Comprehensive assessment of frailty for elderly high-risk patients undergoing cardiac surgery.
Cardiosurgical operative risk can be assessed using the logistic European system for cardiac operative risk evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) score. Factors other than medical diagnoses and laboratory values such as the 'biological age' are not included in these scores. The aim of the study was to evaluate an additional assessment of frailty in routine cardiac surgical practice. 'The comprehensive assessment of frailty' test was applied to 400 patients≥74 years who were admitted to our centre between September 2008 and January 2010. For comparison, the STS score and the EuroSCORE were calculated. The primary end point was the correlation of Frailty score to 30-day mortality. A total of 206 female and 194 male patients were included. Median Frailty score was 11 [7,15]. Median of logistic EuroSCORE was 8.5% [5.8%; 13.9%]. Median of STS score was 3.3% [2.1%; 5.1%]. There were low-to-moderate albeit significant correlations of Frailty score with STS score and EuroSCORE (p<0.05). There was also a significant correlation between Frailty score and observed 30-day mortality (p<0.05). Patients received isolated coronary artery bypass grafting (CABG) (n=90), isolated valve surgery (n=128), trans-catheter valve implantation (n=59) or combined procedures (n=123). The comprehensive assessment of frailty is an additional tool to evaluate elderly patients adequately before cardiac surgical interventions. The Frailty score combines characteristics of the Fried criteria [1], of patient phenotype, of his physical performance and laboratory results. Further analysis on a larger patient population is warranted. A combination of the new Frailty score and the traditional scoring systems may facilitate a more accurate risk scoring in elderly high-risk patients scheduled for conventional cardiac surgery or trans-catheter aortic valve replacement.


The changing pattern of clinical Mycobacterium avium isolation in the Netherlands.
National Mycobacteria Reference Laboratory, The Netherlands. To assess the role of factors other than laboratory improvements in the increasing frequency of isolation of non-tuberculous mycobacteria (NTM) in the Netherlands; laboratory improvements are often considered key factors in this increase. Laboratory database study. All clinically isolated NTM referred to the national reference laboratory between January 2000 and January 2007 were retrieved from the laboratory database and categorised by species, patient age group and sample origin. Data were compared with national demographic data. Clinical Mycobacterium avium isolates accounted for most of the increase in referred NTM. The number of respiratory M. avium samples in patients aged >40 years increased over time. This age group increased in size during the study. In this age group, the prevalence of chronic obstructive pulmonary disease (COPD) increased during the study period. M. avium isolation from lymph nodes in children remained stable, whereas extra-pulmonary M. avium isolation in the middle age group, including human immunodeficiency virus associated bloodstream isolates, decreased. The increasing NTM notification in the Netherlands is unlikely to have been a result of laboratory improvements alone: the ageing population with an increasing prevalence of COPD is likely as important. Environmental characteristics may specifically favour M.avium.


The VA, VCD, Raman and ROA spectra of tri-L-serine in aqueous solution.
The structures of one conformer of the nonionic neutral and zwitterionic species of L-serinyl L-serinyl L-serine (SSS or tri-L-serine), together with its cationic and anionic species and the capped N-acetyl tri-L-serine N'-methylamide analog were optimized with density functional theory with the Becke 3LYP hybrid exchange correlation (XC) functional and the PW91 GGA XC functional and the 6-31G* and aug-cc-pVDZ basis sets. Subsequently, the vibrational absorption, vibrational circular dichroism, Raman and Raman optical activity spectra were simulated in order to compare them to experimentally measured spectra. In addition, we compare to previously reported studies for both structural determination and spectral simulations and measurements. A comparison of the various ways to treat the effects of the environment and solvation on both the structure and the spectral properties is thoroughly investigated for one conformer, with the goal to determine which level of theory is appropriate to use in the systematic search of the conformational space. In addition, the effects of the counterion, here Cl- anion, are also investigated. Here we present the current state of the art in nanobiology, where the latest methods in experimental and theoretical vibrational spectroscopy are used to gain useful information about the coupling of the nuclear, electronic and magnetic degrees of freedom and structure of tri-L-serine and its capped peptide analog with the environment.


A cross-sectional study of website claims related to diagnoses and treatment of non-musculoskeletal conditions.
The Danish Authorisation Act sets out the chiropractic scope of practice. Under this legislation the scope of practice is diagnostics, prevention and treatment of biomechanical disorders of the spine, pelvis and extremities. Despite this and an international movement toward a scientifically active, evidence-based profession with a focus on treatment of musculoskeletal disorders, a large proportion of chiropractors still offer treatment of non-musculoskeletal disorders. This study aimed to investigate the content and characteristics of website claims by chiropractors in Denmark on non-musculoskeletal conditions and to assess whether these were aligned with the Danish Authorisation Act of the chiropractic scope of practice. In this cross-sectional study data on a representative sample were collected from chiropractic clinic websites in Denmark. Information on non-musculoskeletal conditions from the websites was categorised. For each non-musculoskeletal condition, it was noted whether a clarifying explanation justifying the presence of the diagnosis was available and what it said. These explanations were assessed and categorised according to agreement or disagreement with the chiropractic scope of practice as defined by the Danish Authorisation Act. In addition, data on geographic location, clinic size, reimbursement coverage, country of education and special clinical focus (children, athletes, etc) were collected. Differences in characteristics of the clinics and the frequency of reporting non-musculoskeletal conditions were tested using Pearson's chi-squared or Fisher's exact test. A geographically stratified, random sample of 139 (57%) websites was included from chiropractic clinics in Denmark. In total, 36 (26%) of the sampled websites mentioned conditions of non-musculoskeletal origin that was not accompanied by a clarifying explanation in agreement with the chiropractic scope of practice. A positive association between advertising infant or children's care and advertising treatment for non-musculoskeletal disorders (without adequate explanation) was observed. A total of 36 (26%) of the sampled chiropractic websites in Denmark mentioned diagnoses or symptoms of non-musculoskeletal origin on their websites without presenting an adequate clarifying explanation in agreement with the chiropractic scope of practice as defined by the Danish Authorisation Act. This could be misleading for patients seeking care for non-musculoskeletal conditions and consequently lead to inappropriate treatment.


The adjoint of CMAQ.
An adjoint model for the internationally used Community Multiscale Air Quality (CMAQ) modeling platform of the U.S. EPA is developed. The adjoint version for CMAQ (CMAQ-ADJ) provides the user community with forward (decoupled direct method or DDM) and backward (adjoint) sensitivity analysis capabilities. Current implementation is for gas-phase processes. Discrete adjoints are implemented for all processes with the exception of horizontal advection, for which, because of inherent discontinuities in the advection scheme, the continuous approach is superior. The adjoint of chemistry is constructed by interfacing CMAQ with the kinetic pre-processor, which provides for increased flexibility in the choice of chemical solver and facilitates the implementation of new chemical mechanisms. The adjoint implementation is evaluated both on a process-by-process basis and for the full model. In general, adjoint results show good agreement with brute-force and DDM sensitivities. As expected for a continuous adjoint implementation in a nonlinear scheme, the agreement is not perfect for horizontal transport. Sensitivities of various air quality, public health, and environmental metrics with respect to emissions are calculated using the adjoint method. In order to show applicability to regional climate studies, as an example, the sensitivities of these metrics with respect to local temperatures are calculated.


Evidence That the Origin of Naked Kernels During Maize Domestication Was Caused by a Single Amino Acid Substitution in tga1.
teosinte glume architecture1 (tga1), a member of the SBP-box gene family of transcriptional regulators, has been identified as the gene conferring naked kernels in maize vs. encased kernels in its wild progenitor, teosinte. However, the identity of the causative polymorphism within tga1 that produces these different phenotypes has remained unknown. Using nucleotide diversity data, we show that there is a single fixed nucleotide difference between maize and teosinte in tga1, and this difference confers a Lys (teosinte allele) to Asn (maize allele) substitution. This substitution transforms TGA1 into a transcriptional repressor. While both alleles of TGA1 can bind a GTAC motif, maize-TGA1 forms more stable dimers than teosinte-TGA1. Since it is the only fixed difference between maize and teosinte, this alteration in protein function likely underlies the differences in maize and teosinte glume architecture. We previously reported a difference in TGA1 protein abundance between maize and teosinte based on relative signal intensity of a Western blot. Here, we show that this signal difference is not due to tga1 but to a second gene, neighbor of tga1 (not1). Not1 encodes a protein that has 92% amino acid similarity to TGA1 and that is recognized by the TGA1 antibody. Genetic mapping and phenotypic data show that tga1, without a contribution from not1, controls the difference in covered vs. naked kernels. No trait differences could be associated with the maize vs. teosinte alleles of not1. Our results document how morphological evolution can be driven by a simple nucleotide change that alters protein function.


