Position at birth as an important factor for the occurrence of anal sphincter tears: a retrospective cohort study.
This work aimed to analyze the association between maternal position at birth in spontaneous deliveries and the occurrence of anal sphincter tears (AST) given the lack of evidence related to the least traumatic birth position. A total of 7832 vaginal deliveries were included. Vaginal-operative deliveries and deliveries with fundal pressure were excluded. Birth positions on bed, in water, kneeling, and in a squatting position on a low stool were compared. Birth position on bed was considered as the reference group, and a logistic regression analysis adjusting for important fetomaternal parameters was performed. The overall incidence of AST was 1.1%. AST rate was significantly increased in squatting (2.9%) and kneeling (2.1%) positions compared with birth position on bed (1.0%) or in water (0.9%). Logistic regression analysis revealed a significantly higher risk for ASTs in squatting (OR 2.92, CI 95% 1.04-8.18) and in kneeling positions (OR 2.14, CI 95% 1.05-4.37) compared with the reference group on bed. When adjusting for risk factors, birth in a kneeling position remained significantly associated with ASTs (adj. OR 2.21, CI 95% 1.07-4.54). Birth in squatting or in kneeling position is associated with an elevated risk for ASTs. Birth in water is not associated with an increased risk for AST. Based on the results, women should be informed about the association of certain birth positions with the occurrence of AST.


Expression profiling of rice segregating for drought tolerance QTLs using a rice genome array.
Plants alter their gene expression patterns in response to drought. Sometimes these transcriptional changes are successful adaptations leading to tolerance, while in other instances the plant ultimately fails to adapt to the stress and is labeled as sensitive to that condition. We measured the expression of approximately half of the genes in rice ( approximately 21,000) in phenotypically divergent accessions and their transgressive segregants to associate stress-regulated gene expression changes with quantitative trait loci (QTLs) for osmotic adjustment (OA, a trait associated with drought tolerance). Among the parental lines, a total of 662 transcripts were differentially expressed. Only 12 genes were induced in the low OA parent, CT9993, at moderate dehydration stress levels while over 200 genes were induced in the high OA parent, IR62266. The high and low OA parents had almost entirely different transcriptional responses to dehydration stress suggesting a complete absence of an appropriate response rather than a slower response in CT9993. Sixty-nine genes were up-regulated in all the high OA lines and nine of those genes were not induced in any of the low OA lines. The annotation of four of those genes, sucrose synthase, a pore protein, a heat shock and an LEA protein, suggests a role in maintaining high OA and membrane stability. Of the 3,954-probe sets that correspond to the QTL intervals, very few had a differential expression pattern between the high OA and low OA lines that suggest a role leading to the phenotypic variation. However, several promising candidates were identified for each of the five QTL including a snRNP auxiliary factor, a LEA protein, a protein phosphatase 2C and a Sar1 homolog.


Assessment and management of patients with tibial plateau fractures in emergency departments.
Tibial plateau fractures are complex injuries and relatively common presentations in emergency departments (EDs), yet the diagnosis is not always obvious. Patients with this injury are managed increasingly in EDs by registered advanced nurse practitioners (RANPs), who are recognised in Ireland as senior clinical decision-makers. RANPs are broadening their scope of practice to maximise their responses to current and emerging challenges in healthcare services. They use a range of skills, including taking comprehensive health histories, problem solving, clinical decision-making and using their expert judgement to diagnose and create management plans for patients who attend EDs. In Ireland, RANP is a protected title and practitioners work within an agreed scope of practice, meeting criteria set by the Nursing and Midwifery Board of Ireland to register. RANPs ensure continuity of care, improve the quality of care, provide a quick response to patient care, reduce waiting times and improve flow of patients through EDs. The main scope of RANPs' practice in emergency care includes management of patients with non-life-threatening limb conditions or injures, such as a tibial plateau fracture. This article gives an overview of tibial plateau fractures, including anatomy, and presents a case study to analyse critically the management of a patient with this injury and the care provided by a RANP. In the context of the case study, the article reviews the RANP's diagnostic decisions and the available management options.


Vision and Vision-Related Measures in Progressive Multiple Sclerosis.
Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage independent of ON (optic radiation lesions), make the visual system a prime candidate for such endeavors. However, while the visual system makes for a convenient model in early stages of MS, processes which may be true in those stages may drastically change as the disease progresses, due to accumulated disease load. Here, we examine whether vision-related tools reflect demyelinative and axonal damage of the visual pathways and may be used for assessment in the clinical setup in progressive multiple sclerosis (MS) patients, in whom disease load may alter the early stage picture. Methods: Forty-eight progressive MS patients, with and without prior optic neuritis (ON), underwent a battery of behavioral tests, visual evoked potential (VEP) tests, optical coherence tomography (OCT), and structural MRI scans, at two time-points. Data were analyzed for stability between visits and for correlation between behavioral and electrophysiological data. Results: All measures were stable between visits. Significant differences were found in all measures between the affected and fellow eyes of ON patients and in VEP latencies between the affected and non-ON eyes. Motion perception differentially correlated with latencies of both ON eyes and with the non-ON eyes. Retinal nerve fiber layer thickness correlated with the latencies of non-ON eyes but not of either ON eye. No difference in lesion load was found between the ON and non-ON patients. Conclusions: ON still leaves its mark in the patient's visual system over time, with all visual measures of the affected eyes notably reduced compared to fellow eyes. Motion perception, reflecting myelination level along the visual pathway, shows its usefulness also in progressive MS. In the non-ON eyes, axonal loss appears to explain prolonged latencies, unlike in ON eyes, where demyelination appears to be the main mechanism. Lastly, the visual measures assessed herein are applicable as valid assessment tools in therapeutic studies.


Vestibular implants studied in animal models: clinical and scientific implications.
Damage to the peripheral vestibular system can result in debilitating postural, perceptual, and visual symptoms. A potential new treatment for this clinical problem is to replace some aspects of peripheral vestibular function with an implant that senses head motion and provides this information to the brain by stimulating branches of the vestibular nerve. In this review I consider animal studies performed at our institution over the past 15 years, which have helped elucidate how the brain processes information provided by a vestibular (semicircular canal) implant and how this information could be used to improve the problems experienced by patients with peripheral vestibular damage.


Long-term effects of differential early rearing in rhesus macaques: behavioral reactivity in adulthood.
Adverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP). We tested 22 rhesus monkeys who were either nursery-reared (NR) or reared with their mothers (mother-reared; MR). NR monkeys were inhibited in their behavior compared to MR monkeys, with reduced locomotion and exploratory behaviors. NR animals showed a marginal increase in freezing. Together these findings demonstrate that the consequences of differential infant rearing experience on socioaffective behavior persist into adulthood, with evidence of greater inhibition in NR monkeys.


Monolayer Behavior of NbS2 in Natural van der Waals Heterostructures.
Monolayer transition metal dichalcogenides (TMDs) constitute an important family of materials with many intriguing properties and applications. The ability to achieve large-size and high-quality monolayer TMDs is the key prerequisite toward a deep understanding and practical application of TMDs in electronics and optoelectronics. Here, on the basis of high-resolution angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we find a monolayer NbS2-dominated Fermi-level feature in a misfit compound, which is a type of natural heterostructures. Considering the infrequency of the synthesis approach and electronic properties of the NbS2 monolayer, our results cannot only provide direct insight into the electronic structure of van der Waals heterostructures (VDWHs) but also shed light on the way toward rationally investigating the monolayer TMDs, which are hardly obtained and studied.


Formulation factors affecting acceptability of oral medicines in children.
Acceptability of medicines in children and caregivers affects safety and effectiveness of medicinal treatments. The pharmaceutical industry is required to demonstrate acceptability of new paediatric formulations in target age groups as an integrated part of the development of these products (Kozarewicz, 2014). Two questions arise when trying to tackle this task: "which dosage form to choose for each target age group?" and "how to formulate it once the dosage form is decided?". Inevitably, both the regulator and the developer turn to scientific evidence for answers. Research has emerged in recent years to demonstrate age-appropriateness and patient acceptability of different dosage forms; however, such information is still fragmented and far from satisfactory to define efficient formulation development strategies for a diverse patient subset (Ranmal and Tuleu, 2013). This paper highlights how formulation factors affect the acceptability of different oral medicines in children (Table 1), and it is based on a more extensive review article by Liu et al. (Liu et al., 2014). Gaps in knowledge are highlighted in order to stimulate further research. In some areas, findings from studies conducted in adult populations may provide useful guidance for paediatric development and this is also discussed.


Comparison of laboratory methods for analysis of non-nucleoside reverse transcriptase inhibitor resistance in Ugandan infants.
Detailed comparisons of HIV drug resistance assays are needed to identify the most useful assays for research studies, and to facilitate comparison of results from studies that use different methods. We analyzed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in 40 HIV-infected Ugandan infants who had received nevirapine (NVP)-based prophylaxis using the following assays: an FDA-cleared HIV genotyping assay (the ViroSeq HIV-1 Genotyping System v2.0), a commercially available HIV genotyping assay (GeneSeq HIV), a commercially available HIV phenotyping assay (PhenoSense HIV), and a sensitive point mutation assay (LigAmp). ViroSeq and GeneSeq HIV results (NVP resistance yes/no) were similar for 38 (95%) of 40 samples. In 6 (15%) of 40 samples, GeneSeq HIV detected mutations in minor subpopulations that were not detected by ViroSeq, which identified two additional infants with NVP resistance. LigAmp detected low-level mutations in 12 samples that were not detected by ViroSeq; however, LigAmp testing identified only one additional infant with NVP resistance. GeneSeq HIV and PhenoSense HIV determinations of susceptibility differed for specific NNRTIs in 12 (31%) of the 39 samples containing mixtures at relevant mutation positions. PhenoSense HIV did not detect any infants with NVP resistance who were not identified with GeneSeq HIV testing. In this setting, population sequencing-based methods (ViroSeq and GeneSeq HIV) were the most informative and had concordant results for 95% of the samples. LigAmp was useful for the detection and quantification of minority variants. PhenoSense HIV provided a direct and quantitative measure of NNRTI susceptibility.


