Construction of a Hierarchical Architecture of Covalent Organic Frameworks via a Postsynthetic Approach.
Covalent organic frameworks (COFs) represent an emerging class of crystalline porous materials that are constructed by the assembly of organic building blocks linked via covalent bonds. Several strategies have been developed for the construction of new COF structures; however, a facile approach to fabricate hierarchical COF architectures with controlled domain structures remains a significant challenge, and has not yet been achieved. In this study, a dynamic covalent chemistry (DCC)-based postsynthetic approach was employed at the solid-liquid interface to construct such structures. Two-dimensional imine-bonded COFs having different aromatic groups were prepared, and a homogeneously mixed-linker structure and a heterogeneously core-shell hollow structure were fabricated by controlling the reactivity of the postsynthetic reactions. Solid-state nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscopy (TEM) confirmed the structures. COFs prepared by a postsynthetic approach exhibit several functional advantages compared with their parent phases. Their Brunauer-Emmett-Teller (BET) surface areas are 2-fold greater than those of their parent phases because of the higher crystallinity. In addition, the hydrophilicity of the material and the stepwise adsorption isotherms of H2O vapor in the hierarchical frameworks were precisely controlled, which was feasible because of the distribution of various domains of the two COFs by controlling the postsynthetic reaction. The approach opens new routes for constructing COF architectures with functionalities that are not possible in a single phase.


Impact of priming on global soil carbon stocks.
Fresh carbon input (above and belowground) contributes to soil carbon sequestration, but also accelerates decomposition of soil organic matter through biological priming mechanisms. Currently, poor understanding precludes the incorporation of these priming mechanisms into the global carbon models used for future projections. Here, we show that priming can be incorporated based on a simple equation calibrated from incubation and verified against independent litter manipulation experiments in the global land surface model, ORCHIDEE. When incorporated into ORCHIDEE, priming improved the model's representation of global soil carbon stocks and decreased soil carbon sequestration by 51% (12 ± 3 Pg C) during the period 1901-2010. Future projections with the same model across the range of CO2 and climate changes defined by the IPCC-RCP scenarios reveal that priming buffers the projected changes in soil carbon stocks - both the increases due to enhanced productivity and new input to the soil, and the decreases due to warming-induced accelerated decomposition. Including priming in Earth system models leads to different projections of soil carbon changes, which are challenging to verify at large spatial scales.


Measuring the Mechanical Properties of Glass Fiber Reinforcement Polymer Composite Laminates Obtained by Different Fabrication Processes.
The traditional wet hand lay-up process (WL) has been widely applied in the manufacturing of fiber composite laminates. However, due insufficiency in the forming pressure, the mass fraction of fiber is reduced and lots of air bubbles are trapped inside, resulting in low-quality laminates (low stiffness and strength). The wet hand lay-up/vacuum bag (WLVB) process for the fabrication of composite laminates is based on the traditional wet hand lay-up process, using a vacuum bag to remove air bubbles and provide pressure, and then carrying out the heating and curing process. Compared with the traditional hand lay-up process, laminates manufactured by the WLVB process show superior mechanical properties, including better strength and stiffness, higher fiber volume fraction, and lower void volume fraction, which are all benefits for composite laminates. This process is completely manual, and it is greatly influenced by the skills of the preparation personnel. Therefore, the products are prone to defects such as voids and uneven thickness, leading to unstable qualities and mechanical properties of the laminate. Hence, it is necessary to finely describe the WLVB process, finely control steps, and quantify material ratios, in order to ensure the mechanical properties of laminates. This paper describes the meticulous process of the WLVB process for preparing woven plain patterned glass fiber reinforcement composite laminates (GFRPs). The fiber volume content of laminates was calculated using the formula method, and the calculated results showed that the fiber volume content of WL laminates was 42.04%, while that of WLVB laminates was 57.82%, increasing by 15.78%. The mechanical properties of the laminates were characterized using tensile and impact tests. The experimental results revealed that with the WLVB process, the strength and modulus of the laminates were enhanced by 17.4% and 16.35%, respectively, and the specific absorbed energy was increased by 19.48%.


The tracheal accordion and the position of the endotracheal tube.
The purpose of this review is to, first, determine the static factors that affect the length of the human trachea across different populations and, second, to investigate whether or not there are dynamic factors that cause the length of the human trachea to vary within the same individual. We also investigated whether these changes in tracheal length within the same individual are significant enough to increase the risk of endobronchial intubation or accidental extubation. A PubMed/MEDLINE and a Web of Science database English-language literature search was conducted in May 2016 with relevant keywords and MeSH terms when available. We found that gender, extremes of age, patient height, postsurgical changes and co-existing disease are static patient factors that affect the length of the human trachea. Dynamic clinical changes that occur under anaesthesia, including Trendelenburg position, head and neck flexion and extension, paralysis of the diaphragm and pneumoperitoneum, cause the trachea to act as an accordion, decreasing and increasing its length. The length of the human trachea in both awake and anaesthetised and paralysed patients is a critical consideration in preventing both endobronchial intubation and tracheal extubation. It is clear from the literature that tracheal length varies widely across populations and, additionally, with the dynamic clinical changes that occur under anaesthesia, the trachea acts as an accordion decreasing and increasing its length within the same individual. Knowledge of the magnitude of the change in tracheal dimensions in response to these factors is an important clinical consideration.


Radiosensitivity and thermosensitization of thermotolerant Chinese hamster cells and RIF-1 tumors.
CHO cells subline HA-1 were made thermotolerant by a priming heat treatment (43 degrees C, 30 min). Later, 4, 16, or 24 hr, they were either irradiated or heated (43 degrees C, 30 min) and irradiated. Thermotolerance had no effect on the radiation sensitivity of the cells as measured by the D0 value of the clonogenic survival curve. However, the N value of the curve (width of shoulder) showed a significant increase at 24 hr, indicating an increased capacity to accumulate sublethal damage. This indicates that the fractionation schedule 43 degrees C, 30 min + 37 degrees C, 24 hr + 43 degrees C, 30 min + X ray required approximately 100 rad more radiation than 43 degrees C, 30 min + X ray to reduce survival to the same level. The same priming treatment was given to RIF-1 tumors growing in C3H mice. Later, 24 hr, when the tumors were either irradiated or heated (43 degrees C, 30 min) and irradiated, it was found that thermotolerance had no effect on the radiosensitivity of the cells as measured by in vitro assay. However, thermal radiosensitization was not apparent 24 hr after the priming treatment.


The interrelationships between facial areas and other body dimensions.
The data from 35 premenarchial Gujarati, Hindu girls, selected at random, in the age range of 120 months to 144 months were collected to find out statistically the nature and the values of correlation coefficients among various facial areas and other body dimensions such as body weight, stature, chronological and skeletal ages. The correlation coefficients between skeletal, chronological, height and weight ages ranged from 0.413 to 0.8105 showing moderately high association. Height and weight ages turned out to be the most reliable indicators of growth and development of facial areas in this age group and the chronological age as in ineffectual indicator of the same. Maxillary and mandibular areas showed a high value of correlation coefficients (0.67) while the orbitoethmoidal area did not show any correlation with any age variables or with other facial areas. The mandibular areas showed the highest correlation with weight age (0.63) and lowest with chronological age (0.431). The maxillary area showed highest correlation with chronological age (0.62) and lowest with skeletal age (0.42). Fifteen empirical formulae have been developed by which average value of facial areas could be predicted from the other variables.


The tourist as patient.
A review is presented of patients, mainly Australians and New Zealanders, who came to Fiji as tourists. One hundred and seven patients were seen in a six-month period in a general practice near Nadi International Airport, and 39 patients were admitted to the medical unit of the nearby Divisional Hospital over a two-year period. Attention is drawn to the need for informed advice to be given to patients about to embark on holidays abroad, and some of the common problems are discussed.


Falling weight deflectometer dispersion curve method for pavement modulus calculation.
The falling weight deflectometer (FWD) test is a common non-destructive testing method for evaluating the structural capacity of pavements. At present, data processing of the FWD test mainly focuses on the deflection data, while paying less attention to the deflection-time history. Because a FWD is equipped with impulse loads and geophones, which allow for the generation and capture of surface wave signal propagation, it is hypothesized that Rayleigh wave dispersion theory can be applied to calculate the modulus profile along the pavement depth by analysing the dispersive properties of the deflection signal measured during FWD tests. To test this hypothesis, we develop a new methodology for the FWD test and data analysis, referred to as the FWD dispersion curve method. We first introduce the concept of the new method, followed by an illustration of the procedure and the experimental set-up. Case studies on three concrete pavement segments are then presented to evaluate the effectiveness of the FWD dispersion curve method. Modifications to the existing FWD device are further recommended for the impact loading sources and signal collection process so that the modulus of a much shallower layer, such as the concrete slab and upper asphalt layers, can be obtained. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Giant cell myocarditis presenting with acute heart failure.
Idiopathic giant cell myocarditis (GCM) is a rare and rapidly progressing form of myocarditis predominantly affecting younger people. We report a case of a 23-year-old athletic patient who presented with features of acute heart failure due to GCM and discuss his management that included a left ventricular assist device as a bridge to transplant. He died immediately following the transplant.We also review the literature on this rare disease, highlighting the advances in the management of the disease including immunosuppressive therapy, ventricular assist devices and heart transplantation.


