controls. The mean overall utility score for cases 0.774 (95% CI 0.711- 0.837) was significantly lower than for controls 0.866 (95% CI 0.824-0.907) (p-value = 0.0185). Hearing was the most significantly affected health attribute (p-value < 0.006). In cases, males had lower quality of life scores than females (p-value = 0.018), however this was not seen in controls. An episode of pneumococcal meningitis results in a long-term decrement in overall health related quality of life and is significantly related to hearing loss.


Biophysical constraints on the origin of leaves inferred from the fossil record.
The molecular tool kit for producing flat-bladed photosynthetic structures evolved in marine and terrestrial plants during the middle Paleozoic, but it took a further 20 million years before leaves suddenly spread throughout land floras. This delay has long been difficult to explain, given the apparent advantage of leaves for photosynthetic primary production. Theory and experiments predict that exceptionally high atmospheric CO2 levels in the middle Paleozoic delayed the origin of leaves by restricting stomatal development. This would have limited evaporative cooling, leading to lethal overheating of leaves absorbing large quantities of solar energy. Here we test the central prediction of this argument with a morphometric analysis of 300 plant fossils from major European collections. We show a 25-fold enlargement of leaf blades in two phylogenetically independent clades as atmospheric CO2 levels fell during the late Paleozoic. Furthermore, preliminary data suggest that the first abrupt increase in leaf size was accompanied by an 8-fold rise in stomatal density. These evolutionary patterns support the relaxation of biophysical constraints on leaf area predicted by theory and point to a significant role for CO2 in plant evolution.


The comparison of human perception to the measured sweat transfer rate.
The subjective investigation, that is focused on the sensations of a person, is a good tool for the evaluation of an environment that group of people consider comfortable. In the experiment reported here, participants were dressed into 1-layer and 2-layer clothing systems. They performed physical activity and rated the subjective perception of comfort, as well as the thermal and moisture sensation. The aim of this investigation is to compare the subjective human perception during the physical activity wearing different clothing systems to the objective results of sweat absorption.


Genetics in Anti-Platelet Treatment.
Anti-platelet drugs are necessary in treating patients with coronary artery disease, ischemic stroke and peripheral arterial disease. However, despite the use of adequate anti-platelet therapy, some patients will experience a recurrent atherothrombotic vascular event. These patients are characterized as low- or non-responders to therapy. Individual responsiveness to anti-platelet therapy as the use of clopidogrel and/or aspirin varies widely among patients. Such an individual variability is mainly determined by environmental and genetic factors. In this review, we focused on the underlying genetic mechanisms that might influence response to anti-platelet drugs.


Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex.
The nuclear receptor steroidogenic factor 1 (Sf1, Nr5a1) is essential for adrenal development and regulates genes that specify differentiated adrenocortical function. The transcriptional coactivator beta-catenin reportedly synergizes with Sf1 to regulate a subset of these target genes; moreover, Wnt family members, signaling via beta-catenin, are also implicated in adrenocortical development. To investigate the role of beta-catenin in the adrenal cortex, we used two Sf1/Cre transgenes to inactivate conditional beta-catenin alleles. Inactivation of beta-catenin mediated by Sf1/Cre(high), a transgene expressed at high levels, caused adrenal aplasia in newborn mice. Analysis of fetal adrenal development with Sf1/Cre(high)-mediated beta-catenin inactivation showed decreased proliferation in presumptive adrenocortical precursor cells. By contrast, the Sf1/Cre(low) transgene effected a lesser degree of beta-catenin inactivation that did not affect all adrenocortical cells, permitting adrenal survival to reveal age-dependent degeneration of the cortex. These results define crucial roles for beta-catenin--presumably as part of the Wnt canonical signaling pathway--in both embryonic development of the adrenal cortex and in maintenance of the adult organ.


Expansions of chemosensory gene orthologs among selected tsetse fly species and their expressions in Glossina morsitans morsitans tsetse fly.
Tsetse fly exhibit species-specific olfactory uniqueness potentially underpinned by differences in their chemosensory protein repertoire. We assessed 1) expansions of chemosensory protein orthologs in Glossina morsitans morsitans, Glossina pallidipes, Glossina austeni, Glossina palpalis gambiensis, Glossina fuscipes fuscipes and Glossina brevipalpis tsetse fly species using Café analysis (to identify species-specific expansions) and 2) differential expressions of the orthologs and associated proteins in male G. m. morsitans antennae and head tissues using RNA-Seq approaches (to establish associated functional molecular pathways). We established accelerated and significant (P<0.05, λ = 2.60452e-7) expansions of gene families in G. m. morsitans Odorant receptor (Or)71a, Or46a, Ir75a,d, Ionotropic receptor (Ir) 31a, Ir84a, Ir64a and Odorant binding protein (Obp) 83a-b), G. pallidipes Or67a,c, Or49a, Or92a, Or85b-c,f and Obp73a, G. f. fuscipes Ir21a, Gustatory receptor (Gr) 21a and Gr63a), G. p. gambiensis clumsy, Ir25a and Ir8a, and G. brevipalpis Ir68a and missing orthologs in each tsetse fly species. Most abundantly expressed transcripts in male G. m. morsitans included specific Or (Orco, Or56a, 65a-c, Or47b, Or67b, GMOY012254, GMOY009475, and GMOY006265), Gr (Gr21a, Gr63a, GMOY013297 and GMOY013298), Ir (Ir8a, Ir25a and Ir41a) and Obp (Obp19a, lush, Obp28a, Obp83a-b Obp44a, GMOY012275 and GMOY013254) orthologs. Most enriched biological processes in the head were associated with vision, muscle activity and neuropeptide regulations, amino acid/nucleotide metabolism and circulatory system processes. Antennal enrichments (>90% of chemosensory transcripts) included cilium-associated mechanoreceptors, chemo-sensation, neuronal controlled growth/differentiation and regeneration/responses to stress. The expanded and tsetse fly species specific orthologs includes those associated with known tsetse fly responsive ligands (4-methyl phenol, 4-propyl phenol, acetic acid, butanol and carbon dioxide) and potential tsetse fly species-specific responsive ligands (2-oxopentanoic acid, phenylacetaldehyde, hydroxycinnamic acid, 2-heptanone, caffeine, geosmin, DEET and (cVA) pheromone). Some of the orthologs can potentially modulate several tsetse fly species-specific behavioral (male-male courtship, hunger/host seeking, cool avoidance, hygrosensory and feeding) phenotypes. The putative tsetse fly specific chemosensory gene orthologs and their respective ligands provide candidate gene targets and kairomones for respective downstream functional genomic and field evaluations that can effectively expand toolbox of species-specific tsetse fly attractants, repellents and other tsetse fly behavioral modulators.


Topical D-vitamins: multiparametric comparison of the irritant potential of calcipotriol, tacalcitol and calcitriol in a hairless guinea pig model.
The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D3 (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a hairless guinea pig model, Randomized, occlusive patch testing for 2 days was used. Each group of 8 animals was tested simultaneously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5 micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of the patches) and again at day 3. Evaluation was blinded and based on a multiple parameter assessment of skin irritancy, comparing clinical scoring, skin perfusion using high resolution laser Doppler image scanning, skin colour (a*, Minolta ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Skin biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential for calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical irritation score, cutaneous blood flow, skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was dominated by vasodilation and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TEWL remained unaffected. The hairless guinea pig appears a valid model to test irritancy of topical D-vitamins since the same profile of irritancy was previously established in humans for 2 of the compounds tested, calcitriol and calcipotriol.


The role of agricultural mechanization services in reducing pesticide input: promoting sustainable agriculture and public health.
An increasing amount of pesticide input is posing a serious threat to the environment and public health. However, the quantitative analysis of the impact of agricultural mechanization services (AMS) on reducing pesticide input is not yet clear. In this study, the impact of AMS on pesticide input was estimated by using the Chinese Family Database and the endogenous switching regression model. Subsequently, testing the robustness of the model using the substitution variable method. The impact of AMS on different types of pesticides and the influence of farmers' choices of AMS on pesticide input under different terrain conditions and farm sizes were analyzed as well. The results demonstrate that AMS has a significant and negative impact on pesticide input, reducing pesticide expenditures by 56.08% for farmers who adopt AMS. For farmers who do not adopt AMS, adopting such services is assumed to reduce pesticide input by 14.97%. AMS can also reduce the use of insecticides and herbicides by over 54%. Compared to mountainous and hilly areas, AMS in plain areas increase the effectiveness of pesticide input reduction by 30.40%. Furthermore, small-scale farmers who adopt AMS can increase pesticide input reduction by 90 yuan/mu compared with large-scale farmers. Therefore, promoting the development of socialized AMS, strengthening AMS in mountainous and hilly areas, and expanding the scale of operation for small-scale farmers can help improve the effectiveness of pesticide input reduction. The results of this study can inform the development of strategies to reduce chemical pesticide use in agricultural soil.


