Functional feeds reduce heart inflammation and pathology in Atlantic Salmon (Salmo salar L.) following experimental challenge with Atlantic salmon reovirus (ASRV).
Heart and Skeletal Muscle Inflammation (HSMI), recently associated with a novel Atlantic salmon reovirus (ASRV), is currently one of the most prevalent inflammatory diseases in commercial Atlantic salmon farms in Norway. Mortality varies from low to 20%, but morbidity can be very high, reducing growth performance and causing considerable financial impact. Clinical symptoms, including myocarditis, myocardial and red skeletal muscle necrosis, correlate with the intensity of the inflammatory response. In the present study, the effects of two functional feeds (FF1 and FF2) were compared to a standard commercial reference feed (ST) in Atlantic salmon subjected to an ASRV challenge. The functional feeds had reduced levels of total lipid and digestible energy, and different levels and proportions of long-chain polyunsaturated fatty acids (LC-PUFA). The objective was to determine whether these feeds could provide effective protection by decreasing the inflammatory response associated with HSMI. Histopathology, viral load, fatty acid composition and gene expression of heart tissue were assessed over a period of 16 weeks post-infection with ASRV. The viral load and histopathology scores in heart tissue in response to ASRV infection were reduced in fish fed both functional feeds, with FF1 showing the greatest effect. Microarray hierarchical cluster analysis showed that the functional feeds greatly affected expression of inflammation/immune related genes over the course of the ASRV infection. Viral load correlated with up-regulation of pro-inflammatory genes at the early-mid stages of infection in fish fed the ST diet. Expression of inflammatory genes 16-weeks after ASRV challenge reflected the difference in efficacy between the functional feeds, with fish fed FF1 showing lower expression. Thus, severity of the lesions in heart tissue correlated with the intensity of the innate immune response and was associated with tissue fatty acid compositions. The present study demonstrated that dietary modulation through clinical nutrition had major influences on the development and severity of the response to ASRV infection in salmon. Thus, HSMI was reduced in fish fed the functional feeds, particularly FF1. The modulation of gene expression between fish fed the different feeds provided further insight into the molecular mechanisms and progression of the inflammatory and immune responses to ASRV infection in salmon.


Linezolid combined with trimethoprim-sulfamethoxazole therapy for the treatment of disseminated nocardiosis.
We describe a case of disseminated nocardiosis in a 45-year-old male with a history of chronic glomerular nephritis and allograft renal transplantation both treated with immunosuppressive drugs. Clinical symptoms included fever, chest distress, breathlessness, subcutaneous nodules and pustules. Pulmonary computed tomography scans revealed areas of consolidation in both lung fields, pleural effusion and massive pericardial effusion. Bacterial culture of the pus in the subcutaneous abscesses and pericardial effusion showed growth of Nocardia asteroides sensitive to linezolid and trimethoprim-sulfamethoxazole (TMP-SMZ) for both. Treatment with linezolid combined with TMP-SMZ resulted in a clear clinical improvement and bacterial clearance.


Engineering a defect-rich Prussian blue analog composite for enhanced Cs+ removal performance.
Using a novel, irregular honeycombed N-doped porous carbon (NPC) as a support and defect inducer, defect-rich Zn-PBA was formed in situ and evenly anchored on the surface of NPC to obtain a defect-rich Zn-PBA/NPC composite. This composite demonstrated an ultrafast Cs+ adsorption rate that reached equilibrium within 60 s as well as excellent adsorption capacity, stability and reusability. The adsorption mechanism indicated that Cs+ was quickly adsorbed via the defect sites close to the Zn-PBA crystal face accompanied by K(OH2)+ elimination.


An advance in condensable composites.
With the constant advance of technology and the public's increasing awareness of esthetically pleasing restorations, alternatives for amalgam and early composite materials have been brought to the forefront of dentistry. Condensable composites offer characteristics that distinguish them from their traditional hybrid counterparts: decreased wear, packability, and bulk curing with less polymerization shrinkage. Prodigy Condensable expands the first generation of condensables by altering its resin phase to make the material more packable. Through increased filler content and methacryoyloxyethlpolycaprolactonephosphate and rheological control additives, this second-generation condensable composite possesses strength and ease of use comparable to and even exceeding amalgam while demonstrating superior esthetics for all posterior restorations.


Characterization and application of a murine monoclonal antibody that reacts specifically with the serogroup D1 Salmonella.
A murine hybridoma cell line that produces monoclonal antibody (mAb) against the serogroup D1 Salmonella lipopolysaccharide (LPS) antigen was established. The trisaccharide tyvelose alpha 1----3 mannose alpha 1----4 rhamnose was shown to be involved in the reactive epitope of the mAb since this mAb reacted strongly with strains of serogroup D1 Salmonella but not with Salmonella strains from the O serogroups of A, B, and D2, and sodium meta-periodate was found to destroy the reactivity of the serogroup D1 O-antigen with the mAb. As such this mAb was found to be a useful serotyping reagent for the identification of serogroup D1 Salmonella, and for the differentiation of strains of serogroups D1 and D2 Salmonella which have identical flagellar H antigens.


Robust Learning With Kernel Mean -Power Error Loss.
Correntropy is a second order statistical measure in kernel space, which has been successfully applied in robust learning and signal processing. In this paper, we define a nonsecond order statistical measure in kernel space, called the kernel mean- power error (KMPE), including the correntropic loss (C-Loss) as a special case. Some basic properties of KMPE are presented. In particular, we apply the KMPE to extreme learning machine (ELM) and principal component analysis (PCA), and develop two robust learning algorithms, namely ELM-KMPE and PCA-KMPE. Experimental results on synthetic and benchmark data show that the developed algorithms can achieve better performance when compared with some existing methods.


Portable and Rapid Fluorescence Turn-On Detection of Total Pepsin in Saliva Based on Strong Electrostatic Interactions.
Salivary pepsin has been proposed as a promising diagnostic marker for gastroesophageal reflux disease (GERD). However, the activity of human pepsin is strongly influenced by pH, and the acidic condition (pH ∼ 2) is optimal, which is a contradiction for the pepsin detection kit based on its catalytic activity. Thus, its accurate quantification in saliva (neutral pH) by readily rapid tools with simplicity and low cost is still challenging. Herein, a convenient fluorescence assay has been developed for the rapid detection of pepsin at neutral pH based on its electrostatic interaction with SYBR Green (SG) rather than the bioactivity. At neutral pH, the positively charged SG fluorophore can be effectively adsorbed by the negatively charged pepsin due to the low isoelectric point (pI) and large molecular size of pepsin. Thus, the molecular rotation of SG is limited, and its fluorescence intensity is significantly increased. The strategy was further confirmed to have the same fluorescence response as that of normally active and inactivated pepsin. Due to the unique pI of pepsin, the fluorescence strategy is highly selective for pepsin compared to other proteins. On the basis of this strategy, a smartphone-based fluorescence capture device integrated with a programmed Python program was fabricated for both color recognition and the accurate detection of pepsin within 3 min. Under the optimal conditions, this turn-on sensor allowed for the on-site analysis of pepsin with a detection limit of 0.2 μg/mL. Moreover, this strategy was successfully used to assess salivary pepsin to aid in the noninvasive diagnosis of GERD.


Phospholipase C-related catalytically inactive protein (PRIP) regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.
Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis.


Nonspecific stimulation of host defenses against bacterial challenge in immunosuppressed mice.
Muramyl dipeptide (MDP) has been shown to be a safe and effective host defense stimulant in both normal and malnourished hosts exposed to a bacterial challenge. We investigated its effect in mice compromised by pretreatment with either cyclophosphamide or steroids. The bacterial challenge, designed to simulate a surgical wound infection, consisted of a Klebsiella pneumoniae-laden suture. The MDP treatment resulted in lower local and systemic bacterial spread and increased survival in mice immunosuppressed by cyclophosphamide than in untreated controls. No such effect was demonstrated in animals compromised by steroids. These results suggest that MDP exerts its effect primarily on the macrophage.


EPR studies of the generation, structure, and reactivity of n-heterocyclic carbene borane radicals.
N-Heterocyclic carbene boranes (NHC-boranes) are a new "clean" class of reagents suitable for reductive radical chain transformations. Their structures are well suited for their reactivity to be tuned by inclusion of different NHC ring units and by appropriate placement of diverse substituents. EPR spectra were obtained for the boron-centered radicals generated on removal of one of the BH(3) hydrogen atoms. This spectroscopic data, coupled with DFT computations, demonstrated that the NHC-BH(2)* radicals are planar pi-delocalized species. tert-Butoxyl radicals abstracted hydrogen atoms from NHC-boranes more than 3 orders of magnitude faster than did C-centered radicals, although the rate decreased markedly for sterically shielded NHC-BH(3) centers. Combinations of two NHC-boryl radicals afforded 1,2-bis-NHC-diboranes at rates which also depended strongly on steric shielding. The termination rate increased to the diffusion-controlled limit for sterically unhindered NHC-boryls. Bromine atoms were rapidly transferred to imidazole-based NHC-boryl radicals from alkyl, allyl, and benzyl bromides. Chlorine-atom abstraction was, however, much less efficient and only observed for sterically unhindered NHC-boryls reacting with allylic and benzylic chlorides. For an NHC-borane containing a bulky thexyl substituent at boron, the tertiary H atom of the thexyl group was selectively removed. The resulting beta-boron-containing alkyl radical rapidly underwent beta scission of the B-C bond with production of an NHC-boryl radical and an alkene.


