Unraveling the effects of 1,25OH2D3 on global gene expression in pancreatic islets.
Vitamin D deficiency has been linked to type 1 and 2 diabetes, whereas supplementation may prevent both diseases. However, the extent of the effects of vitamin D or its metabolites directly on pancreatic islets is still largely unknown. The aim of the present study was to investigate how active vitamin D, 1,25(OH)2D3, affects beta cells directly by establishing its effects on global gene expression in healthy murine islets. Pancreatic islets were isolated from 2 to 3 week old C57BL/6 mice and cultured in vitro with 1,25(OH)2D3 or vehicle for 6 and 24h. Total RNA was extracted from the islets and the effects on global gene expression were analyzed using Affymetrix microarrays. Exposure to 1,25(OH)2D3 compared to vehicle resulted in 306 and 151 differentially expressed genes after 6 and 24h, respectively (n=4, >1.3-fold, p<0.02). Of these 220 were up-regulated, whereas 86 displayed a decreased expression after 6h. Furthermore, expression levels were increased for 124 and decreased for 27 genes following 24h of exposure. Formation of intercellular junctions, cytoskeletal organization, and intracellular trafficking as well as lipid metabolism and ion transport were among the most affected gene classes. Effects on several genes already identified as being part of vitamin D signaling in other cell types were observed along with genes known to affect insulin release, although with our assay we were not able to detect any effects of 1,25(OH)2D3 on glucose-stimulated insulin release from healthy pancreatic islets. The effects of 1,25(OH)2D3 on the expression of cytoskeletal and intracellular trafficking genes along with genes involved in ion transport may influence insulin exocytosis. However, an effect of 1,25(OH)2D3 on insulin release could not be detected for healthy islets in contrast to islets subjected to pathological conditions such as cytokine exposure and vitamin D deficiency as suggested by other studies. Thus, in addition to previously identified tolerogenic effects on the immune system, 1,25(OH)2D3 may affect basic functions of pancreatic beta cells, with the potential to render them more resistant to the detrimental conditions encountered during type 1 and 2 diabetes. This article is part of a Special Issue entitled 'Vitamin D Workshop'.


Multispectral synthesis of daylight using a commercial digital CCD camera.
Performance of multispectral devices in recovering spectral data has been intensively investigated in some applications, as in spectral characterization of art paintings, but has received little attention in the context of spectral characterization of natural illumination. This study investigated the quality of the spectral estimation of daylight-type illuminants using a commercial digital CCD camera and a set of broadband colored filters. Several recovery algorithms that did not need information about spectral sensitivities of the camera sensors nor eigenvectors to describe the spectra were tested. Tests were carried out both with virtual data, using simulated camera responses, and real data obtained from real measurements. It was found that it is possible to recover daylight spectra with high spectral and colorimetric accuracy with a reduced number of three to nine spectral bands.


Practice of Awake Prone Positioning in Critically Ill COVID-19 Patients-Insights from the PRoAcT-COVID Study.
We describe the incidence, practice and associations with outcomes of awake prone positioning in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) in a national multicenter observational cohort study performed in 16 intensive care units in the Netherlands (PRoAcT−COVID-study). Patients were categorized in two groups, based on received treatment of awake prone positioning. The primary endpoint was practice of prone positioning. Secondary endpoint was 'treatment failure', a composite of intubation for invasive ventilation and death before day 28. We used propensity matching to control for observed confounding factors. In 546 patients, awake prone positioning was used in 88 (16.1%) patients. Prone positioning started within median 1 (0 to 2) days after ICU admission, sessions summed up to median 12.0 (8.4−14.5) hours for median 1.0 day. In the unmatched analysis (HR, 1.80 (1.41−2.31); p < 0.001), but not in the matched analysis (HR, 1.17 (0.87−1.59); p = 0.30), treatment failure occurred more often in patients that received prone positioning. The findings of this study are that awake prone positioning was used in one in six COVID-19 patients. Prone positioning started early, and sessions lasted long but were often discontinued because of need for intubation.


Randomized trial of oral cyclophosphamide versus oral cyclophosphamide with celecoxib for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.
Oral metronomic chemotherapy, which has low toxicity, has demonstrated promising anti-tumor and anti-angiogenic properties that may lead to prolonged progression-free survival and improved response rates in patients with recurrent epithelial ovarian cancer (EOC). These effects may be enhanced by the co-administration of anti-angiogenic agents. We conducted a randomized phase II clinical trial to evaluate the therapeutic benefit of oral metronomic cyclophosphamide (CTX) alone and with the anti-angiogenic drug celecoxib in patients with gynecological malignancies. 52 patients were randomly assigned to two treatments arms: 50 mg oral CTX daily alone (Arm A) or with 400 mg celecoxib twice daily (Arm B). The primary endpoint was response rate. Secondary endpoints included toxicity, time to treatment failure, and overall survival. In Arm A (n = 26), 3 patients (12%) had stable disease >6 months and 1 (4%) had a partial response. In Arm B, 5 (19%) had stable disease >6 months and 1 patient (4%) had a partial response. There were no significant between-group differences in overall survival (9.69 months [95% CI 3.84-13.18] vs. 12.55 months [6.67-17.61]) or in median time to treatment failure (1.84 months [1.68-2.76] vs. 1.92 months [1.64-5.22]). The most common adverse events were nausea, vomiting, and abdominal pain. Oral metronomic CTX has activity with no major toxicities in heavily pretreated recurrent gynecological cancers and may be considered in patients with indolent disease. We did not observe any additional benefit of celecoxib treatment, though this may be due to small sample sizes.


Contact investigation for imported case of Middle East respiratory syndrome, Germany.
On March 19, 2013, a patient from United Arab Emirates who had severe respiratory infection was transferred to a hospital in Germany, 11 days after symptom onset. Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) was suspected on March 21 and confirmed on March 23; the patient, who had contact with an ill camel shortly before symptom onset, died on March 26. A contact investigation was initiated to identify possible person-to-person transmission and assess infection control measures. Of 83 identified contacts, 81 were available for follow-up. Ten contacts experienced mild symptoms, but test results for respiratory and serum samples were negative for MERS-CoV. Serologic testing was done for 53 (75%) of 71 nonsymptomatic contacts; all results were negative. Among contacts, the use of FFP2/FFP3 face masks during aerosol exposure was more frequent after MERS-CoV infection was suspected than before. Infection control measures may have prevented nosocomial transmission of the virus.


Advanced glycation end products facilitate bacterial adherence in urinary tract infection in diabetic mice.
Diabetic individuals have increased susceptibility to urinary tract infection (UTI), a common, painful condition. During diabetes mellitus, non-enzymatic reactions between reducing sugars and protein amine groups result in excessive production of advanced glycation end products (AGEs) that accumulate in tissues. Since bacteria adhere to cell surfaces by binding to carbohydrates, we hypothesized that adherence of bacteria to the bladder in diabetics may be enhanced by accumulation of AGEs on urothelial surface proteins. Using a murine model of UTI, we observed increased adherence of type 1 fimbriated uropathogenic Escherichia coli (UPEC) to the bladder in streptozotocin-induced diabetic female mice compared with age-matched controls, along with increased concentrations of two common AGEs in superficial urothelial cells from diabetic bladders. Several lectins with different specificities exhibited increased binding to urothelial homogenates from diabetic mice compared with controls, and two of those lectins also bound to AGEs. Furthermore, mannose-binding type 1 fimbriae isolated from UPEC bound to different AGEs, and UPEC adherence to the bladder in diabetic mice, were inhibited by pretreatment of mice with the AGE inhibitor pyridoxamine. These results strongly suggest a role for urothelial AGE accumulation in increased bacterial adherence during UTI in diabetes.


A comprehensive survey of miRNA repertoire and 3' addition events in the placentas of patients with pre-eclampsia from high-throughput sequencing.
To gain insight into potential roles of isomiR spectrum and isomiRs with 3' additions in pre-eclampsia, we performed a comprehensive survey of miRNA repertoire and 3' addition events from placental samples with different degrees of pre-eclampsia by applying SOLiD sequencing platform. Over 30% isomiRs were detected with 3' non-template additional nucleotides, especially for additional nucleotide of adenosine. However, these modified isomiRs showed a lower percentage of total miRNA expression (<15%). Generally, 1-3 abundant isomiRs from a given miRNA locus were identified, but none of them was detected with 3' additions. Different miRNAs indicated various isomiR spectrums and expression patterns. The most abundant isomiR spectrum, isomiR profile and expression pattern always were stability, but herein we found several exceptions across samples, especially between normal and diseased samples. At isomiR level, we detected a distinct subset of differentially expressed modified isomiRs between normal and diseased samples or between mild and severe samples. Gene Ontology analysis of their experimentally validated target genes revealed enrichment for specific biological process categories. The phenomenon of multiple isomiRs, especially for isomiRs with 3' additions, is not a random event during pre-miRNA processing. Varieties of isomiRs and expression patterns reveal potential functional implication and should be taken into account. The study enriches association of miRNAs and human disease, including potential roles of various miRNA variants and 3' addition events.


