In-hospital risk prediction for post-stroke depression: development and validation of the Post-stroke Depression Prediction Scale.
The timely detection of post-stroke depression is complicated by a decreasing length of hospital stay. Therefore, the Post-stroke Depression Prediction Scale was developed and validated. The Post-stroke Depression Prediction Scale is a clinical prediction model for the early identification of stroke patients at increased risk for post-stroke depression. The study included 410 consecutive stroke patients who were able to communicate adequately. Predictors were collected within the first week after stroke. Between 6 to 8 weeks after stroke, major depressive disorder was diagnosed using the Composite International Diagnostic Interview. Multivariable logistic regression models were fitted. A bootstrap-backward selection process resulted in a reduced model. Performance of the model was expressed by discrimination, calibration, and accuracy. The model included a medical history of depression or other psychiatric disorders, hypertension, angina pectoris, and the Barthel Index item dressing. The model had acceptable discrimination, based on an area under the receiver operating characteristic curve of 0.78 (0.72-0.85), and calibration (P value of the U-statistic, 0.96). Transforming the model to an easy-to-use risk-assessment table, the lowest risk category (sum score, <-10) showed a 2% risk of depression, which increased to 82% in the highest category (sum score, >21). The clinical prediction model enables clinicians to estimate the degree of the depression risk for an individual patient within the first week after stroke.


Periodic motions and homoclinic orbits in a discontinuous dynamical system on a single domain with multiple vector fields.
In this paper, periodic motions and homoclinic orbits in a discontinuous dynamical system on a single domain with two vector fields are discussed. Constructing periodic motions and homoclinic orbits in discontinuous dynamical systems is very significant in mathematics and engineering applications, and how to construct periodic motions and homoclinic orbits is a central issue in discontinuous dynamical systems. Herein, how to construct periodic motions and homoclinic orbits is presented through studying a simple discontinuous dynamical system on a domain confined by two prescribed energies. The simple discontinuous dynamical system has energy-increasing and energy-decreasing vector fields. Based on the two vector fields and the corresponding switching rules, periodic motions and homoclinic orbits in such a simple discontinuous dynamical system are studied. The analytical conditions of bouncing, grazing, and sliding motions at the two energy boundaries are presented first. Periodic motions and homoclinic orbits in such a discontinuous dynamical system are determined through the specific mapping structures, and the corresponding stability is also presented. Numerical illustrations of periodic motions and homoclinic orbits are given for constructed complex motions. Through this study, using discontinuous dynamical systems, one can construct specific complex motions for engineering applications, and the corresponding mathematical methods and computational strategies can be developed.


[Experience with peflacine in the treatment of osteomyelitis].
Authors report on the treatment of 20 chronic osteomyelitis patients in whom direct antibiotic therapy was performed using the preparation Péflacine. The infected area was exposed in every case, the bony focus was excised and the wound was drained. During the operation, as an induction 800 mg Péflacine in slow drop infusion was given. Oral preparation (2 x 400 mg/die) followed, and was continued for 30 days. The secretion of the wounds ceased in every case, after 3 weeks the latest. In 2 cases mild gastrointestinal symptoms as side effects were observed. Relapse the first time occurred 5-7 months after ending the treatment in 3 patients. These were again explored and after the excision more thorough than before the secretion ceased. According their experience and in conformity with the literature the Péflacine is held an effective medicament in the treatment of the acute exacerbation of chronic osteomyelitis, together with the excision of the focus.


The Effect of High-Dose Radiation Therapy on Healthy Vertebral Bone Density.
Objective Increased rates of insufficiency fractures are reported after radiation therapy without well-defined causality. Here, we conduct a cross-sectional study on the density change of a non-lesioned vertebral bone after irradiation relative to a control bone in patients with spinal metastases. Methods Patients were identified who received radiation therapy for spinal metastases to a region, including an adjacent vertebra without identifiable malignancy on pre-treatment CT. Every patient had an untreated vertebra of a similar type available as a control. A Hounsfield-density calibration curve was used to measure the vertebral body density before and after treatment. Analysis of covariance was used to model vertebral bone density changes with respect to treatment status. Significance was established as p < 0.05. Results We identified 36 patients who fit the study criteria. The irradiated healthy bone received a median dose of 30 Gy. The median biologically effective dose (BED) was 60 Gy (α/β = 3) and 39 Gy (α/β = 10). Median follow-up imaging intervals between pre-treatment and follow-up CT scans was 13.4 months. Levene's test was used to confirm the equality of error variance assumption of ANCOVA (p = 0.093). The mean change in the density of the irradiated vertebral bone was -3.59% (95% CI = -8.51% - 1.32%, p = 0.149). Conclusions We found no significant change in vertebral bone density attributable to radiation treatment. Further work is needed to elucidate if increased fracture rates after radiation are due to factors other than bone density.


Are abatacept and tocilizumab intravenous users willing to switch for the subcutaneous route of administration? A questionnaire-based study.
Choosing the subcutaneous (SC) route of administration of abatacept and tocilizumab is more cost-effective than the intravenous (IV) route. The objective of this study was to examine patients' reasons for choosing to keep with their IV infusions or to switch to subcutaneous SC injections. This study was based upon a self-administered questionnaire given to consecutive rheumatoid arthritis patients treated with abatacept or tocilizumab. Patients were asked to express their opinions concerning reasons explaining why they chose to keep the IV route or switch to the SC route. A total of 201 questionnaires completed by 127 patients treated by tocilizumab and 74 by abatacept were analysed. Overall, 45.8% of the patients chose to keep the IV route of administration. Another ongoing SC treatment was noted more often in patients choosing the SC route (15.9 versus 4.3%, p < 0.05). Reasons guiding the choice of the SC route were concerns about repeated hospital day-care (72%), greater autonomy with SC injections (38.7%) and economic considerations (21.5%). Reasons associated with choosing to maintain the IV route were worries about a lack of follow-up (72.1%), the absence of medical assistance during the SC injection (61.2%), maintaining social relationships with other patients developed at the hospital (40.5%), lower frequency of injection (32.9%), fear of adverse events (27.7%) and fear of SC injections (17.9%). Patients reject the SC switch from the IV route of tocilizumab and abatacept mainly because of fears about the unknown SC route, while those who accept it find it more convenient.


Exosomal long non-coding RNA MSTRG.292666.16 is associated with osimertinib (AZD9291) resistance in non-small cell lung cancer.
Acquired resistance of osimertinib is encountered in clinic treatment of non-small cell lung cancer (NSCLC). However, the molecular mechanisms of osimertinib resistance are not fully revealed. This study aimed to investigate the roles of exosomes in delivering osimertinib resistance in NSCLC. Exosomes were successfully isolated. LncRNA sequencing identified a total of 123 differentially expressed lncRNAs, including 45 upregulated lncRNAs and 78 downregulated lncRNAs. The relative expression level of lncRNA MSTRG.292666.16 was significantly upregulated in osimertinib-resistant plasma, osimertinib-resistant H1975R cells and their derived exosomes, compared with those in osimertinib- sensitive plasma, H1975 cells and exosomes (P < 0.05). Besides, osimertinib-resistant exosomes could regulate gene expressions induced by osimertinib, including miRNA-21, miRNA-125b, TGFβ, ARF6 and c-Kit. Osimertinib-resistant exosomes could be taken up by osimertinib-sensitive H1975 cells and resulting in osimertinib-resistance in vivo. Knockdown of lncRNA MSTRG.292666.16 decreased osimertinib resistance of H1975R cells. Our results suggest that exosomal lncRNA MSTRG.292666.16 might be associated with osimertinib resistance in NSCLC.


Comparison of methods for the measurement of mist and vapor from light mineral oil-based metalworking fluids.
The measurement of oil mist derived from metalworking fluids formulated with light mineral oils can be highly inaccurate when using traditional filter sampling. This is due to evaporation of oil from the filter. In this work the practicability of an alternative approach measuring total oil mist and vapor was investigated. Combinations of inhalable particle samplers with backup sorbent vapor traps and standard vapor sampling on pumped and diffusive sorbent tubes were evaluated with gravimetric, infrared spectroscopic, and gas chromatographic analytical methods against the performance requirements of European Standard EN 482. An artificial aerosol was used to compare the methods against a reference method of filter sampler in series with three impingers. Multi-orifice samplers were used with standard 8-mm diameter charcoal tubes at 2 L/min without any signs of channelling or significant breakthrough, as were conical inhalable samplers with XAD-2 tubes at 1 L/min. Most combinations of samplers had a bias of less than 3 percent, but solitary pumped charcoal tubes underestimated total oil by 13 percent. Diffusive sampling was affected by impaction of mist particles and condensation of oil vapor. Gravimetric analysis of filters revealed significant potential sample loss during storage, with 4 percent being lost after one day when stored at room temperature and 2 percent when refrigerated. Samples left overnight in the balance room to equilibrate lost 24 percent. Infrared spectroscopy gave more precise results for vapor than gas chromatography (p = 0.002). Gas chromatography was less susceptible to bias from contaminating solvent vapors than infrared spectroscopy, but was still vulnerable to petroleum distillates. Under the specific test conditions (one oil type and mist particle size), all combinations of methods examined complied with the requirements of European Standard EN 484. Total airborne oil can be measured accurately; however, care must be taken to avoid contamination by hydrocarbon solvent vapors during sampling.