[A new method for correction of clubhands (author's transl)].
A 17 year old patient is presented who had aplasia of the radius for clubhand described by Clodius. The ulnar was divided at the wrist and the distal fragment was rotated by 90 degrees. Tendons were elongated by z plasties. Results can be described as satisfactory.


[Is there a future for dosimetry control by portal imaging?].
This article deals with the potential benefits of portal imaging as a tool for the dosimetric control of a radiotherapy treatment. In the introduction the advantages of dosimetric control with portal imaging are described. Subsequently, the physical problem is considered between patient exit dose and dose at the level of the portal detector. Measurements with phantoms have shown that this relationship is complex: different algorithms have been developed by groups of researchers and some of them are summarised in this article. Finally, three examples of dosimetric control using portal imaging are presented: in vivo dosimetry on the beam axis, dosimetric profiles in two dimensions and portal dosimetry for intensity modulation.


Overexpression of oncogenic H-Ras in hTERT-immortalized and SV40-transformed human cells targets replicative and specialized DNA polymerases for depletion.
DNA polymerases play essential functions in replication fork progression and genome maintenance. DNA lesions and drug-induced replication stress result in up-regulation and re-localization of specialized DNA polymerases η and κ. Although oncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability, little is known about DNA polymerase expression and regulation in response to oncogene activation. Here, we investigated the consequences of mutant H-RAS G12V overexpression on the regulation of DNA polymerases in h-TERT immortalized and SV40-transformed human cells. Focusing on DNA polymerases associated with the replication fork, we demonstrate that DNA polymerases are depleted in a temporal manner in response to H-RAS G12V overexpression. The polymerases targeted for depletion, as cells display markers of senescence, include the Pol α catalytic subunit (POLA1), Pol δ catalytic and p68 subunits (POLD1 and POLD3), Pol η, and Pol κ. Both transcriptional and post-transcriptional mechanisms mediate this response. Pol η (POLH) depletion is sufficient to induce a senescence-like growth arrest in human foreskin fibroblast BJ5a cells, and is associated with decreased Pol α expression. Using an SV-40 transformed cell model, we observed cell cycle checkpoint signaling differences in cells with H-RasG12V-induced polymerase depletion, as compared to Pol η-deficient cells. Our findings contribute to our understanding of cellular events following oncogene activation and cellular transformation.


Syncytin-1, syncytin-2 and suppressyn in human health and disease.
In this review, we summarized the results of experimental and clinical studies about three human endogenous retroviruses and their products-syncytin-1, syncytin-2, and suppressyn in human physiology and pathophysiology. We summed up the described connection with various pathological processes and diseases, mainly with pregnancy-induced hypertensive diseases such as preeclampsia, oncogenesis, gestational trophoblastic disease, and multiple sclerosis. Supposed mechanisms of action and the potential of clinical applications are also described.


Marital Interactions, Family Intervention, and Disagreements: A Daily Diary Study in a Low-income Sample.
Little research has examined associations between low-income married couples' daily interactions and severity of disagreements. Similarly, few researchers have considered how family-strengthening interventions for low-income couples may affect the quality of daily interactions and associations between interactions and conflict experiences. This study aims to fill these gaps in the literature by leveraging daily diary data from a random assignment study of a family-strengthening intervention with low-income husbands and wives 30 months postenrollment. Married couples randomly assigned to the intervention participated in 10 weeks of relationship education services. Control group couples received no services. Thirty months postrandom assignment, participants reported on the severity of daily marital disagreements over a 15-day period, as well as their positive and negative emotions during inter-spousal interactions. Multi-level models demonstrated associations between reports of emotions in interactions and severity of disagreements. In addition, wives assigned to the family strengthening program reported fewer negative emotions during interactions at follow-up than wives in the control condition. Finally, negative associations between positive emotions in interactions and severity of disagreements were stronger for wives assigned to the intervention, while positive associations between negative emotions in interactions and severity of disagreements were weaker for wives assigned to the intervention. Implications for future research and intervention development are discussed.


[The epidemiology of tumors of the testes in the Netherlands: accurate rendering by the Registry of Histopathology and Cytopathology (PALGA)].
To investigate recent trends in the incidence of testicular cancer and to describe epidemiological characteristics of various subtypes of testicular cancer. Descriptive. Using the nationwide registry of pathology reports (PALGA), the incidence of all newly-diagnosed cases of testicular cancer between the years 1991 and 2002 was analyzed according to age and subtype. To test the accuracy of the PALGA figures, a comparison was made with incidence figures (1991-1998) produced by the Netherlands Cancer Registry. 5856 cases of testicular cancer were diagnosed. The age-adjusted incidence increased from 4.8 to 6.6 per 100,000. The incidence of non-seminoma increased to a larger extent than that of seminoma. The incidence of malignant lymphoma of testicular origin did not increase, but it remained the most frequent testicular tumour beyond the age of 65. Non-seminoma was the most common tumour below the age of 30, while seminoma was the most commonly found tumour between the ages of 30 and 65. When PALGA began recording statistics, the incidence figures showed a difference of up to 10% with the figures produced by the cancer registry, but this has decreased to 1-2% in more recent years. The incidence of testicular cancer increased from the 1990s up to 2002. The incidence figures of histopathologically confirmed cases of cancer in the PALGA registry were timely and accurate.


Neurophysiological studies may provide a misleading picture of how perceptual-motor interactions are coordinated.
Neurophysiological measurement techniques like fMRI and TMS are increasingly being used to examine the perceptual-motor processes underpinning the ability to anticipate the actions of others. Crucially, these techniques invariably restrict the experimental task that can be used and consequently limit the degree to which the findings can be generalised. These limitations are discussed based on a recent paper by Tomeo et al. (2012) who sought to examine responses to fooling actions by using TMS on participants who passively observed spliced video clips where bodily information was, and was not, linked to the action outcome. We outline two particular concerns with this approach. First, spliced video clips that show physically impossible actions are unlikely to simulate a "fooling" action. Second, it is difficult to make meaningful inferences about perceptual-motor expertise from experiments where participants cannot move. Taken together, we argue that wider generalisations based on these findings may provide a misunderstanding of the phenomenon such a study is designed to explore.


Value of diagnostic and therapeutic laparoscopy for abdominal stab wounds.
The purpose of the present study was to evaluate the use of laparoscopy for the diagnosis and treatment for hemodynamically stable patients with abdominal stab wounds. We conducted a retrospective cohort study to compare the outcomes of 86 hemodynamically stable patients with suspected intra-abdominal injuries from abdominal stab wounds who underwent either exploratory laparotomy or diagnostic laparoscopy. Thirty-eight patients (group A) were treated before the adoption of laparoscopy as a diagnostic and therapeutic tool for abdominal stabbing injuries at our hospital, and 48 patients (group B) were treated after. Demographic information, injury severity, operative findings, rates of nontherapeutic interventions, operation time, length of hospital stay, and morbidity of the two groups were evaluated. There was no difference in the demographics and injury severity between the two groups. Laparoscopy decreased the nontherapeutic laparotomy rate from 57.9% in group A to 0% in group B (P < 0.001). The accuracy of diagnostic laparoscopy was 100% in group B. Patients in group B had a significantly shorter hospital stay (5.0 days versus 9.9 days; P < 0.001) and shorter operation time (90.7 min vs. 118.7 min; P = 0.019) than group A. For patients in group B with significant intra-abdominal injuries, therapeutic laparoscopy was successfully performed in 16 of 17 patients (94.1%), treating a total of 22 intra-abdominal injuries. Laparoscopy is feasible and safe for the diagnosis and treatment of hemodynamically stable patients with abdominal stab wounds. It can reduce the nontherapeutic laparotomy rate and shorten the length of hospital stay.


Pioneer Factor Foxa2 Mediates Chromatin Conformation Changes for Activation of Bile Acid Targets of FXR.
Transcription factors regulate gene expression that orchestrates liver physiology. Many bind at distal enhancers and chromatin looping is required to activate their targets. Chromatin architecture has been linked to essential functions of the liver, including metabolism and sexually dimorphic gene expression. We have previously shown that pioneer factor Foxa2 opens chromatin for binding of nuclear receptors farnesoid X receptor (FXR) and liver X receptor-α during acute ligand activation. FXR is activated by bile acids and deletion of Foxa2 in the liver results in intrahepatic cholestasis. We hypothesized that Foxa2 also enables chromatin conformational changes during ligand activation and performed genome-wide studies to test this hypothesis. We performed Foxa2 HiChIP (Hi-C and ChIP) to assess Foxa2-dependent long-range interactions in mouse livers treated with either vehicle control or FXR agonist GW4064. HiChIP contact analysis shows that global chromatin interactions are dramatically increased during FXR activation. Ligand-treated livers exhibit extensive redistribution of topological associated domains and substantial increase in Foxa2-anchored loops, suggesting Foxa2 is involved in dynamic chromatin conformational changes. We demonstrate that chromatin conformation, including genome-wide interactions, topological associated domains, and intrachromosomal and interchromosomal Foxa2-anchored loops, drastically changes on addition of FXR agonist. Additional Foxa2 binding in ligand-activated state leads to formation of Foxa2-anchored loops, leading to distal interactions and activation of gene expression of FXR targets. Ligand activation of FXR, and likely of related receptors, requires global changes in chromatin architecture. We determine a novel role for Foxa2 in enabling these conformational changes, extending its function in bile acid metabolism.


