Confirming and denying in co-construction processes: a case study of an adult with cerebral palsy and two familiar partners.
For individuals with complex communication needs, one of the most frequent communicative strategies is the co-construction of meaning with familiar partners. This preliminary single-case study gives insight into a special sequential pattern of co-construction processes - the search sequence - particularly in relation to the processes of confirming and denying meanings proposed by familiar interaction partners. Five different conversations between an adult with cerebral palsy and complex communication needs and two familiar co-participants were videotaped and analyzed using the methodology of conversation analysis (CA). The study revealed that confirmations and denials are not simply two alternative actions, but that several possibilities to realize confirmations and denials exist that differ in their frequency and that have different consequences for the sequential context. This study of confirmations and denials demonstrates that co-construction processes are more complex than have previously been documented.


Oxygen saturation as a marker for admission or relapse with acute bronchospasm.
Oxygen saturation (SaO2) as measured by pulse oximetry was evaluated as a means of complementing or supplementing peak expiratory flow rate (PEFR) for early identification of the adult patient needing prolonged therapy for acute bronchospasm. SaO2 was recorded at baseline and at the time of peak drop after initial bronchodilator therapy for 28 patient visits. PEFR was recorded at baseline and at 15 minutes after initial bronchodilator therapy. Potential admission criteria based on these parameters were compared to patients actually admitted or returned within 72 hours (prematurely discharged). Mean patient age was 36 +/- 16.8 years. Mean baseline SaO2 was 95.4 +/- 2.3% (92 to 100%) and SaO2 at the peak drop after the first bronchodilator therapy was 91.9 +/- 3.0% (86 to 97%). Of the criteria evaluated, the following had a significant correlation with admission or premature discharge: baseline PEFR less than or equal to 100 L/min (P = .017); PEFR after first bronchodilator therapy less than or equal to 160 L/min (P less than .0004); the combination of a baseline PEFR less than or equal to 100 L/min with an improvement in PEFR less than or equal to 100 L/min (P less than .0003); and the combination of baseline SaO2 less than or equal to 95% with an improvement in PEFR less than or equal to 100 L/min (P = .0017). As isolated variables, SaO2 at baseline and SaO2 at peak drop following bronchodilator therapy were not useful predictors of outcome, although patients severely hypoxemic at presentation were not evaluated.


A new variant position of head-up CPR may be associated with improvement in the measurements of cranial near-infrared spectroscopy suggestive of an increase in cerebral blood flow in non-traumatic out-of-hospital cardiac arrest patients: A prospective interventional pilot study.
This study aimed to investigate the effect of the head-up position implemented during cardiopulmonary resuscitation (CPR) on cerebral blood flow (CBF) using near-infrared spectroscopy in out-of-hospital cardiac arrest patients. Baseline characteristics (age, sex, cerebral performance category before cardiac arrest, witnessed cardiac arrest, bystander CPR, first monitored rhythm, no-flow time, prehospital low-flow time, CPR duration in the emergency department (ED), and reason for stopping CPR in the ED) were recorded. The changes of CBF were derived from the optical oscillation waveform measured by near-infrared spectroscopy in adult patients with out-of-hospital cardiac arrest by alternating head-up and supine positions at 4-minute intervals while performing CPR. The CBF velocity according to the head position was also evaluated using the time derivative of the oscillation waveform. During the study period, 28 patients were enrolled. The median increase in CBF in the prefrontal area in the head-up position was 14.6% (Interquartile range, 8.8-65.0), more than that in the supine position. An increase in CBF was observed in the head-up position compared with the supine position in 83.3% of the patients included in the analysis. CBF increased when the head-up position was used during CPR in non-traumatic out-of-hospital cardiac arrest patients.


Colour patterns: channelling Turing.
Very little is known about how animal colour patterns develop. The stripes of the zebrafish provide a tractable a model for colour pattern formation, which now suggests an unconventional patterning mechanism.


Romosozumab: First Global Approval.
Romosozumab (EVENITY™) is a humanised monoclonal antibody against sclerostin being developed by Amgen and UCB for the treatment of osteoporosis. On the basis of favourable results from several phase III trials in postmenopausal women with osteoporosis, and a single trial in men with osteoporosis, romosozumab is being considered for marketing approval in the US, EU and Canada, and was recently approved for marketing in Japan. This article summarizes the milestones in the development of romosozumab leading to this first approval for the treatment of osteoporosis in patients at high risk of fracture.


Coronary artery bypass in patients with total laryngectomy.
Patients who have undergone laryngectomy pose a challenge when they require coronary artery bypass grafting. The location of the tracheal stoma just above the jugular notch may interfere with the sternotomy, increase the risk of infection, and add some difficulty to the operative procedure. We describe the surgical technique used in 2 such patients.


Ecotoxicogenomics: Microarray interlaboratory comparability.
Transcriptomic analysis can complement traditional ecotoxicology data by providing mechanistic insight, and by identifying sub-lethal organismal responses and contaminant classes underlying observed toxicity. Before transcriptomic information can be used in monitoring and risk assessment, it is necessary to determine its reproducibility and detect key steps impacting the reliable identification of differentially expressed genes. A custom 15K-probe microarray was used to conduct transcriptomics analyses across six laboratories with estuarine amphipods exposed to cyfluthrin-spiked or control sediments (10 days). Two sample types were generated, one consisted of total RNA extracts (Ex) from exposed and control samples (extracted by one laboratory) and the other consisted of exposed and control whole body amphipods (WB) from which each laboratory extracted RNA. Our findings indicate that gene expression microarray results are repeatable. Differentially expressed data had a higher degree of repeatability across all laboratories in samples with similar RNA quality (Ex) when compared to WB samples with more variable RNA quality. Despite such variability a subset of genes were consistently identified as differentially expressed across all laboratories and sample types. We found that the differences among the individual laboratory results can be attributed to several factors including RNA quality and technical expertise, but the overall results can be improved by following consistent protocols and with appropriate training.


The usage of multidisciplinary physical therapies at the Rio de Janeiro 2016 Olympic Summer Games: an observational study.
This observational research study analyses the uptake of physical therapies treatments in the Polyclinic during the Rio 2016 Olympic Games. To describe the usage of physical therapies services - physical therapy, osteopath, chiropractic, and sports massage - by athletes and non-athletes and across different sports. The multidisciplinary team of physical therapies recorded treatment modalities, information on provider discipline and reason for attendance, in an Electronic Medical Record system throughout the 32 days of operation of the Olympic Polyclinic. Cold-therapy total immersion ice baths (TIIB) were provided as part of the services, but were reported and analysed separately. There were 4993 encounters (4038 athletes, 955 non-athlete encounters). 1395 athletes (12.4% of all athletes) and 393 non-athletes sought treatment. For all four provider disciplines, in addition to TIIB, the primary reason for athlete attendance was for recovery (52% of all encounters), followed by injury treatment (30%), and maintenance (16%). Athletes reported "injury" as the main reason for physical therapy (92% of all encounters, 2.8 encounters per athlete), chiropractic (94%, 1.9) and osteopathy (91%, 1.8) visits. Almost all TIIB visits were used for recovery (98% of all TIIB encounters; 2.1 encounters per athlete). Athletes from handball (37% of all handball athletes), followed by judo (22%), and athletics (21%), presented the largest user groups. This Olympic Polyclinic study evaluates the physical therapies' activity, and athlete's reason for use of the multidisciplinary physical therapies team, including total immersion ice bath provision. These results emphasise the importance of a multidisciplinary approach.


Association between Polymorphism eNOS4, tPA, Factor V Leiden, Prothrombin, and Methylenetetrahydrofolate Reductase and the Occurrence of Legg-Calvé-Perthes Disease.
Legg-Calvé-Perthes (LCPD) disease is a complex condition affecting the femoral head's epiphysis in children. It occurs with a prevalence ranging from 0.4 to 29.0 cases per 100,000 children under the age of 15. It involves various factors, including genes associated with coagulation and fibrinolysis, pro-inflammatory factors, and vasoactive substances. We investigated the relationship between genetic mutations associated with coagulation and vascular disorders and the occurrence of LCPD in Polish patients. We performed a study involving 25 patients with LCPD and 100 healthy controls. All subjects were genotyped for eNOS4, Factor V Leiden, prothrombin, tPA25, and MTHFR polymorphism. The analysis revealed that the frequencies of eNOS4 genotypes were significantly different in LCPD patients than in the control group (p = 0.018). The frequencies of 4a allele were significantly higher in patients with LCPD than in the healthy population (26% vs. 9%, p = 0.0012). There were no significant differences in genotype and allele frequencies for Factor V Leiden, prothrombin tPA 25, and MTHFR gene polymorphisms between patients with LCPD and the controls. Genotype and allele frequencies of eNOS4 were significantly higher in patients with LCPD. These findings suggest a potential association between the eNOS gene polymorphism and an increased risk of developing LCPD.


Increased temperature and protein oxidation lead to HSP72 mRNA and protein accumulation in the in vivo exercised rat heart.
Expression of myocardial heat shock protein 72 (HSP72), mediated by its transcription factor, heat shock factor 1 (HSF1), increases following exercise. However, the upstream stimuli governing exercise-induced HSF1 activation and subsequent Hsp72 gene expression in the whole animal remain unclear. Exercise-induced increases in body temperature may promote myocardial radical production, leading to protein oxidation. Conceivably, myocardial protein oxidation during exercise may serve as an important signal to promote nuclear HSF1 migration and activation of Hsp72 expression. Therefore, these experiments tested the hypothesis that prevention of exercise-induced increases in body temperature attenuates cardiac protein oxidation, diminishes HSF1 activation and decreases HSP72 expression in vivo. To test this hypothesis, in vivo exercise-induced changes in body temperature were manipulated by exercising male rats in either cold (4 degrees C) or warm ambient conditions (22 degrees C). Warm exercise increased both body temperature (+3 degrees C) and myocardial protein oxidation, whereas these changes were attenuated by cold exercise. Interestingly, exercise in both conditions did not significantly increase myocardial nuclear localized phosphorylated HSF1. Nonetheless, warm exercise elevated left-ventricular HSP72 mRNA by ninefold and increased myocardial HSP72 protein levels by threefold compared with cold-exercised animals. Collectively, these data indicate that elevated body temperature and myocardial protein oxidation promoted exercise-induced cardiac HSP72 mRNA expression and protein accumulation following in vivo exercise. However, these results suggest that exercise-induced myocardial HSP72 protein accumulation is not a result of nuclear-localized, phosphorylated HSF1, indicating that other transcriptional or post-transcriptional regulatory mechanisms are involved in exercise-induced HSP72 expression.