Can duplex scan arterial mapping replace contrast arteriography as the test of choice before infrainguinal revascularization?
Arteriography is the diagnostic test of choice before lower extremity revascularization, because it is a means of pinpointing stenotic or occluded arteries and defining optimal sites for the origin and termination of bypass grafts. We evaluated whether a duplex ultrasound scan, used as an alternative to arteriography, could be used as a means of accurately predicting the proximal and distal anastomotic sites in patients requiring peripheral bypass grafts and, therefore, replace standard preoperative arteriography. Forty-one patients who required infrainguinal bypass grafts underwent preoperative duplex arterial mapping (DAM). Based on these studies, an observer blinded to the operation performed predicted what operation the patient required and the best site for the proximal and distal anastomoses. These predictions were compared with the actual anastomotic sites chosen by the surgeon. Whether a femoropopliteal or an infrapopliteal bypass graft was required was predicted correctly by means of DAM in 37 patients (90%). In addition, both anastomotic sites in 18 of 20 patients (90%) who had femoropopliteal bypass grafts and 5 of 21 patients (24%) who had infrapopliteal procedures were correctly predicted by means of DAM. DAM is a reliable means of predicting whether patients will require femoropopliteal or infrapopliteal bypass grafts, and, when a patient requires a femoropopliteal bypass graft, the actual location of both anastomoses can also be accurately predicted. Therefore, DAM appears able to replace conventional preoperative arteriography in most patients found to require femoropopliteal reconstruction. Patients who are predicted by means of DAM to require crural or pedal bypass grafts should still undergo preoperative contrast studies to confirm these results and to more precisely locate the anastomotic sites.


CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer.
Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers. Patients with locally advanced or metastatic chemotherapy-refractory gastric, esophageal, or gastroesophageal junction cancer from centers in the United States and Europe received nivolumab or nivolumab plus ipilimumab. The primary end point was objective response rate. The association of tumor programmed death-ligand 1 status with response and survival was also evaluated. Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to 23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups, respectively. Responses were observed regardless of tumor programmed death-ligand 1 status. With a median follow-up of 28, 24, and 22 months across the three groups, 12-month progression-free survival rates were 8%, 17%, and 10%, respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients in the three groups, respectively. Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term OS, and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.


Cyclophosphamide intoxication because of pharmacy error in two dogs.
An 8-year-old spayed female Yorkshire Terrier and 5-year-old castrated male West Highland White Terrier were evaluated because of cyclophosphamide intoxication subsequent to pharmacy error. Both dogs received cumulative doses of approximately 1,080 mg of cyclophosphamide/m(2) after cyclophosphamide was erroneously dispensed instead of cyclosporine by different pharmacies. Both dogs became lethargic, and 1 dog also had anorexia, vomiting, and diarrhea within 2 days after initiation of cyclophosphamide administration. The other dog developed anorexia on the seventh day after initiation of cyclophosphamide administration. The dogs were evaluated by their primary-care veterinarians 9 and 11 days after administration of the first dose of cyclophosphamide, and both had severe leukopenia and thrombocytopenia. One dog was treated on an outpatient basis with broad-spectrum antimicrobials, granulocyte colony-stimulating factor, and an appetite stimulant. The other dog was more severely affected and was hospitalized for 7 days, during which it was treated with broad-spectrum antimicrobials, gastroprotectants, granulocyte colony-stimulating factor, and cryopreserved platelet and packed RBC transfusions. Both dogs fully recovered after treatment. This was the first report of survival for dogs with inadvertent prolonged cyclophosphamide intoxication subsequent to pharmacy error. Although the 2 dogs had similar clinical signs and clinicopathologic findings, the severity of disease and treatment required differed for each dog. Dogs can recover from prolonged cyclophosphamide intoxication provided appropriate supportive care is administered.


High prevalence of Rickettsia gravesii sp. nov. in Amblyomma triguttatum collected from feral pigs.
A survey of ectoparasites on feral pigs identified two commonly occurring ixodid tick species; Amblyomma triguttatum triguttatum and Ixodes australiensis. Molecular screening of A. t. triguttatum and I. australiensis for the presence of Rickettsia species detected the presence of rickettsiae belonging to the Spotted Fever Group (SFG) in 78.4% of screened A. t. triguttatum. None of the screened I. australiensis were positive for rickettsiae. Sequence analysis of the gltA and ompA loci of positive Rickettsia isolates were 100% homologous to the newly described species Rickettsia gravesii sp. nov. BWI-1. Serological screening of feral pigs detected antibodies to SFG Rickettsia in 50% of serum samples tested. These findings suggest that A. t. triguttatum is a vector/reservoir for R. gravesii sp. nov.


Diet and teeth. Dietary hypotheses and human evolution.
Hypotheses concerning the diet of early hominids have played an important role in discussions on human evolution. Three investigations have helped define the extent to which dietary hypotheses may be taken and still be testable. Comparative anatomy is a fairly coarse approach, which despite convergences allows only the most specialized diets to be ruled out. A biomechanical analysis makes it clear that the changes in jaw and tooth form are subtle and outside the resolution given by present understanding of cranial function. Analysis of the microscopic tooth wear of extant species has been carried out. Major dietary types can be distinguished by their microwear. The microwear on fossil hominids appears to rule out certain diets that have been proposed for them.


3D printed reproductions of orbital dissections: a novel mode of visualising anatomy for trainees in ophthalmology or optometry.
The teaching of human head, neck and orbital anatomy forms a critical part of undergraduate and postgraduate medical and allied health professional training, including optometry. While still largely grounded in cadaveric dissection, this method of instruction is constrained in some countries and regional areas by access to real human cadavers, costs of cadaver bequest programmes, health and safety of students and staff and the shortage of adequate time in modern curricula. Many candidates choosing a postgraduate pathway in ophthalmological training, such as those accepted into the Royal Colleges of Ophthalmology in the UK, Australia and New Zealand programmes and the American Academy of Ophthalmologists in the USA, are compelled as adult learners to revise or revisit human orbital anatomy, ocular anatomy and select areas of head and neck anatomy. These candidates are often then faced with the issue of accessing facilities with dissected human cadaveric material. In light of these difficulties, we developed a novel means of creating high-resolution reproductions of prosected human cadaver orbits suitable for education and training. 3D printed copies of cadaveric orbital dissections (superior, lateral and medial views) showing a range of anatomical features were created. These 3D prints offer many advantages over plastinated specimens as they are suitable for rapid reproduction and as they are not human tissue they avoid cultural and ethical issues associated with viewing cadaver specimens. In addition, they are suitable for use in the office, home, laboratory or clinical setting in any part of the world for patient and doctor education.


Computational methods to reduce uncertainty in the estimation of cardiac conduction properties from electroanatomical recordings.
Cardiac imaging is routinely used to evaluate cardiac tissue properties prior to therapy. By integrating the structural information with electrophysiological data from e.g. electroanatomical mapping systems, knowledge of the properties of the cardiac tissue can be further refined. However, as in other clinical modalities, electrophysiological data are often sparse and noisy, and this results in high levels of uncertainty in the estimated quantities. In this study, we develop a methodology based on Bayesian inference, coupled with a computationally efficient model of electrical propagation to achieve two main aims: (1) to quantify values and associated uncertainty for different tissue conduction properties inferred from electroanatomical data, and (2) to design strategies to optimize the location and number of measurements required to maximize information and reduce uncertainty. The methodology is validated in an in silico study performed using simulated data obtained from a human image-based ventricular model, including realistic fibre orientation and a transmural scar. We demonstrate that the method provides a simultaneous description of clinically-relevant electrophysiological conduction properties and their associated uncertainty for various levels of noise. By using the developed methodology to investigate how the uncertainty decreases in response to added measurements, we then derive an a priori index for placing electrophysiological measurements in order to optimize the information content of the collected data. Results show that the derived index has a clear benefit in minimizing the uncertainty of inferred conduction properties compared to a random distribution of measurements, reducing the number of required measurements by over 50% in several of the investigated settings. This suggests that the methodology presented in this work provides an important step towards improving the quality of the spatiotemporal information obtained using electroanatomical mapping.


Influenza like Illness (ILI): prescribing behaviour of 83 sentry doctors in Lazio region in the period 2001-2002. Is it adherent to Italian ILI guidelines?
To describe different doctors' attitudes in drug prescribing in case of influenza-Like-Illness during 2001-2002 influenza season in Lazio region, with regard to consumption and expenditure and its adherence to Italian Guidelines on ILI Management. Prospective study aimed to assess doctors' behaviour in prescribing in respect with the following events: (a) ILI and subsequent controls after diagnosis, (b) complications, (c) adverse events to influenza vaccine. 7,629 subjects, have been identified and only 17% presents one or more comorbidities. There are totally 7,766 cases of ILI: 23% are complicated and out of the remaining 77%, only 14% presents comorbidities. Almost all elderly people have been vaccinated. Antibiotics were prescribed to complicated cases (82%) with comorbidities (55%); 1,075 patients (12%) had second or third contact with doctors in a period longer than 7 days and about 65% of them received antibiotics in case of acute bronchitis; children received mainly ibuprofen and paracetamol for fever control; acetylsalicylic acid in children group has been delivered only in 1% of cases. Overall, doctors' attitude in prescribing is generally coherent with Italian Guidelines on ILI even though a high variability still persists.


