Biogeography and ecology of Ostracoda in the U.S. northern Bering, Chukchi, and Beaufort Seas.
Ostracoda (bivalved Crustacea) comprise a significant part of the benthic meiofauna in the Pacific-Arctic region, including more than 50 species, many with identifiable ecological tolerances. These species hold potential as useful indicators of past and future ecosystem changes. In this study, we examined benthic ostracodes from nearly 300 surface sediment samples, >34,000 specimens, from three regions-the northern Bering, Chukchi and Beaufort Seas-to establish species' ecology and distribution. Samples were collected during various sampling programs from 1970 through 2018 on the continental shelves at 20 to ~100m water depth. Ordination analyses using species' relative frequencies identified six species, Normanicythere leioderma, Sarsicytheridea bradii, Paracyprideis pseudopunctillata, Semicytherura complanata, Schizocythere ikeyai, and Munseyella mananensis, as having diagnostic habitat ranges in bottom water temperatures, salinities, sediment substrates and/or food sources. Species relative abundances and distributions can be used to infer past bottom environmental conditions in sediment archives for paleo-reconstructions and to characterize potential changes in Pacific-Arctic ecosystems in future sampling studies. Statistical analyses further showed ostracode assemblages grouped by the summer water masses influencing the area. Offshore-to-nearshore transects of samples across different water masses showed that complex water mass characteristics, such as bottom temperature, productivity, as well as sediment texture, influenced the relative frequencies of ostracode species over small spatial scales. On the larger biogeographic scale, synoptic ordination analyses showed dominant species-N. leioderma (Bering Sea), P. pseudopunctillata (offshore Chukchi and Beaufort Seas), and S. bradii (all regions)-remained fairly constant over recent decades. However, during 2013-2018, northern Pacific species M. mananensis and S. ikeyai increased in abundance by small but significant proportions in the Chukchi Sea region compared to earlier years. It is yet unclear if these assemblage changes signify a meiofaunal response to changing water mass properties and if this trend will continue in the future. Our new ecological data on ostracode species and biogeography suggest these hypotheses can be tested with future benthic monitoring efforts.


Delivery strategies to enhance oral vaccination against enteric infections.
While the majority of human pathogens infect the body through mucosal sites, most licensed vaccines are injectable. In fact the only mucosal vaccine that has been widely used globally for infant and childhood vaccination programs is the oral polio vaccine (OPV) developed by Albert Sabin in the 1950s. While oral vaccines against Cholera, rotavirus and Salmonella typhi have also been licensed, the development of additional non-living oral vaccines against these and other enteric pathogens has been slow and challenging. Mucosal vaccines can elicit protective immunity at the gut mucosa, in part via antigen-specific secretory immunoglobulin A (SIgA). However, despite their advantages over the injectable route, oral vaccines face many hurdles. A key challenge lies in design of delivery strategies that can protect antigens from degradation in the stomach and intestine, incorporate appropriate immune-stimulatory adjuvants and control release at the appropriate gastrointestinal site. A number of systems including micro and nanoparticles, lipid-based strategies and enteric capsules have significant potential either alone or in advanced combined formulations to enhance intestinal immune responses. In this review we will outline the opportunities, challenges and potential delivery solutions to facilitate the development of improved oral vaccines for infectious enteric diseases.


Sternum-Sparing HVAD Implantation with Attachment of the Outflow Graft to the Descending Aorta.
The standard approach for implanting an HVAD left ventricular assist device (LVAD) is performing a median sternotomy and sewing the outflow graft to the ascending aorta. However, in patients with sternal comorbidities, it may be advantageous to use a sternum-sparing approach. We retrospectively studied eight patients who underwent HVAD implantation for destination therapy via a left subcostal or fifth/sixth intercostal space incision. With this procedure, the outflow graft was sewed to the descending aorta. Ninety-day and one-year survival rates were 87.5% and 75%, respectively. Two patients (25%) died during the perioperative period: one from multisystem organ failure and the other from unrelated causes. We adjusted the HVAD speed to open the aortic valve once every three to four beats. Compared with other continuous-flow LVAD implantations performed at our institution during the study period (n = 437), this technique resulted in shorter bypass times and a lower incidence of infection; it was not associated with an increased incidence of heart failure, aortic root thrombosis, pump thrombosis, progression of aortic insufficiency, or ischemic neurologic dysfunction. Our findings suggest that a sternum-sparing approach for HVAD implantation is feasible and may be a safe option in patients with serious comorbidities that preclude the use of traditional implantation techniques.


Titin is a target of matrix metalloproteinase-2: implications in myocardial ischemia/reperfusion injury.
Titin is the largest mammalian (≈3000 to 4000 kDa) and myofilament protein that acts as a molecular spring in the cardiac sarcomere and determines systolic and diastolic function. Loss of titin in ischemic hearts has been reported, but the mechanism of titin degradation is not well understood. Matrix metalloproteinase-2 (MMP-2) is localized to the cardiac sarcomere and, on activation in ischemia/reperfusion injury, proteolyzes specific myofilament proteins. Here we determine whether titin is an intracellular substrate for MMP-2 and if its degradation during ischemia/reperfusion contributes to cardiac contractile dysfunction. Immunohistochemistry and confocal microscopy in rat and human hearts showed discrete colocalization between MMP-2 and titin in the Z-disk region of titin and that MMP-2 is localized mainly to titin near the Z disk of the cardiac sarcomere. Both purified titin and titin in skinned cardiomyocytes were proteolyzed when incubated with MMP-2 in a concentration-dependent manner, and this was prevented by MMP inhibitors. Isolated rat hearts subjected to ischemia/reperfusion injury showed cleavage of titin in ventricular extracts by gel electrophoresis, which was confirmed by reduced titin immunostaining in tissue sections. Inhibition of MMP activity with ONO-4817 prevented ischemia/reperfusion-induced titin degradation and improved the recovery of myocardial contractile function. Titin degradation was also reduced in hearts from MMP-2 knockout mice subjected to ischemia/reperfusion in vivo compared with wild-type controls. MMP-2 localizes to titin at the Z-disk region of the cardiac sarcomere and contributes to titin degradation in myocardial ischemia/reperfusion injury.


Contextual sensory integration training via head mounted display for individuals with vestibular disorders: a feasibility study.
Virtual reality (VR) interventions can simulate real-world sensory environments. The purpose of this study was to test the feasibility of a novel VR application (app) developed for a Head Mounted Display (HMD) to target dizziness, imbalance and sensory integration in a functional context for patients with vestibular disorders. Here we describe the design of the app as well as self-reported and functional outcomes in vestibular patients before and after participating in vestibular rehabilitation using the app. Our app includes a virtual street, airport, subway or a park. The clinician controls the visual and auditory load including several levels of direction, amount and speed of virtual pedestrians. Clinicians enrolled 28 patients with central (mild-traumatic brain injury [mTBI] or vestibular migraine) and peripheral vestibular disorders. We recorded the Simulator Sickness Questionnaire, Visual Vertigo Analogue Scale (VVAS), Dizziness Handicap Inventory (DHI), Activities-Specific Balance Confidence Scale (ABC), 8-foot up and go (8FUG) and Four-Step Square Test (FSST) before and after the intervention. Within the 15 patients who completed the study, 12 with peripheral hypofunction showed significant improvements on the VVAS (p = 0.02), DHI (p = 0.008) and ABC (p = 0.02) and a small significant improvement on the FSST (p = 0.015). Within-session changes in symptoms were minimal. Two patients with mTBI showed important improvements, but one patient with vestibular migraine, did not. HMD training within increasingly complex immersive environments appears to be a promising adjunct modality for vestibular rehabilitation. Future controlled studies are needed to establish effectiveness.IMPLICATIONS FOR REHABILITATIONVirtual Reality allows for gradual introduction of complex semi-real visual environments.Within VR training patients can re-learn to maintain balance when presented with a sensory conflict in a safe environment.Head Mounted Display training appears to be a promising adjunct modality for vestibular rehabilitation.Portability and affordability of the hardware and software enhance the potential clinical outreach.


The discriminative capacity of CBCL/1½-5-DSM5 scales to identify disruptive and internalizing disorders in preschool children.
This paper studies the discriminative capacity of CBCL/1½-5 (Manual for the ASEBA Preschool-Age Forms & Profiles, University of Vermont, Research Center for Children, Youth, & Families, Burlington, 2000) DSM5 scales attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), anxiety and depressive problems for detecting the presence of DSM5 (DSM5 diagnostic and statistical manual of mental disorders, APA, Arlington, 2013) disorders, ADHD, ODD, Anxiety and Mood disorders, assessed through diagnostic interview, in children aged 3-5. Additionally, we compare the clinical utility of the CBCL/1½-5-DSM5 scales with respect to analogous CBCL/1½-5 syndrome scales. A large community sample of 616 preschool children was longitudinally assessed for the stated age group. Statistical analysis was based on ROC procedures and binary logistic regressions. ADHD and ODD CBCL/1½-5-DSM5 scales achieved good discriminative ability to identify ADHD and ODD interview's diagnoses, at any age. CBCL/1½-5-DSM5 Anxiety scale discriminative capacity was fair for unspecific anxiety disorders in all age groups. CBCL/1½-5-DSM5 depressive problems' scale showed the poorest discriminative capacity for mood disorders (including depressive episode with insufficient symptoms), oscillating into the poor-to-fair range. As a whole, DSM5-oriented scales generally did not provide evidence better for discriminative capacity than syndrome scales in identifying DSM5 diagnoses. CBCL/1½-5-DSM5 scales discriminate externalizing disorders better than internalizing disorders for ages 3-5. Scores on the ADHD and ODD CBCL/1½-5-DSM5 scales can be used to screen for DSM5 ADHD and ODD disorders in general populations of preschool children.


Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).
The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.


