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Sleep is critical for memory consolidation, although the exact mechanisms mediating this process are unknown. Combining reduced network models and analysis of in vivo recordings, we tested the hypothesis that neuromodulatory changes in acetylcholine (ACh) levels during non-rapid eye movement (NREM) sleep mediate stabilization of network-wide firing patterns, with temporal order of neurons' firing dependent on their mean firing rate during wake. In both reduced models and in vivo recordings from mouse hippocampus, we find that the relative order of firing among neurons during NREM sleep reflects their relative firing rates during prior wake. Our modeling results show that this remapping of wake-associated, firing frequency-based representations is based on NREM-associated changes in neuronal excitability mediated by ACh-gated potassium current. We also show that learning-dependent reordering of sequential firing during NREM sleep, together with spike timing-dependent plasticity (STDP), reconfigures neuronal firing rates across the network. This rescaling of firing rates has been reported in multiple brain circuits across periods of sleep. Our model and experimental data both suggest that this effect is amplified in neural circuits following learning. Together our data suggest that sleep may bias neural networks from firing rate-based towards phase-based information encoding to consolidate memories. Author summary: We show that neuromodulatory changes during non-rapid eye movement (NREM) sleep generate stable spike timing relationships between neurons, the ordering of which reflects the neurons' relative firing rates during wake. Learning-dependent ordering of firing in the hippocampus during NREM, acting in tandem with spike timing-dependent plasticity, reconfigures neuronal firing rates across the hippocampal network. This "rescaling" of neuronal firing rates has recently been reported in multiple brain circuits across periods of sleep. Together, our results suggest that the brain is remapping frequency-biased representations of information formed during wake into timing biased-representations during NREM sleep. [ABSTRACT FROM AUTHOR]

Background Recent advances in neurophysiological recording techniques have increased both the spatial and temporal resolution of data. New methodologies are required that can handle large data sets in an efficient manner as well as to make quantifiable, and realistic, predictions about the global modality of the brain from under-sampled recordings. New method To rectify both problems, we first propose an analytical modification to an existing functional connectivity algorithm, Average Minimal Distance (AMD), to rapidly capture functional network connectivity. We then complement this algorithm by introducing Functional Network Stability (FuNS), a metric that can be used to quickly assess the global network dynamic changes over time, without being constrained by the activities of a specific set of neurons. Results We systematically test the performance of AMD and FuNS (1) on artificial spiking data with different statistical characteristics, (2) from spiking data generated using a neural network model, and (3) using in vivo data recorded from mouse hippocampus during fear learning. Our results show that AMD and FuNS are able to monitor the change in network dynamics during memory consolidation. Comparison with other methods AMD outperforms traditional bootstrapping and cross-correlation (CC) methods in both significance and computation time. Simultaneously, FuNS provides a reliable way to establish a link between local structural network changes, global dynamics of network-wide representations activity, and behavior. Conclusions The AMD-FuNS framework should be universally useful in linking long time-scale, global network dynamics and cognitive behavior. [ABSTRACT FROM AUTHOR]

Neoergasilus japonicus, a fish ectoparasite indigenous to eastern and southern Asia, has been introduced to various regions, including Europe and North and South America, where it spreads at an alarming rate. The parasite is not host‐specific. It was also collected from the Vaal‐Orange and Limpopo river systems in South Africa. This report describes the morphology of the wound‐inflecting structures in N. japonicus and relates their morphology to the pathological effect on Tilapia sparrmanii. Host tissue with parasites attached was imbedded in resin for histological sectioning and stained with haematoxylin and eosin. Additional specimens were prepared for scanning electron microscopy. Adult female parasites attach by inserting the hooked tips of the antennae into the epidermis. The maxillulae are minute but have sharp tips. The maxillae have sharp tips on the endopod and brush‐like setae on the exopod. The mandibles are armed with sharp tips. These structures are used to remove the epidermis of the host and brush it into the buccal cavity. Host tissue in the intestine confirms that adult females consume host tissue leaving the dermis exposed to opportunistic diseases. The microscopic size of the parasite prevents casual observation, and its occurrence in Africa is, therefore, probably underreported. [ABSTRACT FROM AUTHOR]

