Increased expression of FOXQ1 is a prognostic marker for patients with gastric cancer.
Altered expression of forkhead box Q1 (FOXQ1) is observed in various types of human cancers. However, the clinical significance of FOXQ1 expression in gastric cancer (GC) remains largely unknown. The present study aims to explore the clinicopathological significance and prognostic value of FOXQ1 in GC. FOXQ1 messenger RNA (mRNA) and protein expression were determined by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot in 20 pairs of fresh frozen GC tissues and corresponding noncancerous tissues. Additionally, FOXQ1 expression was analyzed by immunohistochemistry in 158 clinicopathologically characterized GC cases. The correlation of FOXQ1 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of FOXQ1 mRNA and protein in GC tissues were both significantly higher than those in non-cancerous tissues. Our results showed that the high expression of FOXQ1 in GC was related to tumor size (P = 0.026), histological grade (P = 0.021), lymph node involvement (P = 0.002), and tumor-node-metastasis stage (P = 0.028). Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. Furthermore, Cox multivariates analysis indicated that FOXQ1 expression level was an independent prognostic factor for the overall survival rate of GC patients. In conclusion, overexpression of FOXQ1 is closely related to progression of GC and might be regarded as an independent predictor of poor prognosis for GC.


A new relative contraindication for lumbar myelography.
We have taken myelograms of six patients with grave post-tuberculous thoracic gibbus of the spine and gross deformity of the thoracic cage. Two of these patients suffered violent convulsions and fracture of the neck of the femur. In one patient the myelogram was taken with Conray Meglumine and in another with Dimer X. We suggest that a grave deformity of the thoracic cage is a relative contraindication for lumbar myelography with these water-soluble contrast media. We assume that the reduced tissue oxygenation in these patients results in a lower threshold for convulsions.


Transient endophytic colonizations of plants improve the outcome of foliar applications of mycoinsecticides against chewing insects.
The current work reports how spray application of entomopathogenic fungi on alfalfa, tomato and melon plants may cause an additional Spodoptera littoralis larvae mortality due to a temporal colonization of the leaves and subsequent ingestion of those leaves by the larvae. Most entomopathogenic fungi (EF) (Ascomycota: Hypocreales) endophytes seem to colonize their host plants in a non-systemic pattern, in which case at least a transient endophytic establishment of the fungus should be expected in treated areas after spray application. In this work, all strains were able to endophytically colonize roots, stems and leaves during the first 96h after inoculation. Whilst the treatment of S. littoralis larvae with a 10(8)ml(-1) conidial suspension resulted in moderate to high mortality rates for the Metarhizium brunneum EAMb 09/01-Su (41.7-50.0%) and Beauveria bassiana EABb 01/33-Su (66.7-76.6%) strains, respectively, an additive effect was detected when these larvae were also fed endophytically colonized alfalfa, tomato, and melon leaves, with mortality rates varying from 25.0% to 46.7% as a function of the host plant and total mortality rates in the combined treatment of 75-80% and 33-60% for B. bassiana and M. brunneum, respectively. Fungal outgrowth was not detected in any of the dead larvae feeding on colonized leaves, whereas traces of destruxin A were detected in 11% of the insects fed tomato discs endophytically colonized by M. brunneum. The combined effects of the fungal spray with the mortality caused by the feeding of insects on transient EF-colonized leaves have to be considered to estimate the real acute impact of field sprays with entomopathogenic fungi on chewing insects.


Retracted: Protection and Inheritance of Traditional Culture in Urbanization Construction Based on Genetic Algorithm under the Concept of Environmental Protection.
[This retracts the article DOI: 10.1155/2022/5844732.].


[What's new on antithrombotics?].
Management of venous thromboembolism disease could be improved by new drugs with lower risk of bleeding and without the need of regular monitoring of anticoagulant effect. In this way, idraparinux, anti-Xa inhibitor, has been compared to conventional therapy (coumarins) for the treatment of deep vein thrombosis and pulmonary embolism. Is it worth to treat patients more than six months? This has been evaluated in an interesting study. Prophylaxis after hip replacement surgery is indicated to reduce the risk of venous thromboembolism, new drugs are under investigation. Dabigatran etexilate, a direct thrombin inhibitor, has been shown as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery. In 2007, new european guidelines for non-STsegment elevation acute coronary syndromes have been published. Two new antithrombotic drugs, bivalirudin and fondaparinux, are now part of the different possible choices according to specific considerations. New factor Xa and factor IIa inhibitors are under investigation and are compared to heparin in PCI for NSTE-ACS. Fondaparinux and more recently otamixaban have given interesting results. These new recommendations have not yet taken into account new data published in 2007. What will be the positioning of prasugrel, a new thienopyridine, after the results of theTRITON trial? In patients with SCA treated by PCI, prasugrel reduced the ischemic events, while increasing major bleedings. In 2007, numerous publications and meta-analyses on drug-eluting stents (DES) have been published and tempered the fear about a possible increase in mortality with the use of DES.


[The Incidence of Biomedical Advances in Women. Some Reflections on the Spanish Legislation].
This article will examine how and to what extent advances in biomedical sciences have played a role in transforming the status of women. It will highlight the positive aspects of these transformations but it will also examine the issues which are currently debated and which, in my opinion, require calm and considered reflection.


Self-administration of morphine in the rat: relative influence of fixed ratio and time-out.
Rats were offered 3.2 mg/kg of morphine sulfate on a continuous reinforcement schedule until the daily injection rate had stabilized. The effect of fixed ratio schedules of 4 and 8 were compared to imposing time-out periods of 5 and 10 sec immediately followed each injection. The fixed ratio schedules decreased the injection rate while the time-out schedules had no effect. The hypothesis that the effect of a fixed ratio schedule is a consequence of imposing a time-out period, allowing full effects of the injection to be sensed, is not supported.


Dengue outbreaks prediction in Bangladesh perspective using distinct multilayer perceptron NN and decision tree.
Dengue fever is a disease that has been outbreak worldwide in the last few years. Dengue is a fatal disease; sometimes, it may cause life-threatening complications and even death. Dengue is considered to be one of the critical diseases which is spreading in more than 110 countries. Nearly 45,000 case reports have been found around Bangladesh in the last year. Dengue fever has become a major health hazard in Bangladesh. Hence, early detection would mitigate major casualties of Dengue disease. Distinct studies have been performed concerning Dengue disease; however, no effective study, particularly from Bangladesh's perspective, it seemed that reveals Dengue outbreaks prediction method. In this scenario, this research work aims to analyse the Dengue disease and build an apposite model to predict dengue outbreaks. This paper also aims to find the best technique to early predicts Dengue disease. The real-time data of the patients admitted to different hospitals in Bangladesh is accumulated to achieve the goal of the current research. Then different multilayer perceptron neural networks and a Decision tree are used for Dengue outbreaks prediction. Twenty-five parameters are analysed to find these parameters' infection rates in this work. A comparative study of the developed models' performances is also accomplished to obtain a better Dengue outbreaks prediction model. The results evidence that the Levenberg-Marquardt is the best technique with 97.3% accuracy and 2.7% error in Dengue disease prediction. On the other hand, the Decision tree may have the second choice to assess Dengue disease.


Four novel mutations at the cystathionine beta-synthase locus causing homocystinuria.
We describe four new mutations in the cystathionine beta-synthase gene: three point mutations localized in exons 3, 9 and 10 and one mutation in exon 12 which results in stop codon.


Experimental Design and Data Analysis of In Vivo Fluorescence Imaging Studies.
The objective of this chapter is to provide researchers who conduct in vivo fluorescence imaging studies with guidance in statistical aspects in the experimental design and data analysis of such studies. In the first half of this chapter, we introduce the key statistical components for designing a sound in vivo experiment. Particular emphasis is placed on the issues and designs that pertain to fluorescence imaging studies. Examples representing several popular types of fluorescence imaging experiments are provided as case studies to demonstrate how to appropriately design such studies. In the second half of this chapter, we explain the fundamental statistical concepts and methods used in the data analysis of typical in vivo experiments. We also provide specific examples in in vivo imaging studies to illustrate the key steps of analysis procedure.


Interference between Hieracium pilosella and Arrhenatherum elatius in colliery spoils of north of France : Allelopathy or competition?
On colliery heaps in northern France, a tall grassland community dominated by Arrhenatherum elatius, give place to a thin grassland community in which Hieracium pilosella is very abundant. It has been claimed that Hieracium pilosella is an allelopathic species and this phenomenon has been investigated as an explanation of this phase of plant succession. The importance of osmotic pressure in tested plant extracts is demonstrated and may be responsible for presumed allelopathy. Two phytotoxic compounds have been revealed in roots+rhizomes of Hieracium pilosella (umbelliferon and apigenin-glucoside). A third phytotoxic compound was exuded by roots in hydroponic cultures (7-glucoside-umbelliferon or skimin). However no toxicity of soil has been found and no phytotoxic compounds appeared to be present in the soil under Hieracium pilosella. Experimental mixed cultures (sterile or non-sterile conditions) reveal suppression of Hieracium pilosella by Arrhenatherum elatius rather than the reverse. Allelopathy cannot be invoked to explain this plant succession.


French validation of the compulsive internet use scale (CIUS).
The popularity of using the Internet and related applications has grown in European countries in the last two decades. Despite numerous advantages in terms of optimizing communications among individuals and social systems, the use of the Internet may be associated with excessive use and possible Internet addiction. The goals of the current study were to validate a French version of the compulsive Internet use scale (CIUS) and to assess its links with common psychiatric symptoms such as depression (assessed with the Beck depression inventory: BDI), anxiety (assessed with the trait anxiety inventory: STAI) and alcohol misuse (assessed with the alcohol use disorder identification test: AUDIT). The French versions of the CIUS, BDI, STAI and AUDIT were administered to a sample of Internet users. Exploratory and confirmatory analyses, correlation analysis and logistic regression were performed. As previously found with the original version, a one-factor model of the CIUS had good psychometric properties and fit the data well. Excessive use of the Internet was associated with depressive symptoms.