Marked post-18th century environmental change in high-arctic ecosystems.
Paleolimnological data from three high-arctic ponds on Cape Herschel, Ellesmere Island, Canada, show that diatom assemblages were relatively stable over the last few millennia but then experienced unparalleled changes beginning in the 19th century. The environmental factors causing these assemblage shifts may be related to recent climatic warming. Regardless of the cause, the biota of these isolated and seemingly pristine ponds have changed dramatically in the recent past and any hopes of cataloging natural assemblages may already be fruitless.


Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.
To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.


Age-Dependent Allergic Asthma Development and Cystathionine Gamma-Lyase Deficiency.
The pathogenic mechanisms for the higher prevalence of allergic asthma in children than in adults have not been settled. The aim of the present study is to examine whether the age-dependent development of allergic asthma is caused by age-dependent expression of cystathionine gamma-lyase (CSE), a key enzyme that catalyzes the production of hydrogen sulfide (H2S). Allergic asthma was induced with ovalbumin in wild-type (WT) and CSE knock-out (KO) mice at young and old ages. CSE expression and H2S production were lower in immune cells of young WT mice than in those of old WT mice. Coincidentally, more severe asthmatic symptoms with a greater type-2 immunoreaction were found in young WT mice than old WT mice. H2S supplementation reversed the asthmatic symptoms. Lower expression levels of CSE proteins were also found in human umbilical cord blood mononuclear cells in comparison with that of peripheral blood mononuclear cells from adult people. The age-dependent asthma propensity vanished in CSE-KO mice, but these mice developed more severe asthma than WT mice. More splenocytes were differentiated to type-2 cytokine-generating cells in young WT mice and in CSE-KO mice at all ages. This differentiation was inhibited by H2S donors. GATA3 translocation to the nucleus and type-2 immunoreaction of splenocytes were inhibited after GATA3 was S-sulfhydrated by H2S. Innovation and Conclusion: For the first time, this study demonstrated that lower abundance of CSE expression and H2S production enhances type-2 immunoreaction and renders a higher incidence of allergic asthma at a young age. As such, H2S level may be a biomarker for asthma development and a H2S-based strategy can be perceived for asthma prevention and treatment. Antioxid. Redox Signal. 27, 931-944.


Self-monitoring of blood pressure should be used in clinical trials.
The number of studies of the efficacy of drugs in hypertension and of their effects on morbidity and mortality continues to be large. Traditionally such studies were carried out by measuring the blood pressure (BP) in the office. Recently, there has been an increasing use of other approaches, such as self-measurement. The advantages of this technique may be the achievement of greater precision of measurement, explained by elimination of the white-coat effect, reduction in placebo effect and reduction in variability of BP. Some have even noted a greater reproducibility than using ambulatory BP monitoring. We now have available reference values and normal ranges for self-BP monitoring. The feasibility and the limitations of self-BP measurement are also known. Self-measurement allows multiple recordings of BP over the short term as well as over the long term. Moreover, the compliance of this technique is satisfying. The analysis of the data requires precise recommendations. One cannot refer to trough : peak ratio, which is used in ambulatory recordings. However, other methods of analysis such as evening BP : morning BP ratio or measures taken after taking treatment are useful. The number of subjects needed for a study is much smaller than in a study performed using office measurements for a similar or better statistical power. Such a method has a higher predictive value than clinic measurement both for study of end organ damage and for morbidity and mortality. Finally home measurement is much less costly. In conclusion, provided one uses validated equipment and if one follows recommendations for each measurement and for the succession of measurements, then self-measurement of BP at home seems a useful and practical tool for therapeutic trials.


Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection.
Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.


Changing use of traditional healthcare amongst those dying of HIV related disease and TB in rural South Africa from 2003 - 2011: a retrospective cohort study.
In 2011 there were 5.5 million HIV infected people in South Africa and 71% of those requiring antiretroviral therapy (ART) received it. The effective integration of traditional medical practitioners and biomedical providers in HIV prevention and care has been demonstrated. However concerns remain that the use of traditional treatments for HIV-related disease may lead to pharmacokinetic interactions between herbal remedies and ART drugs and delay ART initiation. Here we analyse the changing prevalence and determinants of traditional healthcare use amongst those dying of HIV-related disease, pulmonary tuberculosis and other causes in a rural South African community between 2003 and 2011. ART was made available in this area in the latter part of this period. Data was collected during household visits and verbal autopsy interviews. InterVA-4 was used to assign causes of death. Spatial analyses of the distribution of traditional healthcare use were performed. Logistic regression models were developed to test associations of determinants with traditional healthcare use. There were 5929 deaths in the study population of which 47.7% were caused by HIV-related disease or pulmonary tuberculosis (HIV/AIDS and TB). Traditional healthcare use declined for all deaths, with higher levels throughout for those dying of HIV/AIDS and TB than for those dying of other causes. In 2003-2005, sole use of biomedical treatment was reported for 18.2% of HIV/AIDS and TB deaths and 27.2% of other deaths, by 2008-2011 the figures were 49.9% and 45.3% respectively. In bivariate analyses, higher traditional healthcare use was associated with Mozambican origin, lower education levels, death in 2003-2005 compared to the later time periods, longer illness duration and moderate increases in prior household mortality. In the multivariate model only country of origin, time period and illness duration remained associated. There were large decreases in reported traditional healthcare use and increases in the sole use of biomedical treatment amongst those dying of HIV/AIDS and TB. No associations between socio-economic position, age or gender and the likelihood of traditional healthcare use were seen. Further qualitative and quantitative studies are needed to assess whether these figures reflect trends in healthcare use amongst the entire population and the reasons for the temporal changes identified.


Effects of pre- and postnatal haloperidol administrations to pregnant and nursing rats on brain catecholamine levels in their offspring.
Effects of perinatal, maternal treatments with haloperidol on brain catecholamine and serotonin concentrations in maturing offspring were examined. The drug was administered orally, at three different dosages, each day from the 14th gestational day to postnatal day 12. At 14, 22, 53 and 90 days of age offspring were selected for regional assays of amine neurotransmitter concentrations. The results indicate that haloperidol can alter the developmental accumulation of central catecholaminergic neurotransmitters. The drug-induced decreases in cortical and spinal norepinephrine levels and in striatal dopamine content in the offspring persisted into adulthood. Regional serotonin concentrations in offspring were not affected by the maternal haloperidol treatments. These findings suggest that central catecholamine receptors are necessary for normal development of dopaminergic and noradrenergic innervation in the central nervous system.


Narrowband UVB treatment increases serum 25-hydroxyvitamin D levels in patients with chronic plaque psoriasis.
The aim of this study was to investigate the effects of narrowband UVB (NB-UVB) phototherapy on serum 25-hydroxyvitamin D (25[OH]D) levels and related parameters in patients with psoriasis. Forty-nine participants with moderate to severe plaque-type psoriasis were included in this study and were treated with NB-UVB therapy 3 times weekly for 6 months or until psoriasis area and severity index (PASI) 75 was achieved. Participants' serum 25(OH)D, calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (ALP) levels were measured at baseline and completion of treatment, along with PASI scores. We observed that the serum 25(OH)D levels increased after NB-UVB treatment, but the only correlation that was found was the number of sessions of NB-UVB. There was no relationship between patient age, Fitzpatrick skin type, PASI score, or maximum NB-UVB dose and serum 25(OH)D levels.


Experience with subcutaneous erythropoietin in CAPD patients.
Experience in the use of subcutaneous erythropoietin in 18 CAPD patients is presented. The total and mean (SD) durations on CAPD were 419 and 23.3 (20.5) months, respectively. Eleven patients started treatment with normal or elevated iron stores, 7 had an initial iron saturation less than 20%. The initial hematocrit was 22.0 (3.1%). Eleven patients reached a steady state hematocrit (34.1 +/- 3.5%) by the end of the study period, and the mean percentage increase in hematocrit for all 18 patients was 47% over the initial hematocrit. All patients responded to EPO. The initial dose of EPO was 157.6 U/kg/wk, and all patients received oral iron supplements. There was no significant change in the means of any iron parameters. Transfusion requirements decreased from a mean of 0.42 transfusions per month per patient during the 12 months, prior to EPO, to 0.22 during the study. There were no significant changes in blood pressure or other measured parameters. Transient pain at the site of injection was noted infrequently.


[VENOUS THROMBOEMBOLISM DURING PREGNANCY AND THE PUERPERIUM - WHO? WHEN? AND HOW TO TREAT?]
Venous thromboembolism (VTE) is a potentially life-threatening medical condition during pregnancy and the puerperium. During pregnancy, the risk of VTE is increased four to tenfold compared to non-pregnant women of comparable age. The risk is even higher in the puerperium. Physician awareness followed by adequate treatment may reduce the number of events. The most important risk factors are previous VTE or thrombophilia, although other acquired risk factors may result in similar impacts. Treatment is based on personalized risk assessment at the first patient visit during pregnancy, followed by repeated assessment of complications or at admission and final assessment at delivery. Hydration and mobilization are advised for all women. Pharmacological prevention by low-molecular-weight heparin (LMWH) is advised based on risk stratification. International guidelines differ by indications and range of management options. The purpose of this review is to summarize our knowledge on risk factors for VTE during pregnancy and puerperium and guide management options.