Human oviductal fluid proteins. V. Identification of human oviductin-I as alpha-fetoprotein.
To investigate whether human oviductin-I (hOV-I) from human oviductal fluid (hOF) and human alpha-fetoprotein (hAFP) are identical molecules. Comparison of amino acid and carbohydrate composition of hOV-I with that of hAFP. Isolation of hAFP from oviductal fluid of a patient and evaluation of its immunochemical properties in relation to hOV-I and authentic hAFP standard. Procedures were performed in an academic research environment. Human oviductin-I was isolated from a pooled sample of hOF obtained from four patients in a third world country. AFP was purified from a sample of oviductal fluid obtained from a single patient during her periovulatory period. Human oviductal fluid was collected coincident to elective tubal ligations. The amino acid and carbohydrate composition of hOV-I was determined. AFP was purified from hOF using ion-exchange chromatography and gel filtration. The identity between hOV-I and hAFP from hOF was assessed using enzyme-linked immunosorbent assay (ELISA) and Western immunoblot analysis. The amino acid and carbohydrate composition of hOV-I indicated similarities between hOV-I and hAFP. Both hOV-I and hAFP reacted with mouse anti-hAFP monoclonal antibody and purified polyclonal rabbit anti-hOV-I immunoglobulin G in an identical manner as observed by noncompetitive ELISA. Purified AFP from hOF of a single patient had a molecular mass of 66 kd and was found to be identical with hOV-I by Western immunoblot analysis. Human oviductin-I and hAFP are chemically similar and immunologically identical molecules. We believe that this finding is the first documentation for the existence of AFP in hOF.


Effect of polymyxin B sulfate on endotoxin activity in a gram-negative septicemia model.
The antiendotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin but not to polymyxin B. Animals pre-treated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed 6 hr after the injection of live organisms. Polymyxin therapy given after the animals had established septicemia-endotoxemia reduced the plasma endotoxin levels and improved the survival, but had no effect on the leukopenia and thrombocytopenia. The best survival data were obtained in rabbits who were treated with both penicillin and polymyxin. The data suggest that polymyxin is effective in neutralizing the endotoxic effects from live organisms and that the timing and perhaps duration of the polymyxin treatment is of critical importance. In addition, a modified Limulus lysate method was developed which showed that quantitative plasma endotoxin determination could be made more sensitive by prior heating of the plasma to remove the natural inhibitors.


Atrioventricular nodal reentrant tachycardia with atrioventricular block.
Atrioventricular block (AVB) during atrioventricular nodal reentrant tachycardia (AVNRT) has been well documented, although it is not a common phenomenon. The mechanism for the initiation and resolution of AVB during AVNRT have been postulated. However, the site of AVB and its implication on the reentrant circuit in AVNRT is not clear. We illustrate two examples of AVNRT with AVB and offer further clarification on the site and mechanism of AVB.


Temperature-dependence of riboflavin phosphorescence in cryosolvents.
The molecular mobility of amorphous excipients is important for the stability of biomaterials during preservation, facilitating matrix formulation and product design. Phosphorescence spectroscopy is a sensitive optical method to study molecular mobility. However, there is a need to expand the pool of probes available for analysis since molecules differ in sensitivity. This research explored the feasibility and limitations of using riboflavin as a phosphorescent probe for monitoring matrix molecular mobility. Phosphorescence decays of riboflavin in four amorphous cryosolvents (aqueous solutions of glycerol, ethanol, sucrose, and dextran) were collected at 77 K to capture its natural phosphorescence lifetime (estimated at 170 ms). Decays were also collected during ballistic heating to assess the sensitivity of riboflavin towards changes in matrix molecular mobility. Riboflavin exhibited good sensitivity towards matrix secondary relaxations in the glass, indicating that riboflavin has excellent potential as an edible phosphorescent probe for molecular mobility in food and pharmaceutical products.


The grading of stomach position for postnatal outcomes in isolated left-sided congenital diaphragmatic hernia: A systematic review and meta-analysis.
To evaluate the correlation between stomach position (SP) grading and postnatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernias (CDHs). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. The corresponding 95% confidence intervals (CIs) were used to assess the differences in the odds of mortality according to the SP graded as level 0 to level 3. To evaluate the reliability of our results, a sensitivity analysis was also conducted. Nine papers with a total of 542 fetuses with isolated left-sided CDH were included. Congenital diaphragmatic hernia pregnancies complicated by an intrathoracic stomach had higher odds of neonatal mortality when compared with intraabdominal stomach (odds ratio [OR] 2.86; 95% CI 1.38-5.94). Four papers with SP grading from level 0 to level 3 were included in a subgroup analysis. Stomach position at level 1 and level 2 had lower odds of neonatal mortality when separately compared to level 3 (OR 0.12; 95% CI 0.04-0.33) and (OR 0.30; 95% CI 0.16-0.54). Stomach position at level 1 had lower odds of neonatal mortality when compared with level 2 + 3 (OR 0.25; 95% CI 0.09-0.66). Survival of fetuses with isolated left-sided CDH is correlated with the SP.


HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency.
Enforced expression of the HOXB4 transcription factor and downregulation of p21(Cip1/Waf) (p21) can each independently increase proliferation of murine hematopoietic stem cells (HSCs). We asked whether the increase in HSC self-renewal generated by overexpression of HOXB4 is enhanced in p21-deficient HSCs. HOXB4 was overexpressed in hematopoietic cells from wild-type (wt) and p21-/- mice. Bone marrow (BM) cells were transduced with a retroviral vector expressing HOXB4 together with GFP (MIGB4), or a control vector containing GFP alone (MIG) and maintained in liquid culture for up to 11 days. At day 11 of the expansion culture, the number of primary CFU-GM (colony-forming unit granulocyte-macrophage) colonies and the repopulating ability were significantly increased in MIGB4 p21-/- BM (p21B4) cells compared with MIGB4-transduced wt BM (wtB4) cells. To test proliferation of HSCs in vivo, we performed competitive repopulation experiments and obtained significantly higher long-term engraftment of expanded p21B4 cells compared with wtB4 cells. The 5-day expansion of p21B4 HSCs generated 100-fold higher numbers of competitive repopulating units compared with wtMIG and threefold higher numbers compared with wtB4. The findings demonstrate that increased expression of HOXB4, in combination with suppression of p21 expression, could be a useful strategy for effective and robust expansion of HSCs.


Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16.
The gene encoding the beta-subunit of rod photoreceptor cGMP phosphodiesterase (gene symbol PDEB, homolog of the mouse rd gene) is mapped to human chromosome 4 using somatic cell hybrids and further localized to the chromosome band 4p16 using in situ hybridization. A mutation in the mouse gene underlies the recessive trait of retinal degeneration in the rd mouse. Thus, the human homolog is a candidate for lesions causing retinal degeneration.


Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells.
Epiregulin belongs to the epidermal growth factor family, binds to the epidermal growth factor receptor, and its expression is upregulated in various cancer cells, but the regulatory mechanism is unclear. We investigated the regulatory mechanism of epiregulin expression in Ki-ras-transformed cancer cells. In 267B1/Ki-ras cells, the RAF/MEK/ERK pathway was constitutively activated, epiregulin was up-regulated, and the expression and phosphorylation of Ets-1 were augmented. The inhibition of ERK by PD98059 decreased epiregulin and Ets-1 expression and suppressed the growth of 267B1/Ki-ras cells. A chromatin immunoprecipitation assay demonstrated that Ets-1 was bound to human epiregulin promoter, and this binding was abolished by PD98059. Silencing of Ets-1 by RNA interference decreased cellular epiregulin transcript expression. We suggest that the Ki-ras mutation in 267B1 prostate cells constitutively activates the RAF/MEK/ERK pathway and induces the activation of the Ets-1 transcription factor, ultimately leading to the increased expression of epiregulin.


The Age-ility Project (Phase 1): Structural and functional imaging and electrophysiological data repository.
Our understanding of the complex interplay between structural and functional organisation of brain networks is being advanced by the development of novel multi-modal analyses approaches. The Age-ility Project (Phase 1) data repository offers open access to structural MRI, diffusion MRI, and resting-state fMRI scans, as well as resting-state EEG recorded from the same community participants (n=131, 15-35 y, 66 male). Raw imaging and electrophysiological data as well as essential demographics are made available via the NITRC website. All data have been reviewed for artifacts using a rigorous quality control protocol and detailed case notes are provided.


Transplantation of fragments from different planaria: A bioelectrical model for head regeneration.
Head-tail planaria morphologies are influenced by the electric potential differences across the animal's primary axis, as evidenced e.g. by voltage-sensitive dyes and functional experiments that create permanent lines of 2-headed but genetically wild-type animals. However, bioelectrical and biochemical models that make predictions on what would happen in the case of spatial chimeras made by tissue transplantation from different planaria (different species and head shapes) are lacking. Here, we use a bioelectrical model to qualitatively describe the effects of tissue transplantation on the shape of the regenerated head. To this end, we assume that the cells may have distinct sets of ion channels and ascribe the system outcome to the axial distributions of average cell potentials over morphologically relevant regions. Our rationale is that the distributions of signaling ions and molecules are spatially coupled with multicellular electric potentials. Thus, long-time downstream transcriptional events should be triggered by short-time bioelectrical processes. We show that relatively small differences between the ion channel characteristics of the cells could eventually give noticeable changes in the electric potential profiles and the expected morphological deviations, which suggests that small but timely bioelectrical actions may have significant morphological effects. Our approach is based on the observed relationships between bioelectrical regionalization and biochemical gradients in body-plan studies. Such models are relevant to regenerative, developmental, and cancer biology in which cells with distinct properties and morphogenetic target states confront each other in the same tissue.


