A novel aptamer-based small RNA delivery platform and its application to cancer therapy.

Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we designed a novel targeting small RNA delivery platform comprising of three oligonucleotides: (1) a guide RNA sequence, (2) part of a passenger sequence linked to a DNA aptamer via a PEG linker, and (3) another passenger sequence conjugated to cholesterol, which assemble through complementary base pair annealing. Remarkably, in the presence of magnesium, this molecule self-assembled into a nanoparticle with a hydrophobic cholesterol core, hydrophilic RNA oligonucleotide shell and PEG-linked DNA aptamer flare. The nanoparticles conferred protection to the RNA oligonucleotides against nuclease degradation, which increased bioavailability, and reduced systemic inflammatory responses. The aptamer allowed targeted delivery of RNA therapeutics through cell-specific surface markers, and once inside the cell, the nanoparticles induced lysosomal leakage that released the RNA oligonucleotides into the cytosol to achieve gene silencing. We created a c-Kit-targeting miR-26a delivery particle that specifically accumulated in c-Kit+ breast cancer, significantly increased T cell recruitment, and inhibited tumor growth. Regression of large established tumors were achieved when the nanoparticle was used in combination with anti-CTLA-4 monoclonal antibody.

Deterioration After Surgery for Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

STUDY DESIGN: A Prospective cohort study. OBJECTIVE: To investigate the incidence, etiology, and outcomes of patients who experience neurological deterioration after surgery for Degenerative Cervical Myelopathy (DCM). SUMMARY OF BACKGROUND DATA: Postoperative neurological deterioration is one of the most undesirable complications that can occur after surgery for DCM. METHODS: We analyzed data from the Canadian Spine Outcomes and Research Network DCM prospective cohort study. We defined postoperative neurological deterioration as any decrease in modified Japanese Orthopaedic Association (mJOA) score by at least one point from baseline to three months after surgery. Adverse events were collected using the Spinal Adverse Events Severity protocol. Secondary outcomes included patient-reported pain, disability, and health-related quality of life. RESULTS: Among a study cohort of 428 patients, 50 (12%) deteriorated by at least one mJOA point after surgery for DCM (21 by one point, 15 by two points, and 14 by three points or more). Significant risk factors included older age, female sex, and milder disease. Among those who deteriorated, 13 experienced contributing intraoperative or postoperative adverse events, six had alternative non-DCM diagnoses, and 31 did not have an identifiable reason for deterioration. Patients who deteriorated had significantly lower mJOA scores at one year after surgery [13.5 (SD 2.7) vs. 15.2 (SD 2.2), P <0.01 and those with larger deteriorations were less likely to recover their mJOA to at least their preoperative baseline, but most secondary measures of pain, disability, and health-related quality of life were unaffected. CONCLUSIONS: The incidence of deterioration of mJOA scores after surgery for DCM was approximately one in 10, but some deteriorations were unrelated to actual spinal cord impairment and most secondary outcomes were unaffected. These findings can inform patient and surgeon expectations during shared decision-making, and they demonstrate that the interpretation of mJOA scores without clinical context can sometimes be misleading.

Nutrition of free-living Neotropical psittacine nestlings and implications for hand-feeding formulas.

Psittacidae is one of the most endangered families of birds in the world. Knowledge of their nutrition is important for understanding their survival and productivity in the wild, as well as for their adequate husbandry under human care. Hand-rearing is a common practice for psittacines, however research on their nutrition is limited. We analysed the predicted metabolisable energy, crude protein, crude fat, minerals and the essential amino acid profiles of the crop contents from free-living nestlings of scarlet macaws (Ara macao) and red-and-green macaws (Ara chloropterus) from southeastern Peru, Cuban Amazons (Amazona leucocephala bahamensis) from the Bahamas, lilac-crowned Amazons (Amazona finschi) from northwestern Mexico and thick-billed parrots (Rhynchopsitta pachyrhyncha) from northern Mexico. The crop content of the different parrot species displayed remarkably similar nutritional profiles, considering their diversity in habitats, geographic ranges and food sources. The crude protein and crude fat concentrations in crop samples were particularly similar for the Ara and Amazona species, while the thick-billed parrot stood out for its higher crude fat and lower crude protein content. Wider variations were found among the concentrations of sodium (Na) and iron (Fe), proline and tryptophan. Compared with the requirements of 6-12 weeks leghorn chickens, all free-ranging parrot diets contained lower crude protein, calcium (Ca), potassium (P) and Na concentrations. The hand-feeding formulas contained lower crude fat, magnesium (Mg), arginine, valine and phenylalanine concentrations, as well as much higher levels of Ca and zinc (Zn), in comparison with parrot crop samples. Our data suggest that a single formulation could be used to hand-rear Ara and Amazona sp. of 3 weeks of age and older, while a different formulation would likely be more appropriated for Rhynchopsitta sp. Experimental studies should evaluate if increasing the concentration of crude fat, Mg, arginine, valine and phenylalanine enhances psittacine chick growth and health.

