Polyvinylidene Fluoride Membrane with a Polyvinylpyrrolidone Additive for Tofu Industrial Wastewater Treatment in Combination with the Coagulation-Flocculation Process.
Wastewater from the tofu industry contains many pollutants that are very harmful to the environment, significantly endangering aquatic life and producing a pungent odor. This study aims to prepare a polyvinylidene fluoride (PVDF) membrane with the additive polyvinylpyrrolidone (PVP), and utilize it to treat tofu wastewater in the ultrafiltration (UF) process. Flat sheet membranes were prepared using PVDF that was dissolved in N,N-dimethylacetamide (DMAc) and then combined with the additive material of PVP at the varying compositions of 14.9/0.1, 14.85/0.15, and 14.8/0.2 g of PVDF/gram of PVP. The addition of PVP was proposed to improve the properties of the membranes. Characterization by scanning electron microscope (SEM), water contact angle, and Fourier transform infrared spectroscopy (FTIR) were performed on the PVDF/PVP membrane flat sheet in order to understand and compare changes in the physical and chemical properties that occurred in the membrane. Prior to the UF process, the tofu wastewater was treated by a coagulation-flocculation process through a jar tester using poly aluminum chloride (PAC) as a coagulant. Based on the membrane characterization, the addition of PVP improved the physical and chemical properties of membranes. The pore size of the membrane becomes larger, which could increase permeability as well as the flux value. The TSS and turbidity of the water produced in the UF process decreased with an increase in feed pressure due to a greater driving force generated to facilitate the penetration of the suspended solids. The UF results showed that the effect of PVP on water flux was greatest for the 14.85/0.15 PVDF/PVP membrane for both pure and wastewater. In addition, the highest percentage of rejection for TSS and turbidity were observed in the 14.9/0.1 PVDF/PVP membrane and rejection for TDS was indicated in the 14.8/0.2 PVDF/PVP membrane. Meanwhile, the resulting pH decreased slightly across all samples as feed pressure increased.


Stability of Phase Relationships While Coordinating Arm Reaches with Whole Body Motion.
The human movement repertoire is characterized by the smooth coordination of several body parts, including arm movements and whole body motion. The neural control of this coordination is quite complex because the various body parts have their own kinematic and dynamic properties. Behavioral inferences about the neural solution to the coordination problem could be obtained by examining the emerging phase relationship and its stability. Here, we studied the phase relationships that characterize the coordination of arm-reaching movements with passively-induced whole-body motion. Participants were laterally translated using a vestibular chair that oscillated at a fixed frequency of 0.83 Hz. They were instructed to reach between two targets that were aligned either parallel or orthogonal to the whole body motion. During the first cycles of body motion, a metronome entrained either an in-phase or an anti-phase relationship between hand and body motion, which was released at later cycles to test phase stability. Results suggest that inertial forces play an important role when coordinating reaches with cyclic whole-body motion. For parallel reaches, we found a stable in-phase and an unstable anti-phase relationship. When the latter was imposed, it readily transitioned or drifted back toward an in-phase relationship at cycles without metronomic entrainment. For orthogonal reaches, we did not find a clear difference in stability between in-phase and anti-phase relationships. Computer simulations further show that cost models that minimize energy expenditure (i.e. net torques) or endpoint variance of the reach cannot fully explain the observed coordination patterns. We discuss how predictive control and impedance control processes could be considered important mechanisms underlying the rhythmic coordination of arm reaches and body motion.


Suitability of eigenvalue beam-forming for discrete multi-frequency hyperthermia treatment planning.
Thermal dose delivery in microwave hyperthermia for cancer treatment is expected to benefit from the introduction of ultra-wideband (UWB)-phased array applicators. A full exploitation of the combination of different frequencies to improve the deposition pattern is, however, a nontrivial problem. It is unclear whether the cost functions used for hyperthermia treatment planning (HTP) optimization in the single-frequency setting can be meaningfully extended to the UWB case. We discuss the ability of the eigenvalue (EV) and a novel implementation of iterative-EV (i-EV) beam-forming methods to fully exploit the available frequency spectrum when a discrete set of simultaneous operating frequencies is available for treatment. We show that the quadratic power deposition ratio solved by the methods can be maximized by only one frequency in the set, therefore rendering EV inadequate for UWB treatment planning. We further investigate whether this represents a limitation in two realistic test cases, comparing the thermal distributions resulting from EV and i-EV to those obtained by optimizing for other nonlinear cost functions that allow for multi-frequency. The classical EV-based single-frequency HTP yields systematically lower target SAR deposition and temperature values than nonlinear HTP. In a larynx target, the proposed single-frequency i-EV scheme is able to compensate for this and reach temperatures comparable to those given by global nonlinear optimization. In a meninges target, the multi-frequency setting outperforms the single-frequency one, achieving better target coverage and 0 . 5 ∘ C higher T 90 in the tumor than single-frequency-based HTP. Classical EV performs poorly in terms of resulting target temperatures. The proposed single-frequency i-EV scheme can be a viable option depending on the patient and tumor to be treated, as long as the proper operating frequency can be selected across a UWB range. Multi-frequency HTP can bring a considerable benefit in regions typically difficult to treat such as the brain.


Mechanical Response of Porcine Liver Tissue under High Strain Rate Compression.
In automobile accidents, abdominal injuries are often life-threatening yet not apparent at the time of initial injury. The liver is the most commonly injured abdominal organ from this type of trauma. In contrast to current safety tests involving crash dummies, a more detailed, efficient approach to predict the risk of human injuries is computational modelling and simulations. Further, the development of accurate computational human models requires knowledge of the mechanical properties of tissues in various stress states, especially in high-impact scenarios. In this study, a polymeric split-Hopkinson pressure bar (PSHPB) was utilized to apply various high strain rates to porcine liver tissue to investigate its material behavior during high strain rate compression. Liver tissues were subjected to high strain rate impacts at 350, 550, 1000, and 1550 s-1. Tissue directional dependency was also explored by PSHPB testing along three orthogonal directions of liver at a strain rate of 350 s-1. Histology of samples from each of the three directions was performed to examine the structural properties of porcine liver. Porcine liver tissue showed an inelastic and strain rate-sensitive response at high strain rates. The liver tissue was found lacking directional dependency, which could be explained by the isotropic microstructure observed after staining and imaging. Furthermore, finite element analysis (FEA) of the PSHPB tests revealed the stress profile inside liver tissue and served as a validation of PSHPB methodology. The present findings can assist in the development of more accurate computational models of liver tissue at high-rate impact conditions allowing for understanding of subfailure and failure mechanisms.


Additional droperidol, not butorphanol, augments epidural fentanyl analgesia following anorectal surgery.
To examine the effects of additional droperidol or butorphanol to epidural fentanyl infusion on postsurgical analgesia. Prospective, randomized, single blinded clinical study. University-affiliated medical center. 60 ASA physical status I and II patients undergoing anorectal surgery by one surgeon. Patients were randomly allocated to the following groups according to the medication that was continuously administered into the epidural space: 1) Group C (n = 20) received 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; 2) Group D (n = 20) received 2.5 mg droperidol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine; and 3) Group B (n = 20) received 2 mg butorphanol and 0.4 mg fentanyl in 40 ml of 0.125% bupivacaine over 24 hours postoperatively. Postsurgical analgesia and the incidence of fentanyl-related complications, such as nausea/vomiting, somnolence, pruritus, and respiratory depression, were assessed for 24 hours postoperatively. At 16 and 24 hours after surgery, 75% of patients in Group D reported no pain versus 35% in Group C (p < 0.05). In addition, the overall visual analogue scale examined at 24 hours was significantly lower in Group D than that in Group C (22 +/- 17 mm vs. 44 +/- 22 mm, respectively; p < 0.05). Simultaneously, the incidence of postoperative nausea/vomiting was lower in Group D compared with Group C (20% vs. 60%; p < 0.05). On the other hand, butorphanol did not modify the analgesic effects or complications of epidural fentanyl infusion. In this study population, additional droperidol, not butorphanol, improved postsurgical analgesia accompanied by less incidence of nausea/vomiting during epidural fentanyl administration.


Epigenetics of Autism Spectrum Disorder.
Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development. In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.


A facile reaction of imines with telluronium allylide. Highly stereoselective synthesis of vinylaziridines.
The reaction of telluronium allylides with alkylimines, generated in situ from alpha-amidoalkyl sulfones, affords cis-alkylvinylarizidines with good stereoselectivity in good yields. However, the same ylides react with N-aryl imines to provide trans-vinylaziridines.


Comanagement of surgical patients between neurosurgeons and hospitalists.
Shared management of surgical patients between surgeons and hospitalists (comanagement) is increasingly common, yet few studies have described its effects. Retrospective, interrupted time-series analysis of data collected from adults admitted to a neurosurgery service at our university-based teaching hospital between June 1, 2005, and December 31, 2008. Data regarding length of stay, costs, inpatient mortality rate, and 30-day readmission rate were collected from administrative sources; patient and caregiver satisfaction was assessed through surveys. We used multivariable models to estimate the effect of comanagement on key outcomes after adjusting for secular trends and patient-specific risk factors. During the study period, 7596 patients were admitted to the neurosurgery service: 4203 (55.3%) before July 1, 2007, and 3393 (44.7%) after comanagement began. Of those admitted during the postimplementation period, 988 (29.1%) were comanaged. After implementation of comanagement, no differences were found in patient mortality rate, readmission, or length of stay. No consistent improvements were seen in patient satisfaction, but strong perceived improvements occurred in care quality reported by nurses and nonnurse health care professionals. In addition, we observed a reduction in hospital costs of $1439 per admission. Implementation of a hospitalist comanagement service had little effect on patient outcomes or satisfaction but appeared to reduce hospital costs and improve health care professionals' perceptions of care quality. As comanagement models are adopted, more emphasis should be placed on developing systems that improve patient outcomes.