The evaluation of first aid and basic life support training for the first year university students.
In Turkey, the first aiders are few in quantity and yet they are required in many settings, such as earthquakes. It was thought that training first year university students in first aid and basic life support (FA-BLS) techniques would serve to increase the number of first aiders. It was also thought that another problem, the lack of first aid trainers, might be addressed by training medical students to perform this function. A project aimed at training first year university students in FA-BLS was conducted at Hacettepe University. In the first phase, medical student first aid trainers (MeSFAT) were trained in FA-BLS training techniques by academic trainers and in the second phase, first year university students were trained in FA-BLS techniques by these peer trainers under the academic trainers' supervision. The purpose of this study was to assess the participants' evaluation of this project and to propose a new program to increase the number of first aiders in the country. In total, 31 medical students were certified as MeSFATs and 12 of these trained 40 first year university students in FA-BLS. Various questionnaires were applied to the participants to determine their evaluation of the training program. Most of the participants and the authors considered the program to be successful and effective. This method may be used to increase the number of first aid trainers and first aiders in the community.


The CT motion quantitation of lung lesions and its impact on PET-measured SUVs.
We previously reported that respiratory motion is a major source of error in quantitation of lesion activity using combined PET/CT units. CT acquisition of the lesion occurs in seconds, rather than the 4-6 min required for PET emission scans. Therefore, an incongruent lesion position during CT acquisition will bias activity estimates using PET. In this study, we systematically analyzed the range of activity concentration changes, hence SUV, for lung lesions. Five lung cancer patients were scanned with PET/CT. In CT, data were acquired in correlation with the real-time positioning. CT images were acquired, in cine mode, at 0.45-s intervals for slightly longer (1 s) than a full respiratory cycle at each couch position. Other scanning parameters were a 0.5-s gantry rotation, 140 kVp, 175 mA, 10-mm couch increments, and a 2.5-mm slice thickness. PET data were acquired after intravenous injection of about 444-555 MBq of (18)F-FDG with a 1-h uptake period. The scanning time was 3 min per bed position for PET. Regularity in breathing was assisted by audio coaching. A commercial software program was then used to sort the acquired CT images into 10 phases, with 0% corresponding to end of inspiration (EI) and 50% corresponding to end of expiration (EE). Using the respiration-correlated CT data, images were rebinned to match the PET slice locations and thickness. We analyzed 8 lesions from 5 patients. Reconstructed PET emission data showed up to a 24% variation in the lesion maximum standardized uptake values (SUVs) between EI and EE phases. Examination of all the phases showed an SUV variation of up to 30%. Also, in some cases the lesion showed up to a 9-mm shift in location and up to a 21% reduction in size when measured from PET during the EI phase, compared with during the EE phase. Using respiration-correlated CT for attenuation correction, we were able to quantitate the fluctuations in PET SUVs. Because those changes may lead to estimates of lower SUVs, the respiratory phase during CT transmission scanning needs to be measured or lung motion has to be regulated for imaging lung cancer in routine clinical practice.


Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells.
We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone-like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different-sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown.


Selenium deficiency impairs corticosterone and leptin responses to adrenocorticotropin in the rat.
Selenium deficiency causes oxidative stress and impairs steroidogenesis in vitro. Leptin is closely related to the hypothalamo-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis at the central level while corticosteroids have been shown to stimulate leptin secretion in most studies. We hypothesized that oxidative stress impairs adrenal steroidogenesis and decreases leptin production in vivo. The goal of this study was to investigate in rats the effects of selenium deficiency and oxidative stress on adrenal function and on leptin concentrations. Weanling rats were fed a selenium-deficient (Se-) or selenium-sufficient (Se+) diet for 4-10 weeks. Selenium deficiency caused a marked decrease in liver (> or = 99%) and adrenal (> or = 81%) glutathione peroxidase (GPx) activities. Selenium deficiency did not affect basal and short-term adrenocorticotropin (ACTH) stimulated corticosterone or leptin concentrations. In contrast, after long-term ACTH stimulation, selenium deficiency caused a doubling in adrenal isoprostane content and blunted the increase in corticosterone and leptin concentrations observed in Se+ animals. Plasma leptin concentrations were 50% lower in Se- compared to Se+ animals following long-term ACTH. Our results suggest that oxidative stress causes a decrease in circulating corticosterone in response to ACTH, and, as a consequence, a decrease in plasma leptin concentrations.


Carbapenem resistant Acinetobacter spp restricted the Therapeutic alternatives.
Carbapenem resistant Acinetobacter has appeared an organism of uncertain resistivity towards antimicrobial agents. Among non-fermenting bacterium Acinetobacter is the second-most-commonly-isolated organisms in human. The fast intensify of their resistance to antibiotics, especially global emergence and extend of Acinetobacter strains resistant to carbapenem more restricted the therapeutic alternatives. The importation of A. baumannii and subsequent presence in hospitals has been well documented. In this study we evaluate the resistivity of Acinetobacter against carbapenem antibiotics at Jinnah University for Women, Karachi. Total 439 isolates of Acinetobacter were collected from different clinical samples of hospitalized patients, identified by standard microbiological methods. Antibiograms were done on Mueller-Hinton agar plates with disk diffusion method (Kirby Bauer method). Disc tested: Meropenem (10μg/disk). Among 439 samples, 300 (68.3%) samples were resistant to Meropenem and the remaining that is 139 (31.7%) showed sensitivity to the drugs. In developing countries including Pakistan the contentment of multi drug resistance and their dissemination in Acinetobacter species is not a simple task. While multiple drug resistance is increasing in this pathogen and Carbapenem conflict is quickly spreading which may become a major threat in future.


Evaluation of the LDBio Aspergillus ICT lateral flow assay for serodiagnosis of allergic bronchopulmonary aspergillosis.
Early recognition and diagnosis of allergic bronchopulmonary aspergillosis (ABPA) is critical to improve patient symptoms, and antifungal therapy may prevent or delay progression of bronchiectasis and development of chronic pulmonary aspergillosis. A recently commercialized lateral flow assay (Aspergillus ICT) (LDBio Diagnostics, Lyons, France) detects Aspergillus-specific antibodies in <30 minutes, requiring minimal laboratory equipment. We evaluated this assay for diagnosis of ABPA compared to diseased (asthma and/or bronchiectasis) controls. ABPA and control sera collected at the National Aspergillosis Centre (Manchester, UK) and/or from the Manchester Allergy, Respiratory and Thoracic Surgery research biobank were evaluated using the Aspergillus ICT assay. Results were read both visually and digitally (using a lateral flow reader). Serological Aspergillus-specific IgG and IgE, and total IgE titres were measured by ImmunoCAP. For 106 cases of ABPA versus all diseased controls, sensitivity and specificity for the Aspergillus ICT were 90.6% and 87.2%, respectively. Sensitivity for 'proven' ABPA alone (n = 96) was 89.8%, and 94.4% for 'presumed' ABPA (n = 18). 'Asthma only' controls (no bronchiectasis) and 'bronchiectasis controls' exhibited 91.4% and 81.7% specificity, respectively. Comparison of Aspergillus ICT result with Aspergillus-specific IgG and IgE titres showed no evident immunoglobulin isotype bias. Digital measurements displayed no correlation between ImmunoCAP Aspergillus-specific IgE level and ICT test line intensity. The Aspergillus ICT assay exhibits good sensitivity for ABPA serological screening. It is easy to perform and interpret, using minimal equipment and resources; and provides a valuable simple screening resource to rapidly distinguish more serious respiratory conditions from Aspergillus sensitization alone.


Lung injury associated with bortezomib therapy in relapsed/refractory multiple myeloma in Japan: a questionnaire-based report from the "lung injury by bortezomib" joint committee of the Japanese society of hematology and the Japanese society of clinical hematology.
Bortezomib is a proteasome inhibitor that can be effective in the treatment of refractory and relapsed multiple myeloma. Recently, severe pulmonary complications associated with bortezomib therapy have been reported in Japan. Because bortezomib has not yet been approved for general use in Japan and is imported by attending physicians on the request of patients, The Japanese Society of Hematology and The Japanese Society of Clinical Hematology sent urgent questionnaires to the councilors of both societies to explore the situation and the details of pulmonary complications associated with bortezomib therapy. Clinical details were available for 46 patients who had been treated with personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who died from respiratory failure, showed complications definitely or probably caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell transplantation (SCT), whereas only 14 of 39 patients without lung injury had received SCT treatment (P = .033, Fisher exact test). Multivariate analysis revealed that the concomitant use of corticosteroids might reduce the risk of lung injury (P = .024; odds ratio, 0.055) and that a previous SCT might increase the risk (P = .042; odds ratio, 13.140). We summarized these data from questionnaires for a limited Japanese cohort and therefore do not know the precise incidence of lung injury linked to fatal progression. Thus, future verification concerning this matter is warranted after the approval of bortezomib for use in Japan. Clinicians should be aware of the possibility of severe pulmonary complications associated with bortezomib therapy.


Chronic migraine - new treatment options.
Chronic migraine (CM) is defined as headache occurring more than fifteen days/month for at least three consecutive months, with headache having the clinical features of migraine without aura for at least eight days per month. Recently, new treatment options became available in chronic migraine patients. Topiramate is effective in chronic migraine, in the presence or absence of medication overuse, and/or other migraine prophylaxis. Efficacy of onabotulinumtoxin A as a preventive treatment of chronic migraine has been shown in the PREEMPT studies. Occipital nerve stimulation (ONS) is an invasive treatment for refractory chronic headaches. ONS has encouraging results in refractory chronic migraine patients in commercially funded, multi-centre randomized trials.