Evaluation of image quality and task performance for a mobile C-arm with a complementary metal-oxide semiconductor detector.

We assessed interventional radiologists' task-based image quality preferences for two- and three-dimensional images obtained with a complementary metal-oxide semiconductor (CMOS) flat-panel detector versus a hydrogenated amorphous silicon (a-Si:H) flat-panel detector. CMOS and a-Si:H detectors were implemented on identical mobile C-arms to acquire radiographic, fluoroscopic, and cone-beam computed tomography (CBCT) images of cadavers undergoing simulated interventional procedures using low- and high-dose settings. Images from both systems were displayed side by side on calibrated, diagnostic-quality displays, and three interventional radiologists evaluated task performance relevant to each image and ranked their preferences based on visibility of pertinent anatomy and interventional devices. Overall, CMOS images were preferred in fluoroscopy ( p = 0.002 ) and CBCT ( p = 0.004 ), at low-dose settings ( p = 0.001 ), and for tasks associated with high levels of spatial resolution [e.g., fine anatomical details ( p = 0.006 ) and assessment of interventional devices ( p = 0.015 )]. No significant difference was found for fluoroscopic imaging tasks emphasizing temporal resolution ( p = 0.072 ), for radiography tasks ( p = 0.825 ), when using high-dose settings ( p = 0.360 ), or tasks involving general anatomy ( p = 0.174 ). The image quality preferences are consistent with reported technical advantages of CMOS regarding finer pixel size and reduced electronic noise.

Treatment of Mild Cervical Myelopathy: Factors Associated With Decision for Surgical Intervention.

STUDY DESIGN: Prospective Cohort OBJECTIVE.: The aim of this study was to evaluate which demographic, clinical, or radiographic factors are associated with selection for surgical intervention in patients with mild cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Surgery has not been shown superior to best conservative management in mild CSM comparative studies; trials of conservative management represent an acceptable alternative to surgical decompression. It is unknown what patients benefit from surgery. METHODS: This is a prospective study of patients with mild CSM, defined as modified Japanese Orthopaedic Association Score (mJOA) ≥15. Patients were recruited from seven sites contributing to the Canadian Spine Outcomes Research Network. Demographic, clinical, radiographic and health related quality of life data were collected on all patients at baseline. Multivariate logistic regression modeling was used to identify factors associated with surgical intervention. RESULTS: There were 122 patients enrolled, 105 (86.0%) were treated surgically, and 17 (14.0%) were treated nonoperatively. Overall mean age was 54.8 years (SD 12.6) with 80 (65.5%) males. Bivariate analysis revealed no statistically significant differences between surgical and nonoperative groups with respect to age, sex, BMI, smoking status, number of comorbidities and duration of symptoms; mJOA scores were significantly higher in the nonoperative group (16.8 [SD 0.99] vs. 15.9 [SD 0.89], P < 0.001). There was a statistically significant difference in Neck Disability Index, SF12 Physical Component, SF12 Mental Component Score, EQ5D, and PHQ-9 scores between groups; those treated surgically had worse baseline questionnaire scores (P < 0.05). There was no difference in radiographic parameters between groups. Multivariable analysis revealed that lower quality of life scores on EQ5D were associated with selection for surgical management (P < 0.018). CONCLUSION: Patients treated surgically for mild cervical myelopathy did not differ from those treated nonoperatively with respect to baseline demographic or radiographic parameters. Patients with worse EQ5D scores had higher odds of surgical intervention. LEVEL OF EVIDENCE: 3.