Serum 25-hydroxyvitamin D concentrations are associated with nuclear factor kappa-B activity but not with inflammatory markers in healthy normoglycemic adults.
Vitamin D has been reported to have anti-inflammatory properties in in vitro and animal studies, which are thought to occur via inhibition of the nuclear factor kappa-B (NFκB) pathway. However, the association between vitamin D and in vivo NFκB activity in humans has not previously been reported. The aim of the present study was to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and NFκB activity in peripheral blood mononuclear cells (PBMCs) as well as plasma inflammatory markers in healthy individuals. We hypothesized that 25(OH)D concentrations would be negatively associated with NFκB activity and pro-inflammatory markers downstream of NFκB, and positively associated with anti-inflammatory markers. We measured circulating 25(OH)D (chemiluminescent immunoassay); anthropometry: body mass index (BMI), waist-to-hip ratio (WHR), and % body fat (dual X-ray absorptiometry); plasma pro- and anti-inflammatory markers: high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and IL-10 (ELISA); and NFκB activity in PBMCs (DNA-binding assay). Forty-nine participants were included in the study (21M/28F; age=31.6±10.2years (mean±SD); BMI=28.4±4.6kg/m2; % body fat=30.2±9.3%). Mean 25(OH)D concentration was 48.2±24.5 nmol/l. There were no differences in 25(OH)D concentrations between genders and no association between 25(OH)D concentrations and age, BMI, or % body fat (all p>0.1). Serum 25(OH)D concentrations were positively associated with NFκB activity in PBMCs (r=0.48, p=0.0008) but not with any of the pro- or anti-inflammatory markers measured (all p>0.1). After adjusting for age, sex, and % body fat, 25(OH)D concentrations remained positively associated with NFκB activity in PBMCs (β=0.55, p<0.0001). Although in-vitro studies suggest that vitamin D inhibits NFκB activity, our novel cross-sectional data from a cohort of healthy individuals suggest that vitamin D may regulate rather than inhibit the NFκB pathway. Large-scale intervention and mechanistic studies are needed to further investigate the effects of vitamin D on NFκB activity in vivo in humans.


Lack of sleep is associated with internet use for leisure.
Previous studies have suggested that excessive internet use may cause lack of sleep. However, recent studies have hypothesized that lack of sleep may instigate internet use for leisure. To elucidate the potential effects of sleep time on internet use, we explored the different associations between sleep time and internet use according to its purpose. The population-based, cross-sectional study group from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) collected data from 57,425 middle school students in 2014 and 2015. Sleep time over the past 7 days was classified into the following groups: < 7 h (6 h); ≥ 7 h, < 8 h (7 h); ≥ 8 h, < 9 h (8 h); and ≥ 9 h (9+ h). Internet use time per day was separately surveyed for leisure and for study and categorized as follows: 0 h; > 0 h, ≤ 1 h (1 h); > 1 h, ≤ 2 h (2 h); and > 2 h (2+ h) per day. Information on age, sex, region of residence, body mass index (BMI), economic level, parental education level, stress level, school performance level, and sleep satisfaction were retrieved. The relationships between sleep time and internet use time for leisure/study were analyzed using multinomial logistic regression with complex sampling. In the subgroup analysis according to sleep satisfaction (good, normal, and poor), the associations of sleep time with internet use for leisure were analyzed using the same methods. Compared to 9+ h of sleep, less sleep was related to a long internet use time (2+ h) for leisure (adjusted odds ratio, AOR [95% confidence interval, CI] of sleep: 8 h = 1.23 [1.14-1.32]; 7 h = 1.42 [1.31-1.54]; and 6 h = 1.56 [1.44-1.70]; P < 0.001). Conversely, a relationship between less sleep and a long internet use time (2+ h) for study was evident only for 6 h of sleep (AOR of sleep: 8 h = 0.84 [0.84-1.04]; 7 h = 1.05 [0.94-1.17]; and 6 h = 1.32 [1.27-1.59]; P < 0.001). In the subgroup analysis according to sleep satisfaction, less sleep was associated with a long internet use time for leisure in all sleep satisfaction groups, although the relationship was more significant in the lower sleep satisfaction group. Less sleep was significantly related to long-term use of the internet for leisure, whereas this association was not definite for internet use for study. Furthermore, poor sleep quality potentiated the relationship between less sleep time and internet use for leisure.


Study of fundamental wave depletion in intracavity second harmonic generation.
In this paper, a novel approach to modelling intracavity second harmonic generation (SHG) in periodically poled MgO-doped lithium niobate (PPLN) is presented and verified against experimental results. This approach involves combining the coupled nonlinear wave equations with a rate equation model for a diode-pumped solid-state Nd:YVO4 laser, taking into account both the depletion of the fundamental wave due to the energy conversion from the fundamental wave to the SHG wave and the reduction of the fundamental wave within a laser cavity due to the loss as a result of the SHG nonlinear process. It was shown that the theoretical simulation matched the experimental results well, while also providing physical insight into the importance of the fundamental wave depletion in the intracavity SHG nonlinear processes. The resulting model is computationally simple and has the potential to generalize to the other nonlinear processes such as three-wave mixing and optical parametric oscillation.


An interconnection between tip-focused Ca2+ and anion homeostasis controls pollen tube growth.
Plant reproduction is the basis for economically relevant food production. It relies on pollen tube (PTs) growth into the female flower organs for successful fertilization. The high cytosolic Ca2+ concentration ([Ca2+]cyt) at the PT tip is sensed by Ca2+-dependent protein kinases (CPKs) that in turn activate R- and S-type anion channels to control polar growth. Lanthanum, a blocker for plant Ca2+-permeable channels was used here to demonstrate a strict dependency for anion channel activation through high PT tip [Ca2+]cyt. We visualized this relationship by live-cell anion imaging and concurrent triggering of Ca2+-elevations with the two-electrode voltage-clamp (TEVC) technique. The anion efflux provoked by a TEVC-triggered [Ca2+]cyt increase was abolished by Lanthanum and was followed by an overall rise in the cytosolic anion concentration. An interrelation between Ca2+ and anion homeostasis occurred also on the transcript level of CPKs and anion channels. qRT-PCR analysis demonstrated a co-regulation of anion channels and CPKs in media with different Cl- and NO3- compositions. Our data provides strong evidence for the importance of a Ca2+-dependent anion channel regulation and point to a synchronized adjustment of CPK and anion channel transcript levels to fine-tune anion efflux at the PT tip.


[Monochromators for cytophotometers and cytofluorimeters].
Two monochromators for microspectrophotometers are described. The attachments have been designed so that the peculiarities of the optical system of microscope have been taken into consideration. Simple, small sized monochromator is executed as a part of biological microscope and will be used mainly in cytophotometry. Another attachment is a commercially available single monochromator which has been easily adapted as a double one for using in cytophluorimetry by means of autoreflector set behing the exit split.


'She thought the same way I that I thought:' a qualitative study of patient-provider concordance among Gulf War Veterans with Gulf War Illness.
Objective: Medically unexplained symptoms (MUS), such as chronic fatigue syndrome, irritable bowel syndrome, and Gulf War Illness (GWI), are difficult to treat. Concordance-shared understanding between patient and provider about illness causes, course, and treatment-is an essential component of high-quality care for people with MUS. This qualitative paper focuses on the experiences of United States military Veterans living with GWI who have endured unique healthcare challenges. Methods & Measures: Qualitative interviews were conducted with 31 Veterans with GWI to explore factors that contribute to and detract from concordance with their Veteran Affairs (VA) healthcare providers. In addition to being seen by VA primary care, over half of participants also sought care at a War Related Illness and Injury Study Center, which specializes in post-deployment health. Deductive and inductive codes were used to organize the data, and themes were identified through iterative review of coded data. Results: Major themes associated with patient-provider concordance included validation of illness experiences, perceived provider expertise in GWI/MUS, and trust in providers. Invalidation, low provider expertise, and distrust detracted from concordance. Conclusion: These findings suggest providers can foster concordance with MUS patients by legitimizing patients' experiences, communicating knowledge about MUS, and establishing trust.


Bayesian hypothesis testing for single-subject designs.
Researchers using single-subject designs are typically interested in score differences between intervention phases, such as differences in means or trends. If intervention effects are suspected in data, it is desirable to determine how much evidence the data show for an intervention effect. In Bayesian statistics, Bayes factors quantify the evidence in the data for competing hypotheses. We introduce new Bayes factor tests for single-subject data with 2 phases, taking serial dependency into account: a time-series extension of Rouder, Speckman, Sun, Morey, and Iverson's (2009) Jeffreys-Zellner-Siow Bayes factor for mean differences, and a time-series Bayes factor for testing differences in intercepts and slopes. The models we describe are closely related to interrupted time-series models (McDowall, McCleary, Meidinger, & Hay, 1980).


Goal-Directed Haemodynamic Therapy Improves Patient Outcomes in Kidney Transplantation.
Introduction: Kidney transplant graft function depends on optimised haemodynamics. However, high fluid volumes risk hypervolaemic complications. The Edwards Lifesciences ClearSight™ device permits fluid titration through markers of preload and beat-to-beat blood pressure monitoring. We evaluated the implementation of a novel goal-directed haemodynamic therapy protocol to determine whether patient outcomes had improved. Design: A retrospective evaluation of standard care versus goal-directed haemodynamic therapy in adults undergoing kidney transplantation was performed in a single centre between April 2016 and October 2019. Twenty-eight standard-of-care patients received intraoperative fixed-rate infusion and 28 patients received goal-directed haemodynamic therapy. The primary outcome was volume of fluid administered intraoperatively. Secondary outcomes included blood product and vasoactive drug exposure, graft and recipient outcomes. Results: Intraoperative fluid administered was significantly reduced in the goal-directed haemodynamic therapy cohort (4325 vs 2751 ml, P < .001). Exposure to vasopressor (67.9% vs 42.9%, P = .060) and blood products (17.9% vs 3.6%, P = .101) was unchanged. Immediate graft function (82.1% vs 75.0%, P = .515), dialysis requirement (14.3% vs 21.4%, P = .729) and creatinine changes post-operatively were unchanged. In the goal-directed haemodynamic therapy cohort, 1 patient had pulmonary oedema (3.6%) versus 21.4% in the standard cohort. Patients in the goal-directed haemodynamic therapy group were more likely to mobilise within 48 hours of surgery (number needed to treat = 3.5, P = .012). Conclusions: Protocolised goal-directed haemodynamic therapy in kidney transplantation was safe and may improve patient, graft, and surgical outcomes. Clinical trials assessing goal-directed approaches are needed.