Human heterophilic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration.
The presence of human heterophilic antibodies against horse immunoglobulins (HHA-HI) was determined by ELISA in sera from healthy volunteers and from patients who received equine antivenom for therapy of snake bite envenoming. These patients were selected from two independent clinical studies: one in Colombia in which patients received antivenom constituted by whole IgG (n=25); and the other in Brazil where an antivenom constituted by F(ab')(2) fragments was administered (n=31). Results show that healthy volunteers have antibodies, mainly of the IgG class, able to react with whole equine IgG. Additionally, patients have IgG antibodies that react both with whole equine IgG and F(ab')(2) fragments. In both clinical studies, no significant differences were observed in the HHA-HI titres between the patients who presented early adverse (anaphylactoid) reactions and those who did not develop them. In addition, no variation in titre was observed in samples collected before and after antivenom administration. These results do not support the hypothesis that the incidence of early adverse reactions to antivenom administration correlates with the titre of HHA-HI in the serum of patients. Nevertheless, participation of these antibodies as part of a multifactorial pathogenic mechanism associated with these reactions cannot be ruled out.


Dpp-mediated TGF-β signaling regulates vitellogenesis through 20-hydroxyecdysone signaling in the cabbage beetle, Colaphellus bowringi.
The Dpp signaling, as one of the branches within the TGF-β superfamily, plays a crucial role in regulating various biological processes in insects. However, its impact on female reproduction through vitellogenesis remains unclear. In this study, the expression profiles implied that the Dpp signaling genes, including Dpp, Punt, Mad, and Medea, were up-regulated during reproductive development in the ovary of Colaphellus bowringi. Knockdown of these five Dpp signaling genes revealed significant effects of Dpp, Tkv, Mad, and Medea on ovarian development through vitellogenesis in the fat body. Our finding further indicated that Dpp signaling influences the expression of 20-hydroxyecdysone (20E) receptor and responsive genes in the fat body. Additionally, knockdown of 20E receptor EcR resulted in similar phenotypes as observed in the Dpp pathway genes knockdown, implying a regulatory role for Dpp signaling via EcR in vitellogenesis. Furthermore, knocking down Dpp, Tkv, and EcR in female adults led to a reduction in total dry weight and protein content, as well as the expression of mTOR, a factor linked to protein intake. These results suggest that the Dpp signaling pathway modulates vitellogenesis by impacting the AA/TOR-mediated 20E pathway in the fat body, providing novel insights into the network governing insect reproduction and offering potential targets for controlling female pest reproduction.


Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration.
The pharmacokinetic properties of pradofloxacin and doxycycline were investigated in serum, saliva, and tear fluid of cats. In a crossover study design, six cats were treated orally with a single dose of pradofloxacin (Veraflox Oral Suspension 2.5%) and doxycycline (Ronaxan 100 mg) at 5 mg/kg body weight. Following administration, samples of serum, saliva, and tear fluid were taken in regular intervals over a period of 24 h and analysed by turbulent flow chromatography/tandem mass spectrometry. All values are given as mean +/- SD. Pradofloxacin reached a mean maximum serum concentration (C(max)) of 1.1 +/- 0.5 microg/mL after 1.8 +/- 1.3 h (t(max)). In saliva and tear fluid, mean C(max) was 6.3 +/- 7.0 and 13.4 +/- 20.9 microg/mL, respectively, and mean t(max) was 0.5 +/- 0 and 0.8 +/- 0.3 h, respectively. Doxycycline reached a mean C(max) in serum of 4.0 +/- 0.8 microg/mL after 4.3 +/- 3.2 h. Whilst only at two time-points doxycycline concentrations close to the limit of quantification were determined in tear fluid, no detectable levels were found in saliva. The high concentrations of pradofloxacin in saliva and tear fluid are promising to apply pradofloxacin for the treatment of conjunctivitis and upper respiratory tract infections in cats. As doxycycline is barely secreted into these fluids after oral application the mechanisms of its clinical efficacy remain unclear.


Zinc metalloenzymes as new targets against the bacterial pathogen Brucella.
Brucella, a facultative intracellular pathogen, is one of the most common zoonotic diseases worldwide. Considering the alarming health problem caused by the emergence of resistance and multi-resistance of intracellular pathogen, the challenge is currently to identify and to validate novel pharmaceutical targets in this bacteria species. Brucella's genome encodes metalloproteins involved in various biosynthetic processes, some of them being essential during intracellular growth phase and virulence. The potential of prokaryotic zinc metalloproteins such as carbonic anhydrase (CA) and histidinol dehydrogenase (HDH) as anti-Brucella targets has only recently been taken into consideration in the search of novel anti-infective agents that lack of cross-resistance to existing drugs. These enzymes have a growing significance in modern medicine as they are required for growth and/or virulence in several intracellular pathogen species. This review illustrates and describes the progress which has been made in the design and the discovery of selective inhibitors of these bacterial enzymes as new potential anti-Brucella agents.


Integrating particle image velocimetry and laser Doppler velocimetry measurements of the regurgitant flow field past mechanical heart valves.
This study investigates the transient regurgitant flow downstream of a prosthetic heart valve using both laser Doppler velocimetry (LDV) and particle image velocimetry (PIV). Until now, LDV has been the more commonly used tool in investigating the flow characteristics associated with mechanical heart valves. The LDV technique allows point-by-point velocity measurements and provides enough information about the temporal variations in the flow. The main drawback of this technique is the time consuming nature of the data acquisition process in order to assess an entire flow field area. The PIV technique, on the other hand, allows measurement of the entire flow field in space in a plane at a given instant. In this study, PIV with spatial resolution of 0 (1 mm) and LDV with a temporal resolution of 0 (1 ms) were used to measure the regurgitant flow proximal to the Björk-Shiley monostrut (BSM) valve in the mitral position. With PIV, the ability to measure 2 velocity components over an entire plane simultaneously provides a very different insight into the flow field compared to a more traditional point-to-point technique like LDV. In this study, a picture of the effects of occluder motion on the fluid flow in the atrial chamber is interpreted using an integration of PIV and LDV measurements. Specifically, fluid velocities in excess of 3.0 m/s were recorded in the pressure-driven jet during valve closure, and a 1.5 m/s sustained regurgitant jet was observed on the minor orifice side. Additionally, the effects of the impact and subsequent rebound of the occluder on the flow also were clearly recorded in spatial and temporal detail by the PIV and LDV measurements, respectively. The PIV results provide a visually intuitive way of interpreting the flow while the LDV data explore the temporal variations and trends in detail. This analysis is an integrated flow description of the effects of valve closure and leakage on the pulsatile regurgitation flow field past a tilting-disc mechanical heart valve (MHV). It further reinforces the hypothesis that the planar flow visualization techniques, when integrated with traditional point-to point techniques, provide significantly more insight into the complex pulsatile flow past MHVs.


A pathway for predation in the brain of the barn owl (Tyto alba): projections of the gracile nucleus to the "claw area" of the rostral wulst via the dorsal thalamus.
The Wulst of birds, which is generally considered homologous with the isocortex of mammals, is an elevation on the dorsum of the telencephalon that is particularly prominent in predatory species, especially those with large, frontally placed eyes, such as owls. The Wulst, therefore, is largely visual, but a relatively small rostral portion is somatosensory in nature. In barn owls, this rostral somatosensory part of the Wulst forms a unique physical protuberance dedicated to the representation of the contralateral claw. Here we investigate whether the input to this "claw area" arises from dorsal thalamic neurons that, in turn, receive their somatosensory input from the gracile nucleus. After injections of biotinylated dextran amine into the gracile nucleus and cholera toxin B chain into the claw area, terminations from the former and retrogradely labeled neurons from the latter overlapped substantially in the thalamic nucleus dorsalis intermedius ventralis anterior. These results indicate the existence in this species of a "classical" trisynaptic somatosensory pathway from the body periphery to the telencephalic Wulst, via the dorsal thalamus, one that is likely involved in the barn owl's predatory behavior. The results are discussed in the context of somatosensory projections, primarily in this and other avian species.


Occupational acute anaphylactic reaction to assault by perfume spray in the face.
Perfumes have been associated with rashes in employees exposed to scented soaps or with allergic conditions, such as rhinitis or asthma, in employees exposed to perfumes or fragrances in the air. Reported here is a case of an anaphylactic reaction and respiratory distress as a result of a deliberate assault with a perfume spray. The medical literature was searched using the key words "fragrances," "respiratory distress," "assault," and "health care workers." A female medical assistant with no history of asthma or reactions to fragrances was assaulted by a patient, who pumped three sprays of a perfume into her face. The employee experienced an acute anaphylactic reaction with shortness of breath, a suffocating sensation, wheezes, and generalized urticaria, and required aggressive medical treatment, a long period of oral bronchodilator therapy, and, finally, weaning from the medications. Perfumes are complex mixtures of more than 4,000 vegetable and animal extracts and organic and nonorganic compounds. Fragrances have been found to cause exacerbations of symptoms and airway obstruction in asthmatic patients, including chest tightening and wheezing, and are a common cause of cosmetic allergic contact dermatitis. In many work settings the use of fragrances is limited. Assault is becoming more common among workers in the health care setting. Workers should be prepared to take immediate steps should an employee go into anaphylactic shock.


Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT.
Recent advances in treatment of metastatic renal cell carcinoma (RCC), such as new molecular therapies that use novel antiangiogenic agents, have led to revision of the most frequently used guideline to evaluate tumor response to therapy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of newer antiangiogenic therapies is more cytostatic than cytotoxic, which leads to disease stabilization rather than to tumor regression. This change in tumor response makes RECIST 1.1--a system whose criteria are based exclusively on tumor size--inadequate to discriminate patients with early tumor progression from those with more progression-free disease and prolonged survival. New criteria such as changes in attenuation, morphology, and structure, as seen at contrast-enhanced multidetector computed tomography (CT), are being incorporated into new classifications used to assess response of metastatic RCC to antiangiogenic therapies. The new classifications provide better assessments of tumor response to the new therapies, but they have some limitations. The authors provide a practical review of these systems--the Choi, modified Choi, and Morphology, Attenuation, Size, and Structure (MASS) criteria--by explaining their differences and limitations that may influence the feasibility and reproducibility of these classifications. The authors review the use of multidetector CT in the detection of metastatic RCC and the different appearances and locations of these lesions. They also provide an overview of the new antiangiogenic therapies and their mechanisms of action and a brief introduction to functional imaging techniques. Functional imaging techniques, especially dynamic contrast-enhanced CT, seem promising for assessing response of metastatic RCC to treatment. Nonetheless, further studies are needed before functional imaging can be used in routine clinical practice.


Late blight resistance linkages in a novel cross of the wild potato species Solanum paucissectum (series Piurana).
The cultivated potato, Solanum tuberosum, is affected by a variety of diseases with late blight, caused by Phytophthora infestans, being the most severe. Wild potato species have proven to be a continuing source of resistance, sometimes of an extreme type, to this disease. The present study constructs the first late blight linkage map of a member of series Piurana, S. paucissectum, a tuber-bearing relative of potato, using probes for conserved sequences from potato and tomato. Eight probes mapped to unexpected linkage groups, but syntenic differences with prior maps of potato were not supported by any blocks of rearranged chromosome segments. All 12 linkage groups were resolved and significant associations with late blight resistance were found on chromosomes 10, 11 and 12. A major quantitative trait locus (QTL) on chromosome 11 accounts for more than 25% of the phenotypic variance measured in a field trial. Crossing of S. paucissectum with cultivated potato resulted in very few seeds indicating partial reproductive barriers. Differential reactions of accessions of this potential donor species with simple and complex isolates of P. infestans suggest that it carries major resistance genes that are not those previously described from the Mexican species, S. demissum. However, the additivity of the QTL effects argues for the quantitative nature of resistance in this cross.


Perception of overweight and self-esteem during adolescence.
To examine sex- and race/ethnicity-specific relationships between adolescents' self-esteem and weight perception. Descriptive analysis and logistic regression of Wave II of the National Longitudinal Study of Adolescent Health (N = 6,427 males, 6,574 females; ages 11-21) examined associations between low self-esteem and perceived overweight within body mass index (BMI) percentile categories, controlling for sociodemographics and stratified by sex and race/ethnicity. 25.1% and 8% of normal weight females and males, respectively, perceived themselves as overweight, with variation by race/ethnicity. Low self-esteem was most strongly associated with misperceived overweight in moderate BMI percentile categories (males: OR = 2.34; 95% CI: 1.60-3.41; females: OR = 2.39; 95% CI: 1.82, 3.16). Odds of correctly perceived overweight were higher for low (versus high) self-esteem in white and black females but not males of any race/ethnicity. Understanding subgroup differences by race/ethnicity in perceived overweight-self-esteem relationships may inform eating disorders' prevention strategies.


The impacts of climate change on groundwater quality: A review.
Groundwater has been known as the second largest freshwater storage in the world, following surface water. Over the years, groundwater has already been under overwhelming pressure to satisfy human needs for artificial activities around the world. Meanwhile, the most noticeable footprint of human activities is the impact of climate change. Climate change has the potential to change the physical and chemical properties of groundwater, thereby affecting its ecological functions. This study summarizes existing research affiliated with the possible effects of a changing climate on the quality of groundwater, including changes in water availability, increased salinity and pollution from extreme weather events, and the potentiality of seawater intrusion into coastal aquifers. Previous works dealing with groundwater-induced responses to the climate system and climate impacts on groundwater quality through natural and anthropogenic processes have been reviewed. The climate-induced changes in groundwater quality including pH, dissolved oxygen level, salinity, and concentrations of organic and inorganic compounds were assessed. Some future research directions are proposed, including exploring the potential changes in the occurrences and fate of micropollutants in groundwater, examining the relationship between the increase of microcystin in groundwater and climate change, studying the changes in the stability of metals and metal complexation, and completing studies across different regional climate regions.


Soluble receptor for advanced glycation end-products and progression of airway disease.
The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role. Reduced plasma levels of soluble RAGE (sRAGE) have been reported in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the association of plasma sRAGE levels with a longitudinal decline of lung function. We have also measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD. Baseline plasma concentrations of sRAGE and HMGB1 were measured in non-smokers (n = 32), smokers without COPD (n = 212), and smokers with COPD (n = 51), and the associations of the plasma sRAGE and HMGB1 levels with longitudinal declines of lung function during a 4-year follow-up period were analysed. The plasma levels of sRAGE were significantly lower in smokers without COPD and in smokers with COPD, as compared to those of non-smokers. Plasma sRAGE levels positively correlated with FVC and FEV1 and inversely correlated with BMI and pack-years. Lower sRAGE levels were associated with greater declines of FEV1/FVC over 4 years in all participants. Moreover, multivariate regression analysis indicated that the baseline plasma sRAGE concentration was an independent predictor of FEV1/FVC decline in all groups. A subgroup analysis showed that decreased sRAGE levels are significantly associated with a more rapid decline of FEV1/FVC in smokers with COPD. There was no significant correlation between plasma HMGB1 levels and longitudinal decline of lung function. Lower plasma concentrations of sRAGE were associated with greater progression of airflow limitations over time, especially in smokers with COPD, suggesting that RAGE might have a protective role in the lung.


DIEP flap donor site versus elective abdominoplasty short-term complication rates: a meta-analysis.
Although over the past decade the DIEP flap has emerged as one of the preferred choices for autologous breast reconstruction and the donor-site closure has much in common with the standard abdominoplasty technique, reports on comparisons of the complication rates between DIEP and elective abdominoplasty patients are not currently available. The purpose of this study was to compare DIEP donor-site and elective abdominoplasty short-term complications rates, in support of surgical choices. Searches of MEDLINE and CENTRAL for English language articles on DIEP and elective abdominoplasty (EA) published from January 1999 through December 2009 identified 33 studies that met the inclusion criteria and included 3,937 patients. A random-effects model was used to calculate the average complication rate in the literature. The rate of seroma/hematoma in EA (16.1%, 95% confidence interval [CI] = 12.2-20.9%) was approximately four times the rate in DIEP flap patients (3.7%, 95% CI = 1.5-8.8%) was found from analyzing the data under a random-effects model. No substantial differences in the rates of infection, abdominal/umbilical necrosis, or wound dehiscence/delayed healing between the two series of patients were detected. This meta-analysis reveals that DIEP donor-site complication rates were comparable to those in elective abdominoplasty, and, the rate of seroma in DIEP is an even lower than that of one of the most performed procedures in plastic surgery. We argue that patients presenting for a DIEP flap should be informed about this interesting comparison.


Design of correlation filters for recognition of linearly distorted objects in linearly degraded scenes.
Generalized correlation filters are proposed to improve recognition of a linearly distorted object embedded in a nonoverlapping background when the input scene is degraded with a linear system and additive noise. Several performance criteria defined for the nonoverlapping signal model are used for the design of filters. The derived filters take into account information about an object to be recognized, disjoint background, noise, and linear degradations of the target and the input scene. Computer simulation results obtained with the proposed filters are discussed and compared with those of various correlation filters in terms of discrimination capability, location errors, and tolerance to input noise.


Circulatory, respiratory and behavioral responses in isoflurane anesthetized llamas.
To evaluate the circulatory, respiratory and behavioral effects of isoflurane (ISO) anesthesia in llamas during mechanical ventilation and spontaneous breathing. Prospective randomised study. Six adult, neutered male llamas (10 ± 1 years [mean ± SD], 179 ± 32 kg). Animals in which the minimum alveolar concentration (MAC) had been previously determined were anesthetized with ISO in oxygen. Inspired and end-tidal (ET) ISO were sampled continuously. Arterial blood pH, respiratory and circulatory variables, and clinical signs of anesthesia were recorded at three doses (1.0, 1.5 and 2.0 times the individual animal's MAC; mean MAC value 1.13%) of ISO during spontaneous and controlled ventilation. A series of Latin squares was used to determine order of dose. Controlled ventilation (CV) (target PaCO2 38 ± 5 mm Hg [5.0 ± 0.6 kPa]) preceded spontaneous ventilation (SV) at each dose. Animals breathed spontaneously for approximately 10 minutes prior to data collection. Body temperature was maintained at 37 ± 0.6 °C. Circulatory and respiratory data were analysed with a mixed model, least squares analysis of variance, for repeated measures taken at equally spaced intervals. p < 0.05. Dose and mode of ventilation had significant influences on measured variables. For example, heart rate increased as dose increased; 67 ± 14 beats minute-1 at 1.0 MAC-CV versus 77 ± 6 beats minute-1 at 2 MAC-CV. Conversely, mean arterial pressure decreased with increasing dose; 82 ± 13 mm Hg at MAC-CV versus 52 ± 15 mm Hg at 2 MAC-CV. Arterial CO2 increased with increasing dose during SV; 45 ± 5 mm Hg [6 ± 0.6 kPa] at MAC versus 53 ± 4 mmHg [7 ± 0.5 kPa] at 2 MAC. Reflex activity (e.g. palpebral reflex) and muscle tone (e.g. jaw tone) decreased while eyelid aperture increased with increasing anesthetic dose. The influence of ISO dose and mode of ventilation on circulatory and respiratory variables in llamas is qualitatively similar to that reported in other species. Changes in reflex activity and muscle tone may be used to guide appropriate anesthetic delivery in ISO-induced llamas.