Sevoflurane anaesthesia causes a transient decrease in aquaporin-2 and impairment of urine concentration.
Sevoflurane anaesthesia is occasionally associated with polyuria, but the exact mechanism of this phenomenon has not been clarified. Aquaporin-2 (AQP2) is an arginine vasopressin (AVP)-regulated water channel protein localized to the apical region of renal collecting duct cells and is involved in the regulation of water permeability. To elucidate the effect of sevoflurane anaesthesia on urine concentration and AQP2, we have compared serum and urinary concentrations of AVP, AQP2 and osmolar changes during sevoflurane and propofol anaesthesia. General anaesthesia was induced with sevoflurane or propofol in 30 patients for a variety of major surgical procedures. Blood and urine samples were obtained from patients at baseline, and 90 and 180 min after induction of anaesthesia. AVP and AQP2 concentrations were measured by radioimmunoassay. In both groups, plasma and urinary concentrations of AVP increased similarly during anaesthesia although plasma osmolality remained unchanged. Although urinary AQP2 excretion in the propofol group increased together with changes in plasma and urinary AVP, urinary AQP2 was significantly lower at 90 min in the sevoflurane group. Urine osmolality in the sevoflurane group also showed a transient but significant decrease in parallel with suppression of AQP2. Our data suggest that sevoflurane anaesthesia transiently produced an impaired AQP2 response to an increase in intrinsic AVP.


Measurement of refractive index by nanoparticle tracking analysis reveals heterogeneity in extracellular vesicles.
Optical techniques are routinely used to size and count extracellular vesicles (EV). For comparison of data from different methods and laboratories, suitable calibrators are essential. A suitable calibrator must have a refractive index (RI) as close to that of EV as possible but the RI of EV is currently unknown. To measure EV, RI requires accurate knowledge of size and light scattering. These are difficult to measure as most EVs cannot be resolved by light microscopy and their diameter is smaller than the wavelength of visible light. However, nanoparticle tracking analysis (NTA) provides both size and relative light scattering intensity (rLSI) values. We therefore sought to determine whether it was possible to use NTA to measure the RI of individual EVs. NTA was used to measure the rLSI and size of polystyrene and silica microspheres of known size and RI (1.470 and 1.633, respectively) and of EV isolated from a wide range of cells. We developed software, based on Mie scattering code, to calculate particle RI from the rLSI data. This modelled theoretical scattering intensities for polystyrene and silica microspheres of known size (100 and 200 nm) and RI. The model was verified using data from the polystyrene and silica microspheres. Size and rLSI data for each vesicle were processed by the software to generate RI values. The following modal RI measurements were obtained: fresh urinary EV 1.374, lyophilised urinary EV 1.367, neuroblastoma EV 1.393, blood EV 1.398, EV from activated platelets 1.390, small placental EV 1.364-1.375 and 1.398-1.414 for large placental EV (>200 nm). Large placental EV had a significantly higher RI than small placental EV (p<0.0001). The spread of RI values was narrower for small EV than for the more heterogeneous large EV. Using NTA and Mie scattering theory, we have demonstrated that it is possible to estimate the RI of sub-micron EV using NTA data. EV typically had a modal RI of 1.37-1.39, whereas values of >1.40 were observed for some large (>200 nm) microvesicles. This method for measuring EV RI will be useful for developing appropriate calibrators for EV measurement.


Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion.
Interleukin-1 (IL-1), an inflammatory/immune mediator, acts directly and selectively on cultured human vascular endothelial cells to alter two important functional properties. First, IL-1 induces endothelial cell biosynthesis and surface expression of a tissue factor-like procoagulant activity. Second, IL-1 dramatically increases the adhesiveness of the endothelial cell surface for human peripheral blood polymorphonuclear leukocytes (6-42-fold increase) and monocytes (2-5-fold increase), as well as the related leukocyte cell lines HL-60 and U937. These IL-1 effects are concentration-dependent (maximum, 5-10 U/ml), time-dependent (peak 4-6 hours), and reversible. Cycloheximide and actinomycin D block these IL-1 actions on endothelium, which suggests the requirement for de novo protein synthesis. Human-monocyte-derived IL-1, cell-line--derived IL-1, and recombinant IL-1 exhibited comparable biologic activities in our assays, whereas two other mediators, IL-2 and immune interferon, were without effect. IL-1 stimulated procoagulant activity and leukocyte adhesion in human endothelial cells cultured from both umbilical veins and adult saphenous veins but not in other cultured cell types, including SV-40-transformed human endothelial cells and human dermal fibroblasts. Similar actions of IL-1 on vascular endothelium in vivo may contribute to the development of intravascular coagulation and enhanced leukocyte--vessel wall adhesion at sites of inflammation.


Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand.
AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.


Decision-making impairments in women with binge eating disorder.
Even though eating is frequently driven by overindulgence and reward rather than by energy balance, few studies so far have analyzed decision-making processes and disturbances in feedback processing in women with binge eating disorder (BED). In an experimental study, 17 women with BED (DSM-IV) and 18 overweight healthy controls (HC) were compared in the game of dice task (GDT). This task assesses decision-making under risk with explicit rules for gains and losses. Additionally, differences in dispositional activation of the behavior inhibition and behavior approach system as well as cognitive flexibility were measured. Main results revealed that women with BED make risky decisions significantly more often than HC. Moreover, they show impaired capacities to advantageously utilize feedback processing. Even though these deficits were not related to disease-specific variables, they may be important for the daily decision-making behavior of women with BED, thus being relevant as a maintenance factor for the disorder.


Social media and the birth of an Islamic social movement: ODOJ (One Day One Juz) in contemporary Indonesia.
The Indonesian democratic transition, which occurred after the collapse of the New Order, was a significant moment that enabled diverse Islamic groups to use media for their own interests. However, little has been discussed regarding the use of media in dakwah (Islamic proselytising) performed by Muslim activists who are not inclined to participate in radical activities. This article focuses on the use of social media in dakwah by One Day One Juz (ODOJ), which endeavours to encourage Muslims to revive the spirit of reading the Qur'an through the mobile application WhatsApp. Given that ODOJ has successfully recruited more than 140,000 followers in Indonesia and abroad, this article investigates the key actors of ODOJ and the extent to which it has mobilised religious sentiments among Muslims from diverse affiliations. It argues that WhatsApp has enabled the birth of a semi-virtual Qur'anic movement, which is rooted in the Tarbiyah movement. Unlike well established Islamic movements in Indonesia that harness global computer networks to strengthen their influence, ODOJ has been dependant on technology since its inception. It demonstrates the capacity of technology in generating and crafting this new semi-virtual socio-religious movement. ODOJ has painted new colour onto the contemporary Islamic public and its presence is imperative to understanding the transformation of the religious media-scape in Indonesia.


Novel expression patterns of PI3K/Akt/mTOR signaling pathway components in colorectal cancer.
The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway plays a critical role in the growth and progression of colorectal cancer (CRC). The purpose of our study was 2-fold: (1) to determine the expression levels of several key components of this pathway, including p85alpha, Akt1, Akt2, p-mTOR(Ser2448), and p-p70S6K(Thr389) in CRCs; and (2) to correlate the expression of these proteins with cancer stage and location (left versus right side). Immunohistochemistry for p85alpha, Akt1, Akt2, p-mTOR(Ser2448), and p-p70S6K(Thr389) was performed on normal colon and CRCs from 154 patients. All proteins investigated were significantly overexpressed in CRCs compared with matched normal colonic tissue from the same patient (p < 0.0001). PI3K pathway component proteins were moderately correlated across normal and malignant colon tissues; correlations tended to be stronger in normal tissues as compared with the same correlations in cancers. Expression levels of p85alpha were significantly higher in stage IV cancers than in stage I to III cancers (p = 0.0005). p85alpha expression was also significantly increased in the adjacent normal colonic mucosa of patients with stage IV CRC compared with earlier stages (p = 0.003). Finally, expression of Akt1, Akt2, and p-p70S6K(Thr389) was higher in left-sided CRCs compared with CRCs in the right colon (p = 0.007, p = 0.0008, and p = 0.04, respectively). The PI3K/Akt/mTOR pathway components, p85alpha, Akt1, Akt2, p-mTOR(Ser2448), and p-p70S6K(Thr389) are highly overexpressed in CRCs, providing the rationale for targeting this pathway therapeutically in CRC patients. The increased expression of p85alpha in the adjacent normal mucosa of stage IV patients suggests an important field defect, which may contribute to the growth and progression of these cancers.


Stem cells as the root of pancreatic ductal adenocarcinoma.
Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulations that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.


