Interaction effects between insomnia and depression on risk of out-of-hospital cardiac arrest: Multi-center study.
Insomnia and depression have been known to be risk factors of several diseases, including coronary heart disease. We hypothesized that insomnia affects the out-of-hospital cardiac arrest (OHCA) incidence, and these effects may vary depending on whether it is accompanied by depression. This study aimed to determine the association between insomnia and OHCA incidence and whether the effect of insomnia is influenced by depression. This prospective multicenter case-control study was performed using Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiology Surveillance (CAPTURES-II) project database for OHCA cases and community-based controls in Korea. The main exposure was history of insomnia. We conducted conditional logistic regression analysis to estimate the effect of insomnia on the risk of OHCA incidence and performed interaction analysis between insomnia and depression. Finally, subgroup analysis was conducted in the patients with insomnia. Insomnia was not associated with increased OHCA risk (0.95 [0.64-1.40]). In the interaction analysis, insomnia interacted with depression on OHCA incidence in the young population. Insomnia was associated with significantly higher odds of OHCA incidence (3.65 [1.29-10.33]) in patients with depression than in those without depression (0.84 [0.59-1.17]). In the subgroup analysis, depression increased OHCA incidence only in patients who were not taking insomnia medication (3.66 [1.15-11.66]). Insomnia with depression is a risk factor for OHCA in the young population. This trend was maintained only in the population not consuming insomnia medication. Early and active medical intervention for patients with insomnia may contribute to lowering the risk of OHCA.


The Flightless I homolog, fli-1, regulates anterior/posterior polarity, asymmetric cell division and ovulation during Caenorhabditis elegans development.
Flightless I (Fli I) is an evolutionarily conserved member of the gelsolin family, containing actin-binding and severing activity in vitro. The physiological function of Fli I during animal development remains largely undefined. In this study, we reveal a key role of the Caenorhabditis elegans Fli I homolog, fli-1, in specifying asymmetric cell division and in establishing anterior-posterior polarity in the zygote. The fli-1 gene also regulates the cytokinesis of somatic cells and the development of germline and interacts with the phosphoinositol-signaling pathway in the regulation of ovulation. The fli-1 reporter gene shows that the localization of FLI-1 coincides with actin-rich regions and that the actin cytoskeleton is impaired in many tissues in the fli-1 mutants. Furthermore, the function of fli-1 in C. elegans can be functionally substituted by the Drosophila Fli I. Our studies demonstrate that fli-1 plays an important role in regulating the actin-dependent events during C. elegans development.


A new screening method for cystinuria. A simple and safe screening kit.
The new kit (Urocystin) presented here utilizes the dark brown coloration which a neutral aqueous solution of cystine develops rapidly upon addition of nickel ion and sodium hydrosulfite (Na2S2O4). What is needed is pouring 4 ml of the urine sample into the kit, and the kit is able to judge without fail any urine sample with a cystine concentration of 50 microgram/ml or more as positive. No pretreatment of the sample is necessary. The kit contains no hazardous reagents at all. The kit has thus turned screening of cystinuria into an extremely simple affair.


Partial dopamine depletions result in an enhanced sensitivity of residual dopamine neurons to apomorphine.
Extracellular recordings from identified dopamine neurons were used to assess the effect of 6-hydroxydopamine-induced partial lesions of the nigrostriatal dopamine system on the sensitivity of the residual dopamine neurons to the dopamine agonist apomorphine. This was done by testing the response of identified nigral dopamine neurons in control and lesioned rats to systemic apomorphine administration at two time points: 1) 6-10 days post-lesion, when the loss of dopamine cells is nearly complete, and 2) 4-8 weeks post-lesion, which should be sufficient time for changes in dopamine receptor density to occur. As reported previously, dopamine neurons in control rats were inhibited by systemic administration of apomorphine, with their sensitivity being inversely related to their initial firing rate. The sensitivity of the residual dopamine neurons to apomorphine was unaltered in rats tested 6-10 days after depletions of at least 60% of striatal dopamine. However, by 4-8 weeks post-lesion, there was a significant increase in the sensitivity to apomorphine; furthermore, sensitivity was no longer related to baseline firing rate, but instead was uniformly high in all dopamine neurons tested at this time. This enhanced sensitivity was not altered by hemisection of the striatonigral projection, suggesting that the increased sensitivity to apomorphine was most likely a result of a time-dependent up-regulation of somatodendritic autoreceptors on the residual dopamine neurons.


Insecticide content of diet and body fat of Alaskan natives.
A study was made of the DDT and DDE content of the diet and body fat of native Alaskans who lived in isolated, primitive areas and had minimal contact with insecticides. No DDT or DDE was detected in any of the native Alaskan foods analyzed with the exception of two white owls, both of which contained low levels of DDE. Eskimos store considerably less DDT and DDE in their body fat than the general population in the United States. These low dietary levels and the resultant low levels in body fat are consistent with previously published data on the relationship between intake and storage of DDT.


Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis.
Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis. Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II. The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen. This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.


Accuracy of volume measurement using helical CT.
Our goal was to determine the accuracy of volume estimation using helical CT. Helical CT scans were conducted with regularly and irregularly shaped polyvinylchloride bags containing saline of varying volumes immersed in peanut oil during various rates of movement of 0, 10, 15, and 20 cycles/min, using a motorized platform, designed to simulate respiratory motion. Ten cancer patients were scanned with CT to determine optimum upper and lower Hounsfield unit thresholds. The volumes of two human livers and kidneys were also measured in vitro under the same conditions. For all conditions, the accuracy and bias of volume estimation for saline bags ranged from 95.0 to 99.2 and -3.46 to 4.04%, respectively, and the accuracy and bias for the estimation of liver and kidney volumes were 95.6 and 3.12%, respectively. This study shows that helical CT is a highly accurate technique for estimating volume, even in the presence of simulated respiratory motion.


Effect of cellular differentiation on cytokine-induced expression of human immunodeficiency virus in chronically infected promonocytic cells: dissociation of cellular differentiation and viral expression.
Cellular differentiation is thought to play an important role in the susceptibility of monocytic lineage cells to human immunodeficiency virus (HIV) infection as well as in their ability to support virus replication. In addition, virus replication in monocytes/macrophages has been demonstrated in vitro to be strongly modulated by several cytokines such as tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor. The purpose of the present study was to investigate the interaction between cellular differentiation and cytokines in the regulation of HIV expression from chronically infected monocytic lineage cells. U1, a persistently HIV-infected promonocytic cell line, is characterized by low levels of virus expression which can be modulated by several cytokines. 1 alpha,-25-Dihydroxyvitamin D3 (Vit.D3), a well-known differentiating agent for myelomonocytic cells which has been previously reported to modulate HIV replication in other in vitro systems, induced maturation of U1 cells toward a macrophage-like phenotype, as demonstrated by the induction of the differentiation-associated cell surface markers CD14 and CD11b. Vit.D3-induced differentiation did not result in induction of HIV expression; however, when U1 cells were stimulated with tumor necrosis factor alpha in the presence of Vit.D3, a synergistic induction of cell differentiation and viral expression was demonstrated. In contrast, Vit.D3 suppressed the induction of HIV expression in U1 cells stimulated with gamma interferon, interleukin-6, and granulocyte-macrophage colony-stimulating factor, although synergy between Vit.D3 and these cytokines was observed in terms of cellular differentiation. These data suggest that differentiation of monocytic cells does not necessarily correlate with increased HIV expression.


Phosphate solubilization potential and phosphatase activity of rhizospheric trichoderma spp.
Trichoderma sp., a well known biological control agent against several phytopathogens, was tested for its phosphate (P) solubilizing potential. Fourteen strains of Trichoderma sp. were isolated from the forest tree rhizospheres of pinus, deodar, bamboo, guava and oak on Trichoderma selective medium. The isolates were tested for their in-vitro P-solubilizing potential using National Botanical Research Institute Phosphate (NBRIP) broth containing tricalcium phosphate (TCP) as the sole P source, and compared with a standard culture of T. harzianum. All the cultures were found to solubilize TCP but with varying potential. The isolate DRT-1 showed maximum amount of soluble phosphate (404.07 εg.ml(-1)), followed by the standard culture of T. harzianum (386.42 εg.ml(-1)) after 96 h of incubation at 30±1(0)C. Extra-cellular acid and alkaline phosphatases of the fungus were induced only in the presence of insoluble phosphorus source (TCP). High extra-cellular alkaline phosphatase activity was recorded for the isolate DRT-1 (14.50 U.ml(-1)) followed by the standard culture (13.41 U.ml(-1)) at 72h. The cultures showed much lesser acid phosphatase activities. Under glasshouse conditions, Trichoderma sp. inoculation increased chickpea (Cicer arietinum) growth parameters including shoot length, root length, fresh and dry weight of shoot as well as roots, in P-deficient soil containing only bound phosphate (TCP). Shoot weight was increased by 23% and 33% by inoculation with the isolate DRT-1 in the soil amended with 100 and 200 mg TCP kg(-1) soil, respectively, after 60 d of sowing. The study explores high P-solubilizing potential of Trichoderma sp., which can be exploited for the solubilization of fixed phosphates present in the soil, thereby enhancing soil fertility and plant growth.