The role of individual variation in flowering and pollination in the reproductive success of a crepuscular buzz-pollinated plant.
Plant individuals within a population differ in their phenology and interactions with pollinators. However, it is still unknown how individual differences affect the reproductive success of plants that have functionally specialized pollination systems. Here, we evaluated whether plant individual specialization in phenology (temporal specialization) and in pollination (pollinator specialization) affect the reproductive success of the crepuscular-bee-pollinated plant Trembleya laniflora (Melastomataceae). We quantified flowering activity (amplitude, duration and overlap), plant-pollinator interactions (number of flowers visited by pollinators) and reproductive success (fruit set) of T. laniflora individuals from three distinct locations in rupestrian grasslands of southeastern Brazil. We estimated the degree of individual temporal specialization in flowering phenology and of individual specialization in plant-pollinator interactions, and tested their relationship with plant reproductive success. Trembleya laniflora presented overlapping flowering, a temporal generalization and specialized pollinator interactions. Flowering overlap among individuals and populations was higher than expected by chance but did not affect the individual interactions with pollinators and nor their reproductive success. In contrast, higher individual generalization in the interactions with pollinators was related to higher individual reproductive success. Our findings suggest that individual generalization in plant-pollinator interaction reduces the potential costs of specialization at the species level, ensuring reproductive success. Altogether, our results highlight the complexity of specialization/generalization of plant-pollinator interactions at distinct levels of organization, from individuals to populations, to species.


The use of back-up units to enhance the safety of unrelated donor cord blood transplantation.
The inability to obtain additional stem cells is a disadvantage of unrelated donor cord blood transplantation (CBT). Moreover, in the event of problems with unit shipment, compromised unit quality, thaw mishaps, or graft failure, the time to secure a back-up graft could be unacceptable. Emergent shipment of 1 to 2 back-up units that have been previously typed and reserved could overcome this limitation. However, the advantages of this approach are not established. Therefore, we present our use of back-up units over a 5.5-year period. Six of 121 CBT recipients (5%) required back-up unit infusion. Indications included shipment mishaps (n = 2), poor unit viability (n = 2), significant infusion reaction (n = 1), and graft failure (n = 1). Lack of back-up units would have caused transplantation delay or infusion of inferior-quality units. Five of the 6 patients achieved sustained donor engraftment. We demonstrate that back-up units are emergently required in a significant minority of patients, supporting the incorporation of at least 1 back-up unit in cord blood (CB) selection algorithms to enhance CBT safety.


Combined effects of exercise capacity and coronary atherosclerotic burden on all-cause mortality in asymptomatic Koreans.
Both exercise capacity and coronary artery calcium score (CACS) are important prognostic factors in cardiovascular outcome. Yet, whether there is a significant interaction between these two factors in influencing clinical outcome is still uncertain. This study investigated the combined effects of exercise capacity and CACS on all-cause mortality in an asymptomatic population. From multicenter registry of health screening, a retrospective cohort of 25,972 asymptomatic subjects, who underwent both CACS and treadmill exercise test, was included in the final dataset for analysis. Outcome was defined as all-cause mortality, which was obtained from national mortality registry. The mean age of study subjects was 53.7 ± 7.7 years and 81.5% of them were males. Median follow-up duration was 5.5 (IQR 3.6-7.5) years and 226 (0.9%) cases of all-cause mortality occurred. In multivariate Cox's proportional hazard model with interaction term, exercise capacity ≥10 METs (HR 0.684, 95% CI 0.483-0.971) and CACS ≥400 (HR 3.328, 95% CI 1.850-5.988) were significant predictors of all-cause mortality. In patients with higher exercise capacity, the effect of high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. The HR for all-cause mortality of CACS ≥400, in those with lower exercise capacity, is estimated to be about three times of that in those with higher exercise capacity (HR 3.328 in <10 METs vs. 1.108 in ≥10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, creatinine, alanine transaminase and albumin. The effect of high CACS on all-cause mortality is lessened by good exercise capacity in the asymptomatic population. Good physical fitness may reduce the adverse effect of high coronary atherosclerotic burden.


Chalcones from Chinese liquorice inhibit proliferation of T cells and production of cytokines.
Licochalcone A (LicA), an oxygenated chalcone, has been shown to inhibit the growth of both parasites and bacteria. In this study, we investigated the effect of LicA and four synthetic analogues on the activity of human peripheral blood mononuclear cell proliferation and cytokine production. Four out of five chalcones tested inhibited the proliferation of lymphocytes measured by thymidine incorporation and by flow cytometry. The production of pro- and anti-inflammatory cytokines from monocytes and T cells was also inhibited by four of five chalcones. Furthermore, intracellular detection of cytokines revealed that the chalcones inhibited the production rather than the release of the cytokines. Taken together, these results indicate that LicA and some analogues may have immunomodulatory effects, and may thus be candidates not only as anti-microbial agents, but also for the treatment of other types of diseases.


The correlation of the visual field with scanning laser ophthalmoscope measurements in glaucoma.
To assess the relationship between Humphrey visual field data and optic disc topographical data collected by the Heidelberg Retina Tomograph (HRT) scanning laser ophthalmoscope in chronic glaucoma patients. The mean deviation (MD) and corrected pattern standard deviation (CPSD) from Humphrey visual fields of 106 eyes of 106 patients with glaucoma were analysed for correlation with the multiple topographical measures calculated by the HRT. Significant correlations were found between MD of the visual field and several optic disc measurements. These included neuroretinal rim volume, mean nerve fibre layer thickness and cross-sectional area, and the cup shape measure. CPSD correlated significantly only with mean nerve fibre layer cross-sectional area. This pattern was common to the whole circumference of the disc with the exception of the directly temporal segment. Optic disc topography performed by HRT reflects the optic disc pathology in correlation with perimetry.


The laparoscopic option in the management of peritoneal dialysis catheter revision.
Long-term functioning of peritoneal dialysis catheters (PDCs) depends on maintenance of pelvic positioning and prevention of the formation of adhesions. The purpose of this study was to evaluate the validity of laparoscopy as a tool for the correction of malfunctioning PDCs and to introduce our specially designed technique. The charts of 12 patients who underwent laparoscopic revisions of malfunctioning PDCs between May 1997 and June 2000 were reviewed for perioperative complications and long-term outcomes. We describe the causes of malfunction of PDCs and the laparoscopic technique for their revision. Of the 12 patients studied, the malfunction of eight catheters resulted from migration of the catheter into the upper abdomen. In 4 patients, formation of adhesion of either small bowel or omentum resulted in the malfunction of the PDC. The only complication we encountered was bleeding. It occurred in 3 patients, 1 of whom needed reoperation in order to achieve hemostasis. Over a median follow-up of 21 months all PDCs treated this way are functioning. The laparoscopic management of malfunctioning PDCs is a valid option for the treatment of such a complication.


Analysis of coordination between urban compactness and green total factor energy efficiency: a case study of 35 cities in China.
Rapid urban expansion and energy transformation are two major challenges facing China. Many researchers have explored urban compactness and energy efficiency, but there is little literature on the coordinated development of the two. Therefore, this paper takes 35 cities in China as research object: The urban compactness evaluation index system is established, and the score is calculated using the entropy weight method; considering the bad output, SBM is used to calculate the green total factor energy efficiency (GTFEE); and the coupling coordination degree model is used to calculate their coordinated degree. The following conclusions can be inferred: (1) Although China's urban compactness has increased, it has not maintained a steady upward trend. Some more developed cities have the phenomenon of compactness rising first and then falling; (2) The overall GTFEE shows a continuous upward trend, but there is still much room for improvement, and regional disparities are significant; (3) The degree of coordination between the two maintains a steady upward trend, and the city's compactness lags behind GTFEE. Based on the findings of the study, this paper proposes policy recommendations that can serve as a reference for key decision-makers and are critical in promoting China's urbanization and energy transformation.


Trichoadenoma of the eyelid.
To report the unique occurrence of a trichoadenoma of the eyelid. An 80-year-old woman underwent surgical resection of a lesion of the right lower eyelid that was suspected to be a basal cell carcinoma. The lesion was studied with light microscopy. Histopathology showed a lesion in the dermis that contained keratin cysts surrounded by a proliferation of eosinophilic epidermoid cells. The findings were characteristic of a trichoadenoma. Trichoadenoma, a rare, benign, cutaneous tumor that usually occurs on the face, can develop on the eyelid and simulate a basal cell carcinoma.


Attitudes and perceptions of patients towards methods of establishing a DNA biobank.
This study aimed to assess patient attitudes as part of the planning process for a large-scale effort to collect genetic samples for research from excess clinical blood specimens ('DNA Databank' project). A pre-tested, 38-item questionnaire was mailed to a random sample of 5,000 inpatients, outpatients, and emergency department patients. Approximately 20% of patients responded (n = 1003). Most were comfortable with anonymized genetic information being used for research (89.3%) and supported the potential benefits (98.7%). A binary logistic regression on the level of comfort with the DNA program shows that the variability in respondents' feelings about the program can best be explained by beliefs, age, and health status. Respondents were attitudinally segmented into 5 distinct categories. These data indicate general acceptance among respondents, but a subset of the population would be opposed to the program. This reinforces the need to broadly and continuously communicate with patients about the program and the ability to exclude a given sample. The effects of prior beliefs would benefit from further exploration.


The ImmC region of phage P1 codes for a gene whose product promotes lytic growth.
The ImmC region of the temperate bacteriophage P1 contains c1, a gene that codes for a repressor of lytic growth. Located in the region upstream of c1 are four open reading frames capable of coding for low-molecular-weight proteins. The efficiency of lysogeny by P1+Cm was found to be reduced by almost 10(5)-fold when the host cells carry this region of ImmC on a multicopy plasmid. The sequences responsible for interfering with lysogen formation were localized to one of the small open reading frames (orf4) within ImmC. Insertions and deletions within orf4 suppress the virulent phenotype of P1virC mutants when introduced into the phage by recombination. These virC-suppressed mutant phage were found to be incapable of lytic growth unless the product of orf4 is provided in trans. The presence of orf4 was observed to interfere with repression by the c1 protein of ImmC-encoded promoters fused to lacZ. For this reason, we suggest that orf4 corresponds to coi, a gene previously proposed to code for an inactivator of c1-mediated repression.