Spectrin and its interacting partners in nuclear structure and function.
Nonerythroid αII-spectrin is a structural protein whose roles in the nucleus have just begun to be explored. αII-spectrin is an important component of the nucleoskelelton and has both structural and non-structural functions. Its best known role is in repair of DNA ICLs both in genomic and telomeric DNA. αII-spectrin aids in the recruitment of repair proteins to sites of damage and a proposed mechanism of action is presented. It interacts with a number of different groups of proteins in the nucleus, indicating it has roles in additional cellular functions. αII-spectrin, in its structural role, associates/co-purifies with proteins important in maintaining the architecture and mechanical properties of the nucleus such as lamin, emerin, actin, protein 4.1, nuclear myosin, and SUN proteins. It is important for the resilience and elasticity of the nucleus. Thus, αII-spectrin's role in cellular functions is complex due to its structural as well as non-structural roles and understanding the consequences of a loss or deficiency of αII-spectrin in the nucleus is a significant challenge. In the bone marrow failure disorder, Fanconi anemia, there is a deficiency in αII-spectrin and, among other characteristics, there is defective DNA repair, chromosome instability, and congenital abnormalities. One may speculate that a deficiency in αII-spectrin plays an important role not only in the DNA repair defect but also in the congenital anomalies observed in Fanconi anemia , particularly since αII-spectrin has been shown to be important in embryonic development in a mouse model. The dual roles of αII-spectrin in the nucleus in both structural and non-structural functions make this an extremely important protein which needs to be investigated further. Such investigations should help unravel the complexities of αII-spectrin's interactions with other nuclear proteins and enhance our understanding of the pathogenesis of disorders, such as Fanconi anemia , in which there is a deficiency in αII-spectrin. Impact statement The nucleoskeleton is critical for maintaining the architecture and functional integrity of the nucleus. Nonerythroid α-spectrin (αIISp) is an essential nucleoskeletal protein; however, its interactions with other structural and non-structural nuclear proteins and its functional importance in the nucleus have only begun to be explored. This review addresses these issues. It describes αIISp's association with DNA repair proteins and at least one proposed mechanism of action for its role in DNA repair. Specific interactions of αIISp with other nucleoskeletal proteins as well as its important role in the biomechanical properties of the nucleus are reviewed. The consequences of loss of αIISp, in disorders such as Fanconi anemia, are examined, providing insights into the profound impact of this loss on critical processes known to be abnormal in FA, such as development, carcinogenesis, cancer progression and cellular functions dependent upon αIISp's interactions with other nucleoskeletal proteins.


THE EFFECTS OF THE MATING SYSTEM ON PROGENY PERFORMANCE IN HYLA CRUCIFER (ANURA: HYLIDAE).
We performed a controlled mating experiment to determine whether genetic variation in larval traits in Hyla crucifer was predictable on the basis of mating status or body size of male parent. Larval growth rate was predictably related to body size of the sire. Males from the upper half of the body-size distribution sired offspring with 6% higher growth rates than those of offspring sired by males from the lower half of the body-size distribution. Offspring sired by males that obtained mates in nature had 3% higher growth rates than their half-siblings sired by males that did not mate in nature. Genetic variation for larval-period duration and size at metamorphosis was detected; however, neither mating status nor body size of sire could be used to predict values of these traits in the progeny. Although all three larval traits can affect fitness, there was no evidence that the offspring of some sires would always outperform the offspring of others in all three traits. The predictable association between adult male size and larval growth rate means that the H. crucifer mating system would have a directional effect on larval growth rate if male body size influences the outcome of male-male competition or female choice.


Totally Laparoscopic Pancreaticoduodenectomy: Technical Notes.
Introduction: Laparoscopic pancreaticoduodendectomy is still rarely adopted due to its inherent complexity. We hereby present our experience of laparoscopic pancreaticoduodenectomy focused on technical notes. Technical description: A 5 trocars technique is used. Vision is provided by a 30 degree scope with 4K technology for the demolitive phase and 3D for the reconstructive phase. The right colic flexure is mobilized and an extensive Kocher maneuver is carried out exposing the inferior vena cava and left renal vein. The gastric antrum is resected with a mechanical stapler. The common hepatic artery is identified behind the superior pancreatic margin; lymphadenectomy of stations 7, 8, 9, 12 a and b is performed, until the gastroduodenal artery is cleared from the lymphatic tissue; a bull-dog clamp is placed to interrupt the arterial flow through the gastroduodenal artery, in order to exclude aberrant vascularization of the liver from the SMA. The common hepatic duct is transected just above the cystic duct. The pancreas is sectioned with monopolar energy, dividing the main pancreatic duct 2-3 mm distal to the parenchymal transection line with cold scissors, as to leave a stump that will facilitate the duct-to-mucosa anastomosis then the first jejunal loop is sectioned. A complete dissection of the mesopancreas is performed, moving from a caudal to cephalad fashion. Prior to perform the pancreatico-jejunal anastomosis, a fistula risk score based on pancreatic parenchymal texture, tumor type, Wirsung diameter, intraoperative blood loss is assessed. The pancreatico-jejunal anastomosis is carried out using prolene and pds sutures. The end-to-side hepaticojejunostomy is performed about 10 cm distant from the pancreaticojejunostomy. The side to- side gastrojejunostomy is performed using a 60 mm linear stapler. Conclusion: Laparoscopic pancreaticoduodenectomy is a demanding procedure affected by high morbidity rates. The standardization of the technique could lead the way to reduce such rates and favor its adoption.


Molecular basis of hypogonadotropic hypogonadism: restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site.
GnRH regulates the synthesis and release of pituitary gonadotropins. Mutations in the human GnRH receptor (hGnRHR) gene have been reported in families with hypogonadotropic hypogonadism. Our group recently described a novel homozygous E(90)K mutation of the hGnRHR in two siblings with the complete form of hypogonadotropic hypogonadism. In the present study, mutational analysis of the E(90)K substitution was performed to assess the functional role of this particular residue, which is located in the second transmembrane helix of the hGnRHR. Although E(90) is highly conserved in all other known mammalian GnRH receptors, this residue has not been previously implicated in GnRH binding and/or GnRHR activation. Transient expression of the mutant E(90)K receptor in COS-7 cells resulted in a virtual abolition of GnRH agonist binding and agonist-stimulated phosphoinositide turnover, initially suggesting that E(90) may be essential for GnRH binding. Furthermore, incubation with 1 microM of different GnRH agonists (D-Trp(6)-GnRH, GnRH, leuprolide, Catfish-1 GnRH, Catfish-2 GnRH, D-Lys(6)-Pro(9)-EA-GnRH, DesGly(10)-GnRH, D-Trp(6)-Pro(9)-EA-GnRH, Buserelin, and D-Lys(6)-GnRH) or antagonists (Antide and "Nal-Arg") did not result in elevated inositol phosphate production from cells expressing the E(90)K mutant. To examine the role of a site known to suppress hGnRHR function, mutants with deletion of K(191) (DeltaK(191)) from the hGnRHR and/or addition of catfish GnRHR intracellular carboxyl-terminal tail (cfCtail) to hGnRHR were prepared. Exposure to the GnRH analog Buserelin resulted in a significant increase in total inositol phosphate production in cells expressing the hGnRHR-cfCtail, hGnRHR(DeltaK(191)) and hGnRHR(DeltaK(191))-cfCtail. Activation of intracellular signaling in response to Buserelin was restored by deletion of K(191) from the E(90)K mutant receptor but minimally by addition of the catfish GnRHR carboxyl-terminal tail. There were no significant differences in total inositol phosphate production between the chimeric receptors bearing the DeltaK(191) or the E(90)K/DeltaK(191) modifications. All but the (E(90)K) and (E(90)K)-cfCtail altered receptors were membrane expressed as disclosed by Western blot analysis of epitope-tagged receptors. This study provides evidence that the E(90)K mutation impairs hGnRHR-effector coupling. The observation that sequence modifications that enhance surface expression of the receptor restore function, presents the possibility that loss of surface expression may underlie the severe phenotype exhibited by hypogonadotropic hypogonadism patients bearing this mutational defect.