Case Report: Successful treatment with methotrexate in a 10-year-old boy with co-occurrence of generalized psoriasis and vitiligo.
The co-occurrence of psoriasis (PsO) and vitiligo is rare in Asian countries, especially in children. This case report presents the first-ever occurrence of PsO combined with vitiligo in an Asian boy under 6 years of age, in whom symptom improvement was observed after the use of methotrexate (MTX) as the sole treatment. Although previous studies have indicated that there is a close correlation between the two diseases, methotrexate (MTX), which is a commonly used treatment for PsO, is not a standard treatment for vitiligo. Even with advanced progress in biologics and Janus kinase inhibitor (JAKi), the biologics and JAKi used in vitiligo are still inconsistent. In our case report, the successful use of MTX indicated that there are shared immune pathways between PsO and vitiligo. Further exploration is needed to optimize the treatment options for this co-occurrence of PsO and vitiligo.


Changes in lipid and lipoprotein values during a cross-over treatment of doxazosin, moduretic and amlodipine in hypertensive patients.
A cross-over study, comparing the effects of doxazosin, moduretic and amlodipine on plasma lipid and lipoprotein levels in 9 hypertensive Nigerians aged 35 to 65 years is presented. Doxazosin therapy had favourable lipid changes characterized by a statistically significant reduction in total cholesterol (TC) at 6 months. Though consistent reduction was observed in total triglycerides (TG) low density lipoprotein cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDLC) upto 6 months, no effect was seen on high density lipoprotein cholesterol (HDLC). This is against unfavourable increments in the mean values of TC, VLDLC, LDLC/HDLC and decrease in HDLC/TC during moduretic treatment phase. Amlodipine therapy did not alter the lipid and lipoprotein levels. The non-significant variation in the mean high density lipoprotein-cholesterol (HDLC) level observed with these agents, seem to suggest that HDL-cholesterol metabolism may be maintained during antihypertensive pharmacotherapy.


From Antimicrobial to Anticancer Peptides: The Transformation of Peptides.
Antimicrobial peptides play an important role in the innate immune system. Possessing broad-spectrum antibacterial activity, antimicrobial peptides can quickly treat and kill various targets, including gram-negative bacteria, gram-positive bacteria, fungi, and tumor cells. An overview of the state of play with regard to the research trend of antimicrobial peptides in recent years and the situation of targeting tumor cells, and to make statistical analysis of the patents related to anticancer peptides published in recent years, is important both from toxicological and medical tumor therapy point of view. Based on the Science Citation Index Expanded version, the Derwent Innovation Index and Innography as data sources, the relevant literature and patents concerning antimicrobial peptides and anticancer peptides were analyzed through the Thomson Data Analyzer. Results of toxicologic and pharmacologic studies that brought to the development of patents for methods to novel tumor drugs were analyzed and sub-divided according to the specific synthesis of anticancer peptides. The literature and patent search data show that the research and development of global antimicrobial peptides and anticancer peptides has been in an incremental mode. Growing patent evidence indicate that bioinformatics technology is a valuable strategy to modify, synthesize or recombine existing antimicrobial peptides to obtain tumor drugs with high activity, low toxicity and multiple targets. These findings may have important clinical implications for cancer treatment, especially in patients with conditions that are not currently treatable by other drugs, or that are resistant to existing cancer drugs.


Complete enzyme set for chlorophyll biosynthesis in Escherichia coli.
Chlorophylls are essential cofactors for photosynthesis, which sustains global food chains and oxygen production. Billions of tons of chlorophylls are synthesized annually, yet full understanding of chlorophyll biosynthesis has been hindered by the lack of characterization of the Mg-protoporphyrin IX monomethyl ester oxidative cyclase step, which confers the distinctive green color of these pigments. We demonstrate cyclase activity using heterologously expressed enzyme. Next, we assemble a genetic module that encodes the complete chlorophyll biosynthetic pathway and show that it functions in Escherichia coli. Expression of 12 genes converts endogenous protoporphyrin IX into chlorophyll a, turning E. coli cells green. Our results delineate a minimum set of enzymes required to make chlorophyll and establish a platform for engineering photosynthesis in a heterotrophic model organism.


Association of selected inflammatory biomarkers with cough reflex sensitivity in asthmatic children.
Bronchial asthma is the most common chronic respiratory disease of childhood. Cough is one of its defining symptoms. This study investigated the associations between selected inflammatory biomarkers and cough reflex sensitivity after capsaicin inhalation in children with mild and moderate well-controlled type 2 endotype asthma compared with non-asthmatic probands. Sensitivity to the cough reflex was measured by recording the cough response after capsaicin inhalation. The sandwich ELISA method was used to measure serum concentrations of the investigated potential inflammatory biomarkers (interleukin 13, interleukin 1beta, eosinophil-derived neurotoxin). The acquired data were statistically evaluated according to descriptive analyses for summarization and comparison between cough reflex sensitivity parameters and individual biomarker values in the observed and control groups modeled by a simple linear regression model. Statistical significance was defined as p<0.05. We showed a statistically significant association (p-value 0.03) between cough reflex sensitivity - C2 value (capsaicin concentration required for two cough responses) and interleukin 1beta serum concentrations in the asthma group compared with the control group of non-asthmatic children. Our results support the possibility of interleukin 1beta as a potential additive inflammatory biomarker used in clinical practice in children with asthma because of its correlation with the activity of the afferent nerve endings in the airways.


The Prevalence of Dementia among Dermatomyositis and Polymyositis Patients: A Retrospective Cohort Study.
Polymyositis (PM) and dermatomyositis (DM) are inflammatory mediated myopathies characterized by progressive symmetric proximal muscle weakness and associated with extra-muscular involvement. Central nervous system complications are rarely reported with these diseases. To investigate the association between dementia and PM/DM. A retrospective cohort study was conducted using a database from Clalit Health Care, the largest health maintenance organization in Israel. Patients with a first recorded diagnosis of PM/DM were included and were compared with age- and sex-matched controls by a ratio of 1:5. The prevalence of dementia among PM/DM patients compared to controls was assessed using a univariate and a multivariable model. Binary logistic regression analysis was conducted to assess the association of different factors with dementia within the PM/DM cohort. The study included 2085 PM/DM cases (17.0%) and 10,193 age- and sex-matched controls (83.0%). During the follow-up time, 36 PM/DM patients were diagnosed with dementia compared to 160 controls, with a univariate hazard ratio (HR) of 1.10 (95% confidence interval [95%CI] 0.77-1.58). Within the PM/DM cohort, significant predictors for the development of dementia included increased age at diagnosis (5 years increment; OR 1.86, 95%CI 1.57-2.21, P < 0.001) and treatment with glucocorticoids (OR 5.40, 95%CI 1.67-17.67, P = 0.005). In our cohort, inflammatory myopathies were not associated with dementia. Age and treatment with glucocorticoids were associated with dementia. If dementia is diagnosed in patients with inflammatory myopathies, other systemic causes should be investigated.


Genome complexity of methanogenic bacteria.
The genome complexities of different methanogenic bacteria were investigated by using an optical method to study renaturation kinetics of single-stranded DNA. The observed genome sizes ranged from 1.0 X 10(9) to 1.8 X 10(9) daltons, which is a typical range for procaryotic cells. Melting profiles of the DNA of three methanogenic species from different families show fractions which have a higher A . T content than the average DNA of that species.


Effects of shallow natural gas well structures and associated roads on grassland songbird reproductive success in Alberta, Canada.
Grassland songbird populations across North America have experienced dramatic population declines due to habitat loss and degradation. In Canada, energy development continues to fragment and disturb prairie habitat, but effects of oil and gas development on reproductive success of songbirds in North American mixed-grass prairies remains largely unknown. From 2010-2012, in southeastern Alberta, Canada, we monitored 257 nests of two ground-nesting grassland songbird species, Savannah sparrow (Passerculus sandwichensis) and chestnut-collared longspur (Calcarius ornatus). Nest locations varied with proximity to and density of conventional shallow gas well structures and associated roads in forty-two 258-ha mixed-grass prairie sites. We estimated the probabilities of nest success and clutch size relative to gas well structures and roads. There was little effect of distance to or density of gas well structure on nest success; however, Savannah sparrow experienced lower nest success near roads. Clutch sizes were lower near gas well structures and cattle water sources. Minimizing habitat disturbance surrounding gas well structures, and reducing abundance of roads and trails, would help minimize impacts on reproductive success for some grassland songbirds.


Interaction and Regulation Between Lipid Mediator Phosphatidic Acid and Circadian Clock Regulators.
Circadian clocks play important roles in regulating cellular metabolism, but the reciprocal effect that metabolism has on the clock is largely unknown in plants. Here, we show that the central glycerolipid metabolite and lipid mediator phosphatidic acid (PA) interacts with and modulates the function of the core clock regulators LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) in Arabidopsis (Arabidopsis thaliana). PA reduced the ability of LHY and CCA1 to bind the promoter of their target gene TIMING OF CAB EXPRESSION1 Increased PA accumulation and inhibition of PA-producing enzymes had opposite effects on circadian clock outputs. Diurnal change in levels of several membrane phospholipid species, including PA, observed in wild type was lost in the LHY and CCA1 double knockout mutant. Storage lipid accumulation was also affected in the clock mutants. These results indicate that the interaction of PA with the clock regulator may function as a cellular conduit to integrate the circadian clock with lipid metabolism.