Implications of the inhibition of animal tumors by dietary zinc deficiency.
Because zinc is an essential nutrient for tissue growth, cellular division, protein synthesis, and DNA and RNA replication, it also ought to play a critical role in the growth of tumors. To test this thesis, a series of experiments were performed to test the effect of zinc deficiency on the lethality of a variety of solid and ascites tumors in mice and rats. Specifically, the following models were tested: Walker 256 carcinosarcomas, solid and ascites forms in rats; three mouse leukemias (L5178yf, L1210, and P388) in CDF, male mice; and Lewis lung carcinoma in C57BI/6 male mice. Rats receiving a zinc-deficient diet showed marked reduction of tumor growth, both of solid or ascites models, and this was accompanied by striking increase in survival. Survival of mice with transplanted leukemia was also significantly prolonged by zinc deficiency. In addition, growth of the Lewis lung carcinoma was inhibited, but the survival through increased, was probably limited by the adverse effects of zinc deficiency. The results suggest that tumor inhibition is a general effect of zinc deficiency, irrespective of cell type, cell growth rate, species, or site of growth. There are numerous potential applications of zinc metabolism to the diagnosis, therapy, and understanding of cancer.


Intracellular Ca2+ oscillations and membrane potential fluctuations in intact human T lymphocytes: role of K+ channels in Ca2+ signaling.
In intact human T lymphocytes, voltage-gated K+ [K(V)] channels and Ca(2+)-activated K+ [K(Ca)] channels have been recorded using the patch clamp technique in the cell-attached configuration. The reversal potential of the voltage-gated current with high K+ solution in the pipette gives a measure for the cell membrane potential (VM). The open probability of the K(Ca) channels gives a measure for intracellular Ca2+ concentration ([Ca2+]i). By simultaneous recording of both types of K+ channels, the interaction of VM and [Ca2+]i in T lymphocytes was investigated. It was demonstrated that VM fluctuates under resting conditions in a 20 mV range around an average value of -60 mV. In response to T cell receptor stimulation by PHA, rises in [Ca2+]i occur, which vary between cells from transient or sustained elevations to Ca2+ oscillations, in parallel with amplification of the hyperpolarizing deflections of VM. The correlation between VM and [Ca2+]i suggests that Ca2+ oscillations are modulated by positive feedback between Ca2+ influx, [Ca2+]i and VM mediated by K(Ca) channels and by intrinsic VM fluctuations caused by negative feedback between VM and the K(V) channel. Differences in the ratio between K(Ca) and K(V) channel numbers can account for the variability in Ca2+ responses between cells. The results predict periodic K(V) channel activity at rest and alternating K(V) and K(Ca) channel activity during Ca2+ signaling, which was consistent with subsequent observations.


Virtual screening and repurposing of approved drugs targeting homoserine dehydrogenase from Paracoccidioides brasiliensis.
Paracoccidioidomycosis is a systemic mycosis endemic in Latin America, and one of the etiological agents of the disease is Paracoccidioides brasiliensis. Currently, available treatments present adversities, such as duration, side effects, and drug interactions. In search of new therapy possibilities, this study evaluates drugs approved for use against the homoserine dehydrogenase enzyme, by an in silico approach, which performs an important biosynthesis phase for the fungus and is not present in the human body. The three-dimensional structure of the homoserine dehydrogenase enzyme from Paracoccidioides brasiliensis was obtained by homology modeling. The model was validated, and simulations were performed for virtual screening of molecules of drugs approved from the Drugs-libs database by the MTiOpenScreen web server. Molecular dynamics in three replicas were used for four drugs with better results, and in two more molecules as a control, the HS9 with inhibition against enzyme and HON which shows inhibition against mold structure. Based on the results of molecular dynamics and the comparison of binding free energy, the drug that obtained the best result was Bemcentinib. In comparison with the controls, it presented a highly relevant affinity with - 44.63 kcal/mol, in addition to good structural stability and occupation of the active site. Therefore, Bemcentinib is a promising molecule for the inhibition of PbHSD protein (homoserine dehydrogenase of Paracoccidioides brasiliensis) and a therapeutic option to be investigated.


Dental health of recent immigrant children in the Newcomer schools, San Francisco.
Dental screenings of 1,012 recent immigrant elementary school children in San Francisco showed 77 per cent of children needed dental treatment on first screening, compared to 25 per cent in the 1979-80 National Institute of Dental Research (NIDR) survey for the western United States. The prevalence of dental caries in primary teeth of the immigrant six and seven year-olds was twice that of their US counterparts. Non-refugee immigrants had more serious dental needs but used dental services less often than children with refugee status.


Conversion of big endothelin-1 to endothelin-1 by two types of metalloproteinases derived from porcine aortic endothelial cells.
Incubation of big endothelin-1 (big ET-1(1-39] with either the cytosolic or membrane fraction obtained from cultured endothelial cells, resulted in an increase in immunoreactive-endothelin (IR-ET), which was markedly inhibited by metal chelators. Phosphoramidon, a metalloproteinase inhibitor, specifically suppressed the membrane fraction-induced increase in IR-ET, whereas the increase in IR-ET observed with the cytosolic fraction was not influenced by phosphoramidon. Reverse-phase (RP)-HPLC of the incubation mixture of big ET-1 with the cytosolic or membrane fraction revealed one major IR-ET component corresponding to the elution position of synthetic ET-1(1-21). Simultaneously, immunoreactivities like the C-terminal fragment (CTF22-39) of big ET-1 were present, as deduced from the RP-HPLC coupled with the radioimmunoassay for CTF. Our results indicate the presence of two types of metalloproteinases, which convert big ET-1 to ET-1 via a single cleavage between Trp21 and Val22, in vascular endothelial cells.


Early processing deficits in object working memory in first-episode schizophreniform psychosis and established schizophrenia.
While there are many studies showing working-memory deficits in schizophrenia there are only a few that disentangle impairments for working-memory subprocesses such as perceptual, attentional, mnemonic and executive function. In this study of delay-dependent memory, 55 patients with schizophreniform psychosis, 50 with established schizophrenia and 56 healthy controls were investigated. Using the delayed matching-to-sample task from the Cambridge Neuropsychological Test Automated Battery (CANTAB), performance deficits were found in both patient groups after controlling for age and pre-morbid IQ. Even after controlling for simultaneous matching-to-sample ability (i.e. perceptual matching), impaired performance in both patient groups was found as soon as the stimuli were no longer present. Impaired performance was not due to different types of errors in patients versus controls. Performance in both patient groups was comparable, except for a slight decrease of overall task performance. This suggests that the deficit is relatively stable during the course of the illness. Our results suggest a deficit in patients with psychotic illness in the initial processes necessary to actively maintain information, such as the ability to form an internal representation of complex objects.


Citrulline as the main precursor of ethyl carbamate in model fortified wines inoculated with Lactobacillus hilgardii: a marker of the levels in a spoiled fortified wine.
The aim of this study was to investigate the production of ethyl carbamate (EC) precursors by Lactobacillus hilgardii in model and Douro fortified wines and to determine the relationship between these compounds and EC levels in this type of wine. Several model fortified wines and fortified wine inoculated with L. hilgardii were analysed for citrulline and EC formation. A good correlation (R > 0.9) was obtained between citrulline and potential EC (that EC which is formed during heating of sample at 80 degrees C for 48 h). This correlation allowed us to calculate the potential EC formed during lactic acid bacteria activity in fortified wine. A good correlation was obtained (R=0.92) between measured and calculated EC in spoiled fortified wines, citrulline apparently being the main EC precursor produced by Lact. hilgardii thus contributing to the potential EC in this type of wine.


Histologic inflammatory changes on the prostatic gland due to immunosuppression for kidney transplantation.
To determine the incidence of type IV prostatitis in patients with kidney transplantation receiving an immunosuppression regimen and to compare it with that of a nonimmunosuppressed control group. We retrospectively reviewed 216 electronic charts of patients who had undergone surgical treatment for benign prostatic hyperplasia from August 2000 to January 2006. Of the 216 patients, 183 did not receive immunosuppressive therapy and were included in the control group (group 1). The other 33 patients had undergone kidney transplantation and were included in the study group (group 2). The patient data were accessed for age at surgery, International Prostate Symptom Score, prostate volume, preoperative serum prostate-specific antigen level, history of acute urinary retention, and surgical approach (open vs transurethral resection of prostate). Histologic findings from the surgical specimens were also recorded. The mean age at surgery, mean serum prostate-specific antigen level, mean prostate volume, and mean International Prostate Symptom Score were not significantly different between both groups. However, histologic evidence of chronic prostatitis was obtained in 145 surgical specimens (78%) from group 1 and in just 3 specimens from group 2 (9%; P < .001). Moreover, nonimmunosuppressed patients had a 38.2 times greater risk of presenting with prostatitis than did the immunosuppressed patients. Immunosuppression therapy in kidney transplantation has a protective factor in the prostatitis incidence.


Porous electrodes: concept, technology and results.
Porous electrodes were designed and implanted to optimize sensing and pacing performance of the cardiac pacemaker. These electrodes were manufactured to create an effective, atraumatic endocardial interface in order to (1) decrease chronic stimulation thresholds and pacemaker current drain; (2) facilitate fibrous protein tissue ingrowth for reduced electrode displacement; and (3) to create a large electrolytic surface area of contact for reduced polarization voltage, thus improving impulse and electrogram transmission. Thus far, clinical results demonstrate reduced long-term threshold and decreased current drain. Long-term advantages of porous electrodes remain to be determined.


Diversity of bacterial species in the nasal cavity of sheep in the highlands of Ethiopia and first report of Histophilus somni in the country.
A study was conducted to isolate bacterial species/pathogens from the nasal cavity of apparently healthy and pneumonic sheep. Nasal swabs were collected aseptically, transported in tryptose soya broth and incubated for 24 h. Then, each swab was streaked onto chocolate and blood agar for culture. Bacterial species were identified following standard bacteriological procedures. Accordingly, a total of 1,556 bacteria were isolated from 960 nasal swabs collected from three different highland areas of Ethiopia, namely Debre Berhan, Asella, and Gimba. In Debre Berhan, 140 Mannheimia haemolytica, 81 Histophilus somni, 57 Staphylococcus species, and 52 Bibersteinia trehalosi were isolated. While from Gimba M. haemolytica, Staphylococcus, Streptococcus, and H. somni were isolated at rates of 25.2, 15.9, 11.4, and 5.9 %, respectively, of the total 647 bacterial species. In Asella from 352 bacterial species isolated, 93 (26.4 %) were M. haemolytica, 48 (13.6 %) were Staphylococcus species, 26 (7.4 %) were B. trehalosi, and 17 (4.8 %) H. somni were recognized. Further identification and characterization using BIOLOG identification system Enterococcus avium and Sphingomonas sanguinis were identified at 100 % probability, while, H. somni and Actinobacillus lignerisii were suggested by the system. The study showed that a variety of bacterial species colonize the nasal cavity of the Ethiopian highland sheep with variable proportion between healthy and pneumonic ones. To our knowledge, this is the first report on isolation of H. somni, an important pathogen in cattle, from the respiratory tract of a ruminant species in the country.