The role of antigen cross-presentation from leukemia blasts on immunity to the leukemia-associated antigen PR1.
Cross-presentation is an important mechanism by which exogenous tumor antigens are presented to elicit immunity. Because neutrophil elastase (NE) and proteinase-3 (P3) expression is increased in myeloid leukemia, we investigated whether NE and P3 are cross-presented by dendritic cells (DC) and B cells, and whether the NE and P3 source determines immune outcomes. We show that NE and P3 are elevated in leukemia patient serum and that levels correlate with remission status. We demonstrate cellular uptake of NE and P3 into lysosomes, ubiquitination, and proteasome processing for cross-presentation. Using anti-PR1/human leukocyte antigen-A2 monoclonal antibody, we provide direct evidence that B-cells cross-present soluble and leukemia-associated NE and P3, whereas DCs cross-present only leukemia-associated NE and P3. Cross-presentation occurred at early time points but was not associated with DC or B-cell activation, suggesting that NE and P3 cross-presentation may favor tolerance. Furthermore, we show aberrant subcellular localization of NE and P3 in leukemia blasts to compartments that share common elements of the classic major histocompatibility class I antigen-presenting pathway, which may facilitate cross-presentation. Our data demonstrate distinct mechanisms for cross-presentation of soluble and cell-associated NE and P3, which may be valuable in understanding immunity to PR1 in leukemia.


Changes in global nitrogen cycling during the Holocene epoch.
Human activities have doubled the pre-industrial supply of reactive nitrogen on Earth, and future rates of increase are expected to accelerate. Yet little is known about the capacity of the biosphere to buffer increased nitrogen influx. Past changes in global ecosystems following deglaciation at the end of the Pleistocene epoch provide an opportunity to understand better how nitrogen cycling in the terrestrial biosphere responded to changes in carbon cycling. We analysed published records of stable nitrogen isotopic values (δ(15)N) in sediments from 86 lakes on six continents. Here we show that the value of sedimentary δ(15)N declined from 15,000 years before present to 7,056 ± 597 years before present, a period of increasing atmospheric carbon dioxide concentrations and terrestrial carbon accumulation. Comparison of the nitrogen isotope record with concomitant carbon accumulation on land and nitrous oxide in the atmosphere suggests millennia of declining nitrogen availability in terrestrial ecosystems during the Pleistocene-Holocene transition around 11,000 years before present. In contrast, we do not observe a consistent change in global sedimentary δ(15)N values during the past 500 years, despite the potential effects of changing temperature and nitrogen influx from anthropogenic sources. We propose that the lack of a single response may indicate that modern increases in atmospheric carbon dioxide and net carbon sequestration in the biosphere have the potential to offset recent increased supplies of reactive nitrogen in some ecosystems.


Fetal blood and tissue PO2 during maternal oxygen breathing.
The effect of 100% oxygen breathing on fetal blood and tissue PO2 was examined in chronically catheterised fetal sheep of 12 pregnant ewes. Blood PO2 was monitored with intravascular polarographic electrodes and tissue PO2 with galvanic electrodes implanted in various tissues. In non-acidotic healthy fetuses, oxygen breathing increased fetal PO2 by 30% within 3 min in arterial blood and within 5 min in tissues. Thereafter blood PO2 increased by a maximum of 40% at 9 min and tissue PO2 rose by a maximum of 52% at 12 min. Blood PO2 returned promptly to control values after 15 min of oxygen breathing but washout of oxygen from tissues was slower and tissue PO2 remained significantly higher in the post-oxygen versus the pre-oxygen period. Continuation of oxygen breathing for 30 min did not lead to any further increase in tissue PO2. Oxygen breathing did not prevent a decrease in fetal PO2 associated with spontaneous myoelectrical activity of the uterus. It is concluded that maternal oxygen breathing leads to a significant increase in both blood and tissue PO2 in the healthy fetus. The majority of the increase occurs within the first 3-4 min and no further increase in either blood or tissue PO2 is observed after 12 min.


Evaluating the Implementation of Evidence-based Kidney Nutrition Practice Guidelines: The AUGmeNt Study Protocol.
Evidence-based nutrition practice guidelines (EBNPGs) inform registered dietitian nutritionist (RDN) care for patients with chronic kidney disease grade 5 treated by dialysis; however, there has been little evaluation of best practices for implementing EBNPGs. In this effectiveness-implementation hybrid study with a quasi-experimental design, United States RDNs in hemodialysis clinics will document initial and follow-up nutrition care for patients with chronic kidney disease grade 5 treated by dialysis using the Academy of Nutrition and Dietetics Health Informatics Infrastructure before and after being randomly assigned to a training model: (1) EBNPG knowledge training or (2) EBNPG knowledge training plus an implementation toolkit. The aims of the study include examining congruence of RDN documentation of nutrition care with the EBNPG; describing common RDN-reported EBNPG acceptability, adoption, and adaptation issues; and determining the feasibility of estimating the impact of RDN care on nutrition-related patient outcomes. The AUGmeNt study can inform effective development and implementation of future EBNPGs. Keywords: Chronic kidney diseases; medical nutrition therapy; implementation science; clinical practice guideline; nutrition care process terminology; dietitian.


The missing NH stretch fundamental in S1 methyl anthranilate: IR-UV double resonance experiments and local mode theory.
The infrared spectra of jet-cooled methyl anthranilate (MA) and the MA-H2O complex are reported in both S0 and S1 states, recorded using fluorescence-dip infrared (FDIR) spectroscopy under jet-cooled conditions. Using a combination of local mode CH stretch modeling and scaled harmonic vibrational character, a near-complete assignment of the infrared spectra is possible over the 1400-3700 cm-1 region. While the NH stretch fundamentals are easily observed in the S0 spectrum, in the S1 state, the hydrogen bonded NH stretch shift is not readily apparent. Scaled harmonic calculations predict this fundamental at just below 2900 cm-1 with an intensity around 400 km mol-1. However, the experimental spectrum shows no evidence of this transition. A local mode theory is developed in which the NH stretch vibration is treated adiabatically. Minimizing the energy of the corresponding stretch state with one quantum of excitation leads to a dislocation of the H atom where there is equal sharing between N and O atoms. The sharing occurs as a result of significant molecular arrangement due to strong coupling of this NH stretch to other internal degrees of freedom and in particular to the contiguous HNC bend. A two-dimensional model of the coupling between the NH stretch and this bend highlights important nonlinear effects that are not captured by low order vibrational perturbation theory. In particular, the model predicts a dramatic dilution of the NH stretch oscillator strength over many transitions spread over more than 1000 cm-1, making it difficult to observe experimentally.


Peritoneal dialysis solutions--at a crossroad.
After many decades of evolution and with many choices available for the formulation of peritoneal dialysis fluids (PDF), we find ourselves at a crossroads. A review of related developments, laboratory trials and clinical evaluations is offered to stimulate future research in this area. The information presented here raises more questions than it provides answers, but opens the door to innumerable possibilities for improvement. The search for a biocompatible osmotic agent designed to replace those currently used has been frustrating and is far from being considered a success. Research on cytokines and other mediators of inflammation produced a huge amount of interesting scientific knowledge that may help our understanding. However, it is unlikely that it will identify a specifically targeted anticytokine, or combination of them, designed to neutralize and/or reverse inflammatory changes resulting from the use of poorly biocompatible PDF. The development of low glucose degradation product (GDP) solutions by means of multi-chambered bags appear to be a step in the right direction and perhaps is the most significant improvement in this field in many decades. GDPs are important, but not the only offenders or the exclusive source of oxidative stress. Thus, the addition of antioxidants to PDF formulations, in our opinion, deserves further consideration. Additionally, repopulation of the mesothelial monolayer by means of periodic autotransplantation of mesothelial cells may well become a useful tool to prevent and/or correct membrane failure. We are fortunate to have choices at this crossroad, which we must evaluate rigorously.


A comprehensive method for GNSS data quality determination to improve ionospheric data analysis.
Global Navigation Satellite Systems (GNSS) are now recognized as cost-effective tools for ionospheric studies by providing the global coverage through worldwide networks of GNSS stations. While GNSS networks continue to expand to improve the observability of the ionosphere, the amount of poor quality GNSS observation data is also increasing and the use of poor-quality GNSS data degrades the accuracy of ionospheric measurements. This paper develops a comprehensive method to determine the quality of GNSS observations for the purpose of ionospheric studies. The algorithms are designed especially to compute key GNSS data quality parameters which affect the quality of ionospheric product. The quality of data collected from the Continuously Operating Reference Stations (CORS) network in the conterminous United States (CONUS) is analyzed. The resulting quality varies widely, depending on each station and the data quality of individual stations persists for an extended time period. When compared to conventional methods, the quality parameters obtained from the proposed method have a stronger correlation with the quality of ionospheric data. The results suggest that a set of data quality parameters when used in combination can effectively select stations with high-quality GNSS data and improve the performance of ionospheric data analysis.


Accelerating what works: using qualitative research methods in developing a change package for a learning collaborative.
Learning (quality improvement) collaboratives are effective vehicles for driving coordinated organizational improvements. A central element of a learning collaborative is the change package-a catalogue of strategies, change concepts, and action steps that guide participants in their improvement efforts. Despite a vast literature describing learning collaboratives, little to no information is available on how the guiding strategies, change concepts, and action items are identified and developed to a replicable and actionable format that can be used to make measurable improvements within participating organizations. The process for developing the change package for the Health Resources and Services Administration's (HRSA) Patient Safety and Clinical Pharmacy Services Collaborative entailed environmental scan and identification of leading practices, case studies, interim debriefing meetings, data synthesis, and a technical expert panel meeting. Data synthesis involved end-of-day debriefings, systematic qualitative analyses, and the use of grounded theory and inductive data analysis techniques. This approach allowed systematic identification of innovative patient safety and clinical pharmacy practices that could be adopted in diverse environments. A case study approach enabled the research team to study practices in their natural environments. Use of grounded theory and inductive data analysis techniques enabled identification of strategies, change concepts, and actionable items that might not have been captured using different approaches. Use of systematic processes and qualitative methods in identification and translation of innovative practices can greatly accelerate the diffusion of innovations and practice improvements. This approach is effective whether or not an individual organization is part of a learning collaborative.