[Determining serum TBG level using the charcoal-cellulose I-125 thyroxine uptake test].
Radiocompetition method for the determination of blood serum TBG level has been presented. The method is based on binding of 125I-thyroxine by the mixture of cellulose and activated charcoal following the saturation of TBG with L-thyroxine at the concentration of 2.9 nmol/l. The method is similar to the previously described labeled thyroxine uptake in many respects including the use of the same reagents and equipment. The method is simple, easily accessible for any radiochemical laboratory, and yields satisfactory results. The values of TBG obtained with the described method cas serve, together with the values of total thyroxine concentration, for the calculation of free thyroxine index (as TT4/TBG). The above index differentiates well various functional states of the thyroid and serves as a good measure of free thyroid hormones in euthyreosis accompanied by variable TBG values.


Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse.
Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same approximately 4 Mb interstitial genomic deletion within chromosome 17p11.2. To investigate the molecular bases of the SMS phenotype, we constructed BAC/PAC contigs covering the SMS common deletion interval and its syntenic region on mouse chromosome 11. Comparative genome analysis reveals the absence of all three approximately 200-kb SMS-REP low-copy repeats in the mouse and indicates that the evolution of SMS-REPs was accompanied by transposition of adjacent genes. Physical and genetic map comparisons in humans reveal reduced recombination in both sexes. Moreover, by examining the deleted regions in SMS patients with unusual-sized deletions, we refined the minimal Smith-Magenis critical region (SMCR) to an approximately 1.1-Mb genomic interval that is syntenic to an approxiamtely 1.0-Mb region in the mouse. Genes within the SMCR and its mouse syntenic region were identified by homology searches and by gene prediction programs, and their gene structures and expression profiles were characterized. In addition to 12 genes previously mapped, we identified 8 new genes and 10 predicted genes in the SMCR. In the mouse syntenic region of the human SMCR, 16 genes and 6 predicted genes were identified. The SMCR is highly conserved between humans and mice, including 19 genes with the same gene order and orientation. Our findings will facilitate both the identification of gene(s) responsible for the SMS phenotype and the engineering of an SMS mouse model.


Strength-balance supplemented with computerized cognitive training to improve dual task gait and divided attention in older adults: a multicenter randomized-controlled trial.
Exercise interventions often do not combine physical and cognitive training. However, this combination is assumed to be more beneficial in improving walking and cognitive functioning compared to isolated cognitive or physical training. A multicenter parallel randomized controlled trial was conducted to compare a motor to a cognitive-motor exercise program. A total of 182 eligible residents of homes-for-the-aged (n = 159) or elderly living in the vicinity of the homes (n = 23) were randomly assigned to either strength-balance (SB) or strength-balance-cognitive (SBC) training. Both groups conducted similar strength-balance training during 12 weeks. SBC additionally absolved computerized cognitive training. Outcomes were dual task costs of walking, physical performance, simple reaction time, executive functions, divided attention, fear of falling and fall rate. Participants were analysed with an intention to treat approach. The 182 participants (mean age ± SD: 81.5 ± 7.3 years) were allocated to either SB (n = 98) or SBC (n = 84). The attrition rate was 14.3%. Interaction effects were observed for dual task costs of step length (preferred walking speed: F(1,174) = 4.94, p = 0.028, η2 = 0.027, fast walking speed: F(1,166) = 6.14, p = 0.009, η2 = 0.040) and dual task costs of the standard deviation of step length (F(1,166) = 6.14, p = 0.014, η2 = 0.036), in favor of SBC. Significant interactions in favor of SBC revealed for in gait initiation (F(1,166) = 9.16, p = 0.003, η2 = 0.052), 'reaction time' (F(1,180) = 5.243, p = 0.023, η² = 0.028) & 'missed answers' (F(1,180) = 11.839, p = 0.001, η² = 0.062) as part of the test for divided attention. Within-group comparison revealed significant improvements in dual task costs of walking (preferred speed; velocity (p = 0.002), step time (p = 0.018), step length (p = 0.028), fast speed; velocity (p < 0.001), step time (p = 0.035), step length (p = 0.001)), simple reaction time (p < 0.001), executive functioning (Trail making test B; p < 0.001), divided attention (p < 0.001), fear of falling (p < 0.001), and fall rate (p < 0.001). Combining strength-balance training with specific cognitive training has a positive additional effect on dual task costs of walking, gait initiation, and divided attention. The findings further confirm previous research showing that strength-balance training improves executive functions and reduces falls. This trial has been registered under ISRCTN75134517.


Estimating the risk for atherothrombosis: are current approaches sufficient?
Atherothrombotic disease is now the leading cause of mortality in the world and there are only a few methods available to estimate risk of vascular disease. Vascular disease risk assessment methods have been developed from a variety of population based studies and the most frequently used approaches include algorithms developed by Framingham (USA), Munster (Germany), and SCORE (Europe). The field of risk estimation is dynamic and inclusion of newer factors and populations is under active consideration and methods such as discrimination and calibration are now available to evaluate the use of risk assessment tools across different world regions.


Natural anticoagulant and fibrinolytic pathways in renal allograft failure.
This is an immunocytochemical study of the relationship between depletion of natural anticoagulant and fibrinolytic pathways and allograft survival following renal transplantation. Patients (n = 44) were classified in three groups according to the length of time between transplantation and allograft failure: group 1 (n = 14) failed within a month of transplantation; group 2 (n = 14) failed between one month and one year after transplantation; and group 3 (n = 16) failed after one year of transplantation. Control biopsies were from donor kidneys (n = 16) prior to transplantation. There were no statistically significant differences in recipient age, gender, donor kidney type (living-related versus cadaver), histocompatibility, and plasma cholesterol, triglycerides, or creatinine concentrations between groups. However, group 1 allografts had a greater depletion of the vascular heparan sulfate proteoglycan-antithrombin III natural anticoagulant pathway than allografts in group 2 or 3 (P < or = 0.05), and this depletion was associated with significantly greater fibrin deposition in group 1 than in either group 2 or 3 (P < or = 0.05). All three groups demonstrated severe depletion of tissue plasminogen activator from arteriolar smooth muscle cells and depressed fibrinolysis as evidenced by increased fibrin/plasmin ratios. However, no significant differences were found for either endothelial thrombomodulin or T cell, neutrophil, or macrophage infiltration between the groups. These data indicate that differences in graft outcome may be determined more by compromised vascular function than by the presence of cellular infiltrates.


Association study between rs2275913 genetic polymorphism and serum levels of IL-17A with risk of coronary artery disease.
Coronary artery disease (CAD) is now considered as a main cause of disability and mortality in Iranian population. Inflammatory processes are the initial events in the development of CAD. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine and its genetic variation may contribute to the development of CAD. This study investigated serum levels and the G-197A polymorphism of IL17A in a group of patients with CAD and healthy controls. The study population included 220 angiographically verified CAD patients and 220 healthy controls. Genotyping of G-197A polymorphism of IL17A was done by PCR-RFLP method and serum level of IL-17 was measured by enzyme immunoassay. Results indicated that serum concentration of IL-17A was significantly higher in CAD group than control group (P<0.001). Also, serum levels of IL-17A was significantly higher in carriers of GA and AA genotype relative to carriers of GG genotype in both study population (P<0.05). The G-197A polymorphism of IL17A increased the risk of CAD in mutant homozygous (P=0.007) but not heterozygous (P=0.104) genotype. Moreover, this polymorphism was associated with higher risk of CAD development in allelic (P=0.041) model. However, no significant association was observed between genotypic distribution of G-197A polymorphism and the number of stenotic vessels (P>0.05). In conclusion, the present study indicated G-197A polymorphism of IL17A as a significant contributor to the development but not to the severity of CAD. Moreover, elevated serum levels of IL-17A were identified as a susceptibility marker of CAD.


Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.
Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.


Perinatal depression: A review.
Perinatal depression affects 10% to 20% of women in the United States during pregnancy, the postpartum period, or both, but it can be difficult to recognize. Identifying and treating this problem can reduce the alarming number of suicides among depressed perinatal women and the possible adverse effects of untreated maternal depression on their child's cognitive and behavioral development. In this review, we discuss the latest developments in screening, treatment, and prevention methods.


A new analysis of the depolymerized fragments of lignin polymer using ToF-SIMS.
Lignin in plant cell walls is a complex, irregular polymer built from phenylpropanoid C6-C3 units that are connected via various C-C and C-O linkages. A recent study using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with Ga primary ion bombardment showed that lignin polymers can be characterized by specific positive ions possessing a substituted aromatic ring (so-called guaiacyl or syringyl rings), which are the basic building units of lignin. To study the relationship between the characteristic ions of lignin and the common interunit linkages, various lignin dimer model compounds were investigated using ToF-SIMS. The resulting dimer spectra showed that the characteristic ions with a guaiacyl ring at m/z 137 and 151 result from rupture of most common interunit linkages, not only 8-O-4' linkages, which are the most abundant in lignin, but also 8-1', 8-5', and 8-8'. There was no evidence of rupture of 5-5' linkages. These results show that ToF-SIMS offers a new tool for the direct analysis of the depolymerized fragments of lignin polymers. The mechanisms for the fragmentation of lignin dimer models in ToF-SIMS were proposed that allow ToF-SIMS fragmentation rules to be deduced. Adduct ions such as [M + 13]+ ([M + CH]+) were also produced in fragmentation of the dimers and are thought to arise from the combination of the molecules with their stable fragments.