Aluminum salts have a long history as safe and effective vaccine adjuvants. In addition, aluminum salts have high adsorptive capacities for vaccine antigens and adjuvant molecules, for example, Toll-like receptor 4 ( TLR4) agonists. However, the physicochemical properties of aluminum salts make direct quantitation of adsorbed molecules challenging. Typical methods for quantifying adsorbed molecules require advanced instrumentation, extreme sample processing, often destroy the sample, or rely on an indirect measurement. A simple, direct, and quantitative method for analysis of adsorbed adjuvant molecules is needed. This report presents a method utilizing Fourier transform infrared spectroscopy with a Zn Se-attenuated total reflectance attachment to directly measure low levels (<30 μg/mL) of TLR4 agonists adsorbed on aluminum salts with minimal sample preparation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:768-774, 2015 [ABSTRACT FROM AUTHOR]

Central pattern generators are neuron networks that produce vital rhythmic motor outputs such as those observed in mastication, walking and breathing. Their activity patterns depend on the tuning of their intrinsic ionic conductances, their synaptic interconnectivity and entrainment by extrinsic neurons. The influence of two commonly found synaptic connectivities – reciprocal inhibition and electrical coupling – are investigated here using a neuron model with subthreshold oscillation capability, in different firing and entrainment regimes. We study the dynamics displayed by a network of a pair of neurons with various firing regimes, coupled by either (i) only reciprocal inhibition or by (ii) electrical coupling first and then reciprocal inhibition. In both scenarios a range of coupling strengths for the reciprocal inhibition is tested, and in general the neuron with the lower firing rate stops spiking for strong enough inhibitory coupling, while the faster neuron remains active. However, in scenario (ii) the originally slower neuron stops spiking at weaker inhibitory coupling strength, suggesting that the electrical coupling introduces an element of instability to the two-neuron network. [ABSTRACT FROM AUTHOR]

Activity of adjuvanted vaccines is difficult to predict in vitro and in vivo. The wide compositional and conformational range of formulated adjuvants, from aluminum salts to oil-in-water emulsions, makes comparisons between physicochemical and immunological properties difficult. Even within a formulated adjuvant class, excipient selection and concentration can alter potency and physicochemical properties of the mixture. Complete characterization of physicochemical properties of adjuvanted vaccine formulations and relationship to biological response is necessary to move beyond a guess-and-check paradigm toward directed development. Here we present a careful physicochemical characterization of a two-component nanosuspension containing synthetic TLR-4 agonist glucopyranosyl lipid adjuvant ( GLA) and 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine ( DPPC) at various molar ratios. Physicochemical properties were compared with potency, as measured by stimulation of cytokine production in human whole blood. We found a surprising, nonlinear relationship between physicochemical properties and GLA- DPPC ratios that corresponded well with changes in biological activity. We discuss these data in light of the current understanding of TLR4 activation and the conformation-potency relationship in development of adjuvanted vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:879-889, 2014 [ABSTRACT FROM AUTHOR]

Stress is a common experience in drug abusers. Methamphetamine (METH) is an abused psychostimulant that damages dopamine and serotonin terminals through pro-oxidant mechanisms and glutamate-mediated excitotoxicity. Both METH and stress increase dopamine and glutamate release in the striatum. Since dopamine inhibits striatal glutamate release and METH depletes dopamine, stress-induced glutamate release may be disinhibited after METH exposure. We examined if repeated stress would worsen excitotoxic damage to the striatum after METH pretreatment. In vivo microdialysis was used to examine stress-induced striatal glutamate release in rats pre-exposed to METH (7.5 mg/kg × 4 injections) or saline. The effects on striatal DA, serotonin, DAT, SERT, and spectrin proteolysis produced by chronic restraint stress (CRS, 6 h/day for 21 days) in the presence or absence of corticosterone synthesis inhibition by metyrapone (50 mg/kg) beginning 7 days after METH were also examined. Stress-induced glutamate release was augmented in rats pre-exposed to METH. CRS 7 days after METH enhanced METH-induced DAT depletions from 23 to 44% in the nonstressed versus stressed rats, respectively. Striatal SERT and serotonin tissue content were decreased by 51 and 36%, respectively, in rats exposed to both METH and CRS but was unchanged by either treatment alone. Spectrin proteolysis was increased by 53% in rats treated with both METH and CRS but was unaffected by either treatment alone. Metyrapone blocked the effects of CRS on METH-induced depletions of SERT but not DAT. Exposure to chronic stress depleted striatal dopamine and serotonin terminal markers possibly through excitotoxic mechanisms in METH-treated rats. [ABSTRACT FROM AUTHOR]