Evidence for a role in stimulus--secretion coupling of prostaglandins derived from release of arachidonoyl residues as a result of phosphatidylinositol breakdown.
That stimulation of secretion in exocrine and endocrine glands is associated with increased turnover of phosphatidylinositol and phosphatidic acid has been known for many years. In the present work, mouse pancreases were prelabeled with [14C]arachidonic acid in the presence of the secretogogue carbamoylcholine. They were then incubated in media containing atropine and 1% albumin. The atropine causes the tissue to revert to the resting state, and the albumin binds free [14C]arachidonic acid. The tissues were finally incubated in media containing no stimulant or the stimulant caerulein, which is not blocked by atropine. Stimulation with caerulein, which is not blocked by atropine. Stimulation with caerulein led to a 44% loss of [1-14C]arachidonic acid from phosphatidylinositol. About half of this released arachidonic acid ended up in phosphatidic acid. The remainder of the loss could not be accounted for in any other lipid. No other phospholipids showed statistically significant changes on stimulation. Several lines of evidence indicated that the missing arachidonic acid was converted to prostaglandins, which play a role in stimulus--secretion coupling. Four nonsteroidal anti-inflammatory drugs inhibited secretogogue-induced amylase secretion from pancreases, and their potencies paralleled their potencies in inhibiting cyclooxygenase, which converts arachidonic acid to prostaglandins. Amylase secretion was stimulated by arachidonic acid, and this stimulation was blocked by the nonsteroidal anti-inflammatory drug indomethacin. Other fatty acids failed to elicit amylase secretion. At concentrations of 3--10 nM, prostaglandins I2, E1, E2, D2, and F2 alpha gave statistically significant stimulations of secretion. Other prostaglandins tested gave no significant stimulation.


Adolescent anxiety and depression: burden of disease study in 53,894 secondary school pupils in the Netherlands.
Prevalence rates of anxiety and depression in adolescence are rising markedly in early adolescence. It is important to quantify the non-fatal disease burden of anxiety and depression, such that early interventions can be well targeted, and resources can be allocated in a just and optimal way. This study aimed to estimate the non-fatal disease burden of anxiety and depression with and without suicidal ideation in girls and boys aged 13, 14, and 15 years. Participants were 53,894 secondary school pupils who completed health questionnaires between September 2018 and July 2019. A design-based approach was used for complex survey data with post-stratification weights and taking clustering at school-level into account. At individual level, disability weights (DWs) were calculated for each disorder. At population level, DWs were multiplied by the point-prevalence per one thousand population of the respective disorders to compute years lived with disability (YLD). DWs and YLD of anxiety and depression were calculated with and without adjustment for comorbid eating disorders, substance use disorders and somatic illnesses. The unadjusted DW of depression with suicidal ideation (0.30) was greater than without suicidal ideation (0.26), and both were greater than the DW of anxiety (0.24). A similar ranking was obtained after adjusting for comorbidities. At population level, where the prevalence of the disorders come into play, the YLD disease burden was greatest for anxiety, followed by depression with suicidal ideation and depression without suicidal ideation with 17.40, 9.85, and 5.28 YLD per one thousand population, unadjusted for comorbidities. This pattern was the same after adjustment, but then the total YLD of depression with and without suicidal ideation was similar to the YLD of anxiety (12.47 and 12.46, respectively). Girls showed a significantly greater YLD burden of anxiety and depression than boys, but no differences were found between different age groups. From an individual clinical perspective, depression, especially when accompanied by suicidal ideation, was identified as a major health concern, especially in girls. From a public health perspective, both anxiety and depression, especially when accompanied by suicidal ideation, were identified as major drivers of disease burden, again most notably in girls.


The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1.
Mitotic exit integrates the reversal of the phosphorylation events initiated by mitotic kinases with a controlled cytokinesis event that cleaves the cell in two. The mitotic exit network (MEN) of budding yeast regulates both processes, whereas the fission yeast equivalent, the septum initiation network (SIN), controls only the execution of cytokinesis. The components and architecture of the SIN and MEN are highly conserved. At present, it is assumed that the functions of the core SIN-MEN components are restricted to their characterized roles at the end of mitosis. We now show that the NDR (nuclear Dbf2-related) kinase component of the fission yeast SIN, Sid2-Mob1, acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. Sid2-Mob1 promotes mitotic commitment by directly activating the NIMA (Never In Mitosis)-related kinase Fin1. Fin1's activation promotes its own destruction, thereby making Fin1 activation a transient feature of G2 phase. This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1.


Methylation: lost in hydroxylation?
Methylation of histone tails is a key determinant in forming active and silent states of chromatin. Histone methylation was regarded as irreversible until the recent identification of a lysine-specific histone demethylase (LSD1), which acts specifically on mono- and dimethylated histone H3 lysine 4. Here, we propose that the fission yeast protein Epe1 is a putative histone demethylase that could act by oxidative demethylation. Epe1 modulates the stability of silent chromatin and contains a JmjC domain. The Epe1 protein can be modelled onto the structure of the 2-oxoglutarate-Fe(II)-dependent dioxygenase, factor inhibiting hypoxia inducible factor (FIH), which is a protein hydroxylase that also contains a JmjC domain. Thus, Epe1 and certain other chromatin-associated JmjC-domain proteins may be protein hydroxylases that catalyse a novel histone modification. Another intriguing possibility is that, by hydroxylating the methyl groups, Epe1 and certain other JmjC-domain proteins may be able to demethylate mono-, di- or trimethylated histones.


cuBLASTP: Fine-Grained Parallelization of Protein Sequence Search on CPU+GPU.
BLAST, short for Basic Local Alignment Search Tool, is a ubiquitous tool used in the life sciences for pairwise sequence search. However, with the advent of next-generation sequencing (NGS), whether at the outset or downstream from NGS, the exponential growth of sequence databases is outstripping our ability to analyze the data. While recent studies have utilized the graphics processing unit (GPU) to speedup the BLAST algorithm for searching protein sequences (i.e., BLASTP), these studies use coarse-grained parallelism, where one sequence alignment is mapped to only one thread. Such an approach does not efficiently utilize the capabilities of a GPU, particularly due to the irregularity of BLASTP in both execution paths and memory-access patterns. To address the above shortcomings, we present a fine-grained approach to parallelize BLASTP, where each individual phase of sequence search is mapped to many threads on a GPU. This approach, which we refer to as cuBLASTP, reorders data-access patterns and reduces divergent branches of the most time-consuming phases (i.e., hit detection and ungapped extension). In addition, cuBLASTP optimizes the remaining phases (i.e., gapped extension and alignment with trace back) on a multicore CPU and overlaps their execution with the phases running on the GPU.


Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma.
Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, IFN-γ, LT-α, and TNF-α were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-1β-511C/T, IL-6-174G/C, IFN-γ +874T/A, LT-α +252A/G, and TNF-α -308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-α +252A/G and TNF-α -308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-γ +874T/A were significantly higher than the variants in CCA cases. IFN-γ +874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6 -174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.


Predictive accuracy of amyloid imaging for progression from mild cognitive impairment to Alzheimer disease with different lengths of follow-up: a meta-analysis. [Corrected].
In the past decade, amyloid deposition has been shown to begin many years before the clinical symptoms of dementia in mild cognitive impairment (MCI) due to Alzheimer disease (AD). Longitudinal studies with different follow-up durations have suggested that C-Pittsburgh compound B positron emission tomography (C-PIB-PET) may play a role in stratifying patients with MCI into risk levels for developing AD. However, the predictive accuracy of amyloid imaging for the progression from MCI to AD with different follow-up durations has not yet been systematically evaluated. A formal systematic evaluation of the sensitivity, specificity, and other properties of C-PIB-PET was performed.This study aimed to systematically review and meta-analyze published data on the diagnostic performance of C-PIB-PET for predicting conversion to AD in patients with MCI and to determine whether long-term follow-up has a positive effect on predictive accuracy. Relevant studies were systematically identified through electronic searches, which were performed in MEDLINE (OvidSP), EMBASE (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (Ovid SP), and LILACS (Bireme). The methodological quality of each study was assessed by QUADAS-2. Sensitivities and specificities of C-PIB-PET in individual studies were calculated, and the studies underwent meta-analysis with a random-effects model. A summary receiver-operating characteristic curve (SROC) was constructed with the Moses-Shapiro-Littenberg method. Pooled estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and the SROC curve of each subgroup were determined. Heterogeneity was tested, and potential sources for heterogeneity were explored by assessing whether certain covariates significantly influenced the relative DOR.Eleven eligible studies consisting of a total of 352 patients with MCI at baseline were included. Overall, the studies were of moderate-to-high methodological quality. The sensitivity and specificity of C-PIB-PET for predicting conversion to AD ranged from 83.3% to 100% and 41.1% to 100%, respectively, with pooled estimates of 94.7% (95% confidence interval [CI]: 89.8%-97.7%) and 57.2% (95% CI: 50.1%-64.2%), respectively . Moderate heterogeneity was observed for specificity between the included studies (I = 42.1%). The pooled estimates for the long-term follow-up subgroup were 95.5% sensitivity (95% CI: 84.5%-99.4%) and 72.4% specificity (95% CI: 59.1%-83.3.8%), whereas the pooled estimates for the short-term follow-up subgroup were 94.4% sensitivity (95% CI: 88.2%-97.9%) and 51.0% specificity (95% CI: 42.6%-59.5%). Homogeneity in each subgroup was significantly higher than that of the included studies, and most diagnostic indicators in the long-term follow-up subgroup were far superior to those in the short-term follow-up subgroup or the entire group. Not all of the methodological quality scores of studies included in this systematic review were high. Current evidence suggests that prolongation of the follow-up duration tended to yield greater accuracy of C-PIB-PET for predicting the progression from MCI to AD. In particular, the specificity, which reflects the exploratory nature of the use of amyloid imaging to identify the process of MCI to AD, was improved with a longer follow-up period.


Consumers' Preferences for a Local Food Product: The Case of a New Carnaroli Rice Product in Lombardy.
Italy, with a cultivated area of 218,000 ha, is a European leader of rice production. In particular Lombardy region accounts for 40% of total rice cultivation and the case study in object accounts for 3.2% of Lombardy total rice area (2773 ha). Starting from 2012, through a regional project titled Buono, Sano e Vicino (good, healthy and close), Riso e Rane rural district supported local rice farmers in developing innovation in rice production and promoting an alternative supply chain to increase farmers bargaining power and promote new market strategies. More specifically, the innovation introduced is a new biotech method for variety certification, named DNA controllato (DNA tested). In the first step of the project, the attention was focused on an Italian traditional variety of rice: Carnaroli rice. Thanks to a commercial agreement with one of the most important large retailers in Lombardy, the Riso e Rane rice is offered for sale both in the traditional and wholegrain version. In this context, this work aims to evaluate the determinants of consumer's quality perception of this product, through a preference study of the commercial rice package. Preliminary results reveal that consumers perceive information about origin, local food-system and tradition more easily than DNA tested certification. In conclusion, this work contributes to evaluate the role of bio economy applications to the food sector and offers new insights for the debate about the relationships between tradition and innovation.