A Hierarchical Phosphorus Nanobarbed Nanowire Hybrid: Its Structure and Electrochemical Properties.
Nanostructured phosphorus-carbon composites are promising materials for Li-ion and Na-ion battery anodes. A hierarchical phosphorus hybrid, SiC@graphene@P, has been synthesized by the chemical vapor deposition of phosphorus on the surfaces of barbed nanowires, where the barbs are vertically grown graphene nanosheets and the cores are SiC nanowires. A temperature-gradient vaporization-condensation method has been used to remove the unhybridized phosphorus particles formed by homogeneous nucleation. The vertically grown barb shaped graphene nanosheets and a high concentration of edge carbon atoms induced a fibrous red phosphorus (f-RP) growth with its {001} planes in parallel to {002} planes of nanographene sheets and led to a strong interpenetrated interface interaction between phosphorus and the surfaces of graphene nanosheets. This hybridization has been demonstrated to significantly enhance the electrochemical performances of phosphorus.


Potential Energy and Environmental Footprint Savings from Reducing Food Loss and Waste in Europe: A Scenario-Based Multiregional Input-Output Analysis.
Food loss and waste (FLW) contribute significantly to the global food system's economic and environmental burdens, including substantial greenhouse gas (GHG) emissions, resource depletion, and waste management challenges. In alignment with the European Commission's sustainability objectives and U.N. Sustainable Development Goal 12.3, this study explores the potential energy and environmental footprint savings achievable by halving FLW in Europe by 2030. Using a multiregional input-output model, we estimated the total global energy and environmental footprint savings across all stages of the food supply chain, considering industry-specific FLW rates and proportion weights. The findings reveal substantial environmental savings across Europe, with aggregate savings potentially reaching 51 Mt CO2e (0.09 t CO2e/p), 4,620 Mm3 (8 m3/p) of blue water, 106,446 km2 (179 m2/p) of cropland, 55,523 km2 (93 m2/p) of grassland, and 0.47 EJ (0.54 TJ/p) of energy. The greatest potential for savings was found in Western Europe, specifically in France, Germany, Belgium, and The Netherlands. However, countries with a lower per capita GDP, such as Greece, Croatia, Bulgaria, and Romania, also demonstrate significant per capita savings potential, indicating that wealth does not necessarily correlate with higher environmental savings. Agricultural production emerged as the stage with the highest footprint reduction potential for GHG and resource footprints across Europe, while the foodservice and institutional stages offer the greatest energy-saving potential. Geographical disparities underscore the need for region-specific policies. These results challenge the wealth-sustainability correlation and advocate for adaptable policies that transcend national wealth and accommodate regional disparities, underlining the pivotal roles of the agricultural production and consumption stages in footprint savings.


Stress urinary incontinence: an overview of diagnosis and treatment options.
Giving birth is known to create risk for various degrees of urinary incontinence (UI) at any time after the birth. Environmental and genetic factors predispose many women to pelvic floor disorders. When a woman determines she is incontinent and has approached her provider, she will need an accurate, proper diagnosis and then consider a selected course of treatment. It is imperative that she is informed of all choices so she can choose the treatment with which she is most comfortable, fits her lifestyle, and will improve her quality of life.


Replication of virulent and attenuated strains of Aujeszky's disease virus in swine alveolar macrophages.
In vitro and in vivo replication of Aujeszky's disease virus (ADV) in swine alveolar macrophages (AM) was studied using two virulent strains and a vaccine strain with deletions in the thymidine kinase and gIII genes. In vitro, AM were highly permissive to virulent ADV infection. Virus progeny titers of virulent strains in the cell phase and in the fluid phase were higher than 10(7.3) TCID50/ml at 84 hr post-inoculation (PI). For vaccine strain infection, AM were less permissive, yielding virus titers of 10(2.3) TCID50/ml at 84 hr PI. To study in vivo replication of ADV in AM, virus isolations were made from AM collected at intervals from pigs inoculated intranasally with both the virulent and vaccine strains. Virus was isolated from AM samples collected from all pigs infected with the virulent strain from days 2 to 22 PI. On the contrary, no virus was detected in AM samples collected from pigs infected with the vaccine strain. The results presented suggested that in vivo virulent ADV replicates for a relatively long period in swine alveolar macrophages.


New method of realization of nursing diagnosis based on 3N in an electronic medical record system.
An electronic medical recording (EMR) system is enlightened as a solution for deciding which nursing diagnosis was selected on the basis of a computerized system; it can help collect and analyze lots of diverse data in an objective way. But there are few reports of successful electronic nursing diagnosis on EMR systems. This study was to develop the objective decision system prior to nursing diagnosis and to adopt it in the Severance EMR system. We adopt a new concept, situational variables, as the key elements of the nursing process, based on the items of nursing intervention. It enables appropriate nursing diagnosis through complex clinical objective data (laboratory results, vital signs, etc.). Through these elements between nursing intervention and nursing diagnosis, we can create reliable evidence-based nursing diagnoses successfully, and make possible fast settlement of nursing intervention in the various clinical fields.


Fluorescence in situ hybridization with peptide nucleic acid probes for rapid identification of Candida albicans directly from blood culture bottles.
A new fluorescence in situ hybridization (FISH) method that uses peptide nucleic acid (PNA) probes for identification of Candida albicans directly from positive-blood-culture bottles in which yeast was observed by Gram staining (herein referred to as yeast-positive blood culture bottles) is described. The test (the C. albicans PNA FISH method) is based on a fluorescein-labeled PNA probe that targets C. albicans 26S rRNA. The PNA probe is added to smears made directly from the contents of the blood culture bottle and hybridized for 90 min at 55 degrees C. Unhybridized PNA probe is removed by washing of the mixture (30 min), and the smears are examined by fluorescence microscopy. The specificity of the method was confirmed with 23 reference strains representing phylogenetically related yeast species and 148 clinical isolates covering the clinically most significant yeast species, including C. albicans (n = 72), C. dubliniensis (n = 58), C. glabrata (n = 5), C. krusei (n = 2), C. parapsilosis (n = 4), and C. tropicalis (n = 3). The performance of the C. albicans PNA FISH method as a diagnostic test was evaluated with 33 routine and 25 simulated yeast-positive blood culture bottles and showed 100% sensitivity and 100% specificity. It is concluded that this 2.5-h method for the definitive identification of C. albicans directly from yeast-positive blood culture bottles provides important information for optimal antifungal therapy and patient management.


Statistical Models for the Analysis and Design of Digital Polymerase Chain Reaction (dPCR) Experiments.
Statistical methods for the analysis and design of experiments using digital PCR (dPCR) have received only limited attention and have been misused in many instances. To address this issue and to provide a more general approach to the analysis of dPCR data, we describe a class of statistical models for the analysis and design of experiments that require quantification of nucleic acids. These models are mathematically equivalent to generalized linear models of binomial responses that include a complementary, log-log link function and an offset that is dependent on the dPCR partition volume. These models are both versatile and easy to fit using conventional statistical software. Covariates can be used to specify different sources of variation in nucleic acid concentration, and a model's parameters can be used to quantify the effects of these covariates. For purposes of illustration, we analyzed dPCR data from different types of experiments, including serial dilution, evaluation of copy number variation, and quantification of gene expression. We also showed how these models can be used to help design dPCR experiments, as in selection of sample sizes needed to achieve desired levels of precision in estimates of nucleic acid concentration or to detect differences in concentration among treatments with prescribed levels of statistical power.


Essential cryofibrinogenaemia, leukocytoclastic vasculitis and chronic purpura.
Cryofibrinogenaemia refers to the presence of cold-precipitable proteins in plasma but not in serum. It is usually associated with malignancy, thromboembolic diseases or various inflammatory processes; rarely it may be essential. The most common clinical presentations of cryofibrinogenaemia are cold-intolerance, purpura, skin necrosis and ulcers. We describe a middle-aged woman with essential cryofibrinogenaemia, leukocytoclastic vasculitis, and chronic purpura for over 25 years with several exacerbations. In patients with otherwise unexplained purpura or skin necrosis, determination of plasma cryofibrinogen should be considered.


Identification of CkSNAP33, a gene encoding synaptosomal-associated protein from Cynanchum komarovii, that enhances Arabidopsis resistance to Verticillium dahliae.
SNARE proteins are essential to vesicle trafficking and membrane fusion in eukaryotic cells. In addition, the SNARE-mediated secretory pathway can deliver diverse defense products to infection sites during exocytosis-associated immune responses in plants. In this study, a novel gene (CkSNAP33) encoding a synaptosomal-associated protein was isolated from Cynanchum komarovii and characterized. CkSNAP33 contains Qb- and Qc-SNARE domains in the N- and C-terminal regions, respectively, and shares high sequence identity with AtSNAP33 from Arabidopsis. CkSNAP33 expression was induced by H2O2, salicylic acid (SA), Verticillium dahliae, and wounding. Arabidopsis lines overexpressing CkSNAP33 had longer primary roots and larger seedlings than the wild type (WT). Transgenic Arabidopsis lines showed significantly enhanced resistance to V. dahliae, and displayed reductions in disease index and fungal biomass, and also showed elevated expression of PR1 and PR5. The leaves of transgenic plants infected with V. dahliae showed strong callose deposition and cell death that hindered the penetration and spread of the fungus at the infection site. Taken together, these results suggest that CkSNAP33 is involved in the defense response against V. dahliae and enhanced disease resistance in Arabidopsis.