Effects of repetitive transcranial magnetic stimulation of the unaffected hemisphere leg motor area in patients with subacute stroke and substantial leg impairment: A pilot study.
To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on mobility among patients with substantial leg impairment after subacute stroke. Double-blinded, stratified, randomized trial involving a sham control group. Patients who developed unilateral hemiplegia after first-ever subacute stroke and underwent inpatient stroke rehabilitation. The 15-day intervention programme used in the present study included the application of rTMS (1 Hz, 15 min) over the leg motor area of the unaffected hemisphere, followed by 45 min physical therapy. Overall, 32 participants were randomly assigned to receive either real rTMS or sham stimulation. Clinical assessments, including the Postural Assessment Scale for Stroke Patients (PASS), balance subscale of the Performance Oriented Mobility Assessment (POMA-b), Fugl-Meyer Assessment, Barthel Index (BI), and Timed Up and Go test, were performed immediately before and after the intervention. Both groups demonstrated significant improvements in all the test results over time. At the post-test assessment, the patients in the real rTMS group demonstrated greater improvements in the PASS, POMA, and BI scores than did the patients in the sham rTMS group. In addition, a significantly higher number of patients in the real rTMS group regained mobility at the post-test assessment compared with the corresponding number of patients in the sham rTMS group. Application of 1-Hz rTMS may improve mobility among patients with substantial leg impairment after subacute stroke.


Play in Children With Life-Threatening and Life-Limiting Conditions: A Scoping Review.
Play is essential to children and provides opportunities to promote their health and well-being. Children living with life-threatening and life-limiting conditions experience deprivation in play. To conduct a scoping review of studies that examined play of children with a life-threatening or life-limiting condition to explore their play characteristics and possible factors influencing their participation in play. A search of literature published between 1990 and 2017 was conducted in the health, social care, and built-environment fields. The scoping review included multiple searches in electronic databases, a gray literature search, and manual searches of relevant journals and reference lists of included articles. Defined criteria were used to select articles describing studies that examined the daily play of children ages 5-11 yr with life-threatening and life-limiting conditions; articles that focused on play as therapy or that used parents' accounts of a service were excluded. The identified articles were critically appraised with the Critical Appraisal Skills Programme and the Joanna Briggs Institute Critical Appraisal Tools. Thirteen articles were reviewed. The findings indicate that children's play is influenced by their health conditions and play opportunities and by the limited availability of appropriate play equipment and spaces allowing play and social interaction. Available appropriate play opportunities need to be maximized for children living with life-threatening and life-limiting conditions. This goal can be achieved by understanding and considering the needs of these children and by facilitating environmental enablers and limiting barriers. Promoting the participation in play of children who live with life-threatening and life-limiting conditions is important to their health and well-being and can be achieved by targeting the cultural, social, and physical environmental factors that shape the children's play.


Life history of Milnesium tardigradum Doyère (tardigrada) under a rearing environment.
A strain of carnivorous tardigrade, Milnesium tardigradum, was reared in water on agar plates at 25 degrees C. The monogonont rotifer Lecane inermis was presented as a food source. This rearing system permitted detailed observation of tardigrade behaviour. Daily measurements of body length allowed the growth rate and moulting cycle of this species to be determined. The life history of M. tardigradum raised under these conditions included up to seven periods of moult. The first and second moults occurred at intervals of 4-5 days, and individuals reached reproductive maturity at the 3rd-instar stage; the first period of egg laying accompanied the third moult. The most rapidly developing animal in the study population laid eggs 12 days after hatching. The egg-laying intervals or moulting intervals of adult animals were around 6-10 days. The mean clutch size was 6.9 eggs. All tardigrades in this laboratory population were female and reproduced by parthenogenesis. The duration of the embryonic stage ranged from 5-16 days. The most long-lived female survived for 58 days after hatching, and laid a total of 41 eggs in 5 separate clutches. The entire life cycle of tardigrades reared under these conditions was recorded and photographed. A brief description of the embryonic development of M. tardigradum was also reported.


SU-E-J-12: Initial Clinical Experiences in Using 4D-CBCT as Image Guidance for Lung SBRT.
The authors started to use Symmetry 4D-CBCT as image guidance for lung SBRT in August 2011. Here the authors present the initial clinical experiences with this novel image guidance technique. In total 118 4D-CBCT scans have been acquired for 17 lung patients among which 15 received SBRT and the other 2 received hypofractionated treatments. 4D-CBCT scans are acquired with Elekta XVI 4.5 usingSymmetry, a procedure module in XVI that acquires 4D-CBCT, registers daily images to reference 3D-CT and generates shifts for patient setup. Typical thoracic 4D-CBCT scans with Symmetry take 3 minutes with a 200 degree gantry rotation. Symmetry automatically sorts images into 10 phases based on automatic detection of diaphragm position. Then Symmetry generates two independent intensity-based registrations, one according to a pre-defined large volume of interest including the tumor, surrounding tissues and bony structures, the other only according to an expanded target volume. The registrations are obtained by registering each phase image to the reference image and averaging across all phases in a time-weighted manner. Eventually Symmetry provides users the freedom to pick either one of the two registrations, a compromise, or a manual tuning. Compared to regular 3D-CBCT, 4D-CBCT enables physicians to visually place the moving target in the center of PTV, greatly reducing the probability of missing target due to respiratory motion, thus enables possible reduction in PTV margin. 4D-CBCT also provides the ability to repeatedly evaluate the quality of ITV. It is possible that ITV does not fully cover the tumor motion due to a low quality 4D-CT simulation for a patient with difficulties in regular breathing. 4D-CBCT is a superior image guidance technique for lung SBRT treatments for its ability to visualize moving target. It provides physicians more confidence in tumor targeting and ability to repeatedly evaluate ITV quality during the treatment course.


MCAT: Motif Combining and Association Tool.
De novo motif discovery in biological sequences is an important and computationally challenging problem. A myriad of algorithms have been developed to solve this problem with varying success, but it can be difficult for even a small number of these tools to reach a consensus. Because individual tools can be better suited for specific scenarios, an ensemble tool that combines the results of many algorithms can yield a more confident and complete result. We present a novel and fast tool ensemble MCAT (Motif Combining and Association Tool) for de novo motif discovery by combining six state-of-the-art motif discovery tools (MEME, BioProspector, DECOD, XXmotif, Weeder, and CMF). We apply MCAT to data sets with DNA sequences that come from various species and compare our results with two well-established ensemble motif-finding tools, EMD and DynaMIT. The experimental results show that MCAT is able to identify exact match motifs in DNA sequences efficiently, and it has a significantly better performance in practice.


Generation of the short RNA transcript in Leishmaniavirus correlates with the growth of its parasite host, Leishmania.
Leishmaniavirus 1 is a double-stranded RNA virus that infects the New World kinetoplastid parasites, Leishmania braziliensis, and Leishmania guyanensis. The isolated virus particles contain an RNA-dependent RNA polymerase which exhibits both transcriptase activity for genome-length plus-strand synthesis and replicase activity for genome-length minus-strand synthesis. Recently, we identified a 320 nucleotide short RNA transcript of Leishmaniavirus 1-4, derived from the 5' end of the viral plus-strand, which is generated by the virus capsid via site-specific cleavage of the full-length positive single-stranded RNA. We have hypothesized that this short RNA transcript functions to regulate the virus life cycle during the growth of its parasite host, Leishmania guyanensis. To address this hypothesis, we measured the relative amount of short RNA transcripts and the absolute number of viral genomes per infected cell from log through stationary phase of the parasite growth cycle. In vitro assays of the viral polymerase showed an overall increase in viral polymerase activity from log growth into stationary phase which mirrored an in vivo increase in the quantity of double-stranded genome as measured by agarose gel electrophoresis. We have developed competitive reverse transcription-polymerase chain reaction (RT-PCR) assays to measure the relative amounts of viral transcripts in infected cells as well as the number of viral genomes per infected cell. The results of these assays show that the amount of full-length virus transcripts peaks in the parasite stationary phase (132 transcripts per cell), and that the short transcript is most abundant in the early stationary phase cells (24 transcripts per cell).


Neocortical focus: experimental view.
All brain normal or pathological activities occur in one of the states of vigilance: wake, slow-wave sleep, or REM sleep. Neocortical seizures preferentially occur during slow-wave sleep. We provide a description of neuronal behavior and mechanisms mediating such a behavior within neocortex taking place in natural states of vigilance as well as during seizures pointing to similarities and differences exhibited during sleep and seizures. A concept of epileptic focus is described using a model of cortical undercut, because in that model, the borders of the focus are well defined. In this model, as in other models of acquired epilepsy, the main factor altering excitability is deafferentation, which upregulates neuronal excitability that promotes generation of seizures. Periods of disfacilitation recorded during slow-wave sleep further upregulate neuronal excitability. It appears that the state of neurons and neuronal network in the epileptic focus produced by deafferentation are such that seizures cannot be generated there. Instead, seizures always start around the perimeter of the undercut cortex. Therefore, we define these areas as the seizure focus. In this zone, neuronal connectivity and excitability are moderately enhanced, lowering the threshold for seizure generation.