The effects of local irradiation on circulating lymphocytes in dogs receiving fractionated radiotherapy.
Localized radiation therapy can be an effective treatment for cancer but is associated with localized and systemic side effects. Several studies have noted changes in complete blood count (CBC) parameters including decreases in the absolute lymphocyte count (ALC) and increases in the neutrophil:lymphocyte ratio (NLR). These changes could reflect immunosuppression and may contribute to decreased efficacy of immunotherapies used to treat cancer. We hypothesized that dogs would demonstrate decreased ALCs during a course of radiotherapy. A retrospective study was conducted on 203 dogs receiving definitive-intent radiotherapy. Demographic information, CBC values and details of the radiotherapy protocol were collected. The mean lymphocyte count pre-treatment was 1630.68 cells/μL (SD ± 667.56) with a mean NLR of 3.66 (SD ± 4.53). The mean lymphocyte count mid-treatment was 1251.07 cells/μL (SD ± 585.96) and the mean NLR was 6.23 (SD ± 4.99). There was a significant decrease in the mean lymphocyte count by 351.41 lymphocytes/μL (SD ± 592.32) between pre-treatment and mid-treatment (P < .0001), and a corresponding significant increase in the mean NLR of 0.93 (P = .02). Lymphopenia grade increased in 33.5% of dogs and was significant (P = .03). The ALC decrease was not correlated with the volume irradiated (P = .27), but correlated with the irradiated volume:body weight ratio (P = .03). A subset of patients (n = 35) with additional CBCs available beyond the mid-treatment time point demonstrated significant and sustained downward trends in the ALC compared with baseline. Although severe lymphopenia was rare, these decreases, especially if sustained, could impact adjuvant therapy for their cancer.


A lectin S-domain receptor kinase mediates lipopolysaccharide sensing in Arabidopsis thaliana.
The sensing of microbe-associated molecular patterns (MAMPs) triggers innate immunity in animals and plants. Lipopolysaccharide (LPS) from Gram-negative bacteria is a potent MAMP for mammals, with the lipid A moiety activating proinflammatory responses via Toll-like receptor 4 (TLR4). Here we found that the plant Arabidopsis thaliana specifically sensed LPS of Pseudomonas and Xanthomonas. We isolated LPS-insensitive mutants defective in the bulb-type lectin S-domain-1 receptor-like kinase LORE (SD1-29), which were hypersusceptible to infection with Pseudomonas syringae. Targeted chemical degradation of LPS from Pseudomonas species suggested that LORE detected mainly the lipid A moiety of LPS. LORE conferred sensitivity to LPS onto tobacco after transient expression, which demonstrated a key function in LPS sensing and indicated the possibility of engineering resistance to bacteria in crop species.


Two-part joint model for a longitudinal semicontinuous marker and a terminal event with application to metastatic colorectal cancer data.
Joint models for a longitudinal biomarker and a terminal event have gained interests for evaluating cancer clinical trials because the tumor evolution reflects directly the state of the disease. A biomarker characterizing the tumor size evolution over time can be highly informative for assessing treatment options and could be taken into account in addition to the survival time. The biomarker often has a semicontinuous distribution, i.e., it is zero inflated and right skewed. An appropriate model is needed for the longitudinal biomarker as well as an association structure with the survival outcome. In this article, we propose a joint model for a longitudinal semicontinuous biomarker and a survival time. The semicontinuous nature of the longitudinal biomarker is specified by a two-part model, which splits its distribution into a binary outcome (first part) represented by the positive versus zero values and a continuous outcome (second part) with the positive values only. Survival times are modeled with a proportional hazards model for which we propose three association structures with the biomarker. Our simulation studies show some bias can arise in the parameter estimates when the semicontinuous nature of the biomarker is ignored, assuming the true model is a two-part model. An application to advanced metastatic colorectal cancer data from the GERCOR study is performed where our two-part model is compared to one-part joint models. Our results show that treatment arm B (FOLFOX6/FOLFIRI) is associated to higher SLD values over time and its positive association with the terminal event leads to an increased risk of death compared to treatment arm A (FOLFIRI/FOLFOX6).


Knowledge Of Maintenance Intravenous Fluid Therapy In Acutely Ill Hospitalized Children Among Residents.
Isotonic saline is recommended as maintenance intravenous fluid therapy (MIVFT) for most of the acutely ill hospitalized children. The aim of this study is to assess the current knowledge of paediatric residents regarding the selection of MIVFT in hospitalized children. We conducted a paper-based questionnaire survey to paediatric residents from ten centres asking selection of MIVFT in four common clinical scenarios in 6-month and 10-year old patients as well as monitoring of fluid balance and electrolyte. 445 responses were collected (>90% response rate). Majority [78.3% (n=348)] of them were FCPS-trainees. The 0.9%, 0.45% and 0.2% solution were selected by 45.8%, 43.98% and 10.92% respectively. The isotonic and hypotonic solution was prescribed in 6- mo (35.22% vs. 64.76% [p<0.001]) and 10-year (54.49% vs. 44.98%) in four different clinical scenarios respectively. 0.45% solution was most commonly prescribed MIVFT in pneumonia (50.22%) and meningitis (45.39%) and 0.9% solution was most commonly selected in acute gastroenteritis (55.05%) and post-operative patients (51.23%). Fluid balance and electrolyte monitoring were selected by 96.9% and 55.7% respondents respectively. Our survey reports that more than fifty percent of paediatric residents have inadequate knowledge about maintenance intravenous fluid therapy in acutely ill hospitalized children.


Discovering breast cancer drug candidates from biomedical literature.
We developed a new paradigm with the ultimate goal of enabling disease-specific drug candidate discovery with molecular-level evidences generated from literature and prior knowledge. We showed how to implement the paradigm by building a prototype literature-mining framework and performing drug-protein association mining for breast cancer drug discovery. In a molecular pharmacology study of breast cancer, 79.2% of 729 enriched drugs in 'Organic Chemicals' category were validated to be disease-related, and the remaining 20.8% were also investigated as potential for future molecular therapeutics studies. 'Doxorubicin', 'Etoposide' and 'Paclitaxel' were identified as having similar pharmacological profiles to treat breast cancer.


Net primary productivity estimates and environmental variables in the Arctic Ocean: An assessment of coupled physical-biogeochemical models.
The relative skill of 21 regional and global biogeochemical models was assessed in terms of how well the models reproduced observed net primary productivity (NPP) and environmental variables such as nitrate concentration (NO3), mixed layer depth (MLD), euphotic layer depth (Zeu), and sea ice concentration, by comparing results against a newly updated, quality-controlled in situ NPP database for the Arctic Ocean (1959-2011). The models broadly captured the spatial features of integrated NPP (iNPP) on a pan-Arctic scale. Most models underestimated iNPP by varying degrees in spite of overestimating surface NO3, MLD, and Zeu throughout the regions. Among the models, iNPP exhibited little difference over sea ice condition (ice-free versus ice-influenced) and bottom depth (shelf versus deep ocean). The models performed relatively well for the most recent decade and toward the end of Arctic summer. In the Barents and Greenland Seas, regional model skill of surface NO3 was best associated with how well MLD was reproduced. Regionally, iNPP was relatively well simulated in the Beaufort Sea and the central Arctic Basin, where in situ NPP is low and nutrients are mostly depleted. Models performed less well at simulating iNPP in the Greenland and Chukchi Seas, despite the higher model skill in MLD and sea ice concentration, respectively. iNPP model skill was constrained by different factors in different Arctic Ocean regions. Our study suggests that better parameterization of biological and ecological microbial rates (phytoplankton growth and zooplankton grazing) are needed for improved Arctic Ocean biogeochemical modeling.


Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma.
Chronic aspiration associated with gastro oesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice. Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57. Chronic aspiration of 10 microL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity was associated with a trend toward decreased production of antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response. These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.


Genome-Wide Transcriptome Profiling Reveals Genes Associated with Meiotic Drive System of Aedes aegypti.
Aedes aegypti is an important mosquito vector of several arboviruses, including dengue, yellow fever, Zika, and Chikungunya, which cause significant human morbidity and mortality globally. In certain populations of this mosquito, a native meiotic drive system causes abnormal spermatogenesis that results in highly male-biased progenies from some matings. Although the basic genetics and cytogenetics of the drive mechanism were elucidated, very little is known on a transcriptome level about how the meiotic drive phenotype is expressed in individual males. To address this question, we conducted a whole-genome microarray expression study of testes from a meiotic-drive-carrying strain (T37) in comparison with testes from a non-drive-carrying strain (RED). Based on bioinformatics analyses of the microarray data, we identified 209 genes associated with the meiotic drive phenotype that were significantly differentially expressed between the two strains. K-means cluster analysis revealed nine clusters, in which genes upregulated in T37 testes were assigned to five clusters and genes downregulated in T37 testes were assigned to four clusters. Our data further revealed that genes related to protein translation, phosphorylation, and binding, as well as to G-protein-coupled receptor (GPCR) and peptidase activities, are differentially upregulated in testes from males with the meiotic drive genotype. Based on pathway analysis of these differentially expressed genes, it was observed that the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway may play a role in the meiotic drive system. Overall, this investigation enhances our understanding of whole-genome gene expression associated with the meiotic drive system in Ae. aegypti.