Performance of broilers fed diets supplemented with two yeast cell wall strains using two feeding strategies.

Different supplements or strategies have been proposed as alternatives to the use of antibiotics at sub-therapeutic levels in chickens. Mannan oligosaccharides and ß-glucans, yeast cell wall fractions (YCW), have been reported to beneficially influence broiler performance and health. Two differently produced yeast cell wall fractions derived from Saccharomyces cerevisiae were evaluated in this study using two different supplementation strategies offered to full-term broilers. The birds were placed in floor pens on used pine-shaving litter to increase potential microbial stress and mimic industry practice. The study utilized a three-phase feeding program with a 1- to 21-day starter, 21- to 35-day grower and 35- to 42-day finisher phases. Five dietary treatments were compared in this study. The experimental diets consisted of a control basal broiler diet; or the basal diet supplemented with the two differently produced fractions of YCW. The YCW products were supplemented at a constant 250 ppm or a decreasing concentration program (500, 250, 125 ppm) throughout the three feeding phases. Birds fed diets supplemented with either YCW products at any inclusion regimen demonstrated higher (P < 0.05) body weight (BW) in all three phases than control birds. The difference in final 42-day BW of the YCW treatments (3041 g) averaged 165 g higher (P < 0.05) than the control group. For all YCW treatments, productivity index was higher (P < 0.05) in the grower (418) and finisher phase (441) versus control birds (389 grower and 415 finisher). These results suggested that both YCW fractions prepared from Saccharomyces cerevisiae can improve broiler performance when added at either a constant rate (250 ppm) or at a decreasing rate from 500 ppm for the starter to 125 ppm for the finisher phase.

Evaluation of high dietary phytase supplementation on performance, bone mineralization, and apparent ileal digestible energy of growing broilers.

The present study was conducted to evaluate four commercially available phytase sources supplemented at regular (R) and super-dose (S) levels on live performance, bone mineralization, and apparent ileal digestible energy. Broiler chickens were allocated in stainless steel battery brooders (six birds per cage and eight pen replicates per treatment). A basal diet formulated to contain 0.2% non-phytate phosphorus (NPP) and 0.7% Ca was subdivided to create 11 dietary treatments: (1) basal diet was kept as the negative control (NC); (2) NC + limestone and monoclacium phosphate to create positive controls 1 and 2 formulated to yield 0.3% and 0.4% NPP; (3) NC + phytase A (250 and 1,500 FTU/kg); (4) NC + phytase B (500 and 1,500 FTU/kg); (5) NC + phytase C (500 and 1,000 FTU/kg); (6) NC + phytase D (1,000 and 2,000 FYT/kg). Performance was evaluated on d 7, 14, and 22. Tibia bone ash, tibia breaking strength, bone mineral content, and bone mineral density were evaluated on d 22. Apparent energy digestibility was evaluated on d 24. At d 7, phytases A and C supplemented at S level improved (P < 0.05) body weight and weight gain when compared to the NC. At d 14 and 22, all phytase sources improved (P < 0.05) body weight, weight gain, and bone mineralization when compared to the chicks under the NC diet. Overall, phytase supplementation at S level improved 17% apparent ileal digestibility at 24 d. Throughout the grow out period, phytase super-dose yield (P < 0.05) better performance, bone characteristics, and energy digestibility than the regular dietary level. In conclusion, all phytase sources were able to compensate the phosphorus deficiency and promote performance and bone mineralization. High levels of phytase showed a higher response when compared to the lower levels of supplementation.

Assessing effects of yeast cell wall supplementation on threonine requirements in broilers as measured by performance and intestinal morphology.