Ultrastructural observations on the terminal segment epithelium of the seminiferous tubule of West African dwarf goats.
In the testes of West African dwarf goats, modified Sertoli cells comprise the major component of the terminal segment epithelium. They resemble Sertoli cells proper but differ in the paucity of agranular endoplasmic reticulum and lipid droplets. Cell attachment devices present include rudimentary desmosomes and occasional multiple contacts of opposing plasma membranes, interrupted by segments of slightly expanded intercellular space. A few generative cells are present in the proximal zone of the epithelium, but their development appears to terminate as early spermatids which hang loosely on the luminal surface. The middle zone epithelium comprises vacuolated cells lying among other cells containing abundant microtubules in their subapical cytoplasm. Globular expansions of the intercellular space are also apparent. The terminal plug contains two cell types. Type I are inclined, columnar cells which contain profuse arrays of agranular endoplasmic reticulum in their apical cytoplasm. Type II are smaller cells located at the apex of the plug. Each possesses cytoplasmic processes, which surround the apices of Type I cells. The modified Sertoli cells of all zones and the Type II plug cells contain remnants of spermatozoa at different stages of degradation. The general absence of developing generative cells in the terminal segment epithelium may be related to the paucity of agranular endoplasmic reticulum in the basal cytoplasm of modified Sertoli cells and the absence of typical Sertoli-Sertoli junctional specialisations. Structural modifications evident in the middle and distal zones facilitate distalward movement of materials, while the attenuation and modification of the lumen distally may facilitate phagocytosis of abnormal spermatozoa.


Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice.
Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice. Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured. Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF. AqSF-P cosupplementation augmented the hepatic lipid-/glucose-lowering effects of FF. BY ameliorated FF-induced liver injury in normal and HCL mice.


Spatio-temporal patterns and movement analysis of pigs from smallholder farms and implications for African swine fever spread, Limpopo province, South Africa.
Infectious and zoonotic disease outbreaks have been linked to increasing volumes of legal and illegal trade. Spatio-temporal and trade network analyses have been used to evaluate the risks associated with these challenges elsewhere, but few details are available for the pig sector in South Africa. Regarding pig diseases, Limpopo province is important as the greater part of the province falls within the African swine fever control area. Emerging small-scale pig farmers in Limpopo perceived pig production as an important means of improving their livelihood and an alternative investment. They engage in trading and marketing their products with a potential risk to animal health, because the preferred markets often facilitate potential longdistance spread and disease dispersal over broad geographic areas. In this study, we explored the interconnectedness of smallholder pig farmers in Limpopo, determined the weaknesses and critical control points, and projected interventions that policy makers can implement to reduce the risks to pig health. The geo-coordinates of surveyed farms were used to draw maps, links and networks. Predictive risks to pigs were determined through the analyses of trade networks, and the relationship to previous outbreaks of African swine fever was postulated. Auction points were identified as high-risk areas for the spread of animal diseases. Veterinary authorities should prioritise focused surveillance and diagnostic efforts in Limpopo. Early disease detection and prompt eradication should be targeted and messages promoting enhanced biosecurity to smallholder farmers are advocated. The system may also benefit from the restructuring of marketing and auction networks. Since geographic factors and networks can rapidly facilitate pig disease dispersal over large areas, a multi-disciplinary approach to understanding the complexities that exist around the animal disease epidemiology becomes mandatory.


TNFα cooperates with IFN-γ to repress Bcl-xL expression to sensitize metastatic colon carcinoma cells to TRAIL-mediated apoptosis.
TNF-related apoptosis-inducing ligand (TRAIL) is an immune effector molecule that functions as a selective anti-tumor agent. However, tumor cells, especially metastatic tumor cells often exhibit a TRAIL-resistant phenotype, which is currently a major impediment in TRAIL therapy. The aim of this study is to investigate the synergistic effect of TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis. The efficacy and underlying molecular mechanism of cooperation between TNFα and IFN-γ in sensitizing metastatic colon carcinoma cells to TRAIL-mediated apoptosis were examined. The functional significance of TNFα- and IFN-γ-producing T lymphocyte immunotherapy in combination with TRAIL therapy in suppression of colon carcinoma metastasis was determined in an experimental metastasis mouse model. We observed that TNFα or IFN-γ alone exhibits minimal sensitization effects, but effectively sensitized metastatic colon carcinoma cells to TRAIL-induced apoptosis when used in combination. TNFα and IFN-γ cooperate to repress Bcl-xL expression, whereas TNFα represses Survivin expression in the metastatic colon carcinoma cells. Silencing Bcl-xL expression significantly increased the metastatic colon carcinoma cell sensitivity to TRAIL-induced apoptosis. Conversely, overexpression of Bcl-xL significantly decreased the tumor cell sensitivity to TRAIL-induced apoptosis. Furthermore, TNFα and IFN-γ also synergistically enhanced TRAIL-induced caspase-8 activation. TNFα and IFN-γ was up-regulated in activated primary and tumor-specific T cells. TRAIL was expressed in tumor-infiltrating immune cells in vivo, and in tumor-specific cytotoxic T lymphocytes (CTL) ex vivo. Consequently, TRAIL therapy in combination with TNFα/IFN-γ-producing CTL adoptive transfer immunotherapy effectively suppressed colon carcinoma metastasis in vivo. TNFα and IFN-γ cooperate to overcome TRAIL resistance at least partially through enhancing caspase 8 activation and repressing Bcl-xL expression. Combined CTL immunotherapy and TRAIL therapy hold great promise for further development for the treatment of metastatic colorectal cancer.


Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum.
In this study, the impact of preoperative chemotherapy and radiation on the histopathology of a subgroup of patients with rectal adenocarcinoma was examined. As well, survival, disease-free survival and pelvic recurrence rates were examined, and compared with a concurrent control group. The optimal treatment of large rectal carcinomas remains controversial; current therapy usually involves abdominoperineal resection plus postoperative chemoradiation; the combination can be associated with significant postoperative morbidity. In spite of these measures, local recurrences and distant metastases continue as serious problems. Fluorouracil, cisplatin, and 4500 cGy were administered preoperatively over a 5-week period, before definitive surgical resection in 43 patients. In this group of patients, all 43 had biopsy-proven lesions > 3 cm (median diameter), involving the entire rectal wall (as determined by sigmoidoscopy and computed tomography scan), with no evidence of extrapelvic disease. The patients ranged from 31 to 81 years of age (median 61 years), with a male:female ratio of 3:1. A concurrent control group consisting of 56 patients (median: 62 years, male:female ration of 3:2) with T2 and T3 lesions was used to compare survival, disease-free survival, and pelvic recurrence rates. The preoperative chemoradiation therapy was well tolerated, with no major complications. All patients underwent repeat sigmoidoscopy before surgery; none of the lesions progressed while patients underwent therapy, and 22 (51%) were determined to have complete clinical response. At the time of resection, 21 patients (49%) had gross disease, 9 (22%) patients had only residual microscopic disease, and 11 (27%) had sterile specimens. Of the 30 patients with evidence of residual disease, 4 had positive lymph nodes. In follow-up, 39 of the 43 remain alive (median follow-up = 25 months), and only 1 of the 11 patients with complete histologic response developed recurrent disease. Six of the 32 patients with residual disease (2 with positive nodes) have developed metastatic disease in follow-up (median time to diagnosis 10 months, range 3-15 months). Three of these patients with metastases have died (median survival after diagnosis of metastases = 36 months). Local recurrence was seen in only 2 of 43 patients (< 5%). Cox-Mantel analysis of Kaplan-Meier distributions demonstrated increased survival (p = 0.017), increased disease-free survival (p = 0.046), and decreased pelvic recurrence (p = 0.031) for protocol versus control patients. This therapeutic regimen has provided enhanced local control and decreased metastases. Furthermore, the marked degree of tumor downstaging, as seen by a 27% incidence of sterile pathologic specimens and a low rate of positive lymph nodes in this group with initially advanced lesions, strongly suggest that less radical surgery and sphincter preservation may be used with increasing frequency.


Prevalence of irritable bowel syndrome: a community survey.
Irritable bowel syndrome (IBS) is a common health problem affecting a substantial proportion of the population. Many individuals with symptoms of IBS do not seek medical attention or have stopped consulting because of disillusionment with current treatment options. Such patients may choose to re-consult with the advent of new therapies with a resulting impact on health services. To generate reliable estimates of the prevalence of IBS by age, sex and symptom group. Postal survey. Patients selected from registers of eight general practices in north and west Birmingham. Eight thousand six hundred and forty-six patients aged >or=18 years were randomly selected from practice lists. Selected patients received a questionnaire, which included diagnostic criteria for IBS. A second questionnaire, seeking more detailed information, was sent to those whose responses indicated the presence of IBS symptoms. Of the 8386 patients surveyed 4807 (57.3%) useable replies were received. The community-based prevalence of IBS was 10.5% (6.6% of men and 14.0% of women). Overall the symptom profiles were characterised by diarrhoea (25.4%), constipation (24.1%) and alternating symptoms (46.7%). Over half (56%) of all patients had consulted their general practitioner within the past 6 months and 16% had seen a hospital specialist. A quarter of patients consulted more than twice and 16% were referred to secondary care; almost half were on prescribed medication. However, the majority of patients were self-treated. Less than half of those currently reporting symptoms of IBS according to the Rome II criteria had received a diagnosis of IBS. Reduced quality of life and a previous diagnosis of a stomach ulcer were identified as predictors of consultation. Quality of life was significantly reduced in patients with IBS. There is a substantial burden on primary healthcare services despite over half of those with symptoms also self- medicating. The Rome II diagnostic criteria identified those most affected by their symptoms and are a valid clinical tool. Population-based health surveys will need to supplement the Rome criteria with questions aiming to identify patients formally diagnosed but whose symptoms are currently under control if prevalence is to be reliably estimated.