[Thymic carcinoid tumors. A clinico-anatomic study of 3 cases].
The carcinoid tumour of the thymus was first detailed by Rosai in 1972. The authors describe three cases of this tumour with particular reference to their histogenesis. It appears to be a tumour predominantly affecting males with an often unfavourable, though slow, progression. Some pathological associations are frequent and characteristic. In one third of cases there is an associated endocrine neoplasia. As a rule the tumour is sited in the anterior mediastinum. The precise diagnosis rests on histochemical criteria (specific granulations). These carcinoids are tumours of the APUD system of endodermal origin. The treatment is surgical.


Enhancing Visuospatial Working Memory Performance Using Intermittent Theta-Burst Stimulation Over the Right Dorsolateral Prefrontal Cortex.
Noninvasive brain stimulation provides a promising approach for the treatment of neuropsychiatric conditions. Despite the increasing research on the facilitatory effects of this kind of stimulation on the cognitive processes, the majority of the studies have used the standard stimulation approaches such as the transcranial direct current stimulation and the conventional repetitive transcranial magnetic stimulation (rTMS) which seem to be limited in robustness and the duration of the transient effects. However, a recent specialized type of rTMS, theta-burst stimulation (TBS), patterned to mimic the natural cross-frequency coupling of the human brain, may induce robust and longer-lasting effects on cortical activity. Here, we aimed to investigate the effects of the intermittent TBS (iTBS), a facilitatory form of TBS, over the right DLPFC (rDLPFC), a brain area implicated in higher-order cognitive processes, on visuospatial working memory (VSWM) performance. Therefore, iTBS was applied over either the rDLPFC or the vertex of 24 healthy participants, in two separate sessions. We assessed VSWM performance using 2-back and 4-back visuospatial tasks before iTBS (at the baseline (BL), and after the iTBS. Our results indicate that the iTBS over the rDLPFC significantly enhanced VSWM performance in the 2-back task, as measured by the discriminability index and the reaction time. However, the 4-back task performance was not significantly modulated by iTBS. These findings demonstrate that the rDLPFC plays a critical role in VSWM and that iTBS is a safe and effective approach for investigating the causal role of the specific brain areas.


Writing about clinical theory and psychoanalytic process.
In the Senior Candidate Case Writing Seminar, the final component of the Writing as Pedagogy Program at the Columbia Center for Psychoanalytic Training and Research, candidates write about one of their longer training cases, with attention to the ways they use clinical theory, particularly transference and countertransference, to deepen their understanding of psychoanalytic process and therapeutic action. Building on the previous four years of the writing program, this seminar teaches advanced candidates to recognize and integrate the lived experience of conducting an analysis, the micro- and macroprocesses, and the theories most relevant to an understanding of the analytic work. The seminar emphasizes the challenge of dealing with the power of the transference, unrecognized or unacknowledged countertransference, and the nature of therapeutic action. Pedagogical emphasis is placed on peer group discussions and group learning, and common problems in integrating theory and practice are described and illustrated.


Radiation therapy and chemotherapy in the treatment of head and neck extranodal non-Hodgkin's lymphoma in early stage with a high grade of malignancy.
Optimal management of patients with localized head and neck extranodal lymphoma remains controversial, both because of the lack of randomized studies and because of the heterogenous grouping of most reported series. Patients treated at our institution between 1974 and 1993 for extranodal head and neck lymphoma were retrospectively analyzed and classified. The therapy and outcome of 92 patients classified as having an intermediate (42) and high (50) level of malignancy according to the Working formulation and in stage I (39) or II (53) of the Ann Arbor Staging System were considered. Fifty-three patients (57.6%) received chemotherapy alone, and 39 (42.4%) combined radiochemotherapy. The different treatment schedules allowed these patients to achieve global actuarial 5-year overall, event-free, and relapse-free survival rates of 81.2%, 78.1% and 89.3%, respectively. The patients that received combined modality treatment reported actuarial 10-year event-free and relapse-free survival rates of 65.3% and 90.7%, respectively, with a suggestion of decreased treatment-related morbidity compared to patients treated with chemotherapy. Our results underscore the important treatment role of combined radiochemotherapy for early stage intermediate and high grade lymphomas.


Are fertility drugs a risk factor for persistent trophoblastic tumour?
The introduction of ovulation-inducing drugs has raised concern that women exposed to these therapies may be at increased risk of cancer. We assessed the potential association between exposure to fertility drugs and the risk of developing persistent trophoblastic tumour (PTT). We conducted a systematic review of the English and non-English language literature using the National Library of Medicine's Medline to identify all observations of patients with hydatidiform mole (HM) after treatment with ovulation-inducers. Fifty-two cases were considered including 26 singleton molar pregnancies and 26 multiple molar pregnancies consisting of an HM and one or more co-existent fetus(es) (HM-and-CF). PTT occurred in 15% of patients with singleton HM and in 42% of patients with HM-and-CF, 15% of whom had a metastatic disease. Of those patients with HM-and-CF, 16 patients delivered at <24 weeks gestation, mostly because of vaginal haemorrhage. Ten patients delivered at > or = 24 weeks of gestation, six of whom (25%) had a normal live child. These results are similar to spontaneously conceived pregnancies. Although women having an HM after therapy with ovulation-inducing drugs seem to have no added risk of PTT, multiple pregnancies are more likely to occur, and the overall risk may be increased.


[Afferent connections of the lateral vestibular nucleus in the cat].
Localization of labelled neurons (sources of projections to the lateral vestibular nucleus) in the brain was studied by means of microiontophoretic injections of horseradish peroxidase. Bilateral projections of the midbrain structures to all parts of the nucleus mentioned (field of Forel, interstitial nucleus of Cajal, oculomotor nerve nucleus and red nucleus) were found. There have been also shown: bilateral projections from more caudally localized structures of the superior, medial and inferior (descending) vestibular nuclei, group "Y" of the vestibular nuclear complex, facial nucleus and hypoglossi, nucleus prepositus nervi hypoglossi and spinal trigeminal nucleus; ipsilateral projections from crus IIa of lobulus ansiformus of the cerebellar hemisphere; contralateral projections from lateral reticular nucleus of medulla oblongata and Deiters' nucleus. Trajectories of the labelled fibre system projecting to Deiters' nucleus are described.


Hysteresis in random-field XY and Heisenberg models: mean-field theory and simulations at zero temperature.
We examine zero-temperature hysteresis in random-field XY and Heisenberg models in the zero-frequency limit of a cyclic driving field. Exact expressions for hysteresis loops are obtained in the mean-field approximation. These show rather unusual features. We also perform simulations of the two models on a simple-cubic lattice and compare them with the predictions of the mean-field theory.


Expression and functionality of transient receptor potential melastatin 4 (TRPM4)-like channels during development of the zebrafish.
Calcium signaling, from localized spikes to coordinated waves, are linked to cleavage, patterning, differentiation, and growth during embryonic development. The basis for control of these Ca(2+) signals is poorly defined. In this study, the expression and functionality of the transient receptor potential melastatin 4 protein (TRPM4), an ion channel that controls Ca(2+) entry into cells, was examined in the zebrafish embryo and adult. Originating with the human TRPM4 gene, Ensembl ortholog, NCBI BLAST, and Homologene searches identified a zebrafish TRPM4 "like" gene encoding a predicted protein of 1199 amino acids and sharing a 42-43% sequence identity with the mouse, rat, and human. Custom-designed zebrafish primers identified TRPM4 transcripts throughout the 0-123h period of embryonic development with greatest and lowest relative expression at 12 and 123h post-fertilization, respectively. Perforated patch clamp recordings in 27h embryonic cells revealed Ca(2+)-activated currents with the characteristics of those described for mammalian TRPM4. Similarly, TRPM4-like expression and functionality was observed in brain and liver cells from adult fish. These findings suggest that a TRPM4-like channel is available for Ca(2+) regulation during early development of the zebrafish.


Sequential Abolition of Antegrade and Retrograde Conduction in Wolff-Parkinson-White Syndrome: A Case Series.
BACKGROUND Radiofrequency ablation in cases of Wolff-Parkinson-White (WPW) syndrome is a relatively safe procedure that yields good results. However, the electrical characteristics of WPW syndrome have not yet been fully elucidated. Herein, we report 2 cases of WPW syndrome, wherein antegrade conduction was abolished first, followed by retrograde conduction. CASE REPORT Case 1: A 15-year-old boy who recently reported experiencing frequent palpitations was diagnosed with type A WPW syndrome by electrocardiography (ECG). Radiofrequency energy was delivered to the earliest activation site using an ablation catheter. This procedure abolished antegrade accessory pathway conduction in 6 seconds, and then the ablation was continued for 60 seconds; however, retrograde accessory pathway conduction remained intact. Hence, radiofrequency ablation was performed to further deliver radiofrequency energy to abolish the retrograde accessory pathway conduction. Case 2: A 19-year-old woman with palpitations since elementary school was diagnosed with type A WPW syndrome by ECG. Radiofrequency energy was delivered to the earliest activation site through an ablation catheter to abolish antegrade accessory pathway conduction in approximately 1 second, and then the ablation was continued for 60 seconds. Retrograde accessory pathway conduction was preserved, and further radiofrequency ablation performed multiple times in the same vicinity abolished retrograde accessory pathway conduction. CONCLUSIONS We managed 2 cases of WPW syndrome wherein antegrade and retrograde accessory pathway conduction were individually abolished. This phenomenon may have been caused by an incomplete lesion that resulted in a functional block.