The distribution of metabolites between spinach chloroplasts and medium during photosynthesis in vitro.
1. The formation of metabolites in the stroma compartment of isolated chloroplasts during carbon fixation, and their export to the medium, have been investigated using improved techniques. 2. Rapid separation of photosynthesising chloroplasts from the medium, accompanied by simultaneous quenching of metabolism was achieved by using silicone oil layer filtering centrifugation under illumination. Metabolites were separated by microscale ion-exchange chromatography. Quantitative determination of each metabolite was based on labelling with 32P. 3. It was found that fixed carbon was exported from the chloroplasts only as triose phosphate and phosphoglycerate, and to a minor extent, as pentose monophosphate. The main compounds accumulating in the stroma were hexose and heptose monophosphates and phosphoglycerate. A marked decrease in the concentration of inorganic phosphate in the stroma during the first 5 min of illumination was accompanied by a complementary increase in organic phosphate so that the total amount of phosphate within the chloroplasts remained constant. 4. The concentration difference for phosphoglycerate between the stroma and the medium was much higher than for triose phosphate or inorganic phosphate, although all three compounds are transported across the inner membrane of the chloroplast envelope by the same carrier. It was concluded that the efflux of phosphoglycerate was restricted.


Sport as Medicine for Dyslipidemia (and Other Risk Factors).
Dyslipidemia is a common condition characterized by abnormal lipid levels in the blood, which can increase the risk of cardiovascular disease. Physical activity and participation in sports have been shown to have a positive impact on lipid profiles and reduce the risk of dyslipidemia. Additionally, regular physical activity can lead to weight loss and improved insulin sensitivity, both of which are associated with improved lipid profiles. This review aims to provide an overview on the utility of physical activity in the management of dyslipidemia. Improvements in lipid profiles were observed across both short- and long-term durations of high-intensity interval training (HIIT) and moderate intensity interval training (MIIT). However, it seems that more significant improvements in lipid profiles can be achieved with longer periods of physical activity and more intense exercise regimens. Several studies have investigated the relationship between aerobic exercise and HDL cholesterol (HDL-C), and the results suggest that HDL-C levels are more responsive to aerobic exercise compared to LDL cholesterol (LDL-C) and triglycerides (TG). Although findings on the effect of aerobic exercise on LDL-C levels have been inconsistent, there may still be beneficial changes in LDL-C subfractions that could provide cardiovascular protection. One such subfraction is plasma Lp(a), which contains Apo(a). However, unlike other LDL subfractions, Lp(a) is determined by genetics and is not influenced by physical activity. Therefore, it cannot be improved through exercise. Exercise is commonly believed to lead to a decrease in plasma TG concentrations. However, it is important to note that the baseline TG level may play a crucial role in determining the effect of exercise on the TG response. Factors such as individual variability and metabolic differences can influence the response of TG levels to exercise. Overall, exercise plays a crucial role in improving lipid profiles and promoting cardiovascular health. In conclusion, sport can be considered a form of medicine for dyslipidemia. Regular physical activity and participation in sports can improve lipid profiles, reduce the risk of cardiovascular disease, and improve overall health. It is essential to incorporate exercise and a healthy lifestyle into one's daily routine to prevent and manage dyslipidemia effectively.


Serum hepatocyte growth factor combined with vascular endothelial growth factor as a predictive indicator for the occurrence of coronary artery lesions in Kawasaki disease.
We investigated the possible use of serum hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) levels as a predictive indicator for the occurrence of coronary artery lesions (CAL) in Kawasaki disease (KD). Serum HGF and VEGF levels were measured by enzyme-linked immunosorbent assay in 41 patients with KD and 25 afebrile controls. Serum HGF levels of patients in the acute phase of KD were significantly higher than those of afebrile controls (Pc < 0.05) and decreased to lower levels during recovery (P < 0.0001). Univariate analysis showed significant correlations between occurrence of CAL and five variables: duration of fever (P=0.018), serum C-reactive protein concentration (P = 0.024), albumin concentration (P=0.009). serum VEGF level (P=0.009) and serum HGF level (P=0.035). Furthermore, multivariate analysis revealed that serum HGF and VEGF levels and presence of oedema were major risk factors for the occurrence of CAL. For prediction of the development of CAL, we established a new risk classification system with these three variables, which showed a sensitivity of 100% and a specificity of 94.4%. these data show that hepatocyte growth factor, together with vascular endothelial growth factor, might play an important role in the pathophysiology of Kawasaki disease and their serum levels could be a powerful predictor for the development of coronary artery lesions.


iTRAQ-based comparative proteomics reveal an enhancing role of PRDX6 in the freezability of Mediterranean buffalo sperm.
Semen cryopreservation is a critical tool for breed improvement and preservation of biodiversity. However, instability of sperm freezability affects its application. The Mediterranean buffalo is one of the river-type buffaloes with the capacity for high milk production. Until now, there is no specific cryopreservation system for Mediterranean buffalo, which influences the promotion of excellent cultivars. To improve the semen freezing extender used in cryopreservation of Mediterranean buffalo, different protein datasets relating to freezability sperm were analyzed by iTRAQ-based proteomics. This study will be beneficial for further understanding the sperm freezability mechanism and developing new cryopreservation strategy for buffalo semen. 2652 quantified proteins were identified, including 248 significantly differentially expressed proteins (DEP). Gene Ontology (GO) analysis indicated that many these were mitochondrial proteins, enriched in the molecular function of phospholipase A2 activity and enzyme binding, and biological processes of regulation of protein kinase A signaling and motile cilium assembly. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 17 significant pathways, including oxidative phosphorylation (OXPHOS). Furthermore, 7 DEPs were verified using parallel reaction monitoring or western blot, which confirmed the accuracy of the iTRAQ data. Peroxiredoxin 6 (PRDX6), which expressed 1.72-fold higher in good freezability ejaculate (GFE) compared to poor freezability ejaculate (PFE) sperms, was selected to explore the function in sperm freezability by adding recombinant PRDX6 protein into the semen freezing extender. The results showed that the motility, mitochondrial function and in vitro fertilization capacity of frozen-thawed sperm were significantly increased, while the oxidation level was significantly decreased when 0.1 mg/L PRDX6 was added compared with blank control. Above results revealed the metabolic pattern of freezability of Mediterranean buffalo sperms was negatively associated with OXPHOS, and PRDX6 had protective effect on cryo-damage of frozen-thawed sperms.


Isolation and characterization of Escherichia coli birA intragenic suppressors.
The biotin (bio) operon in Escherichia coli is negatively regulated by BirA, a bifunctional protein with both repressor and biotin-activating functions. Twenty-five heat-resistant revertants of three temperature-sensitive birA alleles (birA85, birA104 and birA879) were isolated and categorized into five growth and six repression classes. The revertants appear to increase biotin activation by raising the specific activity of BirA and/or increasing the number of enzyme molecules. The 19 birA85 revertants displayed a broad range of activity for both enzyme and repressor functions, and may represent intragenic second-site suppressor mutations. The birA85 revertants included a novel class of bio superrepressor mutations. Repressor titration experiments suggested that many of the birA85 revertants increase BirA concentrations above wild-type levels because the repressors were not competed from the chromosomal bio operator by multicopy bio operator plasmids. The majority of the birA104 revertants resulted in both wild-type repressor and enzyme activity; they are possibly true revertants in which the amino acid residue altered by the birA104 mutation has been substituted by the wild-type or a chemically similar amino acid.


Understanding and treating blast traumatic brain injury in the combat theater.
Blast injury is a frequent cause of traumatic brain injury (TBI) in the modern combat theater. We sought to explain the research and treatment associated with this injury. We reviewed literature on the prevalence of blast TBI (bTBI), blast injury mechanisms, research, and perspectives on the neurosurgical experience treating bTBI. A majority of combat-related casualties in recent wars are due to blast. A majority of survivors of blast injuries are diagnosed with TBI. Blast injury may induce changes in the brain not seen with non-blast-related mechanisms. However, long-term symptoms are not significantly different from non-blast mechanisms. Aggressive decompressive craniectomies are commonly performed in the combat theater. Due to the prevalence and debilitating nature of bTBI, understanding injury mechanisms is crucial in treating the injury before symptoms become permanent. Treatment is currently limited to decompressive craniectomies, which are the most effective treatment for a relatively young and fit military population.


A new heat shock protein that binds nucleic acids.
We describe the isolation of Hsp15, a new, very abundant heat shock protein that binds to DNA and RNA. Hsp15 is well conserved and related to a number of RNA-binding proteins, including ribosomal protein S4, RNA pseudouridine synthase, and tyrosyl-tRNA synthetase. The region shared between these proteins appears to represent a common, but previously unrecognized, RNA binding motif. Filter binding studies showed that Hsp15 binds to a 17-mer single-stranded RNA with a dissociation constant of 9 microM in 22.5 mM Hepes, pH 7. 0, 5 mM MgCl2. A role of Hsp15 in binding nucleic acids puts this protein into a different functional category from that of many other heat shock proteins that act as molecular chaperones or proteases on protein substrates.


Studies on growth cartilage in the horse and their application to aetiopathogenesis of dyschondroplasia (osteochondrosis)
The importance of osteochondrosis (dyschondroplasia) to the horse industry has been well documented since it was first recorded 50 years ago. The condition is known to be multifactorial in origin, arising from focal failure of endochondral ossification at predilection sites in articular/epiphyseal growth cartilage, but specific information on its aetiopathogenesis is sparse. This paper reviews the current knowledge of growth cartilage metabolism and the process of normal endochondral ossification in the horse. It highlights the localization of various protein products of chondrocytes and the differences in the zones of articular cartilage. In the early focal lesions (referred to as dyschondroplasia) there are alterations in the chondrocytes, extracellular matrix and some of the local protein products. The most obvious feature is an alteration in matrix metabolism which may be responsible for triggering a range of other factors leading to the development of a retained core of cartilage and a primary lesion of dyschondroplasia. Based on available evidence, a preliminary hypothesis for pathogenesis is presented. This suggests that there are a number of factors capable of initiating the condition. One of these involves high circulating insulin levels from high energy feeding which may affect chondrocyte maturation leading to altered matrix metabolism and faulty mineralization resulting in the formation of cartilage cores which characterize the condition. Further research to test this hypothesis is needed before there can be a rational basis for prophylaxis.