Rationale: Although positive GABAA modulators can attenuate several cocaine-induced behavioral effects, there is a paucity of data on their interaction with cocaine on transition behavior or learning. Objectives: The current study examined the effects of cocaine (3.2-32 mg/ kg), pregnanolone (3.2-24 mg/kg), and lorazepam (0.1- 10 mg/kg) alone and in combination in rats responding under a multiple schedule of repeated acquisition and performance. Methods: In the acquisition component, subjects acquired a different three-response sequence each session, whereas in the performance component, they responded on the same three-response sequence each session. Results: All three drugs produced dose-dependent rate-decreasing and error-increasing effects. Cocaine was the least effective in decreasing rates and the most effective in increasing the percentage of errors. In combination with pregnanolone (3.2 or 10 mg/kg), the rate-decreasing effects of cocaine were relatively unchanged in both components, but 3.2 mg/ kg of pregnanolone enhanced its error-increasing effects and the 10-mg/kg dose produced a significant dose-dependent interaction on errors. The combination of cocaine with lorazepam (0.32 mg/kg, 70-min pretreatment) produced significantly greater rate-decreasing and error-increasing effects than cocaine alone. A 15-min pretreatment with the same dose of lorazepam enhanced the error-increasing effects of small doses and attenuated the effects of larger doses of cocaine. Combinations of pregnanolone and lorazepam produced greater rate-decreasing and error-increasing effects in both components than either drug alone. Conclusions: The present data show that cocaine is more disruptive to learning in rats than pregnanolone or lorazepam, and that the disruptive effects of cocaine can be enhanced by CNS depressants. [ABSTRACT FROM AUTHOR]

We explore the possible role of network dynamics near a critical point in the storage of new information in silico and in vivo, and show that learning and memory may rely on neuronal network features mediated by the vicinity of criticality. Using a mean-field, attractor-based model, we show that new information can be consolidated into attractors through state-based learning in a dynamical regime associated with maximal susceptibility at the critical point. Then, we predict that the subsequent consolidation process results in a shift from critical to sub-critical dynamics to fully encapsulate the new information. We go on to corroborate these findings using analysis of rodent hippocampal CA1 activity during contextual fear memory (CFM) consolidation. We show that the dynamical state of the CA1 network is inherently poised near criticality, but the network also undergoes a shift towards sub-critical dynamics due to successful consolidation of the CFM. Based on these findings, we propose that dynamical features associated with criticality may be universally necessary for storing new memories. [ABSTRACT FROM AUTHOR]

Injurious pecking is considered a major economic concern and affects all sectors of commercial poultry production. Though extensive research has been performed examining feather pecking in layer chickens, little information exists regarding feather or head pecking behavior in domestic turkey flocks, and less still in commercial settings. The objective of the present field study was to examine the development of injurious feather and head pecking in tom turkeys raised in 2 different commercial environments. At a commercial facility, 49,332 beak-conditioned tom turkeys were placed in 8 barns (5,000–7,500 turkeys/barn) and studied through 16 wk of age. Approximately half were housed in control barns in March 2010; these barns were environmentally controlled (artificial light and tunnel ventilation) in both rearing and growing, with a density of 0.16 m2/bird for rearing through 4.5 wk and 0.39 m2/bird for growing through 16 wk. The remaining turkeys were housed in curtain-sided barns in April 2010; the 4 rearing barns were environmentally controlled with a density of 0.10 m2/bird, whereas the 4 growing barns had natural light and ventilation and a density of 0.36 to 0.38 m2/bird through 16 wk. Two barns from each growing environment were provided with multicolored plastic balls as enrichment. Each housing and enrichment combination had 2 replicate barns. Behavior, weights, and feather condition were assessed every 3 wk. Mortalities and culls were recorded as they occurred. Turkeys in curtain-sided barns had worse feather condition and more culls and mortalities with severe pecking injuries compared with those in control barns. In both environments, severe and gentle pecking was observed throughout production, and the majority of culls and mortalities had severe pecking injuries. More controlled studies are needed to parse the causal factors of injurious pecking in toms. [ABSTRACT FROM AUTHOR]