[Monitoring of parasites in domestic sewage].
The evaluation of the presence of parasites in semisolid and liquid sewage in Argentinian Patagonia in view of the fact that this is a restriction for its use. The samples taken at 4 Domestic Sewage Plants were analyzed in accordance with Standard Methods for the Examination of Water and Wastewater, Environmental Protection Agency, World Health Organization and some other classifications. Only 2 of 6 semisolid samples analyzed had non-viable Ascaris lumbricoides eggs. Of the 10 liquid samples analyzed, only 2 did not contain eggs whereas the remaining ones had pathogens of categories I (Giardia sp., Hymenolepis nana and Enterobius vermicularis) and III (Ascaris lumbricoides, Ancylostoma duodenale and Trichuris trichiura). All semisolid samples turned out to be satisfactory for use as fertilizer as no viable Ascaris lumbricoides eggs were found in any of them. But only 6 of the liquid samples were satisfactory for use as they had no eggs or their concentrations was equal to or less than 1 egg per litre.


Kids helping kids: The lived experience of adolescents who support friends with mental health needs.
Adolescent mental health is a significant health care issue. Friends play an important role in the lives of adolescents with mental health concerns and help to improve outcomes related to depression and suicide. However, little is known about the experiences of adolescents who help their friends with these concerns. A phenomenological research design involving unstructured interviews was used to answer the question: what is the lived experience of adolescents who provide support to friends with anxiety, depression, or who express suicidal ideation?" Participants for this study were aged 16-17 and included both males (n = 2) and females (n = 3). Participants described their experience as "Kids Helping Kids" which is defined by the following themes: Being Fearful, Maintaining Vigilance, Seeking Knowledge, Keeping Secrets, Involving Others, Setting Boundaries, and Feeling Honored. Helping a friend with mental health concerns can be challenging yet rewarding. Nurses should be aware of this role that some adolescents undertake and include the friends of adolescents with mental health concerns as part of plans of care.


Angiosarcoma patients treated with immune checkpoint inhibitors: a case series of seven patients from a single institution.
Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas. We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue. We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities. This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.


Resveratrol-loaded nanocapsules inhibit murine melanoma tumor growth.
In this study, resveratrol-loaded nanocapsules were developed and its antitumor activity tested on a melanoma mice model. These nanocapsules were spherically-shaped and presented suitable size, negative charge and high encapsulation efficiency for their use as a modified-release system of resveratrol. Nanoencapsulation leads to the drug amorphization. Resveratrol-loaded nanoparticles reduced cell viability of murine melanoma cells. There was a decrease in tumor volume, an increase in the necrotic area and inflammatory infiltrate of melanoma when resveratrol-loaded nanocapsules were compared to free resveratrol in treated mice. Nanoencapsulation of resveratrol also prevented metastasis and pulmonary hemorrhage. This modified-release technology containing resveratrol can be used as a feasible approach in order to inhibit murine melanoma tumor growth.


Heat protection behaviors and positive affect about heat during the 2013 heat wave in the United Kingdom.
Heat waves pose serious health risks, and are expected to become more frequent, longer lasting, and more intense in the future under a changing climate. Yet, people in the UK seem to feel positive when thinking about hot weather. According to research on the affect heuristic, any positive or negative emotions evoked by potentially risky experiences may be used as cues to inform concerns about risk protection. If so, then their positive feelings toward hot weather might lead UK residents to lower intentions to adopt heat protection behaviors. Here, we examine the relationships between heat protection behaviors during the July 2013 UK heat wave and self-reports of having heard heat protection recommendations, feeling positive affect about heat, seeing heat protection measures as effective, and trusting the organizations making those recommendations. Responses to a national survey revealed that 55.1% of participants had heard heat protection recommendations during the 2013 UK heat wave. Those who reported having heard recommendations also indicated having implemented more heat protection behaviors, perceiving heat protection behaviors as more effective, feeling more positive about heat, and intending to implement more protection behaviors in future hot summers. Mediation analyses suggested that heat protection recommendations may motivate heat protection behaviors by increasing their perceived effectiveness, but undermine their implementation by evoking positive affect about hot weather. We discuss our findings in the context of the affect heuristic and its implications for heat protection communications.


Minimal role of eastern fence lizards in Borrelia burgdorferi transmission in central New Jersey oak/pine woodlands.
The eastern fence lizard, Sceloporus undulatus , is widely distributed in eastern and central North America, ranging through areas with high levels of Lyme disease, as well as areas where Lyme disease is rare or absent. We studied the potential role of S. undulatus in transmission dynamics of Lyme spirochetes by sampling ticks from a variety of natural hosts at field sites in central New Jersey, and by testing the reservoir competence of S. undulatus for Borrelia burgdorferi in the laboratory. The infestation rate of ticks on fence lizards was extremely low (prevalence = 0.087, n = 23) compared to that on white-footed mice and other small mammals (prevalence = 0.53, n = 140). Of 159 nymphs that had fed as larvae on lizards that had previously been exposed to infected nymphs, none was infected with B. burgdorferi , compared with 79.9% of 209 nymphs that had fed as larvae on infected control mice. Simulations suggest that changes in the numbers of fence lizards in a natural habitat would have little effect on the infection rate of nymphal ticks with Lyme spirochetes. We conclude that in central New Jersey, S. undulatus plays a minimal role in the enzootic transmission cycle of Lyme spirochetes.


Cerebrospinal fluid IgE and the diagnosis of cerebral cysticercosis.
Cerebral cysticercosis (CC) is a common cause of seizures and other central nervous system disorders in the Mexican-American population. The elevation of serum IgE in many parasitic diseases led us to study CSF and serum IgE in patients with CC diagnosed by pathologic, radiologic or clinical criteria. A paper disc radioimmunoassay, sensitive to 0.01 IU/ml, was used to measure CSF and serum IgE in 69 patients. The mean CSF IgE level in Mexicans with CC was 0.44 IU/ml compared to 0.28 IU/ml in Mexicans without CC and 0.07 IU/ml in non-Mexicans without CC.


Atrophy of Swallowing Muscles Is Associated With Severity of Dysphagia and Age in Patients With Acute Stroke.
Sarcopenia has been identified as an independent risk factor for dysphagia. Dysphagia is one of the most important and prognostically relevant complications of acute stroke. The role of muscle atrophy as a contributing factor for the occurrence of poststroke dysphagia is yet unclear. To assess whether there is a correlation between age and muscle volume and whether muscle volume is related to dysphagia in acute stroke patients. This retrospective, single-center study included 73 patients with acute ischemic or hemorrhagic stroke who underwent computed tomography angiography on admission and an objective dysphagia assessment by Fiberoptic Endoscopic Evaluation of Swallowing within 72 hours from admission. With the help of semiautomated muscle segmentation and 3-dimensional reconstruction volumetry of the digastric, temporal, and geniohyoid muscles was performed. For further analysis, participants were first divided into 4 groups according to their age (<61 years, n = 12; 61-75 years, n = 16; 76-85 years, n = 28; ≥86 years, n = 17), secondly into 3 different groups according to their dysphagia severity using the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) (FEDSS 1 and 2, n = 25; FEDSS 3 and 4, n = 32; FEDSS 5 and 6, n = 16). Correlation of muscle volumes with age and dysphagia severity. Muscle volumes of single muscles (except for geniohyoid and the right digastric muscles) as well as the sum muscle volume were significantly and inversely related to dysphagia severity. We found a significant decline of muscle volume with advancing age for most muscle groups and, in particular, for the total muscle volume. Apart from features being determined by the acute stroke itself (eg, site and size of stroke), also premorbid conditions, in particular age-related muscle atrophy, have an impact on the complex pathophysiology of swallowing disorders poststroke.


Detection of HERV-K6 and HERV-K11 transpositions in the human genome.
Mobile genetic elements classed as transposons comprise an estimated 45% of the human genome, and 8% of these elements are human endogenous retroviruses (HERVs). Endogenous retroviruses are retrotransposons, containing 5' and 3' long terminal repeat sequences and encoding envelope, group-specific antigen and DNA polymerase proteins. The aim of the present study was to analyse genome integration polymorphisms of HERV type K member 6 (HERV-K6) and HERV-K11 by using the retrotransposon based molecular marker technique, inter-retrotransposon amplified polymorphism (IRAP). For this purpose, blood samples of 18 healthy individuals within the age range of 10-79 years (10 females and 8 males) were collected, genomic DNAs were isolated and IRAP-polymerase chain reaction (PCR) was performed. IRAP-PCR analyses demonstrated that there were 0-70% polymorphism rates for HERV-K6, and 0-38% polymorphism rates for HERV-K11 among all the samples. Furthermore, the polymorphism rates were 0-70% among females and 11-60% among males for HERV-K6, and 0-38% among females and 0-25% among males for HERV-K11. Age-associated polymorphism was also investigated, but no age-associated polymorphism was observed among the samples. Therefore, HERV-K6 and HERV-K11 polymorphisms may arise on an individual-specific basis. Various previous studies have investigated the associations between the expression of HERVs and cancer or other major diseases. However, few reports have analysed HERV-K movements among individuals. This is the first report to investigate HERV-K6 and HERV-K11 retrotransposon polymorphisms between the genders and different age groups.