Hepatotoxicity with antibody maytansinoid conjugates: A review of preclinical and clinical findings.
Maytansinoids, the potent cytotoxic derivatives of the alkaloid maytansine are used as payloads in antibody maytansinoid conjugates. This article reviews clinical and preclinical hepatotoxicity observed with antibody maytansinoid conjugates used to treat cancer. Specific aspects of drug distribution, metabolism and excretion that may impact hepatotoxicity are reviewed vis-à-vis the kind of maytansinoid in the conjugate, cleavable or non-cleavable linkers, linker-payload combinations, drug to antibody ratio, metabolite formation, hepatic enzyme induction in relation to drug-drug interactions and species, age and gender differences. The article also sheds light on factors that may protect the liver from toxic insults.


Clinical profile of diabetic ketoacidosis in tertiary care hospital of Eastern Nepal.
Diabetes ketoacidoisis (DKA) is characterized by hyperketonaemia, metabolic acidosis, and hyperglycemia. The aim of this study was to describe the demographic profile, clinical characterstics of patients admitted with diabetic ketoacidosis in BPKIHS, medical ward. The hospital based descriptive study. We took all the patients admitted with a diagnosis of diabetic ketoacidosis (DKA) as defined ADA 2006 consensus statement in medical ward from January 2010 to December 2010. The statistical operations was done through Manufactured by IBM Corp. Only sixteen patients (7 type 1 and 9 type 2DM) were with DKA. When compared to the 16 subjects with type 1 DM, the type 2 were older (56.8 s 25.7 years) and had a significantly higher PH levels (7.11 s 7.28 P = 0.04). The mean body mass index was 20.5±2.44 in both Type 1 and type 2 DM. Four were on diet control and Insulin respectively. Five were on oral hypoglycemic agents (OHA) and three on both (insulin and OHA). Infection was most common precipitating factor (56.25%) followed by poor drug compliance (37.5%) and first presentation (6.25%). We found majority of patients were type 2 DM. Metabolic acidosis has significant association in both type of diabetic. We found infection was the most common precipitating factor for DKA.


ATP synthesis catalyzed by the ATP synthase of Escherichia coli reconstituted into liposomes.
The H(+)-translocating F0F1-ATPase from Escherichia coli (EF0F1) was purified and reconstituted into preformed reverse-phase liposomes prepared from egg yolk phosphatidylcholine/phosphatidic acid. The EF0F1 liposomes were energized by an acid/base transition (pHout = 8.3; pHin = 5.0) and a superimposed K+/valinomycin diffusion potential ([K+]out = 100 mM; [K+]in = 0.6 mM) yielding a maximum rate (turnover number) of ATP synthesis of 27 +/- 8 mol ATP . mol EF0F1(-1) . s-1), i.e. 27 +/- 8 s-1. This reaction was inhibited by NH4Cl or by addition of the F0F1 inhibitor N,N'-dicyclohexylcarbodiimide. The rate of ATP synthesis measured as a function of the phosphate and ADP concentrations, can be described by Michaelis-Menten kinetics with a Km of 0.7 +/- 0.2 mM for phosphate ([ADP] = 200 microM) and a Km of 27 +/- 7 microM for ADP ([phosphate] = 5 mM), respectively.


Chaotic EEG patterns during recall of stressful memory related to panic attack.
Chaotic transitions likely emerge in a wide variety of cognitive phenomena and may be linked to specific changes during the development of mental disorders. They represent relatively short periods in the behavior of a system, which are extremely sensitive to very small changes. This increased sensitivity has been suggested to occur also during retrieval of stressful emotional experiences because of their fragmentary, temporally and spatially disorganized character. To test this hypothesis we recorded EEG during retrieval of fearful memories related to panic attack in 7 patients and retrieval of anxiety-related memories in 11 healthy controls. Nonlinear data analysis of EEG records showed a statistically significant increase in degree of chaotic dynamics after retrieval of stressful memories in majority of patients as well as in control subjects. This change correlated with subjective intensity of anxiety induced during the memory retrieval. The data suggest a role of nonlinear changes of neural dynamics in the processing of stressful anxiety-related memories, which may play an important role in the pathophysiology of panic disorder.


The use of an autogenous vaccine in the treatment of sternal wound infections following open heart procedures: a preliminary report.
Five patients, who developed sternal wound infection following open heart surgery and in whom the standard methods of management of this complication had been unsuccessful, were treated with an autogenous vaccine. Complete healing of the sternal wound was obtained in 4 of them, while in one, who had an associated mediastinitis, a slow recovery with persistence of a sternal fistula occurred. The results of this preliminary experience indicate that the use of an autogenous vaccine might be regarded as an alternative method of treatment of sternal infections in selected patients.


Cold loop polypectomy perforation of a tiny colon polyp.
We report the case of a 61-year-old woman having corticoid treatment with corticosteroids for polyarthralgia, who underwent a post-polypectomy surveillance colonoscopy, identifying a 5-mm diameter, flat-elevated polyp in the proximal transverse colon (Paris 0-IIa).


[Identification and significance of a novel degradation system for polyglutamine aggregates].
In neurodegeneration, accumulation of aggregated protein results in the formation of inclusion bodies, which is a pathological hallmark of the diseases. There are various forms of aggregates; from oligomers to filaments and to inclusion bodies, of which small species such as oligomers are considered to be more toxic compared to tightly packed inclusion bodies. In vitro experiments show that artificial inclusion bodies called aggresomes are generated with motor proteins and microtubules, which represents cellular effort to manage aggregated proteins. We showed that the aggresomes are formed in order to concentrate autophagy components and aggregates in order to give specificity to autophagy against aggregated proteins, thus facilitating their selective degradation.


Intercellular junctions in podocytes of the nephrotic glomerulus as seen with freeze-fracture.
The glomeruli of rats rendered nephrotic by administration of aminonucleoside of puromycin were studied with the freeze-fracture technique. The alterations of the podocytes consisted of a progressive blunting of the foot processes and of the disappearance of the extracellular space normally present between the foot processes at the level of the slit pore. In parallel with the closure of the extracellular space, fracture faces of the plasma membrane of the latered podocytes revealed the presence of peculiar membrane differentiations represented mainly by irregular chains of membrane-associated particles in the fracture face A and by variegated grooves in the fracture face B. The presence of grooves in fracture face B indicates that the chains of particles in fracture face A are likely to be tight junctions rather than linear gap junctions. However, since the presence of continuous ridges is exceptional, it is suggested that the tight junctions are the "leaky" -type and that the podocytes many have only limited capacities for assembling junctions of the "tight" -type.


Novel cardioprotective role of a small heat-shock protein, Hsp20, against ischemia/reperfusion injury.
Heat-shock proteins (Hsps) have been shown to render cardioprotection from stress-induced injury; however, little is known about the role of another small heat-shock protein, Hsp20, which regulates activities of vasodilation and platelet aggregation, in cardioprotection against ischemia injury. We recently reported that increased expression of Hsp20 in cardiomyocytes was associated with improved contraction and protection against beta-agonist-induced apoptosis. To investigate whether overexpression of Hsp20 exerts protective effects in both ex vivo and in vivo ischemia/reperfusion (I/R) injury, we generated a transgenic (TG) mouse model with cardiac-specific overexpression of Hsp20 (10-fold). TG and wild-type (WT) hearts were then subjected to global no-flow I/R (45 minutes/120 minutes) using the Langendorff preparation. TG hearts exhibited improved recovery of contractile performance over the whole reperfusion period. This improvement was accompanied by a 2-fold decrease in lactate dehydrogenase released from the TG hearts. The extent of infarction and apoptotic cell death was also significantly decreased, which was associated with increased protein ratio of Bcl-2/Bax and reduced caspase-3 activity in TG hearts. Furthermore, in vivo experiments of 30-minute myocardial ischemia, via coronary artery occlusion, followed by 24-hour reperfusion, showed that the infarct region-to-risk region ratio was 8.1+/-1.1% in TG hearts (n=7), compared with 19.5+/-2.1% in WT hearts (n=11, P<0.001). Our data demonstrate that increased Hsp20 expression in the heart protects against I/R injury, resulting in improved recovery of cardiac function and reduced infarction. Thus, Hsp20 may constitute a new therapeutic target for ischemic heart diseases.


Reversion of the tyrosine ochre strain Escherichia coli WU3610 under starvation conditions depends on a new gene tas.
When 3 x 10(8) bacteria of the Escherichia coli tyrA14(oc) leu308(am) strain WU3610 are plated on glucose salts agar supplemented with leucine only, colonies of slow-growing Tyr+ suppressor mutants begin to appear after about a week and increase in numbers roughly linearly with time thereafter (stationary phase or starvation-associated mutation). From a library constructed from two of these mutants, a clone was obtained that suppressed the tyrosine requirement of WU3610 when present on a multicopy plasmid. The activity was identified to an open reading frame we call tas, the sequence for which has homology with a variety of known genes with aldo-keto reductase activity. The activity of tas complements the prephenate dehydrogenase dysfunction of tyrA14 (the chorismate mutase activity of tyrA possibly being still functional). A strain deleted for tas showed no spontaneous mutation under starvation conditions. Whereas neither tas+ nor tas bacteria showed any increase in viable or total count when plated under conditions of tyrosine starvation at 3 x 10(8) cells per plate, at lower density (approximately 10(7) per plate) tas+ but not tas bacteria showed considerable residual growth. We suggest that the single copy of tas present in WU3610 allows cryptic cell or DNA turnover under conditions of tyrosine starvation and that this is an essential prerequisite for starvation-associated mutation in this system. The target gene for mutation is not tas, although an increase in the expression of this gene, for example, resulting from a suppressor mutation affecting supercoiling, could be responsible for the slow-growing Tyr+ phenotype.