Bis(propyl)-cognitin protects against glutamate-induced neuro-excitotoxicity via concurrent regulation of NO, MAPK/ERK and PI3-K/Akt/GSK3β pathways.
We have previously reported that bis(propyl)-cognitin (B3C), similar to memantine (MEM), is an uncompetitive N-methyl-d-aspartate receptor antagonist with fast off-rate property. In the current study, we further demonstrated that in primary cultures of rat cerebellar granule neurons (CGNs), 2h pretreatment of B3C (IC50, 0.45μM) prevented glutamate-induced excitotoxicity 10 times more potently than memantine (IC50, 4.58 μM), as evidenced by cell viability and lactate dehydrogenase release assays. Additionally, B3C pretreatment could inhibit the increase of intracellular nitric oxide (NO) and the activation of phosphorylated ERK, and reverse the suppression of phosphorylated Akt and GSK3β caused by glutamate. Furthermore, the neuroprotection of B3C was abolished by phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002. Meanwhile, pharmacological inhibition showed that neither the single specific inhibitors of nitric oxide synthase (L-NMMA), MEK1/2 (U0126) and GSK3β (SB415286 and LiCl) nor the combinations of any two of them could fully protect against glutamate-induced apoptosis. However, the co-application of these three inhibitors produced nearly 100% inhibition of glutamate-induced apoptosis. These results taken together suggest that B3C elicits neuroprotection against glutamate-induced neurotoxicity in CGNs via concurrent inhibition of NO, MAPK/ERK pathways and activation of PI3-K/Akt/GSK3β pathway. Combining these and our previous publications, it is conjectured that the dimer might be an ideal candidate drug in delaying the course of neurodegeneration related with Alzheimer's disease.


Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.
Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change.


Using a novel smartphone application for capturing of patient-reported outcome measures among patients with inflammatory arthritis:A randomized, crossover, agreement study.
Objectives: In Denmark, patients with inflammatory arthritis (IA) have completed patient-reported outcome measures (PROMs) via touchscreens in the outpatient clinic since 2006. However, current technology makes it possible for patients to use their own smartphone via an application (app) developed for the Danish Rheumatology Database (DANBIO). This study aims to evaluate the agreement of PROMs between the DANBIO app and outpatient touchscreen in patients with IA.Method: Patients with IA (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis) were enrolled in a randomized, crossover, agreement study. Participants answered PROMs through the two device types in a randomized order. Differences in PROM scores with 95% confidence intervals (CIs) were evaluated for similarity according to prespecified equivalence margins.Results: The touchscreen invitation was accepted by 138 patients. Sixty patients (20 with each diagnosis) were included. The difference in Health Assessment Questionnaire Disability Index between the two device types was -0.007 (95% CI -0.043 to 0.030); thus, equivalence was demonstrated. In addition, all other PROMs obtained with the two device types were equivalent, except for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which was within the limits of minimally clinically important difference (MCID). In total, 78.3% preferred the DANBIO app.Conclusion: In patients with IA, equivalence was demonstrated between two device types for all PROMs except BASDAI; however, BASDAI was within the limits of the MCID. Implementation of the DANBIO app is expected to optimize outpatient visits, thereby improving healthcare for the individual patient and society.


Hyporesponsiveness to PegIFNα2B plus ribavirin in patients with hepatitis C-related advanced fibrosis.
The success of pegylated-interferon (PegIFN)/ribavirin (Rbv) therapy of chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally affects the two PegIFNα-based therapies is unknown. To assess the response to the two PegIFN regimens in patients with different degree of liver fibrosis. A sub-analysis of the MIST study: 431 consecutive naïve patients randomly assigned, based on HCV genotype, to receive either (A) PegIFNα2a 180 μg/wk plus daily Rbv 800-1200 mg or (B) PegIFNα2b 1.5 μg/kg/week plus daily Rbv 800-1200 mg, were stratified according to Ishak staging (S) into mild (S0-S2) or moderate (S3, S4) fibrosis and cirrhosis (S5, S6). In A the sustained virological response (SVR) rates were not significantly influenced by fibrosis stage (71% in S0-S2, 66% in S3, S4, 53% in S5, S6, p=0.12), compared to B where the SVR rates differed according to fibrosis stage (65%, 46%, and 38%, p=0.004, respectively). This was even more so in HCV-1/4 patients treated with PegIFNα2b where the SVR rates were twice as many in S0-S2 vs. S≥3 (44% vs. 22%, p=0.02), while in A the SVR rates were similar between the two fibrosis subgroups (S0-S2: 47% vs. S≥3: 48%, p=0.8). By logistic regression analysis genotype 1/4 and lack of rapid virological response were independent predictors of treatment failure in both treatment groups, while S≥3 fibrosis was associated to PegIFNα2b treatment failure, only (OR 2.83, 95% CI 1.4-5.68, p=0.004). Liver fibrosis was an independent moderator of treatment outcome in patients receiving PegIFNα2b, not in those receiving PegIFNα2a.


Control mechanisms for stochastic biochemical systems via computation of reachable sets.
Controlling the behaviour of cells by rationally guiding molecular processes is an overarching aim of much of synthetic biology. Molecular processes, however, are notoriously noisy and frequently nonlinear. We present an approach to studying the impact of control measures on motifs of molecular interactions that addresses the problems faced in many biological systems: stochasticity, parameter uncertainty and nonlinearity. We show that our reachability analysis formalism can describe the potential behaviour of biological (naturally evolved as well as engineered) systems, and provides a set of bounds on their dynamics at the level of population statistics: for example, we can obtain the possible ranges of means and variances of mRNA and protein expression levels, even in the presence of uncertainty about model parameters.


Patient Perception of Physician Compassion After a More Optimistic vs a Less Optimistic Message: A Randomized Clinical Trial.
Information regarding treatment options and prognosis is essential for patient decision making. Patient perception of physicians as being less compassionate when they deliver bad news might be a contributor to physicians' reluctance in delivering these types of communication. To compare patients' perception of physician compassion after watching video vignettes of 2 physicians conveying a more optimistic vs a less optimistic message, determine patients' physician preference after watching both videos, and establish demographic and clinical predictors of compassion. Randomized clinical trial at an outpatient supportive care center in a cancer center in Houston, Texas, including English-speaking adult patients with advanced cancer who were able to understand the nature of the study and complete the consent process. Actors and patients were blinded to the purpose of the study. Investigators were blinded to the videos observed by the patient. One hundred patients were randomized to observe 2 standardized, roughly 4-minute videos depicting a physician discussing treatment information (more optimistic message vs less optimistic message) with a patient with advanced cancer. Both physicians made an identical number of empathetic statements (5) and displayed identical posture. After viewing each video, patients completed assessments including the Physician Compassion Questionnaire (0 = best, 50 = worst). Patients' perception of physician compassion after being exposed to a more optimistic vs an equally empathetic but less optimistic message. Patients reported significantly better compassion scores after watching the more optimistic video as compared with the less optimistic video (median [interquartile range], 15 [5-23] vs 23 [10-31]; P < .001). There was a sequence effect favoring the second video on both compassion scores (P < .001) and physician preference (P < .001). Higher perception of compassion was found to be associated with greater trust in the medical profession independent of message type: 63 patients observing the more optimistic message ranked the physician as trustworthy vs 39 after the less optimistic message (P = .03). Patients perceived a higher level of compassion and preferred physicians who provided a more optimistic message. More research is needed in structuring less optimistic message content to support health care professionals in delivering less optimistic news. clinicaltrials.gov Identifier: NCT02357108.


Success is all in the measures: androgenousness, curvaceousness, and starring frequencies in adult media actresses.
The debate of whether body-mass index (BMI) or waist-to-hip ratio (WHR) is the primary visual cue to female physical attractiveness (FPA) has generated considerable interest. However, experiments addressing this question typically have limited ecological validity and do not capture the ultimate goal of FPA, which is to elicit male sexual arousal. Hence, using an unobtrusive measures design, we retrieved movie and magazine starring frequencies of 125 adult media actresses from a company's database, operationalized starring frequencies as FPA measures, and tested their relationship to actresses' anthropometric data. Low BMI was related to frequent movie starring, while WHR, waist-to-bust ratio (WBR), and bust size were not. Conversely, low WHR, low WBR, and larger bust size were related to frequent magazine starring, while BMI was not. Visual cues to FPA might be domain-specific, with androgenousness cues salient for attractiveness evaluation of moving bodies and curvaceousness cues salient for posing bodies.