Mania in the elderly.
A retrospective study of 92 patients admitted with mania, aged over 65 years of age, found that 26% had no prior history of affective illness; 30% had previously only experienced depression, and half of these had at least three episodes of depression before the first manic illness. Patients with a family history of affective disorders had a significantly earlier age of onset of illness. There was evidence of cerebral organic impairment in 24% of the patients, and this group had a significantly later age of onset of illness. Prognosis was good, with only 8% still in hospital at six months. Half of the patients were started on lithium prophylaxis, but this did not significantly alter the number of readmissions. A quarter of those started on lithium developed evidence of lithium toxicity.


Comprehensive two-dimensional liquid chromatographic analysis of rooibos (Aspalathus linearis) phenolics.
Rooibos tea is an unique beverage prepared from unfermented and fermented plant material of the endemic Cape fynbos plant, Aspalathus linearis. The well-known health-promoting benefits of rooibos are partly attributed to its phenolic composition. Detailed investigation of the minor phenolic constituents of rooibos is, however, hampered by the limitations associated with conventional HPLC methods used for its analysis. In this study, the applicability of comprehensive two-dimensional liquid chromatographic methods for the in-depth analysis of rooibos phenolics was investigated. Phenolic compounds were separated according to polarity by hydrophilic interaction chromatography (HILIC) in the first dimension, whilst reversed-phase liquid chromatography (RP-LC) provided separation according to hydrophobicity in the second dimension. Ultraviolet photodiode array and electrospray ionisation mass spectrometry were used to identify phenolic compounds. Comprehensive HILIC × RP-LC demonstrated its applicability for the analysis of a diverse range of phenolic compounds in unfermented and fermented rooibos samples, in which large qualitative differences in the phenolic composition were established. The combination of these orthogonal separations provided a significant improvement in resolution, as exemplified by practical peak capacities in excess of 2000 and 500 for off-line and on-line methods, respectively.


Measuring Biodiversity and Extinction-Present and Past.
How biodiversity is changing in our time represents a major concern for all organismal biologists. Anthropogenic changes to our planet are decreasing species diversity through the negative effects of pollution, habitat destruction, direct extirpation of species, and climate change. But major biotic changes-including those that have both increased and decreased species diversity-have happened before in Earth's history. Biodiversity dynamics in past eras provide important context to understand ecological responses to current environmental change. The work of assessing biodiversity is woven into ecology, environmental science, conservation, paleontology, phylogenetics, evolutionary and developmental biology, and many other disciplines; yet, the absolute foundation of how we measure species diversity depends on taxonomy and systematics. The aspiration of this symposium, and complementary contributed talks, was to promote better understanding of our common goals and encourage future interdisciplinary discussion of biodiversity dynamics. The contributions in this collection of papers bring together a diverse group of speakers to confront several important themes. How can biologists best respond to the urgent need to identify and conserve diversity? How can we better communicate the nature of species across scientific disciplines? Where are the major gaps in knowledge about the diversity of living animal and plant groups, and what are the implications for understanding potential diversity loss? How can we effectively use the fossil record of past diversity and extinction to understand current biodiversity loss?


Are first rib fractures a marker for other life-threatening injuries in patients with major trauma? A cohort study of patients on the UK Trauma Audit and Research Network database.
First rib fractures are considered indicators of increased morbidity and mortality in major trauma. However, this has not been definitively proven. With an increased use of CT and the potential increase in detection of first rib fractures, re-evaluation of these injuries as a marker for life-threatening injuries is warranted. Patients sustaining rib fractures between January 2012 and December 2013 were investigated using data from the UK Trauma Audit and Research Network. The prevalence of life-threatening injuries was compared in patients with first rib fractures and those with other rib fractures. Multivariate logistic regression was performed to determine the association between first rib fractures, injury severity, polytrauma and mortality. There were 1683 patients with first rib fractures and 8369 with fractures of other ribs. Life-threatening intrathoracic and extrathoracic injuries were more likely in patients with first rib fractures. The presence of first rib fractures was a significant predictor of injury severity (Injury Severity Score >15) and polytrauma, independent of mechanism of injury, age and gender with an adjusted OR of 2.64 (95% CI 2.33 to 3.00) and 2.01 (95% CI 1.80 to 2.25), respectively. Risk-adjusted mortality was the same in patients with first rib fractures and those with other rib fractures (adjusted OR 0.97, 95% CI 0.79 to 1.19). First rib fractures are a marker of life-threatening injuries in major trauma, though they do not independently increase mortality. Management of patients with first rib fractures should focus on identification and treatment of associated life-threatening injuries.


Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation.
NO, produced from l-arginine in a reaction catalyzed by NO synthase, is an endogenous free radical with multiple functions in mammalian cells. Here, we demonstrate that endogenously produced NO can suppress c-Jun N-terminal kinase (JNK) activation in intact cells. Treatment of BV-2 murine microglial cells with IFN-gamma induced endogenous NO production, concomitantly suppressing JNK1 activation. Similarly, IFN-gamma induced suppression of JNK1 activation in RAW264.7 murine macrophage cells and rat alveolar macrophages. The IFN-gamma-induced suppression of JNK1 activation in BV-2, RAW264.7, or rat alveolar macrophage cells was completely prevented by N(G)-nitro-l-arginine, a NO synthase inhibitor. Interestingly, the IFN-gamma-induced suppression of JNK1 activation was not affected by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylyl cyclase. 8-Bromo-cGMP, a membrane-permeant analogue of cGMP, did not change JNK1 activation in intact cells either. In contrast, S-nitro-N-acetyl-dl-penicillamine (SNAP), a NO donor, inhibited JNK1 activity in vitro. Furthermore, a thiol reducing agent, DTT, reversed not only the in vitro inhibition of JNK1 activity by SNAP but also the in vivo suppression of JNK1 activity by IFN-gamma. Substitution of serine for cysteine-116 in JNK1 abolished the inhibitory effect of IFN-gamma or SNAP on JNK1 activity in vivo or in vitro, respectively. Moreover, IFN-gamma enhanced endogenous S-nitrosylation of JNK1 in RAW264.7 cells. Collectively, our data suggest that endogenous NO mediates the IFN-gamma-induced suppression of JNK1 activation in macrophage cells by means of a thiol-redox mechanism.


Probabilistic linkage in household survey on hospital care usage.
To evaluate the potential advantages and limitations of the use of the Brazilian hospital admission authorization forms database and the probabilistic record linkage methodology for the validation of reported utilization of hospital care services in household surveys. A total of 2,288 households interviews were conducted in the county of Duque de Caxias, Brazil. Information on the occurrence of at least one hospital admission in the year preceding the interview was obtained from a total of 10,733 household members. The 130 records of household members who reported at least one hospital admission in a public hospital were linked to a hospital database with 801,587 records, using an automatic probabilistic approach combined with an extensive clerical review. Seventy-four (57%) of the 130 household members were identified in the hospital database. Yet only 60 subjects (46%) showed a record of hospitalization in the hospital database in the study period. Hospital admissions due to a surgery procedure were significantly more likely to have been identified in the hospital database. The low level of concordance seen in the study can be explained by the following factors: errors in the linkage process; a telescoping effect; and an incomplete record in the hospital database. The use of hospital administrative databases and probabilistic linkage methodology may represent a methodological alternative for the validation of reported utilization of health care services, but some strategies should be employed in order to minimize the problems related to the use of this methodology in non-ideal conditions. Ideally, a single identifier, such as a personal health insurance number, and the universal coverage of the database would be desirable.


Fast serial analysis of active cholesterol at the plasma membrane in single cells.
Previously, our group has utilized the luminol electrochemiluminescence to analyze the active cholesterol at the plasma membrane in single cells by the exposure of one cell to a photomultiplier tube (PMT) through a pinhole. In this paper, fast analysis of active cholesterol at the plasma membrane in single cells was achieved by a multimicroelectrode array without the pinhole. Single cells were directly located on the microelectrodes using cell-sized microwell traps. A cycle of voltage was applied on the microelectrodes sequentially to induce a peak of luminescence from each microelectrode for the serial measurement of active membrane cholesterol. A minimal time of 1.60 s was determined for the analysis of one cell. The simulation and the experimental data exhibited a semisteady-state distribution of hydrogen peroxide on the microelectrode after the reaction of cholesterol oxidase with the membrane cholesterol, which supported the relative accuracy of the serial analysis. An eight-microelectrode array was demonstrated to analyze eight single cells in 22 s serially, including the channel switching time. The results from 64 single cells either activated by low ion strength buffer or the inhibition of intracellular acyl-coA/cholesterol acyltransferase (ACAT) revealed that most of the cells analyzed had the similar active membrane cholesterol, while few cells had more active cholesterol resulting in the cellular heterogeneity. The fast single-cell analysis platform developed will be potentially useful for the analysis of more molecules in single cells using proper oxidases.


Synthesis and antimicrobial activities of some new nitroimidazole derivatives.
In this study, some new nitroimidazole derivatives were obtained from 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylamine dihydrochloride (4) and 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (5), which were prepared using metronidazole. Compound 4 was reacted with arylisothiocyanates (6) to obtain 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-arylthioureas (7) and the latter with alpha-bromoacetophenones (8) to give 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-arylimino-4-aryl-4-thiazolines (9). Also 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-phenyl-4-arylideneimidazolin-5-ones (11) were prepared by reaction of 4 with 2-phenyl-4-arylidene-5-oxazolones (10). The reaction of the other starting material 5 with 5-arylidenethiazolidin-2,4-dione (12) gave 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-5-arylidenethiazolidin-2,4-dione (13) derivatives. Structural elucidation of the compounds was performed by IR, 1H-NMR and MASS spectroscopic data and elemental analysis results. Antimicrobial activities of the compounds were examined and moderate activity was obtained.