Prognostic utility of changes in N-terminal pro-brain natriuretic Peptide combined with sequential organ failure assessment scores in patients with acute lung injury/acute respiratory distress syndrome concomitant with septic shock.
We investigated the prognostic utility of changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with Sequential Organ Failure Assessment (SOFA) score in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) concomitant with septic shock. Forty-nine mechanically ventilated patients with ALI/ARDS concomitant with septic shock were studied. N-terminal pro-brain natriuretic peptide levels were measured on the first 3 days (days 0, 1, and 2) in the intensive care unit. The median NT-proBNP levels in survivors and nonsurvivors were 3,999 vs. 2,819 pg/mL on day 0 (P = 0.719); 4,495 vs. 5,397 pg/mL on day 1 (P = 0.543); and 2,325 vs. 14,173 pg/mL on day 2 (P = 0.028). N-terminal pro-brain natriuretic peptide levels increased significantly from baseline values in nonsurvivors only. We observed a monotonic increase in 28-day mortality associated with increasing quartiles of percent change in NT-proBNP on day 2 (P < 0.0001). Kaplan-Meier survival analysis revealed that mortality was significantly higher in patients with a change in NT-proBNP of 30% or more (log-rank P < 0.0001). On day 2, areas under the receiver operating characteristic curves for predicting 28-day mortality were 0.74 for SOFA alone and 0.85 (P = 0.028) for SOFA combined with percent change in NT-proBNP. In conclusion, in patients with ALI/ARDS concomitant with septic shock, a rising trend (high percent change) in NT-proBNP levels had better prognostic utility than absolute levels. The combination of percent change in NT-proBNP with SOFA may provide superior prognostic accuracy to SOFA alone.


Behavior of obliquely incident vector Bessel beams at planar interfaces.
We investigate the behavior of full-vector electromagnetic Bessel beams obliquely incident at an interface between two electrically different media. We employ a Fourier transform domain representation of Bessel beams to determine their behavior upon reflection and transmission. This transform, which is geometric in nature, consists of elliptical support curves with complex weighting associated with them. The behavior of the scattered field at an interface is highly complex, owing to its full-vector nature; nevertheless, this behavior has a straightforward representation in the transform domain geometry. The analysis shows that the reflected field forms a different vector Bessel beam, but in general, the transmitted field cannot be represented as a Bessel beam. Nevertheless, using this approach, we demonstrate a method to propagate a Bessel beam in the refractive medium by launching a non-Bessel beam at the interface. Several interesting phenomena related to the behavior of Bessel beams are illustrated, such as polarized reflection at Brewster's angle incidence, and the Goos-Hänchen and Imbert-Federov shifts in the case of total reflection.


[Having been exposed to violence increases the risk of health problems later in life].
Violence is a common problem in society worldwide, and recent research has shown links to various signs of ill-health among victims. In a Swedish population based study, 46 per cent of women and 38 per cent of men had, at some point, been subjected to severe sexual, physical or emotional violence. The respondents were also asked about their present health. The study showed a significant over-representation of respondents subjected to serious violence in all ill-health indicators (PTSD, depression, psychosomatic symptoms, self-harm behaviour, risky alcohol intake, low self-rated physical health and heart attacks in the older age group). Several other Swedish studies have addressed abuse and future health. In a study among young people attending youth clinics the last year prevalence of sexual, physical and emotional violence was high, as expected. Young women were to a higher extent than young men exposed to sexual (14 and 4 per cent, respectively) and emotional violence (33 and 18 per cent respectively) and young men more to physical violence than young women (27 and 18 per cent respectively). Those who had been exposed to more than two types of violence were significantly more likely to resort to self-harm behaviour and suicide ideation and rated their psychological wellbeing lower than others. In one study the violence victimization and self-reported physical and mental ill-health among young women belonging to a sexual minority and heterosexual young women was assessed. Being subjected to two or more types of violence was significantly more frequent among the minority women compared to heterosexual women. However all victimized women had significantly higher risk for ill-health in all outcomes (PTSD, sleeping difficulties, and recurrent bowel problems). The impact of being subjected to more than one type of violence has been shown to be even more strongly linked to mental ill-health also in adult patients. Hence, research supports that violence victimisation is associated with various symptoms and conditions for which people seek medical care. Therefore questions about violence victimization should routinely be included in the medical history.


SCReening Evaluation of the Evolution of New Heart Failure Study (SCREEN-HF): early detection of chronic heart failure in the workplace.
Objective The aim of the present study was to determine whether asymptomatic heart failure (HF) in the workplace is subject to the health worker effect, making screening using conventional risk factors combined with a cardiac biomarker, namely N-terminal pro B-type natriuretic peptide (NT-proBNP), as useful as in the general population. Methods Between June 2007 and December 2009 a 'well' population deemed at high risk for development of HF was identified through health insurance records. Blood was collected from volunteer participants for analysis of urea, electrolytes and creatinine, a full blood count and NT-proBNP. An echocardiogram was performed on selected participants based on high NT-proBNP concentrations. Results The mean left ventricular ejection fraction (LVEF) was significantly reduced in participants with the highest compared with the lowest NT-proBNP quintile. In multivariate analysis, log-transformed NT-proBNP was independently associated with impaired LVEF and with moderate to severe diastolic dysfunction after adjustment for age, sex, coronary artery disease, diabetes, hypertension and obesity. Conclusions A large burden of asymptomatic left ventricular dysfunction (AVLD) was observed in subjects aged 60 and over with plasma NT-proBNP in the top quintile that was independent of conventional risk factors and work status. HWE does not appear to operate in AVLD. NT-proBNP testing in a population with HF risk factors may cost-effectively identify those at greatest risk of developing HF in a working population and facilitate early diagnosis, treatment and maintenance of work capacity. What is known about the topic? Chronic heart failure (CHF) has several causes, the most common being hypertension and coronary ischaemia. CHF is a major health problem of increasing prevalence that severely impacts quality of life, shortens lives and reduces worker productivity. It is often not diagnosed early enough to take full advantage of ameliorating medication. What does this paper add? Population screening for CHF is not currently advocated. This may be because conventional risk factors must be used in combination and there is no useful biomarker available. Yet evidence (SOLVD (Studies of Left Ventricular Dysfunction trials) recommends early diagnosis. We believe the work place is an area of potential screening where there is little supporting evidence. This paper provides evidence that the biomarker NT-proBNP is a useful new tool that improves cost-effectiveness of screening in a selected population. Specifically, the paper recommends CHF screening in the population with the highest potential health gain (i.e. the working population) by the sector with the highest economic gain (i.e. employers). What are the implications for practitioners? The paper presents important health screening recommendations for medical and health and safety practitioners within a selected population of workers. We feel practitioners should consider screening for incipient heart failure, particularly within Australia's working population, to save lives, provide economic benefit and extend working longevity.


Peptide desorption kinetics from single molecule force spectroscopy studies.
We use a combined experimental/theoretical approach to determine the intrinsic monomeric desorption rate k0 of polytyrosine and polylysine homopeptides from flat surfaces. To this end, single polypeptide molecules are covalently attached to an AFM cantilever tip and desorbed from hydrophobic self-assembled monolayers in two complementary experimental protocols. In the constant-pulling-velocity protocol, the cantilever is moved at finite velocity away from the surface and the distance at which the constant plateau force regime ends and the polymer detaches is recorded. In the waiting-time protocol, the cantilever is held at a fixed distance above the surface and the time until the polymer detaches is recorded. The desorption plateau force is varied between 10 and 90 pN, by systematically changing the aqueous solvent quality via the addition of ethanol or salt. A simultaneous fit of the experimental data from both protocols with simple two-state kinetic polymer theory allows to unambiguously disentangle and determine the model parameters corresponding to polymer contour length L, Kuhn length a, adsorption free energy λ, and intrinsic monomeric desorption rate k0. Crucial to our analysis is that a statistically significant number of single-polymer desorption experiments are done with one and the same single polymer molecule for different solvent qualities. The surprisingly low value of about k0 ≈ 10(5) Hz points to significant cooperativity in the desorption process of single polymers.


openPrimeR for multiplex amplification of highly diverse templates.
To study the diversity of immune receptors and pathogens, multiplex PCR has become a central approach in research and diagnostics. However, insufficient primer design against highly diverse templates often prevents amplification and therefore limits the correct understanding of biological processes. Here, we present openPrimeR, an R-based tool for evaluating and designing multiplex PCR primers. openPrimeR provides a functional and intuitive interface and uses either a greedy algorithm or an integer linear program to compute the minimal set of primers that performs full target coverage. As proof of concept, we used openPrimeR to find optimal primer sets for the amplification of highly mutated immunoglobulins. Comprehensive analyses on specifically generated immunoglobulin variable gene segment libraries resulted in the composition of highly effective primer sets (oPR-IGHV, oPR-IGKV and oPR-IGLV) that demonstrated to be particularly suitable for the isolation of novel human antibodies.


Patient-based assessments of clinical periodontal conditions in relation to alveolar bone loss.
Limited subject-based information exists on the relationship between clinical and radiographic periodontal data. To use subject-based data to assess the extent of concurrence between clinical and radiographic information, and to study what clinical information best predicts alveolar bone loss (ABL). Subject-based data on smoking habits, bleeding on probing, plaque scores, pocket probing depth (PD), and evidence of alveolar BL were obtained, and functional periodontal pentagon risk diagrams (PPRDs) were studied from 168 consecutive subjects attending a medical clinic. The mean age of the subjects was 62.7 years (SD+/-9.0). The average number of teeth was 21.3 (SD+/-8.0) with on average 5.6 molars remaining (SD+/- 3.9). In this subject cohort, 33.1% had never smoked, 44.2% had quit smoking, and 22.7% were currently smokers. Mean plaque and bleeding scores were high or 60.2% (SD+/-24.0) and 53.1% (SD+/-23.6), respectively. PDs >or=6.0 mm were found in 55.9% of the subjects. Binary logistic regression analysis demonstrated that tooth loss and proportional plaque scores were the predominant factors included in the equations associated with ABL. Wald coefficients varied between 3.99 and 9.15, and with p-values between 0.05 and 0.01. When included, the PPRD score became the exclusive factor at several cut-off levels (Wald's coefficients between 19.8 and 15.6, p<0.001). Consequently, the best receiver operator curve was identified for the PPRD at the >40% cut-off ABL level (area under the curve: 0.81; 95% CI: 0.74-0.89; p<0.001). The number of teeth lost and the proportion of plaque scores provided significant predictive factors for ABL. The functional PPRD demonstrated an exclusive and highly predictable association with ABL. Subject-based proportional data for PDs >4.0 mm provided poor substitute measures for the extent of ABL.