Pneumocystis jirovecii and Cystic Fibrosis in Brittany, France.
Pneumocystis jirovecii is a transmissible fungus with a high pulmonary tropism. The prevalence of P. jirovecii in patients with cystic fibrosis (CF) has been estimated in Germany at 7.4%, in Spain at 21.5% and in Brazil at 38.2%. Data on the prevalence of P. jirovecii in CF patients in France remain scarce, particularly in Brittany, where the prevalence of CF is high (from 1/1600 to 1/4500). Our objectives were to determine the prevalence of colonization of the airways by P. jirovecii in Brittany in CF patients monitored at the "Centre de Ressources et de Compétences de la Mucoviscidose (CRCM)" of Rennes compared to that previously observed at the CRCM of Roscoff-Brest. Sputa from 86 patients (178 specimens) followed in Rennes were analyzed retrospectively. The detection of P. jirovecii was performed using real-time PCR targeting the gene encoding the mitochondrial large subunit of ribosomal RNA. Pneumocystis jirovecii DNA was detected in 3/86 patients (3.5%) monitored at Rennes, whereas it had previously been detected in 1/76 patients (1.3%) monitored at Roscoff-Brest, thus showing an overall prevalence of 2.5% in Brittany. These results obtained from two Breton centers taken together show that P. jirovecii prevalence in patients with CF in Brittany is lower than those observed in Germany, Spain, Brazil or in other regions of France. This study is a preliminary step in determining the risk factors for P. jirovecii acquisition, its epidemiological and clinical significance in CF patients through a prospective multicenter study.


New sialic acids from biological sources identified by a comprehensive and sensitive approach: liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) of SIA quinoxalinones.
Sialic acids are a family of 9-carbon carboxylated sugars, where different substitutions of the backbone define over 30 members. Biological roles of these substitutions have been missed until recently because of their low abundance and lability to conventional isolation/purification methods. This new approach characterizes sialic acids using electrospray ionization-mass spectrometry (ESI-MS) to monitor the HPLC separation of their DMB (1,2-diamino-4,5-methylenedioxy-benzene) derivatives (quinoxalinones). A combination of retention times and spectra characteristics allows definition of the type and position of the various substituents. This approach requires no previous purification, involving a simple derivatization reaction followed by direct injection on the microbore HPLC column. A complete spectrum, including molecular ions and CAD fragments of a sialic acid quinoxalinone, is obtained by injecting 10-20 pmol of the compound. Individual quinoxalinones can be purified by regular RP-HPLC and analyzed by direct-injection ESI-MS or LSIMS. Using this approach, we identified 28 different sialic acids, including the following new species: Neu5Gc9Lt (BSM), anhydro derivatives of Neu5Ac other than the 4,8-anhydro (horse serum hydrolyzates), KDN5(7)Ac and KDN5(7),9Ac2 (amphibian Pleurodeles waltl), four isomers of Neu5Gc8MexAc and three anhydro derivatives of Neu5Gc8Me (glycolipids of the starfish Pisaster brevispinus), and Neu5Ac8S (in addition to Neu5Gc8S, in the glycolipids of the sea urchin Lovenia cordiformis). Results show the usefulness of LC-ESI-MS to study sialic acid diversity, and identification of small amounts of unexpected sialic acids or new members of their family.


Effects of age and indomethacin on response and sensitivity of pulmonary artery to phenylephrine and to histamine in pigs.
The vasoconstrictor effects of phenylephrine and histamine were investigated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels with indomethacin. Potency (pD2 values) and maximal effects (EmaxX) recorded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 +/- 0.17 and 0.76 +/- 0.22 g/mg of dry tissue respectively (mean +/- SEM)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 +/- 0.30 and 1.06 +/- 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were significantly reduced in 26-week-old mature pigs (group 3, n = 6) as indicated by the decrease in pD2 (3.91 +/- 0.23; P < 0.01) and Emax (0.27 +/- 0.13 g/mg of dry tissue; P < 0.05) values observed in this group. Histamine (10(-3) M)-induced maximal responses (Emax) were significantly higher in group 2 (2.23 +/- 0.49 g/mg) than in group 1 (0.85 +/- 0.11 g/mg; P < 0.05) and in group 3 (0.48 +/- 0.10 g/mg; P < 0.01). In 5-week-old animals, indomethacin (3 x 10(-5) M) significantly (P < 0.05) shifted the concentration-response curve to phenylephrine to the right (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% (P < 0.05) in Emax. This cyclo-oxygenase inhibitor had no effect in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)


MyoD- and FoxO3-mediated hotspot interaction orchestrates super-enhancer activity during myogenic differentiation.
Super-enhancers (SEs) are cis-regulatory elements enriching lineage specific key transcription factors (TFs) to form hotspots. A paucity of identification and functional dissection promoted us to investigate SEs during myoblast differentiation. ChIP-seq analysis of histone marks leads to the uncovering of SEs which remodel progressively during the course of differentiation. Further analyses of TF ChIP-seq enable the definition of SE hotspots co-bound by the master TF, MyoD and other TFs, among which we perform in-depth dissection for MyoD/FoxO3 interaction in driving the hotspots formation and SE activation. Furthermore, using Myogenin as a model locus, we elucidate the hierarchical and complex interactions among hotspots during the differentiation, demonstrating SE function is propelled by the physical and functional cooperation among hotspots. Finally, we show MyoD and FoxO3 are key in orchestrating the Myogenin hotspots interaction and activation. Altogether our results identify muscle-specific SEs and provide mechanistic insights into the functionality of SE.


Auxiliary-Assisted Palladium-Catalyzed Direct C(sp3)-H Sulfonamidation To Afford 1,2-Amino Alcohol Derivatives.
An auxiliary-assisted Pd-catalyzed C(sp3)-H sulfonamidation approach using NFSI as both nitrogen source and oxidant to afford 1,2-amino alcohol derivatives is described in this paper. This method is novel and attractive because of its high yields, wide range of substrate scopes, and good tolerance for many functional groups. Oximido and sulfonyl group can be removed with this method.


Understanding Pre-Type 1 Diabetes: The Key to Prevention.
While the incidence of type 1 diabetes continues to rise by 3% each year, the ability to prevent this disease remains elusive. Hybrid closed loop devices, artificial pancreas systems, and continuous glucose monitoring technology have helped to ease the daily burden for many people living with type 1 diabetes. However, the artificial pancreas is not a cure; more research is needed to achieve our ultimate goal of preventing type 1 diabetes. The preceding decades have generated a wealth of information regarding the natural history of pre-type 1 diabetes. Islet autoimmunity in the form of multiple autoantibodies is known to be highly predictive of progression to disease. Staging systems have been devised to better characterize pre-type 1, direct mechanistic understanding of disease, and guide the design of prevention studies. However, there are no evidence-based recommendations for practitioners caring for autoantibody patients other than to encourage enrollment in research studies. Close monitoring of high-risk patients in natural history studies markedly reduces diabetic ketoacidosis rates at diagnosis and research participation is critical to finding a means of preventing type 1 diabetes. The discovery of an effective preventative strategy for type 1 diabetes will justify universal risk screening for all children.


CoVDB: a comprehensive database for comparative analysis of coronavirus genes and genomes.
The recent SARS epidemic has boosted interest in the discovery of novel human and animal coronaviruses. By July 2007, more than 3000 coronavirus sequence records, including 264 complete genomes, are available in GenBank. The number of coronavirus species with complete genomes available has increased from 9 in 2003 to 25 in 2007, of which six, including coronavirus HKU1, bat SARS coronavirus, group 1 bat coronavirus HKU2, groups 2c and 2d coronaviruses, were sequenced by our laboratory. To overcome the problems we encountered in the existing databases during comparative sequence analysis, we built a comprehensive database, CoVDB (http://covdb.microbiology.hku.hk), of annotated coronavirus genes and genomes. CoVDB provides a convenient platform for rapid and accurate batch sequence retrieval, the cornerstone and bottleneck for comparative gene or genome analysis. Sequences can be directly downloaded from the website in FASTA format. CoVDB also provides detailed annotation of all coronavirus sequences using a standardized nomenclature system, and overcomes the problems of duplicated and identical sequences in other databases. For complete genomes, a single representative sequence for each species is available for comparative analysis such as phylogenetic studies. With the annotated sequences in CoVDB, more specific blast search results can be generated for efficient downstream analysis.