Tokenism in psychology: standing on the shoulders of small boys.
Tokenism is a situation in which a member of a distinctive category is treated differently from other people. This article is about the situation in which Tokens (people perceived as distinctive) are considered experts on something for having the properties of a token (the thing which makes them distinctive). Tokens who differ by appearance or by being born into another culture might be considered experts on cultures grouped into the same racial/cultural category. Tokens who differ by being skilled in number-related mathematics might be considered experts on the mathematization of phenomena. Tokens might say that some result is valid for all people in some racial/cultural category without sufficient evidence, or use number-related mathematics as a mathematization of psychological phenomena without trying to find more abstract mathematizations. This harms psychological research. A possible future genesis of cultural and number tokenisms is discussed, and some suggestions to improve the discourse offered. The effect of tokenism might be diminished if psychologists focus on more proper thinking about psychological phenomena.


Haemosporidian infections in the Tengmalm's Owl (Aegolius funereus) and potential insect vectors of their transmission.
Sedentary bird species are suitable model hosts for identifying potential vectors of avian blood parasites. We studied haemosporidian infections in the Tengmalm's Owl (Aegolius funereus) in the Ore Mountains of the Czech Republic using molecular detection methods. Sex of owl nestlings was scored using molecular sexing based on fragment analysis of PCR-amplified CHD1 introns. Observed infection prevalences in nestlings and adult owls were 51 and 86 %, respectively. Five parasite lineages were detected. Most of the infections comprised the Leucocytozoon AEFUN02 and STOCC06 lineages that probably refer to distinct Leucocytozoon species. Other lineages were detected only sporadically. Mixed infections were found in 49 % of samples. The main factor affecting the probability of infection was host age. No effect of individual sex on infection probability was evidenced. The youngest infected nestling was 12 days old. High parasite prevalence in the Tengmalm's Owl nestlings suggests that insect vectors must enter nest boxes to transmit parasites before fledging. Hence, we placed sticky insect traps into modified nest boxes, collected potential insect vectors, and examined them for the presence of haemosporidian parasites using molecular detection. We trapped 201 insects which were determined as biting midges from the Culicoides genus and two black fly species, Simulium (Nevermannia) vernum and Simulium (Eusimulium) angustipes. Six haemosporidian lineages were detected in the potential insect vectors, among which the Leucocytozoon lineage BT2 was common to the Tengmalm's Owl and the trapped insects. However, we have not detected the most frequently encountered Tengmalm's Owl Leucocytozoon lineages AEFUN02 and STOCC06 in insects.


When green enters a room: A scoping review of epidemiological studies on indoor plants and mental health.
Increasing numbers of epidemiological studies are investigating the association between outdoor greenery and various health outcomes. However, in the case of indoor plants, although experimental studies seem relatively abundant, epidemiological studies remain scarce, and research considering the mental health effects is even more limited. Thus, we aim to identify and summarise the relevant epidemiological studies on indoor plant exposure and mental health via this scoping review, thereby presenting the current state of knowledge and research niches. PubMed and PsycINFO were systematically searched for epidemiological studies on indoor plant exposure and mental health, including mental and behavioural disorders, quality of life, and cognitive function. The publication period was from the inception of these two databases to 22nd June 2022. We extracted information on exposure to indoor plants and mental health-related outcomes from the relevant studies. The systematic search yielded 1186 unique results. Six studies met the inclusion criteria and were finally included in this scoping review. All included studies were Europe-based cross-sectional studies on mental and behavioural disorders. One study was conducted in 2015 and investigated the office environment, whereas the other five were conducted during the COVID-19 pandemic and focused on the home environment. Despite considerable heterogeneity in outcome assessments and indoor plant exposure metrics, all six studies generally reported beneficial associations between having indoor plants and mental health, such as reducing stress, depressive symptoms, and negative emotions. Epidemiological evidence on exposure to indoor plants and mental health is currently limited. In general, favourable effects of indoor plants are supported, although most relevant studies were conducted in the context of COVID-19. Before conducting more studies to explore the associations, data collection methods must be refined with more elaborate designs that allow for the measurement of more comprehensive metrics of indoor plants. Open Science Framework, osf.io/5xr6b.


Microvascular responses to norepinephrine and vasopressin during halothane anesthesia in the rat.
This experiment was designed to determine the microvascular responses to the two known naturally occurring vasoconstrictors, norepinephrine (NE) and vasopressin, at known levels of central vasomotor activity before, during and after halothane anesthesia. The responses to topical application of NE and vasopressin were studied in the microvasculature of the mesentery and cremaster muscle, using microscopic methods. Neural (CNS) stimulation was accomplished through electrodes chronically implanted in vasoactive sites of the forebrain and midbrain. The increase in blood pressure in response to CNS stimulation was decreased during halothane anesthesia (32.4 +/- 5.4 per cent before and 24.7 +/- 6.1 per cent during; P less than 0.001). There was no significant change in the steady-state diameter of the microvasculature under study during or after halothane anesthesia. Marked abatement of arteriolar vasoconstriction in response to CNS stimulation was seen prior to halothane. However, the same target vessel showed increased constriction in response to topically applied NE (from 32.3 +/- 4.7 to 53.2 +/- 7.8 per cent; P less than 0.01) during halothane anesthesia. By contrast, the response to vasopressin decreased (from 42.4 +/- 5.7 to 1.0 +/- 6 per cent; P less than 0.001) with halothane. The precise mechanism(s) underlying the described hypersensitivity to NE and hyposensitivity to vasopressin in the same vascular structure during halothane anesthesia remains undetermined.


Reduction in diarrhoeal rates through interventions that prevent unnecessary antibiotic exposure early in life in an observational birth cohort.
Antibiotic treatment early in life is often not needed and has been associated with increased rates of subsequent diarrhoea. We estimated the impact of realistic interventions, which would prevent unnecessary antibiotic exposures before 6 months of age, on reducing childhood diarrhoeal rates. In data from a prospective observational cohort study conducted in Vellore, India, we used the parametric g-formula to model diarrhoeal incidence rate differences contrasting the observed incidence of diarrhoea to the incidence expected under hypothetical interventions. The interventions prevented unnecessary antibiotic treatments for non-bloody diarrhoea, vomiting and upper respiratory infections before 6 months of age. We also modelled targeted interventions, in which unnecessary antibiotic use was prevented only among children who had already stopped exclusive breast feeding. More than half of all antibiotic exposures before 6 months (58.9%) were likely unnecessary. The incidence rate difference associated with removing unnecessary antibiotic use before 6 months of age was -0.28 (95% CI -0.46 to -0.08) episodes per 30 child-months. This implies that preventing unnecessary antibiotic exposures in just 4 children would reduce the incidence of diarrhoea by 1 from 6 months to 3 years of age. Interventions to reduce unnecessary antibiotic use among young children could result in an important reduction in diarrhoeal rates. This work provides an example application of statistical methods which can further the aim of presenting epidemiological findings that are relevant to public health practice.


On the vanadium and tin contents of diet and human blood.
The vanadium and tin contents of total diet samples collected in five Italian towns are given, and discussed in relation to literature data, their status as essential elements and their levels in human blood. Tin in blood was found to be below 2 ng ml-1 in a group of 14 subjects, and barely detectable even after oral consumption of 60 mg of tin.


Enantioselective total synthesis, divergent optimization and preliminary biological evaluation of (indole-N-alkyl)-diketopiperazines.
The first enantioselective total synthesis of the antifungal natural product (indole-N-isoprenyl)-tryptophan-valine diketopiperazine 5 was accomplished. Four stereoisomers of 5 were intentionally prepared, and the (R, R)-isomer is more favorable in enhancing the antifungal bioactivity. Divergent structural optimization of this attractive model was conducted from the chiral pool amino acids. Fine-tuning of the structure protruded the broad-spectrum antifungal 6b, which also showed good preventative efficacy against Sclerotinia scleotiorum. Compound 5d could accelerate both hypocotyl elongation and root growth of Eclipta prostrata even at the concentration of <2.5 ppm. This unique and easily accessible scaffold will be of prime importance in achieving agrochemical candidates with the novel scaffold.


Keratolysis Associated with Methamphetamine Use - Incidental Diagnosis of Corneal Melt in a Patient with Acute Methamphetamine Intoxication.
A 38-year-old male presented to the emergency department with methamphetamine-induced agitation. Physical exam showed clouding of the left cornea, with gelatinous appearance and associated conjunctivitis, consistent with corneal melt, or keratolysis. Keratolysis is dissolution of the corneal stroma that can lead to corneal ulceration and vision loss. Smoking stimulants has been shown to be associated with this pattern of ocular injury, although this is a relatively rare presentation. Acute keratolysis is a unique complication of methamphetamine preparation and ingestion via smoking that can lead to corneal ulceration and loss of vision.