Occupational health in Brazil.
In a positive approach, the authors propose that occupational safety and health in Brazil is an example of how crises and opportunities can come together to produce excellent results. The history provided here as well as the overview of occupational health problems in Brazil together offer a detailed picture of conditions in this country. Also included is a lengthy table covering OSH steps, strategies, and approaches; national needs; and suggestions for international assistance.


SPOCK1 promotes tumor growth and metastasis in human prostate cancer.
Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second leading cause of cancer-related deaths in American males. Metastasis is the primary cause of prostate cancer mortality. Survival rate is only 28% for metastatic patients, but is nearly 100% for patients with localized prostate cancers. Molecular mechanisms that underlie this malignancy remain obscure, and this study investigated the role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) in prostate cancer progression. Initially, we found that SPOCK1 expression was significantly higher in prostate cancer tissues relative to noncancerous tissues. In particular, SPOCK1 expression was also markedly high in metastatic tissues compared with nonmetastatic cancerous tissues. SPOCK1 expression knockdown by specific short hairpin RNA in PC3 cells was significantly inhibited, whereas SPOCK1 overexpression in RWPE-1 cells promoted cell viability, colony formation in vitro, and tumor growth in vivo. Moreover, the SPOCK1 knockdown in PC3 cells was associated with cell cycle arrest in G0/G1 phase, while the SPOCK1 overexpression in RWPE-1 cells induced cell cycle arrest in S phase. The SPOCK1 knockdown in PC3 cells even increased cell apoptosis. SPOCK1 modulation was also observed to affect cancerous cell proliferation and apoptotic processes in the mouse model of prostate cancer. Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression increased cell migration and invasion abilities in vitro. Injection of SPOCK1-depleted PC3 cells significantly decreased metastatic nodules in mouse lungs. These findings suggest that SPOCK1 is a critical mediator of tumor growth and metastasis in prostate cancer.


Macrophage T cell interaction in man: binding of antigen-specific human proliferating and helper T cells to antigen-pulsed macrophages.
Adsorption of T cells over monolayers of autologous, but not allogeneic, macrophages (M phi) pulsed with tetanus toxoid (TT) antigen resulted in the specific depletion of the capacity of the T cells to proliferate and to release T cell helper factor in response to stimulation, with TT antigen. T cells that bound to the TT-pulsed M phi monolayers were specifically enriched in their capacity to proliferate in response to TT. Turkey antiserum to the human B cell glycoprotein p 29,34, but not turkey antiserum to human beta 2 microglobulin, inhibited the binding of TT-reactive T cells to TT-pulsed M phi. This inhibition resulted from the binding of the anti-p 29,34 antiserum to DR determinants expressed on the surface of the M phi. Immunosorbent purified IgG anti-TT, added in great excess, did not inhibit the binding of TT-reactive T cells to TT-pulsed M phi monolayers. Soluble TT antigen and rabbit antiidiotypic IgG, directed against IgG F(ab')2 anti-TT obtained from the cell donor, minimally inhibited the binding of TT-reactive T cells to TT pulsed M phi monolayers. M phi pulsed with urea-denatured TT, which contained less than 1% native TT, depleted T cell reactivity to TT to an extent almost equivalent to that achieved by M phi pulsed with native TT. These results indicate that human antigen-reactive T cells bind to the DR determinants of M phi pulsed with antigen and that the immunogenic moiety of antigen recognized by the majority of antigen reactive human T cells may differ from native antigen.


Triamcinolone acetonide in silicone-filled eyes as adjunctive treatment for proliferative vitreoretinopathy: a randomized clinical trial.
To evaluate the effect of adjunctive intraocular triamcinolone acetonide (TA) in silicone-filled eyes on outcomes of vitreoretinal surgery for proliferative vitreoretinopathy (PVR). Prospective, randomized, controlled clinical trial. Seventy-five eyes with rhegmatogenous retinal detachment and PVR grade C (posterior, anterior, or both) undergoing vitrectomy combined with silicone oil tamponade were included. Of these, 38 eyes were assigned randomly to the adjunctive treatment, whereas 37 eyes served as controls. All eyes underwent pars plana vitrectomy, membrane peeling, and silicone oil exchange, with or without relaxing retinotomy or retinectomy. In the treatment group, 4 mg TA was injected into the silicone-filled vitreous cavity at the end of the procedure. Silicone oil was removed 3 months after surgery in eyes with attached retinas. The primary outcome measure was retinal reattachment rate at 6 months. Secondary outcome measures included visual acuity, rate of recurrent PVR, reoperation rate, and rise of intraocular pressure. Retinal reattachment without any reoperation was achieved in 32 eyes (84.2%) and 29 eyes (78.4%) in the adjunctive treatment and control groups, respectively, at 6 months (P = 0.5). No statistically significant difference was observed between the 2 groups in terms of any of the secondary outcome measures (P>0.05). The outcomes of vitreoretinal surgery for established PVR are not improved significantly by adjunctive TA injection in silicone-filled eyes.


Inflammatory pseudotumour of the trachea: report of a case in an eight-year-old child.
A polypoid inflammatory pseudotumour was diagnosed in the trachea of an eight-year-old child who presented with asthmatic symptoms. The tumour showed 80 per cent blockage of the lower trachea and consisted of proliferating spindly fibroblastic cells admixed with a variable number of inflammatory cells. The literature on childhood inflammatory pseudotumours is reviewed together with the differential diagnosis of other polypoid mesenchymal tumours of the trachea.


Complex Annulations through Silver Carbenoid Intermediate: An Alternative Entry to Transformations of 1,2,3-Triazoles.
An alternative entry to transformations of N-sulfonyl-4-(2-(ethynyl)aryl)-1,2,3-triazoles with various generated in situ or external nucleophiles by means of silver catalysis for producing diverse functionalized isoquinolines is described. Mechanistically, the reaction is proposed to involve a key silver carbenoid intermediate, thus enabling the formation of multiple chemical bonds via ring opening, N2 extrusion, silver carbenoid formation, nucleophilic addition, and complex annulations cascades.


Intracerebral hemorrhage after intravenous thrombolysis in patients with cerebral microbleeds and cardiac myxoma.
Cardiac myxoma is a rare etiology of stroke. Both cerebral microbleeds and cardiac myxoma may increase the risk of intracerebral hemorrhage after intravenous (IV) thrombolysis. However, data are still limited. We report a case of multiple cerebral microbleeds treated with IV thrombolysis with later findings of cardiac myxoma. A 58-year-old-man presented with right-sided hemiplegia and global aphasia. The presumptive diagnosis of acute left middle cerebral artery (MCA) infarction was made. Previous magnetic resonance imaging showed multiple cerebral microbleeds. The patient received IV thrombolysis. Bilateral cerebellar hemorrhage occurred after thrombolysis, and a median suboccipital craniectomy and hematoma removal was performed. Transthoracic echocardiogram found a left atrial myxoma. The tumor was then surgically removed. Six months later, neurological deficit improved. Cerebral microbleeds may be associated with atrial myxoma. IV thrombolysis could benefit acute ischemic stroke patients with both baseline cerebral microbleeds and atrial myxoma.


Some problems of therapeutic trials in hypertension.
It is strongly recommended that a scientific protocol for controlled therapeutic trials in hypertension should include, inter alia, the following: 1. A definition of the level(s) of blood pressure which indicate hypertension (systolic and/or diastolic), preferably related to age and sex. 2. The criteria for defining the type of hypertension (e.g., essential, renovascular, etc.). 3. A statement relative to which diastolic level is to be recorded: phase IV ("muffling") and/or phase V ("disappearance"). 4. Information on the sizes of sphygmomanometer cuffs to be used. 5. A statement of which arm is to be used (throughout the study). 6. A statement of postures in which blood pressure is to be measured (supine, sitting, standing). 7. Information on the conditions under which pressures are to be recorded (e.g., "casual," "near-basal," etc.) and the duration of rest before recording. 8. Details of the times of day at which measurements are to be taken.9. A statement on the method of establishing baseline readings (e.g., mean of three successive readings) and the acceptable degree of variability (e.g., +/- 10 mm Hg). 10. A definition of "endpoints" (e.g., diastolic pressure less than upper limit of normal; reduction in diastolic pressure greater than 10 mm Hg).


Apolipoprotein(a) inhibits in vitro tube formation in endothelial cells: identification of roles for Kringle V and the plasminogen activation system.
Elevated plasma concentrations of lipoprotein(a) are associated with increased risk for atherothrombotic diseases. Apolipoprotein(a), the unique glycoprotein component of lipoprotein(a), is characterized by the presence of multiple kringle domains, and shares a high degree of sequence homology with the serine protease zymogen plasminogen. It has been shown that angiostatin, a proteolytic fragment of plasminogen containing kringles 1-4, can effectively inhibit angiogenesis. Moreover, proteolytic fragments of plasminogen containing kringle 5 are even more potent inhibitors of angiogenesis than angiostatin. Despite its strong similarity with plasminogen, the role of apolipoprotein(a) in angiogenesis remains controversial, with both pro- and anti-angiogenic effects reported. In the current study, we evaluated the ability of apolipoprotein(a) to inhibit VEGF- and angiopoietin-induced tube formation in human umbilical cord endothelial cells. A 17 kringle-containing form of recombinant apo(a) (17K), corresponding to a well-characterized, physiologically-relevant form of the molecule, effectively inhibited tube formation induced by either VEGF or angiopoietin-1. Using additional recombinant apolipoprotein(a) (r-apo(a)) variants, we demonstrated that this effect was dependent on the presence of an intact lysine-binding site in kringle V domain of apo(a), but not on the presence of the functional lysine-binding site in apo(a) kringle IV type 10; sequences within in the amino-terminal half of the molecule were also not required for the inhibitory effects of apo(a). We also showed that the apo(a)-mediated inhibition tube formation could be reversed, in part by the addition of plasmin or urokinase plasminogen activator, or by removal of plasminogen from the system. Further, we demonstrated that apo(a) treated with glycosidases to remove sialic acid was significantly less effective in inhibiting tube formation. This is the first report of a functional role for the glycosylation of apo(a) although the mechanisms underlying this observation remain to be determined in the context of angiogenesis.