Graphene oxide nanoflakes incorporated gelatin-hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells.
In this study, graphene oxide (GO) nanoflakes (0.5 and 1 wt%) were incorporated into a gelatin-hydroxyapatite (GHA) matrix through a freeze drying technique and its effect to enhance mechanical strength and osteogenic differentiation was studied. The GHA matrix with GO demonstrated less brittleness in comparison to GHA scaffolds. There was no significant difference in mechanical strength between GOGHA0.5 and GOGHA1.0 scaffolds. When the scaffolds were immersed in phosphate buffered saline (to mimic physiologic condition) for 60 days, around 50-60% of GO was released in sustained and linear manner and the concentration was within the toxicity limit as reported earlier. Further, GOGHA0.5 scaffolds were continued for cell culture experiments, wherein the scaffold induced osteogenic differentiation of human adipose derived mesenchymal stem cells without providing supplements like dexamethasone, L-ascorbic acid and β glycerophosphate in the medium. The level of osteogenic differentiation of stem cells was comparable to those cultured on GHA scaffolds with osteogenic supplements. Thus biocompatible, biodegradable and porous GO reinforced gelatin-HA 3D scaffolds may serve as a suitable candidate in promoting bone regeneration in orthopaedics.


Exercise training and heart failure: a systematic review of current evidence.
Chronic heart failure (CHEF) is a growing public health problem. Current guidelines provide detailed information regarding pharmacotherapy but little guidance about the value of exercise/cardiac rehabilitation programmes for individuals with this condition. To investigate the effects of exercise training upon CHF patients, a systematic literature review was carried out of trials (from 1966 to December 2000) which used as their main outcome measures the effects of exercise training upon: (a) physical performance; or (b) quality of life; or (c) morbidity/mortality. Databases searched include: MedLine; Science Citation Index; Social Sciences Citation Index; BIDS, Bandolier; Cochrane Database of Systematic Reviews (CDSR); NHS National Research Register (NRR); and Current Research in Britain (CRIB). Relevant bibliographic references from identified articles were also reviewed. Thirty-one trials were identified, comprising randomised controlled trials (RCTs) (14/31), randomised crossover trials (8/31), non-RCTs (2/31), and pre-test/post-test (7/31). Sample sizes were: 25 participants or fewer (20/31); 26 to 50 participants (7/31); 51 to 150 participants (4/31). Participants were predominantly younger with a mean age in 23/31 studies of 65 years or less, and male. Patients with comorbidities were often excluded. Positive effects were reported on physical performance (27/31), quality of life (11/16), mortality (1/31), and readmission rates (1/31). No cost-effectiveness analyses were identfied. We conclude that short-term physical exercise training in selected subgroups of patients with CHF has physiological benefits and positive effects on quality of life. This review highlights the continuing problem of clinical trials that include participants who are not representative of the general population of CHF patients seen in primary care. Further investigation of the utility and applicability of exercise training is essential.


Covalent binding of zomepirac glucuronide to proteins: evidence for a Schiff base mechanism.
Carboxylic acids can undergo irreversible binding to proteins via their acyl glucuronide metabolites. Such binding occurs in humans and in vitro for bilirubin and the anti-inflammatory drugs zomepirac and tolmetin and may have toxicological significance. The mechanism of the binding is uncertain, but is thought to involve nucleophilic displacement of glucuronic acid by free cysteine thiols, tyrosine, or lysine residues of the protein. We now present evidence, using zomepirac glucuronide, for an alternative mechanism where irreversible binding occurs by isomerization of the glucuronide and formation of an imine linkage between the glucuronic acid moiety of the conjugate and a lysine or terminal amino group of the protein. Involvement of a protein thiol in the binding mechanism was ruled out by experiments with the thiol blocking agent, p-hydroxymercuribenzoate. Moreover, significant irreversible binding occurred when the cysteine free protein, alpha s1-casein, was incubated in solution with zomepirac glucuronide in vitro. When zomepirac glucuronide was added to solutions with albumin in the presence of the imine trapping reagent, sodium cyanide, or the reducing agent, sodium cyanoborohydride, irreversible binding of zomepirac increased 8.3- and 5.5-fold relative to controls, respectively, after 6 hr at 37 degrees C. The product formed after treatment of solutions of zomepirac glucuronide and albumin with sodium cyanoborohydride was stable in dilute acid, whereas similar acid treatment of zomepirac-albumin adduct from control incubations, obtained after sodium cyanide exposure, released 30% of the total adduct. Only isomeric conjugates of zomepirac glucuronide were released from zomepirac-albumin adduct by mild acid; no beta 1-isomer was detected.(ABSTRACT TRUNCATED AT 250 WORDS)


Waveguide-detector couplers for integrated optics and monolithic optoelectronic switching arrays.
An integrated waveguide-detector coupler (IWDC), in which a controlled fraction of the optical power in a waveguide is selectively coupled to a detector element, has been investigated. The device structure consists of a rib waveguide formed from a sputtered Corning 7059 glass film on an oxidized silicon substrate. A photoconductive detector is fabricated on the same substrate, and the degree of coupling is controlled by tapering the SiO(2) cladding layer thickness in the region between the electrodes and by varying the interaction length. Couplers with cladding layer thicknesses ranging from 0.15 to 0.80 microm in the detector interaction region were measured to have coupling values from 400 to 1500 dB/cm for TE modes and to 5800 dB/cm for TM modes, in good agreement with theory. The first integrated optoelectronic 2 x 2 switching matrix using IWDCs as switching cross-points has been demonstrated. We have shown that the passive power splitting in the integrated switch is nearly the ideal 50%.


Digitally shaped ethnographic relationships during a global pandemic and beyond.
Social distancing and public safety measures enacted in response to COVID-19 created a surge in methodological "advice" for researchers facing disruption to fieldwork. Resources and publications frequently encouraged changes vis-a-vis digitally enhanced methods or employment of digital ethnography. For ethnographers, the establishment and maintenance of ethnographic relationships in pandemic contexts restricted to virtual interactions has not been thoroughly explored, leaving those trained in recruitment, rapport-building, and field engagement with fewer resources to navigate this integral topic. Here, we provide insights into how ethnographic relationships may be developed when there is limited access to the field and traditional relationship building is not possible. We argue that as ethnographic methods change and adapt, so too must perspectives on ethnographic relationship development. By closely examining ethnographic relationships confined to digital spaces in the context of the Tennessee tornado recovery amid the COVID-19 pandemic, this project sheds light on how to overcome this challenge.


Prognostic factors in soft tissue sarcoma. Tissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence.
In adult soft tissue sarcoma (STS) of the extremities and trunk wall, improved prognostic factors are needed to identify patients at high-risk for metastasis. Various factors are included in the many prognostic systems currently in use and the prognostic value of immunohistochemical (IHC) expression of biological markers is unclear. The tissue-preserving, high throughput tissue microarray (TMA) technique for analysis of immunohistochemical expression of biological markers was validated for Ki-67, and was found to yield results comparable to conventional staining methods. TMA was used to study the IHC expression of multiple markers (Ki-67, p53, cyclin A, bcl-2, beta-catenin, CD44, and Pgp) in 218 malignant fibrous histiocytomas (MFH) and in 140 mixed STS. In the MFH series, tumor size and Ki-67, as the only IHC marker, provided independent prognostic information. In the mixed STS series whole-tumor sections were used and TMA was performed in the peripheral tumor growth zone. Whole-tumor sections facilitated assessment of the strong independent prognostic factors for metastasis vascular invasion, hazard ratio (HR) 3.5, tumor necrosis (HR 2.8), and tumor growth pattern (HR 3.2), and the latter also correlated with local recurrence (LR). In comparison, histological malignancy grade, tumor size, and depth were not of independent prognostic value. When TMA was performed from the peripheral tumor growth zone, the IHC expression of Ki-67 (HR 1.9), beta-catenin (HR 2.7), CD44 (HR 2.1) and Pgp (HR 2.4) were independent prognostic factors. Finally, prognostic factors were found to be time-dependent, and most had lost their prognostic value after 2 years, whereas LR was a strong prognostic factor for metastasis whenever it occurred.


A luminous bacterium that emits yellow light.
A strain of Photobacterium fischeri that emits yellow light has been isolated from seawater. The bimodal spectrum, which is unique among the luminous bacteria, consists of a major band with a maximum at 545 nanometers and a minor band with a maximum at 500 nanometers. The former represents a heretofore unreported range of emission for luminous bacteria, while the latter coincides with the emission spectrum of typical blue-greeen-emitting strains of P. fischeri. The relative contributions of these two bands to the total in vivo luminescence changes as a function of ambient temperature. When luciferase is extracted and luminescence observed in vitro, the emission is entirely blue-green, identical with that of luciferase isolated from other strains of P. fischeri.


A case of monoclonal immunoglobulin light- and heavy-chain deposition disease exhibiting atypical deposition with fibrillary structures, successfully treated with chemotherapy.
We report a case of light and heavy chain deposition disease (LHCDD), a rather rare monoclonal immunoglobulin deposition disease (MIDD) with successful therapeutic effect. A 58-year-old woman suffered from proteinuria and renal insufficiency (serum creatinine 1.0 mg/dl, creatinine clearance 49.2 ml/min) in February 2003. In serum and urine samples, monoclonal IgG-kappa was detected. A bone marrow aspiration showed a slightly hypocellular marrow and plasma cell population was increased to 7.0%. Renal histological findings revealed lobulated glomeruli with nodular lesions on light microscopy, characteristic findings of MIDD. Intense deposition of IgG heavy chains in the linear pattern in the glomerular and tubular basement membranes was observed. Immunohistochemistry revealed both kappa and lambda light chain depositions in glomeruli. Electron-microscopic examination revealed fine granular electron-dense deposits accompanied by microfibrils. Based on these findings, this patient was diagnosed as LHCDD. She received three courses of melphalan and prednisone chemotherapy, resulting in disappearance of proteinuria, prevention of renal functional deterioration and the decrease of monoclonal immunoglobulin. This case clearly demonstrates that the earlier and accurate diagnosis and initiation of chemotherapy at the early stage with serum creatinine level below 4.0 mg/dl are necessary to improve renal and patient outcome.