Neurophysiologic effects at low level 1.8 GHz radiofrequency field exposure: a multiparametric approach on freely moving rats.
Deleterious effects on healthcare and particularly disruption of the cholinergic system have been reported after exposure to radiofrequency field at low power density. This work presents a 72 hours multiparametric study, where cholinergic system was investigated using a neurochemical, electrophysiological and physiological approaches. Free moving rats were exposed 24 hours to RF GSM signal at 1.8 GHz at low power density (1.2 and 9 W/m(2)). Acetylcholine (ACh) release in the hippocampus was simultaneously monitored using the microdialysis technique, electroencephalogram (EEG), electromyogram (EMG) and subcutaneous temperature. A spectral analysis of EEG was also performed and sleep stages were determined. After experimental time, the animals were sacrificed and a NMR study was performed on lipid brain extract. No significant parameters modification was observed under RF exposure. The only significant difference was the lack of increase in time spent in REM sleep, the third day, for the 1.2 W/m(2) group. This observation appeared difficult to explain and could not be reasonably related with RF exposure. Similarly, the NMR study also failed to show any effect of RF.


Chimpanzee adenoviral vectors as vaccines for outbreak pathogens.
The 2014-15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS.


The Thatcher illusion in humans and monkeys.
Primates possess the remarkable ability to differentiate faces of group members and to extract relevant information about the individual directly from the face. Recognition of conspecific faces is achieved by means of holistic processing, i.e. the processing of the face as an unparsed, perceptual whole, rather than as the collection of independent features (part-based processing). The most striking example of holistic processing is the Thatcher illusion. Local changes in facial features are hardly noticeable when the whole face is inverted (rotated 180 degrees ), but strikingly grotesque when the face is upright. This effect can be explained by a lack of processing capabilities for locally rotated facial features when the face is turned upside down. Recently, a Thatcher illusion was described in the macaque monkey analogous to that known from human investigations. Using a habituation paradigm combined with eye tracking, we address the critical follow-up questions raised in the aforementioned study to show the Thatcher illusion as a function of the observer's species (humans and macaques), the stimulus' species (humans and macaques) and the level of perceptual expertise (novice, expert).


Remission in Rheumatoid Arthritis: Working Toward Incorporation of the Patient Perspective at OMERACT 12.
The treatment of rheumatoid arthritis (RA) should target patient-relevant outcomes, making patient perspective on remission essential. In 2010, patients, physicians, health professionals, and researchers at the Outcome Measures in Rheumatology (OMERACT) conference developed an ambitious research agenda to study the concept of remission. Qualitative research has since helped us understand the concept of remission from the patient perspective. During OMERACT 12, the OMERACT working group on patient perspective on remission in RA elaborated on data generated to date and discussed the methodological challenges ahead. Challenges included (1) selection of domains, (2) choice of a patient remission definition or a single domain to add to the current remission definition, and (3) the importance of pain in defining remission from a patient perspective. Focus in the coming years will be on increasing our understanding by identifying the most important domains from the patient perspective regarding remission and investigating how these domains can be measured. Investigation into the Rheumatoid Arthritis Impact of Disease questionnaire, disease flare, as well as the concordance of domains from our ongoing remission survey is appropriate. More data and further discussions are needed to decide on the next steps. Progress summarized over 4 years highlights the main methodological challenges discussed within the working group on patient perspective on remission in RA during OMERACT 12.


Core-satellite populations and seasonality of water meter biofilms in a metropolitan drinking water distribution system.
Drinking water distribution systems (DWDSs) harbor the microorganisms in biofilms and suspended communities, yet the diversity and spatiotemporal distribution have been studied mainly in the suspended communities. This study examined the diversity of biofilms in an urban DWDS, its relationship with suspended communities and its dynamics. The studied DWDS in Urbana, Illinois received conventionally treated and disinfected water sourced from the groundwater. Over a 2-year span, biomass were sampled from household water meters (n=213) and tap water (n=20) to represent biofilm and suspended communities, respectively. A positive correlation between operational taxonomic unit (OTU) abundance and occupancy was observed. Examined under a 'core-satellite' model, the biofilm community comprised 31 core populations that encompassed 76.7% of total 16 S rRNA gene pyrosequences. The biofilm communities shared with the suspended community highly abundant and prevalent OTUs, which related to methano-/methylotrophs (i.e., Methylophilaceae and Methylococcaceae) and aerobic heterotrophs (Sphingomonadaceae and Comamonadaceae), yet differed by specific core populations and lower diversity and evenness. Multivariate tests indicated seasonality as the main contributor to community structure variation. This pattern was resilient to annual change and correlated to the cyclic fluctuations of core populations. The findings of a distinctive biofilm community assemblage and methano-/methyltrophic primary production provide critical insights for developing more targeted water quality monitoring programs and treatment strategies for groundwater-sourced drinking water systems.


In vitro growth inhibition of human small cell lung cancer by physalaemin.
Production and secretion of neuroendocrine peptides by small cell lung cancer (SCLC) has been detected in the past years. Most recently the role of bombesin as an autocrine/paracrine growth modifier has been demonstrated. We used the soft agarose clonogenic assay to evaluate the influence of other neuroendocrine peptides on the in vitro proliferation of SCLC cell lines. Neuroendocrine peptides tested were adrenocorticotropic hormone, arginine vasopressin, calcitonin, glucagon, kassinin, neurotensin, physalaemin, somatostatin, and substance P. Experiments were carried out in serum-free and serum-supplemented media with and without serum-free incubation periods. Our results indicated that the amphibian undecapeptide physalaemin inhibits the clonal and mass culture growth of SCLC cell lines at picomolar concentrations. All other neuroendocrine peptides failed to influence SCLC growth in the test systems used. These results suggest a growth regulating effect of physalaemin and a potential new form of neuroendocrine peptide therapy for SCLC.


Genome Sequencing and analyses of Two Marine Fungi from the North Sea Unraveled a Plethora of Novel Biosynthetic Gene Clusters.
Marine Fungi are potent secondary metabolite producers. However, limited genetic information are available their biosynthetic gene clusters (BGCs) and their biotechnological applications. To overcome this lack of information, herein, we used next-generation sequencing methods for genome sequencing of two marine fungi, isolated from the German Wadden Sea, namely Calcarisporium sp. KF525 and Pestalotiopsis sp. KF079. The assembled genome size of the marine isolate Calcarisporium sp. KF525 is about 36.8 Mb with 60 BGCs, while Pestalotiopsis sp. KF079 has a genome size of 47.5 Mb harboring 67 BGCs. Of all BGCs, 98% and 97% are novel clusters of Calcarisporium sp. and Pestalotiopsis sp., respectively. Only few of the BGCs were found to be expressed under laboratory conditions by RNA-seq analysis. The vast majority of all BGCs were found to be novel and unique for these two marine fungi. Along with a description of the identified gene clusters, we furthermore present important genomic features and life-style properties of these two fungi. The two novel fungal genomes provide a plethora of new BGCs, which may have biotechnological applications in the future, for example as novel drugs. The genomic characterizations will provide assistance in future genetics and genomic analyses of marine fungi.


Long-Term Experience With Reduction Technique in High-Grade Spondylolisthesis in the Young.
Surgical management of high-grade spondylolisthesis in the young is not only challenging but also controversial, from in-situ fusion to complete reduction. It is fraught with dangers such as neurological injury, pseudoarthrosis, and progressive deformity with subsequent global sagittal imbalance. We describe our experience of progressive reduction technique and restoration of lumbosacral alignment. This study is a retrospective review of patients who underwent surgery between 1998 and 2012. The surgical technique involved positioning the hips in extension with traction, pedicle screw fixation, correction of lumbosacral kyphosis with a specific distraction maneuver, wide decompression, and gradual reduction of the deformity and maintenance of reduction with interbody fusion. All patients were serially assessed at 1, 3, and 6 months and yearly thereafter with clinical, radiological, and Oswestry Disability Index and Visual Analogue Scale outcome measures. Twenty-seven patients with high-grade spondylolisthesis at L5-S1 (3 cases grade 3, 7 grade 4, 17 grade 5) with an average age of 13.9 years were reviewed. Mean follow-up was 120 months (range 24-192). All patients presented a solid fusion at the 6-month visit; mean slip percentage was reduced from 89% to 23%, with all cases reduced to grade 2 or less. The slip angle improved from 45° to 3° postoperatively, with improvement in sacral slope from 13° to 35°. Four spondyloptosis patients had concomitant scoliosis which corrected spontaneously after the surgery and did not need further intervention. All but one patient (96.2%) had good functional outcomes and returned to their full normal activities. One patient developed a deep infection necessitating implant removal, with eventual deformity progression leading to a poor outcome. Three patients (11.1%) suffered partial drop foot that resolved in full by 12 weeks. Our technique demonstrated a significant reduction of high grade spondylolisthesis, with restoration of global sagittal balance via correction of the lumbosacral kyphosis. Though surgically demanding, it is safe and reproducible. IV.


CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites.
Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIghi macrophages differed between patients and in the same patient over time, and a high proportion of CRIghi macrophages was associated with reduced disease severity (model for end-stage liver disease) score. As compared with CRIglo macrophages, CRIghi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities among CRIghi cells, human macrophages, and mouse F4/80hi resident peritoneal macrophages and among CRIglo macrophages, human monocytes, and mouse F4/80lo monocyte-derived peritoneal macrophages. These data suggest that CRIghi and CRIglo macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable among patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.


Effect of Ocimum sanctum Linn. on normal and dexamethasone suppressed wound healing.
Ethanolic extract of leaves of O. sanctum was investigated for normal wound healing and dexamethasone depressed healing using incision, excision and dead space wound models in albino rats. The extract of O. sanctum significantly increased the wound breaking strength in incision wound model. The extract treated wounds were found to epithelialize faster and the rate of wound contraction was significantly increased as compared to control wounds. Significant increase in wet and dry granulation tissue weight, granulation tissue breaking strength and hydroxyproline content in dead space wound model was observed. The extract significantly decreased the antihealing activities of dexamethasone in all the wound models. The results indicated that the leaf extract promotes wound healing significantly and able to overcome the wound healing suppressing action of dexamethasone. Histological examination of granulation tissue to determine the pattern of lay-down for collagen confirmed the results.


Automated computer evaluation and optimization of image compression of x-ray coronary angiograms for signal known exactly detection tasks.
We compared the ability of three model observers (nonprewhitening matched filter with an eye filter, Hotelling and channelized Hotelling) in predicting the effect of JPEG and wavelet-Crewcode image compression on human visual detection of a simulated lesion in single frame digital x-ray coronary angiograms. All three model observers predicted the JPEG superiority present in human performance, although the nonprewhitening matched filter with an eye filter (NPWE) and the channelized Hotelling models were better predictors than the Hotelling model. The commonly used root mean square error and related peak signal to noise ratio metrics incorrectly predicted a JPEG inferiority. A particular image discrimination/perceptual difference model correctly predicted a JPEG advantage at low compression ratios but incorrectly predicted a JPEG inferiority at high compression ratios. In the second part of the paper, the NPWE model was used to perform automated simulated annealing optimization of the quantization matrix of the JPEG algorithm at 25:1 compression ratio. A subsequent psychophysical study resulted in improved human detection performance for images compressed with the NPWE optimized quantization matrix over the JPEG default quantization matrix. Together, our results show how model observers can be successfully used to perform automated evaluation and optimization of diagnostic performance in clinically relevant visual tasks using real anatomic backgrounds.


Driving restrictions post-stroke: Physicians' compliance with regulations.
Suffering a stroke might lead to permanent cognitive and/or physical impairment. It has been shown that these impairments could have an impact on an individual's fitness to drive. In Sweden, as in many other countries, there are regulations on driving cessation post-stroke. Information on driving cessation should be given to all patients and noted in the journal. The present study sought to determine physician's compliance to driving regulations post-stroke as well as follow-up and gender aspects. A retrospective study of medical records on stroke patients was carried out. The study covered all of the medical records on stroke incidents (n = 342) during a year at a typical medium to large-sized hospital in Sweden. A journal entry on driving cessation post-stroke was missing in 81% of the medical records. Only 2% of the patients were scheduled for a follow-up meeting specifically concerning fitness to drive. Significantly more men than women had an entry on driving in the journal. We conclude that the Swedish regulations on driving cessation post-stroke were not followed at the participating hospital. It is crucial that all stroke patients receive information on driving cessation because their condition might affect fitness to drive. Analysis of follow-up records showed that there was no consistent method for assessment of a patient's fitness to drive. There was also a gender difference in the material, which warrants further investigation.


GenoBase: comprehensive resource database of Escherichia coli K-12.
Comprehensive experimental resources, such as ORFeome clone libraries and deletion mutant collections, are fundamental tools for elucidation of gene function. Data sets by omics analysis using these resources provide key information for functional analysis, modeling and simulation both in individual and systematic approaches. With the long-term goal of complete understanding of a cell, we have over the past decade created a variety of clone and mutant sets for functional genomics studies of Escherichia coli K-12. We have made these experimental resources freely available to the academic community worldwide. Accordingly, these resources have now been used in numerous investigations of a multitude of cell processes. Quality control is extremely important for evaluating results generated by these resources. Because the annotation has been changed since 2005, which we originally used for the construction, we have updated these genomic resources accordingly. Here, we describe GenoBase (http://ecoli.naist.jp/GB/), which contains key information about comprehensive experimental resources of E. coli K-12, their quality control and several omics data sets generated using these resources.


Anxiolytic and sedative activities of Passiflora edulis f. flavicarpa.
Many plants in the genus Passiflora have long been used in traditional folk medicines as a remedy for many neurogenic diseases in many countries. A number of species of the genus was studied about their neuropharmacological activities, but the results were inconsistent. No literature reported neuropharmacological studies on Passiflora edulis f. flavicarpa as yet. The present study was aimed at evaluating the anxiolytic and sedative activities of Passiflora edulis f. flavicarpa. Swiss albino mice were used as experimental animals in elevated plus-maze (EPM) test and spontaneous activity (SA) test to assay the behavioral effects of ethanolic extract (EE) of the aerial part of Passiflora edulis f. flavicarpa and its fractions, viz. petrol ether extract (PEE), ethyl acetate extract (EAE), n-BuOH extract (BE) and aqueous extract (AE), together with subfractions of BE, viz. BEF-I, BEF-II, BEF-III, BEF-IV and isoorientin, a flavonoid component isolated from BEF-III. In the EPM test, single-dose oral administration of EE (300 mg/kg and 400mg/kg), BE (125 mg/kg and 200mg/kg), AE (200mg/kg and 300 mg/kg), BEF-I (200mg/kg), BEF-II (200mg/kg), BEF-III (100mg/kg), or isoorientin (20mg/kg) resulted in anxiolytic-like effects, but a sedative-like activity was produced at higher doses, such as 300 mg/kg of BE, 200mg/kg of BEF-III, or 40 mg/kg and 80 mg/kg of isoorientin. The results of the SA test manifested that treatment with 400mg/kg of EE, 300 mg/kg of BE, or 40 mg/kg and 80 mg/kg of isoorientin compromised motor activity in mice, which are in line with the results of the EPM test. The aerial part of Passiflora edulis f. flavicarpa was anxiolytic at low dose but sedative at high dose. Flavonoids are important active constituents. Since AE contained little flavonoids, it was conjectured that there were other components responsible for the anxiolytic effect of Passiflora edulis f. flavicarpa besides flavonoids.


How action influences object perception.
Although object perception is typically associated with the parvocellular (P) pathway, a form of fast "gist" object perception may be due to activity in the magnocellular (M) pathway (Kveraga et al., 2007). Because the M-pathway is typically associated with action, we hypothesized that manipulations of action would influence speeded object perception. In three experiments, participants indicated whether the objects shown in low and high spatial frequency (HSF) images were larger or smaller than a prototypical shoebox. In Experiment 1, participants used a proximal (hands on monitor) or distal (hands on keyboard) hand posture in separate blocks. In Experiment 2, only the proximal hand posture was used, but the hands were either action oriented with palms in (palms toward the stimuli) or non-action oriented with palms out (palms away from the stimuli). In Experiment 3, we used the palms-in proximal hand posture but manipulated the type of visual stimuli such that they were either action oriented (easily grasped) or non-action oriented (not easily grasped). In all three experiments, the advantage in identifying the low spatial frequency (LSF) images was greater when action was primed (proximal hands, palms-in, graspable). Together, these experiments show that the M-pathway is involved in rapid "gist" object perception, and this type of object perception is influenced by action.


Iron oxide nanoparticles for targeted imaging of liver tumors with ultralow hepatotoxicity.
Even though iron oxide (Fe3O4) nanoparticles are promising materials for magnetic resonance imaging (MRI) contrast agents, their biocompatibility and targeting efficacy still need to be improved. Herein, we modified glycyrrhetinic acid (GA) groups on Fe3O4 nanoparticles (Fe3O4@cGlu-GA) for liver tumor-targeted imaging. To evaluate the biocompatibility of these nanoparticles, we studied their cytotoxicity, hemolysis, and hepatotoxicity. We measured the uptake of Fe3O4@cGlu-GA nanoparticles in normal and liver tumor cells, then we investigated the specificity of Fe3O4@cGlu-GA nanoparticles in mouse models bearing subcutaneous and orthotopic liver tumors. With good biocompatibility and targeting efficacy both in vitro and in vivo, the Fe3O4@cGlu-GA nanoparticles are promising MRI contrast agents with ultralow hepatotoxicity and show great improvement on existing Fe3O4-based nanoparticles.


