Nucleotide sequence analysis of equine infectious anemia virus proviral DNA.
The nucleotide sequence of the integrated form of the genome of the equine infectious anemia virus was determined. By comparison with LTR sequences of other retroviruses, signals for the control of viral gene transcription and translation could be identified in the EIAV LTR. Open reading frames for gag and pol genes were identified and their sequences matched very closely to those determined previously by others. However, in the present study, the pol gene reading frame was open throughout its entire length. The open reading frame for the env gene product was constructed from the sequences of two independent EIAV clones. Thus, a noninfectious genomic-length clone was shown to contain a frameshift mutation approximately in the middle of the presumed env gene coding sequence, whereas the sequence of another clone was open in this region. The deduced amino acid sequences of the EIAV gag and pol products showed closer evolutionary relationships to those of known lentiviruses than to other retroviruses. There was also partial sequence homology between predicted env gene products of EIAV, visna virus, and HTLV-III/LAV. Sequences analogous to the sor region of other lentiviruses could not be identified in our EIAV clone. A short open reading frame at the 3' end of the genome that overlapped env but not the 3' LTR was present but lacked significant sequence similarity to the 3' open reading frames of other lentiviruses. Thus, the sequence and general structure of EIAV most closely resemble those of known lentiviruses.


[Serologic diagnosis and epidemiology of acute delta hepatitis in Indre-et-Loire].
A 6 years retrospective study (1981-1986) of 153 consecutive cases of HBsAg positive acute hepatitis was carried out to assess the prevalence of delta virus infections in the Indre-et-Loire a district of the Loire Valley in France. Diagnostic value of the various serum markers of delta infection, i. e. HDAg, anti-HD and anti-HD IgM, were evaluated using immunoenzyme assays. During the survey, 22 cases of delta hepatitis were diagnosed (12 co-infections, 10 superinfections). They all involved young adults, 21 of them were drug-addicts, and one young woman was the consort of a drug-addict. In Indre-et-Loire, delta virus infection was responsible for half of acute HBsAg positive hepatitis among drug-users in the last 3 years of our study. Clinical and biological features of acute delta hepatitis were compared to those of the other HBsAg positive hepatitis: two cases of fulminant hepatitis occurred among the 12 co-infections; 4 of 6 superinfection that could be followed up to 6 months developed biopsy-proven chronic active hepatitis. Delta Ag was found constantly during the first week of the disease, its disappearance was always followed by a seroconversion to anti-HD after four weeks. Anti-delta IgM was an inconstant and late marker: it was detected within the first 4 weeks in only one case (a co-infection); it persisted only in superinfections. Our study shows that delta Ag is an efficient serum marker for the early diagnosis of acute delta hepatitis.


Oxilipin, a New Anti-cancer Phospholipase A2-like Protein from Iranian Caspian Cobra, Naja Naja Oxiana.
The discovery of novel anti-cancer agents from natural resources is highly necessary. Concerning the above problem, the purpose of this study was to discover an anti-cancer compound from Caspian cobra venom. Fractionation of Caspian cobra venom was performed by gel filtration and IEX chromatography. The results showed an anti-cancer protein nominated as Oxilipin. Activity and toxicity of Oxilipin were studied on the colon SW480 cancer cell line using MTT, LDH release, PI staining, morphological cell analysis, hemolysis, and anti-proliferation assays. Oxilipin, an 11kDa protein purified from the venom of the Caspian cobra. LC/MS/MS analysis of obtained protein showed homology with Phospholipase A2 from Naja naja oxiana. 40 µg/ml of Oxilipin can induce an apoptotic effect in SW480 cell line up to 90%; meanwhile, this amount can induce only one-third of cytotoxicity on a normal cell. In this study, Iranian cobra venom was found to have cytotoxic effects on SW480 colon cancer tumor cells, with the least cytotoxicity on normal cells on HEK-293. Given that Oxilipin has slight toxicity on normal cells, it can be hypothesized that the obtained peptide can be considered as a drug lead in an animal model study of colon cancer.


Antigen-induced histamine release from peripheral leukocytes of "Konnyaku asthmatic patients".
Histamine release from peripheral leukocytes of "Konnyaku asthmatic patients," patients with a unique occupational bronchial asthma in Japan, was measured after challenge with the antigen. There was an antigen concentration-dependent response with highly significant correlations between the maximal histamine release and the ratio of the radioallergosorbent test (RAST) of the antigen to human serum albumin. These results suggest that the histamine release test from peripheral leukocytes as well as RAST can be a useful diagnostic test in patients with bronchial asthma.


A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects.
Individuals with inclusion body myopathy type 3 (IBM3) display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K) in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in decreased in vitro motility, reduced muscle power output and focal myofibrillar disorganization similar to that seen in individuals with IBM3.


Pulpal response to the application of phosphoric acid to dentin.
Experimental cavities were prepared in forty-six clinically intact premolars of young individuals to evaluate the biologic effects of 50 per cent phosphoric acid etchant containing 7 percent zinc oxide by weight. The experimental periods ranged from 30 minutes to 150 days. The remaining dentin thickness varied from 1.8 to 3.5 mm. The teeth treated with the acid showed no more than a moderate pulpal response at the varying time periods. All of the acid-treated teeth demonstrated pulpal imflammation in the absence of clinical pain. Acid etchants should not be used on exposed or unprotected dentin surfaces.


Functionalized liposomes as drug nanocarriers for active targeted cancer therapy: a systematic review.
Cancer is a broad term used to describe a group of diseases that have more than 270 types. Today, due to the suffering of patients from the side effects of existing methods in the treatment of cancer such as chemotherapy and radiotherapy, the employment of targeted methods in the treatment of this disease has been received much consideration. In recent years, nanoparticles have revolutionized in the treatment of many diseases such as cancer. Among these nanoparticles, liposomes are more considerable. Active targeted liposomes show an important role in the selective action of the drug on cancer cells. Until now, a variety of anti-cancer agents have been reported for targeted delivery to cancer cells using liposomes. The results of in vitro and studies in vivo have been shown that selective action of the targeted liposomes is increased with reduced side effects and toxicity compared with free drugs or non-targeted liposomes. This systematic review expresses the reports of this type of drug delivery system. Search terms were searched through several online databases including PubMed, Scopus, and Science Direct from 1990 to 2019 and the quality evaluation was performed. Out of 11,676 published articles, 196 articles met the inclusion criteria. The current report reviews developments in the liposomes targeted with aptamer, transferrin, folate, and monoclonal antibodies.


Research progress on the forkhead box C1.
FOXC1 is a vital member of FOX families which play important roles in biological processes including proliferation, differentiation, apoptosis, migration, invasion, metabolism, and longevity. Here we are focusing on roles of FOXC1 and their mechanisms in cancers. FOXC1 promoted progress of many cancers, such as breast cancer (especially basal-like breast cancer), hepatocellular carcinoma, gastric cancer and so on. FOXC1 was also found to be associated with drug resistance of cancers. FOXC1 promoted metastasis of cancers by increasing expression of MMP7, NEDD9 and Snail. Proliferation and invasion of cancers were increased by FOXC1 by mediating NF-κB, MST1R and KLF4 expression. FOXC1 was associated with development by regulating expression of FGF19 and MSX1. Recently, FOXC1 was found to be required for niche of stem cells or development of stem cells by mediating expression of Gli2, CXCL12, SCF, NFATC1, BMP and Myh7. Overall, FOXC1 exerts its functions by many mechanisms and may be used as a potential biomarker for diseases.


[New concept of chronic kidney disease and blockade of renin-angiotensin system].
Chronic kidney disease (CKD) is increasingly recognized not only as a cause of end-stage renal disease but also as a cause of cardiovascular disease. Importantly, it is intimately associated with non-healthy lifestyles such as obesity, metabolic syndrome, hypertension, diabetes mellitus, smoking, and heavy drinking. To define CKD direct measurement of GFR or estimation of GFR (eGFR) is required. Japan Society of Nephrology is asking nationwide project to create "original" equation without using ethnic factor to obtain eGFR. Early detection and early treatment are vital to prevent not only CKD progression but also cardiovascular events. A comprehensive health education campaign and screening of the general populace are needed in order to detect CKD early. The control of hypertension, dyslipidemia, proteinuria, obesity, are intervention strategies that retard or prevent progression of CKD. Blockade of the renin-angiotensin system can be beneficial, especially if proteinuria is present.


The pediatric critical care nurse practitioner: evolution and impact.
This nonexperimental, descriptive pilot study evaluated the role and impact of two pediatric critical care nurse practitioners (PCCNPs) in the pediatric intensive care unit (PICU) at a tertiary care children's hospital. Questions posed included: 1) Are parents satisfied with the care their child and family received from the PCCNP in the PICU?; 2) Are staff nurses satisfied with the role of the PCCNP in the PICU?; and 3) Is there a difference between the care delivered by the PCCNP and the pediatric resident staff in nutritional management and discharge planning? Study methodology included a retrospective chart review of 25 PCCNP and 25 pediatric resident staff patient charts and a questionnaire survey of a convenience sample of parents and staff nurses over a 6-month study period. Overall, parents reported that the care their children received from the PCCNP was adequate. Staff nurses were satisfied with nurse practitioner (NP) care and supported the PCCNP role. There were no significant differences in the nutritional management of the children cared for by residents and PCCNPs. However, the PCCNPs initiated documentation of discharge planning with a greater frequency and earlier in the child's hospitalization, as compared to medical staff practice. Study findings support the use of the PCCNP in the PICU as care is comparable to that of the pediatric resident staff.


Arthroscopic release of the medial femoropatellar ligament for canine medial patellar luxation.
Five dogs of varying breeds and ages were presented for evaluation of medial patellar luxation that was unresponsive to conservative treatment. Arthroscopy of each affected stifle was performed, and adequacy of the femoral trochlea and patellar tracking in the trochlea were assessed. Medial femoropatellar ligament release was then performed using a bipolar radiofrequency electrosurgical system with or without a tibial tuberosity transposition. The procedure resulted in good to excellent outcomes for four dogs and a fair outcome for a fifth dog.