Surveillance of handwashing episodes in adult intensive-care units by measuring an index of soap and paper towel consumption.
To determine whether handwashing surveillance could be conducted by measurements of soap and towel consumption. In the medical intensive-care unit (MICU) of the Omaha Veterans' Affairs Medical Center, 10 4-hour day-time observation periods encompassing 409 handwashing episodes were scheduled in a 51-day period. In the surgical intensive-care unit (SICU), 7 4-hour periods encompassing 350 episodes were scheduled in a 49-day period. An observer measured paper towel height, towel weight, and soap weight at each sink. The observer also counted handwashing episodes and bed occupancy. Using handwashing episodes as a dependent variable, stepwise linear regression was performed with changes in towel height, towel weight, and soap weight as independent variables. Mean handwashing episodes per hour per occupied bed were 2.39 +/- 0.80 (standard deviation) in the MICU and 2.83 +/- 0.72 in the SICU. Correlation r with handwashing episodes for MICU changes was 0.891 for towel height, 0.950 for towel weight, and 0.882 for soap weight. Corresponding correlations for the SICU were 0.881, 0.918, and 0.904. For both units, stepwise regression retained changes in the weight of towels and soap as independent variables (P < .0001), with R2 0.965 (MICU) and 0.981 (SICU). Because soap and towel consumption measurements are closely related to handwashing frequency and because these measurements are easy to obtain, they offer a means of handwashing surveillance that can be sustained indefinitely. This can facilitate feedback-based interventions to improve handwashing frequency.


Effect of VOC Emissions from Vegetation on Air Quality in Berlin during a Heatwave.
The potential of emissions from urban vegetation combined with anthropogenic emissions to produce ozone and particulate matter has long been recognized. This potential increases with rising temperatures and may lead to severe problems with air quality in densely populated areas during heat waves. Here, we investigate how heat waves affect emissions of volatile organic compounds from urban/suburban vegetation and corresponding ground-level ozone and particulate matter. We use the Weather Research and Forecasting Model with atmospheric chemistry (WRF-Chem) with emissions of volatile organic compounds (VOCs) from vegetation simulated with MEGAN to quantify some of these feedbacks in Berlin, Germany, during the heat wave in 2006. The highest ozone concentration observed during that period was ∼200 μg/m3 (∼101 ppbV). The model simulations indicate that the contribution of biogenic VOC emissions to ozone formation is lower in June (9-11%) and August (6-9%) than in July (17-20%). On particular days within the analyzed heat wave period, this contribution increases up to 60%. The actual contribution is expected to be even higher as the model underestimates isoprene concentrations over urban forests and parks by 0.6-1.4 ppbv. Our study demonstrates that biogenic VOCs can considerably enhance air pollution during heat waves. We emphasize the dual role of vegetation for air quality and human health in cities during warm seasons, which is removal and lessening versus enhancement of air pollution. The results of our study suggest that reduction of anthropogenic sources of NOx, VOCs, and PM, for example, reduction of the motorized vehicle fleet, would have to accompany urban tree planting campaigns to make them really beneficial for urban dwellers.


Psychotropic drugs in pregnancy: a case-control study.
Psychotropic drug exposure during pregnancy is a common problem. Among the 601 cases exposed to drugs during pregnancy, who were followed by our Toxicology Information and Follow-up Service, 124 cases had used psychotropic drugs for depression, anxiety, or psychotic disorders. As the control group, 248 women, who did not use any drugs were selected. Of the 124 cases, 80 (64.5%) had healthy babies, and 17 (13.7%) decided to terminate the pregnancy. Spontaneous abortions, intrauterine death (in the 38th week) and premature deliveries were observed in the 9 (7.3%), 1 (0.8%) and 3 (2.4%) cases, respectively, in the drug exposure group. Pregnancies of the 14 (11.3%) cases were continuing during the preparation of this manuscript. Of the 248 controls, 151 (60.9%) had healthy babies, 9 (3.6%) experienced spontaneous abortion and 3 (1.2%) decided to terminate their pregnancies, 3 (1.2%) had premature deliveries, and we observed one (0.4%) congenital abnormality, 81 (32.7%) cases were still pregnant. Odds Ratio (95% confidence interval) for spontaneous abortion was found to be 1.35 (1.27-11.82) in the cases exposed to psychotropic drugs (P=0.02). No developmental problems were observed in the babies followed for 12 months. These data may give information about the early- but not the late-term effects of psychotropic drugs used in pregnant women.


Elevated high mobility group A2 expression in liver cancer predicts poor patient survival.
liver cancer is a malignant tumor with a high morbidity and mortality that endangers human health. High mobility group A2 (HMGA2) is a chromosome associated protein that participates in embryogenesis, tissue development, tumorigenesis and development. to explore the relationship between HMGA2 expression and the clinicopathological parameters and survival of liver cancer patients using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (HCC) data. RNA-sequencing data and the corresponding clinical characteristics of the patients were downloaded from the Atlas database. The Chi-squared test was used to assess the relationship between HMGA2 expression and clinical variables. Cox regression analysis was used to compare survival rates between the high- and low-expressing groups; the p-values and Kaplan-Meier survival curves were compared using the log-rank test. RNA-seq data from 373 cases of liver cancer cases were analyzed. HMGA2 was overexpressed in liver cancer and significantly associated with gender (p = 0.0357), T classification (p = 0.0063), clinical classification (p = 0.0026) and overall survival (p = 0.0386). According to the multivariate analysis, HMGA2 could independently predict overall survival in liver cancer. HMGA2 independently predicts poor prognosis in liver cancer and serves as a molecular marker to determine disease prognosis.


Sharpness enhancement of stereo images using binocular just-noticeable difference.
In this paper, we propose a new sharpness enhancement algorithm for stereo images. Although the stereo image and its applications are becoming increasingly prevalent, there has been very limited research on specialized image enhancement solutions for stereo images. Recently, a binocular just-noticeable-difference (BJND) model that describes the sensitivity of the human visual system to luminance changes in stereo images has been presented. We introduce a novel application of the BJND model for the sharpness enhancement of stereo images. To this end, an overenhancement problem in the sharpness enhancement of stereo images is newly addressed, and an efficient solution for reducing the overenhancement is proposed. The solution is found within an optimization framework with additional constraint terms to suppress the unnecessary increase in luminance values. In addition, the reliability of the BJND model is taken into account by estimating the accuracy of stereo matching. Experimental results demonstrate that the proposed algorithm can provide sharpness-enhanced stereo images without producing excessive distortion.


Posttranslational regulation impacts the fate of duplicated genes.
Gene and genome duplications create novel genetic material on which evolution can work and have therefore been recognized as a major source of innovation for many eukaryotic lineages. Following duplication, the most likely fate is gene loss; however, a considerable fraction of duplicated genes survive. Not all genes have the same probability of survival, but it is not fully understood what evolutionary forces determine the pattern of gene retention. Here, we use genome sequence data as well as large-scale phosphoproteomics data from the baker's yeast Saccharomyces cerevisiae, which underwent a whole-genome duplication approximately 100 mya, and show that the number of phosphorylation sites on the proteins they encode is a major determinant of gene retention. Protein phosphorylation motifs are short amino acid sequences that are usually embedded within unstructured and rapidly evolving protein regions. Reciprocal loss of those ancestral sites and the gain of new ones are major drivers in the retention of the two surviving duplicates and in their acquisition of distinct functions. This way, small changes in the sequences of unstructured regions in proteins can contribute to the rapid rewiring and adaptation of regulatory networks.


The logic layout of the TOL network of Pseudomonas putida pWW0 plasmid stems from a metabolic amplifier motif (MAM) that optimizes biodegradation of m-xylene.
The genetic network of the TOL plasmid pWW0 of the soil bacterium Pseudomonas putida mt-2 for catabolism of m-xylene is an archetypal model for environmental biodegradation of aromatic pollutants. Although nearly every metabolic and transcriptional component of this regulatory system is known to an extraordinary molecular detail, the complexity of its architecture is still perplexing. To gain an insight into the inner layout of this network a logic model of the TOL system was implemented, simulated and experimentally validated. This analysis made sense of the specific regulatory topology out on the basis of an unprecedented network motif around which the entire genetic circuit for m-xylene catabolism gravitates. The most salient feature of the whole TOL regulatory network is the control exerted by two distinct but still intertwined regulators (XylR and XylS) on expression of two separated catabolic operons (upper and lower) for catabolism of m-xylene. Following model reduction, a minimal modular circuit composed by five basic variables appeared to suffice for fully describing the operation of the entire system. In silico simulation of the effect of various perturbations were compared with experimental data in which specific portions of the network were activated with selected inducers: m-xylene, o-xylene, 3-methylbenzylalcohol and 3-methylbenzoate. The results accredited the ability of the model to faithfully describe network dynamics. This analysis revealed that the entire regulatory structure of the TOL system enables the action an unprecedented metabolic amplifier motif (MAM). This motif synchronizes expression of the upper and lower portions of a very long metabolic system when cells face the head pathway substrate, m-xylene. Logic modeling of the TOL circuit accounted for the intricate regulatory topology of this otherwise simple metabolic device. The found MAM appears to ensure a simultaneous expression of the upper and lower segments of the m-xylene catabolic route that would be difficult to bring about with a standard substrate-responsive single promoter. Furthermore, it is plausible that the MAM helps to avoid biochemical conflicts between competing plasmid-encoded and chromosomally-encoded pathways in this bacterium.