Adenovirus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor (SR-AI) in LDL receptor knock-out mice.
Macrophage scavenger receptors (MSR) play an important role in the pathogenesis of atherosclerosis. Therefore, modulation of MSR activity could have a beneficial effect on atherogenesis. One way to antagonize the function of a cell surface scavenger receptor is to use a soluble decoy receptor. We have constructed a soluble, chimaeric fusion protein that consists of the bovine growth hormone signal sequence and the human MSR AI extracellular domains. This secreted decoy MSR (sMSR) was cloned into an adenoviral vector and the recombinant adenoviruses were used for gene transfer experiments in vivo. We have previously shown that the secreted MSR inhibits degradation of acetylated LDL and oxidized LDL in mouse macrophages and reduces foam cell formation in vitro. We now report that in comparison to LacZ transfected control mice gene transfer with sMSR adenoviruses via tail vein injection (1 x 10(9) pfu) reduces atherosclerotic lesion area in hypercholesterolemic LDL receptor knock-out mice by 14 (P<0.05) and 19% (P=0.01), 4 and 6 weeks after the gene transfer. However, a statistically significant difference in the aortic root atherosclerosis was not detected. This is the first demonstration that the decoy sMSR can affect atherogenesis in mice after recombinant adenovirus-mediated gene transfer. Even though the achieved reduction in atherosclerosis was relatively modest the results suggest that sMSR may offer new strategies for the treatment of atherosclerosis and lipid accumulation in the vessel wall.


Incidence and risk factors for respiratory complications in patients undergoing esophagectomy for malignancy: a NSQIP analysis.
Respiratory complications are the most frequent adverse events in patients undergoing esophagectomy for cancer, and their occurrence may negatively affect postoperative recovery and outcomes. We queried the American College of Surgeons National Surgical Quality Improvement Program dataset to study the rate and influence of pneumonia, unplanned intubation, and ventilator dependency >48 hours on the early outcomes after esophagectomy and risk factors for their development. We included adult patients with an esophageal or gastric cancer diagnosis who were treated with esophagectomy between 2005 and 2012 and grouped them into 2 categories with respect to development of respiratory complications. Early surgical outcomes (including 30-day mortality, overall morbidity, return to operating room, and length of hospital stay) were compared. Risk factors associated with respiratory complications after esophagectomy were assessed using modified Poisson regression. A total of 2945 patients were identified and respiratory complications were observed in 687 (23.3%) of them. We observed a significant decrease in respiratory complication rates after esophagectomy throughout the studied years. Patients who developed respiratory complications were older and had more comorbidities and longer operative time. These patients also had statistically significantly higher rates of 30-day mortality and overall morbidity and were more likely to return to the operating room and to stay in the hospital longer. On multivariable analysis, numerous factors, including advanced age, smoking, alcohol use, dyspnea, history of chronic obstructive pulmonary disease, and prolonged operative time, were found to be risk factors for developing respiratory complications. As the development of respiratory complications leads to worse early surgical outcomes after esophagectomy, efforts should be made to prevent their occurrence by identifying patients with significant risk factors.


Prenatal Diagnosis of Mosaic Tetrasomy 18p in a Case without Sonographic Abnormalities.
Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they cannot be identified or characterized unambiguously by conventional cytogenetics alone. On the other hand, and perhaps more importantly in prenatal settings, there is a challenging situation for counseling how to predict the risk for an abnormal phenotype, especially in cases with a de novo sSMC. Here we report on the prenatal diagnosis of a mosaic tetrasomy 18p due to presence of an sSMC in a fetus without abnormal sonographic signs. For a 26-year-old, gravida 2 (para 1) amniocentesis was done due to consanguineous marriage and concern for Down syndrome, based on borderline risk assessment. Parental karyotypes were normal, indicating a de novo chromosome aberration of the fetus. FISH analysis as well as molecular karyotyping identified the sSMC as an i(18)(pter->q10:q10->pter), compatible with tetrasomy for the mentioned region. Cordocentesis was done due to normal sonography and the results from amniocentesis were confirmed. The parents opted for pregnancy termination and post mortem examination now noted, low anterior hairline, large philtrum, low-set posteriorly rotated malformed ears with prominent antihelix, lower limbs joint contracture and digital anomalies, including long and narrow toes with clinodactyly of the 1st and 5th toes and postaxial polydactyly of one hand. De novo i(18p) can be considered as a special case in the sense that the major relevant phenotypes mentioned for it, i.e. feeding difficulties, abnormalities in muscle tone and developmental/mental retardation, cognitive and behavioral characteristics, recurrent otitis media and seizures, are mostly postnatal. This emphasizes the necessity to determine the nature of a de novo euchromatic marker chromosome, especially in cases with normal ultrasound result and the suitability of a cordocentesis in order to better predicting the pregnancy outcome and parental counseling.


A randomised controlled trial of the effect of educational outreach by community pharmacists on prescribing in UK general practice.
Educational outreach visits are commonly used to promote changes in prescribing in family practice. However, the effectiveness of outreach visits has not been evaluated across a range of settings. To estimate the effectiveness of educational outreach visits on United Kingdom (UK) general practice prescribing and to examine the extent to which practice characteristics influenced outcome. Randomised controlled trial. General practices in 12 health authorities in England. Educational outreach visits were made to practices that received two of four guidelines. Each practice provided data on treatment of patients for all four guidelines for both pre and post-intervention periods. The primary outcome is average effect across all four guidelines. Secondary analyses examined the predictive effect of practice and guideline characteristics. Seventy per cent of practices approached agreed to take part in the intervention. Overall, educational outreach was associated with a significant improvement in prescribing practice (odds ratio [OR] = 1.24 [95% CI = 1.07 to 1.42]), a 5.2% (95% CI = 1.7% to 8.7%) increase in the number of patients treated within the guideline recommendations. Smaller practices (two or fewer full-time equivalent practitioners) responded much more favourably to educational outreach than larger practices. Smaller practices improved their performance in line with the guidelines by 13.5% (95% CI = 6% to 20.9%) attributable to outreach, while larger practices improved by only 1.4% (95% CI = -2.4% to 5.3%, P-value for interaction <0.001). In large practices, educational outreach alone is unlikely to achieve worthwhile change. There is good evidence to support the use of educational outreach visits in small practices.


Formation of viscoelastic protein layers on polymeric surfaces relevant to platelet adhesion.
The hemocompatibility of biomaterials is highly dependent on the adhesion and activation of platelets. Surface-adsorbed fibrinogen has a dominant role in promoting platelet adhesion to artificial surfaces by binding glycoprotein IIb-IIIa (GPIIb-IIIa), the major platelet membrane receptor. Using quartz crystal microbalance with dissipation monitoring (QCM-D), we have investigated the material-dependent binding kinetics of purified GPIIb-IIIa to polymer-adsorbed fibrinogen. The following ranking of polymer-adsorbed mass (fibrinogen and GPIIb-IIIa) to test polymers could be established: poly[desaminotyrosyl-tyrosine ethyl (DTE) carbonate]/poly(lactide-co-glycolide)>poly[DTE co-5% poly(ethylene glycol) carbonate]. The QCM-D fibrinogen adsorption data were confirmed using an immunofluorescence assay. A synthetic RGD-containing peptide, but not a control peptide, inhibited GPIIb-IIIa binding to polymer-adsorbed fibrinogen, demonstrating the specificity of binding. Importantly, the binding efficiency of purified GPIIb-IIIa to polymer-adsorbed fibrinogen correlated with increased platelet adhesion in an in vitro model. Theoretical simulations using a Voight-based model provided quantitative data on the thickness and viscoelastic properties of the polymer-adsorbed protein layers. The precision of the modeling technique was limited with respect to the shear moduli values, leading to large variations. However, the other modeling parameters showed reproducible results. The thickness of both protein layers was polymer-dependent and ranged from 5 to 35 nm and the viscosity from 0.001 to 0.005 kg/ms, whereas the protein layer densities showed little differences between the test polymers. These results suggest that material-dependent changes in the thickness and viscoelastic properties of adsorbed fibrinogen-GPIIb-IIIa layers are crucial factors in the binding behavior of platelets to biomaterials.


Evaluation of an online knowledge translation intervention to promote cancer risk reduction behaviours: findings from a randomized controlled trial.
Many cancers are preventable through lifestyle modification; however, few adults engage in behaviors that are in line with cancer prevention guidelines. This may be partly due to the mixed messages on effective cancer prevention strategies in popular media. The goal of the McMaster Optimal Aging Portal (the Portal) is to increase access to trustworthy health information. The purpose of this study was to explore if and how knowledge translation strategies to disseminate cancer prevention evidence using the Portal influence participants' knowledge, intentions and health behaviors related to cancer risk. Adults ≥40 years old, with no cancer history were randomized to a 12-week intervention (weekly emails and social media posts) or control group. Quantitative data on knowledge, intentions and behaviors (physical activity, diet, alcohol consumption and use of tobacco products) were collected at baseline, end of study and 3 months later. Participant engagement was assessed using Google Analytics, and participant satisfaction through open-ended survey questions and semi-structured interviews. Participants (n = 557, mean age 64.9) were predominantly retired (72%) females (81%). Knowledge of cancer prevention guidelines was higher in the intervention group at end of study only (+ 0.3, p = 0.01). Intentions to follow cancer prevention guidelines increased in both groups, with no between-group differences. Intervention participants reported greater light-intensity physical activity at end of study (+ 0.7 vs. 0.1, p = 0.03), and reduced alcohol intake at follow u (- 0.2 vs. + 0.3, p < 0.05), but no other between-group differences were found. Overall satisfaction with the Portal and intervention materials was high. Dissemination of evidence-based cancer prevention information through the Portal results in small increases in knowledge of risk-reduction strategies and with little to no impact on self-reported health behaviours, except in particular groups. Further tailoring of knowledge translation strategies may be needed to see more meaningful change in knowledge and health behaviours. ClinicalTrials.gov NCT03186703, June 14, 2017.