HEPA filtration intervention in classrooms may improve some students' asthma.
The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing. Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma (n = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention. For those students with a higher Group 1 mold level in their pre-intervention classroom than home (n = 94), the FEV1% results for those students was significantly (p < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms. HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results.


Novel cognitive enhancer ST101 enhances acetylcholine release in mouse dorsal hippocampus through T-type voltage-gated calcium channel stimulation.
We recently developed a novel cognitive enhancer, ST101 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one), that activates T-type voltage-gated calcium channels (VGCCs). Here, we address whether T-type VGCC activation with ST101 mediates its cognitive effects in vivo and the relevance of T-type VGCC activation to acetylcholine (ACh) release in the hippocampus. Acute intraperitoneal administration of ST101 (1 mg/kg, i.p.) improved memory-related behaviors in both olfactory bulbectomized (OBX) and scopolamine-treated mice. Effects of ST101 administration were abolished by both intraperitoneal and intracerebroventricular pre-administration of the T-type VGCC inhibitor mibefradil. Acute administration of ST101 enhanced basal and nicotine-induced ACh release in the dorsal hippocampus in both OBX and sham-treated mice. Enhanced ACh release was abolished by infusion with mibefradil (10 μM) but not with the L-type VGCC inhibitor nifedipine (10 μM). As expected, significantly reduced CaMKIIα, PKCα, and ERK phosphorylation was restored by acute ST101 administration in the OBX mouse hippocampal CA1 region. Enhancement of CaMKIIα and PKCα but not ERK phosphorylation was inhibited by mibefradil (20 mg/kg, i.p.) preadministration. Increased CaMKIIα and PKCα phosphorylation was confirmed by increased phosphorylation of GluR1, synapsin I, and NR1. Taken together, stimulation of T-type VGCCs is critical for the enhanced hippocampal ACh release and improved cognitive function seen following ST101 administration.


Enhancing the sensitivity of the comet assay as a genotoxicity test, by combining it with bacterial repair enzyme FPG.
The alkaline comet assay, when employed as a genotoxicity test, has relatively low sensitivity because it fails to detect--at non-cytotoxic concentrations--known genotoxins that do not induce breaks or alkali-labile sites. We demonstrate that this limitation is overcome by incorporating in the assay the DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) to convert damaged bases to breaks. We tested 11 chemicals in human TK-6 cells: three non-cytotoxic--D-mannitol, Tris and EDTA; two cytotoxic--Triton X-100 and fluometuron; and six genotoxic--methylmethanesulphonate (MMS), methylnitrosourea (MNU), cyclophosphamide, benzo(a)pyrene, 4-nitroquinoline-1-oxide (4NQO) and etoposide. At concentrations of MMS, MNU, benzo(a)pyrene or 4NQO causing little or no cytotoxicity and few if any DNA breaks, FPG substantially enhanced the cellular response. Etoposide increased breaks but not FPG-sensitive sites. Cyclophosphamide, a DNA cross linker, gave a response without FPG at 1 μM, but there was no increase with FPG. Triton X-100-induced breaks were secondary to cytotoxicity. The remaining compounds induced no damage. Thus, FPG enhances sensitivity of the comet assay without compromising selectivity.


Two Enabling Strategies for the Stereoselective Conversion of Internal Alkynes into Trisubstituted Alkenes.
An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh3 )4 . Under these conditions, the reaction is robust, high yielding, and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that the in situ formation of a reactive organocopper intermediate and its interception by MeI is only barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To guarantee high yields and prevent net protodestannation from occurring, the reaction protocol had to be optimized such that these competing processes are properly decoupled. The new method is particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif that is present in numerous natural products. Alternatively, this particular target structure can be accessed starting from α-hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement/ alkylation sequence. The required substrates are best prepared by ruthenium-catalyzed trans-hydrosilylation or trans-hydrostannation of propargyl alcohols.


Analysis of coronary computed tomography angiography-derived pericoronary fat attenuation index characteristics in the diagnostic assessment of patients with Takayasu arteritis.
The clinical value of pericoronary adipose tissue in assessing Takayasu arteritis (TAK) with coronary artery involvement (CAI) is yet to be determined. The purpose of this study was to investigate the characteristics of pericoronary fat attenuation index (FAI) derived from coronary computed tomography angiography (CTA) in patients with TAK. This is a retrospective study involving enrollment of 111 consecutive patients (mean age, 33.92±12.48 years) who were diagnosed as TAK, of which 52 patients had coronary artery involvement (TAK-CAI) and 59 patients without coronary artery involvement (TAK-nonCAI). Based on the extent of coronary artery lesion, the TAK-CAI group was further classified into localized group (n=25) and diffused group (n=27). Furthermore, patients with TAK were divided into active group (n=33) and inactive group (n=78). Meanwhile, 51 gender-matched individuals with normal appearance in coronary CTA examination were enrolled as the control group. The pericoronary FAI was quantitatively evaluated on each coronary CTA examination groups. The diagnostic value of pericoronary FAI was determined using the area under the curve (AUC) of the receiver operating characteristic. A higher pericoronary FAI was found in TAK-nonCAI group than control group with normal coronary arteries (P<0.001). Multivariate analysis showed that the FAI is an independent risk factor for coronary involvement in TAK patients [odds ratio (OR): 1.23, 95% confidence interval (CI): 1.13-1.35, P<0.001]. With the best cut-off value of -86.50, the pericoronary FAI identified coronary involvement with 67.8% sensitivity and 74.5% specificity (AUC: 0.794, 95% CI: 0.713-0.875, P<0.001). Multivariate analysis showed that the pericoronary FAI is an independent risk factor for determination of active TAK patients (OR: 1.57, 95% CI: 1.25-1.97, P<0.001). With the best cut-off value of -79.50, the pericoronary FAI identified active inflammation with 93.9% sensitivity and 74.4% specificity (AUC: 0.911, 95% CI: 0.860-0.962, P<0.001). Coronary CTA-derived FAI is significantly increased in patients with TAK and can be used as a reliable biomarker to distinguish TAK patients from those with normal coronary arteries, and determine the extent of TAK inflammation.


I am no longer alone - How do university students perceive the possibilities of social media?
An increasing number of people have become users of social media, mostly looking for social contacts and networking. But what kind of social capital do social networking services (SNSs) provide? University students' (N = 90) experiences of and opinions on social media were studied through a semi-structured questionnaire. The following research questions were set for this study: (1) What kinds of benefits do university students perceive in the usage of social media? and (2) What kind of social capital does social media produce according to university students' opinions? Their answers were analysed with the qualitative content analysis method. The results revealed that SNSs can increase students' social capital in many ways, such as in the form of peer support groups and learning environments, and enhance bonding and communality in them. These possibilities should be better studied in educational contexts, as they can have a positive impact on students' well-being, engagement to studies and, thus, study success.


l-Proline and RNA Duplex m-Value Temperature Dependence.
The temperature dependence of l-proline interactions with the RNA dodecamer duplex surface exposed after unfolding was quantified using thermal and isothermal titration denaturation monitored by uv-absorbance. The m-value quantifying proline interactions with the RNA duplex surface area exposed after unfolding was measured using RNA duplexes with GC content ranging between 17 and 83%. The m-values from thermal denaturation decreased with increasing GC content signifying increasingly favorable proline interactions with the exposed RNA surface area. However, m-values from isothermal titration denaturation at 25.0 °C were independent of GC content and less negative than those from thermal denaturation. The m-value from isothermal titration denaturation for a 50% GC RNA duplex decreased (became more negative) as the temperature increased and was in nearly exact agreement with the m-value from thermal denaturation. Since RNA duplex transition temperatures increased with GC content, the more favorable proline interactions with the high GC content duplex surface area observed from thermal denaturation resulted from the temperature dependence of proline interactions rather than the RNA surface chemical composition. The enthalpy contribution to the m-value was positive and small (indicating a slight increase in duplex unfolding enthalpy with proline) while the entropic contribution to the m-value was positive and increased with temperature. Our results will facilitate proline's use as a probe of solvent accessible surface area changes during biochemical reactions at different reaction temperatures.


Modeling Low Muscle Mass Screening in Hemodialysis Patients.
Computed tomography (CT) can accurately measure muscle mass, which is necessary for diagnosing sarcopenia, even in dialysis patients. However, CT-based screening for such patients is challenging, especially considering the availability of equipment within dialysis facilities. We therefore aimed to develop a bedside prediction model for low muscle mass, defined by the psoas muscle mass index (PMI) from CT measurement. Hemodialysis patients (n = 619) who had undergone abdominal CT screening were divided into the development (n = 441) and validation (n = 178) groups. PMI was manually measured using abdominal CT images to diagnose low muscle mass by two independent investigators. The development group's data were used to create a logistic regression model using 42 items extracted from clinical information as predictive variables; variables were selected using the stepwise method. External validity was examined using the validation group's data, and the area under the curve (AUC), sensitivity, and specificity were calculated. Of all subjects, 226 (37%) were diagnosed with low muscle mass using PMI. A predictive model for low muscle mass was calculated using ten variables: each grip strength, sex, height, dry weight, primary cause of end-stage renal disease, diastolic blood pressure at start of session, pre-dialysis potassium and albumin level, and dialysis water removal in a session. The development group's adjusted AUC, sensitivity, and specificity were 0.81, 60%, and 87%, respectively. The validation group's adjusted AUC, sensitivity, and specificity were 0.73, 64%, and 82%, respectively. Our results facilitate skeletal muscle screening in hemodialysis patients, assisting in sarcopenia prophylaxis and intervention decisions.