In vivo tumor active cancer targeting and CT-fluorescence dual-modal imaging with nanoprobe based on gold nanorods and InP/ZnS quantum dots.
In this paper, gold nanorods and InP/ZnS quantum dots were encapsulated together in a silica medium, and the targeting molecular peptide c(RGDfC) was further connected after surface modification with PEG and PEG derivatives to prepare a multifunctional Au@QD@SiO2/PEG-c(RGDfC) probe. Dynamic Light Scattering showed that the probe size was about 215.01 ± 2.72 nm, and its dispersibility was good. In in vitro experiments when the concentration was as high as 200 μg mL-1, the activity of the cells was still 85% due to low toxicity. In vivo experiments showed that the probe had excellent tumor targeting, X-ray computed tomography (CT) imaging and fluorescence imaging capabilities. The experiments revealed that the probe had a long blood circulation time (T1/2 = 7.78 h) in mice. Biochemical analysis, liver enzyme analysis and histomorphological analysis after probe injection showed that the probe had no obvious side effects on the normal functions of the main organs, indicating good biosafety. In vivo imaging experiments showed that 6 d after intravenous injection, the tumor sites of a HeLa tumor-bearing nude mice positive group presented obvious fluorescence and CT signals, indicating that the prepared nanoprobe had good tumor targeting dual-mode imaging capabilities and therefore showed great potential in biomedical imaging applications, especially the diagnosis of cancer.


Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.


An increased intraovarian synthesis of nerve growth factor and its low affinity receptor is a principal component of steroid-induced polycystic ovary in the rat.
A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. The present study was carried out to test the hypotheses that this change in sympathetic tone is related to an augmented production of ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the formation of ovarian cysts induced by EV. Injection of the steroid resulted in increased intraovarian synthesis of NGF and its low affinity receptor, p75 NGFR. The increase was maximal 30 days after EV, coinciding with the elevation in sympathetic tone to the ovary and preceding the appearance of follicular cysts. Intraovarian injections of the retrograde tracer fluorogold combined with in situ hybridization to detect tyrosine hydroxylase (TH) messenger RNA-containing neurons in the celiac ganglion revealed that these changes in NGF/p75 NGFR synthesis are accompanied by selective activation of noradrenergic neurons projecting to the ovary. The levels of RBT2 messenger RNA, which encodes a beta-tubulin presumably involved in slow axonal transport, were markedly elevated, indicating that EV-induced formation of ovarian cysts is preceded by functional activation ofceliac ganglion neurons, including those innervating the ovary. Intraovarian administration of a neutralizing antiserum to NGF in conjunction with an antisense oligodeoxynucleotide to p75 NGFR, via Alzet osmotic minipumps, restored estrous cyclicity and ovulatory capacity in a majority of EV-treated rats. These functional changes were accompanied by restoration of the number of antral follicles per ovary that had been depleted by EV and a significant reduction in the number of both precystic follicles and follicular cysts. The results indicate that the hyperactivation of ovarian sympathetic nerves seen in EV-induced PCO is related to an overproduction of NGF and its low affinity receptor in the gland. They also suggest that activation of this neurotrophic-neurogenic regulatory loop is a component of the pathological process by which EV induces cyst formation and anovulation in rodents. The possibility exists that a similar alteration in neurotrophic input to the ovary contributes to the etiology and/or maintenance of the PCO syndrome in humans.


Enhanced TLR3 responsiveness in hepatitis C virus resistant women from the Irish anti-D cohort.
Natural resistance to infection is an overlooked outcome after hepatitis C virus (HCV) exposure. Between 1977 and 1979, 1,200 Rhesus D-negative Irish women were exposed to HCV-contaminated anti-D immunoglobulin. Here, we investigate why some individuals appear to resist infection despite exposure (exposed seronegative [ESN]). We screen HCV-resistant and -susceptible donors for anti-HCV adaptive immune responses using ELISpots and VirScan to profile antibodies against all know human viruses. We perform standardized ex vivo whole blood stimulation (TruCulture) assays with antiviral ligands and assess antiviral responses using NanoString transcriptomics and Luminex proteomics. We describe an enhanced TLR3-type I interferon response in ESNs compared with seropositive women. We also identify increased inflammatory cytokine production in response to polyIC in ESNs compared with seropositive women. These enhanced responses may have contributed to innate immune protection against HCV infection in our cohort.


Zebra migration strategies and anthrax in Etosha National Park, Namibia.
Partial seasonal migration is ubiquitous in many species. We documented this phenomenon in plains zebra (Equus burchelli) in Etosha National Park, Namibia (ENP), and provided a cost-benefit analysis as it relates to the spatial distribution of water, vegetation and endemic anthrax. This analysis draws upon two years of ENP zebra movement data that reveal two sub-populations: migrators and non-migrators. Migrators are shown to be behaviorally dominant in the way they utilize space and use water holes. We raise the possibility that the co-existence of these two groups reflects an evolutionary process, and the size of each group maintains evolutionary equilibrium.


Prostate cancer postoperative nomogram scores and obesity.
Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity. We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs). In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28-0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01-1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11-1.90). Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making.


Mitigating the impact of oil-palm monoculture on freshwater fishes in Southeast Asia.
Anthropogenic land-cover change is driving biodiversity loss worldwide. At the epicenter of this crisis lies Southeast Asia, where biodiversity-rich forests are being converted to oil-palm monocultures. As demand for palm oil increases, there is an urgent need to find strategies that maintain biodiversity in plantations. Previous studies found that retaining forest patches within plantations benefited some terrestrial taxa but not others. However, no study has focused on aquatic taxa such as fishes, despite their importance to human well-being. We assessed the efficacy of forested riparian reserves in conserving freshwater fish biodiversity in oil-palm monoculture by sampling stream fish communities in an oil-palm plantation in Central Kalimantan, Indonesia. Forested riparian reserves maintained preconversion local fish species richness and functional diversity. In contrast, local and total species richness, biomass, and functional diversity declined markedly in streams without riparian reserves. Mechanistically, riparian reserves appeared to increase local species richness by increasing leaf litter cover and maintaining coarse substrate. The loss of fishes specializing in leaf litter and coarse substrate decreased functional diversity and altered community composition in oil-palm plantation streams that lacked riparian reserves. Thus, a land-sharing strategy that incorporates the retention of forested riparian reserves may maintain the ecological integrity of fish communities in oil-palm plantations. We urge policy makers and growers to make retention of riparian reserves in oil-palm plantations standard practice, and we encourage palm-oil purchasers to source only palm oil from plantations that employ this practice.


Recurrent acute rhinosinusitis: presentation and outcomes of sinus surgery.
Patients with recurrent acute rhinosinusitis (RARS) represent a challenging subset of patients with rhinosinusitis. Data regarding the outcomes of care for these patients is extremely limited. The purpose of this study was to evaluate objective and patient-based measures in patients diagnosed with RARS before and after surgical intervention. A prospective, nested case-control study was performed. Cases of RARS (n = 22) were matched to patients with chronic rhinosinusitis (CRS) without polyposis (n = 22) by age, sex, and race/ethnicity. Preoperative computed tomography (CT) and pre- and postoperative endoscopic examinations, the Chronic Sinusitis Survey, and the Rhinosinusitis Disability Index were scored and compared between cases and controls. Patients with RARS were less likely to have asthma or previous sinus surgery. Patients with CRS underwent more extensive surgery. There were no significant differences in preoperative CT, endoscopy, or patient-based, quality-of-life (QOL) scores. Both groups showed statistically significant improvements in total postoperative QOL scores. Patients with CRS showed significant improvement on endoscopy scores. Patients with RARS used significantly fewer sinus medications after endoscopic sinus surgery. Patients with RARS were more often primary surgical patients and underwent less extensive surgery than their CRS counterparts. Both groups reported improved QOL after surgery.


Fabrication and characterization of electrospun poly(e-caprolactone) fibrous membrane with antibacterial functionality.
This research study is mainly targeted on fabrication and characterization of antibacterial poly(e-caprolactone) (PCL) based fibrous membrane containing silver chloride particles. Micro/nano fibres were produced by electrospinning and characterized with TGA, DSC, SEM and mechanical analysis. It was found that addition of silver particles slightly reduced onset of thermal degradation and increased crystallization temperature of neat PCL. Silver-loaded samples exhibited higher tensile stress and lower strain revealing that the particles behaved as reinforcing agent. Moreover, addition of silver chloride resulted in beaded surface texture and formation of finer fibres as opposed to the neat. Antibacterial properties were tested against Gram-negative and Gram-positive bacteria and remarkable biocidal functionalities were obtained with about six logs reduction of Staphylococcus aureus and Escherichia coli O157:H7.


Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations.
Liver stiffness measurement using FibroScan is a novel rapid and non-invasive technique that evaluates liver fibrosis. In some cases, however, no elasticity measurement is obtained. The aim of this prospective study was to assess the prevalence and factors associated with failure (no value obtained after 10 measurements) of liver stiffness measurement in patients with chronic liver disease. Two thousand one hundred and fourteen liver stiffness measurements were analyzed. Failure was observed in 96 cases (4.5%). Failure was not associated with operator, gender, or transaminase level. By multivariate analysis, the only factor associated with failure was body mass index greater than 28 (odds ratio, 10.0 degrees; 95% confidence interval, 5.7-17.9, P=0.001). In conclusion, liver stiffness is a good method for the evaluation of liver fibrosis that is feasible in more than 95% of patients. Other non-invasive methods such as biochemical methods or liver biopsy could therefore be used only in patients with failure of FibroScan examination.