Perinatal infections with Chlamydia trachomatis.
Much has been relearned and learned anew about perinatal chlamydial infections during the past 10 to 15 years. The adverse effects of infection on pregnancy outcome have been suggested but not fully documented or explained. Epidemiologic, biologic, and immunologic correlates of risk for infection and complications of pregnancy due to C. trachomatis are not yet fully understood. Increased appreciation of the importance of this organism in pregnancy, coupled with more facile methods for diagnosing infection and with further research using modern molecular techniques, promises to add greatly to the completeness of our knowledge and to our eventual complete control of this infection in pregnancy.


Inflammatory markers in palatine tonsils of children with obstructive sleep apnea syndrome.
Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses. Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome. This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods). Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators. After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.


The immediate effects of foam rolling of the hamstrings muscle group on the contractile properties of the knee muscles in football players.
Excessive amounts of intense training, without adequate recovery time, can overload the musculoskeletal, immune, and metabolic systems, resulting in a potentially negative effects on later exercise performance. During the competitive period, the ability to recover after intense training and competition is an important factor of success in soccer. The purpose of this study was to determine the effect of hamstring foam rolling on the knee muscle contractile properties in soccer players, after a sports-specific load. 20 male professional soccer players were included and contractile properties of the biceps femoris, rectus femoris, vastus medialis and vastus lateralis muscles were measured with tensiomyography, before and after a Yo-Yo interval test and after 5 × 45 s of hamstring foam rolling. Additionally, active and passive knee extensibility before and after the intervention were measured. A mixed linear model was performed to determine the differences between the mean values of the groups. The experimental group performed foam rolling, while the control was resting. Five repetitions of 45 s of hamstring foam rolling had no statistically significant effect (p > 0.05) on any of the measured muscles following the Yo-Yo interval test or foam rolling intervention. There were no statistically significant differences in delay time, contraction time and maximum muscle amplitude between groups. Active and passive knee extensibility did not differ between groups. It seems that foam rolling does not affect mechanical properties of the knee muscles or hamstring extensibility in soccer players, after a sports-specific load.


Abdominal Imaging Findings in Neurocutaneous Syndromes: Looking Below the Diaphragm.
Neurocutaneous syndromes are a heterogeneous group of multisystemic disorders. We review the multimodality imaging findings in the disorders with a propensity for intraabdominal disease. We highlight more recently recognized disease patterns and discuss imaging surveillance optimization. Knowledge of varied intraabdominal phenotypic expressions can increase diagnostic rates. Limitation of radiation dose must be considered in screening this tumor-prone population. Early detection of neoplastic findings is critical for morbidity and mortality reduction.


cdc2 family kinases phosphorylate a human cell DNA replication factor, RPA, and activate DNA replication.
RPA is a single-stranded DNA binding protein complex purified from human cells and is essential for the initiation and elongation stages of SV40 DNA replication in vitro. In both human and yeast cells, the 34 kDa polypeptide subunit of RPA is phosphorylated in the S and G2 phases of the cell cycle and not in G1. One of the major RPA kinases present in extracts of human cells was purified and shown to be the cyclin B-cdc2 complex. This purified kinase, and a closely related cyclin A associated cdc2-like kinase, phosphorylated RPA p34 on a subset of the chymotryptic peptides that were phosphorylated in vivo at the G1-S transition. Two serines near the N-terminus of RPA p34 were identified as possible sites of phosphorylation by cdc2 kinase. These same serines were necessary for RPA phosphorylation in vivo. The purified cdc2 kinase stimulated SV40 DNA replication in vitro when added to G1 cell extracts. The kinase also stimulated unwinding at the origin of replication, one of the earliest steps in DNA replication requiring RPA, but only in the presence of an additional factor present in G1 cell extracts. Thus, one or more members of the cyclin-cdc2 kinase family may be required for the initiation and maintenance of S phase, in part due to their ability to phosphorylate and activate a cellular DNA replication factor, RPA.


Toll-like receptor 4 surface expression on human monocytes and B cells is modulated by IL-2 and IL-4.
Human Toll-like receptor 4 (TLR4) has recently been identified, and it has been shown to be the main protein involved in recognizing gram-negative bacteria. We examined the regulation of TLR4 surface expression in human peripheral blood monocytes and B cells by interleukin-2 (IL-2) and IL-4. IL-2 up-regulated TLR4 surface expression on human peripheral blood monocytes, but did not change expression on human peripheral B cells. By contrast, IL-4 down-regulated TLR4 surface expression on human peripheral blood monocytes, but up-regulated TLR4 surface expression on human peripheral B cells. These results indicate that Th1 cytokine IL-2 enhances receptors involved in the response to gram-negative bacteria and that activation of cellular immunity may enhance defense against these pathogens through monocytes, but not B cells, whereas Th2 cytokine IL-4 modulates the receptor response to gram-negative bacteria and that activation of humoral immunity may enhance defense against these pathogens through B cells, but not monocytes.


Multicenter clinical trials comparing cefotetan with moxalactam or cefoxitin as therapy for obstetric and gynecologic infections.
The clinical efficacy and safety of cefotetan was assessed in two multicenter clinical trials involving 335 evaluable patients hospitalized with obstetric and gynecologic infections. In Study I, cefotetan was compared with moxalactam and in Study II, cefotetan was compared with cefoxitin. The clinical response rate in Study I was 67 of 70 patients for cefotetan (96 percent) and 33 of 34 patients (97 percent) for moxalactam. In Study II, the clinical response rate was 138 of 147 patients in the cefotetan group (94 percent) and 76 of 84 patients in the cefoxitin group (91 percent). For the patients with bacteriologic response data, 196 of 205 cefotetan patients (96 percent), 23 of 24 moxalactam patients (96 percent), and 70 of 75 cefoxitin patients (93 percent) had a satisfactory bacteriologic response. Cefotetan was well tolerated and produced no major adverse reactions. The mean amount of cefotetan given was lower than that of moxalactam or cefoxitin.


Absorbable implants in sport medicine and arthroscopic surgery: A narrative review of recent development.
Over the past two decades, advances in arthroscopic and minimally invasive surgical techniques have led to significant growth in sports medicine surgery. Implants such as suture anchors, interference screws, and endo-buttons are commonly used in these procedures. However, traditional implants made of metal or inert materials are not absorbable, leading to complications that affect treatment outcomes. To address this issue, absorbable materials with excellent mechanical properties, good biocompatibility, and controlled degradation rates have been developed and applied in clinical practice. These materials include absorbable polymers, absorbable bioceramics, and absorbable metals. In this paper, we will provide a comprehensive summary of these absorbable materials from the perspective of clinicians, and discuss their clinical applications and related research in sport medicine.


Partial amino acid sequences of botulinum neurotoxins types B and E.
Clostridium botulinum type E neurotoxin, a single-chain protein of Mr 147,000, was purified and subjected to amino acid sequencing. The same was done for single-chain botulinum type B neurotoxin (Mr 152,000), and for the heavy and light chains (Mr 104,000 and 51,000 respectively) derived from type B by limited trypsin digestion. Twelve to eighteen residues were identified and the following conclusions were drawn: The light chain of the nicked (dichain) type B is derived from the N-terminal one-third of the single-chain (unnicked) parent neurotoxin; sequence homologies are present between single-chain types B and E and the light chain of the nicked type A [J. J. Schmidt, V. Sathyamoorthy, and B. R. DasGupta (1984) Biochem. Biophys. Res. Commun. 119, 900-904]; the N-terminal regions of the heavy chains of types A and B have some structural similarity; and activation of type B neurotoxin cannot involve removal of amino acids or peptides from the N terminus.


Mitoxantrone, folinic acid, 5-fluorouracil and prednisone as first-line chemotherapy for advanced breast carcinoma. A phase II study.
The purpose of this prospective clinical trial was an attempt to find an effective and relatively non-toxic schedule for patients with metastatic breast cancer who decline to receive aggressive cytotoxic chemotherapy. A total of 36 patients with disseminated breast cancer were treated with mitoxantrone 8 mg/m2 intravenously (i.v.) day 1, folinic acid 400 mg/m2 in a 2-h i.v. infusion with 5-fluorouracil 500 mg/m2 as an i.v. bolus 1 h later, days 1 and 8 at 3-week intervals plus prednisone 20 mg/m2 orally daily with diminishing doses over several weeks. Objective regressions were observed in 24/36 (67%) patients, 9 being complete (25%). Responses were seen at all disease sites, mainly pleural/lung, bone and liver. The median duration of response was 8 months (range 4-25+) and the median survival 12 months (range 3-26+). Myelosuppression, mainly leucopenia and thrombocytopenia, was the major toxicity but without complications. Other toxicities included mild or moderate nausea and/or vomiting (50%), stomatitis (33%) and diarrhoea (11%). Alopecia was minimal. No cases of cardiotoxicity were detected. The substantial response rate obtained with this relatively well tolerated regimen against advanced breast cancer warrants its assessment in a larger number of patients.


Tissue specific defect of complex I of the mitochondrial respiratory chain.
Deficiency of complex I is one of the most commonly reported defects of the mitochondrial respiratory chain in man. Clinical evidence of tissue specific expression of complex I deficiency has not previously been confirmed biochemically. We report here slow oxidation of NAD+-linked substrates, low activity of complex I and low amounts of immunoreactive complex I peptides in skeletal muscle mitochondria from a patient with muscle weakness and lactic acidosis. In liver mitochondria complex I activity was normal and all the immunoreactive subunits of complex I were present in normal amounts.


Long-term access to the peritoneal cavity in ovarian cancer patients.
One hundred thirty-six totally implanted peritoneal catheter systems were placed in 130 patients. No complications occurred at catheter placement. A total of 629 courses of intraperitoneal therapy were administered. The average catheter has remained in place for 4.5 months (range 1-19 months). Seven catheters (5.1%) were removed for infection. An additional 7 catheters were removed because of blockage, for a total removal rate due to complications of 10.2%. Catheters were not used for drainage of the peritoneal cavity. The totally implanted peritoneal catheter system provides a reliable means for long-term access to the peritoneal cavity in patients with ovarian cancer.