The effects of six root-end filling materials and their leachable components on cell viability.
This study investigated the effect of six root-end filling materials (Retroplast [Retroplast Trading, Dybesøvej, Denmark], Geristore, [DEN-MAT Corporation, Santa Maria, CA], Ketac Fil [3M ESPE, Seefeld, Germany], IRM [Caulk-Dentsply, Milford, DE], Super EBA [Bosworth Company, Skokie, IL], and MTA [Dentsply-Tulsa Dental, Johnson City, TN]) on the viability of Balb/C 3T3 fibroblasts using the [3-4, 5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide succinate (MTT) assay. Ten discs (5 mm x 2 mm) of each material were eluted in tissue culture medium for 24 hours at 37 degrees C for 3 successive days and the elutes used for cell viability testing and for determination of leached components. The results showed that Retroplast, Geristore, and Ketac Fil increased cell proliferation, whereas Super-EBA decreased cell viability. The proliferative effect of Retroplast and Geristore increased with the eluting time (24 hours, 48 hours, and 72 hours), whereas the effects of the other materials did not significantly change. IRM and MTA did not affect cell viability. High-performance liquid chromatography analysis and atomic absorption spectroscopy showed that there was variation in the amount of leached components from the materials. Our results indicate that the reaction of cells to root-end filling materials varies considerably between materials.


The role of host tree condition in attack of white oaks by the twolined chestnut borer, Agrilus bilineatus (Weber) (Coleoptera: Buprestidae).
The twolined chestnut borer, Agrilus bilineatus (Weber) (Coleoptera: Buprestidae), attacks stressed oaks (Quercus spp.) and is associated with extensive mortality of trees in the eastern deciduous forests of North America. We examined host location by the insect and subsequent host mortality in experimentally stressed trees. A. bilineatus adults were able to rapidly and specifically locate stressed oak trees. Up to 160 beetles per week were captured on sticky band traps on the trunks of stressed trees, while beetles rarely landed on unstressed control trees. This suggests that adult borers have an acute perception of host tree "quality", and that this perception is from a distance. One mechanism of host location may be detection of volatile compounds produced by stressed trees.The condition of the host tree appears to regulate both beetle attraction and successful colonization. Mortally wounded (xylem-girdled) trees attracted beetles only until the cambium died. Xylem-girdled trees were attacked early in the beetle flight season, but larvae did not survive to emerge as adults from these trees. In contrast, phloemgirdled trees continued to attract beetles throughout the flight period. Phloem-girdled trees which were heavily attacked by A. bilineatus died late in the season in which they were attacked. Lightly attacked trees survived until the following growing season, and were then heavily attacked and killed. In one stand, phloem-girdled trees were not attacked, healed over the girdling wounds and were still alive three years after girdling. These results indicate that oak trees are only attractive to A. bilineatus within a narrow range of physiological conditions following stress but prior to mortality. A. bilineatus appears to be a proximate agent of mortality in stressed oaks in eastern North America.


Effect of carnosine and related compounds on proliferation of cultured rat pheochromocytoma PC-12 cells.
The study was undertaken to determine the mechanism of carnosine effect on cell proliferation. We studied the effect of carnosine and its derivatives on cell cycle progression in cultured rat pheochromocytoma cells (PC-12). It was found that 48-h incubation of PC-12 cells with carnosine in concentrations of 10-50 mM led to deceleration of cell proliferation, reduction of G0/G1 peak, and accumulation of S- and G2/M-phase cells. Methylation of the carnosine molecule by 1N-position of the imidazole ring potentiated its effect on cell proliferation. Acetylation of the carnosine molecule by free β-amino group attenuated its effect.


State of the Art: The Therapeutic Approaches to Bulimia Nervosa.
Bulimia nervosa (BN) is an eating disorder characterized by binge eating, inappropriate compensatory behaviors, and body image concerns in persons at or above a healthy weight. BN is a serious disorder with medical sequelae and marked psychosocial impairment. To reduce and eliminate symptoms of BN, psychological and pharmacologic treatments for BN have been developed. We review the current state-of-the-art treatments for BN. We conducted a narrative review of the BN treatment literature to synthesize the current evidence base, provide recommendations, and propose future directions for BN treatment research. Currently, the first-line, state-of-the-art treatment for adults with BN is cognitive-behavioral therapy (CBT). Interpersonal therapy is a second-line evidence-based treatment for adults with BN, and dialectical behavior therapy and integrative cognitive-affective therapy are also promising. For BN in adolescents, family-based treatment for BN or CBT are evidence-based approaches. Pharmacotherapy is best considered adjunctive to psychotherapy in adults with BN but may be helpful, depending on the type of psychotherapy and whether psychotherapy is ineffective or unavailable. Fluoxetine 60 mg/d is the medication of choice for adults with BN. Little is known with respect to pharmacologic treatment of BN in adolescents, although fluoxetine 60 mg/d holds promise. Despite decades of treatment-development research in BN, there is room for improvement because nearly 60% of those with BN do not achieve remission with specialty treatment and strikingly few randomized controlled trials for BN in adolescents exist. Moreover, the field should address issues related to treatment dissemination, access, and cost.


SIRT1-modified human umbilical cord mesenchymal stem cells ameliorate experimental peritoneal fibrosis by inhibiting the TGF-β/Smad3 pathway.
Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Combination therapies are emerging as a promising treatment for tissue damage. Here, we investigated the therapeutic potential of SIRT1-modified human umbilical cord mesenchymal stem cells (hUCMSCs) for peritoneal fibrosis. SIRT1 was overexpressed in hUCMSCs to establish SIRT1-modified hUCMSCs. Co-culture and transplantation experiments were performed in TGF-β-stimulated Met-5A cells and peritoneal damage rodent model to assess the therapeutic potential of SIRT1-modified hUCMSCs for peritoneal fibrosis through qPCR, Western blot, and peritoneal function analyses. SIRT1-modified hUCMSC administration had more potent anti-fibrosis ability than hUCMSCs, which significantly inhibited the expression of fibrotic genes and suppressed EMT process, increased ultrafiltration volume, and restored homeostasis of bioincompatible factors in dialysis solution. Mechanistically, SIRT1-modified hUCMSCs attenuated peritoneal fibrosis through reducing peritoneal inflammation and inhibiting the TGF-β/Smad3 pathway in peritoneal omentum tissues. SIRT1-modified hUCMSCs might work as a promising therapeutic strategy for the treatment of peritoneal dialysis-induced peritoneal damage and fibrosis.


Relationship between subjective preference and alpha-wave activity in relation to temporal frequency and mean luminance of a flickering light.
Human cortical responses corresponding to the subjective preference for a flickering light under varying temporal frequency and mean luminance were investigated. Paired-comparison tests were performed to examine the subjective preference for a flickering light, and electroencephalograms (EEGs) were recorded from six electrodes (10-20 International Electrode Placement System) during presentations of the most-preferred and least-preferred flickering lights. The results showed a positive correlation between subjective preference and the effective duration of the autocorrelation function of the alpha waves measured at the visual cortex (O1 and O2 electrodes).


Diagnostic factors in pediatric primary headache.
Primary headaches are frequent in children. They are difficult to diagnose because there is much disagreement about the interpretation of the historical data and the use of signs and/or symptoms in diagnosis. It would be useful, therefore, to standardize this procedure. We used linear discriminant analysis to determine a classification rule capable of diagnosing new cases of chronic and recurrent primary headache in children. We considered 23 symptoms in 118 patients. Through discriminant analysis we chose five variables: frequency of the attacks, type of pain, neurologic deficits, nausea, and vomiting. With this classification rule, we obtained a total correct classification of 84.7% for migraine, psychogenic headache, and non-defined headache in respect to the diagnoses formulated by a pediatrician and a child neuropsychiatrist after 3 months of follow-up. Our method for diagnosing migraine has a sensitivity of 95% and a specificity of 100%. The algorithm, validated on another 105 pediatric patients, produced a total correct result of 82.9%.


Edema formation and neutrophil mobilization in the neutropenic rat.
The relationship between leucocyte mobilization and edema formation was evaluated in the carrageenan pleurisy model. In normal rats carrageenan was able to mobilize between 80 and 100 million cells per ml of fluid. In neutropenic rats the concentration fell to between 20 and 50 million cells per ml, suggesting the edema formed after carrageenan injection is not directly correlated with cellular mobilization.


Predicting outcome after arteriovenous malformation-associated intracerebral hemorrhage with the original ICH score.
To evaluate the predictive ability of the original ICH Score (oICH) in a large independent cohort of patients with arteriovenous malformation-associated intracerebral hemorrhage (AVM-ICH), an important cause of intracerebral hemorrhage (ICH) that is associated with significantly different epidemiology, clinical course, and outcome compared with primary ICH. During the period 1997-2009, 91 patients were admitted to Columbia Medical Center with acute AVM-ICH. Demographic and admission clinical and radiographic variables were obtained for 84 patients through retrospective chart review. Admission oICH and Spetzler-Martin grading scale (SMGS) were calculated. Outcome was assessed at 3 months using the modified Rankin Scale (mRS). Maximum Youden Indices were used to identify cutoffs for age and ICH volume that are associated with optimal predictive accuracy for an unfavorable outcome (mRS ≥ 3). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive performance of oICH, and oICH with new age and ICH cutoff points (new AVM-ICH score based on original ICH Score [AVM-oICH]). The mean age was 35 years ± 14, and mean ICH volume was 22 mL ± 20. At 3-month follow-up, 3 (4%) patients were dead, and 15 (18%) had an unfavorable outcome. Two of the patients who died had oICH of 3, and one had oICH of 5. ICH volume of 37 mL and age of 41 years were identified as optimal cutoffs for predicting an unfavorable outcome. oICH and AVM-oICH showed good predictive accuracies with area under the curve of 0.914 and 0.891 (P = 0.422). AVM-oICH and oICH had similarly high sensitivities (0.889 and 0.944; P = 1.00), but the former had significantly greater specificity (0.879 vs. 0.682; P < 0.001). oICH is a valid clinical grading scale with high predictive accuracy for functional outcome after AVM-ICH. It is unclear whether the score is appropriate for risk stratification with regard to mortality because of the low risk of death associated with AVM-ICH. Simple adjustments of the age and ICH volume cutoff points improve performance of the score and reduce the probability of overestimating a patient's risk of an unfavorable outcome after AVM-ICH.


Studies on bacterial cell wall inhibitors. III. 3-amino-3-deoxy-D-glucose, an inhibitor of bacterial cell wall synthesis.
It was shown that 3-amino-3-deoxy-D-glucose, one of the constituents of the kanamycin molecule and a metabolite of Bacillus sp., inhibits the bacterial synthesis of cell wall. The antibiotic (100 microgram/ml) significantly inhibits the growth of Staphylococcus aureus FDA 209P as well as the incorporation of DL-[14C]alanine into the acid-insoluble macromolecular fraction of its growing cells in the presence of chloramphenicol (100 microgram/ml). In contrast, the antibiotic does not affect the incorporation of [3H]thymidine, [3H]uridine and L-[14C]leucine. The other constituents of kanamycin, 6-amino-6-deoxy-D-glucose and deoxystreptamine do not inhibit the synthesis of bacterial cell wall peptidoglycan.