The objective of this study was to evaluate whether or not the use of a prebiotic yeast cell wall (YCW) affects threonine requirements in starter broilers. Two hundred and forty 1-d-old Ross 308 broiler chickens were distributed among 2 Petersime battery brooder units (48 pens; 5 birds per pen). Different threonine to lysine ratios (0.60, 0.65, and 0.70 to 1.0) with 1.22% available lysine with and without YCW at 250 ppm was fed to the chickens in order to evaluate performance and intestinal morphology over a 21-d trial. A basal diet with 22% protein and 2,980 kcal/kg ME was prepared to create the 6 dietary treatments. The calculated lysine concentration was 1.34%, whereas threonine was 0.81, 0.88, and 0.94%, respectively. Pen weights and feed consumption were recorded at d 1, 7, 14, and 21 of the experiment. Jejunal and ileal samples were collected on d 21 for histology analysis to evaluate villi height (VH), crypt depth, villi width (VW), and muscularis thickness. A threonine to lysine ratio of 0.7:1.0 resulted in significant improvement of performance variables with increased jejunum VW and ileum VH compared with the other threonine to lysine ratios. Adding YCW to starter broiler did not affect the requirement for threonine.

Beta-Alanine Does Not Enhance the Effects of Resistance Training in Older Adults.

To investigate the potential of beta-alanine to increase muscular endurance of elder individuals in specific resistance-training protocols, we randomly assigned 27 participants (60-82 years of age) to a 12-week double-blind intervention using 3.2 g/day beta-alanine or placebo with or without resistance training to determine the effects on anthropometrics, muscular performance, and activities of daily living (ADL). The endurance-based resistance-training program (ERT) was given three times per week and included two sets of 15-25 repetitions on 11 computerized pneumatic machines (alternating upper and lower body) at an intensity of 50% of maximum lifting weight (1RM). Mixed design analysis of variance (ANOVA) revealed no significant group × time interactions (p > .05) for any anthropometric or strength measures except 1RM leg press (p = .010). A post hoc analysis revealed significant improvements in 1RM leg press for both the resistance-training groups (p < .001) but no significant between-group difference attributable to beta-alanine. For the 20-repetition chest and leg press tests, no main effects of beta-alanine or group × time interactions for the exercise versus control groups were observed. Pairwise comparisons, however, did reveal significant improvements in peak and average power for both tests and fatigue index for the chest press in resistance-training groups. Although beta-alanine had no effect on any measures, the ERT program did positively affect three performance variables: 1RM, mechanical power, and fatigue patterns during muscular endurance testing. Future research should examine beta-alanine with different dosages and training programs to expand upon our findings using endurance-based resistance training.

Influence of different yeast cell wall preparations and their components on performance and immune and metabolic pathways in Clostridium perfringens-challenged broiler chicks.

A study was conducted to evaluate the influence of the purification of yeast cell wall (YCW) preparations on broiler performance and immunogenic and metabolic pathways under microbial challenge. A total of 240 (day old) chicks were distributed among two battery brooder units (48 pens; 5 birds/pen; 8 replicates/treatment). A basal starter diet was divided into 5 batches to create 6 dietary treatments; non-challenge (NCh-C) and challenge (Ch-C) controls, semi-purified YCW containing cytosol contents (SPYCW; 250 mg/kg), purified YCW (PYCW; 250 mg/kg), 50% purified beta-glucan (BG; 130 mg/kg), and 99.9% purified mannan-oligosaccharide (MOS; 53 mg/kg). All birds were immunocompromised with infectious bursal disease vaccine (10× the recommended dose) on day 10 and then all birds except NCh-C birds were challenged with Clostridium perfringens (Cp) (107 cfu/mL) via oral gavage on days 16 and 17. On day 21, tissue samples were collected from the jejunum and duodenum for analysis with chicken-specific, peptide arrays to study the influence of YCW supplementation on immune and metabolic kinase pathways. On day 16, SPYCW had significantly lower body weight (BW) and weight gain (WG) than other treatments except BG (P < 0.05). The productivity index (PI) was lower in SPYCW and BG than in NCh-C, Ch-C, and PYCW. On day 21, after the Cp challenge, NCh-C was higher than Ch-C, SPYCW, and BG in BW, WG, and PI (P = 0.03). The PI of PYCW was similar to NCh-C. The addition of purified YCW to the starter broiler diets influenced the immune and metabolic pathways in the gut. A total of 459 and 367 peptides in the duodenum and jejunum, respectively, were changed due to the Cp challenge. The YCW treatments had different degrees of influence on these peptides for both the duodenum and jejunum. These results suggest that relative purification of YCW and specific fractions of the YCW can influence broiler performance differently during microbial challenges and can alleviate the impact of these stressors.