Sonography of Morel-Lavallee lesions.
The purpose of this series was to retrospectively characterize the sonographic appearance of posttraumatic Morel-Lavallée lesions. After Institutional Review Board approval was obtained, a search of the radiology information system database with correlation to medical records identified 21 posttraumatic fluid collections of the hip and thigh in 15 patients. Sonographic images were retrospectively reviewed by 1 author to characterize the echogenicity, homogeneity, shape, margins, location, compressibility, and vascularity of the fluid collection. Results were correlated with the age of the fluid collection and aspiration results where possible. All fluid collections (21/21) were located between the deep fat and fascia, with a shape that was fusiform in 12 (60%) of 20, flat in 5 (25%), and lobular in 3 (15%) (shape not determined in 1 case). Regarding echogenicity, 15 (71%) of the 21 collections were hypoechoic, and 6 (29%) were anechoic; 13 (62%) were heterogeneous, and 8 (38%) were homogeneous. The lobular fluid collections were all less than 2 weeks of age, and the flat fluid collections were all greater than 6 months of age. All homogeneous fluid collections were greater than 8 months of age. There was no relationship between the age of a fluid collection and its echogenicity. Conclusions. Morel-Lavallée lesions had a variable appearance, being more homogeneous and flat or fusiform in shape with a well-defined margin as the lesions aged. All Morel-Lavallée lesions were hypoechoic or anechoic, compressible, and located between the deep fat and overlying fascia.


Biological activities of interleukins and colony-stimulating factors.
The complementary DNAs encoding interleukins (interleukins 1, 2, 3, 4, 5 and 6) and colony-stimulating factors (granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors) have been cloned. These DNA clones have allowed the large-scale production of recombinant forms of these cytokines and the extensive studies of their biological activities. These advances have led to a much better understanding of the role of these cytokines in regulation of immune responses and hematopoiesis, and have clarified that these cytokines have multiple effects on various types of cells.


Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial.
CCR2 is a chemokine receptor expressed by monocytes, macrophages, and a subset of T cells. Its ligand, CCL2 (monocyte chemotactic protein 1), is abundantly present in the synovium of patients with rheumatoid arthritis (RA). Blocking CCR2 prevents CCL2-mediated chemotaxis in vitro and modulates arthritis in animal models of RA. In this study we examined the effects of CCR2 blockade on synovial inflammation in RA. The study was designed as a phase IIa clinical trial with a human CCR2 blocking antibody (MLN1202) in patients with active RA. Thirty-two patients received 3 infusions, over a period of 6 weeks, with either placebo (n = 9) or anti-CCR2 monoclonal antibody at 0.5 mg/kg (n = 7), 1.5 mg/kg (n = 7), or 4.0 mg/kg (n = 9). Safety was monitored with laboratory tests, immunotoxicity assessments, and documenting of adverse events, and European League Against Rheumatism and American College of Rheumatology response criteria were used to assess clinical improvement. Synovial tissue was obtained at baseline and after 43 days of treatment, for pharmacodynamic analysis using immunohistochemistry and digital image analysis. The Kruskal-Wallis test was used to compare groups, and the Wilcoxon signed rank test was used to assess changes within the groups. All patients completed the study. Treatment with CCR2 blocking antibody reduced the levels of free CCR2 on CD14+ monocytes by at least 57% and up to 94% (P < 0.001), demonstrating the biologic activity of the compound. However, there was no reduction in the levels or expression of any of the synovial biomarkers. Accordingly, no clinical improvement was observed. Treatment with anti-CCR2 blocking antibody did not result in amelioration of synovial inflammation in active RA. The results do not support the notion that blockade of CCR2 may be sufficient to induce clinical improvement in RA.


[Polycyclic aromatic hydrocarbons exposure and birth defects].
Birth defects are one of the most common adverse birth outcomes, which create a heavy economic burden to the country, society and family. And they are also one of the biggest problems facing public health today. Polycyclic aromatic hydrocarbons (PAHs) are a group of toxic pollutants existing in the environment widely, resulting from incomplete organic matter combustion, and can be taken into the body through various ways including the digestive tract, respiratory tract and so on. Recent researches suggest that the exposure of PAHs may be associated with various birth defects, while the special mechanism isn't very clear. This paper is a review of the relationship between PAHs and birth defects from the aspects of epidemiological data, experimental evidence on animals, which indicates that exposure of PAHs during pregnancy may be associated with birth defects including congenital heart defects, neural tube defects and cleft lip/plate. Furthermore, we explored the possible mechanism, including oxidative stress, oxidative damage and the changes of signal transduction pathway in order to provide some recommendations and suggestions on the future work.


Heavy-Ion Carbon Radiation Regulates Long Non-Coding RNAs in Cervical Cancer HeLa Cells.
Improving the effects of radiotherapy, such as heavy ion radiation, is currently a research priority for oncotherapy. Long non-coding RNAs (lncRNAs) are a subtype of noncoding RNAs involved in the therapeutic response to tumor radiotherapy. However, little is known about the variations in lncRNAs that occur after heavy ion radiation therapy. In this study, we established two kinds of Agilent Human lncRNA arrays and examined the effects of heavy ion radiation and X-ray irradiation on HeLa cells. We compared the differences in lncRNA expression (>=2-fold changes) between cells treated with the two types of radiation and control cells and identified 504 lncRNAs and 285 mRNAs that were differentially expressed. Among these lncRNAs, TCONS-00009910 was the most highly up-regulated lncRNA, while NONHSAT060631 was the most down-regulated lncRNA in both groups. To validate these sequencing data, RT-PCR was performed, and similar findings were obtained. GO and KEGG pathway analyses were employed to probe the potential functions of the affected lncRNAs. Numerous lncRNAs were changed after radiation exposure, showing that they may have important functions in the response to tumour radiotherapy. The present findings may help to elucidate the mechanism by which lncRNAs affect the clinical responses of cancer to radiation and may provide potential diagnostic and therapeutic targets for cancer therapy.


Analytical Inverse Optimization in Two-Hand Prehensile Tasks.
The authors explored application of analytical inverse optimization (ANIO) method to the normal finger forces in unimanual and bimanual prehensile tasks with discrete and continuously changing constraints. The subjects held an instrumented handle vertically with one or two hands. The external torque and grip force changed across trials or within a trial continuously. Principal component analysis showed similar percentages of variance accounted for by the first two principal components across tasks and conditions. Compared to unimanual tasks, bimanual tasks showed significantly more frequent inability to find a cost function leading to a stable solution. In cases of stable solutions, similar second-order polynomials were computed as cost functions across tasks and condition. The bimanual tasks, however, showed significantly worse goodness-of-fit index values. The authors show that ANIO can be used in tasks with slowly changing constraints making it an attractive tool to study optimality of performance in special populations. They also show that ANIO can fail in multifinger tasks, likely due to irreproducible behavior across trials, more likely to happen in bimanual tasks compared to unimanual tasks.


[Study on regularity of Tibetan medicine in treatment of gZav-Grib disease (apoplexy sequelae) based on HIS clinical medical records].
This research is launched to look for the medication rules and characteristics of Tibetan medicine in the treatment of gZav-Grib( apoplexy sequelae). HIS records of gZav-Grib patients were selected from the Tibetan Hospital of Tibet Autonomous Region and Tibetan Hospital of the city of Naqu. SPSS Modeler,Gephi and other data mining and visualization software were used to study the actual law of drug use in the treatment of gZav-Grib in Tibetan medicine. Finally,479 cases of gZav-Grib patients in Tibetan medicine were included. Their average age is 63 and average hospital stay was 32 days. In total,82 Tibetan medicine prescriptions were used for treating gZav-Grib. The frequency in the front is Twenty-flavor Chenxiang Pills( 338 times),Ruyi Zhenbao Pills( 322 times),and Seventy-flavor Zhenzhu Pills( 315 times). According to the regularity of Tebitan medicine,they were applied in different time periods including the early morning,morning,noon,and evening,for example,in the early morning: Seventy-flavor Zhenzhu Pills,morning: Ruyi Zhenbao Pills,noon: Eighteen-flavor Dujuan Pills,evening: Twenty-flavor Chenxiang Pills. In the clinical joint,18 groups were found in the 10% support and 70% confidence. There are two prescriptions confidence more than 80% which nature focus on Gan,Ruan,Xi,Liang,Dun,Han,Wen. gZav-Grib of Tibetan medicine can be divided into two types: r Lung-Grib type and k Hrag-Grib type,in which the medicine of r Lung-Grib type takes Seventy-flavor Zhenzhu Pills as the core prescription,while the medicine of k Hrag-Grib type takes Ruyi Zhenbao Pills as the core prescription. It is found that the treatment of gZav-Grib by Tibetan medicine is mainly dominated by the treatment idea about " Therapeutic r Lung and blood,Consideration of venous diseases". Treatment functions is promoting the circulation of Qi,clearing blood heat and getting rid of bad blood,achieving the purpose of treating both principal secondary aspect of gZav-Grib. The research methods based on the HIS can't only optimize the Tibetan treating gZav-Grib sequela treatment plan and rule of medication,but also provide the scientific basis for Tibetan medicine treat gZav-Grib.


Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread.
Two variants of equine infectious anemia virus (EIAV) that differed in sensitivity to broadly neutralizing antibody were tested in direct competition assays. No differences were observed in the growth curves and relative fitness scores of EIAVs of principal neutralizing domain variants of groups 1 (EIAV(PND-1)) and 5 (EIAV(PND-5)), respectively; however, the neutralization-resistant EIAV(PND-5) variant was less infectious in single-round replication assays. Infectious center assays indicated similar rates of cell-to-cell spread, which was approximately 1,000-fold more efficient than cell-free infectivity. These data indicate that efficient cell-to-cell spread can overcome the decreased infectivity that may accompany immune escape and should be considered in studies assessing the relative levels of fitness among lentivirus variants, including HIV-1.