Mental stress-induced ischemia and all-cause mortality in patients with coronary artery disease: Results from the Psychophysiological Investigations of Myocardial Ischemia study.
Ischemia during laboratory mental stress tests has been linked to significantly higher rates of adverse cardiac events. Previous studies have not been designed to detect differences in mortality rates. To determine whether mental stress-induced ischemia predicts death, we evaluated 196 patients from the Psychophysiological Investigations of Myocardial Ischemia (PIMI) study who had documented coronary artery disease and exercise-induced ischemia. Participants underwent bicycle exercise and psychological stress testing with radionuclide imaging. Cardiac function data and psychological test results were collected. Vital status was ascertained by telephone and by querying Social Security records 3.5+/-0.4 years and 5.2+/-0.4 years later. Of the 17 participants who had died, new or worsened wall motion abnormalities during the speech test were present in 40% compared with 19% of survivors (P=0.04) and significantly predicted death (rate ratio=3.0; 95% CI, 1.04 to 8.36; P=0.04). Ejection fraction changes during the speech test were similar in patients who died and in survivors (P=0.9) and did not predict death even after adjusting for resting ejection fraction (P=0.63), which was similar in both groups (mean, 56.4 versus 59.7; P=0.24). Other indicators of ischemia during the speech test (ST-segment depression, chest pain) did not predict death, nor did psychological traits, hemodynamic responses to the speech test, or markers of the presence and severity of ischemia during daily life and exercise. In patients with coronary artery disease and exercise-induced ischemia, the presence of mental stress-induced ischemia predicts subsequent death.


Interocular transfer of shape discrimination in the goldfish--a reassessment of the role of the posterior commissure.
Previous work has implicated the hypothalamic horizontal commissure in the interocular transfer of learned shape information in the goldfish. In the experiments reported here, goldfish were classically conditioned to show a differential cardiac response. Fish with transection of this commissure acquired and transferred a circle/square discrimination, whereas animals with transection of the mesencephalic posterior commissure showed acquisition but not transfer of the same task. Other fish were trained on an orientation discrimination. Although all fish acquired the task, those with transection of the horizontal commissure showed transfer failure, whereas those with transection of the posterior commissure demonstrated transfer. We therefore suggest that information relating to shape is transferred via the posterior commissure, but that information relating to rotation transfers through the horizontal commissure.


Capsaicinoid-induced local and systemic antinociception without substance P depletion.
Capsaicin and its analog, dihydrocapsaicin, produced chemogenic and thermal antinociception and depletion of substance P from the dorsal spinal cord and dorsal root ganglia of guinea pigs following a single parenteral dose. Time course and distribution studies indicated that capsaicinoid-induced antinociception resulted from neither depletion of substance P nor nonspecific actions of capsaicinoids at dorsal root ganglia. A site of action for capsaicinoid-induced antinociception is peripheral to the dorsal root ganglia and may involve covalent binding of capsaicinoids to free nerve endings of the dermis. Depletion of substance P by capsaicinoids appears to be mediated at a site more central than that which mediates antinociception and may involve alterations in the retrograde axoplasmic transport of neurotrophic factors.


Insulin-like stimulation of glucose transport in isolated adipocytes by fatty acids.
Glucose transport rate as assessed with the 3-0-Methylglucose method was significantly increased in adipocytes preincubated with aliphatic carboxylic acids. The magnitude of stimulation apparently depended on the chain length of the carboxylic acid, and was highest with palmitic acid (130%). The stimulation was additive to the effect of insulin, and reflected a decrease of km rather than an increase in vmax of the transport rate. The results suggest that fatty acids may modulate the activity of the glucose transporter, providing an insulin-dependent supply of adipose tissue with glycerol-phosphate during lipolysis for reesterification of excess fatty acids. Further, it is suggested that fatty acids mediate the stimulatory effect of catecholamines on glucose transport as observed in isolated fat cells.


Highly efficient and robust treatment of low C/N actual domestic sewage via integrated fermentation, partial-nitrification, partial-denitrification and anammox (IFPNDA).
For achieving efficient and robust treatment of domestic sewage with C/N around 2.8, this study innovatively developed an integrated fermentation, partial-nitrification, partial-denitrification and anammox (IFPNDA) process based on the Anaerobic Baffled Reactor and Continuous-flow Stirred Tank Reactor (ABR-CSTR) bioreactor. Desirable N-removal efficiency of 87.5 ± 2.1% was obtained without external organics, correspondingly effluent total nitrogen (TN) concentration reached 6.1 ± 0.7 mg/L. The N-removal stability was greatly facilitated by the effective linkage between partial nitrification (PN) process and partial denitrification (PD) process in emergency. Highly enriched hydrolytic bacteria (6.9%) and acidogenic bacteria (5.7%) in A1, especially Comamonas (2.8%) and Longilinea (3.5%), induced the significant increase of volatile fatty acids (VFAs) in domestic sewage. Thauera (6.1%) in A2 and Nitrosomonas (5.4%) in A3 acted as the dominant flora of nitrite supplies for anammox in IFPNDA process. Candidatus_Brocadia (2.4%) dominated the advanced nitrogen removal. The IFPNDA process exhibited much potential for achieving energy neutrality during wastewater treatment.


Measurement of signal period on a personal microcomputer and its application to the analysis of cardiac interval and blood pressure.
Personal microcomputers interfaced with analog-digital converters are capable of analyzing almost any biological signal, yet are limited in their ability to directly measure a signal's period/frequency. We describe a short program which measures the interval between periodic events up to 3.5 Hz. In addition, an expanded program which calculates the frequency distribution, distribution statistics, and cross regressions of cardiac interval and blood pressure is described.


"Inflammatory" breast cancer.
"Inflammatory" breast cancer is a rare and very aggressive form of the disease characterised by rapid onset and dismal outcome. This review describes the clinical and molecular aspects of inflammatory breast cancer. The relevant English language literature on of inflammatory breast cancer was searched via Medline and ISI Web of Knowledge Cross Search (1924-2005), cross-referencing with key articles on the subject. An increasing body of evidence demonstrates that inflammatory breast cancer is a unique form of breast cancer. A prompt diagnosis and multidisciplinary approach (based on neoadjuvant chemotherapy, loco-regional treatment with surgery and/or radiotherapy, followed in some cases by adjuvant systemic therapy) are the two factors most likely to have an impact on survival. As the molecular basis of the disease is becoming increasingly more defined, new potential therapeutic targets may arise in the future.


AAGL practice report: practice guidelines for the diagnosis and management of submucous leiomyomas.
Submucous leiomyomas or myomas are commonly encountered by gynecologists and specialists in reproductive endocrinology and infertility with patients presenting with 1 or a combination of symptoms that include heavy menstrual bleeding, infertility, and recurrent pregnancy loss. There exists a variety of interventions that include those performed under hysteroscopic, laparoscopic and laparotomic direction; an evolving spectrum of image guided procedures, and an expanding number of pharmaceutical agents, each of which has value for the appropriately selected and counseled patient. Identification of the ideal approach requires the clinician to be intimately familiar with a given patient's history, including her desires with respect to fertility, as well as an appropriately detailed evaluation of the uterus with any one or a combination of a number of imaging techniques, including hysteroscopy. This guideline has been developed following a systematic review of the evidence, to provide guidance to the clinician caring for such patients, and to assist the clinical investigator in determining potential areas of research. Where high level evidence was lacking, but where a majority of opinion or consensus could be reached, the guideline development committee provided consensus recommendations as well.


Time- and space-resolved Monte Carlo study of water radiolysis for photon, electron and ion irradiation.
Time-dependent yields of the most important products of water radiolysis E(aq)(-), (*)OH, H(*), H(3)O(+), H(2), OH(-) and H(2)O(2) have been calculated for (60)Co-photons, electrons, protons, helium- and carbon-ions incident onto water. G values have been evaluated for the interval from 1 ps to 1 mus after initial energy deposition as a function of time, as well as after 1 ns and at the end of the chemical stage as a function of linear energy transfer (LET), covering an interval from approximately 0.2 up to 750 keV/microm by means of different particle types. In this work, the modules of the biophysical Monte Carlo track structure code PARTRAC dealing with the simulation of prechemical and chemical stages have been improved to extend interaction data sets for heavier ions. Among other newly selected parameter values, the thermalisation distance between the point of generation and hydration of subexcitation electrons has been adopted from recent data in the literature. As far as data from the literature are available, good agreement has been found with the calculated time- and LET-dependent yields in this work, supporting the selection of the revised parameter values.


Tyrosine is a potential site for covalent attachment of activated complement component C3.
Activation of C3 results in the generation of metastable C3b, which has been shown to preferentially react with the hydroxyl groups of carbohydrates and with specific serine and threonine residues in proteins. In this study we have examined the reactivity of metastable C3b with the third type of hydroxyl group present in proteins, tyrosine (Tyr). The results demonstrated that Tyr reacts with the thioester of metastable C3b and that this reactivity was 11-fold better than that of threonine, 47-fold better than serine and 50-fold better than the reactivity of carbohydrates. Model peptides containing Tyr showed even higher reactivity than free Tyr, demonstrating that incorporation into peptide structures does not block C3b attachment. The site of attachment was found to be in the alpha'-chain of C3b and the bond was hydroxylamine sensitive, indicating an ester linkage. The stability of the C3b-Tyr complex was measured under physiological conditions (pH 7.4, 37 degrees C) and compared to the stability of other C3b complexes. C3b-Tyr decayed 50% in 19 hr at 37 degrees C, but C3b bound to a Tyr-containing peptide was more stable, exhibiting a t1/2 of 53 hr. The ester linked complexes C3b-IgG and C3b-glycerol were less stable each exhibiting a t1/2 of approximately 8 hr. As yet, only two specific C3b attachment sites on proteins have been identified, Ser1217 in C4b and Thr144 in IgG1. The present evidence demonstrates that Tyr residues are highly reactive and that the C3b-Tyr linkage is stable. The findings suggest that complexes involving tyrosine residues as the site of attachment will also be found.