Real-world features associated with cancer-related venous thromboembolic events.
The incidence of venous thromboembolism (VTE) is 1-2/1000 individuals. Patients with cancer, especially during chemotherapy, are at enhanced risk, but real-world data on factors associated with VTE events are still scarce. The aim of this retrospective study was to survey the incidence of VTE based on a large hospital database, and to identify comorbidities and features associated with VTE events. We focused on cancer-related VTE events and on factors indicating increased VTE risk during chemotherapy. The cohort included patients treated at Turku University Hospital during years 2005-2013. Health information was derived and analysed from multiple electronic databases. The diagnoses of VTE and all comorbidities, including type of cancer, were based on International Classification of Diseases 10th Revision coding. For further analysis, we focused on 16 common types of cancers treated with chemotherapy. Age, gender, surgery, radiotherapy, distant metastasis, available laboratory values and platinum-based chemotherapy were evaluated for VTE group, and associations were estimated by Cox regression analyses. The entire database contained information from 495 089 patients, of whom 5452 (1.1%) had a VTE diagnosis. Among individuals with VTE, 1437 (26.4%) had diagnosis of coronary heart disease and 1467 (26.9%) had cancer diagnosis. Among 7778 patients with cancer treated with chemotherapy, 282 (3.6%) had a VTE, platinum-based chemotherapy being a major risk factor (HR 1.77, 95% CI 1.40 to 2.24, p<0.001). In multivariate analysis, elevated blood neutrophil counts (>3.25×109 cells/L, HR 1.96, 95% CI 1.33 to 2.89, p<0.001) and plasma creatinine (>62.5 μmol/L; HR 1.60, 95% CI 1.21 to 2.13, p=0.001) values were independent indicators of increased VTE risk during chemotherapy. Longitudinal electronic health record analysis provides a powerful tool to gather meaningful real-world information to study clinical associations, like comorbidities, and to identify markers associated with VTE. The combination of various clinical and laboratory variables could be used for VTE risk evaluation and targeted prevention.


Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma.
s: Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan⁻Meier and Cox's regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox's regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.


Duct-to-duct Biliary Reconstruction in Living-donor Liver Transplantation for Primary Sclerosing Cholangitis: Report of a Case.
Although Roux-en Y hepaticojejunostomy was previously recommended for the biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to-duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage biliary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions.


Othering the Chronically Ill: A Discourse Analysis of New Zealand Health Policy Documents.
It is widely recognized that chronic illnesses pose significant challenges for health care systems around the world. In response, most governments have set health policies in order to manage (or better, reduce) demand and improve the health of their populations. A discourse analysis of four policy documents that shape these strategies in New Zealand reveals that the policies construct the chronically ill as "others," that is, as deviant or different from the "normal" population. The discourse further serves to blame the chronically ill both for being sick, and for placing a serious financial burden on society. We identify problems that arise from this discourse. They relate to (a) the fact that chronic illnesses are so prevalent, (b) the fallacy of categorizing all chronic illnesses as the same,


Dietary Patterns and Gut Microbiota: The Crucial Actors in Inflammatory Bowel Disease.
It is widely believed that diet and the gut microbiota are strongly related to the occurrence and progression of inflammatory bowel disease (IBD), but the effects of the interaction between dietary patterns and the gut microbiota on IBD have not been well elucidated. In this article, we aim to explore the complex relation between dietary patterns, gut microbiota, and IBD. We first comprehensively summarized the dietary patterns associated with IBD and found that dietary patterns can modulate the occurrence and progression of IBD through various signaling pathways, including mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), signal transducer and activator of transcription 3 (STAT3), and NF-κB. Besides, the gut microbiota performs a vital role in the progression of IBD, which can affect the expression of IBD susceptibility genes, such as dual oxidase 2 (DUOX2) and APOA-1 , the intestinal barrier (in particular, the expression of tight junction proteins), immune function (especially the homeostasis between effector and regulatory T cells) and the physiological metabolism, in particular, SCFAs, bile acids (BAs), and tryptophan metabolism. Finally, we reviewed the current knowledge on the interaction between dietary patterns and the gut microbiota in IBD and found that dietary patterns modulate the onset and progression of IBD, which is partly attributed to the regulation of the gut microbiota (especially SCFAs-producing bacteria and Escherichia coli). Faecalibacteria as "microbiomarkers" of IBD could be used as a target for dietary interventions to alleviate IBD. A comprehensive understanding of the interplay between dietary intake, gut microbiota, and IBD will facilitate the development of personalized dietary strategies based on the regulation of the gut microbiota in IBD and expedite the era of precision nutritional interventions for IBD.


The absorption of oral morroniside in rats: In vivo, in situ and in vitro studies.
Morroniside is one of the most important iridoid glycosides from Cornus officinalis Sieb. et Zucc. In the present study, the pharmacokinetics and bioavailability studies of morroniside were conducted on Sprague-Dawley (SD) rats. A rat in situ intestinal perfusion model was used to characterize the absorption of morroniside. Caco-2 cells were used to examine the transport mechanisms of morroniside. The pharmacokinetic study of morroniside exhibited linear dose-proportional pharmacokinetic characteristics and low bioavailability (4.3 %) in SD rats. Its average Peff value for transport across the small intestinal segments changed from (3.09 ± 2.03) × 10-6 to (4.53 ± 0.94) × 10-6 cm s-1. In Caco-2 cells, the Papp values ranged from (1.61 ± 0.53) × 10-9 to (1.19 ± 0.22) × 10-7 cm s-1 for the apical to basolateral side and the Pratio values at three concentrations were all lower than 1.2. Morroniside showed poor absorption and it might not be a specific substrate of P-glycoprotein (P-gp).


Breast cancer screening among adult women--Behavioral Risk Factor Surveillance System, United States, 2010.
Breast cancer continues to have a substantial impact on the health of women in the United States. It is the most commonly diagnosed cancer (excluding skin cancers) among women, with more than 210,000 new cases diagnosed in 2008 (the most recent year for which data are available). Incidence rates are highest among white women at 122.6 per 100,000, followed by blacks at 118 per 100,000, Hispanics at 92.8, Asian/Pacific Islanders at 87.9, and American Indian/Alaskan Natives at 65.6. Although deaths from breast cancer have been declining in recent years, it has remained the second leading cause of cancer deaths for women since the late 1980s with >40,000 deaths reported in 2008. Although white women are more likely to receive a diagnosis of breast cancer, black women are more likely to die from breast cancer than women of any other racial/ethnic group. In addition, studies have demonstrated that nonwhite minority women tend to have a more advanced stage of disease at the time of diagnosis. Breast cancer also occurs more often among women aged ≥50 years, those with first-degree family members with breast cancer, and those who have certain genetic mutations. Understanding who is at risk for breast cancer helps inform guidelines for who should get screened for breast cancer.


Rotational atherectomy in a dire situation: a case report.
Traditionally rotablation is considered as contraindicated in presence of visible thrombus or dissection. However, clinical situations may force us to undertake rotablation in presence of thrombus or dissection. We report a case of coronary rotablation done successfully in setting of acute thrombotic occlusion over an underlying non-healed dissection. A non-dilatable lesion in proximal left anterior descending (LAD) artery after rotablation with a 1.5 mm burr resulting in non-flow limiting Type A dissection with TIMI3 flow was left on conservative management to allow it to heal. But the patient developed ST-elevation myocardial infarction on the 9th post-intervention day due to thrombotic occlusion of the LAD at the site of dissection. At this time, we were compelled to do rotablation as a lifesaving procedure in presence of both thrombus and underlying dissection with a successful outcome. Rotablation in presence of dissection can lead to entrapment of the flap in the rotating burr leading to progression of dissection distally or sometimes there can be subintimal tracking of burr leading to perforation. In thrombotic lesions, rotablation can cause further increase in platelet activation and aggregation by the spinning burr or distal embolization of the thrombotic material promoting slow or no flow. In this unusual case with limited options for achieving successful revascularization, some out of the box steps were taken with all recommended precautions and successful outcome achieved.


Lycopene incorporation into egg yolk and effects on laying hen immune function.
Carotenoids are partially responsible for the colors of plants and when consumed by humans and animals are deposited into tissues (e.g., skin and egg yolk in laying hens) and may have health benefits. Because carotenoids are more available when consumed from egg yolk sources than vegetables, this research examined the ability of the laying hen to deposit dietary lycopene, a carotenoid that imparts red color in tomatoes, into the egg yolk and to investigate effects on immune function. All birds were housed in commercial cages, had ad libitum access to water, and were fed 100 g/bird per day. Experiment 1 consisted of 4 dietary concentrations of lycopene (0, 65, 257, and 650 mg of lycopene/kg of diet). High-performance liquid chromatography analysis confirmed that dietary lycopene was incorporated into egg yolks. Experiment 2 was a completely randomized design, with 3 concentrations of lycopene (0, 420, and 840 mg of lycopene/kg of diet) and 6 concentrations of alpha-tocopherol (0, 84, 164, 200, 284, and 364 mg of alpha-tocopherol/kg of diet). Egg yolk lycopene (P < 0.05) and vitamin E (P < 0.05) were increased with increasing dietary concentrations, whereas lutein and zeaxanthin concentrations remained constant. Immune responses (inflammatory, cutaneous basophil hypersensitivity, 1 degrees and 2 degrees antibody response) were induced but were not affected by dietary lycopene or vitamin E. These data indicate that lycopene can be incorporated into egg yolks, and at these dietary concentrations, alpha-tocopherol and lycopene may not affect the immune system of the laying hen.