Primary lacrimal canaliculitis - A clinical entity often misdiagnosed.
Primary lacrimal canaliculitis (PLC) is a unique disorder which often gets misdiagnosed by the general as well as speciality-trained ophthalmologists. Elderly patients with history of chronic or recurrent epiphora with discharge, often get mislead towards chronic dacryocystitis. The aim of our report is to discuss the misleading diseases in our PLC patients and to revisit this hidden disease. The patients of PLC who were previously misdiagnosed were studied. The clinical history, presenting clinical features, misdiagnosis, and final management of the patients is described. There were 5 misdiagnosed female patients. A history of chronic redness, watering, discharge, and medial canthal region edema lead to the misdiagnosis of chronic dacryocystitis in 3 (60%) and medial marginal chalazion in 2 (40%) cases. Slit-lamp examination revealed localized hyperemia (n = 5), classical pouting of lacrimal punctum (n = 3), and expressible purulent discharge (n = 3). Two patients without punctum pouting had an explicit yellowish hue/discoloration of the canalicular region. Our patients had a mean 4 visits before an accurate diagnosis. Three-snip punctoplasty with canalicular curettage was performed in three while two were managed conservatively. At last follow-up, all patients were symptom-free with punctum and canalicular scarring in three, who underwent surgery. PLC is a frequently misdiagnosed clinical entity which delays the initiation of appropriate treatment. A succinct magnified examination of punctum and canalicular region can provide sufficient clues pivotal for accurate diagnosis.


uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection.
Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery.


MicroRNAs in metal stress: specific roles or secondary responses?
In plants, microRNAs (miRNAs) control various biological processes by negatively regulating the expression of complementary target genes, either (1) post-transcriptionally by cleavage or translational inhibition of target mRNA, or (2) transcriptionally by methylation of target DNA. Besides their role in developmental processes, miRNAs are main players in stress responses, including metal stress responses. Exposure of plants to excess metal concentrations disturbs the cellular redox balance and enhances ROS accumulation, eventually leading to oxidative damage or signaling. Plants modify their gene expression by the activity of miRNAs in response to metal toxicity to regulate (1) complexation of excess metals, (2) defense against oxidative stress and (3) signal transduction for controlling various biological responses. This review focuses on the biogenesis, working mechanisms and functioning of miRNAs in plants. In a final part, our current knowledge on the regulatory roles of miRNAs in plant metal stress responses is highlighted, and whether stress-regulated miRNAs have specific roles or are secondary consequences is discussed.


Conditional probability calculations for the nonlinear Schrödinger equation with additive noise.
The method for the computation of the conditional probability density function for the nonlinear Schrödinger equation with additive noise is developed. We present in a constructive form the conditional probability density function in the limit of small noise and analytically derive it in a weakly nonlinear case. The general theory results are illustrated using fiber-optic communications as a particular, albeit practically very important, example.


Unraveling a municipal effluent's toxicity to Tripneustes gratilla sperm fertilization.
A tiered investigative approach was employed to characterize and identify substances responsible for the persistent toxicity of a primary-treated municipal effluent to gametes of the Hawaiian sea urchin, Tripneustes gratilla. Toxicity identification evaluation (TIE) procedures from the US Environmental Protection Agency were modified to account for the tolerance of T. gratilla gametes to various sample manipulations. Microtox rapid toxicity screening was applied in some aspects of the study after verifying a correlation between the pattern of toxic responses of T. gratilla gametes and that of the bioluminescent bacteria Vibrio fischeri. Toxicity identification evaluation phase I manipulations revealed a toxicity profile implicating surfactants as possible toxicants, and TIE phase II toxicity assessment of isolated fractions coupled with colorimetric surfactant analyses confirmed the possible role of surfactants in effluent toxicity. The toxic effects of standard reference surfactants on T. gratilla fertilization indicated a concordance with the effects of the more nonpolar effluent fractions. Treatability studies showed that biodegradation by activated sludge eliminated effluent toxicity to urchin gametes.


Systematic review--a method for nursing research.
This article by Arja Holopainen, Tuovi Hakulinen-Viitanen and Kerttu Tossavainen explains the five stages of the systematic review process and describes how this method was applied to an analysis of studies dealing with nurse 'teacherhood'. The authors argue that systematic review is an excellent method for summarising research knowledge and for highlighting evidence significant for nursing, nursing education and nursing research.


Disturbance of Antioxidant Enzymes and Purine Metabolism in the Ejaculate of Men Living in Disadvantaged Areas of Kyzylorda Region.
Objective of the study was to evaluate the state of the main indicators of antioxidant status and enzymes of purine metabolism in the germ cells of men living in the zone of ecological catastrophe Aral Sea region. The criterion for inclusion is the stay of an adult in the Aral Sea area is not less than 5 years, employment in occupations with no more than 2 hazard class. Determination of the activity of adenosine deaminase (ADA) was conducted in semen by the method of Nemechek et al., 1993. Determination of the activity of catalase (CAT) was performed according by the method of Korolyuk et al., 1988. Results of the study indicate a change in the activity of catalase and adenosine deaminase, due to increased levels of oxidative stress and the development of the pathological process. According to the results of study, it was put the influence of negative factors of the Aral Sea region in men's sperm of reproductive age gives to disability free-radical processes, that proves changing of ferments of ant oxidative protection Catalase and adenosine deaminase (ADA). This disturbance in men's sperm of reproductive age leading to increased level of oxidative stress and impaired activity of antioxidant enzymes and purine metabolism, responsible for the abnormal transmembrane and intracellular processes, reflecting the degree of imbalance of enzymes.


Core curriculum in emergency medicine integrated in the specialty of anaesthesiology.
Anaesthesiologists, for their knowledge, skills and expertise, have been playing a key role in the development of emergency medicine. In many countries, anaesthesiologists are today fully involved in teaching and practicing emergency medicine, and have leading roles in emergency departments. Proper education and effective interdisciplinary medical cooperation is essential for quality assurance in emergency medicine. This paper, produced by a working party of the European Board of Anaesthesiology of the European Union of Medical Specialists (EUMS/UEMS), gives directions for a core curriculum in emergency medicine integrated in the specialty of anaesthesiology.


The role of PFC networks in cognitive control and executive function.
Systems neuroscience approaches with a focus on large-scale brain organization and network analysis are advancing foundational knowledge of how cognitive control processes are implemented in the brain. Over the past decade, technological and computational innovations in the study of brain connectivity have led to advances in our understanding of how brain networks function, inspiring new conceptualizations of the role of prefrontal cortex (PFC) networks in the coordination of cognitive control. In this review, we describe six key PFC networks involved in cognitive control and elucidate key principles relevant for understanding how these networks implement cognitive control. Implementation of cognitive control in a constantly changing environment depends on the dynamic and flexible organization of PFC networks. In this context, we describe major empirical and theoretical models that have emerged in recent years and describe how their functional architecture and dynamic organization supports flexible cognitive control. We take an overarching view of advances made in the past few decades and consider fundamental issues regarding PFC network function, global brain dynamics, and cognition that still need to be resolved. We conclude by clarifying important future directions for research on cognitive control and their implications for advancing our understanding of PFC networks in brain disorders.


Transcriptome Analysis of Early Responsive Genes in Rice during Magnaporthe oryzae Infection.
Rice blast disease caused by Magnaporthe oryzae is one of the most serious diseases of cultivated rice (Oryza sativa L.) in most rice-growing regions of the world. In order to investigate early response genes in rice, we utilized the transcriptome analysis approach using a 300 K tilling microarray to rice leaves infected with compatible and incompatible M. oryzae strains. Prior to the microarray experiment, total RNA was validated by measuring the differential expression of rice defense-related marker genes (chitinase 2, barwin, PBZ1, and PR-10) by RT-PCR, and phytoalexins (sakuranetin and momilactone A) with HPLC. Microarray analysis revealed that 231 genes were up-regulated (>2 fold change, p < 0.05) in the incompatible interaction compared to the compatible one. Highly expressed genes were functionally characterized into metabolic processes and oxidation-reduction categories. The oxidative stress response was induced in both early and later infection stages. Biotic stress overview from MapMan analysis revealed that the phytohormone ethylene as well as signaling molecules jasmonic acid and salicylic acid is important for defense gene regulation. WRKY and Myb transcription factors were also involved in signal transduction processes. Additionally, receptor-like kinases were more likely associated with the defense response, and their expression patterns were validated by RT-PCR. Our results suggest that candidate genes, including receptor-like protein kinases, may play a key role in disease resistance against M. oryzae attack.


High prevalence of pathogenic Eimeria spp. and the main risk factors associated with infection in goats from a semiarid region of Northeastern Brazil.
This study aimed to analyze the epidemiology of infections caused by Eimeria spp. in goats bred in an extensive production system in Northeast Brazil. To this end, an epidemiological survey was performed, wherein 350 fecal samples were collected from goats ranging from 3 months to 8 years old across 30 farms. The number of oocysts per gram of feces (OPG) was counted using the Mini-FLOTAC method. Species were identified based on their morphological and morphometric characteristics. Frequencies between animal categories were assessed using the chi-square test and known risk factors after multivariate analysis. Eimeria oocysts were found in 99.4% (346/348) of samples and 100% (30/30) of the farms. The OPG was influenced by the age of the animals; therefore, young goats (up to 6 months old) eliminated more oocysts (2302.6 + 5454.8) than adult goats (881.7 + 1551.5). Three pathogenic species were identified, with two demonstrating a high prevalence: Eimeria arloingi (88.83%) and Eimeria christenseni (44.7%), in addition to Eimeria caprina (3.72%). In the study, the habit of ground feeding and the use of cisterns as water sources were identified as risk factors, with odds ratios of 4.04 and 9.82, respectively. However, cleaning facilities at shorter intervals was a protective factor (OR = 0.19). We concluded that there was a high prevalence of Eimeria infection in goats bred in extensive production systems, even those in semiarid regions. This high prevalence can be attributed to the congregation of animals in shaded areas and the substantial accumulation of fecal matter at night.