Highlights: [•] TLR4 ligands are promising vaccine adjuvant candidates. [•] In vitro assays (e.g. macrophage cytokine production) evaluate adjuvant activity. [•] Different formulations of the same TLR4 ligand modulate its in vitro bioactivity. [Copyright &y& Elsevier]

Abstract: Small ruminant lentiviruses (SLRV) are major production limiting diseases of sheep and goats and are major source of economic loss to producers. There is currently no treatment or vaccine, and the prevalence of SRLV infection across the Ontario is unknown. A preliminary study of 45 Ontario goat herds was used to estimate the prevalence of SRLV infection. Blood was sampled and analyzed with an ELISA test for the presence of SRLV-specific antibodies as an indirect indicator of infection. Additionally, a telephone survey was conducted to identify management factors that are associated with prevalence of infection. The prevalence of SRLV in the 482 goats from 30 dairy goat farms was estimated to be 80.4% and 17.0% from the 225 goats on 15 meat goat farms. Significant differences were found between both prevalence and antibody levels risk in young (≤12 months) and older (>12 months) goats in the dairy sector with older goats slowing a greater prevalence and higher antibody levels as farm risk increased. In the meat sector, there was also a significant difference between antibody levels and risk between young and older goats, however, older meat goats tended to have lower antibody levels than younger goats. [Copyright &y& Elsevier]

The objective of this study was to use previously calculated estimated breeding values for cell- (CMIR) and antibody-mediated immune responses (AMIR) to determine associations between immune response (IR) and economically important diseases of dairy cattle. In total, 699 Holsteins were classified as high, average, or low for CMIR, AMIR, and overall IR (combined CMIR and AMIR), and associations with mastitis, metritis, ketosis, displaced abomasums, and retained fetal membranes were determined. The incidence of mastitis was higher among average cows as compared with cows classified as high AMIR [odds ratio (OR) = 2.5], high CMIR (OR = 1.8), or high IR (OR = 1.8). Low-CMIR cows had a higher incidence of metritis (OR = 11.3) and low-IR cows had a higher incidence of displaced abomasum (OR = 4.1) and retained fetal membrane (OR = 2.8) than did average responders. Results of this study show that cows classified as high immune responders have lower occurrence of disease, suggesting that breeding cattle for enhanced IR may be a feasible approach to decrease the incidence of infectious and metabolic diseases in the dairy industry. [ABSTRACT FROM AUTHOR]

1. In the first experiment, the effect of adding purified malva nut gum (PMG) to comminuted poultry breast meat batters formulated with different contents of sodium chloride (NaCl; 10 to 30 g/kg) and tripolyphosphate (TPP; 0 and 5 g/kg) was studied. 2. Increasing salt (sodium chloride) content, along with the addition of 1 g/kg PMG, was beneficial in reducing cooking loss. At all salt contents, batters with PMG showed lower springiness than batters without PMG. Adding PMG to the batter with 20 g/kg salt and TPP decreased fracture force, springiness and chewiness. 3. In a second experiment, the effects of PMG (0·0, 3·0 and 6·0 g/kg), crude malva nut gum (CMG; 3·0 g/kg) and TPP (0·0 and 4·0 g/kg) on cooking loss, fat loss, colour, texture, rheology and microstructure of emulsified chicken meat batters were studied. 4. Increasing PMG reduced cooking and fat losses. Adding TPP increased hardness, springiness, cohesiveness and chewiness. The 1·0 g/kg PMG and TPP provided the greatest hardness. The batter with 3·0 g/kg PMG resulted in the lowest lightness (L*) and highest redness (a*). Adding PMG and TPP resulted in stable batters, as was evident by light microscopy results. The rheological evaluation showed the highest G' in the batter with 4·0 g/kg TPP followed in decreasing order by the batters containing TPP plus 3·0 g/kg PMG, TPP plus 1·0 g/kg PMG, 3·0 g/kg PMG, 1·0 g/kg PMG, 3·0 g/kg CMG and the control. 5. Overall, the results are important for developing new applications where malva nut gum can be used to improve yield and stability of meat products. [ABSTRACT FROM AUTHOR]