Detection of -lactamases in nosocomial gram negative clinical isolates.
-lactamases represent the most common mechanism of -lactam resistance. Extended spectrum -lactamases (ESBLs) represent a major group of -lactamases currently being identified worldwide in large numbers along with inducible AmpC -lactamases and derepressed mutants. The present study was done to detect -lactamase production in clinical isolates by rearranging routine discs used in reporting susceptibility to specifically assess ESBLs, AmpC -lactamases (both inducible and hyperproducers i.e., derepressed mutants). A total of 286 clinical isolates were studied using a novel predictor disc approximation method to detect the above mechanisms of resistance with careful use and placement of antimicrobial discs. Of the 286 isolates, 151(53%) were ESBL producers of which 131(46%) were also derepressed mutants while remaining 20(7%) were plain ESBL producers. Forty (14%) were plain derepressed mutants. Inducible AmpC -lactamase production was detected in 19(7%) of the isolates. The commonest ESBL producers were E.coli and K. pneumoniae. The high incidence of -lactamase production due to multiple mechanisms in clinical isolates is alarming and urgent action needs to be taken from both a therapeutic and infection control perspective.


Caffeine intake in relation to the risk of primary cardiac arrest.
We conducted a population-based case-control study in King County, WA, to evaluate the association between usual caffeine intake and primary cardiac arrest. We identified primary cardiac arrest cases (N = 362) without a history of clinical heart disease or major comorbidity through paramedic incident reports during the period 1988-1994. We identified controls (N = 581), individually matched to cases on age (+/-7 years) and gender and meeting the same general health criteria, through random digit dialing. We interviewed the spouses of cases and controls to obtain information on usual caffeine intake from coffee, tea, and cola during the prior year. After adjusting for cigarette smoking and other risk factors, we observed little association between daily consumption of the caffeine equivalent of fewer than 5 cups per day of drip coffee (< 687 mg per day) and primary cardiac arrest. High usual caffeine consumption (> or = 687 mg per day) was associated with a modestly elevated risk of primary cardiac arrest [odds ratio = 1.44; 95% confidence interval (CI) = 0.82-2.53]. The elevated risk associated with high caffeine consumption appeared to be restricted to never-smokers (odds ratio for > or = 687 mg per day = 3.2; 95% CI = 1.3-8.1).


The PICU perspective on monitoring hemodynamics and oxygen transport.
Alterations of hemodynamics and oxygen transport balance are very common scenarios in the pediatric intensive care unit (PICU), and these alterations are as heterogeneous and diverse in nature as are the patient populations that typically exist in the PICU. Accordingly, the PICU perspective on monitoring of hemodynamics and oxygen transport balance in critically ill children must be understood in this context of heterogeneity and diversity. We provide an interpretation of the evidence supporting various monitoring strategies as presented in the The Pediatric Cardiac Intensive Care Society Evidence Based Review and Consensus Statement on Monitoring of Hemodynamics and Oxygen Transport Balance from a Pediatric Intensive Care perspective.


Investigating impacts of marine sponge derived mycothiazole and its acetylated derivative on mitochondrial function and aging.
Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8- O -acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function. Similar to rotenone (Rote), a widely used ETC complex I inhibitor, these two molecules showed cytotoxicity to cancer cells but strikingly demonstrate a lack of toxicity to non-cancer cells, a highly beneficial feature in the development of anti-cancer therapeutics. Furthermore, in vivo experiments with these small molecules utilizing C.elegans model demonstrate their unexplored potential to investigate aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPR MT ) pathway, that extends lifespan of worms when applied in their adult stage. Interestingly, we also found that these two molecules employ different pathways to extend lifespan in worms. Whereas MTZ utilize the transcription factors ATFS-1 and HSF-1, which are involved in the UPR MT and heat shock response (HSR) pathways respectively, 8-OAc only required HSF-1 and not ATFS-1 to mediate its effects. This observation underscores the value of applying stable, potent, and selective next generation chemical probes to elucidate an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging.


Functional Outcomes Following Surgical Fixation of Paediatric Lateral Condyle Fractures of the Elbow - A Systematic Review.
Lateral humeral condyle fractures are the second most common elbow fractures in children. Both K-wire fixation and screw fixation have been advocated as suitable treatment options for displaced fractures. This study aimed to identify which fixation method was associated with the best functional outcomes. A systematic review was conducted. Studies reporting functional outcomes following surgical fixation of lateral condyle fractures were included for review. The primary outcome measure was functional outcome. The secondary outcome measure was major complications. A narrative analysis was undertaken, as meta-analysis was felt to be inappropriate due to the differences between included studies. Ten retrospective non-randomised, comparative studies were eligible and included. No randomised-controlled trials were identified. The highest rate of excellent functional outcomes was seen with screw fixation (120/126 [95%]), compared with K-wire fixation (135/162 [86%]). The incidence of major complications was comparable, with complications in 6/95 (6%) of screw fixations and 6/141 (4%) K-wire fixations. A small sample of data on closed reduction demonstrated excellent functional results in 73 of 76 (96%) of patients. Closed reduction of displaced fractures is associated with a significant learning curve however. The evidence was of poor quality and comprised of retrospective case series. This prevented meta-analysis and any firm conclusions being drawn from the available data. Screw fixation may be associated with improved functional outcomes. Complication rates between the two methods are comparable. Further prospective studies are recommended.


Electron-beam patterned self-assembled monolayers as templates for Cu electrodeposition and lift-off.
Self-assembled monolayers (SAMs) of 4'-methylbiphenyl-4-thiol (MBP0) adsorbed on polycrystalline gold substrates served as templates to control electrochemical deposition of Cu structures from acidic solution, and enabled the subsequent lift-off of the metal structures by attachment to epoxy glue. By exploiting the negative-resist behaviour of MBP0, the SAM was patterned by means of electron-beam lithography. For high deposition contrast a two-step procedure was employed involving a nucleation phase around -0.7 V versus Cu(2+)/Cu and a growth phase at around -0.35 V versus Cu(2+)/Cu. Structures with features down to 100 nm were deposited and transferred with high fidelity. By using substrates with different surface morphologies, AFM measurements revealed that the roughness of the substrate is a crucial factor but not the only one determining the roughness of the copper surface that is exposed after lift-off.


Evidence for Proinflammatory β-1,6 Glucans in the Pneumocystis carinii Cell Wall.
Inflammation is a major cause of respiratory impairment during Pneumocystis pneumonia. Studies support a significant role for cell wall β-glucans in stimulating inflammatory responses. Fungal β-glucans are comprised of d-glucose homopolymers containing β-1,3-linked glucose backbones with β-1,6-linked glucose side chains. Prior studies in Pneumocystis carinii have characterized β-1,3 glucan components of the organism. However, recent investigations in other organisms support important roles for β-1,6 glucans, predominantly in mediating host cellular activation. Accordingly, we sought to characterize β-1,6 glucans in the cell wall of Pneumocystis and to establish their activity in lung cell inflammation. Immune staining revealed specific β-1,6 localization in P. carinii cyst walls. Homology-based cloning facilitated characterization of a functional P. carinii kre6 (Pckre6) β-1,6 glucan synthase in Pneumocystis that, when expressed in kre6-deficient Saccharomyces cerevisiae, restored cell wall stability. Recently synthesized β-1,6 glucan synthase inhibitors decreased the ability of isolated P. carinii preparations to generate β-1,6 carbohydrate. In addition, isolated β-1,6 glucan fractions from Pneumocystis elicited vigorous tumor necrosis factor alpha (TNF-α) responses from macrophages. These inflammatory responses were significantly dampened by inhibition of host cell plasma membrane microdomain function. Together, these studies indicate that β-1,6 glucans are present in the P. carinii cell wall and contribute to lung cell inflammatory activation during infection.


Overexpression of TC2N is associated with poor prognosis in gastric cancer.
Background: Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods: We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot (WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results: The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was evidently associated with poor overall survival and recurrence-free survival. Conclusions: Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.