When focusing on differences leads to similar perspectives.
The current research investigated whether mind-sets and contexts that afford a focus on self-other differences can facilitate perceptual and conceptual forms of perspective taking. Supporting this hypothesis, results showed that directly priming a difference mind-set made perceivers more likely to spontaneously adopt other people's visual perspectives (Experiment 1) and less likely to overimpute their own privileged knowledge to others (Experiments 2 and 3). Given that intergroup encounters typically evoke a difference mind-set, we also explored the possibility that such contexts might help perceivers to step outside their own perspectives. As predicted, perceivers were less "cursed" by their own privileged knowledge when mentalizing about out-group targets than when mentalizing about in-group targets (Experiment 4) and communicated more effectively with interaction partners whose minimal-group membership differed from their own (Experiment 5). Overall, acknowledging self-other differences allowed perceivers to look beyond the limits of their own perspectives and thereby provided an efficacious route to intuiting other people's minds.


Brain dysfunction in patients with chronic critical illness.
Critically ill patients frequently experience acute brain dysfunction in the form of coma or delirium, both of which are common during acute and chronic critical illness (CCI). These manifestations of brain dysfunction are associated with numerous adverse outcomes during acute critical illness, including prolonged hospitalization, increased healthcare costs, and increased mortality. The prognosis of CCI patients with coma or delirium has not yet been thoroughly studied, but preliminary studies suggest this population is at high risk for detrimental outcomes associated with acute brain dysfunction. Additionally, a high percentage of patients who survive acute or CCI suffer from long-term brain dysfunction, which manifests primarily as memory deficits and executive dysfunction and is predicted by brain dysfunction in the ICU. Interventions directed at reducing the burden of brain dysfunction during critical illness have shown promise in studies of patients with acute critical illness, but these therapies have yet to be studied during CCI. Thus, multicenter randomized trials are needed to determine which interventions are most effective for such patients. Until these data are available, management strategies that have been proven beneficial during acute critical illness-such as reduction of sedative exposure, especially to benzodiazepines, and early use of physical and occupational therapy-should be employed during the treatment of patients with CCI.


An evaluation of point-of-care instrument for monitoring anticoagulation level in adult cardiac patients.
Rapid point-of-care measurement of anticoagulation has become feasible with the advent of new portable devices and offers the potential for home monitoring. This study evaluates the accuracy and feasibility of such a point-of-care device, the ProTime analyser as compared with standard laboratory method (IL MCL2) for monitoring the International Normalised Ratio (INR) level in cardiac patients on oral anticoagulation therapy. Fifty patients were studied. The majority were male (86% versus 14%). Chinese accounted for 37(74%) whereas Malay and Indian, constituted 9(18%) and 4(8%) respectively. The mean age was 55 +/- 12 years. Prosthetic heart valve replacement (46%) and atrial fibrillation (38%) were among the main indications for anticoagulation. The mean dosage of warfarin was 3.0 +/- 1.5 mg (range 1.0 to 6.5 mg) and the INR results ranged from 0.83 to 4.69 (based on the hospital laboratory method). Fingerstick and venous blood samples were collected from every patient and subjected to analysis by ProTime and IL MCL2 analysers. There was a good correlation of INRs between ProTime venous and IL MCL2 venous, ProTime fingerstick and IL MCL2 venous and ProTime venous and ProTime fingerstick samplings, with correlation coefficients (r) of 0.9248, 0.9403 and 0.9557, respectively. The Bland-Altman plot also showed a good correlation between the methods used without any systematic bias (limits of agreement ranged from -0.422 to +0.606 INR units on average). This rapid point-of-care device appears to have an acceptable level of accuracy for measuring INR values in the recommended target ranges in adult cardiac patients on oral anticoagulation therapy.


Simplifying the upper limb peripheral motor screen: Proposing the "K" sign.
The well-recognized erosion of pathoanatomic correlations in basic medical training, combined with the increasing everyday pressures of time-efficacy in patient examination, continue to place strain on junior clinicians. Over the years, many refinements to tried-and-true basic physical examination techniques have been described, allowing improvement in diagnostic yield. A multitude of "screening" techniques are available for physical assessment; however, such approaches are often nonstandardized and inconsistently taught and applied in the clinical realm. Great interexaminer inconsistency in the documentation of many forms of screening techniques also substantively undermines their respective clinical value. The current work presents a novel refinement/combination of previously described examination approaches for the assessment of peripheral upper limb (UL) motor function--the "K" sign. Having been successfully applied in both the acute and ambulatory clinical settings for several years, we feel that the technique has a useful role as a rapid and specific screening technique that is easily taught, learnt, and applied. Arguably, its employment serves to improve time efficacy in the screening examination, and may even improve diagnostic yield through its reliable reproducibility and provision of direct bilateral comparison. Its inherent simplicity also lends itself well to high levels of uptake (and retention) by medical students and junior clinicians alike. On top of presenting the simple screening test itself, we offer a simple means of subsequent notation for the patient's case note record, again in the hope of standardization and endurance of clinical value beyond the time of patient examination.


Factors contributing to adverse perioperative events in adults with congenital heart disease: a structured analysis of cases from the closed claims project.
Prior investigations have suggested that the rapidly growing population of adults with congenital heart disease is at increased risk of perioperative morbidity and mortality, but information is limited on the nature of those perioperative factors that may relate to adverse outcomes. We sought to use a national claims database to describe the contribution of perioperative factors to adverse outcomes and compare contributing factors in cardiac vs. noncardiac operations. The study is a retrospective in-depth structured analysis of cases from the Anesthesia Closed Claims Project database. We examined the largest national anesthesia malpractice claims database. We included all claims cases involving adult patients with congenital heart disease (CHD). Patients in this retrospective analysis were classified by type of surgery (cardiac or noncardiac). Perioperative factors contributing to an adverse event were assessed by an expert panel of cardiac anesthesiologists. Of 21 confirmed cases, 11 (52%) involved cardiac procedures and 10 (48%) noncardiac procedures. The most common factors contributing to the adverse event in cardiac cases were surgical technique (73% of cases) and intraoperative anesthetic care (55%), whereas in noncardiac cases, postoperative monitoring/care (50%), CHD (50%) and preoperative assessment or optimization (40%) were most common. The factors contributing to the patient injury differed similarly: in cardiac cases, the most common factors were intraoperative anesthetic care (55%) and surgical technique (45%) compared with postoperative monitoring/care (50%) and CHD (50%) in noncardiac cases. Within the limitations of a small number of events in a claims-based database, this study offers advantages of being a national, structured analysis of real cases to provide detailed information on phenomena that are otherwise abstract and hypothesized by expert opinion. These results should help affirm the role of anesthesiologists in acquiring and executing expertise as consultants in perioperative medicine for adults with congenital heart disease patients.


Genetic and environmental effects on meat quality.
In order for livestock industries to consistently produce high quality meat, there must be an understanding of the factors that cause quality to vary, as well as the contribution of genetics. A brief overview of meat tenderness is presented to understand how genotype and environment may interact to influence this trait. Essentially, meat tenderness is determined from the contribution of connective tissue, sarcomere length determined pre-rigor and rate of proteolysis during ageing, as well as contributions from intramuscular fat and post-mortem energy metabolism. The influence of mutations in myostatin, the callipyge gene, the Carwell or rib eye muscle gene as well as the calpain system on meat tenderness is presented. Specific examples of interactions between the production or processing environment and genetics are presented for both sheep and cattle. The day-to-day variation in tenderness is evident across experiments and this variation needs to be controlled in order to consistently produce tender meat.


The theory of planned behavior as applied to preoperative smoking abstinence.
Abstinence from smoking on the morning of surgery may improve outcomes. This study examined the explicatory power of the Theory of Planned Behavior (TPB) to predict smoking behavior on the morning of surgery, testing the hypothesis that the constructs of attitude, subjective norm, and perceived behavioral control (PBC) will predict intent to abstain from smoking the morning of surgery, and that intent will predict behavior. TPB constructs were assessed in 169 pre-surgical patients. Smoking behavior on the morning of surgery was assessed by self-report and CO monitoring. Correlations and structural equation modeling (SEM) were used to determine associations between measures and behavior. All TPB measures, including intent as predicted by the TPB, were correlated with both a lower rate of self-reported smoking on the morning of surgery and lower CO levels. The SEM showed a good fit to the data. In the SEM, attitude and PBC, but not subjective norm, were significantly associated with intent to abstain, explaining 46% of variance. The effect of PBC on CO levels was partially mediated by intent. The amount of variance in behavior explained by these TPB constructs was modest (10% for CO levels). Thus, attitude and perceived behavioral control explain a substantial portion of the intent to maintain preoperative abstinence on the morning of elective surgery, and intent and perceived behavioral control explain a more modest but significant amount of the variance in actual smoking behavior. Clinical Trials.gov registration: NCT01014455.


Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the α7 Nicotinic Acetylcholine Receptor.
Osteoarthritis (OA) is a degenerative joint disease that causes chronic disability among the elderly. Despite recent advances in symptomatic management of OA by pharmacological and surgical approaches, there remains a lack of optimal approaches to manage inflammation in the joints, which causes cartilage degradation and pain. In this study, we investigated the efficacy and underlying mechanisms of nicotine exposure in attenuating joint inflammation, cartilage degradation, and pain in a mouse model of OA. A mouse model of OA was induced by injection of monosodium iodoacetate into the knee joint. Cell culture models were also used to study the efficacy and underlying mechanisms of nicotine treatment in attenuating symptoms of OA. Nicotine treatment reduced mechanical allodynia, cartilage degradation, and the upregulation of matrix metalloproteinase-9 (MMP-9), a hallmark of joint inflammation in OA, in mice treated with monosodium iodoacetate. The effects of nicotine were abolished by the selective α7 nicotinic acetylcholine receptor (nAChR) blocker, methyllycaconitine . In RAW264.7 cells and murine primary bone marrow-derived macrophages, nicotine significantly inhibited MMP-9 production induced by LPS. In addition, nicotine significantly enhanced PI3K/Akt and inhibited NF-κB translocation from the cytosol to the nucleus in an α7-nAChR-dependent manner, suggesting that nicotine acts on α7-nAChRs to inhibit MMP-9 production by macrophages through modulation of the PI3K/Akt-NF-κB pathway. Our results provide novel evidence that nicotine can attenuate joint inflammation and pain in experimental OA via α7-nAChRs. α7-nAChR could thus serve as a highly promising target to manage joint inflammation and pain in OA.


Coding of amplitude modulation in primary auditory cortex.
Conflicting results have led to different views about how temporal modulation is encoded in primary auditory cortex (A1). Some studies find a substantial population of neurons that change firing rate without synchronizing to temporal modulation, whereas other studies fail to see these nonsynchronized neurons. As a result, the role and scope of synchronized temporal and nonsynchronized rate codes in AM processing in A1 remains unresolved. We recorded A1 neurons' responses in awake macaques to sinusoidal AM noise. We find most (37-78%) neurons synchronize to at least one modulation frequency (MF) without exhibiting nonsynchronized responses. However, we find both exclusively nonsynchronized neurons (7-29%) and "mixed-mode" neurons (13-40%) that synchronize to at least one MF and fire nonsynchronously to at least one other. We introduce new measures for modulation encoding and temporal synchrony that can improve the analysis of how neurons encode temporal modulation. These include comparing AM responses to the responses to unmodulated sounds, and a vector strength measure that is suitable for single-trial analysis. Our data support a transformation from a temporally based population code of AM to a rate-based code as information ascends the auditory pathway. The number of mixed-mode neurons found in A1 indicates this transformation is not yet complete, and A1 neurons may carry multiplexed temporal and rate codes.


Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review.
Rates of bacterial sexually transmitted infections (STIs) continue to rise, demanding treatments to be highly effective. However, curing infections faces significant challenges due to antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium and especially treating STIs at extragenital sites, particularly rectal chlamydia and oropharyngeal gonorrhoea. As no new antimicrobials are entering the market, clinicians must optimize the currently available treatments, but robust data are lacking on how the properties or pharmacokinetics of antimicrobials can be used to inform STI treatment regimens to improve treatment outcomes. This paper provides a detailed overview of the published pharmacokinetics of antimicrobials used to treat STIs and how factors related to the drug (tissue distribution, protein binding and t½), human (pH, inflammation, site of infection, drug side effects and sexual practices) and organism (organism load and antimicrobial resistance) can affect treatment outcomes. As azithromycin is commonly used to treat chlamydia, gonorrhoea and M. genitalium infections, and its pharmacokinetics are well studied, it is the main focus of this review. Suggestions are also provided on possible dosing regimens when using extended and/or higher doses of azithromycin, which appropriately balance efficacy and side effects. The paper also emphasizes the limitations of currently published pharmacokinetic studies including oropharyngeal gonococcal infections, where very limited data exist around ceftriaxone pharmacokinetics and its use in combination with azithromycin. In future, the different anatomical sites of infections may require alternative therapeutic approaches.


Estimating sedimentation rates in small reservoirs - Suitable approaches for local municipalities in central Europe.
Small reservoirs, as the preferred blue-green engineering infrastructure for use against intensive runoff processes, have risen in number in Central Europe during the past three decades. However, the modelling of sediment siltation is not included in reservoir planning. The unknown temporal sedimentation of a reservoir can lead to the lifespan of the construction being uncertain. The aim of this study is to present a relatively simple process for local managers to model siltation and, consequently, accurately estimate the lifetime of a small reservoir. Three empirical models (USLE, RUSLE and USPED) were applied to two small catchments in Central Europe. This paper takes advantage of real measured and modelled sedimentation during 2012 and 2017, presenting two different terrain measurement approaches. Our study emphasizes the importance of the R-factor value. The temporal development of the R-factor is dependent on climate change, and the R-factor value has been rising steadily during the last decades. The annual mean R-factor has increased 1.04-times due to changes in precipitation patterns between the periods 1961-1980 and 1997-2016. These changes can explain possible growth in the levels of incoming sediment into reservoirs. We identified the correlation (R > 0.7) between observed sedimentation, the R-factor, and precipitation, and we concluded that the supposed rise of precipitation in Central Europe due to climate change will lead to an increase in the levels of stored sediment in reservoirs. Therefore, it is recommended for reservoir managers to use USPED model and to include the estimation of modelling of siltation rate into reservoirs' maintenance projects.


Near-infrared excited state dynamics of melanins: the effects of iron content, photo-damage, chemical oxidation, and aggregate size.
Ultrafast pump-probe measurements can discriminate the two forms of melanin found in biological tissue (eumelanin and pheomelanin), which may be useful for diagnosing and grading melanoma. However, recent work has shown that bound iron content changes eumelanin's pump-probe response, making it more similar to that of pheomelanin. Here we record the pump-probe response of these melanins at a wider range of wavelengths than previous work and show that with shorter pump wavelengths the response crosses over from being dominated by ground-state bleaching to being dominated by excited-state absorption. The crossover wavelength is different for each type of melanin. In our analysis, we found that the mechanism by which iron modifies eumelanin's pump-probe response cannot be attributed to Raman resonances or differences in melanin aggregation and is more likely caused by iron acting to broaden the unit spectra of individual chromophores in the heterogeneous melanin aggregate. We analyze the dependence on optical intensity, finding that iron-loaded eumelanin undergoes irreversible changes to the pump-probe response after intense laser exposure. Simultaneously acquired fluorescence data suggest that the previously reported "activation" of eumelanin fluorescence may be caused in part by the dissociation of metal ions or the selective degradation of iron-containing melanin.


Relationship between pancreatic cancer-associated diabetes and cachexia.
Pancreatic cancer-associated diabetes mellitus (PCDM) is a paraneoplastic phenomenon characterized by worsening hyperglycaemia and weight loss. Galectin-3 and S100A9, mediators of PCDM, have pro-inflammatory functions and might thereby induce systemic inflammation and cachexia. We aimed to examine whether PCDM directly mediates cachexia. Consecutive pancreatic cancer (PC) patients with and without PCDM (n = 88 each) with complete information were included. Cachexia was defined as weight loss >5% within 6 months or weight loss >2% and body mass index <20 kg/m2 or sarcopenia. Skeletal muscle mass was measured with lumbar skeletal muscle index (SMI) using computed tomography images. Cachexia-related parameters (prevalence of cachexia, weight loss, and SMI) were compared between patients with and without PCDM. Relations between cachexia-related parameters and fasting blood glucose or serum levels of galectin-3 and S100A9 were analysed by Spearman correlation and logistic regression analyses. One hundred two (58.0%) patients had cachexia at diagnosis. No significant differences existed between patients with and without PCDM in prevalence of cachexia (64.8% vs. 51.1%, P = 0.093), percentage of weight loss (median 6.8 vs. 4.0, P = 0.085), and SMI (median 45.8 vs. 45.3 cm2 /m2 in men, P = 0.119; 34.9 vs. 36.3 cm2 /m2 in women, P = 0.418). In patients with cachexia, the percentage of weight loss and SMI were also similar between patients with and without PCDM. In patients with PCDM, fasting blood glucose was comparable between patients with and without cachexia (P = 0.458) and did not correlate with the percentage of weight loss (P = 0.085) or SMI (P = 0.797 in men and 0.679 in women). Serum S100A9 level correlated with fasting blood glucose (correlation coefficient 0.213, P = 0.047) but not with the percentage of weight loss (P = 0.977) or SMI (P = 0.247 in men and 0.458 in women). Serum galectin-3 level also did not correlate with the percentage of weight loss (P = 0.226) and SMI (P = 0.201 in men and 0.826 in women). Primary tumour size was associated with cachexia (adjusted odds ratio per 1 cm increase 1.28, 95% confidence interval 1.02-1.60, P = 0.034), whereas PCDM, fasting blood glucose, and levels of galectin-3 and S100A9 were not predictors of cachexia. Neither fasting blood glucose nor levels of galectin-3 and S100A9 were associated with cachexia-related parameters. Mediators of PCDM and hyperglycaemia do not directly mediate PC-induced cachexia.