One of the challenges of manipulating genes in primary cells is that the cells have a finite proliferation capacity. This, combined with the lower gene targeting efficiency of somatic cells, makes identification of targeted clones very difficult. The objective of this study was to establish a system that allows porcine foetal fibroblasts to reach their maximal proliferation capacity in vitro. The influence of fibroblast origin, stage of foetal development, cell seeding densities and concentration of foetal bovine serum (FBS) on the population doublings, the percentage of β-galactosidase-activity-positive cells and the genome stability of foetal fibroblasts during in vitro culture was investigated. It was found that porcine foetal fibroblasts could be cultured for over 80 population doublings in the appropriate culture system. Fibroblasts from earlier stages of foetal development were better candidate cells than those from the later stages. Cells from the heart were more actively proliferative and more resistant to replicative senescence than those from the liver. Compared to 10% FBS content, 15% FBS provided better homeostatic support, not only to proliferative performance, but also in maintaining a normal karyotype. In addition, the proliferative life span of porcine foetal fibroblasts is also dependent on seeding density of the culture. [ABSTRACT FROM AUTHOR]

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Beta (β) blockers reduce the risk of postoperative atrial fibrillation and should be restarted after surgery, but it remains unclear when best to resume β blockers postoperatively. The authors thus evaluated the relationship between timing of resumption of β blockers and atrial fibrillation in patients recovering from noncardiothoracic and nonvascular surgery.Methods: The authors evaluated 8,201 adult β-blocker users with no previous history of atrial fibrillation who stayed at least two nights after noncardiothoracic and nonvascular surgery as a retrospective observational cohort. After propensity score matching on baseline and intraoperative variables, 1,924 patients who did resume β blockers by the end of postoperative day 1 were compared with 973 patients who had not resumed by that time on postoperative atrial fibrillation using logistic regression. A secondary matched analysis compared 3,198 patients who resumed β blockers on the day of surgery with 3,198 who resumed thereafter.Results: Of propensity score-matched patients who resumed β blockers by end of postoperative day 1, 4.9% (94 of 1,924) developed atrial fibrillation, compared with 7.0% (68 of 973) of those who resumed thereafter (adjusted odds ratio, 0.69; 95% CI, 0.50-0.95; P = 0.026). Patients who resumed β blockers on day of surgery had an atrial fibrillation incidence of 4.9% versus 5.8% for those who started thereafter (odds ratio, 0.84; 95% CI, 0.67-1.04; P = 0.104).Conclusions: Resuming β blockers in chronic users by the end of the first postoperative day may be associated with lower odds of in-hospital atrial fibrillation. However, there seems to be little advantage to restarting on the day of surgery itself. [ABSTRACT FROM AUTHOR]

The yeast Saccharomyces cerevisiae and its components are used for the prevention and treatment of enteric disease in different species; therefore, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to identify potential immunomodulatory S. cerevisiae components using a bovine macrophage cell line (BOMAC). The BOMAC phagocytic activity, reactive oxygen species production, and immune-related gene (IL6, IL10, IL12p40, IL13, IL23), transforming growth factor β, ARG1, CASP1, and inducible nitric oxide synthase expression were investigated when BOMAC were cocultured with cell wall components from 4 different strains (A, B, C, and D) and 2 forms of dead yeast from strain A. The BOMAC phagocytosis of mCherry-labeled MAP was concentration-dependently attenuated when BOMAC were cocultured with yeast components for 6 h. Each yeast derivative also induced a concentration-dependent increase in BOMAC reactive oxygen species production after a 6-h exposure. In addition, BOMAC mRNA expression of the immune-related genes was investigated after 6 and 24 h of exposure to yeast components. All yeast components were found to regulate the immunomodulatory genes of BOMAC; however, the response varied among components and over time. The in vitro bioassessment studies reported here suggest that dead yeast and its cell wall components may be useful for modulating macrophage function before or during MAP infection. [ABSTRACT FROM AUTHOR]