[Transcatheteral intra-arterial infusion of drug mixtures in the treatment of severe ischemia of the lower limbs].
Under analysis were results of the treatment of 53 patients with severe ischemic states of lower extremities by the method of transcatheteral intraarterial infusions of drugs. Duration of the treatment was from 7 to 50 days. The composition of the mixtures was chosen individually. The method is found to be sufficiently effective when no radical intervention on the vessels is possible.


Prenatal diagnosis of a long QT syndrome by fetal magnetocardiography in an unshielded bedside environment.
The potentially life threatening long QT syndrome should be diagnosed during pregnancy to improve perinatal care. A patient with a family history for a hereditary long QT syndrome presented at 30 weeks of her first pregnancy with fetal bradycardia and a narrow oscillation bandwidth on cardiotocography without structural abnormalities of the fetal heart. Fetal magnetocardiography was performed with a prototype biomagnetometer/gradiometer device in a magnetically unshielded environment. The cardiac time intervals were determined in the averaged PQRST complex. The QT time and the frequency-corrected QTc showed a marked prolongation to 380 ms and 0.52 s, respectively. The findings were confirmed in the postnatal electrocardiogram after spontaneous term delivery in a perinatal center. The causative mutation on chromosome 11 had been passed on to the newborn from his mother. Bedside fetal magnetocardiography revealed the exact diagnosis of the long QT syndrome in a period of the gestation when the fetus was electrically isolated by the vernix caseosa that hinders electrocardiography. To patients at risk of fetal cardiac abnormalities, magnetocardiography can be offered as a non-invasive diagnostic bedside procedure. The diagnosis should trigger closer surveillance and delivery in a perinatal center.


[Evaluation of mechanisms regulating endolymph pressure in the internal ear. I/].
The review of literature about the inner ear fluid circulation theory was presented. The creation and absorption of fluids were discussed as well as the role of endolymphatic sac in fluid pression regulation.


Pre-Clinical Pharmacokinetic and Pharmacodynamic Characterization of Selected Chiral Flavonoids: Pinocembrin and Pinostrobin.
Delineate the stereospecific pharmacokinetics and pharmacodynamics of the chiral flavonoids pinocembrin and pinostrobin. Characterize for the first time the stereoselective pharmacokinetics of two flavonoids, pinocembrin and pinostrobin and their bioactivity in several in vitro assays with relevant roles in heart disease, colon cancer, and diabetes etiology and pathophysiology. Chiral flavonoids were intravenously and orally administered to male Sprague-Dawley rats. Concentrations in serum and urine were characterized via stereospecific HPLC or LC/MS. Pure enantiomeric forms of each flavonoid were tested, where possible, to identify the stereospecific contribution to bioactivity in comparison to their racemates. Short half-lives (0.2-6 h) in serum were observed, while a better estimation of half-life (3-26 h) and other pharmacokinetic parameters were observed using urinary data. The flavonoids are predominantly excreted via non-renal routes (fe values of 0.3-4.6 %), and undergo rapid and extensive phase II metabolism. Chiral differences in the chemical structure of these compounds result in significant pharmacodynamic differences. The importance of understanding the stereospecific pharmacokinetics and pharmacodynamics of two chiral flavonoids were delineated.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Enhancement of anaerobic digestion sludge dewatering performance using in-situ crystallization in combination with cationic organic polymers flocculation.
Anaerobic digestion (AD) has been widely used in sludge treatment for biogas recovery, organic fraction stabilization, and sludge reduction. However, after AD, sludge filterability is extremely deteriorated due to the release of biopolymers and the formation of fine particles. AD sludge is generally rich in nutrients, mainly ammonium nitrogen and phosphates, that result from biopolymer degradation. We designed a conditioning process that combines the in-situ crystallization of magnesium ammonium phosphate (MAP), as a skeleton builder, with organic polymer flocculation. We show that crystallized MAP can bind with extracellular polymeric substance fractions to increase sludge floc density. The molecular structure and electrical charge of organic polymers importantly influence sludge particle flocculation and aggregation. We found that cationic polyacrylamides form flocs that aggregate with branching structures which are characterized by a larger size and a more compact structure. Simultaneous crystallization and flocculation produced by a magnesium-organic polymer gel improved AD dewaterability more than the separate addition of magnesium ions and organic polymers. The method of sludge conditioning that we propose was tested by extensive use in different AD sludge conditioning protocols. The method reduces the ammonium nitrogen load in AD liquor and increases the suitability of the biosolids for use as land fertilizer.


Development of more erratic heart rate patterns is associated with mortality post-myocardial infarction.
Cardiac patients often have sinus arrhythmia of nonrespiratory origin (erratic sinus rhythm [ESR]). ESR was quantified using hourly Poincaré and power spectral heart rate variability plots from normal-to-normal interbeat intervals and hourly values of the short-term fractal scaling exponent and correlations of normal-to-normal intervals in n = 60 nonsurvivors and n = 66 randomly selected survivors in the Cardiac Arrhythmia Suppression Trial. Hours were coded (ABN) as normal (0), borderline (0.5), or ESR (1). t Tests compared ABN for n = 2413 paired hours at baseline and on therapy. ABN was higher in nonsurvivors (0.38 +/- 0.44 vs 0.28 +/- 0.40, baseline, and 0.51 +/- 0.45 vs 0.34 +/- 0.43, on therapy, P < .001). Increased ABN with treatment were greater in nonsurvivors. Normal hours at baseline (relative risk = 0.77; 095% confidence interval, 0.62-0.96, P = .018) and on treatment (relative risk = 0.47; 95% confidence interval, 0.39-0.58) were significantly associated with decreased mortality compared with ESR. Quantification of ESR may identify more vulnerable patients or help monitor the effects of pharmacologic treatment.


Continuous Non-invasive finger cuff CareTaker® comparable to invasive intra-arterial pressure in patients undergoing major intra-abdominal surgery.
Despite increased interest in non-invasive arterial pressure monitoring, the majority of commercially available technologies have failed to satisfy the limits established for the validation of automatic arterial pressure monitoring by the Association for the Advancement of Medical Instrumentation (AAMI). According to the ANSI/AAMI/ISO 81060-2:2013 standards, the group-average accuracy and precision are defined as acceptable if bias is not greater than 5 mmHg and standard deviation is not greater than 8 mmHg. In this study, these standards are used to evaluate the CareTaker® (CT) device, a device measuring continuous non-invasive blood pressure via a pulse contour algorithm called Pulse Decomposition Analysis. A convenience sample of 24 patients scheduled for major abdominal surgery were consented to participate in this IRB approved pilot study. Each patient was monitored with a radial arterial catheter and CT using a finger cuff applied to the contralateral thumb. Hemodynamic variables were measured and analyzed from both devices for the first thirty minutes of the surgical procedure including the induction of anesthesia. The mean arterial pressure (MAP), systolic and diastolic blood pressures continuously collected from the arterial catheter and CT were compared. Pearson correlation coefficients were calculated between arterial catheter and CT blood pressure measurements, a Bland-Altman analysis, and polar and 4Q plots were created. The correlation of systolic, diastolic, and mean arterial pressures were 0.92, 0.86, 0.91, respectively (p < 0.0001 for all the comparisons). The Bland-Altman comparison yielded a bias (as measured by overall mean difference) of -0.57, -2.52, 1.01 mmHg for systolic, diastolic, and mean arterial pressures, respectively with a standard deviation of 7.34, 6.47, 5.33 mmHg for systolic, diastolic, and mean arterial pressures, respectively (p < 0.001 for all comparisons). The polar plot indicates little bias between the two methods (90%/95% CI at 31.5°/52°, respectively, overall bias = 1.5°) with only a small percentage of points outside these lines. The 4Q plot indicates good concordance and no bias between the methods. In this study, blood pressure measured using the non-invasive CT device was shown to correlate well with the arterial catheter measurements. Larger studies are needed to confirm these results in more varied settings. Most patients exhibited very good agreement between methods. Results were well within the limits established for the validation of automatic arterial pressure monitoring by the AAMI.


Reoperation directed by carcinoembryonic antigen level: the importance of a thorough preoperative evaluation.
Many asymptomatic patients suspected to have recurrent colorectal cancer based on an elevated carcinoembryonic antigen level will be spared unnecessary operation if strict attention is paid to their preoperative evaluation. Liver and renal function should be assessed. Unresectable extraabdominal and intraabdominal recurrence or metastases should be excluded. Patients being evaluated for recurrence after curative resection of a rectosigmoid cancer should undergo a bone scan. Having satisfactorily ensured normal results for these investigations, the surgeon should then proceed to search for an intraabdominal source of tumor recurrence.


The microcirculation in two transplantable melanomas of the hamster. II. Scanning electron microscopy.
Normal and tumor vessels observed in vivo on the hamster cheek pouch membrane in transparent chambers were examined by scanning electron microscopy. Large, thin walled veins were found in the reactive zone around the 2 amelanotic melanomas of the hamster. Sinusoidal vessels and channels contained red cells, which did not possess any vascular wall, were seen in the main substance of the tumors. In this system all the vessels within the central mass of the tumor transplant comprise newly formed vessels. The surfaces of the tumor cells and the lining of the tumor vessels were examined by this technique. The biological history i.e., age of the vessel and location from the growing edge of the tumor, were known. The surface of the tumor cells on cut section differed in appearance from the areolar tissue of the pouch membrane. Scanning electron microscopy of the inner aspect of newly formed tumor vessels permits much greater sampling of the tissue than transmission electron microscopy and further work should reveal aspects of the interaction of the blood with tumor stroma.