Crystalline ribulose 1,5-bisphosphate carboxylase-oxygenase from spinach.
Spinach fraction I protein (ribulose 1,5-bisphosphate carboxylase-oxy genase, E.C. 188.8.131.52) was crystallized on both an analytical and a preparative scale by vapor diffusion with polyethylene glycol (molecular weight, 6000) used as the precipitant. The identity of the crystalline material with fraction I protein was shown by gel electrophoresis in the presence of sodium dodecyl sulfate and immunological properties. The carboxylase and oxygenase activities copurify during crystallization, and the crystalline enzyme lacks copper and iron.


Intramesenteric dynamic contrast pediatric MR lymphangiography: initial experience and comparison with intranodal and intrahepatic MR lymphangiography.
To report on our initial experience with intramesenteric (IM) dynamic contrast magnetic resonance lymphangiography (DCMRL) for evaluation of the lymphatics in patients with concern for mesenteric lymphatic flow disorders and to compare IM-DCMRL with intrahepatic (IH) and intranodal (IN) DCMRL. This is a retrospective review of imaging findings in 15 consecutive patients who presented with protein losing enteropathy (PLE) and/or ascites undergoing IM-DCMRL, IH-DCMRL, and IN-DCMRL. The IM-DCMRL technique involves the injection of a gadolinium contrast agent into the mesenteric lymphatic ducts or lymph nodes followed by imaging of the abdomen and chest with dynamic time-resolved MR lymphangiography. IM-DCMRL was successfully performed in 14/15 (93%) of the patients. When comparing IN-DCMRL with IM-DCMRL, there was a significant difference in the visualization of dermal backflow (p = 0.014), duodenal perfusion (p = 0.003), duodenal leak (p = 0.014), and peritoneal leak (p = 0.003). IM-DCMRL demonstrated peritoneal leak in 7 patients in contrast to IH-DCMRL which demonstrated leak in 4 patients and IN-DCMRL which did not demonstrate any peritoneal leaks. Duodenal leaks were seen by IH-DCMRL in 9 patients versus 5 with IM-DCMRL and none with IN-DCMRL. In one patient with congenital PLE, the three modalities showed different disconnected flow patterns with duodenal leak only seen by IM-DCMRL. There were no short-term complications from the procedures. IM-DCMRL is a feasible imaging technique for evaluation of the mesenteric lymphatics. In certain mesenteric lymphatic flow abnormalities, such as PLE and ascites, this imaging may be helpful for diagnosis and the planning of interventions and warrants further studies. • Intramesenteric dynamic contrast magnetic resonance lymphangiography (IM-DCMRL) is a new imaging technique to evaluate mesenteric lymphatic flow disorders such as ascites. • IM-DCMRL is able to image lymphatic leaks in patients with ascites and protein losing enteropathy not seen with intranodal (IN-DCMRL) imaging.


Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.
HIV-1 infection is associated with increased risk of tuberculosis and a safe and effective vaccine would assist control measures. We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1. We did a randomised, double-blind, placebo-controlled, phase 2 trial of MVA85A in adults infected with HIV-1, at two clinical sites, in Cape Town, South Africa and Dakar, Senegal. Eligible participants were aged 18-50 years, had no evidence of active tuberculosis, and had baseline CD4 counts greater than 350 cells per μL if they had never received antiretroviral therapy or greater than 300 cells per μL (and with undetectable viral load before randomisation) if they were receiving antiretroviral therapy; participants with latent tuberculosis infection were eligible if they had completed at least 5 months of isoniazid preventive therapy, unless they had completed treatment for tuberculosis disease within 3 years before randomisation. Participants were randomly assigned (1:1) in blocks of four by randomly generated sequence to receive two intradermal injections of either MVA85A or placebo. Randomisation was stratified by antiretroviral therapy status and study site. Participants, nurses, investigators, and laboratory staff were masked to group allocation. The second (booster) injection of MVA85A or placebo was given 6-12 months after the first vaccination. The primary study outcome was safety in all vaccinated participants (the safety analysis population). Safety was assessed throughout the trial as defined in the protocol. Secondary outcomes were immunogenicity and vaccine efficacy against Mycobacterium tuberculosis infection and disease, assessed in the per-protocol population. Immunogenicity was assessed in a subset of participants at day 7 and day 28 after the first and second vaccination, and M tuberculosis infection and disease were assessed at the end of the study. The trial is registered with ClinicalTrials.gov, number NCT01151189. Between Aug 4, 2011, and April 24, 2013, 650 participants were enrolled and randomly assigned; 649 were included in the safety analysis (324 in the MVA85A group and 325 in the placebo group) and 645 in the per-protocol analysis (320 and 325). 513 (71%) participants had CD4 counts greater than 300 cells per μL and were receiving antiretroviral therapy; 136 (21%) had CD4 counts above 350 cells per μL and had never received antiretroviral therapy. 277 (43%) had received isoniazid prophylaxis before enrolment. Solicited adverse events were more frequent in participants who received MVA85A (288 [89%]) than in those given placebo (235 [72%]). 34 serious adverse events were reported, 17 (5%) in each group. MVA85A induced a significant increase in antigen 85A-specific T-cell response, which peaked 7 days after both vaccinations and was primarily monofunctional. The number of participants with negative QuantiFERON-TB Gold In-Tube findings at baseline who converted to positive by the end of the study was 38 (20%) of 186 in the MVA85A group and 40 (23%) of 173 in the placebo group, for a vaccine efficacy of 11·7% (95% CI -41·3 to 44·9). In the per-protocol population, six (2%) cases of tuberculosis disease occurred in the MVA85A group and nine (3%) occurred in the placebo group, for a vaccine efficacy of 32·8% (95% CI -111·5 to 80·3). MVA85A was well tolerated and immunogenic in adults infected with HIV-1. However, we detected no efficacy against M tuberculosis infection or disease, although the study was underpowered to detect an effect against disease. Potential reasons for the absence of detectable efficacy in this trial include insufficient induction of a vaccine-induced immune response or the wrong type of vaccine-induced immune response, or both. European & Developing Countries Clinical Trials Partnership (IP.2007.32080.002), Aeras, Bill & Melinda Gates Foundation, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium.


Shape and Phase Transitions in a PEGylated Phospholipid System.
Poly(ethylene glycol) (PEG) polymers and PEG-conjugated lipids are widely used in bioengineering and drug transport applications. A PEG layer in a drug carrier increases hydrophilic repulsion, inhibits membrane fusion and serum opsonin interactions, and prolongs the storage and circulation time. It can also change the carrier shape and have an influence on many properties related to the content release of the carrier. In this paper, we focus on the physicochemical effects of PEGylation in the lipid bilayer. We introduce laurdanC as a fluorophore for shape recognition and phase transition detection. Together with laurdanC, cryogenic transmission electron microscopy, differential scanning calorimetry, molecular dynamics simulations, and small-angle X-ray scattering/wide-angle X-ray scattering, we acquire information of the particle/bilayer morphology and phase behavior in systems containing 1,2-dipalmitoyl- sn-glycero-3-phosphocholine:1,2-distearoyl- sn-glycero-3-phosphoethanolamine-PEG(2000) with different fractions. We find that PEGylation leads to two important and potentially usable features of the system. (1) Spherical vesicles present a window of elevated chain-melting temperatures and (2) lipid packing shape-controlled liposome-to-bicelle transition. The first finding is significant for targets requiring multiple release sequences and the second enables tuning the release by composition and the PEG polymer length. Besides drug delivery systems, the findings can be used in other smart soft materials with trigger-polymers as well.


The Inverted Multi-Index.
A new data structure for efficient similarity search in very large datasets of high-dimensional vectors is introduced. This structure called the inverted multi-index generalizes the inverted index idea by replacing the standard quantization within inverted indices with product quantization. For very similar retrieval complexity and pre-processing time, inverted multi-indices achieve a much denser subdivision of the search space compared to inverted indices, while retaining their memory efficiency. Our experiments with large datasets of SIFT and GIST vectors demonstrate that because of the denser subdivision, inverted multi-indices are able to return much shorter candidate lists with higher recall. Augmented with a suitable reranking procedure, multi-indices were able to significantly improve the speed of approximate nearest neighbor search on the dataset of 1 billion SIFT vectors compared to the best previously published systems, while achieving better recall and incurring only few percent of memory overhead.


Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons.
The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of Lmx1a and Lmx1b recreates cellular features observed in Parkinson's disease. We found that Lmx1a/b control the expression of key genes involved in mitochondrial functions, and their ablation results in impaired respiratory chain activity, increased oxidative stress, and mitochondrial DNA damage. Lmx1a/b deficiency caused axonal pathology characterized by α-synuclein(+) inclusions, followed by a progressive loss of dopaminergic neurons. These results reveal the key role of these transcription factors beyond the early developmental stages and provide mechanistic links between mitochondrial dysfunctions, α-synuclein aggregation, and the survival of dopaminergic neurons.