The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions.
Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K-adenosine triphosphatase (ATPase) alpha subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane's electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis alpha1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain-sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 microM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump-induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the binding pocket. Gating measurements of palytoxin-opened Na/K pump channels additionally imply that the C-terminal contacts also help stabilize pump conformations with occluded K ions.


Biochemical tests for diagnosis of phaeochromocytoma: urinary versus plasma determinations.
Fifteen patients with hypertension due to phaeochromocytoma and 35 controls with essential hypertension were studied to assess the diagnostic value of urinary and plasma biochemical determinations in phaeochromocytoma. In every case of phaeochromocytoma the urinary concentration of vanillylmandelate, metanephrines, or adrenaline plus noradrenaline was diagnostic of the disease irrespective of whether the patient was normotensive or hypertensive at the time. Plasma determinations of adrenaline and noradrenaline, however, gave falsely negative results on three occasions. These findings suggest that urinary biochemical determinations--particularly of metanephrines--are more reliable than plasma catecholamine measurements as a test for phaeochromocytoma. The test is particularly useful in patients with intermittent hypertension.


Astaxanthin Improves Human Sperm Capacitation by Inducing Lyn Displacement and Activation.
Astaxanthin (Asta), a photo-protective red pigment of the carotenoid family, is known for its multiple beneficial properties. In this study, the effects of Asta on isolated human sperm were evaluated. Capacitation involves a series of transformations to let sperm acquire the correct features for potential oocyte fertilization, including the generation of a controlled amount of reactive oxygen species (ROS), cholesterol depletion of the sperm outer membrane, and protein tyrosine phosphorylation (Tyr-P) process in the head region. Volunteers, with normal spermiogram values, were divided in two separate groups on the basis of their ability to generate the correct content of endogenous ROS. Both patient group (PG) and control group (CG) were analysed for Tyr-phosphorylation (Tyr-P) pattern and percentages of acrosome-reacted cells (ARC) and non-viable cells (NVC), in the presence or absence of Asta. In addition, the involvement of ROS on membrane reorganization and the presence of Lyn, a Src family kinase associated with lipid rafts, were investigated. Results show that Lyn is present in the membranes of human sperm, mainly confined in midpiece in resting conditions. Following capacitation, Lyn translocated to the head concomitantly with raft relocation, thus allowing the Tyr-P of head proteins. Asta succeeded to trigger Lyn translocation in PG sperm thus bypassing the impaired ROS-related mechanism for rafts and Lyn translocation. In this study, we showed an interdependence between ROS generation and lipid rafts and Lyn relocation leading the cells to undergo the successive acrosome reaction (AR). Asta, by ameliorating PG sperm functioning, may be utilised to decrease male idiopathic infertility.


DNA unwinding heterogeneity by RecBCD results from static molecules able to equilibrate.
Single-molecule studies can overcome the complications of asynchrony and ensemble-averaging in bulk-phase measurements, provide mechanistic insights into molecular activities, and reveal interesting variations between individual molecules. The application of these techniques to the RecBCD helicase of Escherichia coli has resolved some long-standing discrepancies, and has provided otherwise unattainable mechanistic insights into its enzymatic behaviour. Enigmatically, the DNA unwinding rates of individual enzyme molecules are seen to vary considerably, but the origin of this heterogeneity remains unknown. Here we investigate the physical basis for this behaviour. Although any individual RecBCD molecule unwound DNA at a constant rate for an average of approximately 30,000 steps, we discover that transiently halting a single enzyme-DNA complex by depleting Mg(2+)-ATP could change the subsequent rates of DNA unwinding by that enzyme after reintroduction to ligand. The proportion of molecules that changed rate increased exponentially with the duration of the interruption, with a half-life of approximately 1 second, suggesting that a conformational change occurred during the time that the molecule was arrested. The velocity after pausing an individual molecule was any velocity found in the starting distribution of the ensemble. We suggest that substrate binding stabilizes the enzyme in one of many equilibrium conformational sub-states that determine the rate-limiting translocation behaviour of each RecBCD molecule. Each stabilized sub-state can persist for the duration (approximately 1 minute) of processive unwinding of a DNA molecule, comprising tens of thousands of catalytic steps, each of which is much faster than the time needed for the conformational change required to alter kinetic behaviour. This ligand-dependent stabilization of rate-defining conformational sub-states results in seemingly static molecule-to-molecule variation in RecBCD helicase activity, but in fact reflects one microstate from the equilibrium ensemble that a single molecule manifests during an individual processive translocation event.


Comparative effects of technical-grade and formulated chlorantraniliprole to the survivorship and locomotor activity of the honey bee, Apis mellifera (L.).
The loss of honey bee colonies is a nationally recognized problem that demands attention from both the scientific community and the beekeeping industry. One outstanding threat is the unintended exposure of these pollinators to agricultural pesticides. Anthranilic diamides, such as chlorantraniliprole, are registered for use in stone and pome fruits, vegetables, turf, and grains. There are few publicly available studies that provide an analysis of chlorantraniliprole effects on the survivorship and locomotion activity of beneficial, pollinating insects such as honey bees. The data gathered in this study provide the acute toxicity, 30-day survivorship, and locomotor activity of honey bees exposed to technical-grade chlorantraniliprole and three formulated products with chlorantraniliprole as the active ingredient. Neither the technical-grade nor the formulated products of chlorantraniliprole were acutely toxic to honey bees following 4 or 72h treatments at the tested concentrations. A 4 h treatment of technical-grade and formulated chlorantraniliprole did not significantly affect the 30-day survivorship, although significantly higher mortality was observed after 30 days for bees receiving a 72 h treatment of technical-grade chlorantraniliprole and two formulated products. The locomotion activity, or total walking distance, of bees receiving a 4 h treatment of one chlorantraniliprole formulation was significantly reduced, with these individuals recovering their normal locomotion activity at 48 h post exposure. Conversely, there was observed lethargic behavior and significantly reduced walking distances for bees provided with a 72 h treatment of technical-grade chlorantraniliprole and each formulated product. This study provides evidence for the effect of long-term exposure of chlorantraniliprole on the survivorship and locomotor activity of honey bees. Bees receiving a more field-relevant short-term exposure survived and moved similarly to untreated bees, reiterating the relative safety of chlorantraniliprole exposure to adult honey bees at recommended label concentrations. © 2020 Society of Chemical Industry.


Fungal bioconversion of lignocellulosic residues; opportunities & perspectives.
The development of alternative energy technology is critically important because of the rising prices of crude oil, security issues regarding the oil supply, and environmental issues such as global warming and air pollution. Bioconversion of biomass has significant advantages over other alternative energy strategies because biomass is the most abundant and also the most renewable biomaterial on our planet. Bioconversion of lignocellulosic residues is initiated primarily by microorganisms such as fungi and bacteria which are capable of degrading lignocellulolytic materials. Fungi such as Trichoderma reesei and Aspergillus niger produce large amounts of extracellular cellulolytic enzymes, whereas bacterial and a few anaerobic fungal strains mostly produce cellulolytic enzymes in a complex called cellulosome, which is associated with the cell wall. In filamentous fungi, cellulolytic enzymes including endoglucanases, cellobiohydrolases (exoglucanases) and beta-glucosidases work efficiently on cellulolytic residues in a synergistic manner. In addition to cellulolytic/hemicellulolytic activities, higher fungi such as basidiomycetes (e.g. Phanerochaete chrysosporium) have unique oxidative systems which together with ligninolytic enzymes are responsible for lignocellulose degradation. This review gives an overview of different fungal lignocellulolytic enzymatic systems including extracellular and cellulosome-associated in aerobic and anaerobic fungi, respectively. In addition, oxidative lignocellulose-degradation mechanisms of higher fungi are discussed. Moreover, this paper reviews the current status of the technology for bioconversion of biomass by fungi, with focus on mutagenesis, co-culturing and heterologous gene expression attempts to improve fungal lignocellulolytic activities to create robust fungal strains.


"Like Yin and Yang": Perceptions of Methamphetamine Benefits and Consequences Among People Who Use Opioids in Rural Communities.
The objective of this study was to investigate methamphetamine use among people who use opioids in rural Oregon communities to explore reasons for use and perceptions of methamphetamine consequences. We conducted interviews and surveys with participants who inject drugs or misuse prescription opioids in 2 rural Oregon counties with high opioid overdose rates. Survey participants were identified through participant-driven sampling initiated in syringe service programs and field outreach (n = 144). Semi-structured interviews with participants were recruited from the same locations (n = 52). Of 144 surveys completed, 112 reported using opioids in the past 30 days; 96% of the 112 also report methamphetamine use. Among the 124 reporting injection drug use, 50% indicated they injected both methamphetamine and heroin in the past 30 days. Interview participants reported early exposure to methamphetamine and indicated that methamphetamine was more widely available, less expensive, and less stigmatized compared to heroin. Participants reported using methamphetamine to improve work-life functioning and because they enjoy the high produced from simultaneous use. Several participants reported a conscious effort to shift to methamphetamine from heroin as a harm reduction strategy.Some participants reported being involuntarily discharged from treatment for opioid use disorder due to methamphetamine use. Several participants perceived methamphetamine as conveying overdose prevention or reversal benefits, while fentanyl contamination in methamphetamine was reported or suspected. As rural communities respond to evolving drug supply and demand, there is increasing need for public health efforts to address the emerging issue of concurrent methamphetamine and opioid use.