Evaluation of fetal midface anatomy related to facial clefts: use of US.
To identify the sonographic appearance of normal fetal midface anatomy of in vitro fetal specimens and to correlate the appearance with that of in utero fetuses to determine which aspects of this anatomy can be evaluated clinically. The midface structures of 12 normal fetal specimens were examined in the axial, sagittal, and coronal planes with ultrasound. The results were correlated with those of other modalities. One hundred consecutive, normal in utero fetuses were scanned in the same planes in an attempt to identify the same anatomic landmarks identified in the fetal specimens. In the fetal specimens, the upper lip (coronal plane), alveolar ridge, tooth sockets, point of fusion of primary and secondary palates (axial plane), and fusion line of the secondary palate (sagittal plane) were consistently observed. In the 100 in utero fetuses, the same anatomy was visualized in the coronal plane in 95 (95%), in the axial plane in 97 (97%), and in the sagittal plane in 26 (26%). The mean scanning time was 2.8 minutes. Important aspects of fetal midface anatomy that relate to facial clefts can be observed in utero at prenatal sonography in the coronal and axial planes.


Obstetrics and Gynaecology as a Future Career for Medical Graduates in Oman: Factors that attract and discourage graduates.
Obstetrics and gynaecology (OBGYN) is a major speciality in the medical field that is often demanding yet rewarding; however, OBGYN receives the least number of applicants in Oman. This study aimed to determine the factors that influence graduates in choosing OBGYN as their speciality. This cross-sectional questionnaire-based study was conducted from February to March 2017 at Sultan Qaboos University Hospital, Royal Hospital, Khoula Hospital and Al Nahdha Hospital, Muscat, Oman. The questionnaire was distributed to 150 Omani medical graduates (interns and post-intern doctors). A total of 145 Omani graduates took part in the study (response rate: 96.7%) and the participants' average age was 26 years. Family medicine ranked as the first choice followed by paediatrics and emergency medicine. OBGYN was the first choice for eight female graduates. The top factors attracting male graduates to the OBGYN speciality were its surgical opportunities (80.6%), intellectual content (77.4%), faculty interactions and the opportunity to care for a healthy population (54.8% each); however, the top factors attracting females were the intellectual content (88.6%), patients' desire for female physicians (85.1%), the opportunity to care for a healthy population (76.3%) and cultural expectations (69.5%). The most discouraging factors for male graduates were cultural expectations (100%), the patients' desire for a female physician (93.5%) and the level of stress (71%), while the discouraging factors for female graduates were the level of stress (82.5%), time demands (78.1%), night duties and the length of the residency (71.9% each). Most of the factors that discourage female graduates from choosing OBGYN are to some extent modifiable. These changes should be considered to encourage the selection of OBGYN as a career by medical students.


The demoiselle of X-inactivation: 50 years old and as trendy and mesmerising as ever.
In humans, sexual dimorphism is associated with the presence of two X chromosomes in the female, whereas males possess only one X and a small and largely degenerate Y chromosome. How do men cope with having only a single X chromosome given that virtually all other chromosomal monosomies are lethal? Ironically, or even typically many might say, women and more generally female mammals contribute most to the job by shutting down one of their two X chromosomes at random. This phenomenon, called X-inactivation, was originally described some 50 years ago by Mary Lyon and has captivated an increasing number of scientists ever since. The fascination arose in part from the realisation that the inactive X corresponded to a dense heterochromatin mass called the "Barr body" whose number varied with the number of Xs within the nucleus and from the many intellectual questions that this raised: How does the cell count the X chromosomes in the nucleus and inactivate all Xs except one? What kind of molecular mechanisms are able to trigger such a profound, chromosome-wide metamorphosis? When is X-inactivation initiated? How is it transmitted to daughter cells and how is it reset during gametogenesis? This review retraces some of the crucial findings, which have led to our current understanding of a biological process that was initially considered as an exception completely distinct from conventional regulatory systems but is now viewed as a paradigm "par excellence" for epigenetic regulation.


Complications of central nervous system hydatid disease.
Central nervous system hydatid cyst disease presents with different clinical pictures depending on the involvement of cerebral and spinal structures. The majority of cerebral echinococcosis cases are in the pediatric age group, mostly involving the white matter, and their treatment is mainly surgical. Complications of this entity depend on several factors including the location, size, and multiplicity of the cysts, as well as the presence of contamination. The most common complication is a rupture of the cyst into the subarachnoid space which leads to widespread dissemination followed by severe inflammatory or anaphylactic response. However, vertebral lesions are usually invasive and cause neurological symptoms due to compression. Almost all patients complain of radicular pain and motor deficits; and up to one half of patients present with paraparesis. This paper examines the natural history and complications which may arise during the treatment of cerebral and vertebral hydatid cysts, and discusses their clinical management.


High prevalence of the c.74A>C SPINK1 variant in miniature and standard Schnauzers.
Variants in the serine protease inhibitor Kazal type 1 (SPINK1) gene have been associated with pancreatitis in Miniature Schnauzers. Replication of the association in an independent population is necessary to determine if genetic screening for SPINK1 variants should be considered in clinical practice. An association between the SPINK1 exonic variant c.74A > C and pancreatitis exists in Miniature Schnauzers. In addition, the variant is absent or rare in Standard Schnauzers, a related breed that is not reported to have an increased risk for pancreatitis. Case-control study. Seventeen Miniature Schnauzers with pancreatitis (cases), 60 mature Miniature Schnauzers with no substantial history of gastrointestinal signs in their lifetime (controls), and 31 Standard Schnauzers of unknown pancreatitis status. A PCR-RFLP assay was used to genotype dogs for the c.74A > C SPINK1 variant. Allele and genotype frequencies were reported for Schnauzers and compared between case and control Miniature Schnauzers. The c.74A > C variant was the major allele in both Schnauzer breeds with a frequency of 0.77 in Miniatures and 0.55 in Standards. The allele and genotype frequencies were similar between Miniature Schnauzers with and without a history of pancreatitis and did not impart an increased risk for pancreatitis. Genotyping a larger population of the Miniature Schnauzer breed than a previous study, along with a Standard Schnauzer cohort, demonstrated that the SPINK1 c.74A > C variant is a common polymorphism in the Schnauzer lineage. Furthermore, we were unable to confirm a relationship between the variant and clinically detectable pancreatitis in Miniature Schnauzers.


The use and misuse of upper gastrointestinal endoscopy.
To determine how appropriately physicians in 1981 did upper gastrointestinal endoscopy in a randomly selected, community-based sample of Medicare patients. We developed a comprehensive and clinically detailed list of 1069 indications for upper gastrointestinal endoscopy. A national panel of nine clinicians rated the appropriateness of the indications. We categorized the indications as appropriate, inappropriate, or equivocal. We did a clinically detailed medical record review of a random sample of 1585 patients having upper gastrointestinal endoscopy to assess the appropriateness of using upper gastrointestinal endoscopy. Patients were sampled from large geographic areas in three states. Two areas represented high use, and one area, low use. Random sample of patients 65 years of age or older receiving diagnostic upper gastrointestinal endoscopy. None; the study was retrospective. Patient characteristics, histories, and clinical indications for upper gastrointestinal endoscopy were similar across low- and high-use areas. Overall, 72% of the endoscopies were done for appropriate indications, 11% for equivocal indications, and 17% for inappropriate indications. Upper gastrointestinal bleeding (26%), follow-up to an abnormal upper gastrointestinal series (21%), dysphagia (18%), and dyspepsia (15%) were the most frequent clinical reasons for doing endoscopy. Inpatient endoscopies were more often appropriate and less often inappropriate than outpatient endoscopies. This analysis of practice patterns among study sites provides the clinical basis for understanding the use of upper gastrointestinal endoscopy. The finding of 17% inappropriate use may be cause for concern.


Effect of combined support for people with dementia and carers versus regular day care on behaviour and mood of persons with dementia: results from a multi-centre implementation study.
A previous study in Amsterdam showed that combined family support in the Meeting Centres Support Programme, in which dementia patients and their carers are both supported by one professional staff member, is more effective in influencing behaviour problems and mood of dementia patients living in the community than non-integrated support, such as day care only. A multi-centre implementation study tests if similar effects are achieved in other regions of The Netherlands. A pretest-posttest control group design was applied. 112 dementia patients who visited psychogeriatric day care in eight community centres across the country and in three nursing homes, and their carers participated in the study. The patients in the experimental group (n = 89) received support from the Meeting Centres Support Programme together with their carers, while the control group (n = 23) received day care only. Behaviour problems (agressive behaviour, inactivity, non-social behaviour) and mood (dissatisfaction, depressive behaviour) were assessed using standardized observation scales. Quality of life was assessed by interviewing the patients. After 7 months the Meeting Centres Support Programme, compared to regular day care, showed a moderately positive effect on the degree of total behaviour problems (effect size = 0.52), especially on inactivity (effect size = 0.37) and non-social behaviour (effect size = 0.60), a large effect on depressive behaviour (effect size = 0.92) and a moderate effect on self-esteem (effect size = 0.43). The Meeting Centres Support Programme proves to be more effective than regular day care in influencing behaviour problems, especially inactivity and non-social behaviour, and depressed mood. Participation in the programme also seems to have a positive effect on self-esteem, an important aspect of quality of life. These findings surpass the results of the Amsterdam study and confirm the surplus value of the combined family support in the Meeting Centres Support Programme as compared to regular day care for people with mild to severe dementia.