Time-resolved observation of interatomic excitation-energy transfer in argon dimers.
The ultrafast transfer of excitation energy from one atom to its neighbor is observed in singly charged argon dimers in a time-resolved extreme ultraviolet (XUV)-pump IR-probe experiment. In the pump step, bound 3s-hole states in the dimer are populated by single XUV-photon ionization. The excitation-energy transfer at avoided crossings of the potential-energy curves leads to dissociation of the dimer, which is experimentally observed by further ionization with a time-delayed IR-probe pulse. From the measured pump-probe delay-dependent kinetic-energy release of coincident Ar+ + Ar+ ions, we conclude that the transfer of energy occurs on a time scale of about 800fs. This mechanism represents a fast relaxation process below the energy threshold for interatomic Coulombic decay.


The Italian Version of the Severe Respiratory Insufficiency Questionnaire.
The Severe Respiratory Insufficiency Questionnaire (SRI) is a multidimensional instrument for health-related quality of life (HRQL) assessment in patients with chronic respiratory failure (CRF). The SRI has originally been developed in German in 2003, but 15 translated versions have been created during the last 18 years with the exclusion of the Italian translation. The present project was aimed at creating an Italian version of the SRI. Professional forward-translation and back-translation procedures have been provided based on the original German version by independent translators, and this was followed by final reconciliation. The Italian SRI contains 49 items covering 7 different subscales which can summarize to one Summary Score. The Italian SRI is a multidimensional instrument, which can be used for HRQL assessment in Italian-speaking patients with CRF. Validation of the Italian version of the questionnaire is formally required in the future.


Proton Therapy for Locally Advanced Oropharyngeal Cancer: Initial Clinical Experience at the University of Washington.
Proton therapy can potentially improve the therapeutic ratio over conventional radiation therapy for oropharyngeal squamous cell cancer (OPSCC) by decreasing acute and late toxicity. We report our early clinical experience with intensity-modulated proton therapy (IMPT). We retrospectively reviewed patients with OPSCC treated with IMPT at our center. Endpoints include local regional control (LRC), progression-free survival (PFS), overall survival (OS), tumor response, and toxicity outcomes. Toxicity was graded as per the Common Terminology Criteria for Adverse Events v4.03. Descriptive statistics and Kaplan-Meier method were used. We treated 46 patients from March 2015 to August 2017. Median age was 58 years, 93.5% were male, 67% were nonsmokers, 98% had stage III-IVB disease per the 7th edition of the AJCC [American Joint Committee on Cancer] Cancer Staging Manual, and 89% were p16 positive. Twenty-eight patients received definitive IMPT to total dose of 70 to 74.4 Gy(RBE), and 18 patients received postoperative IMPT to 60 to 66 Gy(RBE) following transoral robotic surgery (TORS). Sixty-four percent of patients received concurrent systemic therapy. There were no treatment interruptions or observed acute grade 4 or 5 toxicities. Eighteen patients had percutaneous endoscopic gastrostomy (PEG) tube placement; the majority (14) were placed prophylactically. The most common grade 3 acute toxicities were dermatitis (76%) and mucositis (72%). The most common late toxicity was grade 2 xerostomia (30%). At a median follow-up time of 19.2 months (interquartile range [IQR], 11.2-28.4), primary complete response was 100% and nodal complete response was 92%. One patient required a salvage neck dissection owing to an incomplete response at 4 months. There were no recorded local regional or marginal recurrences, PFS was 93.5%, and OS was 95.7%. Our early results for IMPT in OPSCC are promising with no local regional or marginal recurrences and a favorable toxicity profile. Our data add to a body of evidence that supports the clinical use of IMPT. Randomized comparative trials are encouraged.


[Assessment of consumer exposure to chemical agents on the example of the ConsExpo model].
Not only employees in industrial plants but also consumers, by using finished products, are exposed to chemical substances. Therefore, consumer exposure assessment is also important. To assess the risk for the consumer, the exposure magnitude is needed but measuring these values in residential conditions of consumers is usually impossible. ConsExpo has been designed to facilitate the exposure assessment to substances in consumer products. It is available in English as a free web application at www. consexpoweb.nl. The ConsExpo Web tool, developed by the Netherlands National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu), contains a set of models that help in the assessment of exposure to the substances in consumer products. These are mathematical models with increasing complexity, describing exposure by inhalation, dermal and oral routes. Available models are described in this work. ConsExpo is also equipped with a products database with defined exposure scenarios and default values, which could be a starting point for the models. The aim of this work was to review the literature regarding ConsExpo and to present the application to Polish users through the description of the models contained therein and by providing assessments examples. The review was based on databases of scientific journals. ConsExpo is a commonly known tool, and one of its applications is exposure estimation in comparative studies and the development of new models. For lower-tier analyses ConsExpo can be used by less advanced users. The most favorable for Polish users would be the creation of the Polishlanguage version of the ConsExpo application or a detailed Polish-language instruction manual. Med Pr. 2019;70(6):747-62.


[The use of drinking mineral water and low-intensity electromagnetic radiation at an early stage of metabolic syndrome development (experimental study)].
To reveal the features of adaptive metabolic development, light-optical and ultrastructural reactions under the combined action of drinking mineral water (MW) and low-intensity electromagnetic radiation (EMR) of ultrahigh frequency (UHF) at an early stage of development of the experimental metabolic syndrome. The study was performed on 28 non-linear male rats weighing 180-200 g. Animals of the experimental group on the background of a high-calorie diet received at first (from the 8th day of the experiment) a course of drinking sulfate MW (24 procedures), and after its completion - a course of low-intensity EMR UHF (12 procedures), daily, 2 minutes per lumbar region in the zone projections of the adrenal glands using the Aquaton-2 device (power flux density 1 μW/cm2, frequency 1000 MHz). Animals fed only a high-calorie diet served as controls; intact animals were also used. The objects of study were the liver, blood, thymus. Biochemical, histological, electron microscopic and morphometric research methods were used. The combined use of drinking MW and low-intensity UHF EMR contributed to the development of adaptive metabolic and regenerative processes: the level of glucose and high-density lipoproteins decreased in the blood, antioxidant activity clearly increased in the liver, the content of RNA, DNA and total protein increased, and the number of dystrophic and necrobiotic cells decreased. Strengthening of the processes of intracellular regeneration was manifested in an increase in the number of mitochondria, peroxisomes, as well as protein-synthesizing organelles - ribosomes and polysomes. Functional activity of the lysosomal system increased. The number of nuclei increased In thymus and specific activity of the thymocyte genome increased as well. The revealed effects were mainly due to the antioxidant, membrane stabilizing, detoxifying, and immunomodulatory effects of MW and UHF EMR. Based on the data obtained, it can be concluded that the combined use of drinking MW and low-intensity UHF EMR can be very promising in the light of the development of new approaches to the treatment and prevention of metabolic syndrome in the early stages of its development. To optimize the adaptive-protective and compensatory processes, more adequate modes of combined exposure to MW and UHF EMR should be used.


Interleukin-1 receptor antagonist prevents expression of the metalloproteinase-generated neoepitope VDIPEN in antigen-induced arthritis.
To investigate the relationship between occurrence of the matrix metalloproteinase-generated neoepitope VDIPEN and proteoglycan (PG) loss in arthritis, and to examine the role of interleukin-1 (IL-1) in VDIPEN expression. VDIPEN expression was investigated in murine antigen-induced arthritis by immunolocalization studies on joint sections. The involvement of IL-1 in VDIPEN expression was studied by blocking of IL-1 using IL-1 receptor antagonist (IL-1Ra). Profound PG loss was evident early in arthritis, without significant VDIPEN expression. Full expression of the neoepitope appeared after a few days, when PG depletion was severe, and disappeared at late stages when cartilage showed recovery from PG depletion. At sites where chondrocyte death occurred and cartilage did not recover from the initial cartilage depletion, VDIPEN expression remained present. Prophylactic IL-1Ra treatment of arthritic mice resulted in almost complete prevention of VDIPEN expression. However, IL-1Ra had only a minor effect on PG depletion, emphasizing that there is no correlation between VDIPEN and early PG depletion. This study indicates that IL-1 is involved in VDIPEN expression. Although VDIPEN-inducing metalloproteinases do not seem to be involved in early PG depletion during antigen-induced arthritis, metalloproteinase neoepitopes are present when PG depletion is severe.


[Structural characteristics of the hippocampus in various strains of rats and mice].
Original data together with those from literature are presented concerning structural peculiarities of the hippocamp in rats and mice. Structural differences are revealed not only in these species, but in separate strains from a single species. Fine structural differences may account for different modes of realization of the behavioural reaction.