A pooled analysis of 12 cohort studies of dietary fat, cholesterol and egg intake and ovarian cancer.
Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case-control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86-1.34 comparing > or =45 to 30-<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01-1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation.


To nibble at plant resistance proteins.
To intercept invading microbes that threaten growth and reproduction, plants evolved a sophisticated innate immune system. Recognition of specialized pathogens is mediated by resistance proteins that function as molecular switches. Pathogen perception by these multidomain proteins seems to trigger a series of conformational changes dependent on nucleotide exchange. The activated resistance protein switches on host defenses, often culminating in the death of infected cells. Given their control over life and death, activity of these proteins requires tight regulation that involves intramolecular interactions between the various domains.


New progestagens for contraceptive use.
The progestins have different pharmacologic properties depending upon the parent molecule, usually testosterone or progesterone (P), from which they are derived. Very small structural changes in the parent molecule may induce considerable differences in the activity of the derivative. In hormonal contraceptives, progestins represent the major agent designed for suppressing ovulation and are used in combination with estrogen (E) usually ethinyl-estradiol (EE). The development of new generations of progestins with improved selectivity profiles has been a great challenge. Steroidal and nonsteroidal progesterone receptor (PR) agonists have been synthesized as well, although the latter are still in a very early stage of development. Several new progestins, have been synthesized in the last two decades. These include dienogest (DNG), drospirenone (DRSP), Nestorone (NES), nomegestrol acetate (NOMAc) and trimegestone (TMG). These new progestins have been designed to have no androgenic or estrogenic actions and to be closer in activity to the physiological hormone P. DRSP differs from the classic progestins as it is derived from spirolactone. It is essentially an antimineralocorticoid steroid with no androgenic effect but a partial antiandrogenic effect. The antiovulatory potency of the different progestins varies. TMG and NES are the most potent progestins synthesized to date, followed by two of the older progestins, keto-desogestrel (keto-DSG) and levonorgestrel (LNG). The new molecules TMG, DRSP and DNG also have antiandrogenic activity. Striking differences exist regarding the side effects among the progestins and the combination with EE leads to other reactions related to the E itself and whether the associated progestin counterbalances, more or less, the estrogenic action. The 19-norprogesterone molecules and the new molecules DRSP and DNG are not androgenic and, therefore, have no negative effect on the lipid profile. Given their pharmacological properties, it is likely that the new progestins may have neutral effects on metabolic or vascular risks. However, this hypothesis must be confirmed in large clinical trials.


Can You Trust What You Watch? An Assessment of the Quality of Information in Aesthetic Surgery Videos on YouTube.
Videos on YouTube can be posted without regulation or content oversight. Unfortunately, many patients use YouTube as a resource on aesthetic surgery, leading to misinformation. Currently, there are no objective assessments of the quality of information on YouTube about aesthetic surgery. YouTube was queried for videos about the 12 most common aesthetic surgical procedures, identified from the 2015 American Society of Plastic Surgeons procedural statistics between May and June of 2016. The top 25 results for each search term were scored using the modified Ensuring Quality Information for Patients criteria based on video structure, content, and author identification. Average Ensuring Quality Information for Patients score, view count, and video duration were compared between authorship groups. A total of 523 videos were graded after excluding duplicates. The mean modified Ensuring Quality Information for Patients score for all videos was 13.1 (SE, 0.18) of a possible 27. The videos under the search "nose reshaping" had the lowest mean score of 10.24 (SE, 0.74), whereas "breast augmentation" had the highest score of 15.96 (SE, 0.65). Physician authorship accounted for 59 percent of included videos and had a higher mean Ensuring Quality Information for Patients score than those by patients. Only three of the 21 search terms had a mean modified Ensuring Quality Information for Patients score meeting criteria for high-quality videos. The information contained in aesthetic surgery videos on YouTube is low quality. Patients should be aware that the information has the potential to be inaccurate. Plastic surgeons should be encouraged to develop high-quality videos to educate patients.


Investigating predictors of true and false guilty pleas.
An estimated 90% to 95% of convictions are obtained via guilty pleas, and roughly 11% of individuals exonerated with the help of the Innocence Project falsely pleaded guilty (innocenceproject.org). Despite the prevalence of guilty pleas (and the existence of false guilty pleas), relatively little scholarship has examined what influences a defendant to plead guilty (Redlich, 2010). In this study, we investigated factors that affected whether guilty and innocent students who were accused of cheating pleaded guilty or took their case before the Student Conduct Committee in a hearing (analogous to a trial). Using social psychological literature on social influence (Cialdini & Goldstein, 2004), we manipulated two legally and theoretically relevant factors: the attorney's recommendation and the guilt of the defendant. Overall, guilty individuals were more likely to accept a guilty plea than innocent individuals. Advocate recommendation affected innocent and guilty participants' plea decisions; however, the effect was stronger for innocent individuals. Innocent participants advised to go to trial were less likely to falsely plead guilty (M = 4%) compared with those without an advocate (M = 35%), those who were given educational information (M = 47%), or those who were advised to plead guilty (M = 58%). Overall, findings suggest that innocent individuals may be more vulnerable to the effects of social influence when considering advice from an advocate compared with guilty individuals. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Sudden sensorineural hearing loss in patients with vestibular schwannoma.
Clinical features of sudden sensorineural hearing loss (SSNHL) associated with vestibular schwannoma (VS) are not fully understood. Determining a treatment plan and explaining it to patients requires clinicians to clearly understand the clinical features related to the tumor, including SSNHL. To identify the full range of clinical features of VS-associated SSNHL, especially recovery of hearing following multiple episodes of SSNHL and what factors predict recovery and recurrence. A multicenter retrospective chart review was conducted in seven tertiary care hospitals between April 1, 2011, and March 31, 2020. We collected and analyzed dose of administered steroid, pure-tone audiometry results, and brain MRIs of patients diagnosed with VS-associated SSNHL. Seventy-seven patients were included. They experienced 109 episodes of audiogram-confirmed SSNHL. The highest proportion of complete recoveries occurred in patients with U-shaped audiograms. The recovery rates for the first, second, and third and subsequent episodes of SSNHL were 53.5%, 28.0%, and 9.1%, respectively. Recovery rate decreased significantly with increasing number of SSNHL episodes (P =0 .0011; Cochran-Armitage test). After the first episode of SSNHL, the recurrence-free rate was 69.9% over 1 year and 57.7% over 2 years; the median recurrence time was 32 months. Logarithmic approximation revealed that there is a 25% probability that SSNHL would recur within a year. SSNHL in patients with VS is likely to recur within one year in 25% of cases. Also, recovery rate decreases as a patient experiences increasing episodes of SSNHL.


Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes.
There is compelling evidence to indicate an important role for increased local renin-angiotensin system activity in the pathogenesis of cardiac hypertrophy and heart failure. Resveratrol is a natural polyphenol that activates SIRT1, a novel cardioprotective and longevity factor having NAD(+)-dependent histone deacetylase activity. We tested the hypothesis whether resveratrol could prevent from angiotensin II (Ang II)-induced cardiovascular damage. Four-week-old double transgenic rats harboring human renin and human angiotensinogen genes (dTGR) were treated for 4 weeks either with SIRT1 activator resveratrol or SIRT1 inhibitor nicotinamide. Untreated dTGR and their normotensive Sprague-Dawley control rats (SD) received vehicle. Untreated dTGR developed severe hypertension as well as cardiac hypertrophy, and showed pronounced cardiovascular mortality compared with normotensive SD rats. Resveratrol slightly but significantly decreased blood pressure, ameliorated cardiac hypertrophy and prevented completely Ang II-induced mortality, whereas nicotinamide increased blood pressure without significantly influencing cardiac hypertrophy or survival. Resveratrol decreased cardiac ANP mRNA expression and induced cardiac mRNA expressions of mitochondrial biogenesis markers peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), mitochondrial transcription factor (Tfam), nuclear respiratory factor 1 (NRF-1) and cytochrome c oxidase subunit 4 (cox4). Resveratrol dose-dependently increased SIRT1 activity in vitro. Our findings suggest that the beneficial effects of SIRT1 activator resveratrol on Ang II-induced cardiac remodeling are mediated by blood pressure-dependent pathways and are linked to increased mitochondrial biogenesis.


Robustly Superhydrophobic Conductive Textile for Efficient Electromagnetic Interference Shielding.
Superhydrophobic electromagnetic interference (EMI) shielding textile (EMIST) is of great significance to the safety and long-term service of all-weather outdoor equipment. However, it is still challenging to achieve long-term durability and stability under external mechanical deformations or other harsh service conditions. Herein, by designing and implementing silver nanowire (AgNW) networks and a superhydrophobic coating onto a commercial textile, we demonstrate a highly robust superhydrophobic EMIST. The resultant EMIST shows a synergy of high water contact angle (160.8°), low sliding angle (2.9°), and superior EMI shielding effectiveness (51.5 dB). Remarkably, the EMIST still maintains its superhydrophobic feature and high EMI shielding level (42.6 dB) even after 5000 stretching-releasing cycles. Moreover, the EMIST exhibits strong resistance to ultrasonic treatment up to 60 min, peeling test up to 100 cycles, strong acidic/alkaline solutions, and different organic solvents, indicating its outstanding mechanical robustness and chemical durability. These attractive features of the EMIST are mainly a result of the joint action of AgNWs, carbon nanotubes, polytetrafluoroethylene nanoparticles, and fluoroacrylic polymer. This work offers a promising approach for the design of future durable, superhydrophobic EMISTs, which are capable of remaining fully functional against long-time exposure to extreme conditions, for example, wet and corrosive environments.