Maternity telehealth: ringing the changes.
This article describes NHS Scotland's Maternity telehealth options project and the implementation of the recommendations made. This 17-month project resulted in the development of national documentation for recording telehealth calls; the development of a self-directed eLearning tool on maternity telehealth call structure which was made available to all health boards in Scotland; a comprehensive programme of training on telehealth for student midwives; a programme of 'Train-the-trainer' events for qualified midwives to enable the cascade of learning throughout the service. The project also involved collaboration with Health Scotland, signposting for women to contact the appropriate caregiver at the appropriate time.


Effects of Rhizophagus irregularis on Photosynthesis and Antioxidative Enzymatic System in Robinia pseudoacacia L. under Drought Stress.
Arbuscular mycorrhizal (AM) fungi colonize roots improving plant water status and tolerance to drought. However, it is not clear whether the presence of AM would affect the photosynthesis and antioxidant gene-enzymes response, which help to alleviate drought stress of the host plant. Here, pot experiments were performed to investigate the effects of Rhizophagus irregularis, an AM fungus, on the tissue water content, photosynthesis, reactive oxygen species (ROS) production, antioxidant enzyme activity and gene expression in black locust (Robinia pseudoacacia L.) seedlings which were subjected to well-watered or moderate drought stress. Mycorrhizal symbiosis increased relative water content (RWC) of plant roots and leaves, promoted the accumulation of biomass and chlorophyll (Chl) content, and improved photochemistry efficiency, regardless of watering regimes. Mycorrhizal plants had higher SOD, POD, CAT, APX, and GR activities, and the transcript levels of Cu/Zn-SOD. APX and GR, but lower O2-, H2O2 and MDA concentrations in leaves and roots of black locust under drought and well-watered conditions. Results from the present study indicate that AM fungus (R. irregularis) symbiosis can enhance photosynthesis and ROS scavenging capabilities and increase RWC of leaves and roots to alleviate drought stress in black locust. Further research is needed to elucidate the relations among AM fungi and the metabolic pathways of antioxidant enzymes, and the function of antioxidant genes regulated by mycorrhizal symbiosis with the purpose of revealing the mechanisms of mycorrhizal-induced plant tolerance to drought stress.


[Saccadic eye movements in the diagnosis of disseminated encephalomyelitis].
Saccadic eye movements were examined in 40 healthy subjects and 30 patients suffering from multiple sclerosis and the effective predictors for diagnosis were determined by discriminant analyses. Saccades indicated a higher diagnostic relevance compared with brainstem auditory evoked potentials and visual evoked potentials.


pH- and temperature-responsive radially porous silica nanoparticles with high-capacity drug loading for controlled drug delivery.
The design of smart and functional nanocarriers for drug delivery systems that use a variety of organic and inorganic materials has led to the development of nanomedicines with improved therapeutic efficiency and reduced side effects. In this study, a pH- and temperature-responsive, controlled-release system with a high capacity for drug loading was developed based on radially porous silica nanoparticles composed of functionalized ligands and polymer encapsulation. This drug delivery system uses radially oriented mesoporous silica nanoparticles as the drug carrier, and control of the surface chemistry of those nanocarriers allows high-capacity loading efficiency of target drugs and stimuli-responsive release kinetics governed by pH and temperature. The delivery of ibuprofen was chosen to test this system, and a maximum loading efficiency of ca. 270 wt% was established, which was 3 times greater than that in previous studies for silica nanoparticles such as SBA-15, MCA-41, and MCM-48. In addition, the pH- and temperature-responsive release of ibuprofen was achieved when the surface of the nanocarriers was treated by pH-responsive amine functionalization and a temperature-responsive surface coating of agarose gel. Finally, cytotoxicity testing using the fibroblast cells showed that the developed silica nanocarriers have no toxicity on the cells, which should allow these nanocarriers to be applied as a nanomedicine in drug delivery systems.


Contemporary considerations in treatment planning.
Correct planning of treatment is central to clinical dental practice, given that the skillful completion of an inappropriate procedure may be little or no benefit to the patient. Effective treatment planning is dependent on a number of factors, including good communication with the patient, recognition of the problems that require and influence treatment, and an awareness of the prognosis of the potential alternatives.


Human embryonic stem cell-derived NK cells acquire functional receptors and cytolytic activity.
Human embryonic stem cells (hESCs) provide a unique resource to analyze early stages of human hematopoiesis. However, little is known about the ability to use hESCs to evaluate lymphocyte development. In the present study, we use a two-step culture method to demonstrate efficient generation of functional NK cells from hESCs. The CD56(+)CD45(+) hESC-derived lymphocytes express inhibitory and activating receptors typical of mature NK cells, including killer cell Ig-like receptors, natural cytotoxicity receptors, and CD16. Limiting dilution analysis suggests that these cells can be produced from hESC-derived hemopoietic progenitors at a clonal frequency similar to CD34(+) cells isolated from cord blood. The hESC-derived NK cells acquire the ability to lyse human tumor cells by both direct cell-mediated cytotoxicity and Ab-dependent cellular cytotoxicity. Additionally, activated hESC-derived NK cells up-regulate cytokine production. hESC-derived lymphoid progenitors provide a novel means to characterize specific cellular and molecular mechanisms that lead to development of specific human lymphocyte populations. These cells may also provide a source for innovative cellular immune therapies.


The syndrome dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly and lissencephaly (DREAM-PL): Report of two additional patients.
We have recently described a newly recognized syndromic form of congenital microcephaly as part of a large cohort of apparently novel dysmorphic syndromes. The reported Saudi Arabian patients have severe primary microcephaly, ambiguous male genitalia, dysmorphic facies, polydactyly, and renal agenesis. The same homozygous CTU2 mutation was identified in all patients. Although the nucleotide change c.873G>A does not change the codon, it completely abolishes a consensus donor site resulting in frameshift and premature truncation ((NM_001012762.1): p.Thr247Alafs*21). In this report, we describe two cousins from United Arab Emirates whose clinical presentation was consistent with this recently described syndrome and both were found to have the same mutation on the same haplotypic background. We propose the acronym DREAM-PL to highlight the main clinical features of this syndrome, which we believe is underdiagnosed by exome sequencing based on the high carrier frequency, most likely due to the apparently synonymous nature of the mutation. © 2016 Wiley Periodicals, Inc.


Mindfulness-Based Stress Reduction and Group Support Decrease Stress in Adolescents with Cardiac Diagnoses: A Randomized Two-Group Study.
Adolescents with cardiac diagnoses face unique challenges that can cause psychosocial distress. This study compares a Mindfulness-Based Stress Reduction (MBSR) program to a video online support group for adolescents with cardiac diagnoses. MBSR is a structured psycho-educational program which includes yoga, meditation, cognitive restructuring, and group support. A published feasibility study by our group showed significant reduction in anxiety following this intervention. Participants were randomized to MBSR or video online support group, and completed measures of anxiety, depression, illness-related stress, and coping pre- and post-6-session interventions. Qualitative data were obtained from post-intervention interviews. A total of 46 teens participated (mean 14.8 years; 63% female). Participants had congenital heart disease and/or cardiac device (52%), or postural orthostatic tachycardia syndrome (48%). Illness-related stress significantly decreased in both groups. Greater use of coping skills predicted lower levels of depression in both groups post-study completion. Higher baseline anxiety/depression scores predicted improved anxiety/depression scores in both groups. Each group reported the benefits of social support. The MBSR group further expressed benefits of learning specific techniques, strategies, and skills that they applied in real-life situations to relieve distress. Both the MBSR intervention and video support group were effective in reducing distress in this sample. Qualitative data elucidated the added benefits of using MBSR techniques to manage stress and symptoms. The video group format is useful for teens that cannot meet in person but can benefit from group support. Psychosocial interventions with stress management techniques and/or group support can reduce distress in adolescents with cardiac diagnoses.