[Tracing hepatitis C virus transmission by using high-throughput sequencing technique].
An approach for analysis of hepatitis C virus (HCV) quasispecies using Hiseq high-throughput sequencing (hereinafter referred to as Hiseq sequencing) technique was developed and then applied to investigate a possible case of HCV needle sharing transmission. One case of HCV antibody seroconversion (P1) was found in a methadone clinic on January 15, 2015. Four HCV antibody positive injecting drug users (IDUs), P2 to P5, suspected to be involved in needle sharing transmission with P1 during the period (after March 24, 2014) that P1 may be infected with HCV were investigated, and another 28 HCV antibody positive IDUs were selected as controls (C1 to C28). These controls came from the same methadone clinic or lived in the same town with P1. The RNAs were extracted from the plasma specimens and then reverse-transcribed into cDNA. After HCV subtyping, Hiseq sequencing was performed to detect and sequence the HCV quasispecies (263 bp) in the specimens with the same subtype as P1. The frequency of quasispecies was counted and ranked. Intrapersonal and interpersonal genetic distance and phylogenetic tree were calculated. The HCV subtype of specimen P1 was 3b. All the other specimens with the same subtype were P2, C7, C12, C14, C15, C16, C19, C20 and C28. Hiseq sequencing was successfully performed in 9 out of these 10 specimens, and 249 753 to 1 086 333 (average 869 608) cleaned sequences representing 3 to 172 (average 48) unique HCV quasispecies were obtained. The medians (P50) of intrapersonal genetic diversities from the 9 specimens were 0.4% to 12.3%. The P50 (P25, P75) of genetic diversities between P1 and the other 8 specimens were 19.0% (18.4%, 19.8%), 10.4% (2.8%, 18.3%), 19.6% (17.8%, 21.4%),24.9% (23.8%, 26.1%), 19.8% (18.7%, 20.7%), 20.1% (18.9%, 21.2%), 20.6% (20.0%, 21.1%), 23.6% (22.4%, 24.8%). There were no significant difference between the genetic diversities of P1 and P2 and those of P1 and other 7 specimens (H=9.40, P=0.100). The genetic diversities between few HCV quasispecies from P1 and few ones from C7 were 0. Phylogenetic tree analysis indicated that there was no HCV transmission relationship between P1 and P2, but there was HCV transmission relationship between P1 and C7. With the feature of high-throughput, easier operation and lower cost, Hiseq sequencing technique has high practical value in tracing HCV transmission at the quasispecies level.


Many-body green function of degenerate systems.
A rigorous nonperturbative adiabatic approximation of the evolution operator in the many-body physics of degenerate systems is derived. This approximation is used to solve the long-standing problem of the choice of the initial states of H(0) leading to eigenstates of H(0) + V for degenerate systems. These initial states are eigenstates of P(0)VP(0), where P(0) is the projection onto a degenerate eigenspace of H(0). This result is used to give the proper definition of the Green function, the statistical Green function and the nonequilibrium Green function of degenerate systems. The convergence of these Green functions is established.


Modelling the activated sludge flocculation process combining laser light diffraction particle sizing and population balance modelling (PBM).
A technique based on laser light diffraction is shown to be successful in collecting on-line experimental data. Time series of floc size distributions (FSD) under different shear rates (G) and calcium additions were collected. The steady state mass mean diameter decreased with increasing shear rate G and increased when calcium additions exceeded 8 mg/l. A so-called population balance model (PBM) was used to describe the experimental data. This kind of model describes both aggregation and breakage through birth and death terms. A discretised PBM was used since analytical solutions of the integro-partial differential equations are non-existing. Despite the complexity of the model, only 2 parameters need to be estimated; the aggregation rate and the breakage rate. The model seems, however, to lack flexibility. Also, the description of the floc size distribution (FSD) in time is not accurate.


Giant cystic lymphangioma in childhood: a rare differential for the acute abdomen.
Cystic lymphangiomata are rare benign tumours of childhood resulting from an abnormal development of the lymphatic system, most commonly arising in the head and axillary region. We report a case of haemorrhagic intra-abdominal cystic lymphangiomata presenting as an acute abdomen. A 5-year-old girl was admitted with low-grade fever, generalised abdominal pain and elevated inflammatory markers, and a clinical diagnosis of acute appendicitis was made. At operation, two large fluid-filled haemorrhagic cystic lesions were found to occupy most of the abdominal cavity. The lesions were completely excised and histological examination identified them as cystic lymphangiomata. This case report and literature review highlights aspects of the presentation which might have resulted in a preoperative diagnosis, which is seldom achieved.


[The application of evoked potentials to the evolutive control of continuous spike/wave epilepsy during slow wave sleep].
We studied 4 patients (14-21 years old) with continuous spike/wave epilepsy during slow wave sleep with visual evoked potentials (VEP) and somatosensory evoked potentials (SEP). All the patients presented the same focality and received the same medication (primidone plus sodium valproate). No case had another pathology not related with epilepsy which could alter the evoked potential findings. The results obtained in the initial evoked potentials were compared with those achieved after 5 years of treatment. In the initial study interhemispheric asymmetry in the latency of the early component (L.N1) of the SEP was observed with a mean of 10%. Five years later normal SEP were obtained with the asymmetry having disappeared thus leading to the deduction that the physiopathologic improvement found in these patients was due to the treatment of sodium valproate together with primidone.


Oxidative changes associated with beta-carotene and alpha-tocopherol enrichment of human low-density lipoproteins.
To determine what effects enrichment of human low-density lipoprotein (LDL) with combinations of alpha-tocopherol and beta-carotene would exert on LDL oxidation and attempt to define the nature of the effects. Human plasma was pooled and alpha-tocopherol and beta-carotene was added in a four-by-four design resulting in the enrichment of LDL with alpha-tocopherol and beta-carotene in varying concentrations. Enriched and control LDL was oxidized in Cu2+ mediated oxidation system and resistance of LDL to oxidation was determined by lag time, thiobarbituric acid reactive substances (TBARS) activity, and rate of oxidation. Increasing LDL alpha-tocopherol concentration had a linear relationship with lag time and a negative correlation with rate of oxidation. LDL beta-carotene concentration was linearly correlated with the rate of LDL oxidation and beta-carotene loss, and exponentially related to TBARS concentration. These results support earlier findings for the protective effect of a-tocopherol against LDL oxidation, and suggest that beta-carotene participates as a prooxidant in the oxidative degradation of LDL under these conditions. Since high levels of alpha-tocopherol did not mitigate the prooxidative effect of beta-carotene, these result indicate that increased LDL beta-carotene may cancel the protective qualities of alpha-tocopherol.


Paroxysmal bundle branch block of supraventricular origin: a possible source of misdiagnosis in detecting ventricular tachycardia using time domain analyses of intraventricular electrograms.
Current implantable antitachycardia devices use several methods for differentiating sinus rhythm (SR) from supraventricular tachycardia (SVT) or ventricular tachycardia (VT). These methods include sustained high rate, the rate of onset, changes in cycle length, and sudden onset. Additional methods for detecting VT include techniques based upon ventricular electrogram morphology. The morphological approach is based on the assumption that the direction of cardiac activation, as sensed by a bipolar electrode in the ventricle, is different when the patient is in SR as compared to VT. Whether paroxysmal bundle branch block of supraventricular origin (BBB) can be differentiated from VT has not been determined. In this study, we compared the morphology of the ventricular electrogram during sinus rhythm with a normal QRS (SRNIQRS) or SVT with a normal QRS (SVTNIQRS) with the morphologies of BBB and VT in 30 patients undergoing cardiac electrophysiology studies. Changes in ventricular electrogram morphology were determined using three previously proposed time domain methods for VT detection: Correlation Waveform Analysis (CWA), Area of Difference (AD), and Amplitude Distribution Analysis (ADA). CWA, AD, and ADA distinguished VT from SRNIQRS or SVTNIQRS in 16/17 (94%), 14/17 (82%), and 12/17 (71%) patients, and BBB from SRNIQRS or SVTNIQRS in 15/15 (100%), 13/15 (87%), and 6/15 (40%) patients, respectively. However, the ranges of values during BBB using these methods overlapped with ranges of values during VT in all cases for CWA, AD, and ADA. Hence, BBB may be a source of misdiagnosis in detecting VT when these time domain methods are used for ventricular electrogram analysis.


Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa.
Since identification of the genetic component in anorexia nervosa (AN), genes that partake in serotonergic and dopaminergic systems and in hormonal and weight regulation have been suggested as potential candidates for AN susceptibility. We propose another set of candidate genes. Those are genes that are involved in the signaling pathway using NMDA-R and SK channels and have been suggested as possible effectors of NMDA-R driven signaling. The role of NMDA-R in the etiology of schizophrenia has already been substantiated on various levels. Several studies based on population and family groups have implicated SK3 in schizophrenia and more recently in AN as well. Our study group consisted of 90 AN family trios. We examined the transmission of two potentially functional polymorphisms, 5073T>G polymorphism in the gene encoding the NR2B subunit of NMDA-R and CAG repeats in the coding region of SK3 channel gene. Using HHRR and TDT approaches, we found that both polymorphisms were preferentially transmitted to AN offspring (TDT yielded chi(2)=5.01, p=0.025 for NR2B 5073G alleles and chi(2)=11.75, p<0.001 for SK3 L alleles including >19 repeats). Distribution analysis of the combined NR2B/SK3 genotypes suggests that the contribution of both polymorphisms to AN risk is independent and cumulative (OR=2.44 for NR2B GG genotype and OR=3.01 for SK3 SL and LL genotypes, and OR=6.8 for the combined NR2B/SK3 genotypes including high-risk alleles). These findings point to the contribution of genes associated with the NMDA-R signaling pathway to predisposition and development of AN.


Diversity and structure of the microbial community in rhizosphere soil of Fritillaria ussuriensis at different health levels.
Fritillaria wilt is a kind of soil-borne disease that causes a large reduction in the yield of Fritillaria ussuriensis. The diversity and structure of the soil microbial community are important factors affecting the health of Fritillaria ussuriensis. The analysis of the microbial community in the diseased and healthy soils provided a theoretical basis for revealing the pathological mechanism and prevention of Fritillaria wilt disease. In the present study, we sequenced the soil microorganisms from healthy (H), pathology (P) and blank (B) soil samples by Illumina MiSeq. Determined the soil physicochemical properties respectively, analyzed the soil microbial diversity and structure, and constructed single factor co-correlation networks among microbial genera. The results showed that Ascomycota (48.36%), Mortierellomycota (23.06%), Basidiomycota (19.00%), Proteobacteria (31.74%), and Acidobacteria (20.95%) were dominant in the soil. The diversity of healthy soil was significantly greater than that of diseased soil samples (P and B) (P < 0.05). The populations of Fusarium and Humicola significantly increased in the diseased soil sample (P and B) (P < 0.05). RB41 (4.74%) and Arthrobacter (3.30%) were the most abundant genera in the healthy soil. Total nitrogen (TN), available nitrogen (AN), total potassium (TK), available potassium (AK), and inorganic salt (salt) were significantly correlated with soil microbial communities (P < 0.05). The relationship between fungi and the plant was mostly positive, whereas bacteria showed the opposite trend. In conclusion, the diversity and structure of the soil microbial community were closely related to the health level of Fritillaria ussuriensis. Fusarium and Humicola affect the severity of Fritillaria wilt disease, while RB41 and Arthrobacter are the important indicators for maintaining the health of Fritillaria ussuriensis. Moreover, environmental factors greatly affect the abundance and formation of soil microbial community. The interactions in microbial communities also influence the healthy growth of Fritillaria ussuriensis.