Clinical investigation of mucosal thickness stability after soft tissue grafting around implants: a 3-year retrospective study.
To assess the long-term stability of gingival grafts placed around dental implants at the time of second surgery uncovering and to further investigate the association between mucosal thickness (MTh) by demographic variables and clinical investigation. Fourteen patients with submerged dental implants covered by inadequate keratinized mucosa were studied. The subjects underwent a periimplant plastic surgery (PPS) at the second-stage dental implant surgery and free gingival autograft orsubepithelial connective tissue graft were used according to the patients' clinical situation. Clinical measurement of MTh was assessed by bone sounding with a periodontal probe using customized acrylic stents andthe values were recorded at baseline (day of graft) and at 0.5, 1.5, 4, 12, 24 and 36 months after grafting. At 12 months postoperatively, the mean MTh was 2.89 mm, with a mean additional increase of 1.75 mm when compared with baseline (P=0.0001). No statistically significant differences in MTh were found between the 12- and the 36-month observations (P=0.09). In addition, at 36 months, a thin mucosa was associated with a greater increase in the MTh compared with a thick mucosa (2.14 and 0.64 mm, respectively, P=0.006). Similarly, the mandibular sites were associated with a greater increase in the MTh in comparison with the maxillary sites (2.17 and 0.81 mm, respectively; P=0.02). Within the limitations of this investigation, the data suggest that PPS at the second-stage dental implant surgery could results in additional increases in MTh, especially when it is performed in areas where the mucosa is of a thin biotype.


Prediction accuracy of soft tissue profile in orthognathic surgery.
The purpose of this study was to compare soft tissue prediction accuracy of model surgery combined with computer software prediction with that of computer software prediction alone and to assess surgical accuracy by comparing the immediate postsurgical cephalogram with the planned movement of skeletal hard tissue. The predicted and actual soft tissue changes and the corresponding skeletal changes of 16 patients were compared using the Quick Ceph Image cephalometric treatment simulation software. A custom analysis was created to measure the hard tissue and soft tissue changes that occurred as a result of the surgical procedure. On average, the predictions were not significantly different from the actual postsurgical profile changes. Surgical changes of hard tissues from presurgery to postsurgery were accurate as planned except for the position of N-ANS. All lower soft tissue points moved significantly during treatment. Quick Ceph Image offers a rapid and reliable method of profile prediction that does not require artistic skill. If predictions are interpreted with caution and transferred accurately to the model surgery, they can provide an excellent visual aid during presurgical treatment planning and patient presentation.


Glucocorticoid regulation of insulin receptor and substrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo.
To test the hypothesis that glucocorticoid-induced insulin resistance might originate from abnormalities in insulin receptor signaling, we investigated the effects of glucocorticoids on in vivo tyrosine phosphorylation of the insulin receptor and the insulin receptor substrate IRS-1 in rat skeletal muscle. Male Sprague-Dawley rats were treated with cortisone (100 mg/kg for 5 d) and compared to pair-fed controls. Cortisone treatment of rats resulted in both hyperglycemia and hyperinsulinemia. Anesthetized animals were injected with 10 U/kg insulin via cardiac puncture and, after 2 min, hindlimb muscles were removed, snap-frozen, and homogenized in SDS. Protein tyrosine phosphorylation was studied by immunoblotting with phosphotyrosine antibody. Insulin receptors and substrate IRS-1 were identified and quantified with specific antibodies. Cortisone treatment increased the amount of insulin receptor protein by 36%, but decreased the total level of receptor tyrosine phosphorylation (69 +/- 4% of control, P < 0.05). The decreased level of receptor phosphorylation was explained by a reduced number of receptors containing phosphorylated tyrosine residues (64.6 +/- 5% of control, P < 0.05). Glucocorticoid excess decreased skeletal muscle IRS-1 content by 50%, but did not significantly alter the total level of IRS-1 tyrosine phosphorylation. The apparent M(r) of IRS-1 was reduced by approximately 10 kD. Treatment with protein phosphatase-2A reduced IRS-1 M(r) in control but not in glucocorticoid-treated muscle indicating that the lower M(r) likely results from lower phosphoserine and/or phosphothreonine content. To investigate the role of hyperinsulinemia in the glucocorticoid response, rats were made insulin-deficient with streptozotocin (100 mg/kg, i.p.). Subsequent treatment with cortisone for 5 d had no effects on insulin levels, tyrosine phosphorylation of insulin receptors or IRS-1, or the M(r) of IRS-1. In conclusion, glucocorticoid-treated skeletal muscle is characterized by: (a) decreased total tyrosine phosphorylation of insulin receptors as a result of a reduction in the pool of receptors undergoing tyrosine phosphorylation; (b) decreased IRS-1 content and reduced serine and/or threonine phosphorylation of IRS-1. Glucocorticoid-induced hyperinsulinemia appears to be essential for the development of these alterations.


Silica Nanoparticles Functionalized with Zwitterionic Sulfobetaine Siloxane for Application as a Versatile Antifouling Coating System.
The growing need to develop surfaces able to effectively resist biological fouling has resulted in the widespread investigation of nanomaterials with potential antifouling properties. However, the preparation of effective antifouling coatings is limited by the availability of reactive surface functional groups and our ability to carefully control and organize chemistries at a materials' interface. Here, we present two methods of preparing hydrophilic low-fouling surface coatings through reaction of silica-nanoparticle suspensions and predeposited silica-nanoparticle films with zwitterionic sulfobetaine (SB). Silica-nanoparticle suspensions were functionalized with SB across three pH conditions and deposited as thin films via a simple spin-coating process to generate hydrophilic antifouling coatings. In addition, coatings of predeposited silica nanoparticles were surface functionalized via exposure to zwitterionic solutions. Quartz crystal microgravimetry with dissipation monitoring was employed as a high throughput technique for monitoring and optimizing reaction to the silica-nanoparticle surfaces. Functionalization of nanoparticle films was rapid and could be achieved over a wide pH range and at low zwitterion concentrations. All functionalized particle surfaces presented a high degree of wettability and resulted in large reductions in adsorption of bovine serum albumin protein. Particle coatings also showed a reduction in adhesion of fungal spores (Epicoccum nigrum) and bacteria (Escherichia coli) by up to 87 and 96%, respectively. These results indicate the potential for functionalized nanosilicas to be further developed as versatile fouling-resistant coatings for widespread coating applications.


On the accuracy of techniques for obtaining the calibration coefficient N(K) of 192Ir HDR brachytherapy sources.
The accuracy of interpolation or averaging procedures for obtaining the calibration coefficient N(K) for 192Ir high-dose-rate brachytherapy sources has been investigated using the EGSnrc Monte Carlo simulation system. It is shown that the widely used two-point averaging procedure of Goetsch et al. [Med. Phys. 18, 462 (1991)] has some conceptual problems. Most importantly, they recommended, as did the IAEA, averaging A(wall)N(K) values whereas one should average 1/N(K) values. In practice this and other issues are shown to have little effect except for Goetsch et al.'s methods for determining A(wall) values. Their method of generalizing the A(wall) values measured in one geometry to other geometries is incorrect by up to 2%. However, these errors in A(wall) values cause systematic errors of only 0.3% in 192Ir calibration coefficients. It is shown that A(wall) values need not be included in the averaging technique at all, thereby simplifying the technique considerably. It is demonstrated that as long as ion chambers with a flat response are used and/or very heavily filtered 250 kV (or higher) beams of x rays are used in the averaging, then almost all techniques can provide adequate accuracy.


Whisker touch sensing guides locomotion in small, quadrupedal mammals.
All small mammals have prominent facial whiskers that they employ as tactile sensors to guide navigation and foraging in complex habitats. Nocturnal, arboreal mammals tend to have the longest and most densely packed whiskers, and semi-aquatic mammals have the most sensitive. Here we present evidence to indicate that many small mammals use their whiskers to tactually guide safe foot positioning. Specifically, in 11, small, non-flying mammal species, we demonstrate that forepaw placement always falls within the ground contact zone of the whisker field and that forepaw width is always smaller than whisker span. We also demonstrate commonalities of whisker scanning movements (whisking) and elements of active control, associated with increasing contact with objects of interest, across multiple small mammal species that have previously only been shown in common laboratory animals. Overall, we propose that guiding locomotion, alongside environment exploration, is a common function of whisker touch sensing in small, quadrupedal mammals.


Atrial fibrillation in Indigenous and non-Indigenous Australians: a cross-sectional study.
To examine the prevalence of atrial fibrillation (AF) and cardiac structural characteristics in Indigenous and non-Indigenous Australians. Retrospective cross-sectional study linking clinical, echocardiography and administrative databases over a 10-year period. A tertiary, university teaching hospital in Adelaide, Australia. Indigenous and non-Indigenous Australians. AF prevalence and echocardiographic characteristics. Indigenous Australians with AF were significantly younger compared to non-Indigenous Australians (55±13 vs 75±13 years, p<0.001). As a result, racial differences in AF prevalence and left atrial diameter varied according to age. In those under 60 years of age, Indigenous Australians had a significantly greater AF prevalence (2.57 vs1.73%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001) compared to non-Indigenous Australians. In those aged 60 years and above, however, non-Indigenous Australians had significantly greater AF prevalence (9.26 vs 4.61%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001). Left ventricular ejection fractions were less in Indigenous Australians under 60 years of age (49±14 vs 55±11%, p<0.001) and not statistically different in those aged 60 years and above (47±11 vs 52±13, p=0.074) compared to non-Indigenous Australians. Despite their younger age, Indigenous Australians with AF had similar or greater rates of cardiovascular comorbidities than non-Indigenous Australians with AF. Young Indigenous Australians have a significantly greater prevalence of AF than their non-Indigenous counterparts. In contrast, older non-Indigenous Australians have a greater prevalence of AF compared to their Indigenous counterparts. These observations may be mediated by age-based differences in comorbid cardiovascular conditions, left atrial diameter and left ventricular ejection fraction. Our findings suggest that AF is likely to be contributing to the greater burden of morbidity and mortality experienced by young Indigenous Australians. Further study is required to elucidate whether strategies to prevent and better manage AF in Indigenous Australians may reduce this burden.