Sphinganine to sphingosine ratio and predictive biochemical markers of fumonisin B1 exposure in ducks.
The kinetics of free sphinganine (Sa), sphinganine to sphingosine ratio (Sa/So), proteins, cholesterol, alanine aminotransferase (ALAT) and lactate dehydrogenase (LDH) were investigated in the course of fumonisin B1 (FB1) exposure in ducks (20 growing males divided into four groups of 5 receiving, respectively, a daily dose of 0, 5, 15 or 45 mg/kg FB1 via oral administration over 12 days). Descriptive statistics of these parameters were also studied in a large number of ducks not exposed to mycotoxins and free of known pathology. Although the toxin at the end of the treatment affected all the parameters investigated, only 2 days of treatment appeared necessary to increase free Sa concentrations in serum, whereas 6 days were necessary to detect a significant effect on Sa/So ratio. Significant differences between control and treated ducks were observed after 4 days of treatment for ALAT and LDH and after 6 and 8 days for cholesterol and proteins concentrations. The minimum doses of FB1 required to determine an effect were assessed using three different methods. This approach reveals that FB1 has greater effects when it is ingested at a low dose for a long time than when ingested at a high dose for a short time. Although the minimum toxic dose of FB1 in ducks remains to be determined, this result must be considered in the context of chronic exposure to the toxin, not only in avian populations.


Influence of direct current on the electrical activity of the heart and on its susceptibility to ventricular fibrillation.
Isolated perfused guinea pig hearts (Langendorff preparation) were used to study the influence of direct current (DC) on the shape of the electrogram and to determine the thresholds for extrasystoles and for fibrillation. DC impulse durations ranged between 30 ms and 5 s. During DC flow through the heart, marked deformations of the electrogram occur mainly concerning the repolarization phase and increasing with growing current strength. At an intensity of twice the diastolic threshold for stimulation, constant DC induces extrasystoles, which are suggested to result from an enhancement of the intrinsic automatic activity by cathodal polarization. Compared with the diastolic threshold for stimulation, the threshold for fibrillation is higher by a factor of about 15. The curve relating the threshold for fibrillation to the impulse duration shows a marked decline between 30 ms and 60 ms, followed by a slight increase and adjustment to a constant level beyond about 80 ms. In the used setup, the threshold for fibrillation is independent on the reversal of polarity of the electrodes. Long-lasting DC pulses are able to induce fibrillation even if they are switched on in the absolute refractory period of a normal beat. Application of 50-Hz alternating current revealed a higher threshold for stimulation and a three times lower fibrillation threshold compared with the effects of DC in the same heart.


Metagenomic analysis of virome cross-talk between cultivated Solanum lycopersicum and wild Solanum nigrum.
Wild plants and weeds growing close to crops constitute a potential reservoir for future epidemies or for the emergence of novel viruses but the frequency and directionality of viral flow between cultivated and wild plants remains poorly documented in many cases. Here, we studied the diversity of viral populations between tomato (Solanum lycopersicum) and neighboring european black nightshade (Solanum nigrum) using high throughput sequencing (HTS) based metagenomics. A large variability in virome richness with only 17.9% shared Operational Taxonomy Units between tomato and nightshade, but this richness could not be linked to a particular host or to local conditions. A detailed population analysis based on assembled contigs for potato virus Y (PVY), broad wilt bean virus 1 and a new ilarvirus tentatively named Solanum nigrum ilarvirus 1 provides information on the circulation of these viruses between these two Solanum species and enriches our knowledge of the tomato virome.


Meteorological determinants of spider ballooning: the roles of thermals vs. the vertical windspeed gradient in becoming airborne.
Spiders disperse by ballooning, a form of aeronautic behavior which they initiate by launching themselves into thermals. An attempt was made to define meteorological variables related to production and maintenance of thermals and use them as predictors of the number of aeronauts. Ballooning spiders were collected throughout a full growing season at an agricultural site and a native tall grass prairie 25 km distant, and numbers of ballooners were regressed against variables derived from meteorological data taken at locations near each site. The variables were the proportions of cloud cover and of possible sunshine, differences between maximum and minimum daily temperature (DT), wind speed, and a modification of the aeronautic index of Vugts and van Wingerden (1976). Ballooner numbers and meteorological variables used in the regressions were all weekly means. Significant one-step models were derived for both sites, but the addition of a second variable did not significantly increase the proportion of variation explained in either model. The modified aeronautic index explained 23% of the variation in ballooner numbers at the prairie site, while the proportion of possible sunshine explained 82% of the variation at the agricultural site. However the signs of the partial regression coefficients were contrary to expected. This may be due to the masking of short term meteorological and behavioral events by the averaging of meteorological variables and aeronaut numbers over a week. Alternatively it may indicate that the source of updrafts used by aeronauts may not always be thermals, but may sometimes be the vertical gradient in windspeed, a model which is consistent with the contrary signs of the regression coefficients.


Centrally administered bombesin activates COX-containing spinally projecting neurons of the PVN in anesthetized rats.
The paraventricular nucleus (PVN) of the hypothalamus has a heterogenous structure containing different types of output neurons that project to the median eminence, posterior pituitary, brain stem autonomic centers and sympathetic preganglionic neurons in the spinal cord. Presympathetic neurons in the PVN send mono- and poly-synaptic projections to the spinal cord. In the present study using urethane-anesthetized rats, we examined the effects of centrally administered bombesin (a homologue of the mammalian gastrin-releasing peptide) on the mono-synaptic spinally projecting PVN neurons pre-labeled with a retrograde tracer Fluoro-Gold (FG) injected into T8 level of the spinal cord, with regard to the immunoreactivity for cyclooxygenase (COX) isozymes (COX-1/COX-2) and Fos (a marker of neuronal activation). FG-labeled spinally projecting neurons were abundantly observed in the dorsal cap, ventral part and posterior part of the PVN. The immunoreactivity of each COX-1 and COX-2 was detected in FG-labeled spinally projecting PVN neurons in the vehicle (10 μl of saline/animal, i.c.v.)-treated group, while bombesin (1 nmol/animal, i.c.v.) had no effect on the number of these immunoreactive neurons for each COX isozyme with labeling of FG. On the other hand, the peptide significantly increased the number of double-immunoreactive neurons for Fos and COX-1/COX-2 with FG-labeling in the PVN (except triple-labeled neurons for FG, COX-2 and Fos in the dorsal cap of the PVN), as compared to those of vehicle-treated group. These results suggest that centrally administered bombesin activates spinally projecting PVN neurons containing COX-1 and COX-2 in rats.


Further new milbemycin antibiotics from Streptomyces bingchenggensis. Fermentation, isolation, structural elucidation and biological activities.
Three new alpha-class milbemycins from Streptomyces bingchenggensis, named milbemycins alpha28, alpha29 and alpha30, have been isolated and characterized. On the basis of detailed spectroscopic analysis and comparison with reported data, their structures were determined to be the 22alpha-hydroxy, 23beta-O-(2-methylbutanoyl) milbemycin alpha9, 22alpha-hydroxy, 23beta-O-(2,4-dimethylpentanoyl) milbemycin alpha9 and 22alpha-hydroxy, 23beta-O-(2-methylbutanoyl) milbemycin A4, respectively. Milbemycins alpha28 and alpha29 are the first reported milbemycins that possess both C-26 and C-23 substituents. These three new milbemycins possess potent acaricidal and nematocidal activity.


Lacrimal sweating in a patient with Reader's syndrome.
A patient is described with a right-sided Reader's syndrome and extensive sweating in the frontal area above the right eye. This pathological sweating can be explained by sprouting of lacrimal parasympathetic fibres in the previous denervated sympathetic sudomotor pathways to that area.


Receptors for platelet-derived growth factor on microvascular endothelial cells.
Endothelial cells are widely thought to be unresponsive to platelet-derived growth factor (PDGF) and devoid of PDGF receptors. However, in examining the growth factor responses of microvascular endothelial cells isolated from human omental adipose tissue, we detected PDGF-induced tyrosine phosphorylation of an 180-kD glycoprotein, subsequently identified as the cellular receptor for PDGF by specific immunoprecipitation. Scatchard analysis of 125I-PDGF binding to human microvascular endothelial cells revealed 30,000 PDGF receptors/cell with a kD of 0.14 nM. PDGF stimulated tyrosine phosphorylation of PDGF and other cellular proteins in a dose- and time-dependent manner, with half-maximal receptor phosphorylation occurring at 0.3 nM recombinant human PDGF-BB within 1 min of PDGF exposure. Normal cellular consequences of receptor activation were also observed, including tyrosine phosphorylation of a 42-kD protein and serine phosphorylation of ribosomal protein S6. Furthermore, PDGF was mitogenic for these cells. The finding of functional PDGF receptors on human microvascular endothelial cells suggests an important direct role for PDGF in neovascularization.


Relationship between mean platelet volume and varicocele: a preliminary study.
To examine the relationship between the mean platelet volume (MPV) and varicocele to clarify the etiopathogenesis of varicocele. MPV levels were measured in 60 varicocele subjects (group I) and 57 healthy controls (group II) from 2009-2010. Ages were similar between the 2 groups. The diagnosis of varicocele was based on the findings from both physical examination and color Doppler ultrasound. The average patient age at the time of examination was 28.12 ± 6.4 years in group I and 28.10 ± 5.8 in group II. MPV levels were statistically significantly higher in group I than in group II (P < .001). Positive correlations were found between MPV and varicocele grade as between MPV and diameter of left spermatic vein (P < .05). The increase in MPV is independent of the disease, and the increase in varicocele grade is associated with higher MPV in varicocele patients. On the basis of the importance of the vascular component in the pathophysiology of varicocele, we would suggest conducting more studies with platelets in varicocele patients.


Building Long-Term Care Staff Capacity During COVID-19 Through Just-in-Time Learning: Evaluation of a Modified ECHO Model.
The onset of the COVID-19 pandemic significantly challenged the capacity of long-term care (LTC) homes in Canada, resulting in new, pressing priorities for leaders and health care providers (HCPs) in the care and safety of LTC residents. This study aimed to determine whether Project ECHO (Extension for Community Healthcare Outcomes) Care of the Elderly Long-Term Care (COE-LTC): COVID-19, a virtual education program, was effective at delivering just-in-time learning and best practices to support LTC teams and residents during the pandemic. Mixed methods evaluation. Interprofessional HCPs working in LTC homes or deployed to work in LTC homes primarily in Ontario, Canada, who participated in 12 weekly, 60-minute sessions. Quantitative and qualitative surveys assessing reach, satisfaction, self-efficacy, practice change, impact on resident care, and knowledge sharing. Of the 252 registrants for ECHO COE-LTC: COVID-19, 160 (63.4%) attended at least 1 weekly session. Nurses and nurse practitioners represented the largest proportion of HCPs (43.8%). Overall, both confidence and comfort level working with residents who were at risk, confirmed, or suspected of having COVID-19 increased after participating in the ECHO sessions (effect sizes ≥ 0.7, Wilcoxon signed rank P < .001). Participants also reported impact on intent to change behavior, resident care, and knowledge sharing. The results demonstrate that ECHO COE-LTC: COVID 19 effectively delivered time-sensitive information and best practices to support LTC teams and residents. It may be a critical platform during this pandemic and in future crises to deliver just-in-time learning during periods of constantly changing information.