The tsunami and its aftermath in Sri Lanka: explorations of a Buddhist perspective.
This paper discusses the tsunami disaster in Sri Lanka with special reference to Buddhism, which is the majority religion in the island. The role of religious beliefs and of religion in general in strengthening coping skills is well known. Buddhism, with its specific views on the human condition and its use of psychological strategies, is almost unique among world religions. The Buddhist responses to the tsunami have been discussed widely, if largely informally, in Sri Lanka, and many concepts and practices have been highlighted and focused on. This paper provides an overview of the relationship between culture and traumatic experiences, with a brief discussion of the role of religion in mental health. It then goes on to explore some relevant Buddhist concepts and practices which can be used in clinical settings.


Work characteristics, socioeconomic position and health: a systematic review of mediation and moderation effects in prospective studies.
Social inequalities in health persist in modern societies. The contribution of adverse work and employment conditions towards their explanation is analysed by two approaches, mediation and moderation. Yet the relative significance of each approach remains unclear in respective research. We set out to study this question by conducting a systematic literature review. We included all original papers based on prospective observational studies of employed cohorts that were published between January 1980 and October 2012 meeting our search criteria, by using major databases and by observing established quality criteria. 26 reports were included after quality assessment. 17 studies examined the mediation hypothesis and nine studies tested the moderation hypothesis. Moderate support was found for the mediation hypothesis where OR or HR of health according to socioeconomic position (SEP) were reduced in a majority of analyses after introducing work characteristics in multivariate models. Evidence in favour of the moderation hypothesis was found in some studies, demonstrating stronger effects of adverse work on health among people with low SEP. Despite some support in favour of the two hypotheses future research should aim at reducing the heterogeneity in defining and measuring core variables and at applying advanced statistical analyses. Policy recommendations would benefit from a higher degree of consistency of respective research evidence.


Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma.
Besides asbestos exposure, the factors that determine susceptibility to malignant mesothelioma are unknown. We evaluated the risk of GSTM1 null genotype and slow acetylation-associated NAT2 genotype for malignant mesothelioma in relation to asbestos exposure. Both the GSTM1 null genotype and the NAT2 slow acetylator genotype placed individuals at about 2-fold increased risk of developing malignant mesothelioma [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.5 and OR = 2.1, 95% CI = 1.1-4.1, for the GSTM1 and NAT2 genes, respectively]. When the patients were divided into low/moderate and high exposure groups according to their asbestos exposure histories, the effect of the at-risk genotypes was mostly attributable to the high exposure groups (OR = 2.3, 95% CI = 1.0-5.6 and OR = 3.7, 95% CI = 1.3-10.2, for the GSTM1 and NAT2 genes, respectively). The individuals with combined GSTM1 and NAT2 defects had about a 4-fold risk of developing malignant mesothelioma compared to those with the GSTM1 gene and NAT2 fast acetylator genotype (OR = 3.6; 95% CI = 1.3-9.6). Moreover, the risk among subjects highly exposed to asbestos with the double at-risk genotype was more than 7-fold greater compared to those with the more beneficial genotypes of both GSTM1 and NAT2 genes (OR = 7.4; 95% CI = 1.6-34.0).


Feasibility of working with a wholesale supplier to co-design and test acceptability of an intervention to promote smaller portions: an uncontrolled before-and-after study in British Fish & Chip shops.
To explore the feasibility of working with a wholesale supplier to co-design and deliver, and to assess the acceptability of, an intervention to promote smaller portions in Fish & Chip shops. Uncontrolled before-and-after study. Fish & Chip shops in northern England, 2016. Owners (n=11), a manager and customers (n=46) of Fish & Chip shops; and intervention deliverers (n=3). Supplier-led, three-hour engagement event with shop owners and managers, highlighting the problem of excessive portion sizes and potential ways to reduce portion sizes; provision of box packaging to serve smaller portions; promotional posters and business incentives. In-store observations and sales data collected at baseline and postintervention. Exit survey with customers. Semistructured interviews with owners/managers and intervention deliverers postintervention. Twelve Fish & Chip shops were recruited. Observational data were collected from eight shops: at baseline, six shops did not promote the availability of smaller portion meals; at follow-up, all eight did and five displayed the promotional poster. Seven out of 12 shops provided sales data and all reported increased sales of smaller portion meals postintervention. Of 46 customers surveyed: 28% were unaware of the availability of smaller portion meals; 20% had bought smaller portion meals; and 46% of those who had not bought these meals were interested to try them in the future. Interviews revealed: owners/managers found the intervention acceptable but wanted a clearer definition of a smaller portion meal; the supplier valued the experience of intervention co-production and saw the intervention as being compatible with their responsibility to drive innovation. The co-design of the intervention with a supplier was feasible. The partnership facilitated the delivery of an intervention that was acceptable to owners and customers. Sales of smaller meal packaging suggest that promotion of such meals is viable and may be sustainable.


Reduction of intermetatarsal angle following Keller arthroplasty.
A composite retrospective radiographic analysis of 71 patients who had undergone the Keller arthroplasty and 76 who had undergone the Keller with hemi-implant was performed. The combined mean preoperative intermetatarsal angle was 11.4 degrees, the mean postoperative intermetatarsal angle was 9.4 degrees, and the mean change in intermetatarsal angle was 2.0 degrees. Although the reduction of the metatarsus primus adductus deformity obtained was less than previous studies, the amount of correction was directly proportional to the magnitude of deformity. The authors conclude that through reverse buckling at the first metatarsophalangeal joint, adequate reduction in the positional component of metatarsus primus adductus can be obtained with the Keller arthroplasty alone or with a hemi-implant. These procedures are preferred over metatarsal osteotomies in the physiologically older patient, especially when a severe metatarsus primus adductus deformity exists.


Ivermectin 1% (CD5024) for the treatment of rosacea.
Rosacea is a chronic and recurrent disease with a variety of cutaneous manifestations. The disorder is a centrofacial inflammatory dermatosis with significant financial, physical and psychological impacts. There are a number of topical, oral and systemic treatments available. Yet, treatment for rosacea remains difficult. The multifactorial nature of the disease combined with an incomplete understanding of the pathophysiology is challenging for providers and patients. Areas covered: This article provides an in-depth review of rosacea treatment and emerging use of ivermectin 1% cream for papulopustular rosacea based on multiple clinical trials. The PubMed database was searched using the combination of keywords "ivermectin, rosacea, and papulopustular." Expert opinion: Topical ivermectin 1% cream has emerged as a novel agent for treatment of papulopustular rosacea. The drug targets the Demodex mite which is increased in patients with rosacea. Though ivermectin 1% is a clinically efficacious medication, poor adherence continues to remain an issue due to topical application. Ultimately, the agent has the potential to be an effective drug when used as a single or combination agent. With the move to limit chronic antibiotic use, topical agents such as ivermectin 1% will continue to thrive as a specialized niche in the rosacea market.


A preliminary investigation of postmortem tooth loss.
Forensic anthropologists have found a seemingly increased frequency of dismemberment cases and subsequent scattering of the elements that mandates developing unconventional methods of estimating postmortem interval. The chronological sequence in postmortem tooth loss has been investigated as an indicator for estimation of time since death. The anterior dentitions of cadavera were observed to discern patterns in "drop time" based on age, periodontal health, seasonality and location of body placement. Individuals deposited in the summer months lost teeth much more rapidly than those deposited in the late fall or winter months. Similarly, individuals exposed to direct sunlight, a micro-environment where rapid decomposition has been noted, lost teeth before individuals in shaded locales. Since tooth loss is dependent on the deterioration of the soft tissues which bind the tooth into the alveolar bone, we found tooth loss to be correlated with general soft tissue decomposition rates as dictated by season and environment. When utilized as sole indicator, the patterns of postmortem tooth loss can not be used for estimating time since death. However, when used in conjunction with other indicators, tooth loss patterns may provide useful information for more accurate estimation of the postmortem interval.


Initiation, influence, and impact: adolescents and parents discuss the marketing of gambling products during Australian sporting matches.
Harmful gambling is a significant public health issue. Alongside the rapid diversification of gambling products, are rapid increases in the marketing for specific types of gambling products, such as online wagering. While concern has been raised about the impact of gambling promotions during sporting matches on the gambling beliefs and behaviours of adolescents, very little research has explored adolescents' and parents' attitudes towards the marketing of gambling products within sport. A qualitative study was conducted with 59 family groups comprising of at least one parent and one adolescent (14-18 years old) in Victoria, Australia. Parents and adolescents were interviewed separately and asked questions relating to their gambling attitudes and behaviours. They were then brought together, and advertising reception techniques were utilised to prompt discussions about the marketing of gambling during sport. A thematic approach to analysis was used, constantly comparing similarities and differences between and across groups. Three main themes emerged. First, was initiation of sport as a platform for the promotion of gambling. Adolescents perceived that the use of embedded promotions (for example during the match) and the use of athletes in gambling promotions were significant mechanisms for creating an alignment between gambling companies and sporting teams and codes. Second, was the influence of marketing messages in creating a perception that gambling was always accessible, and was an integral part of the sporting experience. Third was the impact of marketing messages on adolescent's discourses about sport. Parents described that they had noticed that wagering, and 'odds' discussions, had become embedded in adolescents narratives about sporting matches. Gambling marketing during sport has significantly increased. While the gambling industry states that it does not aim to intentionally target young people, adolescents are increasingly aware of the relationship between gambling and sport. Future research should explore the impacts and influence of gambling promotions during sport on the gambling attitudes and consumption intentions of adolescents. Effective public health policy is needed to develop comprehensive regulatory frameworks to protect young people from unnecessary exposure to the marketing for this potentially harmful adult product.