Bluegenics: Bioactive Natural Products of Medicinal Relevance and Approaches to Their Diversification.

Nature provides a valuable resource of medicinally relevant compounds, with many antimicrobial and antitumor agents entering clinical trials being derived from natural products. The generation of analogues of these bioactive natural products is important in order to gain a greater understanding of structure activity relationships; probing the mechanism of action, as well as to optimise the natural product's bioactivity and bioavailability. This chapter critically examines different approaches to generating natural products and their analogues, exploring the way in which synthetic and biosynthetic approaches may be blended together to enable expeditious access to new designer natural products.

Experience Drives Synchronization: The phase and Amplitude Dynamics of Neural Oscillations to Musical Chords Are Differentially Modulated by Musical Expertise.

Musical expertise is associated with structural and functional changes in the brain that underlie facilitated auditory perception. We investigated whether the phase locking (PL) and amplitude modulations (AM) of neuronal oscillations in response to musical chords are correlated with musical expertise and whether they reflect the prototypicality of chords in Western tonal music. To this aim, we recorded magnetoencephalography (MEG) while musicians and non-musicians were presented with common prototypical major and minor chords, and with uncommon, non-prototypical dissonant and mistuned chords, while watching a silenced movie. We then analyzed the PL and AM of ongoing oscillations in the theta (4-8 Hz) alpha (8-14 Hz), beta- (14-30 Hz) and gamma- (30-80 Hz) bands to these chords. We found that musical expertise was associated with strengthened PL of ongoing oscillations to chords over a wide frequency range during the first 300 ms from stimulus onset, as opposed to increased alpha-band AM to chords over temporal MEG channels. In musicians, the gamma-band PL was strongest to non-prototypical compared to other chords, while in non-musicians PL was strongest to minor chords. In both musicians and non-musicians the long-latency (> 200 ms) gamma-band PL was also sensitive to chord identity, and particularly to the amplitude modulations (beats) of the dissonant chord. These findings suggest that musical expertise modulates oscillation PL to musical chords and that the strength of these modulations is dependent on chord prototypicality.

Improved meta-analytic methods show no effect of chromium supplements on fasting glucose.

The trace mineral chromium has been extensively researched over the years in its role in glucose metabolism. Dietary supplement companies have attempted to make claims that chromium may be able to treat or prevent diabetes. Previous meta-analyses/systematic reviews have indicated that chromium supplementation results in a significant lowering of fasting glucose in diabetics but not in nondiabetics. A meta-analysis was conducted using an alternative measure of effect size, d(ppc2) in order to account for changes in the control group as well as the chromium group. The literature search included MEDLINE, the Cochrane Controlled Trials Register, and previously published article reviews, systematic reviews, and meta-analyses. Included studies were randomized, placebo-controlled trials in the English language with subjects that were nonpregnant adults, both with and without diabetes. Sixteen studies with 809 participants (440 diabetics and 369 nondiabetics) were included in the analysis. Screening for publication bias indicated symmetry of the data. Tests of heterogeneity indicated the use of a fixed-effect model (I² = 0 %). The analysis indicated that there was no significant effect of chromium supplementation in diabetics or nondiabetics, with a weighted average effect size of 0.02 (SE = 0.07), p = 0.787, CI 95 % = -0.12 to 0.16. Chromium supplementation appears to provide no benefits to populations where chromium deficiency is unlikely.

Cognitive control in auditory working memory is enhanced in musicians.

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.

Bringing in the negative reinforcements: the avoidance feedback-related negativity.

The feedback-related negativity (FRN) is an event-related potential thought to reflect a reward prediction error, when an outcome is worse than expected. Behavior motivated by the avoidance of negative outcomes is sustained through negative reinforcement processes. Escaping or avoiding a negative outcome may be successful or not, resulting in an analogous situation to that which elicits the FRN. We observed that when expected avoidance of an aversive outcome fails to occur, there occurs a negative deflection in the frontocentral event-related potential at approximately 350 ms, but with a slow wave following. We suggest that the FRN may be considered an index of a broader class of reward-based learning that also includes avoiding negative outcomes as well as expecting positive ones.