Opaganib (ABC294640) Induces Immunogenic Tumor Cell Death and Enhances Checkpoint Antibody Therapy.
Antibody-based cancer drugs that target the checkpoint proteins CTLA-4, PD-1 and PD-L1 provide marked improvement in some patients with deadly diseases such as lung cancer and melanoma. However, most patients are either unresponsive or relapse following an initial response, underscoring the need for further improvement in immunotherapy. Certain drugs induce immunogenic cell death (ICD) in tumor cells in which the dying cells promote immunologic responses in the host that may enhance the in vivo activity of checkpoint antibodies. Sphingolipid metabolism is a key pathway in cancer biology, in which ceramides and sphingosine 1-phosphate (S1P) regulate tumor cell death, proliferation and drug resistance, as well as host inflammation and immunity. In particular, sphingosine kinases are key sites for manipulation of the ceramide/S1P balance that regulates tumor cell proliferation and sensitivity to radiation and chemotherapy. We and others have demonstrated that inhibition of sphingosine kinase-2 by the small-molecule investigational drug opaganib (formerly ABC294640) kills tumor cells and increases their sensitivities to other drugs and radiation. Because sphingolipids have been shown to regulate ICD, opaganib may induce ICD and improve the efficacy of checkpoint antibodies for cancer therapy. This was demonstrated by showing that in vitro treatment with opaganib increases the surface expression of the ICD marker calreticulin on a variety of tumor cell types. In vivo confirmation was achieved using the gold standard immunization assay in which B16 melanoma, Lewis lung carcinoma (LLC) or Neuro-2a neuroblastoma cells were treated with opaganib in vitro and then injected subcutaneously into syngeneic mice, followed by implantation of untreated tumor cells 7 days later. In all cases, immunization with opaganib-treated cells strongly suppressed the growth of subsequently injected tumor cells. Interestingly, opaganib treatment induced crossover immunity in that opaganib-treated B16 cells suppressed the growth of both untreated B16 and LLC cells and opaganib-treated LLC cells inhibited the growth of both untreated LLC and B16 cells. Next, the effects of opaganib in combination with a checkpoint antibody on tumor growth in vivo were assessed. Opaganib and anti-PD-1 antibody each slowed the growth of B16 tumors and improved mouse survival, while the combination of opaganib plus anti-PD-1 strongly suppressed tumor growth and improved survival (p < 0.0001). Individually, opaganib and anti-CTLA-4 antibody had modest effects on the growth of LLC tumors and mouse survival, whereas the combination of opaganib with anti-CTLA-4 substantially inhibited tumor growth and increased survival (p < 0.001). Finally, the survival of mice bearing B16 tumors was only marginally improved by opaganib or anti-PD-L1 antibody alone but was nearly doubled by the drugs in combination (p < 0.005). Overall, these studies demonstrate the ability of opaganib to induce ICD in tumor cells, which improves the antitumor activity of checkpoint antibodies.


[A study on the decomposition kinetics of vitamin C powder].
The effect of temperature and humidity on the discoloration and degradation of vitamin C powder was studied via accelerated test under isothermal and constant humidity conditions. The changes of color and concentration of vitamin C were monitored by diffuse reflectance spectroscopy and iodimetry respectively. Under the condition of relative humidity less than the critical relative humidity, the apparent rate constant of discoloration of Kc of vitamin C powder is: kc = 'exp (-Ea/RT) exp (m 'RH), where k' and m' are constants, RH is relative humidity and Ea is activation energy, when RH less than 70%, Ea = 104.33 kJ . mol-1. The degradation curve of vitamin C powder under various temperatures and humidities can be expressed by C = N/(1 + Btn), the rate equation of degradation of vitamin C powder is: -dC/dt = kdC(1 + 1/n) (N-C)(1 - 1/n), where kd is the apparent rate constant of degradation, B and n are constants, N is the initial content of vitamin C and C is the content of vitamin C at time t. When RH are 97, 93, and 79.5%, Ea are 86.87, 88.22 and 202.64 kJ.mol-1, respectively.


Trends in the prescription of inappropriate drugs for the elderly between 1995 and 1999.
Using criteria developed by Beers et al between 1991 and 1997, previous studies have reported high levels of inappropriate drug prescribing for community-dwelling elderly patients (age>or=65 years). However, it is not known whether the Beers criteria have had a beneficial effect on prescribing practices. The aims of this study were to compare the prevalence of potentially inappropriate drug use (based on the Beers list) among older Americans between 1995 and 1999; to determine whether any decreases in such use were more likely to be the result of improved adherence to guidelines or of replacement of older medications by newer drugs; and to examine individual characteristics that place elderly patients at increased risk for inappropriate drug use. This was a panel study involving nationally representative samples of community-dwelling elderly persons from the 1995 and 1999 Medicare Current Beneficiary Surveys (MCBS). For comparison, data were analyzed from samples of disabled Medicare beneficiaries aged <65 years for the same periods. The samples were assessed for the use of 36 individual drugs, drug classes, and combinations carrying a risk for adverse out comes in the elderly based on the 1997 Beers criteria for drugs to be avoided in this population. The study samples contained 7628 community-dwelling elderly persons from the 1995 MCBS and 8902 from the 1999 MCBS, and 1863 and 1851 disabled Medicare beneficiaries aged <65 years for the respective survey years. The proportion of elderly patients taking >or=1 drug on the Beers list declined from 24.8% in 1995 to 21.3% in 1999 (P<0.05). There was a nonsignificant increase in the proportion of disabled Medicare beneficiaries taking >or=1 drug on the Beers list from 31.1% in 1995 to 31.5% in 1999. There was a significant decline in the use of potentially inappropriate drugs by elderly patients between 1995 and 1999, particularly in the use of those drugs linked to the most severe outcomes. However, approximately 7 million elderly patients still received potentially inappropriate drugs in 1999, underscoring the continued need for effective interventions to improve prescribing for this vulnerable population.


Correlation between virulence and colony morphology in Vibrio vulnificus.
Of 38 isolates of Vibrio vulnificus examined, all avirulent strains produced only translucent colonies. All virulent strains, with the exception of biogroup 2 (eel pathogens), exhibited both opaque and translucent colonies. Isogenic morphotypes were examined for a variety of phenotypic and virulence traits. Only the ability to utilize transferrin-bound iron and the presence of a surface polysaccharide were found to correlate with colony opacity and virulence.


Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland.
Genetic studies of Neolithic and Bronze Age skeletons from Europe have provided evidence for strong population genetic changes at the beginning and the end of the Neolithic period. To further understand the implications of these in Southern Central Europe, we analyze 96 ancient genomes from Switzerland, Southern Germany, and the Alsace region in France, covering the Middle/Late Neolithic to Early Bronze Age. Similar to previously described genetic changes in other parts of Europe from the early 3rd millennium BCE, we detect an arrival of ancestry related to Late Neolithic pastoralists from the Pontic-Caspian steppe in Switzerland as early as 2860-2460 calBCE. Our analyses suggest that this genetic turnover was a complex process lasting almost 1000 years and involved highly genetically structured populations in this region.


Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease.
Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias.


Three stage semelparous Leslie models.
Nonlinear Leslie matrix models have a long history of use for modeling the dynamics of semelparous species. Semelparous models, as do nonlinear matrix models in general, undergo a transcritical equilibrium bifurcation at inherent net reproductive number R(0) = 1 where the extinction equilibrium loses stability. Semelparous models however do not fall under the purview of the general theory because this bifurcation is of higher co-dimension. This mathematical fact has biological implications that relate to a dichotomy of dynamic possibilities, namely, an equilibration with over lapping age classes as opposed to an oscillation in which age classes are periodically missing. The latter possibility makes these models of particular interest, for example, in application to the well known outbreaks of periodical insects. While the nature of the bifurcation at R(0) = 1 is known for two-dimensional semelparous Leslie models, only limited results are available for higher dimensional models. In this paper I give a thorough accounting of the bifurcation at R(0) = 1 in the three-dimensional case, under some monotonicity assumptions on the nonlinearities. In addition to the bifurcation of positive equilibria, there occurs a bifurcation of invariant loops that lie on the boundary of the positive cone. I describe the geometry of these loops, classify them into three distinct types, and show that they consist of either one or two three-cycles and heteroclinic orbits connecting (the phases of) these cycles. Furthermore, I determine stability and instability properties of these loops, in terms of model parameters, as well as those of the positive equilibria. The analysis also provides the global dynamics on the boundary of the cone. The stability and instability conditions are expressed in terms of certain measures of the strength and the symmetry/asymmetry of the inter-age class competitive interactions. Roughly speaking, strong inter-age class competitive interactions promote oscillations (not necessarily periodic) with separated life-cycle stages, while weak interactions promote stable equilibration with overlapping life-cycle stages. Methods used include the theory of planar monotone maps, average Lyapunov functions, and bifurcation theory techniques.


Absorption spectra of xanthines in aqueous solution: a computational study.
We present a detailed computational analysis of the UV/Vis spectra of caffeine, paraxanthine and theophylline in aqueous solution. A hierarchy of solvation approaches for modeling the aqueous environment have been tested, ranging from the continuum model to the non-polarizable and polarizable quantum mechanical (QM)/molecular mechanics (MM) models, with and without the explicit inclusion of water molecules in the QM portion. The computed results are directly compared with the experimental data, thus highlighting the role of electrostatic, polarization and hydrogen boding solute-solvent interactions.