Introduction: There remains a paucity of recent data on right-sided colonic diverticulitis, especially those undergoing colectomy. We sought to describe the clinical features of patients undergoing both a laparoscopic and open surgery for right-sided diverticulitis.Methods: This study is a review of all cases of a right colectomy or ileocecectomy for diverticulitis from the National Inpatient Sample (NIS) from 2006 to 2012. Demographics, comorbidities, and postoperative outcomes were identified for all cases. A comparative analysis of a laparoscopic versus open approach was performed.Results: We identified 2233 admissions (laparoscopic = 592; open = 1641) in the NIS database. The majority of cases were Caucasian (67 %), with 6 % of NIS cases identified as Asian/Pacific Islander. The overall morbidity and in-hospital mortality rates were 24 and 2.7 %, respectively. The conversion rate from a laparoscopic to open procedure was 34 %. Postoperative complications were greater in the open versus laparoscopic cohorts (25 vs. 19 %, p < 0.01), with pulmonary complications as the highest (7.0 vs. 1.7 %; p < 0.01).Conclusion: This investigation represents one of the largest cohorts of colon resections to treat right-sided diverticulitis in the USA. In this series, right-sided diverticulitis undergoing surgery occurred most commonly in the Caucasian population and is most often approached via an open surgical technique; however, laparoscopy is a safe and feasible option. [ABSTRACT FROM AUTHOR]

Background: The impact of modern medical management of inflammatory bowel disease (IBD) on surgical necessity and outcomes remains unclear. We hypothesized that surgery rates have decreased while outcomes have worsened due to operating on "sicker" patients since the introduction of biologic medications.Methods: The Nationwide Inpatient Sample and ICD-9-CM codes were used to identify inpatient admissions for Crohn's disease and ulcerative colitis. Trends in IBD nutrition, surgeries, and postoperative complications were determined.Results: There were 191,743 admissions for IBD during the study period. Surgery rates were largely unchanged over the study period, ranging from 9 to 12 % of admissions in both Crohn's disease and ulcerative colitis. The rate of poor nutrition increased by 67 % in ulcerative colitis and by 83 % in Crohn's disease. Rates of postoperative anastomotic leak (10.2-13.9 %) were unchanged over the years. Postoperative infection rates decreased by 17 % in Crohn's disease (18 % in 2003 to 15 % in 2012; P < 0.001) but did not show a trend in any direction in ulcerative colitis.Conclusions: Rates of IBD surgery have remained stable while postoperative infectious complications have remained stable or decreased since the implementation of biologic therapies. We identified an increase in poor nutrition in surgical patients. [ABSTRACT FROM AUTHOR]