Training paediatric healthcare staff in recognising, understanding and managing conflict with patients and families: findings from a survey on immediate and 6-month impact.
Conflict is a recognised component of healthcare. Disagreements about treatment protocols, treatment aims and poor communication are recognised warning signs. Conflict management strategies can be used to prevent escalation, but are not a routine component of clinical training. To report the findings from a novel training intervention, aimed at enabling paediatric staff to identify and understand the warning signs of conflict, and to implement conflict resolution strategies. Self-report measures were taken at baseline, immediately after the training and at 6 months. Questionnaires recorded quantitative and qualitative feedback on the experience of training, and the ability to recognise and de-escalate conflict. The training was provided in a tertiary teaching paediatric hospital in England over 18 months, commencing in June 2013. A 4-h training course on identifying, understanding and managing conflict was provided to staff. Baseline data were collected from all 711 staff trained, and 6-month follow-up data were collected for 313 of those staff (44%). The training was successful in equipping staff to recognise and de-escalate conflict. Six months after the training, 57% of respondents had experienced conflict, of whom 91% reported that the training had enabled them to de-escalate the conflict. Learning was retained at 6 months with staff more able than at baseline recognising conflict triggers (Fischer's exact test, p=0.001) and managing conflict situations (Pearson's χ2 test, p=0.001). This training has the potential to reduce substantially the human and economic costs of conflicts for healthcare providers, healthcare staff, patients and relatives.


Targeting of viral capsids to nuclear pores in a cell-free reconstitution system.
Many viruses deliver their genomes into the nucleoplasm for viral transcription and replication. Here, we describe a novel cell-free system to elucidate specific interactions between viruses and nuclear pore complexes (NPCs). Nuclei reconstituted in vitro from egg extracts of Xenopus laevis, an established biochemical system to decipher nuclear functions, were incubated with GFP-tagged capsids of herpes simplex virus, an alphaherpesvirus replicating in the nucleus. Capsid binding to NPCs was analyzed using fluorescence and field emission scanning electron microscopy. Tegument-free capsids or viral capsids exposing inner tegument proteins on their surface bound to nuclei, while capsids inactivated by a high-salt treatment or covered by inner and outer tegument showed less binding. There was little binding of the four different capsid types to nuclei lacking functional NPCs. This novel approach provides a powerful system to elucidate the molecular mechanisms that enable viral structures to engage with NPCs. Furthermore, this assay could be expanded to identify molecular cues triggering viral genome uncoating and nuclear import of viral genomes.


Discovery of an amylose-free starch mutant in cassava (Manihot esculenta Crantz).
One of the objectives of the cassava-breeding project at CIAT is the identification of clones with special root quality characteristics. A large number of self-pollinations have been made in search of useful recessive traits. During 2006 harvests an S1 plant produced roots that stained brownish-red when treated with an iodine solution, suggesting that it had lower-than-normal levels of amylose in its starch. Colorimetric and DSC measurements indicated low levels (3.4%) and an absence of amylose in the starch, respectively. SDS-PAGE demonstrated the absence of GBSS enzyme in the starch from these roots. Pasting behavior was analyzed with a rapid visco-analyzer and resulted in larger values for peak viscosity, gel breakdown, and setback in the mutant compared with normal cassava starch. Solubility was considerably reduced, while the swelling index and volume fraction of the dispersed phase were higher in the mutant. No change in starch granule size or shape was observed. This is the first report of a natural mutation in cassava that drastically reduces amylose content in root starch.


Probing effective slippage on superhydrophobic stripes by atomic force microscopy.
While the effective slippage of water past superhydrophobic surfaces has been studied over a decade, theoretical predictions have never been properly confirmed by experiments. Here we measure a drag force on a sphere approaching a plane decorated by superhydrophobic grooves and compare the results with the predictions of semi-analytical theory developed here, which employs the gas cushion model to calculate the local slip length at the gas sectors. We demonstrate that at intermediate and large (compared to a texture period) separations the half-sum of longitudinal and transverse effective slip lengths can be deduced from the force-distance curve by using the known analytical theory of hydrodynamic interaction of a sphere with a homogeneous slipping plane. This half-sum is shown to depend on the fraction of gas sectors and its value is in excellent agreement with theoretical predictions. At small distances the half-sum of effective longitudinal and transverse slip lengths becomes separation-dependent, and is in quantitative agreement with the predictions of our semi-analytical theory.


Proteomic Study of Response to Copper, Cadmium, and Chrome Ion Stress in Yarrowia lipolytica Strains Isolated from Andean Mine Tailings in Peru.
Mine tailings are produced by mining activities and contain diverse heavy metal ions, which cause environmental problems and have negative impacts on ecosystems. Different microorganisms, including yeasts, play important roles in the absorption and/or adsorption of these heavy metal ions. This work aimed to analyze proteins synthesized by the yeast Yarrowia lipolytica AMJ6 (Yl-AMJ6), isolated from Andean mine tailings in Peru and subjected to stress conditions with common heavy metal ions. Yeast strains were isolated from high Andean water samples impacted by mine tailings from Yanamate (Pasco, Peru). Among all the isolated yeasts, the Yl-AMJ6 strain presented LC50 values of 1.06 mM, 1.42 mM, and 0.49 mM for the Cr+6, Cu+2, and Cd+2 ions, respectively. Proteomic analysis of theYl-AMJ6 strain under heavy metal stress showed that several proteins were up- or downregulated. Biological and functional analysis of these proteins showed that they were involved in the metabolism of proteins, nucleic acids, and carbohydrates; response to oxidative stress and protein folding; ATP synthesis and ion transport; membrane and cell wall; and cell division. The most prominent proteins that presented the greatest changes were related to the oxidative stress response and carbohydrate metabolism, suggesting the existence of a defense mechanism in these yeasts to resist the impact of environmental contamination by heavy metal ions.


Acceleration of bursty multiprotein target search kinetics on DNA by colocalisation.
Proteins are capable of locating specific targets on DNA by employing a facilitated diffusion process with intermittent 1D and 3D search steps. Gene colocalisation and coregulation-i.e. the spatial proximity of two communicating genes-is one factor capable of accelerating the target search process along the DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of gene colocalisation for minimising the search time in a model DNA-protein system. We use a simple diffusion model to mimic the search for targets by proteins, produced initially in bursts of multiple proteins and performing the first-passage search on the DNA chain. The behaviour of the mean first-passage times to the target is studied as a function of distance between the initial position of proteins and the DNA target position, as well as versus the concentration of proteins. We also examine the properties of bursty target search kinetics for varying physical-chemical protein-DNA binding affinity. Our findings underline the relevance of colocalisation of production and binding sites for protein search inside biological cells.


Correctness of local probability in graphical models with loops.
Graphical models, such as Bayesian networks and Markov networks, represent joint distributions over a set of variables by means of a graph. When the graph is singly connected, local propagation rules of the sort proposed by Pearl (1988) are guaranteed to converge to the correct posterior probabilities. Recently a number of researchers have empirically demonstrated good performance of these same local propagation schemes on graphs with loops, but a theoretical understanding of this performance has yet to be achieved. For graphical models with a single loop, we derive an analytical relationship between the probabilities computed using local propagation and the correct marginals. Using this relationship we show a category of graphical models with loops for which local propagation gives rise to provably optimal maximum a posteriori assignments (although the computed marginals will be incorrect). We also show how nodes can use local information in the messages they receive in order to correct their computed marginals. We discuss how these results can be extended to graphical models with multiple loops and show simulation results suggesting that some properties of propagation on single-loop graphs may hold for a larger class of graphs. Specifically we discuss the implication of our results for understanding a class of recently proposed error-correcting codes known as turbo codes.


Effects of regular and decaffeinated roasted coffee (Coffea arabica and Coffea canephora) extracts and bioactive compounds on in vitro probiotic bacterial growth.
The aim of this study was to investigate the effects of coffee species, roast degree and decaffeination on in vitro probiotic bacterial growth, and to identify the major coffee compounds responsible for such effects. Six C. arabica and C. canephora extracts (regular medium and dark roasted and decaffeinated medium roasted), and five bioactive compounds (chlorogenic acid, galactomannan, type 2 arabinogalactan, caffeine and trigonelline) were individually incorporated into a modified low-carbon broth medium-(mMRS), at different concentrations (0.5 to 1.5% soluble coffee and 0.05 to 0.8 mg mL-1 standard solutions). Inulin and fructooligosaccharides (FOS) were used as prebiotic references. MRS and mMRS were used as rich and poor medium controls, respectively. The growth of Lactobacillus rhamnosus GG ATCC 53103-(GG), L. acidophilus LA-5-(LA), Bifidobacterium animalis DN-173010-(BA) and B. animalis subsp. lactis BB12-(BB12), as well as the growth inhibition of non-probiotic Escherichia coli ATCC 25922 were evaluated. Differences in growth between mMRS and treatments (Δlog CFU mL-1) were compared by ANOVA and Tukey's test, and considered when p ≤ 0.05. Overall, after 48 h incubation, the medium roasted arabica coffee extract increased the growth of GG, LA and BA (range: Δlog CFU mL-1 = 0.5 to 1.8), while the dark roasted arabica coffee extract increased BB12 growth (range: Δlog CFU mL-1 = 0.9 to 1.7), in a dose dependent manner. Improved performances of GG, LA and BA were promoted by higher polysaccharides and CGA concentrations, with better performance for Lactobacillus sp. The tested coffee bioactive compounds promoted the poor growth of BB12. Plain caffeine did not promote Bifidobacterium sp. growth and limited the growth of Lactobacillus sp. Regular C. arabica and C. canephora extracts inhibited the growth of E. coli, while the decaffeinated extracts promoted its growth. The present results show that coffee consumption can selectively improve the growth of probiotic strains, thus exerting a prebiotic effect, and show that coffee roasting and decaffeination affect this property and that different strains utilize different coffee components to grow.