Elliptically polarized coherent anti-Stokes Raman scattering microscopy.
We report an approach to coherent anti-Stokes Raman scattering (CARS) microscopy that significantly suppresses the nonresonant background for high-contrast vibrational imaging. We employ an elliptically polarized pump field with an aspect ratio of 1:3 of the ellipse combined with a linearly polarized Stokes field for elliptically polarized CARS (EP-CARS) microscopy. The EP-CARS technique yields a 6-7-fold improvement in signal-to-background ratios compared with normal CARS, while providing an approximately 1.25-fold improvement in resonant CARS signal compared with normal polarization-sensitive CARS microscopy. We demonstrate this technique by imaging 1.5 microm polystyrene beads in water and lipid droplets in unstained fibroblast cells.


PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS: Results From the Population-Based Gutenberg Health Study.
To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with history of stroke (OR, 6.8; 95% CI, 2.9-16.1; P < 0.001). Myelinated retinal nerve fibers was not associated with age, sex, cardiovascular conditions other than stroke or ocular parameters, such as refraction, visual acuity, intraocular pressure, or central corneal thickness. This population-based study provides novel data on the prevalence of MRNF in Western Europe. We report a positive association between history of stroke and MRNF. It adds an additional retinal sign for stroke and calls for further studying of the behavior of oligodendrocytes within cerebrovascular diseases.


Comparison of the angiotensin II receptor antagonist irbesartan with atenolol for treatment of hypertension.
In this multicenter, double-blind study, the antihypertensive efficacy and safety of irbesartan were compared with those of atenolol in patients with mild-to-moderate hypertension. Following a 4- to 5-week placebo lead-in period, 231 patients with seated diastolic blood pressure (SeDBP) 95-110 mmHg were randomized to irbesartan 75 mg or atenolol 50 mg once daily for 24 weeks. Doses were doubled at Week 6 for SeDBP > or = 90 mmHg. At Week 12, or anytime thereafter, doses were doubled for SeDBP > or = 90 mmHg if not done at Week 6, and hydrochlorothiazide and then nifedipine were added. Efficacy was determined by change from baseline in blood pressure and by therapeutic response rates. Safety was assessed by monitoring adverse events (AEs). Both treatments significantly lowered blood pressure from baseline. There were no significant differences between treatment groups with respect to blood pressure changes or therapeutic response. Atenolol significantly reduced seated heart rate compared with irbesartan at Week 12. The incidences of serious AEs and discontinuations due to AEs were approximately twice as high in the atenolol group compared with the irbesartan group. Thus, in comparison to atenolol, irbesartan < or = 150 mg provided at least equivalent blood pressure control while demonstrating an excellent safety and tolerability profile.


ChIP-seq Analysis to Explore DNA Replication Profile in Trifluridine-treated Human Colorectal Cancer Cells In Vitro.
Trifluridine (FTD) is a key component of the novel oral antitumor drug trifluridine/tipiracil that has been approved for the treatment of metastatic colorectal cancer. In this study, a comprehensive analysis of DNA replication profile in FTD-treated colon cancer cells was performed. HCT-116 cells were exposed to BrdU or FTD and subjected to DNA immunoprecipitation. Immunoprecipitated DNA was sequenced; the density of aligned reads along the genome was calculated. Peak finding, gene ontology, and motif analysis were performed using MACS, GREAT, and MEME, respectively. We identified 6,043 and 5,080 high-confidence FTD and BrdU peaks in HCT-116 cells, respectively. Of 6,043 FTD peaks, 2,911 peaks were uncommon to BrdU. We observed that FTD was preferentially incorporated into genomic regions containing simple repeats, CpG islands, and gene bodies. Conserved motifs in FTD peaks contained dinucleotide repeats such as (GT)n. Global FTD incorporation patterns delineated FTD, preferentially incorporating loci in cancer cells.


Simultaneous occurrence of hepatic adenoma and focal nodular hyperplasia: report of a case and review of the literature.
We report the case of a 28-year-old woman with a history of oral contraceptive use and the simultaneous occurrence of histologically proven hepatic adenoma and focal nodular hyperplasia. A review of the literature discloses that the simultaneous occurrence of these hepatic lesions is a rare event. Epidemiologic evidence suggests that hepatic adenomas are etiologically related to oral contraceptive use, whereas focal nodular hyperplasia does not seem to be caused by these agents. The finding of the two lesions in the same liver may represent the chance occurrence of two rare diseases.


Effects of Combined Phase III and Phase II Cardiac Exercise Therapy for Middle-aged Male Patients with Acute Myocardial Infarction.
[Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET.


Plant phenolic compounds and oxidative stress: integrated signals in fungal-plant interactions.
Upon invasion of a host, fungal pathogens are exposed to a variety of stresses. Plants release reactive oxygen species, and mount a variety of preformed and induced chemical defenses. Phenolic compounds are one example: they are ubiquitous in plants, and an invading pathogen encounters them already at the leaf surface, or for soil-borne pathogens, in the rhizosphere. Phenolic and related aromatic compounds show varying degrees of toxicity to cells. Some compounds are quite readily metabolized, and others less so. It was known already from classical studies that phenolic substrates induce the expression of the enzymes for their degradation. Recently, the ability to degrade phenolics was shown to be a virulence factor. Conversely, phenolic compounds can increase the effectiveness of antifungals. Phenolics are known antioxidants, yet they have been shown to elicit cellular responses that would usually be triggered to counter oxidant stress. Here, we review the evidence for a connection between the fungal response to phenolics as small-molecule signals, and the response to oxidants. The connections proposed here should enable genetic screens to identify specific fungal receptors for plant phenolics. Furthermore, understanding how the pathogen detects plant phenolic compounds as a stress signal may facilitate new antifungal strategies.


Negotiating social medicine in a postcolonial context: Halfdan Mahler in India 1951-61.
This article investigates how World Health Organisation (WHO) Director-General Halfdan Mahler's views on health care were formed by his experience in India between 1951 and 1961. Mahler spent a large part of the 1950s in India assigned as WHO medical officer to tuberculosis control projects. It argues that Mahler took inspiration from the official endorsement of the doctrine of social medicine that prevailed in India; even if it was challenged by an increasing preference for vertical, techno-centric campaigns. It shows how, from the outset, Mahler was remarkably hostile towards the highly skilled, clinically oriented doctors, but embraced prevalent ideas of community participation. It suggests that Mahler - although he remained silent on the issue - was impressed by the importance and resilience of indigenous traditions of medicine, despite hostility from leading political figures. In this way, the article attempts to establish links to Mahler's advocacy of primary health care in the 1970s. A broad approach to health, scepticism toward clinically oriented doctors, preference for simple technologies and community participation, as well as an accommodating attitude towards indigenous practitioners, were all features of primary health care, which correlate well with views developed by Mahler as he negotiated social medicine in India between 1951 and 1961.


Comparison Of Positivity Of Tuberculin Skin Test With Diagnostic Bcg In Children Suffering From Tuberculosis.
Tuberculosis is major public health problem in Pakistan and it is often unrecognized cause of morbidity and mortality in children living in endemic areas. Children with age less than 5 years, and especially those who are immune compromised, are at higher risk of developing tuberculosis following exposure. Tuberculosis in children is usually difficult to diagnose compare to adult patients due to its atypical presentation. Tuberculin skin test and Bacille Calmette-Guerin (BCG) are widely used as diagnostic tests for tuberculosis. It was a Cross sectional study carried out from May 2017 to Nov 2018 in the department of Paediatrics, Ayub Teaching Hospital Abbottabad.. Both BCG and tuberculin skin test were performed at the same time by the same doctor. Personal data like age, gender and address, type of tuberculosis, positivity of tuberculin skin test and positivity of diagnostic BCG were recorded. The induration was read 48- 72 hours after administration. As per frequencies and percentages for positivity of tuberculin skin, 51 (67.10%) patients showed positivity for tuberculin skin while 71 (93.42%) patients showed positive results via BCG Test. In paediatric age group, diagnostic BCG test has got better diagnostic value over Tuberculin Skin Test in diagnosis of tuberculosis.


Assessment of educational environment of surgical theatre at a teaching hospital of a saudi university: using surgical theatre educational environment measures.
This study was aimed to determine how medical interns perceive the important factors of the learning environment the surgical theatre at the teaching hospital of the medical school, University of Dammam (UoD). The study also investigated the relationships between the learning environment and academic achievements. Finally, it determined the role and significance of gender on the above perceptions and relationships. The Surgical Theatre Educational Environment Measure (STEEM) was used to identify the perceptions of interns on the most important factors prevalent in the surgical theatre as an educational environment. STEEM was administered to all interns during the period of June-September 2009. Ninety-one out of 145 students completed the questionnaire representing a response rate of 63%. Non-parametric statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 17. The STEEM was shown to be internally consistent for the assessment of the overall educational environment in the surgical theatre of UoD. The overall STEEM mean score was 110. For male and female students, the mean scores were 114 and 107 respectively. There were statistically significant gender differences in the perceptions of "learning opportunities" and "teaching and training". Females rated these subscales lower than males. There were no significant associations between academic achievements and perceptions of the educational environment. The interns perceived the learning environment of the surgical theatre as less than satisfactory. In comparison with the males; the perception of the females was less positive, particularly in the areas of learning opportunities, and teaching and training. The study also revealed some other problematic areas in the learning environment of surgical theatre of the teaching hospital of UoD. The results imply that there is much room for improvement. They also indicate that equal opportunities for learning and training should be given to both sexes.