Background: Detection of colorectal cancer ideally occurs at an early stage through proper screening. We sought to establish methods by which colorectal cancers are diagnosed within an equal access military health care population and evaluate the correlation between TNM stage at colorectal cancer diagnosis and diagnostic modality (i.e., symptomatic detection vs screen detection).Materials and Methods: A retrospective chart review of all newly diagnosed colorectal cancer patients from January 2007 to August 2014 was conducted at the authors' equal access military institution. We evaluated TNM stage relative to diagnosis by screen detection (fecal occult blood test, flexible sigmoidoscopy, CT colonography, colonoscopy) or symptomatic evaluation (diagnostic colonoscopy or surgery).Results: Of 197 colorectal cancers diagnosed (59 % male; mean age 62 years), 50 (25 %) had stage I, 47 (24 %) had stage II, 70 (36 %) had stage III, and 30 (15 %) had stage IV disease. Twenty-five percent of colorectal cancers were detected via screen detection (3 % by fecal occult blood testing (FOBT), 0.5 % by screening CT colonography, 17 % by screening colonoscopy, and 5 % by surveillance colonoscopy). One hundred forty-eight (75 %) were diagnosed after onset of signs or symptoms. The preponderance of these was advanced-stage disease (stages III-IV), although >50 % of stage I-II disease also had signs or symptoms at diagnosis. The most common symptoms were rectal bleeding (45 %), abdominal pain (35 %), and change in stool caliber (27 %). The most common overall sign was anemia (60 %). Screening FOBT (odds ratio (OR) 8.7, 95 % confidence interval (CI) 1.0-78.3; P = 0.05) independently predicted early diagnosis with stage I-II disease. Patient gender and ethnicity were not associated with cancer stage at diagnosis.Conclusions: Despite equal access to colorectal cancer screening, diagnosis after development of symptomatic cancer remains more common. Fecal occult blood screen detection is associated with early stage at colorectal cancer diagnosis and is the focus for future initiatives. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a severe muscular disease caused by a frame-shift mutation in the DMD gene. DMD symptom onset occurs in early childhood (2-3 years old) and is progressive. Long-term clinical trials in a pediatric population are often required to evaluate novel therapies. Biomarkers are important tools to enable understanding disease progression and determining acute pharmacodynamic effect and how the treatment can correlate with clinical efficacy and the success rate of clinical trials. Blood Creatinine Kinase (CK) is widely used as muscle injury marker. However, levels can be confounded by the stress response elicited by blood sampling in pediatric patients. Urine samples are easier to collect and less invasive, therefore allowing for more frequent monitoring of analytes of interest over time. Titin is a muscle cell protein which contributes to muscle relaxation and contraction. Proteomic bioanalysis in urine samples revealed that fragmented titin is significantly elevated in patients with DMD. Here, we investigate whether urine titin can be used as a pharmacodynamic (PD) or progression biomarker for DMD. In mdx mice, a DMD model with a mutation on exon 23 of the DMD gene, we show that urine titin is significantly higher than in WT mice between 7 and 24 weeks of age. Furthermore, mdx mice treated with peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO), a cell penetrating oligomer that triggers exon 23 skipping, demonstrated a dramatic decrease in both blood CK and urine titin. All PPMO-treated mice demonstrated recovery of dystrophin expression, suggesting that decreases in urine titin levels reflect rescue of dystrophin levels. A quantitative immunoassay was developed and demonstrated that urine titin in DMD patients is dramatically higher than in healthy volunteers, and declines slowly with age, even though urine creatinine levels do not change. The results from this study, along with previous data, suggest that urine titin may be a useful disease progression marker and PD marker for therapies designed to restore dystrophin levels. [ABSTRACT FROM AUTHOR]

Abstract: Next-generation rationally-designed vaccine adjuvants represent a significant breakthrough to enable development of vaccines against challenging diseases including tuberculosis, HIV, and malaria. New vaccine candidates often require maintenance of a cold-chain process to ensure long-term stability and separate vials to enable bedside mixing of antigen and adjuvant. This presents a significant financial and technological barrier to worldwide implementation of such vaccines. Herein we describe the development and characterization of a tuberculosis vaccine comprised of both antigen and adjuvant components that are stable in a single vial at sustained elevated temperatures. Further this vaccine retains the ability to elicit both antibody and TH1 responses against the vaccine antigen and protect against experimental challenge with Mycobacterium tuberculosis. These results represent a significant breakthrough in the development of vaccine candidates that can be implemented throughout the world without being hampered by the necessity of a continuous cold chain or separate adjuvant and antigen vials. [Copyright &y& Elsevier]