Revealing the reasons for the pasting property changes of rice during aging from the perspective of starch granule disaggregation.
The pasting properties of rice change markedly after aging, although the mechanism for this still remains unknown. Aged and fresh rice grains were ground and the flours were fractionated by particle size, and then the pasting properties, particle size distribution and microscopic morphology of the heated flour fractions were evaluated. Compared to the corresponding fresh flour fractions with the same particle size, a lower peak viscosity for those aged flour fractions from 80 μm to 450 μm and a higher peak viscosity for those aged flour fractions from 20 μm to 60 μm were observed. The amounts of smaller particles disaggregated from the aged flour fractions were significantly less and the separated entities were always larger than the corresponding fresh rice fractions. Disaggregation difficulty of starch granules was the reason for the changes in the pasting properties of rice after aging. This finding is helpful for understanding rice aging mechanisms and regulating eating quality of rice flour as an ingredient. © 2022 Society of Chemical Industry.


Ultrafast spectroscopy of biological photoreceptors.
We review recent new insights on reaction dynamics of photoreceptors proteins gained from ultrafast spectroscopy. In Blue Light sensing Using FAD (BLUF) domains, a hydrogen-bond rearrangement around the flavin chromophore proceeds through a radical-pair mechanism, by which light-induced electron and proton transfer from the protein to flavin result in rotation of a conserved glutamine that switches the hydrogen bond network. Femtosecond infrared spectroscopy has shown that in photoactive yellow protein (PYP), breaking of a hydrogen bond that connects the p-coumaric acid chromophore to the backbone is crucial for trans-cis isomerization and successful entry into the photocycle. Furthermore, isomerization reactions of phycocyanobilin in phytochrome and retinal in the rhodopsins have been revealed in detail through application of femtosecond infrared and femtosecond-stimulated Raman spectroscopy.


A phase I/II study of intraperitoneally administered doxorubicin entrapped in cardiolipin liposomes in patients with ovarian cancer.
A phase I and II clinical trial of intraperitoneally administered liposome-encapsulated doxorubicin in patients with advanced ovarian cancer is being evaluated. Doxyrubicin liposomes were prepared with cardiolipin, phosphatidyl choline, cholesterol, and sterarylamine and sized by flow cytometry before administration. Fifteen patients have been treated with 42 cycles of intraperitoneal liposome-encapsulated doxrubicin. Liposome-encapsulated doxorubicin in 2 L of normal saline solution was infused over 1 hour through an infusaport into the peritoneal cavity with a dwell time of 4 hours every 21 days. Liposome-encapsulated doxorubicin has been administered at escalating doses up to 100 mg/2 L and has been well tolerated. Increased bowel motility with mild-to-moderate abdominal distress has been encountered during the first 24 hours after administration. There has been one patient with presumed chemically induced peritonitis after a temperature elevation to 39.5 degrees C. There has been no myelosuppression, abnormalities of liver function tests, or alopecia. Nausea and vomiting were minimal. Liposome-encapsulated doxorubicin was extravasated in two patients without sequelae. Drug levels were measured after completion of infusion. At a dose of 70 mg, the peak intraperitoneal concentration was 28.6 micrograms/microliter, which was reduced to 23.6 micrograms/microliter by 2 hours. Concurrent plasma levels were in the range of 0.2 to 0.5 micrograms/microliter. A similar pattern was observed at other doses. The maximum tolerable dose has not yet been obtained. There were three responders in the 10 evaluable patients. The preliminary experience with intraperitoneal liposome-encapsulated doxorubicin is encouraging.


Conventional Radiology in Crystal Arthritis: Gout, Calcium Pyrophosphate Deposition, and Basic Calcium Phosphate Crystals.
This article reviews the main radiographic features of crystal deposition diseases. Gout is linked to monosodium urate crystals. Classic radiographic features include subcutaneous tophi, large and well-circumscribed paraarticular bone erosions, and exuberant bone hyperostosis. Calcium pyrophosphate deposition (CPPD) can involve numerous structures, such as hyaline cartilages, fibrocartilages, or tendons. CPPD arthropathy involves joints usually spared by osteoarthritis. Basic calcium phosphate deposits are periarticular or intraarticular. Periarticular calcifications are amorphous, dense, and round or oval with well-limited borders, and most are asymptomatic. When resorbing, they become cloudy and less dense with an ill-defined shape and can migrate into adjacent structures.


Investigating the Transcriptomic and Expression Presence-Absence Variation Exist in Japanese Eel (Anguilla japonica), a Primitive Teleost.
The pan-genome was defined as the complete gene set across strains, and it is built upon genes displaying presence-absence variations (PAVs); the pan-transcriptome is defined by recalling the pan-genome. Indeed, a PAV is reflected from the expression presence-absence variation (ePAV). In this study, treated with androgen, eels, which are a primitive fish from the basal lineage of Teleost, with different ovarian developments were chosen and submitted to RAN-sequencing. Transcriptomes were the assembly against eel genome scaffolds; a pair was the unit (the same eel before and after treatment) to analyze DEGs (differentially expressed genes); the core, unique, or accessory genes were identified, and the list of DEGs was analyzed to investigate ePAV. The results suggest that there was ePAV in Japanese eel, and the ePAV of eel was analyzed by pathway enrichment. These results signify the importance of genetic differential expression on the variations of phenotypes by androgen, and a transcriptomic approach appears to enable extracting multiple layers of genomic data.


Complete kinetic follow-up of symptoms and complement parameters during a hereditary angioedema attack.
We studied the kinetics of C1-inhibitor (C1-INH) and other complement parameters in a self-limited edematous attack (EA) in a patient with hereditary angioedema due to C1-INH deficiency to better understand the pathomechanism of the evolution, course, and complete resolution of EAs. C1-INH concentration and functional activity (C1-INHc+f ), C1(q,r,s), C3, C4, C3a, C4a, C5a, and SC5b-9 levels were measured in blood samples obtained during the 96-hour observation period. The highest C1-INHc+f , C4, and C1(q,r,s) levels were measured at baseline, and their continuous decrease was observed during the entire observation period. C4 depletion started at prodromal phase, and C4 was lowest after the maximum severity peak. Compared to baseline, C4a level was four times higher 7 hours before the onset of the attack. C1-INH did not increase after resolution of the attack suggesting that factors other than C1-INH may be important in this process. C4a may be a useful biomarker for the prediction of EAs.


Genomic and Phenotypic Characterization of a Colistin-Resistant Escherichia coli Isolate Co-Harboring bla NDM-5, bla OXA-1, and bla CTX-M-55 Isolated from Urine.
Colistin is one of the few options for treating carbapenem-resistant Enterobacterales (CREs). There is little available information about the epidemic status of colistin-resistant CREs in Southern Sichuan, China. This study mainly investigated the genomic and phenotypic characteristics of an extensively drug resistant E. coli LZ00114 isolated from Luzhou, China. In 2020, LZ00114 was isolated from the urine of a patient with hydronephrosis and urinary tract infection in Luzhou, China. We assessed the resistance profile of LZ00114 in the presence and absence of the protonophore carbonyl cyano-m-chlorophenylhydrazine (CCCP) and 1-(1-naphthylmethyl)-piperazine (NMP) by antimicrobial susceptibility testing. The growth kinetics, motility, and pathogenicity of LZ00114 were determined to evaluate its microbial characteristics. In combination with whole genome sequencing (WGS) and real-time reverse transcription PCR (RT-PCR), we comprehensively analyzed the resistance mechanisms of LZ00114. LZ00114 was resistant to various antimicrobial agents, including meropenem, tetracycline, ciprofloxacin, gentamicin, fosfomycin, and polymyxin B. Notably, CCCP reversed the resistance of LZ00114 to polymyxin B. LZ00114 displayed high pathogenicity in the infection model (P<0.01) compared with the Lab-WT strain, and its growth rate and motility were not significantly different from the Lab-WT strain. WGS and conjugation revealed that LZ00114 belonged to ST410 and carried a bla NDM-5-harboring self-transmissible IncX3 plasmid and a multi-replicon IncFII/FIA/FIB plasmid carrying bla OXA-1-bla CTX-M-55-tet(B)-aac(6')-Ib-cr-dfrA17-sul1-fosA3. Comparative genomics revealed genetic relatedness between LZ00114 and strains isolated from other regions. Furthermore, there were point mutations in pmrA (S29G, G144S), pmrB (D283G, Y358N), marR (G103S, Y137H), emrA (I219V), and emrD (G323D) of LZ00114. RT-PCR confirmed the overexpression of efflux pumps and PmrABC in LZ00114. This study provides valuable information for the surveillance of antimicrobial resistance and a theoretical basis for the prevention and control of colistin-resistant E. coli. There is still a need to be vigilant about the clone spread of the high-risk clone group E. coli ST410.


H2A.Z deposition by SWR1C involves multiple ATP-dependent steps.
Histone variant H2A.Z is a conserved feature of nucleosomes flanking protein-coding genes. Deposition of H2A.Z requires ATP-dependent replacement of nucleosomal H2A by a chromatin remodeler related to the multi-subunit enzyme, yeast SWR1C. How these enzymes use ATP to promote this nucleosome editing reaction remains unclear. Here we use single-molecule and ensemble methodologies to identify three ATP-dependent phases in the H2A.Z deposition reaction. Real-time analysis of single nucleosome remodeling events reveals an initial priming step that occurs after ATP addition that involves a combination of both transient DNA unwrapping from the nucleosome and histone octamer deformations. Priming is followed by rapid loss of histone H2A, which is subsequently released from the H2A.Z nucleosomal product. Surprisingly, rates of both priming and the release of the H2A/H2B dimer are sensitive to ATP concentration. This complex reaction pathway provides multiple opportunities to regulate timely and accurate deposition of H2A.Z at key genomic locations.