Real-world impact of infliximab precision-guided dosing on management of patients with IBD.
Evaluate the clinical utility of a precision-guided dosing test for infliximab (IFX) and its impact on treatment decision-making for inflammatory bowel disease (IBD). Prospective, multisite, clinical experience program. Health care providers were given access to PredictrPK IFX, a precision-guided dosing test, for their patients with IBD on maintenance IFX therapy. Blood samples were drawn 20 to 56 days post infusion. A Bayesian data assimilation tool used clinical and serologic data to generate individual pharmacokinetic profiles and forecast trough IFX. Results were reported to providers to aid in-therapy management decisions and the decision-making process was assessed through questionnaires. Relationships between forecasted IFX concentration, disease activity, and therapy management decisions were analyzed by logistic regression. PredictrPK IFX was used for 275 patients with IBD by 37 providers. In 58% of cases, providers modified treatment plans based on the results, including dose modifications (41%; of these, one-third decreased dose) and discontinuation (8%) of IFX. Of the 42% where treatment was not modified, 97.5% had IFX levels of 5 µg/mL or greater. Patients with IFX concentrations less than 5 µg/mL were 3 and 7.3 times more likely to have active disease or discontinue IFX, respectively. There was unanimous agreement among providers who completed a postprogram survey that PredictrPK IFX was beneficial in guiding treatment decisions and added more value to their practice than routine therapeutic drug monitoring. PredictrPK IFX enables earlier and more precise dose optimization of IFX in patients with IBD, exerting a substantial impact on treatment decisions that may result in improved health outcomes and overall cost savings.


A study on modification of nanoporous rice husk silica for hydrophobic nano filter.
Nanoporous rice husk silica (RHS) was modified with alkylsilylation reagents, hexamethyldisilazane, diethoxydiphenylsilane, dichlorodimethylsilane and n-octodecyltrimethoxysilane. The silica samples were characterized with Raman spectrometer, thermal gravimetric analyzer, scanning electron microscope, nitrogen adsorption measurement and solid state nuclear magnetic resonance spectrometer. Raman spectra of the modified silica showed growth of the peaks of C-H stretching and CH3 bending at approximateluy 3000 cm(-1) and approximately 1500 cm(-1), respectively. Weight losses of 3 approximately 5% were observed in thermo gravimetric profiles of the modified silica. The microscopic shape of RHS, approximately 20 nm primary particles and their aggregates was almost not changed by the modification but there were colligations of the silica particles in the sample treated with dichlorodimethylsilane or diethoxydiphenylsilane. BET adsorption experiment showed the modification significantly decreased the mean pore size of the silica from approximately 5 nm to approximately 4 nm as well as the pore volume from 0.5 cm3/g to 0.4 cm3/g except the case of treatment with n-octodecyltrimethoxysilane. 29Si Solid NMR Spectra of the silica samples showed that there were decrease in the relative intensities of Q2 and Q3 peaks and large increments in Q4 after the modification except for the case of bulky n-octodecyltrimethoxysilane. From the results, it was concluded that the alkylsilylation reagents reacted with hydroxyl groups on the silica particles as well as in the nano pores while the size of the reagent molecule affected its diffusion and reaction with the hydroxyl groups in the pores.


The burden of injuries in Iranian children in 2005.
Child injury is recognized as a global health problem. Injuries caused the highest burden of disease among the total population of Iran in 2003. We aimed to estimate the morbidity, mortality, and disease burden caused by child injuries in the 0- to 14-year-old population of Iran in 2005. We estimated average age- and sex-specific mortality rates for different types of child injuries from 2001 to 2006 using Iran's death registration data. Incidence rates for nonfatal outcomes of child injuries in 2005 were estimated through a time- and place-limited sample hospital registry study for injuries. We used the World Health Organization's methods for estimation of years of life lost due to premature mortality and years lived with disability in 2005. Injuries were the most important cause of death in children ages 1 to 14, with 35, 33.4, 24.9, and 22.9 deaths per 100,000 in the 0-14, 1-4, 5-9, and 10-14 age groups respectively. Road transport injuries were responsible for the highest death rate per 100,000 population among all types of injuries in children, with 15.5 for ages 0-14, 16.1 for ages 1-4, 16.3 for ages 5-9, and 13.1 for ages 10-14. Incidence rates of injuries leading to hospitalization were 459, 530, and 439 per 100,000 in the 0-14, 1-4, and 5-14 age groups respectively. Incidence rates of injuries leading to outpatient care were 1,812, 2,390, and 1,650 per 100,000 in the same age groups respectively. Among injury types, falls and burns had the highest hospitalization and outpatient care incidence rates. Injuries, particularly road transport injuries, were the most important health problem of children in Iran in 2003 and 2005. Strong social policy is needed to ensure child survival.


Order Matters: Children's Evaluation of Underinformative Teachers Depends on Context.
The ability to evaluate "sins of omission"-true but pragmatically misleading, underinformative pedagogy-is critical for learning. This study reveals a developmental change in children's evaluation of underinformative teachers and investigates the nature of their limitations. Participants rated a fully informative teacher and an underinformative teacher in two different orders. Six- and 7-year-olds (N = 28) successfully distinguished the teachers regardless of the order (Experiment 1), whereas 4- and 5-year-olds (N = 82) succeeded only when the fully informative teacher came first (Experiments 2 and 3). After seeing both teachers, 4-year-olds (N = 32) successfully preferred the fully informative teacher (Experiment 4). These results are discussed in light of developmental work in pragmatic implicature, suggesting that young children might struggle with spontaneously generating relevant alternatives for evaluating underinformative pedagogy.


Salicylates in the treatment of arthritic disease. How safe and effective?
Despite the adverse effects of aspirin, many physicians still consider it to be the drug of choice for initial treatment of arthritic disorders. Nonsteroidal antiinflammatory drugs (NSAIDs) are better tolerated than aspirin but have similar, although milder, side effects. The nonacetylated salicylates appear to have fewer adverse effects than either aspirin or the NSAIDs and therefore may warrant greater consideration as first-line therapy for arthritis.


[The Dutch College of General Practitioners' 'Irritable bowel syndrome' standard; reaction from the field of general practice].
In the recently published Dutch College of General Practitioners' standard entitled 'Irritable bowel syndrome', questions for use in establishing this difficult syndrome are provided. Being reserved during examination and using moderation in choosing a treatment regime are the most important recommendations. The emphasis should be on explaining that this is usually a harmless syndrome. This guideline is very helpful to the general practitioner.


Design and Implementation of a Novel Web-Based E-Learning Tool for Education of Health Professionals on the Antibiotic Vancomycin.
Traditional approaches to health professional education are being challenged by increased clinical demands and decreased available time. Web-based e-learning tools offer a convenient and effective method of delivering education, particularly across multiple health care facilities. The effectiveness of this model for health professional education needs to be explored in context. The study aimed to (1) determine health professionals' experience and knowledge of clinical use of vancomycin, an antibiotic used for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and (2) describe the design and implementation of a Web-based e-learning tool created to improve knowledge in this area. We conducted a study on the design and implementation of a video-enhanced, Web-based e-learning tool between April 2014 and January 2016. A Web-based survey was developed to determine prior experience and knowledge of vancomycin use among nurses, doctors, and pharmacists. The Vancomycin Interactive (VI) involved a series of video clips interspersed with question and answer scenarios, where a correct response allowed for progression. Dramatic tension and humor were used as tools to engage users. Health professionals' knowledge of clinical vancomycin use was obtained from website data; qualitative participant feedback was also collected. From the 577 knowledge survey responses, pharmacists (n=70) answered the greatest number of questions correctly (median score 4/5), followed by doctors (n=271; 3/5) and nurses (n=236; 2/5; P<.001). Survey questions on target trough concentration (75.0%, 433/577) and rate of administration (64.9%, 375/577) were answered most correctly, followed by timing of first level (49%, 283/577), maintenance dose (41.9%, 242/577), and loading dose (38.0%, 219/577). Self-reported "very" and "reasonably" experienced health professionals were also more likely to achieve correct responses. The VI was completed by 163 participants during the study period. The rate of correctly answered VI questions on first attempt was 65% for nurses (n=63), 68% for doctors (n=86), and 82% for pharmacists (n=14; P<.001), reflecting a similar pattern to the knowledge survey. Knowledge gaps were identified for loading dose (39.2% correct on first attempt; 64/163), timing of first trough level (50.3%, 82/163), and subsequent trough levels (47.9%, 78/163). Of the 163 participants, we received qualitative user feedback from 51 participants following completion of the VI. Feedback was predominantly positive with themes of "entertaining," "engaging," and "fun" identified; however, there were some technical issues identified relating to accessibility from different operating systems and browsers. A novel Web-based e-learning tool was successfully developed combining game design principles and humor to improve user engagement. Knowledge gaps were identified that allowed for targeting of future education strategies. The VI provides an innovative model for delivering Web-based education to busy health professionals in different locations.


Neurovascular Cell Sheet Transplantation in a Canine Model of Intracranial Hemorrhage.
Cell-based therapy for intracerebral hemorrhage (ICH) has a great therapeutic potential. However, methods to effectively induce direct regeneration of the damaged neural tissue after cell transplantation have not been established, which, if done, would improve the efficacy of cell-based therapy. In this study, we aimed to develop a cell sheet with neurovasculogenic potential and evaluate its usefulness in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory neuroepithelium and vascular progenitors from human adipose tissue-derived stromal cells. We also generated a physiologic canine ICH model by manually injecting and then infusing autologous blood under arterial pressure. We transplanted the sheet cells (cell sheet group) or saline (control group) at the cortex over the hematoma at subacute stages (2 weeks from ICH induction). At 4 weeks from the cell transplantation, cell survival, migration, and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between the groups. As a result, the cell sheet was rich in extracellular matrices and expressed neurotrophic factors as well as the markers for neuronal development. After transplantation, the cells successfully survived for 4 weeks, and a large portion of those migrated to the perihematomal site and differentiated into neurons and pericytes (20% and 30% of migrated stem cells, respectively). Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy (p = 0.042) and showed tendency for improving functional recovery (p = 0.062). Therefore, we concluded that the cell sheet transplantation technique might induce direct regeneration of neural tissue and might improve outcomes of intracerebral hemorrhage.