Molecular physiology and pathophysiology of stromal interaction molecules.
Ca2+ release from the endoplasmic reticulum is an important component of Ca2+ signal transduction that controls numerous physiological processes in eukaryotic cells. Release of Ca2+ from the endoplasmic reticulum is coupled to the activation of store-operated Ca2+ entry into cells. Store-operated Ca2+ entry provides Ca2+ for replenishing depleted endoplasmic reticulum Ca2+ stores and a Ca2+ signal that regulates Ca2+-dependent intracellular biochemical events. Central to connecting discharge of endoplasmic reticulum Ca2+ stores following G protein-coupled receptor activation with the induction of store-operated Ca2+ entry are stromal interaction molecules (STIM1 and STIM2). These highly homologous endoplasmic reticulum transmembrane proteins function as sensors of the Ca2+ concentration within the endoplasmic reticulum lumen and activators of Ca2+ release-activated Ca2+ channels. Emerging evidence indicates that in addition to their role in Ca2+ release-activated Ca2+ channel gating and store-operated Ca2+ entry, STIM1 and STIM2 regulate other cellular signaling events. Recent studies have shown that disruption of STIM expression and function is associated with the pathogenesis of several diseases including autoimmune disorders, cancer, cardiovascular disease, and myopathies. Here, we provide an overview of the latest developments in the molecular physiology and pathophysiology of STIM1 and STIM2. Impact statement Intracellular Ca2+ signaling is a fundamentally important regulator of cell physiology. Recent studies have revealed that Ca2+-binding stromal interaction molecules (Stim1 and Stim2) expressed in the membrane of the endoplasmic reticulum (ER) are essential components of eukaryote Ca2+ signal transduction that control the activity of ion channels and other signaling effectors present in the plasma membrane. This review summarizes the most recent information on the molecular physiology and pathophysiology of stromal interaction molecules. We anticipate that the work presented in our review will provide new insights into molecular interactions that participate in interorganelle signaling crosstalk, cell function, and the pathogenesis of human diseases.


A simple and time saving cold mini caloric test.
A simple and time-saving office procedure is presented. The test consists of placing a small piece of cotton-wool soaked in ice water against the tympanic membrane. We term this test the Cold mini caloric test. Our method has been compared quantitatively with the Bithermal caloric test in 20 normal controls, 50 unspecific dizzy patients with no vestibular or obvious neurological disorder, 22 Menière ears, 12 acoustic neuromas and 20 cases of vestibular neuronitis. The comparison between the two methods has shown the Cold mini caloric test to present consistently similar, though somewhat shorter, nystagmic reactions. There was no difference in the clinical information obtained by the two methods.


Very-short-answer questions: reliability, discrimination and acceptability.
Single-best-answer questions (SBAQs) have been widely used to test knowledge because they are easy to mark and demonstrate high reliability. However, SBAQs have been criticised for being subject to cueing. We used a novel assessment tool that facilitates efficient marking of open-ended very-short-answer questions (VSAQs). We compared VSAQs with SBAQs with regard to reliability, discrimination and student performance, and evaluated the acceptability of VSAQs. Medical students were randomised to sit a 60-question assessment administered in either VSAQ and then SBAQ format (Group 1, n = 155) or the reverse (Group 2, n = 144). The VSAQs were delivered on a tablet; responses were computer-marked and subsequently reviewed by two examiners. The standard error of measurement (SEM) across the ability spectrum was estimated using item response theory. The review of machine-marked questions took an average of 1 minute, 36 seconds per question for all students. The VSAQs had high reliability (alpha: 0.91), a significantly lower SEM than the SBAQs (p < 0.001) and higher mean item-total point biserial correlations (p < 0.001). The VSAQ scores were significantly lower than the SBAQ scores (p < 0.001). The difference in scores between VSAQs and SBAQs was attenuated in Group 2. Although 80.4% of students found the VSAQs more difficult, 69.2% found them more authentic. The VSAQ format demonstrated high reliability and discrimination and items were perceived as more authentic. The SBAQ format was associated with significant cueing. The present results suggest the VSAQ format has a higher degree of validity.


Association of Plasma Semaphorin 3A With Phenotypes of Diabetic Retinopathy and Nephropathy.
To investigate whether diabetic retinopathy phenotypes and albuminuria are associated with the overexpression of plasma semaphorin 3A (Sema3A). The study group with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR), the diabetes without diabetic retinopathy group, and the control group without diabetes consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve diabetic macular edema (DME) and senile cataract surgery, respectively. In all subjects, the plasma Sema3A levels before intravitreal bevacizumab injections or cataract surgery were measured by enzyme-linked immunosorbent assay. In the patients with DME, the capillary nonperfusion area (measured by fluorescein angiography), total macular volume (measured by spectral-domain optical coherence tomography), and the urine albumin-to-creatinine ratio were determined. Severe NPDR (57 eyes) and PDR groups (51 eyes) both had significantly higher Sema3A levels than the control (58 eyes) and diabetes without diabetic retinopathy groups (54 eyes) (P < 0.001). Moreover, the PDR group had higher Sema3A levels than the severe NPDR group (P < 0.001). Plasma Sema3A levels correlated positively with the retinal nonperfusion area size (r = 0.844, P = 0.004), total macular volume (r = 0.765, P = 0.005), and the urine albumin-to-creatinine ratio (r = 0.752, P < 0.001). When DME patients were divided into normo-, micro-, and macroalbuminuria groups, the macroalbuminuria group had significantly higher plasma Sema3A levels than the microalbuminuria group or the normoalbuminuria group (P = 0.002 and P < 0.001, respectively). The plasma Sema3A levels correlated significantly with the phenotypes of diabetic retinopathy and albuminuria. This suggests that Sema3A may be a potential biomarker for diabetic retinopathy and nephropathy.


Inactivation of ANAMMOX communities under concurrent operation of anaerobic ammonium oxidation (ANAMMOX) and denitrification.
A concurrent operation of anaerobic ammonium oxidation (ANAMMOX) and denitrification was investigated in a well known UASB reactor seeding with both ANAMMOX and anaerobic granular sludges. ANAMMOX activity was confirmed by hydroxylamine test and the hybridization of biomass using the gene probes of Amx 820 and EUB 338 mixed. Denitrification was observed through the reductions of both COD and nitrate-nitrite concentrations under anaerobic/anoxic conditions. By providing a stoichiometric ratio of nitrite to ammonium nitrogen with addition nitrate nitrogen, a gradual reduction of ANAMMOX activity was found with an increase of COD concentration in a range of 100-400 mg l(-1). This is equivalent to the COD to N ratio of 0.9-2.0. The COD concentration was found to be a control variable for process selection between ANAMMOX reaction and denitrification. A reduction of COD and nitrite-nitrate concentrations in all reactors confirmed the undergone concurrent denitrification which thrives when sufficient organic matter is available. COD concentration over 300 mg l(-1) was found to inactivate or eradicate ANAMMOX communities.


Can the greater trochanter/femoral neck signal intensity ratio on coronal T1 weighted images of the hip differentiate normal-abnormal bone mineral density?
A simple index calculated by dividing the greater trochanter signal intensity by that of the femoral neck on coronal T1-weighted magnetic resonance images of the hip may be useful as an opportunistic screening tool to differentiate normal vs. abnormal bone mineral density. The aim of this study is to evaluate the efficacy of the greater trochanter/femoral neck (T/N) signal intensity (SI) ratio on T1 weighted images of the hip in differentiating patients with normal vs. abnormal bone mineral density (BMD) using hip dual-energy x-ray absorptiometry (DXA) as the reference. Three BMD groups according to the T score of the femoral neck (i.e., normal, osteopenia, and osteoporosis) were created, and 20 patients were included for each group. The T/N ratio was calculated by dividing the greater trochanter SI by that of the femoral neck on coronal T1-weighted images. Receiver-operator characteristic (ROC) analysis was performed to determine diagnostic efficacy. The mean age was 59.2±9.4; there were 57 women and 3 men. The mean BMD was 0.67±0.14 g/cm2. The mean T/N ratio for the normal, osteopenia, and osteoporosis groups were 1.37 (±0.12), 1.19 (±0.10), and 1.18 (±0.13), respectively. When the osteopenia and osteoporosis groups were combined into one group, i.e., low BMD group, the mean T/N ratio was 1.18 (±0.11), and it was significantly different from that of the normal BMD group (p<0.00001). In ROC analysis, the area under curve (AUC) for the T/N ratio in the diagnosis of low BMD was 0.870. An optimal cutoff value of 1.28 was found for the differentiation of normal vs. abnormal BMD with 80% sensitivity and 80% specificity. The T/N ratio seems to be effective at differentiating patients with normal vs. abnormal BMD and may help triage patients for additional evaluation.