Geometry-driven collective ordering of bacterial vortices.
Controlling the phases of matter is a challenge that spans from condensed materials to biological systems. Here, by imposing a geometric boundary condition, we study the controlled collective motion of Escherichia coli bacteria. A circular microwell isolates a rectified vortex from disordered vortices masked in the bulk. For a doublet of microwells, two vortices emerge but their spinning directions show transition from parallel to anti-parallel. A Vicsek-like model for confined self-propelled particles gives the point where the two spinning patterns occur in equal probability and one geometric quantity governs the transition as seen in experiments. This mechanism shapes rich patterns including chiral configurations in a quadruplet of microwells, thus revealing a design principle of active vortices.


Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial.
Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22-1·36), and the risk was similar for those without known PFO (1·06; 0·84-1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51-8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69-4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24-0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Bayer and Janssen.


Public Concern About Monitoring Twitter Users and Their Conversations to Recruit for Clinical Trials: Survey Study.
Social networks such as Twitter offer the clinical research community a novel opportunity for engaging potential study participants based on user activity data. However, the availability of public social media data has led to new ethical challenges about respecting user privacy and the appropriateness of monitoring social media for clinical trial recruitment. Researchers have voiced the need for involving users' perspectives in the development of ethical norms and regulations. This study examined the attitudes and level of concern among Twitter users and nonusers about using Twitter for monitoring social media users and their conversations to recruit potential clinical trial participants. We used two online methods for recruiting study participants: the open survey was (1) advertised on Twitter between May 23 and June 8, 2017, and (2) deployed on TurkPrime, a crowdsourcing data acquisition platform, between May 23 and June 8, 2017. Eligible participants were adults, 18 years of age or older, who lived in the United States. People with and without Twitter accounts were included in the study. While nearly half the respondents-on Twitter (94/603, 15.6%) and on TurkPrime (509/603, 84.4%)-indicated agreement that social media monitoring constitutes a form of eavesdropping that invades their privacy, over one-third disagreed and nearly 1 in 5 had no opinion. A chi-square test revealed a positive relationship between respondents' general privacy concern and their average concern about Internet research (P<.005). We found associations between respondents' Twitter literacy and their concerns about the ability for researchers to monitor their Twitter activity for clinical trial recruitment (P=.001) and whether they consider Twitter monitoring for clinical trial recruitment as eavesdropping (P<.001) and an invasion of privacy (P=.003). As Twitter literacy increased, so did people's concerns about researchers monitoring Twitter activity. Our data support the previously suggested use of the nonexceptionalist methodology for assessing social media in research, insofar as social media-based recruitment does not need to be considered exceptional and, for most, it is considered preferable to traditional in-person interventions at physical clinics. The expressed attitudes were highly contextual, depending on factors such as the type of disease or health topic (eg, HIV/AIDS vs obesity vs smoking), the entity or person monitoring users on Twitter, and the monitored information. The data and findings from this study contribute to the critical dialogue with the public about the use of social media in clinical research. The findings suggest that most users do not think that monitoring Twitter for clinical trial recruitment constitutes inappropriate surveillance or a violation of privacy. However, researchers should remain mindful that some participants might find social media monitoring problematic when connected with certain conditions or health topics. Further research should isolate factors that influence the level of concern among social media users across platforms and populations and inform the development of more clear and consistent guidelines.


Association of serum biomarker neurofilament light concentration with post-stroke depression: A preliminary study.
To investigate serum neurofilament light (sNfL) levels in acute ischemic stroke and to assess whether sNfL are related to the severity of disease and a potential prognostic marker of post-stroke depression (PSD) during a 3-month follow-up period. This was a single-center prospective cohort study. The sNfL concentration was measured in baseline samples using the Simoa platform- Single Molecule Array technology. A psychiatrist administered the Structural Clinical Interview for Diagnostic and Statistical Manual IV to all patients and made a diagnosis of PSD 3 months after stroke. The logistic regression was used to examine the association between sNfL and PSD. In total, 236 ischemic stroke cases were included and finished the follow-up. In the follow-up, 55 patients were defined as PSD, thus the incidence rate was 23.3% (95% confidence intervals [CI]: 17.9%-28.7%). Significant differences were observed between the sNfL levels in patients with PSD (124.8 pg/ml [interquartile range {IQR}: 59.6-159.2]) and in patients without PSD (35.9 pg/ml [IQR: 18.2-60.4]) levels (P < 0.001). After adjusting for age, family history of depression, marital status, National Institutes of Health and Stroke Scale score, C-reactive protein and homocysteine levels, sNfL levels independently predicted the development of post-stroke depression. The crude and adjusted odds ratios [OR] (and 95%CI) of PSD associated with an IQR increase for sNfL were 3.38(2.29, 4.98) and 2.65(1.59, 4.04), respectively. According to receiver operating characteristic curves (ROC) curves, the cut-off value of sNfL to predict PSD was 111.4 pg/ml with an area under the curve (AUC) of 0.84(95% CI, 0.78-0.90) and with the highest sensitivity (61.8%) and specificity (95.4%). In this study, elevated level of sNfL is associated with higher risk of 3-month depression in patients with ischemic stroke and makes early diagnoses of depression. The study needs replication to ensure the validity of our preliminary results.


Bacterial subversion of lipid rafts.
Bacteria rely on numerous basic cellular functions of their target cells to reach successful infection. The recent discovery that the plasma membrane contains specialized microdomains, called lipid rafts, with many specific functions but in particular with the ability to concentrate signaling molecules, has therefore attracted the attention of cellular microbiologists. Since then an increasing number of bacteria and their products have been shown to interact with lipid rafts to promote infection or intoxication. Here we review why certain bacteria and/or their products are attracted toward these lipid microdomains.


CD154 regulates primate humoral immunity to influenza.
Current methods of immunosuppression for the purposes of allowing solid organ transplantation in humans are broadly inhibitory and thus are associated with an increased risk of opportunistic infections and neoplasia. We have shown previously that a selective blockade of CD40-CD154 interactions during heart transplantation in cynomolgus macaques significantly delays immune-mediated graft injury. Here, we determined the effect of anti-CD154 mAb therapy on primate serologic responses to immunization with influenza virus hemagglutinin (HA), a T-cell-dependent Ag. We found that CD154 blockade attenuated primary and secondary serum Ab responses of IgM and IgG isotypes to influenza, even when anti-CD154 treatment was discontinued prior to reimmunization. These findings show that in primates CD40-CD154 interactions are necessary for both primary and secondary Ab responses to viral Ags. Furthermore, the data suggest that viral Ag stimulation of primates in the absence of CD154 stimulation may have a tolerizing effect on that Ag.


CD30+ Large Cell Transformation of Mycosis Fungoides During Pregnancy.
Mycosis fungoides (MF) a cutaneous T-cell lymphoma, is a subgroup of non-Hodgkin's lymphomas, characterized by skin infiltration and occasionally systemic involvement. MF coincidence with pregnancy is rare. The effect of pregnancy on MF and the effect of this disease on pregnancy are still unknown. There are few case reports about pregnancy and its deleterious effect on the clinical course of MF. This case report is about a 30-years-old female with MF who became pregnant and after delivery developed CD30+ large cell transformation; this is the first report of large cell transformation of MF related to pregnancy.


SNR and Spectral Broadening in Turbulence Structure Measurement Using a cw Laser.
A symmetrical method of optical heterodyning of the doppler shifted signal has been developed possessingminimal instrumental spectral broadening and high SNR. These advantages can be gainfully employed in measuringturbulence structure using a cw laser. The method employs two beams incident on the moving scatterer. Thedoppler signal frequency is independent of the scattering angle and the signal possesses no receiving aperturebroadening. Typical values of signal-to-noise ratio are around 30 dB for a signal strength of 3 x 10(-9) W. Optical alignment is simple. Relative merits of this technique compared to the localoscillator heterodyning method are briefly described.


The metabolic and muscular differences between two stair-climbing strategies of young adults.
When climbing stairs, there are 2 practical strategies, contact each step with alternating feet (single) or contact every other step (double) with alternating feet. Our purpose was to evaluate the metabolic cost and muscular activity of these single and double stair-climbing strategies. We hypothesized that metabolic cost would not differ between the 2 strategies, because the subjects would complete the 2 protocols with a similar speed that would minimize cost. Likewise, we hypothesized that muscle activity during stance would not differ between the 2 stepping strategies. Twelve subjects completed baseline and experimental protocols. For the baseline protocol, the subjects walked up a stairwell with a single-step and a double-step strategy. For the experimental protocol, each subject walked on a treadmill inclined to the same degree as the stairs at the speed and step frequency determined from the baseline protocol. Every subject completed the baseline testing with a faster average speed during the double-step protocol. After mimicking each strategy with our experimental methods, we calculated that the double-step strategy would yield a greater use of metabolic energy, equal to approximately 1.0-1.3 kcalxkg-1xh-1, on average 70-90 additional kcalxh-1. This double-step strategy required a greater activity for propulsion during stance for the ankle and knee extensors. In summary, to maximize metabolic cost and muscular activity, we recommend a double-stair-climbing (skip a step) strategy.