Heavy metal ATPase 3 (HMA3) confers cadmium hypertolerance on the cadmium/zinc hyperaccumulator Sedum plumbizincicola.
Cadmium (Cd) is highly toxic to most organisms, but some rare plant species can hyperaccumulate Cd in aboveground tissues without suffering from toxicity. The mechanism underlying Cd detoxification by hyperaccumulators is interesting but unclear. Here, the heavy metal ATPase 3 (SpHMA3) gene responsible for Cd detoxification was isolated from the Cd/zinc (Zn) hyperaccumulator Sedum plumbizincicola. RNA interference (RNAi)-mediated silencing and overexpression of SpHMA3 were induced to investigate its physiological functions in S. plumbizincicola and a nonhyperaccumulating ecotype of Sedum alfredii. Heterologous expression of SpHMA3 in Saccharomyces cerevisiae showed Cd-specific transport activity. SpHMA3 was highly expressed in the shoots and the protein was localized to the tonoplast. The SpHMA3-RNAi lines were hypersensitive to Cd but not to Zn, with the growth of shoots and young leaves being severely inhibited by Cd. Overexpressing SpHMA3 in the nonhyperaccumulating ecotype of S. alfredii greatly increased its tolerance to and accumulation of Cd, but not Zn. These results indicate that elevated expression of the tonoplast-localized SpHMA3 in the shoots plays an essential role in Cd detoxification, which contributes to the maintenance of the normal growth of young leaves of S. plumbizincicola in Cd-contaminated soils.


Dominant A1: angiographic and clinical correlations with anterior communicating artery aneurysms.
It has been observed but never proven that anomalies of the anterior communicating artery complex are associated with anterior communicating artery aneurysms (ACAA). Therefore, in an effort to understand the significance of haemodynamic factors in the genesis, as well as the clinical course of ACAA, we evaluated the correlation between certain angiographic patterns of flow in the anterior circulation and the clinical findings of 51 patients with ACAA compared with 50 matched controls. Four significant associations which have never been validated were identified: 1) a dominant A1 (filling both A2's) was found in 57% of ACAA patients versus 14% of controls (p less than 0.001). 2) Unilateral hypoplasia of the opposite A1 was present in 24% of ACAA patients versus 6% of controls (p = 0.01). 3) Exclusive filling of the ACAA from one A1 occurred in 78%. 4) No statistically significant relationship was found between the anatomic flow patterns studied and the patients clinical presentation including age, sex, or grade. We conclude that anterior communicating artery aneurysms are significantly related in a majority of patients with the presence of a dominant A1, probably as the result of enhanced haemodynamic stress caused by this anatomic abnormality in the circulation. However, this association is not constant, and a dominant pattern of flow did not correlate with the clinical course. This is probably a reflection of the differences between factors initiating aneurysm formation and those influencing its growth, as well as of the relative limitations of angiography when pathophysiological extrapolations are attempted.


Epidermal cyst of the breast.
Two cases of epidermal cyst of the breast are presented. Mammography and ultrasonography merely confirmed that the masses were solid. As is usual with these extremely rare lesions, the initial diagnoses (fibroadenoma and carcinoma) were incorrect.


A high performance computing technology powered multimedia fusion model in university English translation.
Various forms of materials, such as pictures, videos and texts, have rapidly brought the college English translation teaching model into the era of multimedia integration. This makes it difficult for English teachers to improve college English translation by using unique materials, so as to form their own unique teaching style. In view of this, a multimedia comprehensive English translation framework based on the combination of big data technology and multimedia teaching mode is proposed. At the same time, the idea of building the framework is introduced from two perspectives: the integration of big data technology and multimedia, and the integration of multimedia and English teaching process. Then, a recursive neural network algorithm based on ant colony optimization algorithm is proposed and tested. Finally, the simulation results show that the proposed method has significantly improved the accuracy and retention rate, indicating the effectiveness of the framework.


Crotoxin Inhibits Endothelial Cell Functions in Two- and Three-dimensional Tumor Microenvironment.
Antitumor property of Crotoxin (CTX), the major toxin from Crotalus durissus terrificus snake venom, has been demonstrated in experimental animal models and clinical trials. However, the direct action of this toxin on the significant events involved in neovascularization, which are essential for tumor growth and survival, has not been confirmed. This study investigated the effects of CTX on the key parameters of neovascularization in two- and three-dimensional culture models. Murine endothelial cell lines derived from thymus hemangioma (t.End.1) were treated at different concentrations of CTX (6.25-200 nM). Endothelial cell proliferation, cell adhesion, and actin cytoskeletal dynamics on laminin (10 µg/ml), type I collagen (10 µg/ml), and fibronectin (3 µg/ml) were evaluated along with the endothelial cell migration and formation of capillary-like tubes in 3D Matrigel. CTX concentration of 50 nM inhibited tube formation on 3D Matrigel and impaired cell adhesion, proliferation, and migration under both culture medium and tumor-conditioned medium. These actions were not accountable for the loss of cell viability. Inhibition of cell adhesion to different extracellular matrix components was related to the reduction of αv and α2 integrin distribution and cytoskeletal actin polymerization (F-actin), accompanied by inhibition of focal adhesion kinase (FAK), Rac1 (GTPase) signaling proteins, and actin-related protein 2/3 (Arp 2/3) complex. This study proved that CTX inhibits the major events involved in angiogenesis, particularly against tumor stimuli, highlighting the importance of the anti-angiogenic action of CTX in inhibition of tumor progression.


In Vivo Evaluation of the Mechanical and Viscoelastic Properties of the Rat Tongue.
The tongue is a highly innervated and vascularized muscle hydrostat on the floor of the mouth of most vertebrates. Its primary functions include supporting mastication and deglutition, as well as taste-sensing and phonetics. Accordingly, the strength and volume of the tongue can impact the ability of vertebrates to accomplish basic activities such as feeding, communicating, and breathing. Human patients with sleep apnea have enlarged tongues, characterized by reduced muscle tone and increased intramuscular fat that can be visualized and quantified by magnetic resonance imaging (MRI). The abilities to measure force generation and viscoelastic properties of the tongue constitute important tools for obtaining functional information to correlate with imaging data. Here, we present techniques for measuring tongue force production in anesthetized Zucker rats via electrical stimulation of the hypoglossal nerves and for determining the viscoelastic properties of the tongue by applying passive Lissajous force/deformation curves.


A study of the binding of NADP coenzymes to dihydrofolate reductase by raman difference spectroscopy.
We report here the Raman spectra of NADPH, NADP+, 3-acetylpyridine adenine dinucleotide (AcPdADP+), NADH and a fragment of these molecules, 2'-phospho-adenosine-5'-diphosphoribose (Ado2'p5'ppRib), bound to Escherichia coli dihydrofolate reductase (DHFR). The positions that are observed for the bound adenosine 'triplet' bands are consistent with a protein binding pocket for this group which is quite hydrophobic in nature. No binding effect is observed on Raman bands associated with the nicotinamide group of NADP+ as a binary complex with DHFR, suggesting very loose, if any, binding of this group. In contrast, changes in the Raman spectrum of the nicotinamide group of NADP+ bound to an inhibitor (trimethoprim) ternary complex of DHFR are clearly observed which indicate substantial binding interaction. The carboxamide group of bound NADPH (and NADH) adopts the trans conformation. A 35-cm-1 upshift is observed in the rocking motion of the carboxamide -NH2 group of NADPH, and a 5-cm-1 upward shift is seen in the C=O stretch mode of AcPdADP+ upon binding to the enzyme-trimethoprim complex. These results suggest that the -NH2 group of the carboxamide moiety is more tightly hydrogen bonded in the protein binding pocket than in solution while that of the C=O group is less tightly hydrogen bonded; these hydrogen bonds would appear to be responsible for holding the nicotinamide headgroup in place properly for catalysis. We have compared this with the results obtained previously in other protein complexes, and interpret the observed shifts in these bands as a measure of the hydrogen bonding enthalpy of the -NH2 and C=O groups with their protein environments. Perhaps surprisingly, the magnitude of the hydrogen bonding enthalpy takes on a limited number of discrete values over five protein complexes rather than over a continuous range. The effect that this has on the catalytic properties of DHFR and the other NAD dehydrogenases that we have studied to date, particularly their stereochemistry, is discussed. A small downward shift is observed for the P = O stretch of the 2'-phosphate moiety of NADP. This indicates that the 2'-phosphate moiety binds to DHFR in the dianionic form. Furthermore, the local enthalpic interaction that the 2'-phosphate group has with protein is stronger than its interaction with water.