New phenylenediamine antiozonants for commodities based on natural and synthetic rubber.
For protection of elastomeric materials against ageing, antioxidants such as UV-stabilizers and antiozonants are used. Although historically N-phenyl-N'-(1,3-dimethylbutyl)-p-phenylenediamine (6PPD) was the only approved antiozonant in Germany, a range of other phenylene diamine antiozonants (excluding 6PPD) are permitted for use in rubber articles intended for repeat food-contact use in the US (FDA regulations chapter 21 Part 177.2600). The biggest disadvantage of 6PPD is its partial decomposition during the vulcanization leading to the formation of toxic primary aromatic amines (PAA), such as aniline and secondary aromatic amines (SAA). A number of new PPDs have been developed and patented, that due to their chemical structures, are far less soluble in aqueous solutions but a lot more soluble within the rubber matrix. They therefore show significantly less migration of PAA and SAA. These new antiozonants were investigated and compared to 6PPD using commercial rubber materials with a certain content of antiozonant with regard to their migration of PAA and SAA into three different food simulants. The lowest concentration of PAA and SAA in all food simulants was measured in the RU 997 stabilized elastomer. Due to this fact RU 997 was permitted as a new antiozonant for commodities based on rubber according to the Recommendation XXI 'Articles based on natural and synthetic rubber' of the Federal Institute for Risk Assessment (BfR). RU 997 therefore represents an alternative for 6PPD with less migration of aromatic amines.


Endobronchial Valve Used as Salvage Therapy in a Mechanically Ventilated Patient with Intractable Life-Threatening Haemoptysis.
Treatment options for intractable life-threatening haemoptysis in mechanically ventilated patients with structural lung disease who do not respond to bronchial artery embolisation (BAE) and who are deemed unfit for surgery are limited. A 26-year-old HIV-positive male with a poorly preserved CD4 count and active pulmonary tuberculosis was intubated and mechanically ventilated for persistent life-threatening haemoptysis. Two attempts at BAE failed, and life-threatening haemoptysis recurred daily for 14 days despite antituberculous therapy. He was deemed unfit for surgery during that period. We proceeded to identify the source of bleeding endoscopically and implanted an endobronchial valve in the left upper lobe bronchus. Following the collapse of the affected lobe, haemoptysis ceased and the patient was promptly liberated from mechanical ventilation. He remained haemoptysis free for the duration of his hospitalisation. Endobronchial valves, therefore, may be a viable option in patients mechanically ventilated with persistent life-threatening haemoptysis in whom all other conventional measures fail and who are considered unfit for surgery.


Resting-state neural activity across face-selective cortical regions is behaviorally relevant.
Interest has increased recently in correlations across brain regions in the resting-state fMRI blood oxygen level-dependent (BOLD) response, but little is known about the functional significance of these correlations. Here we directly test the behavioral relevance of the resting-state correlation between two face-selective regions in human brain, the occipital face area (OFA) and the fusiform face area (FFA). We found that the magnitude of the resting-state correlation, henceforth called functional connectivity (FC), between OFA and FFA correlates with an individual's performance on a number of face-processing tasks, not non-face tasks. Further, we found that the behavioral significance of the OFA/FFA FC is independent of the functional activation and the anatomical size of either the OFA or FFA, suggesting that face processing depends not only on the functionality of individual face-selective regions, but also on the synchronized spontaneous neural activity between them. Together, these findings provide strong evidence that the functional correlations in the BOLD response observed at rest reveal functionally significant properties of cortical processing.


Isolation and reactivation of highly-coupled newt lung cilia.
The paired lungs of the newt, Taricha granulosa, are simple, unbranched sacs, 3.5-5.0 cm in length. The inner epithelium overlying the pulmonary vein is differentiated into a mucociliary tract that extends the entire length of the lung. Populations of single, demembranated ciliary axonemes, 12-13 micron in length, can be isolated by extracting whole lungs or primary cultures of the ciliated epithelium with Triton X-100. The motile capabilities of the isolated axonemes are the highest yet obtained for any ciliary model. When exposed to a suitable reactivating medium containing Mg2+ and ATP, nearly 100% of the axonemes become motile. Uniform reactivation of high quality requires short extraction times, minimization of mechanical damage, and strict adherence to optimal conditions throughout the extraction, storage, and reactivation procedures. Significant deviations from either pH 7.0 or 0.12 M salt can lead to a rapid, irreversible decrease in the beat frequency of reactivated axonemes. Both DTT and EDTA serve to stabilize their motility. The isolated axonemes beat at 29.5 Hz in the presence of 1.75 mM ATP at 21 degrees C, matching the beat frequencies measured for cultured cells at the same temperature. With 5 mM ATP, beat frequencies over 40 Hz are measured. Our results show that neither the plasma membrane, accessory structures, nor hydrodynamic coupling of cilia are required for this activity and imply that the lack of these factors is not responsible for the low motile capabilities of ciliary models isolated previously.


Two newly synthesized 5-methyltetrahydrofolate-like compounds inhibit methionine synthase activity accompanied by cell cycle arrest in G1/S phase and apoptosis in vitro.
Cobalamin-dependent methionine synthase, with a cofactor of vitamin B12, catalyzes the reaction of 5-methyltetrahydrofolate and homocysteine to form methionine and tetrahydrofolate, which takes a core position in folate cycle, one-carbon-unit transfer, and sulfur amino acid pathways. The 'methyl folate trap' hypothesis suggests that methionine synthase is a potential target for anticancer drug development. ZL031 and ZL033 are 5-methyltetrahydrofolate-like compounds that have been newly synthesized as potential inhibitors of the enzyme. To identify the effect of these two compounds on methionine synthase activity, a spectrophotometric assay was used and the results proved that ZL031 and ZL033 inactivated methionine synthase in HL-60 cells with an IC50 dose of 10.0 and 1.4 mumol/l, respectively. Moreover, obvious inhibitory effect on proliferation of HL-60 cells was observed, leading to our further investigation of the underlying anticancer mechanism. Under the circumstances of methionine synthase deficiency and subsequent folate depletion, cell cycle was arrested in G1/S phase and apoptosis was also observed. Analysis of cell cycle regulatory proteins demonstrated that cyclin E and cyclin-dependent kinase 2 were both increased. Furthermore, reduction of caspase-3, poly (ADP-ribose) polymerase, caspase-8, and caspase-9 protein levels were observed. In all the biological experiments we have performed, ZL033 has shown a better efficacy compared with ZL031. These results suggest that ZL031 and ZL033, as novel methionine synthase inhibitors, caused G1/S phase delay and apoptosis and eventually inhibit the proliferation of HL-60 cells in vitro. ZL033, with a carboxylic acid substituent, might have a better potential for drug development than ZL031 with an ester substituent.


Pseudomembranous tracheobronchitis caused by methicillin-resistant Staphylococcus aureus.
We report a case of severe tracheobronchitis caused by methicillin-resistant Staphylococcus aureus in a man exhibiting symptoms of upper airway obstruction after infection with influenza. Bronchoscopy revealed diffuse pseudomembrane formation throughout the trachea and bilateral bronchi, which were nearly obstructed. In this case, it was helpful to perform bronchoscopy, protected brushing and tracheotomy immediately in order to avoid choking.


The modulating effect of culture on the expression of dental anxiety in children: a literature review.
The experience of anxiety is a universal human phenomenon. Studies have shown a world-wide variation in the prevalence of dental anxiety with estimates ranging between 3% and 43%. The aetiology of dental anxiety is multifactorial, with factors acting in synergy to affect its expression. For children, age and gender play fundamental roles in its expression. However, these two factors are modulated by other variables such as culture which may influence the context in which anxiety is experienced, the interpretation of its meaning and responses to it. The modulating effect of culture in synergy with other variables may be one of the reasons why reports on dental anxiety have varied from region to region. This paper attempts to identify the interrelating roles of culture, age and gender, and how these relationships may affect variability in the expression and measurement of dental anxiety in children.