Controlling the structure of proteins at surfaces.
With the help of single molecule force spectroscopy and molecular dynamics simulations, we determine the surface-induced structure of a single engineered spider silk protein. An amyloid like structure is induced in the vicinity of a surface with high surface energy and can be prohibited in the presence of a hydrophobic surface. The derived molecular energy landscapes highlight the role of single silk protein structure for the macroscopic toughness of spider silk.


Efficient use of cement and concrete to reduce reliance on supply-side technologies for net-zero emissions.
Decarbonization strategies for the cement and concrete sector have relied heavily on supply-side technologies, including carbon capture and storage (CCS), masking opportunities for demand-side intervention. Here we show that cross-cutting strategies involving both the supply and demand sides can achieve net-zero emissions by 2050 across the entire Japanese cement and concrete cycle without resorting to mass deployment of CCS. Our analysis shows that a series of mitigation efforts on the supply side can reduce 2050 CO2 emissions by up to 80% from baseline levels and that the remaining 20% mitigation gap can be fully bridged by the efficient use of cement and concrete in the built environment. However, this decarbonization pathway is dependent on how CO2 uptake by carbonation and carbon capture and utilization is accounted for in the inventory. Our analysis underscores the importance of including demand-side interventions at the heart of decarbonization strategies and highlights the urgent need to discuss how to account for CO2 uptake in national inventories under the Paris Agreement.


Regional and global concerns over wetlands and water quality.
Water quality in many stream catchments and river basins is severely impacted by nutrient enrichment as a result of agriculture. Water-resource managers worldwide are considering the potential role of riparian zones and floodplain wetlands in improving stream-water quality, as there is evidence at the site scale that such wetlands are efficient at removing nutrients from through-flowing water. However, recent studies have highlighted disadvantages of such use of wetlands, including emissions of greenhouse gases and losses of biodiversity that result from prolonged nutrient loading. Here, we discuss the water purification function of wetlands at the site and catchment scale and suggest ways in which these disadvantages could be overcome.


Studying bacterial chemosensory array with CryoEM.
Bacteria direct their movement in respond to gradients of nutrients and other stimuli in the environment through the chemosensory system. The behavior is mediated by chemosensory arrays that are made up of thousands of proteins to form an organized array near the cell pole. In this review, we briefly introduce the architecture and function of the chemosensory array and its core signaling unit. We describe the in vivo and in vitro systems that have been used for structural studies of chemosensory array by cryoEM, including reconstituted lipid nanodiscs, 2D lipid monolayer arrays, lysed bacterial ghosts, bacterial minicells and native bacteria cells. Lastly, we review recent advances in structural analysis of chemosensory arrays using state-of-the-art cryoEM and cryoET methodologies, focusing on the latest developments and insights with a perspective on current challenges and future directions.


Phytochemical investigation and hair growth studies on the rhizomes of Nardostachys jatamansi DC.
Nardostachys jatamansi DC rhizomes were subjected to extraction, fractionation, and isolation of terpenoid compounds. Three terpenoid compounds were isolated which are nardal, jatamansic acid, and nardin. These compounds were identified based on physical and spectral data (UV, IR,(1)H and(13)C NMR, 2D NMR, Mass) and comparison with authentic compounds. The crude extract, fractions, and two of the isolated compounds were tested for their hair growth activity. The hair growth studies showed good activities for the extract, fraction, and the isolated compounds.


Species delimitation of neotropical Characins (Stevardiinae): Implications for taxonomy of complex groups.
Accurate species delimitation is crucial for studies of phylogeny, phylogeography, ecology, conservation and biogeography. The limits of species and genera in the Characidae family are controversial due to its uncertain phylogenetic relationships, high level of morphological homoplasy and the use of ambiguous morphological characters for descriptions. Here we establish species boundaries for Bryconamericus, Hemibrycon, Knodus and Eretmobrycon (Stevardiinae: Characidae), previously diagnosed with morphology, using three different barcoding approaches (GMYC, PTP, ABGD). Results revealed that species delimitation was successful by the use of a single-gene approach and by following a workflow in the context of integrative taxonomy, making evident problems and mistakes in the cataloging of Characidae species. Hence, it was possible to infer boundaries at genus level for clusters in the trees (GMYC and PTP) and automatic partitions (ABGD) which were consistent with some of recent taxonomic changes proposed in Characidae. We found that discordance cases between methods were linked to limitations of the methods and associated to putative species cluster closely related, some historically problematic in their diagnosis and identification. Furthermore, we suggested taxonomic changes and possibly new species, revealing a high degree of hidden diversity. Finally, we propose a workflow as a fast, accurate and objective way to delimit species from mitochondrial DNA sequences and to help clarify the classification of this group.


Prospective study of gestational diabetes and fatty liver scores 9 to 16 years after pregnancy.
Women with gestational diabetes mellitus (GDM) may be at an increased risk of liver complications because chronic hyperglycemia is a risk factor for liver fat accumulation and potential liver dysfunction. Large prospective studies examining liver fat accumulation following a GDM pregnancy are lacking. The Diabetes & Women's Health Study (2012-2014) examined the association between GDM and subsequent fatty liver scores among 607 women with and 619 women without GDM in the Danish National Birth Cohort. Nine to 16 years postpartum, a clinical examination was performed, with measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase, from which fatty liver scoring indices were calculated to assess liver fat score, fatty liver index, hepatic steatosis index, and liver fat percentage. Relative risks (RR) with 95% confidence intervals (CI) for elevated liver scoring indices by GDM status were assessed adjusting for major risk factors, including prepregnancy body mass index. Women with prior GDM had higher adjusted ALT and AST levels than women without GDM (by 6.7% [95% CI 1.7-12.0] and 4.8% [95% CI 0.6-9.1], respectively). Women with GDM also had adjusted increased risks for elevated liver fat score (RR 2.34; 95% CI 1.68-3.27), fatty liver index (RR 1.59; 95% CI 1.27-1.99), and hepatic steatosis index (RR 1.44; 95% CI 1.21-1.71). Women with GDM during pregnancy were at an increased risk for fatty liver 9 to 16 years postpartum. Gestational diabetes mellitus may serve as another risk indicator for the early identification and prevention of liver fat accumulation.


Biogenic amorphous silica as main driver for plant available water in soils.
More frequent and longer drought periods are predicted threatening agricultural yield. The capacity of soils to hold water is a highly important factor controlling drought stress intensity for plants. Biogenic amorphous silica (bASi) pools in soils are in the range of 0-6% and are suggested to help plants to resist drought. In agricultural soils, bASi pools declined to values of ~1% or lower) due to yearly crop harvest, decreasing water holding capacity of the soils. Here, we assessed the contribution of bASi to water holding capacity (WHC) of soil. Consequently, ASi was mixed at different rates (0, 1, 5 or 15%) with different soils. Afterwards, the retention curve of the soils was determined via Hyprop method. Here we show that bASi increases the soil water holding capacity substantially, by forming silica gels with a water content at saturation higher than 700%. An increase of bASi by 1% or 5% (weight) increased the water content at any water potential and plant available water increased by up to > 40% or > 60%, respectively. Our results suggest that soil management should be modified to increase bASi content, enhancing available water in soils and potentially decreasing drought stress for plants in terrestrial ecosystems.


A quality-of-life method for estimating the value of avoided morbidity.
We developed a quality-of-life method for valuing changes in health status. Our model determines changes in health attributes for different illnesses and then estimates the dollar value of the corresponding welfare losses. We used our quality-of-life approach to estimate willingness to pay to avoid asthma, a headache, a cough, bronchitis, and arthritis. Estimates derived using our method are similar to those obtained from more expensive and restrictive traditional methods.


Influence of Isolation Method on Recovery of Pythium Species from Forest Nursery Soils in Oregon and Washington.
Pythium species are common damping-off pathogens that can cause stunting, chlorosis, and death of conifer seedlings in the Pacific Northwest (PNW) region of the United States. Despite the prevalence and importance of these pathogens in forest nurseries, relatively little is known about the identity of Pythium species associated with forest nursery soils in Washington and Oregon. A limited number of studies have reported P. aphanidermatum, P. irregulare, P. mamillatum, and P. ultimum as the predominant species in the PNW, but most studies of this genus in forest nurseries have not reported Pythium species identity. In an attempt to identify Pythium species associated with forest nursery soils, field surveys were conducted at three forest nurseries (two in Oregon and one in Washington) in 2008 using three isolation methods. Pythium species were isolated by plating soil onto a semiselective medium or by baiting soil with rhododendron leaf disks and Douglas-fir needle segments. One hundred isolates were randomly selected from each isolation method at each nursery (900 isolates total) and identified on the basis of the internal transcribed spacer (ITS) sequence. Nineteen Pythium species were identified during the survey. Species richness and abundance were strongly influenced by both nursery and isolation method. Of the 300 isolates obtained from each nursery, P. irregulare was the most commonly isolated species from nursery A in Washington (65% incidence). P. 'vipa' and P. dissotocum were the most commonly isolated species from nurseries B and C in Oregon, respectively (53 and 47% incidence, respectively).