Association of dietary fibre intake and gut microbiota in adults.
Increasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet-microbiota relationships for future development of colorectal cancer prevention strategies.


Milder Autumns May Increase Risk for Infection of Crops with Turnip Yellows Virus.
Climate change has increased the risk for infection of crops with insect-transmitted viruses. Mild autumns provide prolonged active periods to insects, which may spread viruses to winter crops. In autumn 2018, green peach aphids (Myzus persicae) were found in suction traps in southern Sweden that presented infection risk for winter oilseed rape (OSR; Brassica napus) with turnip yellows virus (TuYV). A survey was carried out in spring 2019 with random leaf samples from 46 OSR fields in southern and central Sweden using DAS-ELISA, and TuYV was detected in all fields except one. In the counties of Skåne, Kalmar, and Östergötland, the average incidence of TuYV-infected plants was 75%, and the incidence reached 100% for nine fields. Sequence analyses of the coat protein gene revealed a close relationship between TuYV isolates from Sweden and other parts of the world. High-throughput sequencing for one of the OSR samples confirmed the presence of TuYV and revealed coinfection with TuYV-associated RNA. Molecular analyses of seven sugar beet (Beta vulgaris) plants with yellowing, collected in 2019, revealed that two of them were infected by TuYV, together with two other poleroviruses: beet mild yellowing virus and beet chlorosis virus. The presence of TuYV in sugar beet suggests a spillover from other hosts. Poleroviruses are prone to recombination, and mixed infection with three poleroviruses in the same plant poses a risk for the emergence of new polerovirus genotypes. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.


Modelling the effects of cell-cycle heterogeneity on the response of a solid tumour to chemotherapy: biological insights from a hybrid multiscale cellular automaton model.
The therapeutic control of a solid tumour depends critically on the responses of the individual cells that constitute the entire tumour mass. A particular cell's spatial location within the tumour and intracellular interactions, including the evolution of the cell-cycle within each cell, has an impact on their decision to grow and divide. They are also influenced by external signals from other cells as well as oxygen and nutrient concentrations. Hence, it is important to take these into account when modelling tumour growth and the response to various treatment regimes ('cell-kill therapies'), including chemotherapy. In order to address this multiscale nature of solid tumour growth and its response to treatment, we propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the level of cells, linking individual cell behaviour with the macroscopic behaviour of cell organisation and the microenvironment. The individual tumour cells are modelled by using a cellular automaton (CA) approach, where each cell has its own internal cell-cycle, modelled using a system of ODEs. The internal cell-cycle dynamics determine the growth strategy in the CA model, making it more predictive and biologically relevant. It also helps to classify the cells according to their cell-cycle states and to analyse the effect of various cell-cycle dependent cytotoxic drugs. Moreover, we have incorporated the evolution of oxygen dynamics within this hybrid model in order to study the effects of the microenvironment in cell-cycle regulation and tumour treatments. An important factor from the treatment point of view is that the low concentration of oxygen can result in a hypoxia-induced quiescence (G0/G1 arrest) of the cancer cells, making them resistant to key cytotoxic drugs. Using this multiscale model, we investigate the impact of oxygen heterogeneity on the spatio-temporal patterning of the cell distribution and their cell-cycle status. We demonstrate that oxygen transport limitations result in significant heterogeneity in HIF-1 α signalling and cell-cycle status, and when these are combined with drug transport limitations, the efficacy of the therapy is significantly impaired.


NEUROPSYCHOLOGY: Language Affects Sound Perception.
At the 140th meeting of the Acoustical Society of America here last week, a psychologist demonstrated that an auditory illusion based on the tritone--two notes a half-octave apart played together--is perceived differently by listeners with different linguistic histories. And those perceptions might help psychologists understand how the brain rewires itself during childhood.


Highly efficient gel-state dye-sensitized solar cells prepared using poly(acrylonitrile-co-vinyl acetate) based polymer electrolytes.
Poly(acrylonitrile-co-vinyl acetate) (PAN-VA) is utilized as a gelation agent to prepare gel-state electrolytes for dye-sensitized solar cell (DSSC) applications. Based on the synergistic effect of PAN-VA and TiO(2) fillers in the electrolyte, the gel-state DSSC can achieve a conversion efficiency higher than that of a liquid counterpart. The high performance of the gel-electrolyte is attributed to the in situ gelation property of the gel-electrolyte, the contribution of the PAN-VA to the charge transfer, as well as the enhancement effect of TiO(2) fillers on the charge transfer at the Pt-electrolyte interface. The experimental results show that the efficiencies of the gel-state cells have little dependence on the conductivity of the electrolytes with various contents of PAN-VA, but are closely related to the penetration situation of the electrolyte in the TiO(2) film. For PAN-VA concentrations ≤15 wt%, the electrolyte can be easily injected at room temperature based on its in situ gelation property. For higher PAN-VA concentrations, good penetration of the high viscous electrolyte can be achieved by elevating the operation temperature. By utilizing a heteroleptic ruthenium dye (coded CYC-B11), gel-state DSSCs with an efficiency of above 10% are obtained. Acceleration tests show that the cell is stable under one-sun illumination at 60 °C.


[Prevalence of cardiovascular risk factors in HIV-infected patients].
To determine the prevalence of cardiovascular risk factors in human immunodeficiency virus (HIV)-infected patients. A cross-sectional study was performed with HIV-infected patients aged 20 or over managed at the outpatient Infectious Disease Unit during 2003. Clinical and epidemiological characteristics of HIV infection and cardiovascular risk factors were evaluated. The final 760 patients included in the study had a mean of 1.5 cardiovascular risk factors, with smoking being the most prevalent (66.8%; CI 95%: 63.4-70.2). The cardiovascular risk factor of age and gender was present in 26.4% (CI 95%: 23.3-29.7) of patients and family history of premature coronary heart disease in 14.3% (CI 95%: 11.8-16.9). The prevalence of hypertension and diabetes mellitus was 13.2% (CI 95%: 10.8-15.8) and 4.3% (CI 95%: 3.0-6.0), respectively. High density lipoprotein (HDL) cholesterol concentration under 40 mg/dl was found in 29.3% (CI 95%: 26.1-32.7) and above 60 mg/dl in 16.3% (CI 95%: 13.8-19.1). Twenty-five patients (3.3%; CI 95%: 2.1-4.8) had suffered overt cardiovascular disease. Smoking and HDL cholesterol were the main cardiovascular risk factors in this HIV-infected cohort.


Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia.
Desmoplasia in human pancreatic cancer (PC) promotes cancer progression and hinders effective drug delivery. The objectives of this study were to characterize a homologous orthotopic model of PC in Syrian golden hamster and investigate the effect of anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) and anti-addiction (disulfiram, DSF) drugs on desmoplasia and tumor growth in this model. The HapT1 PC cells when implanted orthotopically into hamsters formed tumors with morphological, cellular and molecular similarities to human PC. Protein profiling of activated hamster pancreatic stellate cells (ha-PSCs) revealed expression of proteins involved in fibrosis, cancer cells growth and metastasis. Pirfenidone, suppressed growth of HapT1 cells and the desmoplastic response in vivo; these effects were enhanced by co-administration of NAC. Disulfiram alone or in combination with copper (Cu) was toxic to HapT1 cells and PSCs in vitro; but co-administration of DSF and Cu accelerated growth of HapT1 cells in vivo. Moreover, DSF had no effect on tumor-associated desmoplasia. Overall, this study identifies HapT1-derived orthotopic tumors as a useful model to study desmoplasia and tumor-directed therapeutics in PC. Pirfenidone in combination with NAC could be a novel combination therapy for PC and warrants investigation in human subjects.


Photoaffinity labelling of carnitine acetyltransferase with S-(p-azidophenacyl)thiocarnitine.
A photolabile reagent, p-azidophenacyl-DL-thiocarnitine, was synthesized and tested as a photoaffinity label for carnitine acetyltransferase (EC 18.104.22.168) from pigeon breast. p-Azidophenacyl-DL-thiocarnitine is an active-site-directed reagent for this acetyltransferase, since it is a competitive inhibitor (Ki 10 microM) versus carnitine. U.v. irradiation of a mixture of p-azidophenacyl-DL-thiocarnitine and enzyme produces irreversible inhibition. Acetyl-DL-carnitine protects the enzyme from inhibition by photoactivated p-azidophenacyl-DL-thiocarnitine. In the presence of 30 mM-2-mercaptoethanol as a scavenger, the relationship between loss of activity and photoincorporation of reagent suggests that one molecule of reagent is incorporated per molecule of inhibited enzyme. However, peptide maps of enzyme labelled with p-azidophenacyl[14C]thiocarnitine indicate that several (about six) tryptic peptides (of a possible 60-65) are modified. The presence of 5 mM-acetyl-DL-carnitine significantly decreases the incorporation of reagent in each labelled tryptic peptide.


Enzyme-responsive polyion complex (PIC) nanoparticles for the targeted delivery of antimicrobial polymers.
Here we present new enzyme-responsive polyion complex (PIC) nanoparticles prepared from antimicrobial poly(ethylene imine) and an anionic enzyme-responsive peptide targeting Pseudomonas aeruginosa's elastase. The synthetic conditions used to prepare these nanomaterials allowed us to optimise particle size and charge, and their stability under physiological conditions. We demonstrate that these enzyme responsive PIC nanoparticles are selectively degraded in the presence of P. aeruginosa elastase without being affected by other endogenous elastases. This enzyme-responsive PIC particle can exert an elastase-specific antimicrobial effect against P. aeruginosa without affecting non-pathogenic strains of these bacteria. These targeted enzyme-responsive PIC nanoparticles constitute a novel platform for the delivery of antimicrobial peptides and polymers, and can be a powerful tool in the current race against antimicrobial resistance.