Cognitive and emotional modulation of brain default operation.

Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful state. Previously, the nature of these processes was probed by varying cognitive task parameters, but the presence of emotional processes, while often assumed, was little investigated. With fMRI, we studied the effect of systematic variations of both cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant dissonant musical sounds, there was an interaction between the experimental condition and the stimulus type. The current results are consistent with the previously reported effect of task difficulty on task-related brain activation decreases. The results also indicate that task-related decreases may be further modulated by the emotional stimulus connotation.

Predictive coding of music--brain responses to rhythmic incongruity.

During the last decades, models of music processing in the brain have mainly discussed the specificity of brain modules involved in processing different musical components. We argue that predictive coding offers an explanatory framework for functional integration in musical processing. Further, we provide empirical evidence for such a network in the analysis of event-related MEG-components to rhythmic incongruence in the context of strong metric anticipation. This is seen in a mismatch negativity (MMNm) and a subsequent P3am component, which have the properties of an error term and a subsequent evaluation in a predictive coding framework. There were both quantitative and qualitative differences in the evoked responses in expert jazz musicians compared with rhythmically unskilled non-musicians. We propose that these differences trace a functional adaptation and/or a genetic pre-disposition in experts which allows for a more precise rhythmic prediction.

Neural discrimination of nonprototypical chords in music experts and laymen: an MEG study.

At the level of the auditory cortex, musicians discriminate pitch changes more accurately than nonmusicians. However, it is not agreed upon how sound familiarity and musical expertise interact in the formation of pitch-change discrimination skills, that is, whether musicians possess musical pitch discrimination abilities that are generally more accurate than in nonmusicians or, alternatively, whether they may be distinguished from nonmusicians particularly with respect to the discrimination of nonprototypical sounds that do not play a reference role in Western tonal music. To resolve this, we used magnetoencephalography (MEG) to measure the change-related magnetic mismatch response (MMNm) in musicians and nonmusicians to two nonprototypical chords, a "dissonant" chord containing a highly unpleasant interval and a "mistuned" chord including a mistuned pitch, and a minor chord, all inserted in a context of major chords. Major and minor are the most frequently used chords in Western tonal music which both musicians and nonmusicians are most familiar with, whereas the other chords are more rarely encountered in tonal music. The MMNm was stronger in musicians than in nonmusicians in response to the dissonant and mistuned chords, whereas no group difference was found in the MMNm strength to minor chords. Correspondingly, the length of musical training correlated with the MMNm strength for the dissonant and mistuned chords only. Our findings provide evidence for superior automatic discrimination of nonprototypical chords in musicians. Most likely, this results from a highly sophisticated auditory system in musicians allowing a more efficient discrimination of chords deviating from the conventional categories of tonal music.

Guar meal ameliorates Eimeria tenella infection in broiler chicks.

Guar meal contains relatively high levels of saponins, which are known to have antiprotozoal activity and may be effective against coccidiosis. A 2x2 factorial experiment investigated the impact of guar meal (0 or 5%) corn-soy-based starter broiler diets on chicks unchallenged or challenged with Eimeria tenella. At 1 day of age, 120 unsexed RossxRoss broiler chicks were randomly distributed among four treatment groups. Chicks were challenged with 5x10(3) sporulated oocysts of E. tenella in 0.5 ml at 10 days of age by oral gavage. Weekly body weight, body weight gains, feed conversion ratio and mortality rate were recorded for chicks fed from 0 to 21 days of age. Oocysts shed per gram feces were recorded from 6 to 10 days post-challenge. Results showed that challenged chicks fed 0% guar meal had significantly higher oocysts per gram shed in feces than the other groups. No significant differences among treatment groups in mortality rate were observed. Body weights of unchallenged and challenged chicks fed 0% guar meal were significantly higher than those fed 5% guar meal at 2 weeks of age. Results indicated that including 5% guar meal in the diet of chicks challenged with E. tenella decreased oocysts shed per gram feces and prevented bloody diarrhea, but without affects on body weight and feed conversion ratio at 11 days post-challenge.

To musicians, the message is in the meter pre-attentive neuronal responses to incongruent rhythm are left-lateralized in musicians.

Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.