Effect of wave exposure dynamics on gut content mass and growth of young-of-the-year fishes in the littoral zone of lakes.
Total length, body mass and gut content mass of young-of-the-year (YOY) perch Perca fluviatilis, dace Leuciscus leuciscus and bleak Alburnus alburnus were recorded over the summer of 2006 at three littoral sites at Upper Lake Constance. In P. fluviatilis and L. leuciscus, gut content mass correlated positively with wave-induced energy flux (E(F)) of the respective site and sampling day, while no correlation of gut content mass with E(F) was found in A. alburnus. It was assumed that benthivorous P. fluviatilis and L. leuciscus profited from suspended or uncovered benthic food items generated by wave action at sites and periods with high E(F). Alburnus alburnus, in contrast, feeding mainly on zooplankton in upper parts of the water column, could not profit from increased E(F). In P. fluviatilis, increased gut content mass during periods of high E(F) resulted in higher growth rates. For L. leuciscus, no real growth rates in local fish populations could be determined, as individuals were less sedentary, and when increased growth occurred at sites during the periods of high E(F), migration of fish levelled out the resulting size differences within few days. The results of this study show that dynamic habitat variables affect site profitability in the littoral zone of lakes, especially in benthivorous fishes. Therefore, dynamic habitat variables should be considered in addition to fixed habitat properties in analyses of habitat choice of fishes in the littoral zone of lakes.


Meta-analysis of transanal versus laparoscopic total mesorectal excision for rectal cancer: a 'New Health Technology' assessment in South Korea.
Under the South Korea's unique health insurance structure, any new surgical technology must be evaluated first by the government in order to consider whether that particular technology can be applied to patients for further clinical trials as categorized as 'New Health Technology,' then potentially covered by the insurance sometime later. The aim of this meta-analysis was to assess the safety and efficacy of transanal total mesorectal excision (TaTME) for rectal cancer, activated by the National Evidence-based Healthcare Collaborating Agency (NECA) TaTME committee. We systematically searched Ovid-MEDLINE, Ovid-Embase, Cochrane, and Korean databases (from their inception until August 31, 2019) for studies published that compare TaTME with laparoscopic total mesorectal excision (LaTME). End-points included perioperative and pathological outcomes. Sixteen cohort studies (7 for case-matched studies) were identified, comprising 1,923 patients (938 TaTMEs and 985 LaTMEs). Regarding perioperative outcomes, the conversion rate was significantly lower in TaTME (risk ratio, 0.19; 95% confidence interval, 0.11-0.34; P < 0.001); whereas other perioperative outcomes were similar to LaTME. There were no statistically significant differences in pathological results between the 2 procedures. Our meta-analysis showed comparable results in preoperative and pathologic outcomes between TaTME and LaTME, and indicated the benefit of TaTME with low conversion. Extensive evaluations of well-designed, multicenter randomized controlled trials are required to come to unequivocal conclusions, but the results showed that TaTME is a potentially beneficial technique in some specific cases. This meta-analysis suggests that TaTME can be performed for rectal cancer patients as a 'New Health Technology' endorsed by NECA in South Korea.


Alternatives to intravenous rehydration in dehydrated pediatric patients with difficult venous access.
Intravenous (IV) catheter placement in the pediatric patient population can be challenging. Many health care providers automatically choose IV fluid administration to treat dehydration, often not considering other routes. This article reviews the available literature on difficulties in obtaining IV access in the pediatric population and discusses alternative methods for fluid replacement, their respective advantages and disadvantages, and place in therapy.


Predicting western corn rootworm (Coleoptera: Chrysomelidae) larval injury to rotated corn with Pherocon AM traps in soybeans.
Crop rotation for portions of east central Illinois and northern Indiana no longer adequately protects corn (Zea mays L.) roots from western corn rootworm, Diabrotica virgifera virgifera LeConte. Seventeen growers in east central Illinois monitored western corn rootworm adults in soybean (Glycine max L.) fields with unbaited Pherocon AM traps during 1996 and 1997. In the following years (1997 and 1998), growers left untreated strips (no insecticide applied) when these fields were planted with corn. Damage to rotated corn by rootworms was more severe in untreated than in treated strips of rotated corn, ranging from minor root scarring to a full node of roots pruned. Densities of western corn rootworms in soybean fields from 1996 were significantly correlated with root injury to rotated corn the following season. Adult densities from 1997 were not significantly correlated with root injury in 1998, due to heavy precipitation throughout the spring of 1998 and extensive larval mortality. Twenty-eight additional growers volunteered in 1998 to monitor rootworm adults in soybean fields with Pherocon AM traps based on recommendations that resulted from our research efforts in 1996 and 1997. In 1999, these 28 fields were rotated to corn, and rootworm larval injury was measured in untreated strips. Based on 1996-1997 and 1998-1999 data, a regression analysis revealed that 27% of the variation in root injury to rotated corn could be explained by adult density in soybeans the previous season. We propose a sampling plan for soybean fields and a threshold for predicting western corn rootworm larval injury to rotated corn.


Microbiota Analysis of an Environmental Slurry and Its Potential Role as a Reservoir of Bovine Digital Dermatitis Pathogens.
At present, very little information exists regarding what role the environmental slurry may play as an infection reservoir and/or route of transmission for bovine digital dermatitis (DD), a disease which is a global problem in dairy herds. To investigate whether DD-related bacteria belong to the indigenous microbiota of the dairy herd environment, we used deep amplicon sequencing of the 16S rRNA gene in 135 slurry samples collected from different sites in 22 dairy farms, with and without DD-infected cows. Both the general bacterial populations and digital dermatitis-associated Treponema were targeted in this study. The results revealed significant differences in the bacterial communities between the herds, with only 12 bacterial taxa shared across at least 80% of all the individual samples. These differences in the herd microbiota appeared to reflect mainly between-herd variation. Not surprisingly, the slurry was dominated by ubiquitous gastrointestinal bacteria, such as Ruminococcaceae and Lachnospiraceae Despite the low relative abundance of spirochetes, which ranged from 0 to 0.6%, we were able to detect small amounts of bacterial DNA from DD-associated treponemes in the slurry. However, the DD-associated Treponema spp. were detected only in samples from herds with reported DD problems. These data indicate that treponemes involved in the pathogenesis of DD are not part of the normal environmental microflora in dairy herds without clinical DD and, consequently, that slurry is not a primary reservoir of infection.IMPORTANCE Bovine digital dermatitis (DD), a dermal disease which causes lameness in dairy cattle, is a serious problem worldwide. To control this disease, the infection reservoirs and transmission routes of DD pathogens need to be clarified. The dairy herd slurry may be a pathogen reservoir of DD-associated bacteria. The rationale for the present study was, therefore, to examine whether DD-associated bacteria are always present in slurry or if they are found only in DD-afflicted herds. The results strongly indicated that DD Treponema spp. are not part of the indigenous slurry and, therefore, do not comprise an infection reservoir in healthy herds. This study applied next-generation sequencing technology to decipher the microbial compositions of environmental slurry of dairy herds with and without digital dermatitis.


Management of low back pain in Australian emergency departments.
To describe the diagnoses of people who present to the emergency department (ED) with low back pain (LBP), the proportion of people with a lumbar spine condition who arrived by ambulance, received imaging, opioids and were admitted to hospital; and to explore factors associated with these four outcomes. In this retrospective study, we analysed electronic medical records for all adults presenting with LBP at three Australian EDs from January 2016 to June 2018. Outcomes included discharge diagnoses and key aspects of care (ambulance transport, lumbar spine imaging, provision of opioids, admission). We explored factors associated with these care outcomes using multilevel mixed-effects logistic regression models and reported data as ORs. There were 14 024 presentations with a 'visit reason' for low back pain, of which 6393 (45.6%) had a diagnosis of a lumbar spine condition. Of these, 31.4% arrived by ambulance, 23.6% received lumbar imaging, 69.6% received opioids and 17.6% were admitted to hospital. Older patients (OR 1.79, 95% CI 1.56 to 2.04) were more likely to be imaged. Opioids were less used during working hours (OR 0.81, 95% CI 0.67 to 0.98) and in patients with non-serious LBP compared with patients with serious spinal pathology (OR 1.65, 95% CI 1.07 to 2.55). Hospital admission was more likely to occur during working hours (OR 1.74, 95% CI 1.48 to 2.05) and for those who arrived by ambulance (OR 2.98, 95% CI 2.53 to 3.51). Many ED presentations of LBP were not due to a lumbar spine condition. Of those that were, we noted relatively high rates of lumbar imaging, opioid use and hospital admission.


Development of beta-amino acid transport in the kidney.
This study focuses on the maturation of the renal beta-amino acid transport system and uses dietary manipulation as a probe. The epithelial surface of the renal proximal tubule is responsible for the conservation of ions and organic solutes including beta-amino acids. This beta-amino acid transport system is stimulated during periods of reduced dietary intake and permits increased excretion following dietary excess. We have examined transport of the sulfur-containing beta-amino acid, taurine, as a measure of this renal adaptive response to fluctuations in dietary sulfur amino acid intake and as a substrate for the beta-amino acid transport system. A precession of taurine uptake values by brush border membrane vesicles (BBMV) prepared from nursing rats from youngest to oldest was evident. However, these membranes demonstrate the full renal adaptive response to altered sulfur amino acid intake after the first week of life. This adaptive response is expressed at the brush border surface by transport changes in both directions ("up regulation" and "down regulation"), through changes in the initial rate (15 sec) of Na+-taurine cotransport. No alterations in the lipid microenvironment of the membrane, as detected by altered membrane fluidity, were uncovered. Although vesicles from 7-day-old pups demonstrate adaptation and accumulate taurine to a limited extent, the accumulation of Na+, which energizes uptake, may be altered, thereby preventing full expression of the adaptive response and of transport capacity at this age.


Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome.
Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-->methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.