[Experiences in long-term therapy of rheumatoid arthritis with sulfasalazine tablets].
To demonstrate the efficacy and compatibility of sulphasalazine as a long term treatment of rheumatoid arthritis, use of the substance (known in Britain as Salazopyrin EN and in Germany as Azulfidine RA) has been compared with that of intramuscular gold. Using very stringent and novel criteria for success--a patient must have no more than one swollen joint after a minimum of 2 years treatment, with less than 30 min of early morning stiffness and still be receiving the drug--the cumulative efficacy of each drug was very similar (32% with sulphasalazine vs 44% with gold). Toxic events leading to drug withdrawal, however, were twice as frequent with gold, and the type of toxic event encountered was considered to be potentially much more serious than those with sulphasalazine (96% of the toxic events on gold fell into the mucocutaneous, renal or haematological groups).


Prevalence of antibody to Brucella in asymptomatic well individuals in Saudi Arabia.
Two populations of asymptomatic well individuals resident in central Saudi Arabia were tested for antibody to brucella antigen. A relatively high prevalence of antibody (as measured by the standard agglutination test) was found in both populations. A much lower prevalence of antibody was demonstrated by the 2-mercaptoethanol test in these populations. There follows a discussion of the utility of brucella serological tests in developing countries in which the disease is endemic.


Novel Pyran-Linked Phthalazinone-Pyrazole Hybrids: Synthesis, Cytotoxicity Evaluation, Molecular Modeling, and Descriptor Studies.
A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.


Association between ambient temperature, particulate air pollution and emergency room visits for conjunctivitis.
Numerous studies have confirmed the association of ambient temperature and air pollution with a higher risk of morbidities, yet few have addressed their effect on the ocular system. The purpose of this study was to assess the association between temperature, air pollution, and emergency room visits for conjunctivitis. In this case-crossover study, the records of all emergency room visits to Soroka University Medical Center (SUMC) from 2009 to 2014 were reviewed for patients with conjunctivitis. Daily exposure to fine and coarse particulate matter and temperature were determined by a hybrid model involving satellite sensors. Mean relative humidity was obtained from the Ministry of Environmental Protection meteorological monitoring station located in Beer-Sheva. Six hundred one patients were diagnosed with conjunctivitis in the SUMC emergency room. We discovered a positive association between temperature increments and incidence of conjunctivitis. The strongest effect was found during summer and autumn, with an immediate (lag0) incidence increase of 8.1% for each 1 °C increase in temperature (OR = 1.088, 95%CI: 1.046-1.132) between 24 and 28 °C in the summer and 7.2% for each 1 °C increase in temperature (OR = 1.072, 95%CI: 1.036-1.108) between 13 and 23 °C in the autumn. There was no statistically significant association between fine and coarse particulate matter and conjunctivitis incidence. Temperature increases during summer and autumn are significantly associated with an increased risk of conjunctivitis. Conjunctivitis is not associated with non-anthropogenic air pollution. These findings may help community clinics and hospital emergency rooms better predict conjunctivitis cases and will hopefully lead to improved prevention efforts that will lower the financial burden on both the individual and the public.


Tyrosine phosphorylation of CD19 in pre-B and mature B cells.
Cross-linking of B cell surface immunoglobulins (sIg) results in activation of mature B cells and stimulates a molecular signaling mechanism for antigen-specific B cell expansion and differentiation. This signaling pathway is dependent on tyrosine (Tyr) phosphorylation and results in the activation of sIg-associated src family kinases and p72SYK. Rapid Tyr phosphorylation occurs on multiple protein substrates. Here we show that activation of B cells by cross-linking sIg results in an increase in Tyr phosphorylation of the lineage-restricted B cell surface antigen CD19, and show that it is a major substrate of activated Tyr kinase following sIg stimulation. Lower levels of constitutive CD19 Tyr phosphorylation occurred in most sIg+ mature B cell lines examined and in normal dense tonsillar B cells. We also find that when CD19 is Tyr-phosphorylated it becomes competent to interact with SH2 domains suggesting a mechanism whereby, following B cell activation, CD19 could be linked to intracellular signaling pathways. In sIg- pre-B cell lines, CD19 was expressed but was not constitutively phosphorylated on tyrosine. Upon CD19 cross-linking, Tyr phosphorylation of CD19 was induced in sIg- pre-B cell lines. CD19 cross-linking also directly induced Tyr phosphorylation of CD19 and other substrates in mature B cells. The ability of CD19 to signal in the absence of sIg expression may provide important stimulation in pre-B cell development.


Molecular systematics of the deep-sea hydrothermal vent endemic Brachyuran family Bythograeidae: a comparison of three Bayesian species tree methods.
Brachyuran crabs of the family Bythograeidae are endemic to deep-sea hydrothermal vents and represent one of the most successful groups of macroinvertebrates that have colonized this extreme environment. Occurring worldwide, the family includes six genera (Allograea, Austinograea, Bythograea, Cyanagraea, Gandalfus, and Segonzacia) and fourteen formally described species. To investigate their evolutionary relationships, we conducted Maximum Likelihood and Bayesian molecular phylogenetic analyses, based on DNA sequences from fragments of three mitochondrial genes (16S rDNA, Cytochrome oxidase I, and Cytochrome b) and three nuclear genes (28S rDNA, the sodium-potassium ATPase a-subunit 'NaK', and Histone H3A). We employed traditional concatenated (i.e., supermatrix) phylogenetic methods, as well as three recently developed Bayesian multilocus methods aimed at inferring species trees from potentially discordant gene trees. We found strong support for two main clades within Bythograeidae: one comprising the members of the genus Bythograea; and the other comprising the remaining genera. Relationships within each of these two clades were partially resolved. We compare our results with an earlier hypothesis on the phylogenetic relationships among bythograeid genera based on morphology. We also discuss the biogeography of the family in the light of our results. Our species tree analyses reveal differences in how each of the three methods weighs conflicting phylogenetic signal from different gene partitions and how limits on the number of outgroup taxa may affect the results.


Hidden Charge Order in an Iron Oxide Square-Lattice Compound.
Since the discovery of charge disproportionation in the FeO_{2} square-lattice compound Sr_{3}Fe_{2}O_{7} by Mössbauer spectroscopy more than fifty years ago, the spatial ordering pattern of the disproportionated charges has remained "hidden" to conventional diffraction probes, despite numerous x-ray and neutron scattering studies. We have used neutron Larmor diffraction and Fe K-edge resonant x-ray scattering to demonstrate checkerboard charge order in the FeO_{2} planes that vanishes at a sharp second-order phase transition upon heating above 332 K. Stacking disorder of the checkerboard pattern due to frustrated interlayer interactions broadens the corresponding superstructure reflections and greatly reduces their amplitude, thus explaining the difficulty of detecting them by conventional probes. We discuss the implications of these findings for research on "hidden order" in other materials.


Best evidence topic reports. Gastric lavage in paracetamol poisoning.
A short cut review was carried out to establish whether gastric lavage is better than activated charcoal in cases of poisoning with paracetamol. Altogether 63 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.


Rabbit VX2 Liver Tumor Model: A Review of Clinical, Biology, Histology, and Tumor Microenvironment Characteristics.
The rabbit VX2 is a large animal model of cancer used for decades by interventional radiologists to demonstrate the efficacy of various locoregional treatments against liver tumors. What do we know about this tumor in the new era of targeted therapy and immune-oncology? The present paper describes the current knowledge on the clinics, biology, histopathology, and tumor microenvironment of VX2 based on a literature review of 741 publications in the liver and in other organs. It reveals the resemblance with human cancer (anatomy, vascularity, angiogenic profile, drug sensitivity, immune microenvironment), the differences (etiology, growth rate, histology), and the questions still poorly explored (serum and tissue biomarkers, genomic alterations, immune checkpoint inhibitors efficacy).


Mouse islet of Langerhans isolation using a combination of purified collagenase and neutral protease.
The interrogation of beta cell gene expression and function in vitro has squarely shifted over the years from the study of rodent tumorigenic cell lines to the study of isolated rodent islets. Primary islets offer the distinct advantage that they more faithfully reflect the biology of intracellular signaling pathways and secretory responses. Whereas the method of islet isolation using tissue dissociating enzyme (TDE) preparations has been well established in many laboratories(1-4), variations in the consistency of islet yield and quality from any given rodent strain limit the extent and feasibility of primary islet studies. These variations often occur as a result of the crude partially purified TDEs used in the islet isolation procedure; TDEs frequently exhibit lot-to-lot variations in activity and often require adjustments to the dose of enzyme used. A small number of reports have used purified TDEs for rodent cell isolations(5, 6), but the practice is not widespread despite the routine use and advantages of purified TDEs for human islet isolations. In collaboration with VitaCyte, LLC (Indianapolis, IN), we developed a modified mouse islet isolation protocol based on that described by Gotoh(7, 8), in which the TDEs are perfused directly into the pancreatic duct of mice, followed by crude tissue fractionation through a Histopaque gradient(9), and isolation of purified islets. A significant difference in our protocol is the use of purified collagenase (CIzyme MA) and neutral protease (CIzyme BP) combination. The collagenase was characterized by the use of a(6) fluorescence collagen degrading activity (CDA) assay that utilized fluorescently labeled soluble calf skin fibrils as substrate(6). This substrate is more predictive of the kinetics of collagen degradation in the tissue matrix because it relies on native collagen as the substrate. The protease was characterized with a sensitive fluorescent kinetic assay(10). Utilizing these improved assays along with more traditional biochemical analysis enable the TDE to be manufactured more consistently, leading to improved performance consistency between lots. The protocol described in here was optimized for maximal islet yield and optimal islet morphology using C57BL/6 mice. During the development of this protocol, several combinations of collagenase and neutral proteases were evaluated at different concentrations, and the final ratio of collagenase:neutral protease of 35:10 represents enzyme performance comparable to Sigma Type XI. Because significant variability in average islet yields from different strains of rats and mice have been reported, additional modifications of the TDE composition should be made to improve the yield and quality of islets recovered from different species and strains.