Mechanical flower thinning improves the fruit quality of apples.
Apple 'Golden Delicious Reinders' and 'Gala Mondial' trees were mechanically blossom-thinned with 30-77 x g (300-480 rpm rotation) and 5 or 7.5 km h(-1) vehicle speed to improve fruit quality, minimise leaf damage, reduce hand and chemical thinning and to prevent or overcome alternate bearing; adjacent untreated or manually thinned apple trees served as controls. Mechanical thinning (43 x g, 360 rpm, 5-7.5 km h(-1)) had a positive effect on fruit size (15% larger), firmness (8.4 in Gala vs. 7.6 kg cm(-2) in the unthinned control), sweetness (124 vs. 117 g kg(-1) sugar in the control), contained the largest malic acid content (4 g kg(-1) vs. 3.4 g kg(-1) in the control) and 17% more anthocyanin (normalised anthocyanin index = 0.8 in Gala vs. 0.7 in the control); fruit of Golden and Gala showed additionally advanced starch breakdown and ripened earlier. Since increases in rotor speed, viz. centrifugal force, versus increases in the vehicle speed resulted in opposing effects, an integrated coefficient of thinning (ICT) was devised with optimum values of 10-40 (at 43 x g, 5-7.5 km h(-1)), where an ICT > 50 led to tree damage and ICT < 8 led to sub-optimum thinning efficacy.


Pragmatic clinical trials.
Both pragmatic and explanatory randomised controlled trials have a useful role to play in the evaluation of health care interventions. In this descriptive article, the key steps in conducting a pragmatic trial are described. The strengths and limitations of pragmatic trials are also discussed. The main strength of pragmatic trials is that they can evaluate a therapy as it is used in normal practice. Comparisons are made between pragmatic and explanatory trials, on the understanding that trials may have aspects to them that make the trial more of a hybrid. A case is made for the appropriate use and relevance of pragmatic trials in the evaluation of alternative and complementary medicine.


In Vitro Influence of Prophylaxis Cleaning on Enamel Remineralization with Casein Phosphopeptide-Amorphous Calcium Phosphate.
This randomized controlled in vitro 4-arm trial study aimed to study the remineralization potential of Recaldent™ and assess the effects of prophylaxis cleaning and MI Varnish® on enhancing this remineralization potential. Sixty human teeth were randomly assigned into equal samples (A/B). Sample A was prophylactically cleaned, randomly divided into equal samples (1/2). Sample A1 received treatment with MI Varnish® and Recaldent™ for 30 days. Sample A2 was treated similarly but without MI Varnish®. Sample B did not receive prophylaxis cleaning and was divided into equal samples (1/2). Sample B1 was treated as A1 and sample B2 as A2. The teeth were examined for mineral composition at baseline, after the interventions (T1), and after prophylaxis cleaning (T2). Study outcomes were mineral content (% weight of carbon [C], phosphorus [P], calcium [Ca], oxygen [O], chlorine [Cl], sodium [Na] and silicon [Si]) and calcium-phosphorus ratio (Ca/P). All groups had similar mineral composition at baseline. At T1, sample B2 exhibited least P, Ca and Ca/P content. Samples A1 and B1 showed higher content of P and Ca, compared to B2 (A1 only exhibited higher Ca/P). Sample A2 exhibited lowest Cl and Na content. At T2, sample A1 exhibited lowest C, P, O and Si content (highest Ca/P). Sample A2 showed least Ca/P, and highest Na content. Teeth treated by Recaldent™ proceeded by prophylaxis cleaning or MI Varnish® showed remineralization, especially when receiving both interventions. This superior effect persisted even after a second cleaning. Further trials are necessary to provide conclusive evidence in humans.


Laparoscopic hysterectomy.
Laparoscopic hysterectomy, an alternative to abdominal hysterectomy, is associated with a faster recovery rate than conventional surgery, but training in the new surgical techniques is needed and complications can occur.


Anti-passivation ability of sulfidated microscale zero valent iron and its application for 1,1,2,2-tetrachloroethane degradation.
The performance of sulfidated zero valent iron (ZVI) for the degradation of chlorinated hydrocarbons under aerobic conditions remains unclear. In this study, sulfidated microscale ZVI (S-mZVI) was prepared for 1,1,2,2-tetrachloroethane (TeCA) degradation under aerobic conditions. Compared with mZVI, S-mZVI showed excellent passivation resistance during the degradation of TeCA and its hydrolysis/reduction products. This was probably because the existence of FeSx shell (FeS/FeS2/FeSn) protected the internal ZVI core from passivation. Though the outer layer of FeSx shell could be oxidized to FeSn and Fe2(SO4)3 as the reaction proceeded, the inner layer remained stable, which maintained the fast electron transfer capability of S-mZVI. The high temperature could enhance the degradation of TeCA, without compromising the anti-passivation and reusability of S-mZVI. Even after the fifth cycle, S-mZVI could still efficiently degrade 90% of TeCA within 24 h. Furthermore, it was found that the degradation of TeCA and its reduction products (e.g., dichloroethylene (DCE)) by S-mZVI relied on direct electron transfer and hydrogen radical (H•), respectively, which might explain the lower levels of toxic DCE in the S-mZVI system. This study provides valuable information for the practical application of S-mZVI in the treatment of wastewater containing halogenated hydrocarbons under ambient conditions.


Managing variances in case management.
Timely management of variances is vital for cost effective patient care. A multifaceted approach that involves the healthcare team, patient, and family facilitates the identification and management of variances as they occur. The critical path can be used to monitor variances that influence fiscal outcomes in select patient populations. Strategies are described that can be used to monitor and manage variances, including developing a mechanism for monitoring and managing variances, implementing that mechanism, and evaluating the process for usability. Monitoring variances includes choosing tools that will be used and staff who will assume primary responsibility, and initiating an outcome analysis program. Managing variances comprises organizing an interdisciplinary committee, establishing a communication plan, creating strategies, and using continuous quality improvement teams.


Novel Insights into Tat Pathway in Xanthomonas oryzae pv. oryzae Stress Adaption and Virulence: Identification and Characterization of Tat-Dependent Translocation Proteins.
Xanthomonas oryzae pv. oryzae, an economically important bacterium, causes a serious disease in rice production worldwide called bacterial leaf blight. How X. oryzae pv. oryzae infects rice and causes symptoms remains incompletely understood. Our earlier works demonstrated that the twin-arginine translocation (Tat) pathway plays an vital role in X. oryzae pv. oryzae fitness and virulence but the underlying mechanism is unknown. In this study, we used strain PXO99A as a working model, and identified 15 potential Tat-dependent translocation proteins (TDTP) by using comparative proteomics and bioinformatics analyses. Combining systematic mutagenesis, phenotypic characterization, and gene expression, we found that multiple TDTP play key roles in X. oryzae pv. oryzae adaption or virulence. In particular, four TDTP (PXO_02203, PXO_03477, PXO_02523, and PXO_02951) were involved in virulence, three TDTP (PXO_02203, PXO_03477, and PXO_02523) contributed to colonization in planta, one TDTP (PXO_02671) had a key role in attachment to leaf surface, four TDTP (PXO_02523, PXO_02951, PXO_03132, and PXO_03841) were involved in tolerance to multiple stresses, and two TDTP (PXO_02523 and PXO_02671) were required for full swarming motility. These findings suggest that multiple TDTP may have differential contributions to involvement of the Tat pathway in X. oryzae pv. oryzae adaption, physiology, and pathogenicity.


Measuring the Association Between Body Mass Index and All-Cause Mortality in the Presence of Missing Data: Analyses From the Scottish National Diabetes Register.
Incorrectly handling missing data can lead to imprecise and biased estimates. We describe the effect of applying different approaches to handling missing data in an analysis of the association between body mass index and all-cause mortality among people with type 2 diabetes. We used data from the Scottish diabetes register that were linked to hospital admissions data and death registrations. The analysis was based on people diagnosed with type 2 diabetes between 2004 and 2011, with follow-up until May 31, 2014. The association between body mass index and mortality was investigated using Cox proportional hazards models. Findings were compared using 4 different missing-data methods: complete-case analysis, 2 multiple-imputation models, and nearest-neighbor imputation. There were 124,451 cases of type 2 diabetes, among which there were 17,085 deaths during 787,275 person-years of follow-up. Patients with missing data (24.8%) had higher mortality than those without missing data (adjusted hazard ratio = 1.36, 95% confidence interval: 1.31, 1.41). A U-shaped relationship between body mass index and mortality was observed, with the lowest hazard ratios occurring among moderately obese people, regardless of the chosen approach for handling missing data. Missing data may affect absolute and relative risk estimates differently and should be considered in analyses of routinely collected data.


[Epidemiological analysis of imported malaria in Xiaogan City from 2008 to 2013].
The epidemiological features of 27 imported malaria cases during 2008-2013 in Xiaogan were analyzed. Among the cases, 21(77.8%) were falciparum malaria,and 6(22.2%) were vivax malaria. Twenty-five (97.3%) cases were among 19-47 year-old males. The reported cases increased from 2010 to 2013, and there was no significant difference among seasons. The cases were reported from all the seven counties. Eleven cases (40.7%) were reported by Xiaonan District. Twenty-three cases were infected in Africa.