Protonation of lysine residues inverts cation/anion selectivity in a model channel.
A dimeric alamethicin analog with lysine at position 18 in the sequence (alm-K18) was previously shown to form stable anion-selective channels in membranes at pH 7.0 [Starostin, A. V., R. Butan, V. Borisenko, D. A. James, H. Wenschuh, M. S. Sansom, and G. A. Woolley. 1999. Biochemistry. 38:6144-6150]. To probe the charge state of the conducting channel and how this might influence cation versus anion selectivity, we performed a series of single-channel selectivity measurements at different pH values. At pH 7.0 and below, only anion-selective channels were found with P(K(+))/P(Cl(-)) = 0. 25. From pH 8-10, a mixture of anion-selective, non-selective, and cation-selective channels was found. At pH > 11 only cation-selective channels were found with P(K(+))/P(Cl(-)) = 4. In contrast, native alamethicin-Q18 channels (with Gln in place of Lys at position 18) were cation-selective (P(K(+))/P(Cl(-)) = 4) at all pH values. Continuum electrostatics calculations were then carried out using an octameric model of the alm-K18 channel embedded in a low dielectric slab to simulate a membrane. Although the calculations can account for the apparent pK(a) of the channel, they fail to correctly predict the degree of selectivity. Although a switch from cation- to anion-selectivity as the channel becomes protonated is indicated, the degree of anion-selectivity is severely overestimated, suggesting that the continuum approach does not adequately represent some aspect of the electrostatics of permeation in these channels. Side-chain conformational changes upon protonation, conformational changes, and deprotonation caused by permeating cations and counterion binding by lysine residues upon protonation are considered as possible sources of the overestimation.


Pharmaceutical care in the neonatal intensive care unit: Perspectives of Polish medical and pharmacy students.
The concepts of ward-based pharmaceutical care as well as collaborative practice are still relatively novel in Poland, particularly in specialty areas of practice such as the neonatal intensive care unit (NICU). The purpose of this study was to identify the opinions and perceptions of Polish medical and pharmacy students towards the provision of pharmaceutical care services in the NICU as well as pharmacist integration into the ward-based multi-disciplinary NICU treating team. A cross-sectional, mixed-method survey was distributed among medical and pharmacy students at a large Polish medical university. A total of 147 students completed the survey (74 pharmacy and 73 medical). Overall, there were statistically significant differences between the perspectives of medical and pharmacy students towards the provision of pharmaceutical care services in the NICU. For 11 out of 15 proposed clinical roles, a significantly lower proportion of medical students (M) agreed that pharmacists should perform these in the NICU compared to pharmacy students (P). These roles included participation in ward rounds (P = 82.4%, M = 38.4%, p < 0.001), therapeutic drug monitoring (P = 98.6%, M = 78.1%, p < 0.001), and monitoring total parenteral nutrition (P = 87.8%, M = 37%, p ≤ 0.001). Further investigation is needed to develop educational strategies directed at clinical, patient-centered, collaborative roles, particularly for specialty areas of practice such as the NICU, that have the potential to facilitate the provision of a more advanced and comprehensive level of pharmaceutical care.


Evaluation of potential human health risk associated with consumption of edible products from livestock fed ration supplemented with Red Lake Diatomaceous Earth.
Red Lake Diatomaceous Earth (DE) is a naturally occurring blend of diatomaceous earth and calcium bentonite that can be used as an anti-caking agent in animal feed and contains naturally occurring dioxins. A quantitative risk assessment was conducted to assess potential human health risk associated with consumption of edible tissues from livestock exposed to dioxins via feed containing Red Lake DE. Empirical data characterising the transfer of dioxins to eggs and other tissues in chickens demonstrate that resulting concentrations in eggs are lower than those found in the general food supply. These data also provided product-specific input for a risk assessment conducted both with default parameters and with media-specific input from the feed study. Results demonstrate that exposure to dioxins in edible tissue from livestock that consumed Red Lake DE in feed would not be associated with an increased risk to humans. Findings from this assessment highlight the utility and importance of accounting for bioavailability as part of health-based risk assessment and provide information critical to risk managers in determining the safe use of Red Lake DE as an anticaking agent in livestock and pet feed.


Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.
To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8(.)6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with Δ (95% CI) = - 0.795 (- 1.436 to - 0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.


Strong guided mode resonant local field enhanced visible harmonic generation in an azo-polymer resonant waveguide grating.
Guided mode resonance (GMR) enhanced second- and third-harmonic generation (SHG and THG) is demonstrated in an azo-polymer resonant waveguide grating (RWG), comprised of a poled azo-polymer layer on top of a textured SU8 substrate with a thin intervening layer of TiO2. Strong SHG and THG outputs are observed by matching either in-coming fundamental- or out-going harmonic-wavelength to the GMR wavelengths of the azo-polymer RWG. Without the azo-polymer coating, pure TiO2 RWGs, do not generate any detectable SHG using a fundamental beam peak intensity of 2 MW/cm(2). Without the textured TiO2 layer, a planar poled azo-polymer layer results in 3650 times less SHG than the full nonlinear RWG structure under identical excitation conditions. Rigorous coupled-wave analysis calculations confirm that this enhancement of the nonlinear conversion is due to strong local electric fields that are generated at the interfaces of the TiO2 and azo-polymer layers when the RWG is excited at resonant wavelengths associated with both SHG and THG conversion processes.


The role of evidence, context, and facilitation in an implementation trial: implications for the development of the PARIHS framework.
The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful understandings of how interventions work. In this paper, we provide an explanation of implementation processes from one of the first national implementation research randomized controlled trials with embedded process evaluation conducted within acute care, and a proposed extension to the Promoting Action on Research Implementation in Health Services (PARIHS) framework. The PARIHS framework was prospectively applied to guide decisions about intervention design, data collection, and analysis processes in a trial focussed on reducing peri-operative fasting times. In order to capture a holistic picture of implementation processes, the same data were collected across 19 participating hospitals irrespective of allocation to intervention. This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention. Data were analysed using content analysis within, and then across data sets. A robust and uncontested evidence base was a necessary, but not sufficient condition for practice change, in that individual staff and patient responses such as caution influenced decision making. The implementation context was challenging, in which individuals and teams were bounded by professional issues, communication challenges, power and a lack of clarity for the authority and responsibility for practice change. Progress was made in sites where processes were aligned with existing initiatives. Additionally, facilitators reported engaging in many intervention implementation activities, some of which result in practice changes, but not significant improvements to outcomes. This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework. Consistent with the underlying tenant of PARIHS, a multi-faceted and dynamic story of implementation was evident. However, the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework. We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals, evidence, and context to promote evidence-informed practice. This proposal will enhance the potential of the PARIHS framework for explanation, and ensure theoretical development both informs and responds to the evidence base for implementation.


Pleurotus ostreatus inhibits colitis-related colon carcinogenesis in mice.
Colorectal cancer is one of the leading causes of cancer deaths in both men and women in the world. However, colon cancer can be prevented to some extent by consumption of edible natural products with chemopreventive properties. Therefore, we investigated, whether edible mushroom Pleurotus ostreatus (PO) has chemopreventive effect on inflammation-associated colon carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS). PO treatment, at both doses (100 and 500 mg/kg), significantly reduced by 50 and 78% the number of aberrant crypt foci and the multiplicity of colon neoplasms by 43 and 89%, respectively. However, incidence of colon tumors and high grade dysplasia was reduced by 50 and 63% only in the dose 500 mg/kg of PO, respectively. Colon shortening and dysplastic index was significantly reduced by PO treatment in dose-dependent manner. The immunohistochemistry of colons revealed that treatment with PO suppressed expression of cyclin D1, Ki-67, COX-2 and F4/80. In summary, our data suggest that PO may prevent inflammation-associated colon carcinogenesis with exposure to PhIP through combined modulatory mechanisms of inflammation and tumor growth via suppression of COX-2, F4/80, Ki-67 and cyclin D1 expression in mice.


Work-related self-reported musculoskeletal disorders in hypermarket cashiers: a study in south of Portugal.
Work-related musculoskeletal disorders are a group of painful disorders which arise from work situations with continuous repetitive movements, carried out with speed and without time for recovery. In the performance of their job tasks, supermarket cashiers are exposed to this type of ergonomic stress. This study aimed to determine the incidence of self-reported injuries in Portuguese hypermarket cashiers and to identify the related factors. The sample included 176 hypermarket cashiers, aged between 18 and 65 years (39.57±11.11), 167 (94.9%) of them women. Symptoms and exposure of interest have been collected through an interview-based questionnaire. The presence of carpal tunnel syndrome was assessed by Phalen's test. One hundred and seventeen (66.5%) cashiers reported an injury during employment, 100 (56.8%) of them reporting an injury in the previous 6 months. A total of 166 injuries were reported, corresponding to 1.14 injuries per 1,000 hours of work. The most common injuries were non-specific pain (30.4%), located in the shoulder (23.2%), cervical (22%) and lumbar spine (22%). Part-time workers showed a 2.25 times greater risk of injury (95% CI: 1.17-4.32; p=0.015) than full-time workers. Cashiers with more than 6 years of employment length had a 3.59 times higher risk of injury (95% CI: 1.84-6.99; p≤0.001) than those who had been working for a shorter period. Our data showed a high rate of reported injuries among hypermarket cashiers, especially among part-time workers and those with the highest length of employment.