Survival trends of grade I, II, and III astrocytoma patients and associated clinical practice patterns between 1999 and 2010: A SEER-based analysis.
The survival trends and the patterns of clinical practice pertaining to radiation therapy and surgical resection for WHO grade I, II, and III astrocytoma patients remain poorly characterized. Using the Surveillance, Epidemiology and End Results (SEER) database, we identified 2497 grade I, 4113 grade II, and 2755 grade III astrocytomas during the period of 1999-2010. Time-trend analyses were performed for overall survival, radiation treatment (RT), and the extent of surgical resection (EOR). While overall survival of grade I astrocytoma patients remained unchanged during the study period, we observed improved overall survival for grade II and III astrocytoma patients (Tarone-Ware P < .05). The median survival increased from 44 to 57 months and from 15 to 24 months for grade II and III astrocytoma patients, respectively. The differences in survival remained significant after adjusting for pertinent variables including age, ethnicity, marital status, sex, tumor size, tumor location, EOR, and RT status. The pattern of clinical practice in terms of EOR for grade II and III astrocytoma patients did not change significantly during this study period. However, there was decreased RT utilization as treatment for grade II astrocytoma patients after 2005. Results from the SEER database indicate that there were improvements in the overall survival of grade II and III astrocytoma patients over the past decade. Analysis of the clinical practice patterns identified potential opportunities for impacting the clinical course of these patients.


The effects of oxygen and hyperinflation on arterial oxygen tension after endotracheal suctioning.
The effects of hyperinflation and increasing the FIO2 to 1.0 on PaO2 after endotracheal suctioning were examined in 28 patients after cardiac surgery. The changes in PaO2 immediately after and at 5- and 10-minutes after suctioning were compared with control values. Hyperinflation at the patient's baseline FIO2 produced a mean decrease in PaO2 of 18 mm Hg immediately after suctioning in over 75% of the sample. Preoxygenation with an increase in the ventilator FIO2 to 1.0 produced a mean increase in PaO2 of 48 mm Hg in 75% of the sample. Delivering preoxygenation by hyperinflation provided greater protection for all patients with a mean increase in PaO2 of 100 mm Hg. No statistically significant differences existed between the 5- and 10-minute PaO2 value and the control PaO2 values for any of the procedures. Experimental hyperinflation was aborted in two patients who experienced significant hypotension in association with the hyperinflation. The hypotension was transient, with arterial blood pressure immediately returning to baseline values on termination of the experimental hyperinflation. In conclusion, 100% oxygen administered by hyperinflation for 1 minute before and after endotracheal suctioning protects patients after cardiac surgery from a fall in PaO2. Because hyperinflation can cause alterations in arterial blood pressure and heart rate, these vital signs should be visually monitored during the endotracheal suctioning procedure.


Aural polyp with facial asymmetry in an unfortunate infant.
Temporal bone rhabdomyosarcoma is an aggressive entity that simulates chronic otitis ear infection. It is the most common soft tissue sarcoma amongst pediatric patients. Herein, we would like to report a case of temporal bone rhabdomyosarcoma involving a 2-year-old boy who presented with a one-month history of otorrhea with facial asymmetry. Early treatment led to remission of this severe neoplasm.


[Mycoplasma-like sturctures in podzol soils of the southern taiga in the Irtysh region].
Mycoplasm-like organisms were found in taiga podzolic soils of the South Irtish region. They were detected in close contact with soil bacteria more ofter than in a free state. The mycoplasm-like organisms either were absorbed on the bacterial cell walls or grew inside the cytoplasm as filamentous forms; sometimes they filled the whole inner space of the cells, disrupted the cell wall, and were liberated into the surrounding medium.


Opposing functions of IKKbeta during acute and chronic intestinal inflammation.
NF-kappaB is a key transcriptional regulator of inflammatory responses, but also controls expression of prosurvival genes, whose products protect tissues from damage and may thus act indirectly in an antiinflammatory fashion. The variable importance of these two distinct NF-kappaB-controlled responses impacts the potential utility of NF-kappaB inhibition as a treatment strategy for intractable inflammatory conditions, such as inflammatory bowel disease. Here, we show in murine models that inhibition of IKKbeta-dependent NF-kappaB activation exacerbates acute inflammation, but attenuates chronic inflammatory disease in the intestinal tract. Acute ulcerating inflammation is aggravated because of diminished NF-kappaB-mediated protection against epithelial cell apoptosis and delayed mucosal regeneration secondary to reduced NF-kappaB-dependent recruitment of inflammatory cells that secrete cytoprotective factors. In contrast, in IL-10-deficient mice, which serve as a model of chronic T cell-dependent colitis, ablation of IKKbeta in the intestinal epithelium has no impact, yet IKKbeta deficiency in myeloid cells attenuates inflammation and prolongs survival. These results highlight the striking context and tissue dependence of the proinflammatory and antiapoptotic functions of NF-kappaB. Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration.


Differentiation inducing effects of butyrate and DMSO on human intestinal tumor cell lines in culture.
In the present report, we have studied the effects of butyrate and dimethyl sulfoxide (DMSO) on the characteristics of four human intestinal tumor cell lines in vitro; namely a duodenal adenocarcinoma HTB-40 and three adenocarcinomas of colon: HT-29, CCL-218, and CCL-222. In the presence of concentrations of 2 mM butyrate and 2% DMSO the growth of all these four cell lines was significantly inhibited. Both these agents lengthened the doubling time of these cell lines by about twofold. In addition, the morphology of the treated cells was altered. All four cell lines grow in semisolid agar and form characteristic colonies. Butyrate and DMSO inhibited the colony forming efficiency of these cell lines by 40-60%. Using flow cytometric analysis, the cells that were grown in the presence of butyrate and DMSO were analyzed for their lectin-binding properties. For this purpose the lectins used were concanavalin-A (Con-A), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and succinylated wheat germ agglutinin (SWGA). All four cell lines showed an increase in lectin-binding cells. CCL-218, which showed no PNA binding when grown without these agents, acquired about 25% reactivity when grown in the presence of butyrate or DMSO. All these cell lines showed an increase in the percentage of positive cells for the lectin SWGA that unlike WGA does not bind to sialic acid on the cell surface, suggesting an increase in nonsialated residues on all the treated cells. These results indicate a differentiation inducing effect of butyrate and DMSO on these cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)


Current concepts in locking plate fixation of proximal humerus fractures.
Despite numerous available treatment strategies, the management of complex proximal humeral fractures remains demanding. Impaired bone quality and considerable comorbidities pose special challenges in the growing aging population. Complications after operative treatment are frequent, in particular loss of reduction with varus malalignment and subsequent screw cutout. Locking plate fixation has become a standard in stabilizing these fractures, but surgical revision rates of up to 25% stagnate at high levels. Therefore, it seems of utmost importance to select the right treatment for the right patient. This article provides an overview of available classification systems, indications for operative treatment, important pathoanatomic principles, and latest surgical strategies in locking plate fixation. The importance of correct reduction of the medial cortices, the use of calcar screws, augmentation with bone cement, double-plate fixation, and auxiliary intramedullary bone graft stabilization are discussed in detail.


[Pharmacokinetics of vancomycin in neonates of postconceptional age less than or equal to 32 weeks].
The objective of the present study was to analyze the pharmacokinetic behavior of vancomycin in neonates of postconceptional age < or = 32 weeks (n = 44). The elimination of the antibiotic was influenced by the concomitant treatment with indomethacin and mechanical ventilation. Close monitoring of renal function of the neonate and vancomycin dosage individualization are mandatory when the above factors are present. Vancomycin dosage guidelines have been determined according to serum creatinine of these premature patients.


Regeneration potential of the young permanent tooth: what does the future hold?
During the last 10-15 years, there has been a tremendous increase in our clinical "tools" (ie, materials, instruments, and medications) and knowledge from the trauma and tissue engineering fields that can be applied to regeneration of a functional pulp-dentin complex. In addition, recent case reports indicate that biologically based endodontic therapies can result in continued root development, increased dentinal wall thickness, and apical closure when treating cases of necrotic immature permanent teeth. The purpose of this review was to summarize these findings and illustrate a path forward for the development and evaluation of regenerative endodontic therapies.


Haptic pop-out in a hand sweep.
Visually, a red item is easily detected among green items, whereas a mirrored S among normal Ss is not. In visual search, the former is known as the pop-out effect. In daily life, people often also conduct haptic (tactual) searches, for instance, when trying to find keys in their pocket. The aim of the present research was to determine whether there is a haptic version of the pop-out effect. Blindfolded subjects had to search for a target item which differed in roughness from the surrounding distractor items. We report reaction time slopes as low as 20 ms/item. When target and distractor identities were interchanged the slopes increased indicating a search asymmetry. Furthermore, we show that differences in search slope were accompanied by search strategy differences. In some conditions a single-hand sweep over the display was sufficient, while in others a more detailed search strategy was used. By relating haptic search slopes to parallel and serial search strategies we show, for the first time, that pop-out effects occur under free manual exploration.