Cyclic AMP-receptor proteins in human salivary glands.
In mammalian species, cyclic AMP receptor proteins (cARP) are the regulatory (R) subunits of cyclic AMP-dependent protein kinase (PKA), the cellular effector of cyclic AMP-mediated signal transduction. An isoform of the PKA type II R subunit (RII), cARP, is a polyfunctional protein, present in most tissues and cells. It is expressed in salivary and other glands of rodents, and secreted into the saliva of rats and Man. The aim of the present study was to determine the expression of cARP in human salivary glands using immunoelectron microscopy. Thin sections of normal salivary glands embedded in LR Gold resin were labeled with anti-cARP primary antibody, then with gold-conjugated secondary antibody. Labeling was present in the secretory granules and cytoplasm of parotid, submandibular (SMG) and sublingual gland serous cells. Quantitative analysis showed considerable variability in granule labeling from sample to sample, indicating shifts in expression and cellular location of cARP. Unlike rodent salivary glands, the granules of intercalated and striated duct cells also were labeled. The cytoplasm and granules of mucous cells of the SMG and sublingual glands were unlabeled, while the Golgi complex and filamentous bodies in these cells showed moderate reactivity. Mitochondria and nuclei of both serous and mucous cells were unlabeled. Labeling also was present in the connective tissue adjacent to the epithelial cells. The results indicate that serous cells of the parotid and SMG are the major source of salivary cARP. They also reveal significant species differences in the glandular distribution of RII. RII binds to cytoskeletal and nuclear proteins, and may function to regulate extracellular cyclic AMP levels. Thus, the tissue and cellular distribution of RII may serve as an index of regulation of gene expression and cell differentiation.


[Use of Patient Specific Instruments at Total Knee Arthroplasty. One-Year Results of a Prospective Randomised Study].
PURPOSE OF THE STUDY The aim of this prospective study was to evaluate, at one year of follow-up, radiographic and clinical results of total knee arthroplasty (TKA) performed with use of Zimmer® Patient Specific Instruments (PSIs) which allow for planning and customising each patient's TKA. MATERIAL AND METHODS Of the patients with knee arthritis who were eligible for joint replacement, 23 were randomly selected and included in this study. There were 11 men and 12 women, with 11 right and 12 left knee joints. On the basis of pre-operative CT scans, PSI custom-made pin guides, which conformed to the individual patient's anatomy, were produced and then used in the THA surgery involving a NexGen (CR) system. All patients were examined before surgery and at 1 year after THA. The evaluation at a follow-up visit included standing full-length radiographs (antero-posterior and lateral), Knee Score results, range of motion (ROM), patient's satisfaction report, and post-operative complications. The X-ray views were examined for mechanical leg axis alignment, TKA alignment in antero-posterior and lateral projection and signs of potential loosening. RESULTS At 1 post-operative year, the average Knee Society Score (KSS) was 85.5 points and the average functional score was 82.6 point. The satisfaction rate was 94% and, on a school rating system, the average mark was 1.3. The average postoperative ROM value was 116°. All patients were willing to undergo the surgery again. The only complication was thrombosis in one patient. Radiographic findings of knee alignment were optimal in 18, correct (up to 3° deviation) in three and incorrect (above 3° deviation) in two patients. Radiographic signs of loosening were not recorded. DISCUSSION Correct knee alignment is one of the requirements for achieving a good TKA outcome. Various techniques are used to improve the total knee process (computer-aided surgery, customised guides). Zimmer Patient Specific Instruments provide advanced pre-operative planning and more accurate implant sizing and alignment. An experienced surgeon can achieve the same good results with conventional planning under standard conditions but the use of PSIs is clearly more beneficial in patients with extra-articular deformities and in patients in whom femoral intramedullary guides cannot be employed. To produce a custom-made pin guide requires a CT scan of the whole leg and is also associated with additional paperwork. The PSIs simplify the total knee process from start to finish and surgeons have complete flexibility to make fine-tuning adjustments during the procedure. CONCLUSIONS Zimmer Patient Specific Instruments allow for exact alignment of both the femoral and the tibial component in a TKA process. Under standard circumstances, clinical and radiographic outcomes are comparable with those of conventional planning. However, the use of PSIs is clearly more beneficial in patients with extra-articular deformities and in patients in whom femoral intramedullary guides cannot be employed. total knee arthroplasty, TKA, Patient Specific Instruments, PSIs.


Antioxidant Capacity, Phenolic Constituents and Toxicity of Hot Water Extract from Red Maple Buds.
The present study reports, for the first time, the results of the antioxidant capacity and the phenolic composition of a hot water extract from red maple buds (RMB), as well as its safety. In this regard and comparatively to antioxidant standards, this extract exhibits a significant antiradical capacity when tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH· ) and anion superoxide trapping assays. High-resolution mass spectrometric and nuclear magnetic resonance analyses permitted to determine for the first time, in red maple species, cyanidin-3-O-glucoside, quercetin-3-O-galactoside, quercetin-3-O-arabinoside, and quercetin. Also, the quantification of individual phenolics by high-performance liquid chromatography method revealed that ginnalin A at 117.0 mg/g is the major compound of RMB hot water extract. Finally, using flow cytometry evaluation, the extract of RMB was determined to have no toxicity neither to cause significant modification of apoptosis process, up to concentration of 100 μg/ml, on human peripheral blood neutrophils. These results allow anticipating various fields of application of RMB water extract.


The role of the envelope protein in the stability of a coronavirus model membrane against an ethanolic disinfectant.
Ethanol is highly effective against various enveloped viruses and can disable the virus by disintegrating the protective envelope surrounding it. The interactions between the coronavirus envelope (E) protein and its membrane environment play key roles in the stability and function of the viral envelope. By using molecular dynamics simulation, we explore the underlying mechanism of ethanol-induced disruption of a model coronavirus membrane and, in detail, interactions of the E-protein and lipids. We model the membrane bilayer as N-palmitoyl-sphingomyelin and 1-palmitoyl-2-oleoylphosphatidylcholine lipids and the coronavirus E-protein. The study reveals that ethanol causes an increase in the lateral area of the bilayer along with thinning of the bilayer membrane and orientational disordering of lipid tails. Ethanol resides at the head-tail region of the membrane and enhances bilayer permeability. We found an envelope-protein-mediated increase in the ordering of lipid tails. Our simulations also provide important insights into the orientation of the envelope protein in a model membrane environment. At ∼25 mol. % of ethanol in the surrounding ethanol-water phase, we observe disintegration of the lipid bilayer and dislocation of the E-protein from the membrane environment.


Isolation and characterization of Bacteroides nodosus fimbriae: structural subunit and basal protein antigens.
We examined the isolation of fimbriae from Bacteroides nodosus. It was found that the best preparations were obtained from the supernatant of washed cells cultured on solid medium, from which fimbriae could be recovered in high yield and purity by a simple one-step procedure. Analysis of such preparations by sodium dodecyl sulfate gel electrophoresis showed that greater than 98% of the protein consisted of fimbrial structural subunits whose molecular weight was ca. 17,000. These preparations also usually exhibited minor contamination with a polypeptide of ca. 80,000 molecular weight, as well as trace amounts of lipopolysaccharide. Attempts to release additional fimbriae by the traditional means of subjecting the bacterial cells to physical stress, such as shearing or heating, resulted primarily in an increase in the level of contamination, without significant gain in the yield of fimbriae. Removal of the 80,000-dalton component could not be achieved by any of a variety of techniques normally used in fimbriae purification, including isoelectric precipitation, MgCl2 precipitation, and CsCl gradient ultracentrifugation, implying a direct physical association with the fimbrial strand. Electron micrographs of fractions containing this protein show cap-shaped structures attached to the ends of what appeared to be fimbrial stubs. These observations suggest that the 80,000-dalton polypeptide may actually constitute the basal attachment site which anchors the fimbria to the outer membrane, analogous to a similar protein recently described in enterotoxigenic strains of Escherichia coli. In B. nodosus, this 80,000-dalton protein is a major surface antigen, and like the fimbrial subunit, exhibited variation in electrophoretic mobility between serotypically different isolates.


Enzymatic cleavage of the C-glucosidic bond of puerarin by three proteins, Mn(2+), and oxidized form of nicotinamide adenine dinucleotide.
We previously isolated the human intestinal bacterium, strain PUE, which can cleave the C-glucosidic bond of puerarin to yield its aglycone daidzein and glucose. In this study, we partially purified puerarin C-glucosidic bond cleaving enzyme from the cell-free extract of strain PUE and demonstrated that the reaction was catalyzed by at least three proteins, Mn(2+), and oxidized form of nicotinamide adenine dinucleotide (NAD(+)). We completely purified one of the proteins, called protein C, by chromatographic separation in three steps. The molecular mass of protein C was approximately 40 kDa and the amino acid sequence of its N-terminal region shows high homology to those of two putative proteins which belong to Gfo/Idh/MocA family oxidoreductase. Protein C catalyzed hydrogen-deuterium exchange reaction of puerarin to 2"-deuterated puerarin in D(2)O condition, which closely resembles those of glycoside hydrolase family 4 and 109.