Estimates of seaweed nutrient sequestration ability in open-water, Integrated Multi-Trophic Aquaculture (IMTA) required to ‘balance’ nutrients from fish cages have typically assigned a specific nutrient load for a specific fish biomass. The resultant culture area and densities of seaweeds required for full equivalent nutrient sequestration may have meaning only to experienced aquaculturists. Consequently, a novel ratio model is proposed which determines the weight ratio of harvested seaweeds required to sequester an equivalent weight of soluble inorganic nutrients loaded per unit growth of fish. Soluble inorganic nutrient excretion from Atlantic salmon, Salmo salar, was estimated using a semi-stochastic nutritional mass balance approach. Oxygen demand was estimated using respiratory quotients. Nutrient contents of the IMTA kelps, Alaria esculenta and Saccharina latissima, were measured at harvest times, and net oxygen production was estimated using the photosynthetic equation. To quantify uncertainty, input parameters were assigned theoretical distributions (based on empirical or literature data) and the model was run using a stratified sampling approach (Latin Hypercube) over multiple iterations, to generate distributions of weight ratios for the various nutrients. A mathematical simulation of nutrient loading from a salmon farm over a full production cycle was estimated using mean loading values per unit growth, with monthly growth estimated by a thermal growth coefficient (TGC). Results showed that one kilogramme of Atlantic salmon growth (large fish fed a typical commercial feed, ±standard deviation) resulted in the excretion of 29.49±4.20g nitrogen, 2.26±2.25g phosphorus and the respiration of 243.38±48.28g carbon. Dissolved oxygen requirements for 1kg of growth were 455.29±86.24g. Salmon smolts placed in cages in spring and harvested 21months later, load approximately 4 times more nutrients in the second grow-out season. The mean ratios of A. esculenta weight required to sequester nutrients excreted per unit weight of S. salar production were 6.7(±1.5):1 for nitrogen, 4.8(±3.0):1 for phosphorus, and 5.8(±1.4):1 for carbon. Oxygen could be supplied at a weight ratio of 4.1(±1.0):1. The mean ratios of S. latissima were 12.9(±2.7):1 for nitrogen, 10.5(±6.2):1 for phosphorus, and 10.2(±2.2):1 for carbon. Oxygen could be supplied at a weight ratio of 7.2(±1.5):1. A. esculenta appears to have almost twice the nutrient sequestration capacity per wet weight than S. latissima. However, culture densities of S. latissima are 1.5 times greater than those for A. esculenta and when spatially weighted this difference is reduced to 1–1.5 times. Numbers of rafts for both kelp species required for full nutrient sequestration from a commercial scale salmon farm exceed the number of rafts which can be practically deployed within a typical site lease area. However, not all inorganic nutrients from cultured fish will be available to IMTA seaweeds, nor should 100% nutrient sequestration need be the only successful endpoint in such systems. These aspects should be considered when assessing the net value of kelps in open-water IMTA systems. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about patterns and risks in spinal trauma.

Marek’s disease virus (MDV) is a cell-associated oncogenic herpesvirus that targets B cells and T cells, inducing lymphoid tumours in chickens. Genetic resistance to Marek’s disease (MD) is regulated in a polygenic fashion. In this study, we sought to compare the gene expression profiles following infection of birds that are genetically resistant or susceptible to MD (with the B21 and B19 haplotypes respectively at the MHC locus), including comparisons to uninfected controls. On days 4, 7, 14 and 21 post-infection, gene expression profiles in spleen tissue were obtained using a chicken immune-specific microarray. A number of genes showed significant ( P ≤ 0.05) differential expression across time and treatments. These included the chemokine AH221, B-cell marker Bu-1, IgG, IgA, IgM, MHC class II β chain, granzyme A ( GZMA) and signal transducers and activators of transcription 2 ( STAT2) genes. In several comparisons, genes such as GZMA and STAT2 were induced in infected birds regardless of their genetic background. However, only immunoglobulin genes were differentially expressed by ≥2-fold in resistant compared with susceptible infected chickens. IgM and IgG were significantly induced on day 7 post-infection in susceptible chickens compared to resistant birds, whereas both of these genes were repressed in susceptible birds on day 14 post-infection. Overall, gene expression profiles in the chicken spleen observed after MDV infection were dependent on time and host genetic background. These gene expression profiles provide a platform for defining novel candidate genes for resistance or susceptibility to MD. [ABSTRACT FROM AUTHOR]