Chondrosarcoma in a family with multiple hereditary exostoses.
Multiple hereditary exostoses is an autosomal dominant skeletal disorder in which there are numerous cartilage-capped excrescences in areas of actively growing bone. The condition is genetically heterogeneous, and at least three genes, ext1, ext2 and ext3 are involved. The reported risk for malignant transformation to chondrosarcoma has been from 0.6% to 2.8%. We have reviewed six generations of a family with 114 living adult members, 46 of them with multiple exostoses. Four have had operations for chondrosarcoma, giving the risk for malignant transformation as 8.3% in this family. Clinical and radiological examination revealed two additional patients with a suspicion of malignancy, but in whom the histological findings were benign. Reported elsewhere in detail, genetic linkage analysis mapped the causative gene to chromosome 11 and molecular studies revealed a guanine-to-thymine transversion in the ext2 gene. Patients with multiple hereditary exostoses carry a relatively high risk of malignant transformation. They should be informed of this possibility and regularly reviewed.


The preceptor--preceptee model for faculty "cross-training".
In the review of the literature, the author notes several discussions concerning collaboration between nursing education and service agencies for updating faculty clinical practice. This article addresses the Preceptor-Preceptee model for Faculty "Cross-training," including the permission process, method, needs analysis, and evaluation. A concluding statement by the author strongly recommends the utilization of the faculty practice model to enhance the faculty's competence in clinical nursing areas.


Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation.
Previous studies have shown that nitric oxide (NO) supplements may prevent bone loss and fractures in preclinical models of estrogen deficiency. However, the mechanisms by which NO modulates bone anabolism remain largely unclear. Argininosuccinate lyase (ASL) is the only mammalian enzyme capable of synthesizing arginine, the sole precursor for nitric oxide synthase-dependent (NOS-dependent) NO synthesis. Moreover, ASL is also required for channeling extracellular arginine to NOS for NO production. ASL deficiency (ASLD) is thus a model to study cell-autonomous, NOS-dependent NO deficiency. Here, we report that loss of ASL led to decreased NO production and impairment of osteoblast differentiation. Mechanistically, the bone phenotype was at least in part driven by the loss of NO-mediated activation of the glycolysis pathway in osteoblasts that led to decreased osteoblast differentiation and function. Heterozygous deletion of caveolin 1, a negative regulator of NO synthesis, restored NO production, osteoblast differentiation, glycolysis, and bone mass in a hypomorphic mouse model of ASLD. The translational significance of these preclinical studies was further reiterated by studies conducted in induced pluripotent stem cells from an individual with ASLD. Taken together, our findings suggest that ASLD is a unique genetic model for studying NO-dependent osteoblast function and that the NO/glycolysis pathway may be a new target to modulate bone anabolism.


Risk factors for corneal inflammatory and mechanical events with extended wear silicone hydrogel contact lenses.
To identify risk factors for contact lens-related corneal inflammatory events and mechanical events in wearers of silicone hydrogel lenses on a 30-night extended wear (EW) schedule in India. An interventional study with 188 subjects wearing silicone hydrogel lenses bilaterally on a 30-night EW schedule. Subjects were dispensed with lenses and reviewed at scheduled visits up to 6 months of EW. Multivariate logistic regression, after adjusting for within subject correlation, was used to develop the statistical model. Occupations in non-ideal environments were found to predispose a lens wearer to inflammatory events (p = 0.003). Wearers in the non-ideal group, who had varying degrees of exposure to ocular irritants in their work environment had highest incidence of inflammatory events (19.2%). Wearers in a controlled, ideal environment had lowest levels of events (3.3%). Students occupied a position between the two groups (9.3%). Inflammatory rate was higher among wearers with increased microbial contamination of lenses (p = 0.002). Wearers with an inflammatory event had mean colony forming unit of 1.97 log compared with mean colony forming unit of 1.45 log in group with no inflammatory event. Corneal vascularization was associated with the development of inflammatory events (p = 0.001) with 50% of wearers with vascularization experiencing events compared with 7.6% of subjects with no vascularization. Reduced lens movement was associated with inflammatory events with subjects more likely to develop inflammatory events compared with those wearers with optimal lens movement (p = 0.027). A multitude of factors, including environmental influences, lens contamination, ocular characteristics, and lens fit, contributes to the development of inflammatory events, information that is of clinical relevance to practitioners worldwide. Occupational environment was also a contributory factor, confirming that a duty of clinicians is to ascertain the nature of the work environment of lens wearers (and potential wearers) and to balance the needs of the wearer with the potential risks.


Hereditary haemorrhagic teleangiectasia: diagnostic imaging of visceral involvement.
Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber disease, is an autosomal-dominant vascular disease characterised by mucocutaneous or visceral angiodysplastic lesions (telangiectases and arteriovenous malformations), which may be widely distributed throughout the cardiovascular system. Its diagnosis is based on clinical criteria. Liver, lungs and brain, in order of prevalence, are the most frequently involved visceral districts of the body other than skin and nasal mucosa. Liver involvement is frequent and characterised by the presence of intrahepatic shunts, disseminated intraparenchymal telangiectases and other vascular lesions. Although it is usually asymptomatic, congestive cardiac failure, portal hypertension, portosystemic encephalopathy, cholangitis or atypical cirrhosis are possible complications. Pulmonary arteriovenous malformations involve more than one third of HHT patients and can consist of diffuse telangiectases or high-flow low-pressure shunts between pulmonary arteries and veins. Pulmonary involvement can cause serious complications: hypoxaemia, pulmonary or pleural hemorrhage, paradoxical embolism into cerebral circulation. Various types of cerebrovascular malformations can affect HHT patients and the most common are arteriovenous malformations, consisting of one or more feeding arteries connected to one or more draining veins. Diagnostic imaging has a fundamental role in detecting the alterations involving these various districts in the body. The possibility to perform fast and complete studies and to provide high quality multiplanar and angiographic reconstructions, gives multi-detector row helical computed tomography and magnetic resonance the ability to detect and characterise the complex anatomo-pathological alterations typical of HHT. Ultrasonography seems to be the best screening modality for hepatic and pulmonary involvement.


Elasticity of MoS2 Sheets by Mechanical Deformation Observed by in Situ Electron Microscopy.
MoS2 has been the focus of extensive research due to its potential applications. More recently, the mechanical properties of MoS2 layers have raised interest due to applications in flexible electronics. In this article, we show in situ transmission electron microcsopy (TEM) observation of the mechanical response of a few layers of MoS2 to an external load. We used a scanning tunneling microscope (STM) tip mounted on a TEM stage to induce deformation on nanosheets of MoS2 containing few layers. The results confirm the outstanding mechanical properties on the MoS2. The layers can be bent close to 180°. However, when the tip is retrieved the initial structure is recovered. Evidence indicates that there is a significant bond reconstruction during the bending with an outstanding capability to recover the initial bond structure. The results show that flexibility of three layers of MoS2 remains the same as a single layer while increasing the bending modulus by 3 orders of magnitude. Our findings are consistent with theoretical calculations and confirm the great potential of MoS2 for applications.


[The application of artificial protein premixes for nutritive support of patients with chronic renal insufficiency, being treated by perinateal dialysis].
As a result of a survey of 56 patients with chronic renal insufficiency, who undergone hemodialysis, it was established, that clinical condition of patients, biochemical and hematological blood indices as well as results of anthropometric research improve upon application of artificial balanced high-protein premixes -"Nutrinil" and "Nutrien-Nefro". Irrespective of way of administration - introperitoneal ("Nutrinil" solution) or enteral ("Nutrien-Nefro" mixture) protein-energetic insufficiency diminishes or totally disappears, body weight, fat and muscle content of the body weight, as well as indices of whole protein, albumine, lymphocytes, haemoglobin, pH approache the norm. Intraperitoneal way of administration of artificial protein premixes increase patients adherence to this procedure, though enteral way of their administration is more preferable from economic point of view.


Hypolipidemic effect of garlic and thyroid function.
Male Sprague-Dawley rats were maintained on cholesterol and garlic oil for 12 weeks. Cholesterol induced hyperlipidemia was controlled by garlic feeding. Garlic treatment did not alter the concentrations of circulating thyroid hormones and thyroidal uptake of radioiodine. The results indicate that the hypolipidemic effect of garlic is probably not mediated through the thyroid.


Should Trazodone Be First-Line Therapy for Insomnia? A Clinical Suitability Appraisal.
Trazodone is one of the most commonly used prescription medications for insomnia; however, some recent clinical guidelines do not recommend its use for treating insomnia. This clinical appraisal critically reviews the scientific literature on trazodone as a first-line treatment for insomnia, with the focus statement "Trazodone should never be used as a first-line medication for insomnia." In addition, field surveys were sent to practicing physicians, psychiatrists, and sleep specialists to assess general support for this statement. Subsequently, a meeting with a seven-member panel of key opinion leaders was held to discuss published evidence in support and against the statement. This paper reports on the evidence review, the panel discussion, and the panel's and healthcare professionals' ratings of the statement's acceptability. While the majority of field survey responders disagreed with the statement, the majority of panel members agreed with the statement based on the limited published evidence supporting trazodone as a first-line agent as they understood the term "first-line agent".