Targeted therapies in malignant pleural mesothelioma: a review of clinical studies.
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis, whose exposure to asbestos fibers is the main etiology. The incidence of MPM is anticipated to increase worldwide during the first half of this century. MPM is notoriously refractory to most treatments, and the only standard of care is cisplatin and antifolate first-line chemotherapy. The urgent need for additional therapeutic agents, in parallel with advances in the knowledge of the molecular events of oncogenesis, has resulted in the development of the so-called 'targeted agents' that specifically inhibit critical pathways in malignant cells and in their microenvironment. We carried out a comprehensive review of the literature from January 2000 to May 2010 on studies that assessed targeted agents for the systemic treatment of MPM. Although tyrosine kinase inhibitors directed against the epidermal growth factor and the platelet-derived growth factor receptors did not show significant clinical activity in phase II studies, some other targeted therapies seemed promising, notably histone deacetylase inhibitors and antiangiogenic agents. However, none of these has yet reached daily practice. That is the reason why efforts must continue in the area of clinical and translational research for MPM.


When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment.
Measurement of stress hormone metabolites in fecal samples has become a common method to assess physiological stress in wildlife populations. Glucocorticoid metabolite (GCM) measurements can be collected noninvasively, and studies relating this stress metric to anthropogenic disturbance are increasing. However, environmental characteristics (e.g., temperature) can alter measured GCM concentration when fecal samples cannot be collected immediately after defecation. This effect can confound efforts to separate environmental factors causing predeposition physiological stress in an individual from those acting on a fecal sample postdeposition. We used fecal samples from American pikas (Ochotona princeps) to examine the influence of environmental conditions on GCM concentration by (1) comparing GCM concentration measured in freshly collected control samples to those placed in natural habitats for timed exposure, and (2) relating GCM concentration in samples collected noninvasively throughout the western United States to local environmental characteristics measured before and after deposition. Our timed-exposure trials clarified the spatial scale at which exposure to environmental factors postdeposition influences GCM concentration in pika feces. Also, fecal samples collected from occupied pika habitats throughout the species' range revealed significant relationships between GCM and metrics of climate during the postdeposition period (maximum temperature, minimum temperature, and precipitation during the month of sample collection). Conversely, we found no such relationships between GCM and metrics of climate during the predeposition period (prior to the month of sample collection). Together, these results indicate that noninvasive measurement of physiological stress in pikas across the western US may be confounded by climatic conditions in the postdeposition environment when samples cannot be collected immediately after defecation. Our results reiterate the importance of considering postdeposition environmental influences on this stress metric, especially in multiregional comparisons. However, measurements of fecal GCM concentration should prove useful for population monitoring within an eco-region or when postdeposition exposure can be minimized.


Lysosomal phospholipase A2 and phospholipidosis.
A lysosomal phospholipase A2, LPLA2, was recently characterized and shown to have substrate specificity for phosphatidylcholine and phosphatidylethanolamine. LPLA2 is ubiquitously expressed but is most highly expressed in alveolar macrophages. Double conditional gene targeting was employed to elucidate the function of LPLA2. LPLA2-deficient mice (Lpla2-/-) were generated by the systemic deletion of exon 5 of the Lpla2 gene, which encodes the lipase motif essential for the phospholipase A2 activity. The survival of the Lpla2-/- mice was normal. Lpla2-/- mouse mating pairs yielded normal litter sizes, indicating that the gene deficiency did not impair fertility or fecundity. Alveolar macrophages from wild-type but not Lpla2-/- mice readily degraded radiolabeled phosphatidylcholine. A marked accumulation of phospholipids, in particular phosphatidylethanolamine and phosphatidylcholine, was found in the alveolar macrophages, the peritoneal macrophages, and the spleens of Lpla2-/- mice. By 1 year of age, Lpla2-/- mice demonstrated marked splenomegaly and increased lung surfactant phospholipid levels. Ultrastructural examination of Lpla2-/- mouse alveolar and peritoneal macrophages revealed the appearance of foam cells with lamellar inclusion bodies, a hallmark of cellular phospholipidosis. Thus, a deficiency of lysosomal phospholipase A2 results in foam cell formation, surfactant lipid accumulation, splenomegaly, and phospholipidosis in mice.


The social and gender composition of nursing students in Australia: a comparison between 1987-1990 and 1995 recruits.
This national study compares the social and gender characteristics of an earlier group of 1551 students in higher-education programs in 1987 and 1990 with the national study group of 2295 students sampled in 1995. Using a specially constructed socio-economic variable for comparison, the analyses demonstrated a significant difference in the socio-economic level of the household for the female but not the male group. There was a significant difference in the proportion of males entering nursing between the earlier and latter groups. Further, in the latter group, these males were more likely to enter nursing programs directly from school. Members of the female group in the latter sample were more likely to have attended a school in a less populated area, come from households with a reduced family size, have mothers who were earning an income and have mothers who had achieved a higher level of education than was found in the earlier group. Logic analysis revealed that there was a significant interaction between the household variables, socio-economic status, number of siblings and income received by the mother of the respondents in the early and latter groups for females but not for males. This interaction for the female group, plus the finding that members of the latter group were more likely than other university students to defer their Higher Education Contribution Scheme (HECS) payments, suggests that if politicians were to make changes to the HECS it may affect the delicate social balance currently achieved in nursing recruitment in Australia.


Essentials of filoviral load quantification.
Quantitative measurement of viral load is an important parameter in the management of filovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of filovirus disease.


Confirmation of microevolutionary increase in spina bifida occulta among Swiss birth cohorts.
Previous studies on the prevalence of spina bifida occulta have indicated a microevolutionary increase in its frequency and possible population differences in the prevalence of the condition. We studied the frequencies of closed and open sacral canals at each sacral level among two birth cohorts in Switzerland. Transverse CT scans and multiplanar reconstruction images of sacra of 95 males and 96 females born in 1940-1950 and 99 males and 94 females born in 1970-1980 in Switzerland were reviewed. We found that individuals born later have significantly more open sacral arches at all sacral levels compared to those born 30-40 years earlier. When results were related to previously published data on Australian cohorts, the trend was the same, but Swiss in both cohorts were less likely to have an open section than Australians at all locations apart from S2. This study confirmed a microevolutionary trend in the opening of sacral canal among two different generations in Switzerland and demonstrated a population difference in the prevalence of spina bifida occulta.


Capture and release of cells using a temperature-responsive surface that immobilizes an antibody through DNA duplex formation.
We synthesized a temperature-responsive surface that immobilized an antibody via DNA duplex formation for selective capture and release of target cells. Polyethylene films were modified by grafting poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)), which were prepared at various ratios of NIPAAm/AAc. The increased hydrophilicity of P(NIPAAm-co-PAA) film with decreased temperature was confirmed by water contact angle measurement. Single strand DNA (20mer) was chemically immobilized on the surface and then antibody (anti-mouse CD45, mCD45) modified with the complementary single strand DNA was immobilized on the surface through DNA duplex formation. The mCD45 antibody immobilization was confirmed by immunostaining. HeLa cells (mCD45 negative) and mouse bone marrow (BM) cells (mCD45 positive) were adhered on the surfaces at 37 °C. Although HeLa cells were detached by 4 °C incubation, BM cells were still adhered on the surface and then the adhered cells were released by DNase treatment. From these results, it was suggested that cells could be selectively captured and collected by using a film having surface that immobilizes an antibody via DNA duplex formation.


Pseudo-dyadic "interaction" on Amazon's Mechanical Turk.
Psychological researchers have begun to utilize Amazon's Mechanical Turk (MTurk) marketplace as a participant pool. Although past work has established that MTurk is well suited to examining individual behavior, pseudo-dyadic interactions, in which participants falsely believe they are interacting with a partner, are a key element of social and cognitive psychology. The ability to conduct such interdependent research on MTurk would increase the utility of this online population for a broad range of psychologists. The present research therefore attempts to qualitatively replicate well-established pseudo-dyadic tasks on MTurk in order to establish the utility of this platform as a tool for researchers. We find that participants do behave as if a partner is real, even when doing so incurs a financial cost, and that they are sensitive to subtle information about the partner in a minimal-groups paradigm, supporting the use of MTurk for pseudo-dyadic research.