Prevalence of Salmonella spp in selected birds captured on California dairies.
To determine the prevalence of Salmonella spp in wild birds commonly found on California dairies. Prospective study. 7 selected species of birds were captured on 9 dairies in Kings and Tulare counties, California. Birds were captured (using traps and nets) and euthanatized, and the entire gastrointestinal tract was removed. Contents of the gastrointestinal tract were subjected to culture for Salmonella spp. 892 birds were captured, and Salmonella spp were isolated from 22 birds. The prevalence by dairy ranged from 0.7 to 16.7%, whereas the prevalence by bird species ranged from 1.2 to 3.2%. Cowbirds and English sparrows had the highest prevalence of Salmonella organisms. Five serotypes of Salmonella organisms were isolated, including Meleagridis, Montevideo, Muenster, Typhimurium, and an untyped serotype. On the basis of our findings, birds that commonly inhabit California dairies harbor Salmonella organisms. However, because of the low prevalence of Salmonella organisms in birds and the Salmonella serotypes isolated, birds are not important reservoirs of Salmonella organisms on California dairies.


An intermediate in a new synthesis approach to beta-substituted beta-hydroxyaspartame.
The crystal and molecular structure of 1-tert-butyl 4-ethyl (2'R,3'R,5'R,2S,3S)-3-bromomethyl-3-hydroxy-2-[(2'-hydroxy-2',6',6'-trimethylbicyclo[3.1.1]hept-3'-ylidene)amino]succinate, C(21)H(34)BrNO(6), is presented. This compound is an intermediate in the new synthetic route to beta-substituted beta-hydroxyaspartates, which are blockers of glutamate transport.


Plastic ingestion by fishing cats suggests trophic transfer in urban wetlands.
Recent studies have suggested that plastic contamination in some terrestrial and freshwater environments is estimated to be greater than that detected in marine environments. Urban wetlands are prone to plastic pollution but levels of contamination in their wildlife are poorly quantified. We collected 276 fishing cat (Prionailurus viverrinus) scat samples in Colombo, Sri Lanka for a dietary study of urban fishing cats. We used traditional dietary analysis methodology to investigate the contents of the scats by washing, isolating, and identifying prey remains; while sorting prey remains of individual scats, we unexpectedly detected macroscopic (>1 mm) plastic debris in six (2.17%) of the samples. Across all scat samples, we detected low occurrences of microplastics (0.72%), mesoplastics (1.09%) and macroplastics (1.45%). All three plastic types were found in scats containing rodent remains, while meso-, and macroplastics were found in scats with avian remains, and micro- and macroplastics in scats containing freshwater fish remains. Given that felids are obligate generalist carnivores that eat live or recently dead prey and do not consume garbage, our findings suggest that trophic transfer of plastics occurred whereby fishing cats consumed prey contaminated with plastic. Although macroscopic plastic detection was low, our findings suggest that accumulation of plastics is occurring in wetland food webs, and plastic pollution in freshwater terrestrial systems could pose a risk to predators that do not directly consume plastics but inhabit contaminated environments.


Cultural threat perceptions predict violent extremism via need for cognitive closure.
Understanding the psychological processes that drive violent extremism is a pressing global issue. Across six studies, we demonstrate that perceived cultural threats lead to violent extremism because they increase people's need for cognitive closure (NFC). In general population samples (from Denmark, Afghanistan, Pakistan, France, and an international sample) and a sample of former Mujahideen in Afghanistan, single-level and multilevel mediation analyses revealed that NFC mediated the association between perceived cultural threats and violent extremist outcomes. Further, in comparisons between the sample of former Afghan Mujahideen and the general population sample from Afghanistan following the known-group paradigm, the former Mujahideen scored significantly higher on cultural threat, NFC, and violent extremist outcomes. Moreover, the proposed model successfully differentiated former Afghan Mujahideen participants from the general Afghan participants. Next, two preregistered experiments provided causal support for the model. Experimentally manipulating the predictor (cultural threat) in Pakistan led to higher scores on the mediator (NFC) and dependent variables (violent extremist outcomes). Finally, an experiment conducted in France demonstrated the causal effect of the mediator (NFC) on violent extremist outcomes. Two internal meta-analyses using state-of-the-art methods (i.e., meta-analytic structural equation modeling and pooled indirect effects analyses) further demonstrated the robustness of our results across the different extremist outcomes, designs, populations, and settings. Cultural threat perceptions seem to drive violent extremism by eliciting a need for cognitive closure.


Structure elucidation of hexabromocyclododecanes--a class of compounds with a complex stereochemistry.
Hexabromocyclododecanes (HBCDs) are high production volume chemicals (16700 t worldwide in 2001) used as flame-retardants for plastics and textiles. HBCDs exhibit typical properties of persistent organic pollutants (POPs). They are highly lipophilic and accumulate in biota. Increasing environmental concentrations of HBCDs, mostly reported as sum values, have been observed. As such, HBCDs have to be considered as potential emerging POPs, but their occurrence and environmental fate have not yet been addressed at the level of individual HBCD stereoisomers. Considering the six stereogenic centers of HBCDs, 16 stereoisomers, six diastereomeric pairs of enantiomers as well as four meso forms, can be deduced. Herein, we report spectroscopic and chromatographic data for eight out of 16 possible HBCD stereoisomers, which were isolated from a technical product. Six stereoisomers were identified as three pairs of enantiomers ((+/-) alpha-, beta-, and gamma-HBCDs), differing in optical rotation and chromatographic retention on a chiral phase. The crystal structures of these pairs of enantiomers were determined. Another two of these eight HBCD stereoisomers, not yet described in the literature, showed no optical rotation and are tentatively assigned as meso forms (delta- and epsilon-HBCD). The given spectroscopic and chromatographic information allows the unambiguous identification of eight HBCD stereoisomers and the occurrence, fate, and toxicology of these individual stereoisomers can now be studied.


TM4SF19-AS1 facilitates the proliferation of lung squamous cell carcinoma by recruiting WDR5 to mediate TM4SF19.
As reported, long non-coding RNAs are a pivotal player in lung squamous cell carcinoma (LSCC) progression. We noticed the remarkably upregulated transmembrane-4-l-six-family-19 antisense RNA 1 (TM4SF19-AS1) in LSCC and further demonstrated the function it played in LSCC and the possible molecular mechanism. Via bioinformatics approach, we evaluated TM4SF19-AS1 and TM4SF19 levels in LSCC tissue, and real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot revealed their mRNA and protein levels in LSCC cells. Cell Counting Kit-8 and colony formation assays analyzed the proliferation ability of LSCC cells, and cell adhesion ability was detected via cell adhesion assay. RNA immunoprecipitation and chromatin immunoprecipitation analyzed the underlying mechanism of TM4SF19-AS1 regulating its target, while methylation-specific PCR indicated the methylation level of TM4SF19-AS1. TM4SF19-AS1 was markedly upregulated in LSCC. Functional assays revealed that TM4SF19-AS1 could facilitate the proliferation and adhesion of LSCC. Besides, we revealed the mechanism of TM4SF19-AS1 regulation that it directly bound to WD repeat-containing protein 5 (WDR5), and was then recruited to TM4SF19 promoter region, which activated DNA demethylation, thereby suppressing malignant LSCC progression. Our research demonstrated that TM4SF19-AS1 affected LSCC cell proliferation by recruiting WDR5 to manipulate transmembrane-4-lsix-family-member-19 (TM4SF19), which offers a new observation on LSCC pathogenesis, indicating that TM4SF19-AS1 is able to be a promising target for LSCC treatment.


Six-year retrospective study of reconstructive options for defects of the skull base after resection of tumour.
The successful management of tumours that involve the skull base depends on resection and reconstruction of the defect. The challenge is to create a protective vascularised seal between the intracranial contents and the adjacent paranasal sinuses, nasopharynx, and oral cavity. Failure to create a protective barrier for the intracranial contents can result in cerebrospinal fistulas, potentially fatal infections, and radiotherapy being delayed. Local or regional flaps may be adequate for small defects, but larger ones require microsurgical free tissue transfer. As a part of the skull base surgical team, we present our experience in the reconstruction of defects after resection of tumours. A total of 41 patients had operations over a 6-year period from January 2004 to January 2010, and 26 free tissue transfer flaps and 20 local or regional flaps (46 flaps) were used for reconstruction. Ninety-two percent of the free flaps were successful. We also report details on disease, complications, and survival at 3, 6, and 12 months. Survival depended not only on the type of disease, coexisting conditions, and adequate resection of tumour, but equally on the reconstruction of the defect.


British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011.
The British Thoracic Society first published management guidelines for community acquired pneumonia in children in 2002 and covered available evidence to early 2000. These updated guidelines represent a review of new evidence since then and consensus clinical opinion where evidence was not found. This document incorporates material from the 2002 guidelines and supersedes the previous guideline document.


Isolation and characterization of feeding behavior mutants in Drosophila melanogaster.
Feeding behavior mutants of the fruit fly Drosophila melanogaster having point-mutations were isolated. The defects were analyzed in order to study the mechanism of feeding behavior. Point-mutations named febB (three allele) and febA (three allele) were located between the X-chromosome markers cho and cv and between the markers cv and v, respectively. The febB mutants showed a higher acceptance threshold of the proboscis extension reflex than wild-type flies and showed a normal chemosensory response to the electrophysiological test. The mutant (febB2) showed a higher starvation tolerance than the wild-type fly, but this was not a cause of the high acceptance threshold. Mosaic analysis was applied to the mutant. Internal tissues were suspected to be the primary focus of the abnormal behavior.


Increased thorn length in Acacia depranolobium -an induced response to browsing.
I report here longer thorns induced by large mammal herbivory on the tree Acacia depranolobium. I compared trees that had been browsed by domestic goats to trees protected from goat browsing. Thorns on browsed branches within the reach of goats (<125 cm above the ground) were significantly longer than thorns from higher branches on the same browsed trees, and significantly longer than branches at similar heights on unbrowsed trees. It appears that increased thorn length was an induced response to large mammal herbivory in Acacia depranolobium, both among and within individual trees.