Systematic review of diagnostic utility and therapeutic effectiveness of thoracic facet joint interventions.
Chronic mid back and upper back pain caused by thoracic facet joints has been reported in 34% to 48% of the patients based on the responses to controlled diagnostic blocks. Systematic reviews have established moderate evidence for controlled comparative local anesthetic blocks of thoracic facet joints in the diagnosis of mid back and upper back pain, moderate evidence for therapeutic thoracic medial branch blocks, and limited evidence for radiofrequency neurotomy of therapeutic facet joint nerves. To determine the clinical utility of diagnostic and therapeutic thoracic facet joint interventions in diagnosing and managing chronic upper back and mid back pain. Systematic review of diagnostic and therapeutic thoracic facet joint interventions. Review of the literature for utility of facet joint interventions in diagnosing and managing facet joint pain was performed according to the Agency for Healthcare Research and Quality (AHRQ) criteria for diagnostic studies and observational studies and the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials. The level of evidence was classified as Level I, II, or III based on the quality of evidence developed by United States Preventive Services Task Force (USPSTF) for therapeutic interventions. Recommendations were based on the criteria developed by Guyatt et al. Data sources included relevant literature of the English language identified through searches of Medline and EMBASE from 1966 to July 2008 and manual searches of bibliographies of known primary and review articles. Results of the analysis were performed for diagnostic and therapeutic interventions separately. For diagnostic interventions, studies must have been performed utilizing controlled local anesthetic blocks. For therapeutic interventions, the primary outcome measure was pain relief (short-term relief = up to 6 months and long-term relief > 6 months) with secondary outcome measures of improvement in functional status, psychological status, return to work, and reduction in opioid intake. Based on the controlled comparative local anesthetic blocks, the evidence for the diagnosis of thoracic facet joint pain is Level I or II-1. The evidence for therapeutic thoracic medial branch blocks is Level I or II-1. The recommendation is IA or 1B/strong for diagnostic and therapeutic medial branch blocks. The evidence for the diagnosis of thoracic facet joint pain with controlled comparative local anesthetic blocks is Level I or II-1. The evidence for therapeutic facet joint interventions is Level I or II-1 for medial branch blocks. Recommendation is 1A or 1B/strong for diagnostic and therapeutic medial branch blocks.


Gain-guiding in transverse grating waveguides for large modal area laser amplifiers.
A new optically pumped waveguide amplifier with ultra-large mode area is proposed. This amplifier is based on gain guiding in a transverse grating waveguide in which the pump is confined by the photonic bandgap while the signal is guided by optical gain. Characteristics of the propagating modes of the waveguide amplifier are analyzed theoretically using the transfer matrix method, indicating robust single-transverse-mode operation with large modal gain.


Addressing taxane resistance in metastatic castration-resistant prostate cancer: a focus on chaperone proteins.
Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel. Another treatment, currently in development, targets the prosurvival molecule clusterin. Custirsen, an antisense molecule that inhibits clusterin production, has shown promise in combination with docetaxel in mCRPC patients at risk for poor outcomes. Although optimal sequence and combination of available therapies is unclear, the heterogeneity of mCRPC suggests a continuing need for personalized treatment regimens and improved abilities to predict which patients will respond to the available treatment options.


Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes.
The in vivo metabolism in humans of the anticonvulsant mephenytoin exhibits stereoselectivity as well as genetic polymorphism of the 4-hydroxylation pathway. The characteristics of the involved cytochrome P-450 isozyme are, however, not known completely. Accordingly, the ability of human liver microsomes to metabolize mephenytoin and its enantiomers was investigated in vitro, and the ability of related anticonvulsants and other compounds to inhibit 4-hydroxylation was studied. Marked stereoselectivity was observed in the conversion of S-mephenytoin to its 4-hydroxy metabolite, but N-demethylation was essentially similar for both enantiomers. The intrinsic clearance (Vmax/Km) for 4-hydroxymephenytoin formation showed an almost 10-fold range in five livers and was 150- to 1000-fold greater than that for N-demethylation. Competitive inhibition of 4-hydroxylation was observed with ethotoin, mephobarbital, methsuximide and phensuximide, but not other commonly used anticonvulsants such as ethosuximide, phenobarbital, phenytoin and primidone. However, synthetic N-alkyl analogs of the latter compounds were found to be inhibitory. An aryl residue alpha to the carbonyl carbon of an N-alkyl lactam in a 5- or 6-membered ring, therefore, appears to be a minimal requirement for strong interaction with the 4-hydroxylase. Warfarin, but not diazepam, ketoconazole or iodochlorohydroxyquin, were also competitive inhibitors, but at much higher concentrations than the anticonvulsants. Competitive inhibition at concentrations similar to the Km of 4-hydroxymephenytoin formation (30-350 microM) may indicate that the isozyme is involved in the metabolism of the substrates under consideration and, therefore, their in vivo metabolism may be regulated to some extent by the same genetic factor(s) that determine mephenytoin's biotransformation.


CD4 T Cells Mediate Both Positive and Negative Regulation of the Immune Response to HIV Infection: Complex Role of T Follicular Helper Cells and Regulatory T Cells in Pathogenesis.
HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B-cells, and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely, regulatory T cells (Tregs) and T follicular helper cells (Tfh). These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B-cell hyperplasia and increased germinal center activity. Antiretroviral therapy may reduce the lymphocyte activation, but not completely, and therefore, there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B-cell, or Treg dysfunction.


Error-prone translesion synthesis by human DNA polymerase eta on DNA-containing deoxyadenosine adducts of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
When human DNA polymerase eta (pol eta) encounters N6-deoxyadenosine adducts formed by trans epoxide ring opening of the 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE) isomer with (+)-7R,8S,9S,10R configuration ((+)-BaP DE-2), misincorporation of A or G and incorporation of the correct T are equally likely to occur. On the other hand, the enzyme exhibits a 3-fold preference for correct T incorporation opposite adducts formed by trans ring opening of the (-)-(7S,8R,9R,10S)-DE-2 enantiomer. Adducts at dA formed by cis ring opening of these two BaP DE-2 isomers exhibit a 2-3-fold preference for A over T incorporation, with G intermediate between the two. Extension one nucleotide beyond these adducts is generally weaker than incorporation across from them, but among mismatches the (adducted A*) x A mispair is the most favored for extension. Because mutations can only occur if mispairs are extended, this observation is consistent with the occurrence of A x T to T x A transversions as common mutations in animal cells treated with BaP DE-2 isomers. Adducts with S absolute configuration at the point of attachment of the hydrocarbon to the base inhibit incorporation and extension by pol eta to a lesser extent than their R counterparts. Template-primers containing each of the four isomeric dA adducts derived from BaP DE-2 and two adducts derived from 9,10-epoxy-7,8,9,10-tetrahydrobenzo-[a]pyrene in which the 7- and 8-hydroxyl groups of the DEs are replaced with hydrogens exhibit reduced electrophoretic mobilities relative to the unadducted oligonucleotides. This effect is largely independent of DNA sequence. Decreased mobility correlates with an increased rate of incorporation by pol eta, suggesting a systematic relationship between the overall DNA structure and efficiency of the enzyme.


A bacterial acetyltransferase destroys plant microtubule networks and blocks secretion.
The eukaryotic cytoskeleton is essential for structural support and intracellular transport, and is therefore a common target of animal pathogens. However, no phytopathogenic effector has yet been demonstrated to specifically target the plant cytoskeleton. Here we show that the Pseudomonas syringae type III secreted effector HopZ1a interacts with tubulin and polymerized microtubules. We demonstrate that HopZ1a is an acetyltransferase activated by the eukaryotic co-factor phytic acid. Activated HopZ1a acetylates itself and tubulin. The conserved autoacetylation site of the YopJ / HopZ superfamily, K289, plays a critical role in both the avirulence and virulence function of HopZ1a. Furthermore, HopZ1a requires its acetyltransferase activity to cause a dramatic decrease in Arabidopsis thaliana microtubule networks, disrupt the plant secretory pathway and suppress cell wall-mediated defense. Together, this study supports the hypothesis that HopZ1a promotes virulence through cytoskeletal and secretory disruption.


Using Functional Near-Infrared Spectroscopy to Assess Brain Activation Evoked by Guilt and Shame.
Functional near-infrared spectroscopy (fNIRS) is a promising brain imaging modality for studying the neural substrates of moral emotions. However, the feasibility of using fNIRS to measure moral emotions has not been established. In the present study, we used fNIRS to detect the brain activation evoked by two typical moral emotions-guilt and shame. We presented the participants with guilt and shame context to evoke emotional responses and measured the brain activity by using fNIRS. The univariate general linear model analysis showed significant activations for both emotions in the orbitofrontal cortex, dorsolateral prefrontal cortex, and middle temporal gyrus, and specific activation for guilt in the right temporoparietal junction. The multivariate classification analysis showed an overall recognition accuracy of 52.50%, which was significantly higher than the chance level in classifying the guilt, shame, and neutral emotions. These results suggested the feasibility of using fNIRS to assess the brain activation evoked by guilt and shame and demonstrated the potentials of fNIRS in studying the neural correlates of moral emotions.


HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis.
Human leucocyte antigen (HLA) genes predict disease severity in psoriasis (HLA-Cw6) and rheumatoid arthritis (shared epitope (SE)), but the situation is unclear for psoriatic arthritis (PsA). To determine the association of the HLA-Cw6 and HLA-DRB1 gene with disease severity in a large UK cohort with PsA. Genotyping of the HLA-Cw and HLA-DRB1 loci was undertaken in DNA samples from patients with PsA (n = 480). Stratification and regression analysis were used within the PsA cases to determine whether HLA-Cw6, HLA-DRB1 or the presence of the SE alleles predicted disease severity as measured by the Health Assessment Questionnaire score, the total number of damaged or involved joints adjusted for disease duration and disease-modifying antirheumatic treatments. HLA-Cw6 was found to be in linkage disequilibrium with HLA-DRB1*07 (r(2) = 0.46). Patients with PsA who carried both HLA-Cw6 and HLA-DRB1*07 had fewer damaged or involved joints (41% fewer damaged (95% CI 23% to 55%, p = 0.02) and 31% fewer involved joints (95% CI 16% to 44%, p<0.001)) compared with those who carried neither HLA-Cw6 nor HLA-DRB1*07 alleles. Those who carried either HLA-Cw6 or HLA-DRB1*07 alleles alone had no evidence of a reduction in joint involvement. The SE, HLA-DRB1*03 and HLA-DRB1*04 alleles did not predict severity using these outcome measures. Patients with PsA carrying both HLA-Cw6 and HLA-DRB1*07 alleles have a less severe course of arthritis. This suggests that a protective locus lies on a haplotype marked by these alleles. No association was detected with disease severity and SE status.