A bimodal multianalyte simple molecule chemosensor for Mg2+, Zn2+, and Co2+.
The well-known 8-aminoquinoline framework offers an ideal model for the development of fluorescence-enhanced chemosensors through simple and convenient syntheses. Herein, a novel and simple molecule chemosensor, 5-diethylamino-2-(quinolin-8-yliminomethyl)-phenol (HL), has been designed by combining an 8-aminoquinoline moiety and a 4-(diethylamino)salicylaldehyde in a single molecule to prove the selectivity and sensitivity for Mg(2+), Zn(2+), and Co(2+) in a dual-channel mode (fluorescence emission and UV/Vis). When binding Mg(2+), HL not only showed an obvious fluorescence enhancement but also enabled the Mg(2+) detection range over 1.68 ppb. Meanwhile, in mixed solvent media, HL displayed selectivity for Zn(2+) over other cations by the emission spectrum. It was worth noting that HL could be a colorimetric sensor for Co(2+) in a semi-aqueous solution by monitoring the absorption spectral behavior and be a colorimetric reagent for sensing and staining of Co(2+) in the cells. The results indicate that HL can be applied in multianalyte detection.


Imaging patients with cardiac trauma.
In the United States, trauma is the leading cause of death among those who are 1-44 years old, with cardiovascular injuries representing the second most common cause of traumatic death after central nervous system injuries. Evaluation of trauma patients with suspected cardiac injury may be complex and include electrocardiography, measurement of cardiac biomarkers, and imaging examinations. Contrast material-enhanced computed tomography (CT) has become one of the most valuable imaging tools available for evaluating hemodynamically stable patients with suspected cardiac injury. The presence of hemopericardium, with or without cardiac tamponade, is one of the most significant findings of cardiac injury. Other complications that result from blunt cardiac injury, such as pericardial rupture and cardiac herniation, may be readily depicted at multidetector CT. Assessment of patients with cardiac injuries, particularly those with penetrating injuries, is a challenging and time-critical matter, with clinical and imaging findings having complementary roles in the formation of an accurate diagnosis. Patients who are hemodynamically stable, particularly those with penetrating cardiac injuries, also may benefit from a timely imaging examination. In addition to chest radiography, other available modalities such as transthoracic and transesophageal echocardiography, nuclear medicine, and magnetic resonance imaging may play a role in selected cases.


Bacterial infection as an adverse effect of telaprevir-based triple therapy for chronic hepatitis C infection.
There is little information regarding the incidence of bacterial infections as an adverse effect of telaprevir (TVR)-based triple therapy. This study was performed in order to evaluate the baseline and on-treatment predictors of bacterial infections in patients treated with TVR-based triple therapy. This multicenter study evaluated 430 patients with chronic hepatitis C who received 12 weeks of TVR in combination with 24 weeks of pegylated interferon α2b plus ribavirin. The occurrence of a bacterial infection during anti-viral treatment was defined as the onset of local or systemic inflammation as a result of pathogenic bacteria. Bacterial infections occurred in 21 of the 430 (4.9%) patients during TVR-based triple therapy. Among these subjects, 71.4% (15 of 21) experienced bacterial infections during the initial eight weeks of treatment. Urinary tract infections were the most frequent infection, observed in 2.8% of cases (12 of 430). The rate of urinary tract infection among women (11 of 215, 5.1%) was significantly higher than that observed among men (1 of 215, 0.5%) (p<0.0001). According to a multivariable logistic regression analysis, the only significant independent predictor was the pretreatment serum albumin level (p=0.0008). Of the 21 patients who experienced bacterial infections, only one (4.8%) had to discontinue the treatment; however, the others were able to continue anti-viral treatment in combination with antibiotic treatment. Clinicians should be concerned regarding the incidence of bacterial infections among patients treated with TVR-based triple therapy, especially those with a low serum albumin level.


Radiographic evaluation of posttraumatic osteoarthritis of the ankle: the Kellgren-Lawrence scale is reliable and correlates with clinical symptoms.
To assess reliability and construct validity of the Kellgren-Lawrence (K&L) scale in posttraumatic ankle osteoarthritis (OA); additionally evaluate the validity of including tibiotalar tilting in the scale. One-hundred and fifty ankle radiographs (75 patients, unilateral malleolar fractures) evaluated at average of 18 years after surgery. American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot (HF) score and pain (visual analog scale) were recorded. Grading of OA according to K&L criteria and identification of OA features was performed on standardized radiographs by four physicians. Minimal joint space width, sclerosis, and talar tilt angle were quantified by digital measurements. A modified K&L scale including talar tilting is presented. Validity of original and modified scale was evaluated and expressed as ability to (1) Identify those with clinical symptoms of ankle OA; and (2) Distinguish between different degrees of fracture severity. Inter- and intra-observer reliability of OA assessment according to K&L were good (ICC 0.61 and 0.75). Original and modified K&L grades significantly increased with decreasing AOFAS ankle-HF scores and greater pain. A talar-tilt angle > 2° compared with ≤ 2° in grade 3 was associated with significantly higher pain levels (VAS pain 4.2 vs 1.4, respectively; mean difference 2.8, 95% CI 0.5-5.1). More severe fracture patterns at time of surgery were more often in patients with the highest K&L grades. The K&L scale is a valid and reliable radiographic grading system for assessment of ankle OA. Inclusion of the talar tilt angle might allow for better differentiation with respect to clinical outcomes.


Nickel-containing nano-sized islands grown on Ge(111)-c(2 × 8) and Ag/Ge(111)-(√3 × √3) surfaces.
The formation of nano-islands on both a Ge(111)-c(2 × 8) surface and an Ag/Ge(111)-(√3 × √3) surface evaporated with 0.1 ML Ni was investigated by scanning tunneling microscopy (STM). We have noticed that at temperatures lower than 670 K, the reaction between Ni and the individual substrate surfaces proceeds to form different structures: flat-topped islands with a 2√7 × 2√7 or a 3 × 3 reconstruction on the Ni/Ge(111)-c(2 × 8) surface vs. islands with a 7 × 7 reconstruction on the Ni/Ag/Ge(111)-(√3 × √3) surface. From this we have inferred that within a temperature range between room temperature and 670 K, the intermediate Ag layer retards mixing between Ni and Ge atoms. As a result, the grown islands are composed of pure Ni atoms. Within a temperature range from 670 to 770 K, most islands produced on the Ag/Ge(111)-(√3 × √3) surface are identical with those formed on the Ni/Ge(111)-c(2 × 8) surface, suggesting that above 670 K, Ni atoms are likely to bind with Ge atoms. However, an essential difference between STM images of the surfaces under study exists in the appearance of large elongated islands on the Ni/Ag/Ge(111)-(√3 × √3) surface. The formation of the latter is explained in terms of a difference in energy for Ni diffusion on the Ge(111)-c(2 × 8) and Ag/Ge(111)-(√3 × √3) surfaces.


Binding of Myomesin to Obscurin-Like-1 at the Muscle M-Band Provides a Strategy for Isoform-Specific Mechanical Protection.
The sarcomeric cytoskeleton is a network of modular proteins that integrate mechanical and signaling roles. Obscurin, or its homolog obscurin-like-1, bridges the giant ruler titin and the myosin crosslinker myomesin at the M-band. Yet, the molecular mechanisms underlying the physical obscurin(-like-1):myomesin connection, important for mechanical integrity of the M-band, remained elusive. Here, using a combination of structural, cellular, and single-molecule force spectroscopy techniques, we decode the architectural and functional determinants defining the obscurin(-like-1):myomesin complex. The crystal structure reveals a trans-complementation mechanism whereby an incomplete immunoglobulin-like domain assimilates an isoform-specific myomesin interdomain sequence. Crucially, this unconventional architecture provides mechanical stability up to forces of ∼135 pN. A cellular competition assay in neonatal rat cardiomyocytes validates the complex and provides the rationale for the isoform specificity of the interaction. Altogether, our results reveal a novel binding strategy in sarcomere assembly, which might have implications on muscle nanomechanics and overall M-band organization.


High-sensitivity epidermal growth factor receptor immunostaining for colorectal carcinomas, compared with EGFR PharmDx™: a study of diagnostic accuracy.
Immunostaining for epidermal growth factor receptor (EGFR) is important in the contemporary therapeutic strategy of colorectal carcinomas. We tried to increase detection sensitivity, and compared the high-sensitivity EGFR immunostaining with a worldwide standard, EGFR PharmDx™ (Dako). In order to pursue high-sensitivity EGFR detection, deparaffinized sections were pressure-cooked in 1 mM EDTA solution, pH 8.0. Two mouse monoclonal antibodies against EGFR, clone EGFR2.5 and DAK-H1-WT, and six kinds of secondary detection reagents, including biotin-free catalyzed signal amplification (CSA II), Simple Stain MAX-PO, PolyVue, Novolink, EnVision™ FLEX+, and MACH3, were evaluated to compare the results with those with EGFR PharmDx™, employing a combination of 2-18-C9 as the primary monoclonal antibody and EnVision™ as the secondary reagent. Furthermore, we replaced EnVision™ in the EGFR PharmDx™ kit with CSAII. EGFR detection sensitivity was higher with DAK-H1-WT than with EGFR2.5, and among the secondary reagents, the strongest signals were observed with Novolink. All 30 colorectal carcinomas showed distinct expression of EGFR with our high-sensitivity EGFR immunostaining, while only 16 (53%) gave focal positivity with EGFR PharmDx™. When EnVision™ in EGFR PharmDx™ was replaced by CSA II, strong signals were seen in all cases, and the expression pattern was comparable with our sequence. Non-neoplastic crypt epithelial cells often showed weakly signal with the standard EGFR PharmDx™, but consistently revealed strong membrane staining in the two high-sensitivity sequences. EGFR PharmDx™ frequently gave false negativity. Importantly, EGFR was consistently and sensitively detected when the secondary polymer in the EGFR PharmDx™ kit was simply replaced by CSA II.