Low N Fertilizer Application and Intercropping Increases N Concentration in Pea (Pisum sativum L.) Grains.
Sustainable intensification of pulses needs reduced input of nitrogen (N) fertilizer with enhanced crop nutritional quality and yield. Therefore, increasing N harvest in grains (sink organs) by improving N remobilization is of key importance. Previous research has shown that a lower dose of N fertilizer effectively increases the rate of N remobilization, while intercropping improves the grain N concentration in pea (Pisum sativum L.). However, it is unknown whether intercropping can facilitate this N fertilizer effect to increase N remobilization, and thereby enhance the N harvest index (NHI). In this study, we determined N allocation among different organs of pea plants, N translocation from leaf and stem tissues to pods, N2 fixation, N utilization efficiency, and NHI of pea plants grown alone or intercropped with maize (Zea mays L.) with different N fertilization treatments in a field experiment in northwestern China from 2012 to 2014. A base application of 90 kg N ha-1 at sowing and top-dress application of 45 kg N ha-1 at flowering integrated with maize-pea intercropping increased N allocation to pod tissues, N translocation to grains, and NHI of pea plants. Compared with the application of 90 kg N ha-1 at sowing and 135 kg N ha-1 top-dressed at flowering, reducing the top-dress application of N fertilizer to 45 kg N ha-1 increased N allocation to intercropped pea plants by 8%. Similarly, N translocation to grains from leaf and stem tissues was increased by 37.9 and 43.2%, respectively, enhancing the NHI by 40.1%. A positive correlation between N2 fixation and NHI was observed, implying that N2 fixation improves N concentration in grain sinks. Thus, our data show that growing pulses in an intercropping system with reduced N fertilization are essential for maximizing N translocation, improving nutritional quality, and preventing the loss of N through leaching, thereby avoiding potential groundwater contamination.


Gender differences in cancer carer psychological distress: an analysis of moderators and mediators.
Women cancer carers report higher rates of distress than men; however, there is little understanding of the mechanisms underlying these gender differences. The aim of this study was to examine the potential mediating roles of burden of care, unmet needs, self-silencing, self-efficacy and optimism, and the potential moderating influence of social support, cancer stage, patient gender, time spent caring and other responsibilities, on gender differences in carer distress. Of 329 informal cancer carers (245 women, 119 men), women reported significantly more anxiety, burden of care and unmet needs than men. In the mediation analysis, gender differences in anxiety were fully explained by both the independent contribution and combination of: Disrupted Schedule, Health Problems and Emotional and Spiritual Unmet Needs. Women cared for both men and women patients, across a broad range of relationships, whereas men predominantly cared for their female partner. There was no gender difference in number of hours spent caring or in companionship, amount of support received, and additional responsibilities for children, housework or studies, and none of these factors acted as moderators of gender differences in anxiety. It is concluded that women's gendered role is associated with unmet needs and burden of care, resulting in greater anxiety.


Local Impacts of Religious Discourses on Rights to Express Same-Sex Sexual Desires in Peri-Urban Rio de Janeiro.
This article reports on a study that examined how religious discourses of inclusion and exclusion-in Roman Catholic, evangelical Protestant, and Afro-Brazilian religious traditions-affected people's rights to express same-sex sexual desires, behaviors, and identities in the socioeconomically marginalized urban periphery of Rio de Janeiro, Brazil. Using extended ethnographic observation of institutions and religious events over a period of 2 years, the authors identified how sexual rights were constructed within religious discourses and conducted ethnographic interviews with 45 religious leaders. In the low-income and violent urban periphery of Rio de Janeiro, religious leaders and institutions play key roles in molding community inclusion and exclusion. A comparison of the 3 major religious denominations shows a diversity of discourses about same-sex sexual desires and their impacts on community formation.


Fecal Metabolomic Signatures in Colorectal Adenoma Patients Are Associated with Gut Microbiota and Early Events of Colorectal Cancer Pathogenesis.
Colorectal adenomas are precancerous lesions of colorectal cancer (CRC) that offer a means of viewing the events key to early CRC development. A number of studies have investigated the changes and roles of gut microbiota in adenoma and carcinoma development, highlighting its impact on carcinogenesis. However, there has been less of a focus on the gut metabolome, which mediates interactions between the host and gut microbes. Here, we investigated metabolomic profiles of stool samples from patients with advanced adenoma (n = 102), matched controls (n = 102), and patients with CRC (n = 36). We found that several classes of bioactive lipids, including polyunsaturated fatty acids, secondary bile acids, and sphingolipids, were elevated in the adenoma patients compared to the controls. Most such metabolites showed directionally consistent changes in the CRC patients, suggesting that those changes may represent early events of carcinogenesis. We also examined gut microbiome-metabolome associations using gut microbiota profiles in these patients. We found remarkably strong overall associations between the microbiome and metabolome data and catalogued a list of robustly correlated pairs of bacterial taxa and metabolomic features which included signatures of adenoma. Our findings highlight the importance of gut metabolites, and potentially their interplay with gut microbes, in the early events of CRC pathogenesis.IMPORTANCE Colorectal adenomas are precursors of CRC. Recently, the gut microbiota, i.e., the collection of microbes residing in our gut, has been recognized as a key player in CRC development. There have been a number of gut microbiota profiling studies for colorectal adenoma and CRC; however, fewer studies have considered the gut metabolome, which serves as the chemical interface between the host and gut microbiota. Here, we conducted a gut metabolome profiling study of colorectal adenoma and CRC and analyzed the metabolomic profiles together with paired microbiota composition profiles. We found several chemical signatures of colorectal adenoma that were associated with some gut microbes and potentially indicative of future CRC. This study highlights potential early-driver metabolites in CRC pathogenesis and guides further targeted experiments and thus provides an important stepping stone toward developing better CRC prevention strategies.


Current Trends and Controversies in the Management of Warthin Tumor of the Parotid Gland.
To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol. A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality. The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient's wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases. The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies.


Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment.
To investigate low-dose hypersensitivity to cisplatin and increased resistance at higher doses of cisplatin for the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP, and to examine the effects of pre- and post-treatment of SCC-25 cells with low-doses of gamma-rays on their resistance to cisplatin. SCC-25 and SCC-25/CP cells were treated with various cisplatin concentrations (0.1 to 20 microM for 1 h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5 cGy to 2.5 Gy) were given either 10 or 60 min before the cisplatin challenge dose as well as either 10 or 60 min after the cisplatin challenge dose. Low-dose (0.5, 0.75 and 1 microM for 1 h) hypersensitivity to cisplatin and increased resistance at higher doses was detected for the SCC-25 cell line, but not for its cisplatin-resistant derivative, SCC-25/CP. Pretreatment of SCC-25 cells with an acute low-dose of 5, 25 cGy or 1 Gy gamma-rays given 60 min before a low-dose cisplatin challenge (0.1 and 1 microM for 1 h) resulted in a significant increase in resistance (p=0.2, 0.01 and <0.001 respectively). For pretreatment of SCC-25 cells with similar low-doses of gamma-rays 10 min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25 cGy and a challenge cisplatin dose of 0.1 microM for 1 h (p = 0.02). Similar acute low-doses of y-rays given either 10 or 60 min after the challenge cisplatin dose did not increase resistance. The human squamous carcinoma cell line SCC-25 showed a low-dose hypersensitivity to cisplatin followed by increased resistance at higher doses. Treatment of SCC-25 cells with low-doses of gamma-rays can induce a protective effect to a subsequent low-dose cisplatin challenge.


Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.
A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.


Efficient immortalization of human dental pulp stem cells with expression of cell cycle regulators with the intact chromosomal condition.
Clinical studies have recently demonstrated that autologous transplantation of mobilized dental pulp stem cells is a safe and efficacious potential therapy for pulp regeneration. However, some limitations need to be addressed, such as the high cost of the safety and quality control tests for isolated individual dental pulp cell products before transplantation. Therefore, more efficient in vitro culturing of human dental pulp stem cells might be useful for providing low cost and high reliability testing for pulp regeneration therapy. In this study, we established a novel immortalized dental pulp stem cell line by co-expressing a mutant cyclin-dependent kinase 4 (CDK4R24C), Cyclin D1, and telomerase reverse transcriptase (TERT). The established cell line maintained its original diploid chromosomes and stemness characteristics and exhibited an enhanced proliferation rate. In addition, we showed the immortalized human dental pulp stem cells still keeps their osteogenic and adipogenic differentiation abilities under appropriate culture conditions even though the cell proliferation was accelerated. Taken together, our established cell lines could serve as a useful in vitro tool for pulp regeneration therapy, and can contribute to reproducibility and ease of cell handling, thereby saving time and costs associated with safety and quality control tests.


Robotic-assisted laparoscopic and radical retropubic prostatectomy generate similar positive margin rates in low and intermediate risk patients.
Robotic-assisted laparoscopic prostatectomy (RALP) is being increasingly utilized. To assess the efficacy of the operation, we compared apical and overall margin status for RALP with radical retropubic prostatectomy (RRP) in a group of contemporary patients. We retrospectively reviewed 98 consecutive RRPs and then 94 RALPs from a single institution. Groups were analyzed and matched with regard to preoperative prostate-specific antigen (PSA), cancer grade, pathologic stage, and tumor volume. Surgical margins were quantitated. Clinicopathologic parameters were compared and additional high risk patients were observed in the RRP vs. RALP group. To risk-adjust these patient groups, those meeting preoperative high risk criteria were excluded from further positive margin analysis. Postoperatively, the average tumor volume was 13% in both groups. Pathologic stage pT3 was similar between RRP (14%) and RALP (11%). A positive surgical margin (PSM) was found in 12 cases (14%) after RRP and 11 cases (13%) after RALP including apical margins. Positive margins at the apex, non-apex, and both were statistically similar between groups. In this study, no differences were seen between robotic prostatectomy with regard to apical or overall margin status compared with open prostatectomy in lower risk patients. This suggests that despite improved visualization, RALP generates a similar margin status as RRP.