Parameterization of aerosol and cirrus cloud effects on reflected sunlight spectra measured from space: application of the equivalence theorem.
An original methodology to account for aerosol and cirrus cloud contributions to reflected sunlight is described. This method can be applied to the problem of retrieving greenhouse gases from satellite-observed data and is based on the equivalence theorem with further parameterization of the photon path-length probability density function (PPDF). Monte Carlo simulation was used to validate this parameterization for a vertically nonhomogeneous atmosphere including an aerosol layer and cirrus clouds. Initial approximation suggests that the PPDF depends on four parameters that can be interpreted as the effective cloud height, cloud relative reflectance, and two additional factors to account for photon path-length distribution under the cloud. We demonstrate that these parameters can be efficiently retrieved from the nadir radiance measured in the oxygen A-band and from the H(2)O-saturated area of the CO(2) 2.0 microm spectral band.


Sex education and knowledge of pregnancy risk among U.S. teenage women.
Seven in 10 never-married U.S. women aged 15-19 have had a sex education course, almost all of them in school. Young black women are slightly more likely than whites to have had such a course. About half of all never-married teenagers have had courses which included some teaching about modern contraceptive methods; six in 10 have had some formal instruction about VD, and seven in 10 have had courses that included detailed instruction about the monthly menstrual cycle. Six in 10 of those who have had a course with information on the menstrual cycle claim to know the period of greatest pregnancy risk; but only one-third of those who have had such a course can in fact correctly identify the time when the risk of pregnancy is highest. Young white women are nearly two times more likely than blacks to identify the period of risk correctly. Knowledge of the period of risk is a particularly important issue in relation to teenage pregnancy, because many sexually active teenagers say that they do not use contraception because they believe they are protected from the risk of pregnancy by the time of month when they have intercourse. Among those who claim to know the period of greatest risk, a sex education course is the most common source of information for both blacks and whites, with home a distant second. Medical personnel and facilities convey information about pregnancy risk the most effectively, but they are the first source for only a tiny fraction of teenagers.(ABSTRACT TRUNCATED AT 250 WORDS)


[Characteristics of nucleolar organization and function under condition of complete spatial in situ disassembly of its main structural components].
It is well known that fibrillar centers (FC) constitute an essential structural component of the active nucleolus in mammalian cells, yet their role in regulation of ribosomal gene transcription still remains an open question. Here, we studied the activity of endogenous RNA polymerase I upon partial and complete unraveling of nucleoli and FCs. The pattern of BrUTP incorporation in nuclei of hypotonically-treated cells was shown to be essentially the same as in the control untreated cells. Moreover, the sites of BrUTP incorporation, which revealed the active PNA polymerase I, were completely coincident with UBF-binding sites. These observations allow to conclude that structural integrity of FCs is not a prerequisite for maintenance of the active RNA polymerase I transcriptional complex. When the action of hypotonic shock was ceased and the cells were transferred to a complete cultural medium, the swollen nucleoli recovered to the control state. Therefore it is possible to conclude that none of the main morphological nucleolar counterparts, such as FCs, dense fibrillar component or the pars granulosa, is responsible for the maintenance of the nucleolar structural and functional integrity. A suggestion is made that this role may be played by the nucleolar matrix associated with the RNA polymerase I transcriptional complex.


First Draft Genome Sequence of Balamuthia mandrillaris, the Causative Agent of Amoebic Encephalitis.
The free-living amoeba Balamuthia mandrillaris is a rare but highly lethal agent of amoebic encephalitis in humans and many other mammalian species. Here, we announce the first draft genome sequence of the original 1990 isolate cultured from the brain of a deceased mandrill baboon.


Subfoveal choroidal neovascular membranes in age-related macular degeneration. Visual prognosis in eyes with relatively good initial visual acuity.
We determined the visual prognosis of 94 eyes in 92 patients having age-related macular degeneration, a discrete choroidal neovascular membrane directly under the center of the foveal avascular zone (subfoveal), and an initial visual acuity of 20/100 or better. Of the patients who were reexamined 24 months following their initial presentation, 77% had lost at least four lines of vision and 64% had lost at least six lines. Estimation of visual loss using a conservative assessment procedure showed four-line visual loss in 65% of the patients and six-line loss in 50%. In general, the better the visual acuity at the initial examination, the more likely the patient was to have a smaller choroidal neovascular membrane. These results suggest that it may be reasonable to consider a randomized clinical trial of laser photocoagulation for this group of patients with a relatively poor visual prognosis.


Minimally invasive anterior, lateral, and oblique lumbar interbody fusion: a literature review.
Lumbar interbody fusion involves insertion of a structural graft into an intervertebral disc space to promote bony arthrodesis. It is a well-established surgical strategy for multiple spinal disorders ranging from degenerative conditions to trauma, neoplastic diseases, and deformities requiring correction. Since the inception of lumbar interbody fusion, the most established techniques have been two posterior approaches, the posterior lumbar interbody fusion (PLIF) and the transforaminal lumbar interbody fusion (TLIF). Within the past 15 years, multiple anterolateral approaches to the spine have become widely adopted. These approaches can be performed minimally invasively and spare disruption of the paraspinal muscles and posterior spinal column while enabling wide exposure of the disc space for insertion of interbody grafts much larger than PLIF and TLIF instrumentation. This review highlights three minimally invasive anterolateral approaches: the anterior lumbar interbody fusion (ALIF), the transpsoas lateral lumbar interbody fusion (LLIF), and prepsoas or anterior to the psoas oblique lumbar interbody fusion (OLIF). Relevant topics for discussion and comparison include patient selection, surgical techniques, outcomes, and complications for the three surgical approaches.


The fine structure and cell kinetics of mouse epidermis after wounding.
A variable amount of cornified tissue removed from mouse dorsal epidermis results in stimulation of the entire basal layer. Stimulation does not appear to be dependent on damage to an indiviaual epidermal proliferative unit (EPU). The immediate reaction to wounding is a rapid movement of cells from the basal layer to the differentiating compartment resulting in depopulation of the basal layer, which is followed by a burst in DNA-synthetic activity. The result of the increased transit of cells through the epidermis is that various aspects of keratinization can appear abnormal. The Langerhans cells show several changes, often appearing suprabasal and becoming smaller, rounded cells with a less-clear cytoplasm and fewer granules. The initial migratory reaction results in a largely normal epidermis on the third day. This reaction is followed by a transient hyperplasia which reaches its peak on the sixth to seventh day and gradually returns to normal by the fourteenth to fifteenth day. The hyperplasia is characterized by a loss of the ordered stacking of cornified cells which become shorter and thicker than normal. There is a return to the stacked state beginning on the tenth day. The Langerhans frequency is apparently at its lowest on days 6-7 when the proliferation levels are at their maximum. An inverse relationship appears to exist between relative Langerhans cell frequency and cell proliferation rate. The data suggest that the frequency of Langerhans granules also changes during the course of the hyperplasia, peak levels being observed just before the decline in proliferative activity.


Radiation therapy for pineal parenchymal tumor of intermediate differentiation: A case series and literature review.
Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare, primary tumor of the pineal gland. Due to its rarity, there is no consensus on optimal therapeutic strategies or standard characterization of the tumor's behavior. Here, we report 2 new cases of PPTID and an extensive review of the literature involving the use and extent of radiation therapy. Patient 1 is a 54-year-old male who presented with PPTID and drop metastases in the spinal cord, received cranial spinal irradiation (CSI), and experienced recurrence 3.5 years after treatment. Stereotactic body radiation therapy (SBRT) helped the patient into remission for 9 months. Patient 2 is a 32-year-old male with a local PPTID at presentation who went on to receive surgical resection followed by focused adjuvant radiation therapy to the pineal tumor bed. He then presented 6 years after treatment with extensive disseminated recurrence and died due to leptomeningeal disease (LMD) about 4 years after recurrence. The available literature on PPTID is limited and reported cases of LMD with ongoing follow-up in PPTID are scarce. Our report adds to the current known PPTID cases, contributing to the information available regarding prognosis and treatment response. Although an optimal therapeutic strategy for PPTID still cannot be determined, data from the literature suggest that utilizing radiation therapy in patients with low-risk disease and gross total resections as well as the use of upfront CSI have the potential to improve patient progression and survival outcomes.


Differences in Clinical Manifestations, Antimicrobial Susceptibility Patterns, and Mutations of Fluoroquinolone Target Genes between Chryseobacterium gleum and Chryseobacterium indologenes.
Chryseobacterium infections are uncommon, and previous studies have revealed that Chryseobacterium gleum is frequently misidentified as Chryseobacterium indologenes We aimed to explore the differences in clinical manifestations and antimicrobial susceptibility patterns between C. gleum and C. indologenes The database of a clinical microbiology laboratory was searched to identify patients with Chryseobacterium infections between 2005 and 2017. Species were reidentified using 16S rRNA gene sequencing, and patients with C. gleum and C. indologenes infections were included in the study. A total of 42 C. gleum and 84 C. indologenes isolates were collected from consecutive patients. A significant increase in C. indologenes incidence was observed. C. gleum was significantly more associated with bacteremia than C. indologenes Patients with C. gleum infections had more comorbidities of malignancy and liver cirrhosis than those with C. indologenes infections. The overall case fatality rate was 19.8%. Independent risk factors for mortality were female sex and C. indologenes infection. These isolates were most susceptible to minocycline (73%), followed by trimethoprim-sulfamethoxazole (47.6%), tigecycline (34.1%), and levofloxacin (32.5%). C. gleum exhibited a significantly higher rate of susceptibility than C. indologenes to piperacillin, piperacillin-tazobactam, ceftazidime, tigecycline, and levofloxacin. Alterations in DNA gyrase subunit A were identified to be associated with fluoroquinolone resistance in C. indologenes No nonsynonymous substitutions were observed in the quinolone resistance-determining regions (QRDRs) of C. gleum Differences in epidemiology, clinical manifestations, and antimicrobial susceptibility patterns exist between C. gleum and C. indologenes Additional investigations are needed to explore the significance of these differences.