TMaCS: a hybrid template matching and classification system for partially-automated particle selection.
Selection of particle images from electron micrographs presents a bottleneck in determining the structures of macromolecular assemblies by single particle electron cryomicroscopy (cryo-EM). The problem is particularly important when an experimentalist wants to improve the resolution of a 3D map by increasing by tens or hundreds of thousands of images the size of the dataset used for calculating the map. Although several existing methods for automatic particle image selection work well for large protein complexes that produce high-contrast images, it is well known in the cryo-EM community that small complexes that give low-contrast images are often refractory to existing automated particle image selection schemes. Here we develop a method for partially-automated particle image selection when an initial 3D map of the protein under investigation is already available. Candidate particle images are selected from micrographs by template matching with template images derived from projections of the existing 3D map. The candidate particle images are then used to train a support vector machine, which classifies the candidates as particle images or non-particle images. In a final step in the analysis, the selected particle images are subjected to projection matching against the initial 3D map, with the correlation coefficient between the particle image and the best matching map projection used to assess the reliability of the particle image. We show that this approach is able to rapidly select particle images from micrographs of a rotary ATPase, a type of membrane protein complex involved in many aspects of biology.


High-Modulus Low-Cost Carbon Fibers from Polyethylene Enabled by Boron Catalyzed Graphitization.
Currently, carbon fibers (CFs) from the solution spinning, air oxidation, and carbonization of polyacrylonitrile impose a lower price limit of ≈$10 per lb, limiting the growth in industrial and automotive markets. Polyethylene is a promising precursor to enable a high-volume industrial grade CF as it is low cost, melt spinnable and has high carbon content. However, sulfonated polyethylene (SPE)-derived CFs have thus far fallen short of the 200 GPa tensile modulus threshold for industrial applicability. Here, a graphitization process is presented catalyzed by the addition of boron that produces carbon fiber with >400 GPa tensile modulus at 2400 °C. Wide angle X-ray diffraction collected during carbonization reveals that the presence of boron reduces the onset of graphitization by nearly 400 °C, beginning around 1200 °C. The B-doped SPE-CFs herein attain 200 GPa tensile modulus and 2.4 GPa tensile strength at the practical carbonization temperature of 1800 °C.


Osteocyte-specific monoclonal antibody MAb OB7.3 is directed against Phex protein.
Osteocytes are the most abundant cells in bone; however, relatively little is known about their properties and functions. The development of monoclonal antibody MAb OB7.3 directed against chicken osteocytes enabled us to purify osteocytes from enzymatically isolated bone cells. Cultures of purified osteocytes were used to gain better insight into the role of osteocytes in bone metabolism. Until now, the antigen of MAb OB7.3 has not been elucidated. In this study, we examined the antigen to which this osteocyte-specific antibody is directed. Immunoprecipitation and purification of the protein, followed by amino acid sequence analysis of two isolated peptides, revealed that the antigen has high homology to human and murine PHEX/Phex protein sequences (PHosphate-regulating gene with homology to Endopeptidases on the X chromosome). The OB7.3 antigen was therefore identified as chicken Phex protein. In addition, using suppression subtractive hybridization, we obtained a complementary DNA (cDNA) sequence of 502 base pairs (bp) with high homology to the human and murine PHEX/Phex genes. This method was applied to identify genes, which are differentially expressed in osteocytes compared with osteoblasts. The results also suggest that Phex is expressed at higher levels in chicken osteocytes compared with osteoblasts. Reverse-transcription polymerase chain reaction (RT-PCR) and Northern blot analyses supported these findings. The function of Phex is not completely understood. However, it is known that the gene is preferentially expressed in bone and that mutations in PHEX/Phex lead to X-linked hypophosphatemia and bone mineralization abnormalities. Our findings suggest that osteocytes play an important role in the Phex-regulated phosphate handling in the kidney and in bone.


Reintervention following stage 1 palliation: A report from the NPC-QIC Registry.
Single ventricle heart disease with aortic arch hypoplasia has high morbidity and mortality, with the greatest risk after stage 1 palliation. Residual lesions often require catheter-based or surgical reintervention to minimize risk. We sought to describe the types, frequency, and risk factors for re-intervention between stage 1 and stage 2 palliation, utilizing the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry. The NPC-QIC registry, consisting of patients discharged after stage 1 palliation, was queried. Hybrid stage 1 palliation patients were excluded from this study. The primary risk factor was shunt type and the primary outcome was re-intervention. Of 1156 patients, (50%) had re-intervention. There was no difference in total rate of re-intervention by shunt type (BT shunt 52% vs. RVPA shunt 48%; P = .17). Patients with a BT shunt had increased re-intervention during stage 1 hospitalization (P =.002). During the interstage period, following discharge from stage 1 palliation, patients with a BT shunt had increased aortic arch re-intervention (P < .005), while patients with an RVPA shunt had increased re-intervention on the shunt and the pulmonary arteries (P = .02). Postoperative mechanical ventilation >14 d (P < .01) was the only risk factor associated with re-intervention by multivariable analysis, regardless of shunt type. Re-intervention between stage I and stage 2 palliation is common. There is no difference in cumulative frequency of re-intervention between shunt types, though types and timing of re-intervention varied between shunt types. Longitudinal assessment of the NPC-QIC database is important to identify long term outcomes of patients requiring re-intervention.


Bifurcational mechanisms of synchronization of a resonant limit cycle on a two-dimensional torus.
We study synchronization of a resonant limit cycle on a two-dimensional torus with an external harmonic signal. The regime of the resonant limit cycle is realized in a system of two coupled Van der Pol oscillators; we consider the resonances 1:1 and 1:3. We analyze the influence of coupling strength between the oscillators. We show that the resonant limit cycle can be generally synchronized on the torus through the resonance destruction followed by the locking of one and then another one of the basic frequencies. We consider the bifurcational mechanism of the synchronization effect.


Familial hyper-angiotensin converting enzyme (ACE)-emia: increased production of ACE by monocyte-macrophage.
We report here a familial clustering of elevated serum angiotensin converting enzyme (ACE) levels. The patient was a 58-year-old Japanese female. She had been in excellent health until the age of 45, when she noticed a decrease in visual acuity of her left eye. Despite intensive therapy under the diagnosis of occulusion of the central retinal vein, she lost her visual acuity at the age of 45. Thereafter, she has been in excellent health. The only abnormality found in this case has been a markedly elevated level of serum ACE (625 n mol/min/ml; normal range; 22-40 n mol/min/ml of serum). Her blood pressure was within normal limits (140/80 mmHg). There was no evidence for the diagnosis of sarcoidosis, Gaucher's disease, leprosy, hyperthyroidism, diabetic retinopathy, or liver disease. One of her two sisters also showed a marked increase in serum ACE activity (303 n mol/min/ml), and remarkably high levels of serum ACE (276 and 294 n mol/min/ml) were demonstrated in both of two sons of this sister. All the members of this family have been in excellent health. The serum ACE activity was activated by chloride and cobalt ions, and inhibited by EDTA, captopril and rabbit antiserum to purified human plasma ACE. Thus, our study showed a familial clustering of "hyper-ACE-emia", and the disorder appears to have been inherited as an autosomal dominant trait.


Gender differences among medically serious suicide attempters aged 15-54 years in rural China.
China is one of few countries which reported higher female suicide rates in the worldwide. However, little is known about the gender differences among Chinese rural suicide attempters. This study aims to analyze the gender differences among medically serious suicide attempters aged 15-54 years in rural China. Subjects were 791 medically serious suicide attempters and 791 controls aged 15-54 years in rural China. Socio-demographic, psychological and some critical variables were assessed in the interview. The results showed that all of the factors (education years, family suicide history, negative life events, social support, impulsivity and mental disorder) associated with male suicide attempters also could be found for females. Physical disease, mental disorder and pesticide ingestion played more roles on male suicide attempters. Ever married, peasant, religious belief, and less social support played more roles on female suicide attempters. Compared with male suicide attempters, female ones are mainly influenced by social factors. A gender-specific approach should be emphasized in suicide prevention.


Profiling of phytochemicals from aerial parts of Terminalia neotaliala using LC-ESI-MS2 and determination of antioxidant and enzyme inhibition activities.
Owing to extraordinary healing power, Terminalia species have been used in traditional medicine systems to treat various diseases. Many folklore uses of Terminalia neotaliala (Madagascar's almond) included treating arterial hypertension, diabetes, diarrhea, dysentery, colic, oral and digestive candidiasis, intestinal parasitic infections, inflammatory skin conditions, postpartum care, and mycotic infections but nevertheless scientifically explored for its medicinal and pharmacological importance. Therefore, the current study intended to prepare methanolic extract and its fractionation with hexane, chloroform, and butanol followed by evaluation of their polyphenolic content, biological activities, and LCMS analysis. The biological study included antioxidant activity and enzyme inhibition assay i.e., α-glucosidase and urease. The insight study of biologically active secondary metabolites of butanol fraction (BUAE) was performed through LCMS. The total phenolic content (TPC) and total flavonoid content (TFC) of hydroalcoholic and its fractions were estimated using the Folin-Ciocalteu and aluminum chloride method. The total tannin content (TTC) was determined using the Folin-Denis spectrophotometric method. Similarly, the antioxidant potential of HAAE, HEAE, CFAE, and BUAE was determined using four methods as DPPH (1,1-diphenyl-2-picrylhydrazyl), 2,2-azinobis(3-ethylbenothiazoline)-6-sulfonic acid, cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP). The sample extracts were also evaluated against two clinically important enzymes i.e., α-glucosidase and urease. The BUAE (butanol aerial fraction) showed the highest TPC (234.79 ± 0.12 mg.GAE.g-1 DE), TFC (320.75 ± 12.50 mg.QE.g-1 DE), and TTC (143.36 ± 4.32 mg.TA.Eq.g-1 DE). The BUAE also showed the highest scavenging potential determined by DPPH (642.65 ± 1.11 mg.TEq.g-1 DE) and ABTS (543.17 ± 1.11 mg.TEq.g-1 DE), and the metal-reducing capacity determined by CUPRAC (1510.41 ± 4.45 mg.TEq.g-1 DE) and FRAP (739.81 ± 19.32 mg.TEq.g-1 DE). The LCMS of BUAE identified 18 different biologically active phytoconstituents validating a rich source of hydrolyzable tannins including ellagitannins and gallitannins. The present study concluded that T. neotaliala is a rich source of polyphenols capable of neutralizing the damage caused by free radical accumulation in the cells and tissues. The significant antioxidant results and identification of high molecular weight hydrolyzable tannins enlightened the medicinal importance of T. neotaliala.