Trifluoromethylated Nucleic Acid Analogues Capable of Self-Assembly through Hydrophobic Interactions.
An artificial nucleic acid analogue capable of self-assembly into duplex merely through hydrophobic interactions is presented. The replacement of Watson-Crick hydrogen bonding with strictly hydrophobic interactions has the potential to confer new properties and facilitate the construction of complex DNA nanodevices. To study how the hydrophobic effect works during the self-assembly of nucleic acid bases, we have designed and synthesized a series of fluorinated nucleic acids (FNA) containing 3,5-bis(trifluoromethyl) benzene (F) and nucleic acids incorporating 3,5-dimethylbenzene (M) as hydrophobic base surrogates. Our experiments illustrate that two single-stranded nucleic acid oligomers could spontaneously organize into a duplex entirely by hydrophobic base pairing if the bases were size-complementary and the intermolecular forces were sufficiently strong.


Chemical profile and antihyperlipidemic effect of Portulaca oleracea L. seeds in streptozotocin-induced diabetic rats.
Hypolipidemic effect of Portulaca oleracea L. seed extract and its fractions have been studied on streptozotocin (STZ) at dose 75 mg/kg b.wt. After fractionation of the alcoholic extract; petroleum ether fraction was the most active fraction that decreased different hyperlipidemia biochemical parameters. After chromatographic analysis; oleamide, ethylpalmitate, β-amyrin, stigmasterol and β-sitosterol were identified. The GLC analysis of unsaponifiable matter revealed the presence of; lignoceric acid as a major constituent in the most bioactive fraction. In conclusion, petroleum ether fraction possessed a hypolipidemic effect in STZ-induced diabetic rats, which may be attributed to its phytosterols, fatty acid and amide compounds. The finding of the present investigation strongly demonstrates the potential of non-polar fraction of P. oleracea L. seed in combating hyperlipidemia in diabetic condition. So the petroleum ether fractions and its constituents can be used as hypolipdemic supplement in the developing countries towards the development of new therapeutic agents.


Discography: an element of decision. Surgery versus chemonucleolysis.
It is a well known fact that both surgery and chemonucleolysis can cure a patient suffering from root pain due to a prolapsed intervertebral disc. However, the failure rate after intradiscal injection of chymopapain remains important. Analysis of the cases operated after unsuccessful chemonucleolysis show that about two thirds are due to a remaining discal fragment. Considering the possibility of a bad penetration of the enzyme in the herniated area, neither computed tomography (CT) scan nor myelography, but only discography, can demonstrate invasion of the prolapsed area. On a series of 165 patients injected with chymopapain in only one disc, discographic data were correlated with the result of the treatment on the root pain. Three items were analyzed: the size of the protruding area located at the back of the disc (closely related to operative findings, as shown on a previous study), the density of the contrast medium filling the protruding area, and the pain response during the injection. A large, well-filled protruding area characterizes a "good" image and correlated with 76% of good results. Likewise when the pain response is lateralized (in the buttock or the affected lower limb), it correlates with 42% of success and 13% of failures. In 24.8% of the cases a combination of good images and lateralized pain correlates with 97.5% of good results. Therefore discography should be an element of decision between surgery and chemonucleolysis, and should be considered as a preoperative examination.


Effect of four weeks' high dose ipratropium bromide treatment on lung mucociliary clearance.
In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 micrograms three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity.


Evaluation of a community program for the control of cardiovascular risk factors: the CHAD program in Jerusalem.
A community-focused program for the control of cardiovascular risk factors, the CHAD program, was instituted in a family practice in western Jerusalem in 1971. Its effectiveness was evaluated by comparing the changes detected by surveys conducted in 1970 and 1975 with those observed in an adjacent control neighborhood. Hypertension decreased in prevalence by 33%, hypercholesterolemia by 31%, cigarette smoking by 23% (among men), and overweight by 13%. Allowing for the reductions observed in the control population, the net percent reductions in prevalence were 20% for hypertension, 15% for hypercholesterolemia, 11% for cigarette smoking (men) and 13% for overweight. The net reductions in hypertension, smoking and overweight were statistically significant. The net reductions in mean systolic and diastolic pressures and weight were also significant. The results suggest that intervention centered in primary health care can have an appreciable effect on cardiovascular risk factors in the population.


Combined use of sonographic and elastosonographic parameters can improve the diagnostic accuracy in thyroid nodules at risk of malignancy at cytological examination.
Thyroid nodules diagnosed as Thy3B at fine-needle aspiration biopsy have a relevant risk of malignancy (15-30%) and are usually addressed to surgery. However surgery will result unnecessary in most cases. The present study aims at evaluating the possible increase of diagnostic accuracy for predicting malignancy using novel sonographic and elastographic parameters. In fifty patients undergoing thyroidectomy because of a Thy3B thyroid nodule, sonographic and elastosonographic evaluation was carried out by single operator before surgery. Five sonographic parameters (echogenicity, irregular margins, microcalcifications, intra-nodule blood flow and its irregularity) and two elastosonographic parameters (intra-nodule stiffness and its extension to adjacent tissue) were considered. After obtaining histological diagnosis, diagnostic accuracy was calculated. When the two procedures were analyzed separately, sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were 100%, 85%, 63% and 100% for ultrasonography and 60%, 92.5%, 67%, 90% for elastrosonography, respectively. The newly introduced evaluation procedures increased sensitivity. When a combined sonographic and elastosonographic evaluation was introduced, diagnostic accuracy was significantly improved: when ≥4 out of the seven parameters indicated were present, the risk of malignancy was very high (sensitivity 100%, specificity 92.55%, PPV 77%, NPV 100%). A novel combined sonographic and elastosonographic parameter evaluation improved diagnostic accuracy for identifying thyroid nodules suspicious of malignancy.


Mutational activation of a Galphai causes uncontrolled proliferation of aerial hyphae and increased sensitivity to heat and oxidative stress in Neurospora crassa.
Heterotrimeric G proteins, consisting of alpha, beta, and gamma subunits, transduce environmental signals through coupling to plasma membrane-localized receptors. We previously reported that the filamentous fungus Neurospora crassa possesses a Galpha protein, GNA-1, that is a member of the Galphai superfamily. Deletion of gna-1 leads to defects in apical extension, differentiation of asexual spores, sensitivity to hyperosmotic media, and female fertility. In addition, Deltagna-1 strains have lower intracellular cAMP levels under conditions that promote morphological abnormalities. To further define the function of GNA-1 in signal transduction in N. crassa, we examined properties of strains with mutationally activated gna-1 alleles (R178C or Q204L) as the only source of GNA-1 protein. These mutations are predicted to inhibit the GTPase activity of GNA-1 and lead to constitutive signaling. In the sexual cycle, gna-1(R178C) and gna-1(Q204L) strains are female-fertile, but produce fewer and larger perithecia than wild type. During asexual development, gna-1(R178C) and gna-1(Q204L) strains elaborate abundant, long aerial hyphae, produce less conidia, and possess lower levels of carotenoid pigments in comparison to wild-type controls. Furthermore, gna-1(R178C) and gna-1(Q204L) strains are more sensitive to heat shock and exposure to hydrogen peroxide than wild-type strains, while Deltagna-1 mutants are more resistant. In contrast to Deltagna-1 mutants, gna-1(R178C) and gna-1(Q204L) strains have higher steady-state levels of cAMP than wild type. The results suggest that GNA-1 possesses several Gbetagamma-independent functions in N. crassa. We propose that GNA-1 mediates signal transduction pathway(s) that regulate aerial hyphae development and sensitivity to heat and oxidative stresses, possibly through modulation of cAMP levels.


Photonic Topological Mode Bound to a Vortex.
We report the observation of a mode associated with a topological defect in the bulk of a 2D photonic material by introducing a vortex distortion to a hexagonal lattice analogous to graphene. The observed modes lie midgap at zero energy and are closely related to Majorana bound states in superconducting vortices. This is the first experimental demonstration of the Jackiw-Rossi model [R. Jackiw and P. Rossi, Nucl. Phys. B190, 681 (1981)NUPBBO0550-321310.1016/0550-3213(81)90044-4].


Asymmetric microtubule arrays organize the endoplasmic reticulum during polarity establishment in the brown alga Silvetia compressa.
Polarity is a fundamental characteristic of most cell types, and is crucial to early development of the brown alga Silvetia compressa. In eukaryotes the cytoskeleton plays an important role in generating cellular asymmetries. While it is known that F-actin is required for polarization and growth in most tip-growing cells, the roles of microtubules are less clear. We examined the distribution and function of microtubules in S. compressa zygotes as they polarized and initiated tip growth. Microtubules formed asymmetric arrays oriented toward the rhizoid hemisphere early in the polarization process. These arrays were spatially coupled with polar adhesive deposition, a marker of the rhizoid pole. Reorientation of the light vector during polarization led to sequential redistribution of polar axis components, with the microtubules and the polar axis reorienting nearly simultaneously, followed by cell wall loosening and then deposition of new polar adhesive. These findings suggested that microtubules may organize and target endomembrane arrays. We therefore examined the distribution of the endoplasmic reticulum during polarization and found it colocalized with microtubules and became targeted toward the rhizoid pole as microtubule asymmetry was generated. Endoplasmic reticulum association with microtubules remained fully intact following pharmacological disruption of F-actin, whereas microtubule disruption led to aggregation of the endoplasmic reticulum around the nucleus. We propose that brown algae utilize microtubules for organization of the endoplasmic reticulum and migration of exocytotic components to the rhizoid cortex, and present a model for polarity establishment to account for these new findings.