Prevention of autoimmune type I diabetes in biobreeding (BB) rats by a newly established, autoreactive T cell line from acutely diabetic BB rats.
An autoreactive T cell line, BNY-2, was established from lymphocytes isolated from the islets of acutely diabetic BioBreeding (BB) rats after continuous stimulation of the isolated lymphocytes by irradiated lymph node cells. Flow cytometric analysis showed that BNY-2 cells were positive for CD4 and CD5 and were negative for CD8 and RT6, indicating that these cells were phenotypically Th cells rather than cytotoxic T cells. mAbs against rat MHC class II Ags (anti-RT1.D) blocked the proliferation response of BNY-2 cells, suggesting that these cells recognize the MHC class II Du molecule. When splenic T lymphocytes from diabetes-prone BB rats were stimulated by Con A in the presence of irradiated BNY-2 cells or irradiated lymph node cells, the BNY-2 cells had a significant suppressive effect on splenic T cell proliferation, whereas lymph node cells had no effect. When we injected diabetes-prone BB rats i.v. at 30 and 60 days of age with activated BNY-2 cells, the incidence of diabetes was significantly reduced compared with that seen in saline-injected control rats (diabetic incidences were 12 and 80%, respectively). On the basis of these observations, we conclude that autoreactive BNY-2 T cells, established from the pancreatic islets of acutely diabetic BB rats, can prevent the development of autoimmune diabetes in the diabetes-prone BB rat by an immunosuppressive effect.


Loss of perivascular aquaporin-4 in idiopathic normal pressure hydrocephalus.
Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of dementia that may be successfully treated with cerebrospinal fluid (CSF) diversion. Recently, magnetic resonance imaging (MRI) using a MRI contrast agent as a CSF tracer revealed impaired clearance of the CSF tracer from various brain regions such as the entorhinal cortex of iNPH patients. Hampered clearance of waste solutes, for example, soluble amyloid-β, may underlie neurodegeneration and dementia in iNPH. The goal of the present study was to explore whether iNPH is associated with altered subcellular distribution of aquaporin-4 (AQP4) water channels, which is reported to facilitate CSF circulation and paravascular glymphatic drainage of metabolites from the brain parenchyma. Cortical brain biopsies of 30 iNPH patients and 12 reference individuals were subjected to AQP4 immunogold cytochemistry. Electron microscopy revealed significantly reduced density of AQP4 water channels in astrocytic endfoot membranes along cortical microvessels in patients with iNPH versus reference subjects. There was a significant positive correlation between density of AQP4 toward endothelial cells (perivascular) and toward parenchyma, but the reduced density of AQP4 toward parenchyma was not significant in iNPH. We conclude that perivascular AQP4 expression is attenuated in iNPH, potentially contributing to impaired glymphatic circulation, and waste clearance, and subsequent neurodegeneration. Hence, restoring normal perivascular AQP4 distribution may emerge as a novel treatment strategy for iNPH.


[A case of superficial carcinoma in a diverticulum of the thoracic esophagus].
An upper gastrointestina(l GI) series revealed a diverticulum in the anterior wall of the middle thoracic esophagus of a 72-year-old man. Endoscopy revealed a type 0-IIc lesion in the esophageal diverticulum. The margin of the lesion was unclear. Biopsy proved that it was squamous cell carcinoma. Endoscopic ultrasonography showed that the deepest layer of the tumor was the lamina propria mucosae (cT1a-LPM) and that the underlying muscularis propria was thinning. No distant metastasis or regional lymph node metastasis was detected. Diverticulectomy or endoscopic submucosal dissection (ESD) was out of indication due to the unclear margin and thin muscularis propria. We conducted mediastinoscopy-assisted esophagectomy. The pathological diagnosis of the resected specimen was moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosae (pT1a-LPM). Pathological examination proved the thinning of the underlying muscularis propria in the diverticulum. The patient is alive without recurrence at 6 months after surgery.


[A case report of successful control of liver metastasis from duodenal cancer with combined S-1 and docetaxel chemotherapy].
A 70-year-old man with abdominal pain and anemia was diagnosed with duodenal cancer upon upper gastrointestinal endoscopy and biopsy. Pancreatoduodenectomy was performed. Pathological findings were duodenal cancer, T 4 SI (Panc) N0P0V0A0H0. Three months after operation, abdominal CT showed multiple liver metastasis. He then underwent combined chemotherapy consisting of two weeks administration of S-1 (80 mg/body) followed by one week rest and injections of docetaxel (40 mg/body) every three weeks as one course. Metastatic tumors were gradually reduced and successfully controlled,and there was no other recurrence until he died about three years later of another illness. Combined S-1 and docetaxel chemotherapy is known to be effective for esophageal cancer, gastric cancer and other digestive cancer, as well as for duodenal cancer.


CHARMM-GUI-Based Induced Fit Docking Workflow to Generate Reliable Protein-Ligand Binding Modes.
Molecular docking is a preferred method to predict ligand binding modes and their binding energy to target protein receptors, which is critical in early phase structure-based drug discovery. However, there is a persistent challenge in docking that can be attributed to the induced fit effect, as receptor binding sites undergo induced fit conformational changes upon ligand binding to achieve better binding modes. In this work, based on CHARMM-GUI LBS Finder& Refiner and High-Throughput Simulator, we present a straightforward CHARMM-GUI induced fit docking (CGUI-IFD) workflow to generate reliable protein-ligand binding modes. The CGUI-IFD workflow generates an ensemble of receptor binding site conformations through ligand-binding site (LBS) refinement, runs rigid receptor docking, and performs high-throughput molecular dynamics (MD) simulations of protein-ligand complex structures in explicit solvents. The results are evaluated based on the ligand root-mean-square deviation (RMSD)-based binding stability and the molecular mechanics generalized Born surface area binding energy. For a benchmark test, we used 258 cross-docking protein-ligand pairs across 41 target proteins from the Schrodinger IFD-MD data set. The application of CGUI-IFD on this data set shows 80% success rate (within 2.5 Å RMSD from the experimental structures). We expect that the CGUI-IFD workflow can be useful to generate reliable ligand binding modes for cross-docking cases.


LncRNA PTCSC3 affects drug resistance of anaplastic thyroid cancer through STAT3/INO80 pathway.
LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study. Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively. MTT assay was performed to detect cytotoxicity. Chromatin immunoprecipitation was conducted to identify interactions between STAT3 and DNA promoter of INO80. LncRNA PTCSC3 was low-expressed in ATC tissues and cells. Over-expressed PTCSC3 inhibited the drug resistance of ATC to doxorubicin. PTCSC3 negatively regulated STAT3, and STAT3 promoted expression of INO80. PTCSC3 regulated INO80 through STAT3. PTCSC3 suppressed stem cells properties and drug resistance of ATC to doxorubicin. LncRNA PTCSC3 inhibits INO80 expression by negatively regulating STAT3, and thereby attenuating drug resistance of ATC to chemotherapy drug doxorubicin.


Do lesbians overestimate alcohol use norms? Exploring the potential utility of personalized normative feedback interventions to reduce high-risk drinking in Southern California lesbian communities.
This study examines the potential utility of social norms-based approaches to reduce heavy alcohol use in lesbian community settings. In a sample of 278 Southern Californian lesbians recruited from social media networks to complete an online survey, the majority of participants overestimated the quantity of alcohol consumed by their lesbian peers and more frequent lesbian bar attendance was associated with elevated perceptions of how much other lesbians drink. Greater than 90% of participants expressed interest in receiving personalized normative feedback, suggesting that culturally tailored personalized normative feedback interventions focused on correcting perceptions of heavy drinking may be successful in mitigating the alcohol-related risks of lesbians in Southern California, and potentially beyond.


[Efficacy of somatostatin analogues in the treatment of neuroendocrine tumours based on the results of recent clinical trials].
Due to their inhibitory effects on hormone secretion, somatostatin analogues are of pivotal importance in the symptomatic treatment of hormone-secreting neuroendocrine tumours. Although several earlier clinical observations supported the view that these biological agents are capable of inhibiting the growth of neuroendocrine tumours, the PROMID study published in 2009 was the first to confirm the inhibitory effect of octreotide on tumour growth and demonstrated the prolongation of progression free survival. These findings have been confirmed and extended by the most recent CLARINET trial with lanreotide published in 2014. Somatostatin analogues are capable of inhibiting tumour growth and stabilizing disease irrespective of the hormonal activity of the tumour and, therefore, their applicability is expected to be extended to the treatment of hormonally inactive neuroendocrine tumours, as well.


Verticillium Species Skin Infection in a Renal Transplant Patient.
Verticillium species is a filamentous fungus that inhabits decaying vegetation and soil. It is known to cause disease in plants. Four cases of human infections have been reported previously in nontransplant patients. Here, we report the first case of Verticillium species skin infection in a transplant patient who was successfully treated with fluconazole monotherapy.


Turn-on and blue-shift fluorescence sensor toward L-histidine based on stable CdII metal-organic framework with tetranuclear cluster units.
A novel CdII-based two-fold interpenetrated metal-organic framework (MOF), namely {[Cd2(BTDB)2(4,4-bpy)]·DMF}n (JXUST-14), (H2BTDB = 4,4'-(benzo[c][1,2,5]thiadiazole-4,7-diyl)dibenzoic acid and 4,4-bpy = 4,4-bipyridine), has been prepared and characterized. Single-crystal structure determination reveals that JXUST-14 has a tetranuclear cluster based 6-connected pcu topological network with Schlafli symbol {412·63}. When soaked in common organic solvents and aqueous solutions with diverse pH values of 2-12 for 48 h, JXUST-14 remains stable. JXUST-14 is a highly selective and sensitive luminescent sensor for L-histidine (His) with a detection limit of 11.1 ppm. JXUST-14 is the first CdII-based MOF for the detection of His via turn-on and fluorescence blue-shift effects. Experimental study and theoretical calculation suggest that the sensing process can be mainly attributed to a charge transfer and energy transfer mechanism. More interestingly, LED lamps of JXUST-14 and JXUST-14@His were successfully developed, which endowed efficient sensitivity for His detection and thus provide great potential for future applications.