A perspective on surfaces and interfaces.
The importance of surfaces and interfaces cannot be overstated, with their reach extending from the hardware of the digital age to the processes of life. The past half-century has seen the development of a full and varied toolkit for characterizing them. This toolkit is now serving a growing interdisciplinary community and is providing a powerful platform for scientific research and manufacturing technology.


CD36 as a biomarker of atherosclerosis.
Atherosclerosis is a chronic inflammatory disorder occurs as a result of mononuclear lymphocyte infiltration to the arterial wall accompanied by smooth muscle cell proliferation and damage in the arterial wall caused by extracellular matrix accumulation. Besides several genetic and environmental factors, increased serum cholesterol and oxidized low density lipoproteins are considered to be major risk factors of the disease. During atherosclerosis, lipoproteins such as LDL become trapped at the site of lesion and are converted to oxLDL. Smooth muscle cells become activated by oxLDL, start to proliferate, and migrate into the intima of the arterial wall. OxLDL provokes a cascade of cellular responses at the atherosclerotic lesion, ultimately leading to formation of atherosclerotic plaques. In this process, scavenger receptors could play a critical role because of their ability to bind oxLDL and their function in transporting lipids and cholesterol into and out of the cells. Scavenger receptors are expressed on macrophages and foam cells in atherosclerotic lesions. CD36 is the most important one among them playing role in atherosclerotic process. CD36 is a raft associated glycosylated protein with an 88kDa molecular weight and various ligands such as oxLDL, apoptotic cells, advanced glycation end products bind to this receptor. It has been shown that mice knockouts for the apolipoprotein E exhibited a marked decrease in atherosclerotic lesions if CD36 gene was made inactive. Previously we have shown that the aortas of cholesterol-fed rabbits showed typical atherosclerotic lesions, detected by macroscopic and microscopic examination, and exhibited an increase in CD36 mRNA expression. In this study, we planned to compare CD36 mRNA expressions in the aortic tissue and peripheral blood mononuclear cells in cholesterol induced atherosclerosis. Our results suggests that CD36 mRNA levels in peripheral blood mononuclear cells reflect the levels in aorta and this might be used as a marker for diagnosis of atherosclerosis.


[The ICD-10 Symptom Rating questionnaire for assessment of psychological comorbidities in chronic tinnitus patients].
Psychological comorbidities are frequent in tinnitus patients and their diagnosis is important for both interventions as well as treatment success. The selection of suitable questionnaires is thus crucial. The present study aimed to investigate the ICD-10 Symptom Rating (ISR) questionnaire for the diagnosis of psychological comorbidities. The current study investigated tinnitus burden and psychological comorbidities in a sample of n = 311 patients with chronic tinnitus. All participants completed an intensive 7‑day multimodal tinnitus-specific therapy. Tinnitus burden was measured using the German version of the Tinnitus Questionnaire (TQ). Psychological comorbidities were measured using the ISR (total score, depressive disorder, anxiety disorder, obsessive-compulsive disorder, somatoform disorder, and eating disorder), the Perceived Stress Questionnaire (PSQ; total score, tension, worries, joy, and demands), and the General Depression Scale (Allgemeine Depressionsskala, ADS). Psychological comorbidities were suffered by 65% of participants. Treatment response comprised improvements in TQ, ISR, PSQ, and ADS. At baseline, tinnitus burden correlated with the ISR total, ISR obsessive-compulsive disorder, and PSQ tension scores. Post-treatment, the now reduced tinnitus burden was also predicted by the ISR depressive and eating disorder scores. The ISR is a useful tool for measuring psychological comorbidities in patients with chronic tinnitus as well as for assessing short-term treatment response. Therapeutic approaches for chronic tinnitus should also consider stress-related tension, depressive symptomatology, and coping strategies such as maladaptive eating behaviors.


As bone marrow scintigraphy in patients treated with chemotherapy and/or radiotherapy.
Bone marrow scintigraphy after the application of indium 111In was compared with the results of bone marrow puncture in 18 patients with Hodgkin's disease treated with radiotherapy and/or chemotherapy. Agreement was found in 85% of the cases. When the results of bone marrow puncture were compared with the general state of haemopoiesis estimated scintigraphically agreement was found in only 65%. Bone marrow scintigraphy gives a more detailed knowledge of the general state of haemopoiesis and serves as a guide for the control of therapy with cytostatics and/or irradiation.


Microinjected clonidine inhibits noradrenergic neurons of the locus coeruleus in freely moving cats.
Microinjection of the alpha 2-adrenoceptor agonist, clonidine (CLON; 1.0 microgram/0.1 microliter) effected a virtually complete suppression of the spontaneous activity of noradrenergic neurons of the locus coeruleus in freely moving cats. This effect lasted for approximately 90 min and was reversible by systemic administration of the alpha 2-adrenoceptor antagonist, yohimbine. In contrast, CLON had no consistent effect on the activity of neighboring non-noradrenergic neurons. These results provide additional evidence for the direct inhibition of central noradrenergic neurons by CLON by demonstrating such effects independent of anesthesia or the behavioral effects of systemic drug administration. More generally, these findings demonstrate the usefulness of a technique in which small amounts of drug can be applied in small volumes to produce a neuropharmacologically specific effect upon locally recorded neurons in behaving animals.


Does photoperiodism involve a seasonal and non-pathological Warburg effect?
The precise means whereby mammals recognize and respond to changing day length so as to adjust their physiology to the seasons (photoperiodism) remains enigmatic. We present a new hypothesis according to which aerobic glycolysis (AG) within selected astrocytic syncytia plays a central role in photoperiodism. We focus on the response of the mammal breeding in longer days (LD) to the shorter days (SD) of autumn. It is posited that AG in the brain of the SD organism is activated within a specified circuitry and temporal window. The circuitry involves regions targeted by the medullary norepinephrine (NE) system including but not limited to the anterior bed nucleus of the stria terminalis; the temporal window in question is defined by the autumnal extension of darkness into a segment of the organism's circadian activity cycle that was illuminated on the previous day. Lactate generated from glucose during SD serves primarily as a signaling entity as opposed to a fuel, instructing astrocytes, for example, gradually to replace the LD genome with one specific to SD. The requirement to provision glucose to the brain for AG through SD accounts for the frequent findings of mild autumnal hyperglycemia and elevated carbohydrate appetite across many different mammalian species including human beings. So long as the sidereal environment enveloping life on earth featured its extraordinarily predictable pattern of photoperiodic change, the dangers of exposing the organism to augmented glucose and lactate within a strictly delimited window were easily outweighed by the benefits of a precision mechanism ensuring the alignment of the animal's reproductive cycle with the seasonal one. With "light pollution," that delicate balance may now be at risk.


Balloon dilation of subaortic stenosis due to a thick fibrous shelf.
A young patient with discrete subaortic stenosis due to a thick fibrous shelf was subjected to transcatheter balloon dilation. The outcome of the procedure and its probable mechanism is discussed.


Model calculations of the spontaneous curvature, mean and Gaussian bending constants for a thermodynamically open surfactant film.
The spontaneous curvature (H(0)), mean and Gaussian bending constants (k(c) and k (c)), as defined in the well-known Helfrich expression, have been calculated from a detailed model for a thermodynamically open surfactant layer. The effect of head group cross-section area, surfactant tail length and electrolyte concentration for monovalent ionic surfactants have been investigated. Geometrical packing constraints subjected to the aggregated hydrocarbon tails and electrostatics are found to be the dominant contributions to H(0), k(c) and k (c). In addition, the transition from spherocylindrical micelles to vesicles were investigated in terms of the three parameters and the following simple expressions were derived as criteria for coexistence between micelles and vesicles H(0)=1/4 xi and N(ves)/N(mic)=exp[4 pi(k(c)+k (c))/kT], where xi is the thickness of the hydrocarbon part of the film and N(mic) and N(ves) the average aggregation numbers of micelles and vesicles, respectively. However, it is found that the ratio N(ves)/N(mic) is order of magnitudes too large for vesicles to form at all in charged single-surfactant systems where the surfactant head is of moderate size.


Parent-Teacher Disagreement on Ratings of Behavior Problems in Children with ASD: Associations with Parental School Involvement Over Time.
ASD symptomology and behavioral problems pose challenges for children with ASD in school. Disagreement between parents and teachers in ratings of children's behavior problems may provide clinically relevant information. We examined parent-teacher disagreement on ratings of behavior problems among children with ASD during the fall and spring of the school year. When child, teacher, and class characteristics were considered simultaneously, only ASD symptom severity predicted informant disagreement on internalizing and externalizing behavior problems. We also examined associations between informant disagreement and parent school involvement. Cross-lagged panel analyses revealed that higher informant disagreement on children's behavior problems in the fall predicted lower parent school involvement in the spring, suggesting that greater informant agreement may foster parental school involvement over time.


Null variants in DYSF result in earlier symptom onset.
We investigated the clinical, laboratory, and genetic spectra in Korean patients with dysferlinopathy to clarify its genotype-phenotype correlation. We retrospectively reviewed 101 patients from 96 unrelated families with pathogenic variants of DYSF. The most common initial phenotype was Miyoshi myopathy in 50 patients. Median ages at examination and symptom onset were 23 [interquartile range (IQR): 18-30] and 36 years [IQR: 27-48], respectively. We observed 38 variants, including nine novel variants. Four variants (c.2494C > T, c.1284 + 2 T > C, c.663 + 1G > C, and c.2997G > T) in DYSF accounted for 62% of total allele frequencies of pathogenic variants. To analyze the genotype-phenotype correlation, we compared the clinical phenotype between patients with null/null (N/N; n = 55) and null/missense variants (N/M; n = 35). The N/N group had an earlier symptom onset age (median: 20 years [IQR: 17-25]) than the N/M group (median: 29 years [IQR: 23-35], p < .001). Total manual muscle testing scores in lower extremities were lower in the N/N group (median: 80 [IQR: 56-92]) than in the N/M group (median: 89 [IQR: 78-98], p = .013). Our study is the first to report that null variants in DYSF result in an earlier symptom onset than missense variants.