'Candidatus Mycoplasma haemosphiggurus' a novel haemoplasma species in orange-spined hairy dwarf porcupines (Sphiggurus villosus) from Southern Brazil.
In Brazil, the orange-spined hairy dwarf porcupine (Sphiggurus villosus) is widely distributed in the Atlantic Rainforest biome being amongst the most frequently road-killed animal. Porcupines may also be commonly found on forest borders and occasionally, near urban areas where human and domestic dogs injuries caused by its spines may occur. Therefore, the aims of this study were (a) to screen porcupines for TBD pathogens and haemoplasmas and (b) to identify the tick species parasitizing these rodents in Paraná State, southern Brazil. Blood and/or spleen samples were collected from nine orange-spined hairy dwarf porcupines. A total of 275 ticks (34 males, 11 females, 7 nymphs and 223 larvae) were collected from eight porcupines: Amblyomma longirostre, A. parkeri and Amblyomma spp. larvae. Two out of nine (22%; 95% CI: 3%-60%) porcupines were PCR-positive for haemoplasmas. All animals tested negative for Theileria/Babesia spp. and Ehrlichia/Anaplasma spp. by PCR. Phylogenetic and network analysis of the 16S and 23S rRNA gene fragments confirmed that animals were infected by a potentially novel haemotropic Mycoplasma sp. The name 'Candidatus Mycoplasma haemosphiggurus' is proposed for this novel organism that should be further fully characterized.


Has the practice of radiation oncology for locally advanced and metastatic non-small-cell lung cancer changed in Canada?
Previous surveys have revealed wide variations in the management by radiation oncologists of non-small-cell lung cancer (NSCLC) in Canada. The aim of the present study was to determine the current patterns of practice for locally advanced and metastatic NSCLC among Canadian radiation oncologists. An online survey was distributed electronically to all members of the Canadian Association of Radiation Oncologists. Those who treat lung cancer were invited to participate. The survey consisted of three scenarios focusing on areas of nsclc treatment in which the radiotherapy (RT) regimen that provides the best therapeutic ratio is unclear. Replies from 41 respondents were analyzed. For an asymptomatic patient with stage IIIB NSCLC unsuitable for radical treatment, 22% recommended immediate RT, and 78% recommended RT only if the patient were to become symptomatic. Those who believed that immediate RT prolongs survival were more likely to recommend it (p = 0.028). For a patient with a bulky stage IIIB tumour and good performance status, 39% recommended palliative treatment, and 61% recommended radical treatment (84% concurrent vs. 16% sequential chemoradiation at 60-66 Gy in 30-33 fractions). Those who believed that chemoradiation has a greater impact on survival were more likely to recommend it (p < 0.001). For a symptomatic patient with stage IV NSCLC, 54% recommended external-beam RT (EBRT) alone, 41% recommended other modalities (brachytherapy, endobronchial therapy, or chemotherapy) with or without EBRT, and 5% recommended best supportive care. A majority (76%) prescribed 20 Gy in 5 fractions for EBRT. Compared with previous surveys, more radiation oncologists now offer radical treatment for locally advanced NSCLC. Management of nsclc in Canada may be evidence-based, but perception by radiation oncologists of the treatment's impact on survival also influences treatment decisions.


Ultra-low-loss tunable piezoelectric-actuated metasurfaces achieving 360° or 180° dynamic phase shift at millimeter-waves.
Phase shifting metasurfaces typically consist of an ordered metallic geometry that is patterned onto a dielectric substrate and incorporate active devices or materials that enable dynamic tuning. Existing methods at mm-wave and submillimeter bands typically suffer from high losses, which are predominantly produced by the inherent limitations of the tuning elements or materials. This report presents a new, ultra-low-loss and phase-tunable, reflection type metasurface design, which outperforms previously reported technologies in terms of phase shifting and loss. The proposed technique utilizes a variable air cavity, formed between a periodic array and a ground plane, which is controlled by means of a piezoelectric actuator. Two metasurface designs are presented and experimentally tested. Firstly, a square patch element metasurface that is capable of achieving a continuous 180° phase shift across a wide bandwidth, between 35 and 65 GHz. Also presented is a double-cross element metasurface that provides full 360° phase control between 57 and 62 GHz. The variable air cavity is controlled by means of a piezoelectric actuator that supports and varies the height of a ground plane, providing highly accurate, millisecond, displacement. Unlike conventional tuning methods, the tuning mechanism, in this case the moving ground plane, introduces no additional sources of loss and enables an average loss performance of 1 dB. Full-wave simulations are presented and experimentally validated with measurements of both metasurface prototypes. The proposed approach is scalable from microwave up to THz frequencies, due to the electro-mechanical and low loss nature of the tuning.


A novel high-throughput imaging system for automated analyses of avoidance behavior in zebrafish larvae.
Early brain development can be influenced by numerous genetic and environmental factors, with long-lasting effects on brain function and behavior. The identification of these factors is facilitated by recent innovations in high-throughput screening. However, large-scale screening in whole organisms remains challenging, in particular when studying changes in brain function or behavior in vertebrate model systems. In this study, we present a novel imaging system for high-throughput analyses of behavior in zebrafish larvae. The three-camera system can image 12 multiwell plates simultaneously and is unique in its ability to provide local visual stimuli in the wells of a multiwell plate. The acquired images are converted into a series of coordinates, which characterize the location and orientation of the larvae. The developed imaging techniques were tested by measuring avoidance behaviors in seven-day-old zebrafish larvae. The system effectively quantified larval avoidance and revealed an increased edge preference in response to a blue or red 'bouncing ball' stimulus. Larvae also avoid a bouncing ball stimulus when it is counter-balanced with a stationary ball, but do not avoid blinking balls counter-balanced with a stationary ball. These results indicate that the seven-day-old larvae respond specifically to movement, rather than color, size, or local changes in light intensity. The imaging system and assays for measuring avoidance behavior may be used to screen for genetic and environmental factors that cause developmental brain disorders and for novel drugs that could prevent or treat these disorders.


Diet and cancer - some results from Singapore.
The notion that diet has an aetiological role in cancer is generally accepted, although the actual agents and mechanisms are still subjects of much research. A major problem in this work is the lack of effective instruments in determining dietary exposures. The wide margin given as the likely population attributable risk (10-70%) is an indication of the relative imprecision of our state of knowledge at this moment. In Singapore, digestive tract cancers account for about 30% of all cancers in males and 24% in fem les. In addition, other cancers that have a strong dietary link include lung (24% males, 10% females), liver (9% males, 4% females), nasopharynx (7% males, 4% females), female breast (17%) and prostate (3%). Therefore, this is a very important subject for continued study in view of the preventive potential. Based on recent studies conducted in Singapore, a review is provided of factors associated with colorectal and breast cancers. The main thrust of our findings point to the rob of me t s ~ predisposing factor and vegetables/fruits as protective foods. Possible agents and mechanisms of action will be discussed.


Some reflections on a few of the pitfalls in the world of foundation grant making.
This paper offers some reflections on the grant-making process from a former foundation executive. Some of the opportunities, challenges, and pitfalls inherent in the foundation world are described, and one approach to grant making, the "call for proposals," is examined as an example of the need for greater attention to and investment in the science of grant making itself, to maximize the potential return from philanthropy.


Novel oxidative coupling reactions of cisapride or metaclopramide with phenoxazines and their applications in the determination of nitrite at trace level in environmental samples.
Phenoxazine (PNZ), 2-chlorophenoxazine (CPN) and 2-trifluoromethylphenoxazine (TPN) were used as new class of spectrophotometric reagents for the determination of nanoamounts of nitrite in presence of cisapride (CSP) and metaclopramide (MCP) as new electrophilic coupling reagents. The methods were based on the oxidation of CSP or MCP by nitrite in hydrochloric acid medium and coupling with PNZ, CPN or TPN to yield red color derivatives which were stable for about 3h and having an absorbance maximum in the range 520-530 nm. Beer's law is obeyed for nitrite in the concentration range 0.08-0.80 and 0.13-1.60 microg ml(-1) for phenoxazine-cisapride and phenoxazine-metaclopramide, respectively. The optimum reaction conditions and other important analytical parameters were established to enhance the sensitivity of these methods. Interference due to various non-target ions was also investigated. The methods were applied to the analysis of nitrite in environmental samples. The performance of proposed methods were evaluated by Student's t-test and variance ratio F-test indicated the significance of proposed methods over the reference spectrophotometric method (Association of Official Analytical Communities (AOAC) method for the determination of nitrite in water samples).