Quality of life in male hemodialysis patients. Role of erectile dysfunction.
Health-related quality of life (QOL) is affected in hemodialysis patients (HD). A number of factors such as age, anemia, and comorbidity had been implicated in decreased QOL. Erectile dysfunction (ED) is a frequent and potentially treatable complication in HD patients. In this cross-sectional study, we aimed to evaluate the possible relation between the QOL and ED in HD patients. Among the 511 chronic HD patients dialyzed in 11 outpatient HD centers, 148 male patients (mean age: 46 +/- 9 years) were included. The mean time on dialysis was 41 +/- 35 months (range: 3-203 months). Biochemical parameters such as BUN, creatinine, hemoglobin, serum albumin and Kt/V were measured. The QOL of the patients were measured with the short form of Medical Outcomes Study (SF-36), physical component scores (PCS) and mental component scores (MCS) were calculated. The ED was evaluated by the International Index of Erectile Function (IIEF). One hundred and four of the 148 patients (70%) had ED. Hemoglobin levels were correlated with PCS (r = 0.197, p = 0.02) and MCS (r = 0.20, p = 0.019). Patients with ED had lower scores in nearly all the components related to PCS and MCS as compared to patients without ED. IIEF score was correlated with PCS (r = 0.369, p < 0.001) and MCS (r = 0.308, p < 0.001). In linear regression analysis, IIEF score and hemoglobin levels were the independent variables that predicted both PCM and MCS. ED, a frequent complication in HD patients, was related to QOL together with anemia. Successful treatment of ED and anemia may lead to improvement in QOL in HD patients.


Tourette's disorder with and without obsessive-compulsive disorder in adults: are they different?
Clinical research has documented a bidirectional overlap between Tourette's disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic, phenomenological, comorbidity, and natural history perspectives. Patients with Tourette's disorder plus obsessive-compulsive disorder (TD + OCD), a putative subtype, share features of both. The purpose of this exploratory study was to evaluate correlates of patients with TD, OCD, and TD + OCD to determine whether TD + OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects with TD, OCD, or TD + OCD were evaluated with the Structured Clinical Interview for DSM-III-R supplemented with additional modules. The three groups differed in the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and substance use disorders (p < .04). These findings were accounted for by the elevated rates of the disorders in the TD + OCD group compared with the TD and OCD groups. These finding are most consistent with the hypothesis that TD + OCD is a more severe disorder than TD and OCD and may be more etiologically linked to TD than to OCD. These findings highlight the importance of assessment of the full spectrum of psychiatric comorbidity in patients with TD and OCD.


Permethylation and Microfractionation of Sulfated Glycans for MS Analysis.
Sulfated glycans are barely detectable in routine mass spectrometry (MS)-based glycomic analysis due to ion suppression by the significantly more abundant neutral glycans in the positive ion mode, and sialylated non-sulfated glycans in the negative ion mode, respectively. Nevertheless, the negative charge imparted by sulfate can be advantageous for selective detection in the negative ion mode if the sialic acids can first be neutralized. This is most conveniently achieved by a concerted sample preparation workflow in which permethylation is followed by solid phase fractionation to isolate the sulfated glycans prior to MS analysis. Importantly, we demonstrated that conventional NaOH/DMSO slurry permethylation method can retain the sulfates. Instead of extracting permethylated glycans into chloroform for sample clean-up, reverse phase C18 cartridge coupled with self-packed amine-tip or mixed mode weak anion exchange cartridge can be utilized to obtain in good yield the non-sulfated, mono-sulfated, and multiply sulfated permethylated glycans in separate fractions for sulfoglycomic analysis.


Incidence of cancer in children in the United States. Sex-, race-, and 1-year age-specific rates by histologic type.
Rates of cancer in children usually are presented in 5-year age groups, despite large variations of incidence within these groups. The purpose of this report is to provide histology-specific incidence rates within single-year age groups, stratified by sex and race, among children. Data from the National Cancer Institute's SEER Program were used to calculate incidence rates among children younger than 15 years of age at diagnosis. The SEER population denominator file was modified to allow calculation of rates within single years of age. Large differences in rates within 5-year age groups were found for many histologic types. Retinoblastoma and Wilms' tumor, for instance, had up to eight-fold differences. Substantial differences also were observed for non-Hodgkin's lymphoma, neuroblastoma, Hodgkin's disease, acute lymphoid leukemia, acute myeloid leukemia, and osteosarcoma. In general, rates were higher among males than females, although female rates were often higher among young children. Rates of white children were generally higher than those of black children, especially during the first 5 years of life. Embryonal tumors comprised the majority of neoplasms during the first 2 years of life.


Temporal trend of Food and Nutrition Surveillance System coverage among children under 5 in the Northern Region of Brazil, 2008-2017.
Objective to analyze the temporal trend of Web Food and Nutrition Surveillance System (SISVAN Web) coverage of children under 5 years old in the Northern Region of Brazil between 2008-2017. Methods this was an ecological time series study with data from SISVAN Web; coverage annual percentage change (APC) was estimated using the Prais-Winsten regression model. Results SISVAN Web coverage in the Northern Region in 2008 and 2017 was 12.2% and 37.9%, respectively, with a rising trend (APC=14.2% - 95%CI 10.9;17.6); the states and health regions showed similar trends; Acre was the state with the highest APC (17.3% - 95%CI 13.6;21.1). Conclusion there was a rising trend in SISVAN Web coverage in the Northern Region as a whole, in all its states and in all its health regions.


Health care reform: through the lens of change.
Change theory concepts--drivers, vision, current and future states, and social buy-in--provide some analytical leverage in understanding current reform challenges. Various contentious issues in the health care reform battle have long served to polarize stakeholders and differentiate conservative and liberal positions. Successful change efforts are led by the development of a compelling vision, which has certain attributes. Change theory postulates that if there is not strong dissatisfaction with the current state, the future state is less feasible. Social systems change theory is another way to conceptualize and broaden our understanding of health policy as a form of social change, how environmental or external forces influence policy design, and how the ongoing media presentation of a policy influences direction of the outcome.


Sudden death due to rupture of an omental metastatic tumor arising from cardiac angiosarcoma. A case report.
A 32-year-old man underwent surgical excision of a malignant hemangioendothelioma of the heart and received multidisciplinary treatment. Thirty-three months later, he underwent a second surgical treatment for a recurrent tumor of the posterior chest wall of the right thorax. Five months after this surgery (thirty-eight months after the initial surgery), a second recurrent tumor in the right thorax developed. Although radiotherapy and recombinant interleukin-2 were administered, anemia of unknown origin (hemoglobin 6.7 g/dl) developed. The patient died of sudden shock due to a rupture of an omental metastatic tumor. The patient survived for 41 months after the first surgical resection. We present this case because it is the first reported case of sudden death due to bleeding from an omental metastatic tumor, and because our patient was the second-longest survivor after surgical treatment for cardiac angiosarcoma.


Ras-sensitive IMP modulation of the Raf/MEK/ERK cascade through KSR1.
The E3 ubiquitin ligase IMP (impedes mitogenic signal propagation) was isolated as a novel Ras effector that negatively regulates ERK1/2 activation. Current evidence suggests that IMP limits the functional assembly of Raf/MEK complexes by inactivation of the KSR1 adaptor/scaffold protein. Interaction with Ras-GTP stimulates IMP autoubiquitination to relieve limitations on KSR function. The elevated sensitivity of IMP-depleted cells to ERK1/2 pathway activation suggests IMP acts as a signal threshold regulator by imposing reversible restrictions on the assembly of functional Raf/MEK/ERK kinase modules. These observations challenge commonly held concepts of signal transmission by Ras to the MAPK pathway and provide evidence for the role of amplitude modulation in tuning cellular responses to ERK1/2 pathway engagement. Here we describe details of the methods, including RNA interference, ubiquitin ligase assays, and protein complex analysis, that can be used to display the Ras-sensitive contribution of IMP to KSR-dependent modulation of the Raf/MEK/ERK pathway.


Cytokines and mucosal immunity.
Cytokines are integral mediators for maintaining intestinal mucosal homeostasis, as well as prominent effector molecules during chronic gut inflammatory diseases. This review focuses on recent studies of the role of specific cytokines in mucosal immunity. Dichotomous, or even opposing, functions have been described for several cytokines involved in intestinal innate immunity (most notably for members of the interleukin-1 family), which depend on the specific inflammatory conditions within the intestinal mucosa. For example, both interleukin-1α and interleukin-33 exhibit 'alarmin'-type properties that can signal tissue or cell damage, which further add to their well described proinflammatory roles. Costimulatory molecules of the tumor necrosis factor/tumor necrosis factor receptor superfamily, such as TNF-like cytokine 1A and LIGHT, are actively involved in mucosal proinflammatory pathways, but also may exert protection against infectious agents to facilitate recovery from acute inflammation. Finally, innate lymphoid cells are increasingly recognized as important cellular sources of pivotal mucosal cytokines, including the interleukin-23/T helper 17 cytokine, interleukin-22. Elucidating the complexity of cytokine signaling within the normal mucosa and during acute and chronic inflammation will be a pivotal step toward understanding the pathogenesis of immune-mediated gut diseases and developing effective therapies to treat them.