Performance evaluation of two immunoassays for 25-hydroxyvitamin D.
Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2.


Modelling the Interplay between Responsive Individual Vaccination Decisions and the Spread of SARS-CoV-2.
The uptake of COVID-19 vaccines remains low despite their high effectiveness. Epidemic models that represent decision-making psychology can provide insight into the potential impact of vaccine promotion interventions in the context of the COVID-19 pandemic. We coupled a network-based mathematical model of SARS-CoV-2 transmission in Georgia, USA with a social-psychological vaccination decision-making model in which vaccine side effects, post-vaccination infections, and other unidentified community-level factors could "nudge" individuals towards vaccine resistance while hospitalization spikes could nudge them towards willingness. Combining an increased probability of hospitalization-prompted resistant-to-willing switches with a decreased probability of willing-to-resistant switches prompted by unidentified community-level factors increased vaccine uptake and decreased SARS-CoV-2 incidence by as much as 30.7% and 24.0%, respectively. The latter probability had a greater impact than the former. This illustrates the disease prevention potential of vaccine promotion interventions that address community-level factors influencing decision-making and anticipate the case curve instead of reacting to it.


Rational design and synthesis of new polymeric material.
Polymers constitute one of the four main areas of materials science. Modern research in polymers focuses on the ways in which tailored macromolecules organize themselves in the solid state and on materials design and synthesis at the interface between polymer science and the fields of ceramics, metals, and electroactive or electrooptical materials.


Antisense oligonucleotides targeting human telomerase mRNA increases the radiosensitivity of nasopharyngeal carcinoma cells.
Nasopharyngeal carcinoma (NPC) is associated with a high incidence rate in South China and is predominantly treated with radiotherapy; however, the survival rate remains low. The therapeutic effects of radiation and chemotherapy may be enhanced when combined with anti‑sense oligonucleotides targeting human telomerase RNA (hTR ASODN). However, the influence of hTR ASODN on the anti‑tumor effects of radiation in NPC remain unknown. The present study investigated the effects of hTR ASODN on the proliferation and radiosensitivity of NPC cells, and further explored the underlying mechanisms. hTR ASODN significantly inhibited the proliferation and decreased the telomere length of CNE‑2 human NPC cells. Furthermore, combined treatment of hTR ASODN with radiation significantly enhanced anti‑tumor efficacy. The apoptotic rate and cleavage of caspase 9 were increased in the cells treated with the combined therapy, as compared with the cells treated with hTR ASODN or radiotherapy alone. In conclusion, these results suggest that hTR ASODN may inhibit the proliferation of NPC cells and enhance the anti‑tumor effects of radiation by inducing cell apoptosis. Therefore hTR ASODN may be a potential adjuvant agent for the treatment of NPC combined with radiation therapy, and these findings are of translational importance.


Jewelled spiders manipulate colour-lure geometry to deceive prey.
Selection is expected to favour the evolution of efficacy in visual communication. This extends to deceptive systems, and predicts functional links between the structure of visual signals and their behavioural presentation. Work to date has primarily focused on colour, however, thereby understating the multicomponent nature of visual signals. Here I examined the relationship between signal structure, presentation behaviour, and efficacy in the context of colour-based prey luring. I used the polymorphic orb-web spider Gasteracantha fornicata, whose yellow- or white-and-black striped dorsal colours have been broadly implicated in prey attraction. In a manipulative assay, I found that spiders actively control the orientation of their conspicuous banded signals in the web, with a distinct preference for near-diagonal bearings. Further field-based study identified a predictive relationship between pattern orientation and prey interception rates, with a local maximum at the spiders' preferred orientation. There were no morph-specific effects on capture success, either singularly or via an interaction with pattern orientation. These results reveal a dynamic element in a traditionally 'static' signalling context, and imply differential functions for chromatic and geometric signal components across visual contexts. More broadly, they underscore how multicomponent signal designs and display behaviours may coevolve to enhance efficacy in visual deception.


Divergent behaviors and underlying mechanisms of cell migration and invasion in non-metastatic T24 and its metastatic derivative T24T bladder cancer cell lines.
Previous studies on cancer cell invasion were primarily focused on its migration because these two events were often considered biologically equivalent. Here we found that T24T cells exhibited higher invasion but lower migration abilities than T24 cells. Expression of Rho-GDPases was much lower and expression of SOD2 was much higher in T24T cells than those in T24 cells. Indeed, knockdown of SOD2 in T24T cells can reverse the cell migration but without affecting cell invasion. We also found that SOD2 inhibited the JNK/c-Jun cascade, and the inhibition of c-Jun activation by ectopic expression of TAM67 impaired Rho-GDPases expression and cell migration in T24T shSOD2 cells. Further, we found that Sp1 can upregulate SOD2 transcription in T24T cells. Importantly, matrix metalloproteinase-2 (MMP-2) was overexpressed in T24T and participated in increasing its invasion, and MMP-2 overexpression was mediated by increasing nuclear transport of nucleolin, which enhanced mmp-2 mRNA stability. Taken together, our study unravels an inverse relationship between cell migration and invasion in human bladder cancer T24T cells and suggests a novel mechanism underlying the divergent roles of SOD2 and MMP-2 in regulating metastatic behaviors of human bladder T24T in cell migration and invasion.


Artificial neural network based particle size prediction of polymeric nanoparticles.
Particle size of nanoparticles and the respective polydispersity are key factors influencing their biopharmaceutical behavior in a large variety of therapeutic applications. Predicting these attributes would skip many preliminary studies usually required to optimize formulations. The aim was to build a mathematical model capable of predicting the particle size of polymeric nanoparticles produced by a pharmaceutical polymer of choice. Polymer properties controlling the particle size were identified as molecular weight, hydrophobicity and surface activity, and were quantified by measuring polymer viscosity, contact angle and interfacial tension, respectively. A model was built using artificial neural network including these properties as input with particle size and polydispersity index as output. The established model successfully predicted particle size of nanoparticles covering a range of 70-400nm prepared from other polymers. The percentage bias for particle prediction was 2%, 4% and 6%, for the training, validation and testing data, respectively. Polymer surface activity was found to have the highest impact on the particle size followed by viscosity and finally hydrophobicity. Results of this study successfully highlighted polymer properties affecting particle size and confirmed the usefulness of artificial neural networks in predicting the particle size and polydispersity of polymeric nanoparticles.


Frequency and Factors Associated with Adult Immunization in Patients Visiting Family Medicine Clinics at a Tertiary Care Hospital, Karachi.
Objective The goal of this study was to determine the frequency and factors associated with adult immunization in patients visiting family medicine clinics at a tertiary care hospital in Karachi. Methods A cross-sectional study was conducted from March 2014 to March 2015 in a tertiary care hospital in Karachi, Pakistan. Participants more than 18 years were invited to participate in the study. A pretested questionnaire was used to collect information. Data were entered and analyzed using IBM SPSS Statistics for Windows, version 19.0 (Armonk, NY: IBM Corp). Results A total of 340 patients were surveyed. The majority of patients were female (69.5%) with a mean age of 35.47 years. The majority were married (61.1%), and 30% of the participants had completed graduation or postgraduate education (20%). Most of the patients believed that vaccines can be used in adults to prevent disease (62.2%). Patients believed that the hepatitis B vaccine, influenza vaccine, and hepatitis A vaccine can be administered to adults (58.1%, 29.9%, 33.8%, respectively). The major sources of their information regarding vaccination in adults were friends or relatives (25%) and media (23.2%). Regarding availability of vaccines, 71.3% thought a hepatitis B vaccine is available, 54.9% thought a tuberculosis vaccine is available, and 49.3% thought a tetanus toxoid vaccine is available. Only 36.4% respondents received any vaccine in adulthood. The majority of patients (62.2%) received the hepatitis B vaccine in adulthood. The major reason given for not receiving vaccines was lack of awareness (62.4%). Conclusion Low adult vaccination coverage rates and awareness, as highlighted by the results of this study, show the dire need to address this major preventive strategy. This information can be utilized to conduct larger community-based surveys, to conduct health awareness sessions in the community, and to educate our doctors regarding the availability and benefits of adult vaccines.


Acute lymphoblastic leukemia complicated by acute renal failure: a case report and review of the literature.
The patient, a previously healthy woman, presenting with acute renal failure and anemia, was admitted to our hospital. Her serum creatinine (Scr) had increased from 0.79 - 2.69 mg/dl over three days and hemoglobin had decreased from 12.1 - 7.8 g/dl over 4 weeks. Mild compression fracture and degeneration of the lumbar vertebra and skull were observed in X-ray. The renal biopsy showed acute proximal tubular lesions induced by multiple calcium deposition. A bone marrow biopsy showed that primitive lymphocyte was up to 92.5%. After making a diagnosis of acute lymphoblastic leukemia complicated with acute kidney injury induced by hypercalcemia, CRRT (continued renal replacement therapy) and chemotherapy were used immediately. Ten days later, the blood calcium had gradually decreased from 3.88 to normal range (1.8 mmol/l) and the renal function was back to normal (Scr 0.93 mg/dl). This unusual case shows that a patient who has a syndrome of acute renal failure, electrolyte disturbances, anemia, and elevated LDH needs bone marrow puncture to eliminate renal injury caused by hematologic diseases.