Time-resolved spectroscopy of laser emission from dye-doped droplets.
Micrometer-sized droplets of Rhodamine 6G solution in water and ethanol are irradiated by high-intensity nanosecond pulses from a frequency-doubled Nd:YAG laser. Coupling of the spontaneous fluorescence emission with natural resonant modes of the spherical droplets results in stimulated emission, with each droplet behaving like a laser cavity. Spectral observations suggest that droplet lasing emission is supported by resonances of a single mode order. The emission exhibits faster rise times and is shorter lived than corresponding bulk-liquid fluorescence. Lasing in droplets is generally initiated almost simultaneously with elastic scattering, unlike stimulated Raman scattering, which is significantly delayed.


Interaction of ribosomes and the cell envelope of Escherichia coli mediated by lysozyme.
Evidence is presented suggesting the existence of a natural ribosome-membrane complex. A reconstruction system is described wherein free ribosomes form a complex which appears to involve cell fragments. The reconstructed complex is similar in stability to the inferred natural complex. The reconstructed complex is generated by lysozyme, and it is concluded that at least part of the inferred natural complex is also generated by lysozyme. These results are discussed with reference to existing data concerning certain membrane-associated systems in bacteria.


Impact of speed cameras on trauma centers.
While studies, mostly from Europe and Australia, have examined the effect of speed cameras on motor vehicle collisions, limited data exist regarding their impact on charges and number of patients taken to Level 1 trauma centers (L1TCs). Because of conflicting perceptions and data on their value, speed cameras were implemented along select Arizona highways in 2008 but then removed in 2010. The hypotheses of our study were twofold. (1) Speed cameras reduce admissions to L1TCs, and (2) speed cameras reduce crash kinetic energy, resulting in lower Injury Severity Score (ISS), mortality, hospital costs, and length of stay (LOS). A retrospective review of all patients admitted to L1TCs who were injured in motor vehicle crashes along a 26-mile segment of interstate I-10 in urban Phoenix was performed. Patients were identified using both the Arizona State Trauma Registry and the Arizona Department of Transportation collision data for 2009 to 2011. This specific 26-mile segment of I-10 was selected because it contained at least one speed camera within 1 mile along its entire length from October 2008 to October 2010. Two time frames were evaluated: January 1 to December 31, 2009, when cameras were in place (2009 camera group) and January 1 to December 31, 2011, when no cameras were in place (2011 no-camera group). Variables analyzed include number of collisions, number of injuries, on-scene mortality, trauma center admissions, number of collisions with admissions, in-hospital mortality, ISS, hospital charges, LOS, age, sex, race, and ethnicity. Five confounding variables were eliminated. Analysis was performed using Fisher's exact test and linear regression. Camera removal was associated with a twofold increase in L1TC admissions as well as increased resource use. There were no significant differences between the two time frames for ISS, mortality, median charges, or median LOS. In this study, removal of speed cameras resulted in increased trauma center admissions and resource use. Care management study, level IV.


Chondrogenic potential and anti-senescence effect of hypoxia on canine adipose mesenchymal stem cells.
Mesenchymal stem cells (MSCs) have the ability to differentiate into multi-lineage cells, which confers great promise for use in regenerative medicine. In this study, canine adipose MSCs (cAD-MSCs) were isolated from canine adipose tissue. These cells clearly represented stemness (Oct4, Sox2, and Nanog) and differentiation potential into the mesoderm (adipocytes, chondrocytes, and osteoblasts) at early passages. The aim of this study was to evaluate the effects of hypoxia on the differentiation potential into mesoderm, and the expression of anti-apoptotic genes associated with cell survival for the optimal culturing of MSCs. We observed that the proliferation of the cAD-MSCs meaningfully increased when cultured under hypoxic condition than in normoxic condition, during 7 consecutive passages. Also, we found that hypoxia strongly expressed anti-senescence related genes such as HDAC1 (histone deacetylase 1), DNMT1 (DNA (cytosine-5)-methyltransferase 1), Bcl-2 (inhibitor of apoptosis), TERT (telomerase reverse transcriptase), LDHA (lactate dehydrogenase A), SLC2A1 (glucose transporter), and DKC1 (telomere holoenzyme complex) and differentiation potential of cAD-MSCs into chondrocytes, than seen under the normoxic culture conditions. We also examined the multipotency of hypoxic conditioned MSCs using quantitative real-time RT-PCR. We found that the expression levels of stemness genes such as Oct-4, Nanog, and Sox-2 were increased in hypoxic condition when compared to the normoxic condition. Collectively, these results suggest that hypoxic conditions have the ability to induce proliferation of MSCs and augment their chondrogenic potential. This study suggests that cell proliferation of cAD-MSC under hypoxia could be beneficial, when considering these cells for cell therapies of canine bone diseases.


Creation of a bacterial cell controlled by a chemically synthesized genome.
We report the design, synthesis, and assembly of the 1.08-mega-base pair Mycoplasma mycoides JCVI-syn1.0 genome starting from digitized genome sequence information and its transplantation into a M. capricolum recipient cell to create new M. mycoides cells that are controlled only by the synthetic chromosome. The only DNA in the cells is the designed synthetic DNA sequence, including "watermark" sequences and other designed gene deletions and polymorphisms, and mutations acquired during the building process. The new cells have expected phenotypic properties and are capable of continuous self-replication.


Natural phenolic compounds as cardiovascular therapeutics: potential role of their antiinflammatory effects.
A number of epidemiological studies have shown that diets rich in plant-derived phenolic compounds reduce the risk of coronary heart disease. The chronic antioxidant and hypolipidemic activities of these compounds have important roles in prevention of lipoprotein oxidation and atherosclerotic lesion development. In recent years, it has been recognized that inflammation is directly involved in development of cardiovascular disease and clinical events such as atherosclerotic plaque rupture (which is the trigger of acute coronary syndrome), arterial restenosis, and myocardial ischemia-reperfusion injury. Phenolic compounds have significant antiinflammatory effects, including inhibition of adhesion molecule, cytokine and chemokine gene expression; inhibition of platelet function; augmentation of endothelial nitric oxide release; suppression of smooth muscle activation; and other effects on proinflammatory factors such as endothelin and matrix metalloproteinases. However, direct evidence of acute therapeutic benefits of phenolic compounds in cardiovascular disorders remains sparse. This review attempts to integrate the inflammatory mechanisms involved in these cardiovascular diseases with recent findings on the antiinflammatory effects of phenolic compounds. Findings from the limited in vivo studies in this regard are discussed. It is suggested that searching for novel phenolic compounds with higher specificity and efficacy may represent a fruitful approach in development of new cardiovascular therapeutics.


BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion injury in rats.
To assess the efficacy of the newly synthesized selective adenosine A1 receptor agonist, BN-063 (1-cyclopropylisoguanosine), against myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. Animals were randomly assigned to four groups: control, I0.5-R0.5, in which BN-063 (0.5 mg/kg i.v. bolus) was administered during both ischemia and reperfusion, R-0.5 and R-1.0, in which BN-063 was administered only during reperfusion at 0.5 and 1.0 mg/kg, respectively. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, which was performed by retightening the ligature at the end of reperfusion, and infarct size was determined by incubation of heart slices in nitro blue tetrazolium chloride. A significant reduction in infarct size, as a percentage of the area at risk, was noted with all three BN-063 treatment groups (control: 63.5 +/- 4.0%, I0.5-R0.5: 39.6 +/- 3.7%, R-0.5: 37.5 +/- 3.5%, R-1.0: 38.1 +/- 5.2%). However, the I0.5-R0.5 group did not shown a more beneficial effect than the other two BN-063-treated groups. In addition, BN-063 exerted a protective effect on the number of ventricular premature contractions associated with reperfusion (control: 906 +/- 52, I0.5-R0.5: 325 +/- 61, R-0.5: 321 +/- 95, R-1.0: 340 +/- 46). The results of this study demonstrate that BN-063, through activation of adenosine A1 receptors, exerts antiarrhythmic and anti-infarct effects during myocardial ischemia-reperfusion. Therefore, BN-063 would be useful clinically in the treatment and prevention of acute myocardial infarction.


On the use of a convolution-superposition algorithm for plan checking in lung stereotactic body radiation therapy.
Stereotactic body radiation therapy (SBRT) aims to deliver a highly conformal ablative dose to a small target. Dosimetric verification of SBRT for lung tumors presents a challenge due to heterogeneities, moving targets, and small fields. Recent software (M3D) designed for dosimetric verification of lung SBRT treatment plans using an advanced convolution-superposition algorithm was evaluated. Ten lung SBRT patients covering a range of tumor volumes were selected. 3D CRT plans were created using the XiO treatment planning system (TPS) with the superposition algorithm. Dose was recalculated in the Eclipse TPS using the AAA algorithm, M3D verification software using the collapsed-cone-convolution algorithm, and in-house Monte Carlo (MC). Target point doses were calculated with RadCalc software. Near-maximum, median, and near-minimum target doses, conformity indices, and lung doses were compared with MC as the reference calculation. M3D 3D gamma passing rates were compared with the XiO and Eclipse. Wilcoxon signed-rank test was used to compare each calculation method with XiO with a threshold of significance of p < 0.05. M3D and RadCalc point dose calculations were greater than MC by up to 7.7% and 13.1%, respectively, with M3D being statistically significant (s.s.). AAA and XiO calculated point doses were less than MC by 11.3% and 5.2%, respectively (AAA s.s.). Median and near-minimum and near-maximum target doses were less than MC when calculated with AAA and XiO (all s.s.). Near-maximum and median target doses were higher with M3D compared with MC (s.s.), but there was no difference in near-minimum M3D doses compared with MC. M3D-calculated ipsilateral lung V20 Gy and V5 Gy were greater than that calculated with MC (s.s.); AAA- and XiO-calculated V20 Gy was lower than that calculated with MC, but not statistically different to MC for V5 Gy. Nine of the 10 plans achieved M3D gamma passing rates greater than 95% and 80%for 5%/1 mm and 3%/1 mm criteria, respectively. M3D typically calculated a higher target and lung dose than MC for lung SBRT plans. The results show a range of calculated doses with different algorithms and suggest that M3D is in closer agree-ment with Monte Carlo, thus discrepancies between the TPS and M3D software will be observed for lung SBRT plans. M3D provides a useful supplement to verification of lung SBRT plans by direct measurement, which typically excludes patient specific heterogeneities.