RNA aptamers that specifically bind to the Ras-binding domain of Raf-1.
RNA aptamers that bind to the Ras-binding domain (RBD) of a proto-oncogene product, Raf-1, were isolated from a pool of random sequences using a glutathione S-transferase-fused RBD (GST-RBD). The RNA molecules bind to the GST-RBD, but not to GST, with dissociation constants of about 300 nM. In contrast, these RNA aptamers do not bind to the Ras-binding domain of the RGL protein, which is also known to be activated by Ras. The aptamers actually compete with Ras for binding to the Raf-1 RBD. The anti-Raf-1 aptamers may be used to specifically inhibit the Ras-Raf interaction in the complicated signaling network in mammalian cells.


Forward osmosis treatment of effluents from dairy and automobile industry - results from short-term experiments to show general applicability.
Forward osmosis (FO) is a potential membrane technology to treat wastewater energy efficiently with low fouling. In laboratory-scale experiments, six effluents from a dairy and an automobile production plant were tested to find out if FO is an applicable treatment technology. Permeate flux and reverse salt flux were determined in nine test series with three subsequent 5 h experiments each. In between, the membrane was cleaned with deionized water. Membrane performance tests before each experiment were used to monitor membrane performance and fouling. Samples were analysed and the T/M-value was introduced to indicate which substances caused fouling. Dairy cheese brine was a suitable DS. Here, permeate fluxes were 21.0 and 15.1 L/(m²·h). Automobile cooling tower water and wastewater from cathodic dip painting were also used as DS. However, permeate fluxes were below 1.1 L/(m²·h). The tested FS, reverse osmosis concentrate from dairy wastewater treatment, rinsing water and wastewater from automobile cathodic dip painting, as well as wastewater from automobile paint shop pre-treatment, showed good performance regarding the permeate flux of between 7.9 and 19.4 L/(m²·h). Membrane performance test showed that some of the effluents lead to permeate flux reduction due to fouling. Different cleaning-in-place methods were examined. Eventually, permeate flux was restored.


Spermidine is bound to a unique protein in early sea urchin embryos.
Spermidine is rapidly taken up and becomes bound to protein during the very early hours of sea urchin embryogenesis. During the first 6 hr after fertilization of freshly obtained sea urchin eggs (Strongylocentrotus purpuratus), which are incubated in the presence of exogenous [3H]-spermidine, up to 7% of the total cell-associated spermidine appears uniquely as spermidine bound in macromolecular form. This unique protein containing spermidine migrates as a single radioactive band in gel electrophoresis. It has a Mr of approximately equal to 30,000 and is readily distinguishable from the protein initiation factor eIF-4D, which has a Mr of 18,000, the only other identifiable protein known to date to be posttranslationally modified by polyamines.


Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience.
Parotid neoplasms are usually solitary and multiple tumours occurring in an individual are uncommon. The incidence and implications of multiple synchronous and metachronous tumours remains relatively unknown. We reviewed the case notes of 606 patients who had parotidectomies for neoplastic lesions over a 30 year period and identified 30 patients (5%) with multiple primary tumours. There were 24 patients with synchronous tumours and 6 with metachronous tumours. Sixteen of the synchronous tumours (67%) were ipsilateral, whereas all six metachronous tumours were contralateral. Preoperative examination was effective at detecting bilateral tumours but poor at detecting multiple ipsilateral tumours. Multiple tumours were likely to be of the same histology (n=24, 80%) and Warthin's was by far the most common multiple tumour. Ipsilateral tumours of differing histological types and identical tumours other than Wartin's were uncommon. All but one patient had superficial parotidectomies and there were no recurrences.


Effect of UV exposure and beta-carotene supplementation on delayed-type hypersensitivity response in healthy older men.
The aims of this study were to determine if ultraviolet light (UV) is immunosuppressive in healthy older males, if beta-carotene (betaC) supplementation could prevent any observed UV-induced immunosuppression, and to compare these effects with those observed previously in younger men. The study was a placebo-controlled, randomized trial that employed a 2 x 2 factorial design. Healthy older men (mean age 65.5 years) received 30 mg betaC or placebo daily throughout the 47-day trial, while on a low carotenoid diet. After 28 days, half of each group received 12 suberythemic exposures to UV over a 16-day period. Delayed-type hypersensitivity (DTH) tests and plasma carotenoid assays were performed at baseline, pre-UV and post-UV time points, with DTH testing performed on an area of skin protected from UV exposure. UV exposure resulted in significantly suppressed DTH response in the placebo group but not in the betaC-UV group. While there was no significant interaction between betaC supplementation and UV on DTH response, there was a significant inverse relationship between final plasma betaC concentration and extent of UV-induced suppression of DTH response. A similar correlation existed among subjects not exposed to UV. Suberythemic UV exposure was immunosuppressive, as measured by DTH response, in healthy older men as in younger men. Higher plasma betaC was significantly associated with maintenance of DTH response, although the extent of protective effect of betaC appeared less than previously observed in younger subjects. The attenuated effect of betaC in the older UV-exposed subjects may have resulted in part from muted plasma betaC responses to betaC supplementation and/or higher plasma vitamin E levels than those of younger men. The finding that stronger DTH responses were associated with higher plasma betaC concentrations in both UV and non-UV subjects further supports a role for this nutrient in immunomodulation.


Novel single-stranded, circular DNA virus identified in cats in Japan.
We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. FeSCV is a circular DNA virus containing a genome with a total length of 2,046 nt encoding 2 open reading frames. Phylogenetic analyses indicated that FeSCV is classified into a clade different from that of circovirus and cyclovirus. Since the FeSCVs detected in several cats in the same household had genetically similar genomes, these viruses are most likely derived from the same origin.


Development of a procedure for the determination of perfluorocarboxylic acids in sediments by pressurised fluid extraction, headspace solid-phase microextraction followed by gas chromatographic-mass spectrometric determination.
A procedure for the determination of perfluorocarboxylic acids (i.e. PFC7-10A) in sediment by pressurized fluid extraction (PFE), derivatization, headspace solid-phase microextraction and GC-MS determination in the negative ion chemical ionisation mode was developed. The PFE extraction variables such as solvent composition, number and time per extraction cycle, and extraction temperature were optimised. In the optimum extraction conditions, recoveries exceeding 95% with a limit of detection and RSDs of 0.5-0.8 ng g(-1) and 15.5-16.8%, respectively, were obtained. The developed analytical procedure was applied to harbour sediments where PFC8A and PFC10A were detected for the first time at low ppb concentrations (i.e. 8-11 ng g(-1).


Nuclear migration, nucleokinesis and lissencephaly.
During the past 20 years, biologists have become used to finding that proteins first identified in simple, genetically manipulable eukaryotic organisms are conserved in higher eukaryotes. This article draws attention to the similarity between NUDF protein, which is required for nuclear migration in the filamentous fungus Aspergillus nidulans, and a mammalian homologue, LIS1, whose malfunction causes lissencephaly, a neuronal migration disease. The authors suggest that there might be an underlying similarity of mechanism between nuclear migration in the fungus and neuronal migration in the brain.


[Machine output of standardized operation reports. Rationatlization by means of small computers (author's transl)].
Report on measures of rationalization in daily surgery by using the small computer C8205 for printing of standardized operation reports. Description of the questionnaire, explanation of the machine programme and the organisational process in making the operation reports.


Ranolazine: clinical applications and therapeutic basis.
Ranolazine is currently approved for use in chronic angina. The basis for this use is likely related to inhibition of late sodium channels with resultant beneficial downstream effects. Randomized clinical trials have demonstrated an improvement in exercise capacity and reduction in angina episodes with ranolazine. This therapeutic benefit occurs without the hemodynamic effects seen with the conventional antianginal agents. The inhibition of late sodium channels as well as other ion currents has a central role in the potential use of ranolazine in ischemic heart disease, arrhythmias, and heart failure. Despite its QTc-prolonging action, albeit minimal, clinical data have not shown a predisposition to torsades de pointes, and the medication has shown a reasonable safety profile even in those with structural heart disease. In this article we present the experimental and clinical data that support its current therapeutic role, and provide insight into potential future clinical applications.


Contributions of diurnal and nocturnal insects to the pollination of common milkweed (Asclepias syriaca L.) in a pollen-limited system.
Milkweed (Asclepias syriaca L.: Asclepiadaceae) flowers exposed only to diurnal pollinators (primarily bumble bees, Bombus spp.) matured about eight times as many pods as did flowers exposed only to nocturnal visitors (moths). Rates of pollinaria removal and pollinia insertion were similarly higher during the day than at night. Moths deposited a much lower proportion of their pollinia in stigmatic chambers (one-fifth) than did diurnal pollinators. In spite of the poor service provided by nocturnal pollinators, flowers produced four times as much nectar at night as at day, and sugar production (sucrose equivalents) at night was twice that of the daytime.Supplemental hand pollinations doubled the production of mature pods, indicating normal pollinia limitation. Mature pod production of clones within a 5-km diameter varied between 0.1 and 3.5 per flowering stem, and numbers of pollinia vectors at these clones were closely correlated with numbers of mature pods produced.Pollinia-limited clones should thus attract both diurnal and nocturnal pollinators, if costs are not too extreme. Pollinia-limitation should decrease selection for pollinator specialization, especially if the relative importance of different pollinators varies over time, as in this study.


An alternative conditioning regimen for induction of specific skin graft tolerance across full major histocompatibility complex barriers.
Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose total body irradiation (TBI; 3-6 Gy) and allogeneic bone marrow cells. An alternative cytoreductive strategy that is well-recognized in bone marrow transplantation, but has not been evaluated extensively in organ allograft recipients, involves the use of a combined chemotherapeutic drug treatment. The present data show that conditioning with low dose TBI, in a MHC-disparate donor-recipient combination, can be successfully substituted by a combined single low-dose dimethyl myleran (DMM)/cyclophosphamide (CY) therapy, resulting in both stable, mixed chimerism and specific skin graft tolerance.