Semi-automated segmentation of pre-operative low grade gliomas in magnetic resonance imaging.
Segmentation of pre-operative low-grade gliomas (LGGs) from magnetic resonance imaging is a crucial step for studying imaging biomarkers. However, segmentation of LGGs is particularly challenging because they rarely enhance after gadolinium administration. Like other gliomas, they have irregular tumor shape, heterogeneous composition, ill-defined tumor boundaries, and limited number of image types. To overcome these challenges we propose a semi-automated segmentation method that relies only on T2-weighted (T2W) and optionally post-contrast T1-weighted (T1W) images. First, the user draws a region-of-interest (ROI) that completely encloses the tumor and some normal tissue. Second, a normal brain atlas and post-contrast T1W images are registered to T2W images. Third, the posterior probability of each pixel/voxel belonging to normal and abnormal tissues is calculated based on information derived from the atlas and ROI. Finally, geodesic active contours use the probability map of the tumor to shrink the ROI until optimal tumor boundaries are found. This method was validated against the true segmentation (TS) of 30 LGG patients for both 2D (1 slice) and 3D. The TS was obtained from manual segmentations of three experts using the Simultaneous Truth and Performance Level Estimation (STAPLE) software. Dice and Jaccard indices and other descriptive statistics were computed for the proposed method, as well as the experts' segmentation versus the TS. We also tested the method with the BraTS datasets, which supply expert segmentations. For 2D segmentation vs. TS, the mean Dice index was 0.90 ± 0.06 (standard deviation), sensitivity was 0.92, and specificity was 0.99. For 3D segmentation vs. TS, the mean Dice index was 0.89 ± 0.06, sensitivity was 0.91, and specificity was 0.99. The automated results are comparable with the experts' manual segmentation results. We present an accurate, robust, efficient, and reproducible segmentation method for pre-operative LGGs.


The Addition of Platelet-Rich Plasma to Scaffolds Used for Cartilage Repair: A Review of Human and Animal Studies.
To review the available literature on studies focusing on platelet-rich plasma (PRP)-enhanced scaffolds for cartilage lesion repair in animals and to analyze the clinical outcomes of similar biologically augmented cartilage regeneration techniques in humans. We conducted a literature search and subsequent review investigating the potential of PRP to enhance articular cartilage repair using scaffolds or bioengineered implants. Of the 14 animal model studies reviewed, 10 reported positive effects with PRP whereas only 2 showed negative overall effects. The remaining 2 studies reported no significant differences, or neutral results, with the use of PRP. With the addition of PRP, the gross appearance and histologic analysis of repair cartilage were improved or no difference was seen compared with control (11 of 12 studies that looked at this). Human studies of the knee or talar dome showed improvements in clinical assessment scores as soon as 6 months after surgery. There was great variability in the method of PRP preparation, choice of scaffold, and cell source between studies. PRP-augmented scaffolds have been shown to be beneficial in the articular cartilage repair process in animals and humans based on macroscopic, histologic, and biochemical analysis and based on clinical outcome scores, respectively. Comparison between studies is difficult because there is great variability in PRP preparation and administration. Level IV, systematic review of Level III and IV studies.


High Variability in Cellular Stoichiometry of Carbon, Nitrogen, and Phosphorus Within Classes of Marine Eukaryotic Phytoplankton Under Sufficient Nutrient Conditions.
Current hypotheses suggest that cellular elemental stoichiometry of marine eukaryotic phytoplankton such as the ratios of cellular carbon:nitrogen:phosphorus (C:N:P) vary between phylogenetic groups. To investigate how phylogenetic structure, cell volume, growth rate, and temperature interact to affect the cellular elemental stoichiometry of marine eukaryotic phytoplankton, we examined the C:N:P composition in 30 isolates across 7 classes of marine phytoplankton that were grown with a sufficient supply of nutrients and nitrate as the nitrogen source. The isolates covered a wide range in cell volume (5 orders of magnitude), growth rate (<0.01-0.9 d-1), and habitat temperature (2-24°C). Our analysis indicates that C:N:P is highly variable, with statistical model residuals accounting for over half of the total variance and no relationship between phylogeny and elemental stoichiometry. Furthermore, our data indicated that variability in C:P, N:P, and C:N within Bacillariophyceae (diatoms) was as high as that among all of the isolates that we examined. In addition, a linear statistical model identified a positive relationship between diatom cell volume and C:P and N:P. Among all of the isolates that we examined, the statistical model identified temperature as a significant factor, consistent with the temperature-dependent translation efficiency model, but temperature only explained 5% of the total statistical model variance. While some of our results support data from previous field studies, the high variability of elemental ratios within Bacillariophyceae contradicts previous work that suggests that this cosmopolitan group of microalgae has consistently low C:P and N:P ratios in comparison with other groups.


Genotypic and phenotypic characterization of genetic differentiation and diversity in the USDA rice mini-core collection.
A rice mini-core collection consisting of 217 accessions has been developed to represent the USDA core and whole collections that include 1,794 and 18,709 accessions, respectively. To improve the efficiency of mining valuable genes and broadening the genetic diversity in breeding, genetic structure and diversity were analyzed using both genotypic (128 molecular markers) and phenotypic (14 numerical traits) data. This mini-core had 13.5 alleles per locus, which is the most among the reported germplasm collections of rice. Similarly, polymorphic information content (PIC) value was 0.71 in the mini-core which is the highest with one exception. The high genetic diversity in the mini-core suggests there is a good possibility of mining genes of interest and selecting parents which will improve food production and quality. A model-based clustering analysis resulted in lowland rice including three groups, aus (39 accessions), indica (71) and their admixtures (5), upland rice including temperate japonica (32), tropical japonica (40), aromatic (6) and their admixtures (12) and wild rice (12) including glaberrima and four other species of Oryza. Group differentiation was analyzed using both genotypic distance Fst from 128 molecular markers and phenotypic (Mahalanobis) distance D(2) from 14 traits. Both dendrograms built by Fst and D(2) reached similar-differentiative relationship among these genetic groups, and the correlation coefficient showed high value 0.85 between Fst matrix and D(2) matrix. The information of genetic and phenotypic differentiation could be helpful for the association mapping of genes of interest. Analysis of genotypic and phenotypic diversity based on genetic structure would facilitate parent selection for broadening genetic base of modern rice cultivars via breeding effort.


Three randomized clinical trials to assess the short-term efficacy of anhydrous 0.454% w/w stannous fluoride dentifrices for the relief of dentin hypersensitivity.
To assess the short-term efficacy of dentifrices containing 0.454% weight/weight (w/w) stannous fluoride applied using a focused brushing methodology for the relief of dentin hypersensitivity (DH). Three randomized, examiner blind, controlled, two treatment arm, parallel group studies were conducted utilizing a novel application method in which, prior to brushing the whole mouth, the stannous fluoride dentifrice was applied to two sensitive teeth by focused brushing. DH was assessed with an evaporative (air) stimulus (with the Schiff Sensitivity Scale and a Visual Analogue Scale [VAS, Studies 1 and 3 only]) and a tactile stimulus (using a Yeaple Probe). Clinical assessments were made at baseline, immediately after first use of study dentifrice and after 3 and 14 days of twice daily brushing. Study 1 compared a marketed 0.454% w/w stannous fluoride dentifrice indicated for short-term DH relief to a marketed standard fluoride dentifrice (negative control). Studies 2 and 3 compared a novel anhydrous 0.454% w/w stannous fluoride dentifrice to the same negative control. For Studies 1, 2 and 3, 118, 113 and 120 subjects respectively were randomized to treatment and included in the intent-to-treat populations. Study 1 showed significant DH improvements in all measures for the test dentifrice compared to the negative control at Day 14. Study 2 showed significant differences in favor of the test dentifrice for all measures at all time points (Immediate, Days 3 and 14). In Study 3, treatment with both test and control dentifrices resulted in significant improvements over baseline, but there were no significant between-treatment differences. While these studies provide evidence for relief of DH with 0.454% w/w stannous fluoride dentifrices after short-term use (14 days) using a novel focused brushing methodology, the evidence, especially at the earliest time points, is inconclusive and further testing is needed. Study dentifrices were well tolerated. ClinicalTrials.gov trial registration numbers: Study 1 NCT01494649; Study 2: NCT01592851; Study 3: NCT01724008; funded by GSK Consumer Healthcare.


Fabrication and 3D tomographic characterization of nanowire arrays and meshes with tunable dimensions from shear-aligned block copolymers.
We demonstrate a scalable method to create metallic nanowire arrays and meshes over square-centimeter-areas with tunable sub-100 nm dimensions and geometries using the shear alignment of block copolymers. We use the block copolymer poly(styrene)-b-poly(2-vinyl pyridine) (PS-P2VP) since the P2VP block complexes with metal salts like Na2PtCl4, thereby enabling us to directly pattern nanoscale platinum features. We investigate what shear alignment processing parameters are necessary to attain high quality and well-ordered nanowire arrays and quantify how the block copolymer's molecular weight affects the resulting Pt nanowires' dimensions and defect densities. Through systematic studies of processing parameters and scanning transmission electron microscopy (STEM) tomography, we determine that the equivalent of 2-3 monolayers of PS-P2VP are required to produce a single layer of well-aligned nanowires. The resulting nanowires' widths and heights can be tuned between 11-27 nm and 9-50 nm, respectively, and have periodicites varying between 37 and 63 nm, depending on the choice of block copolymer molecular weight. We observe that the height-to-width ratio of the nanowires also increases with molecular weight, reaching a value of almost 2 with the largest dimensions fabricated. Furthermore, we demonstrate that an additional layer of Pt nanowires can be orthogonally aligned on top of and without disturbing an underlying layer, thereby enabling the fabrication of Pt nanowire meshes with tunable sub-100 nm dimensions and geometries over a cm2-area.