A comparison of resting state EEG and structural MRI for classifying Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease (AD) is the leading cause of dementia, accounting for 70% of cases worldwide. By 2050, dementia prevalence will have tripled, with most new cases occurring in low- and middle-income countries. Mild cognitive impairment (MCI) is a stage between healthy aging and dementia, marked by cognitive deficits that do not impair daily living. People with MCI are at increased risk of dementia, with an average progression rate of 39% within 5 years. There is urgent need for low-cost, accessible and objective methods to facilitate early dementia detection. Electroencephalography (EEG) has potential to address this need due to its low cost and portability. Here, we collected resting state EEG, structural MRI (sMRI) and rich neuropsychological data from older adults (55+ years) with AD, amnestic MCI (aMCI) and healthy controls (~60 per group). We evaluated a range of candidate EEG markers (i.e., frequency band power and functional connectivity) for AD and aMCI classification and compared their performance with sMRI. We also tested a combined EEG and cognitive classification model (using Mini-Mental State Examination; MMSE). sMRI outperformed resting state EEG at classifying AD (AUCs â€‹= â€‹1.00 vs 0.76, respectively). However, both EEG and sMRI were only moderately good at distinguishing aMCI from healthy aging (AUCs â€‹= â€‹0.67-0.73), and neither method achieved sensitivity above 70%. The addition of EEG to MMSE scores had no added benefit relative to MMSE scores alone. This is the first direct comparison of EEG and sMRI for classification of AD and aMCI.

Restructuring an evolving Irish trauma system: What can we learn from Europe and Australia?

AIM: Major trauma is a leading cause of mortality and disability. Internationally, major trauma centres and comprehensive trauma networks are associated with improved outcomes. This study aimed to examine selected international trauma systems in Europe and Australia to identify common themes that may aid reconfiguration of the Irish trauma service. METHODS: An electronic search strategy was utilised using Medline, and a search of the grey literature using Google and Google Scholar. Search terms included "trauma systems", "trauma care", "major trauma centre" and "trauma network". Relevant articles were reviewed and data summarised in a narrative format. RESULTS: Republic of Ireland currently lacks designated major trauma centres and surrounding trauma networks. Lessons from international models and data from the on-going national trauma audit may guide reconfiguration. Well-functioning trauma systems internationally bear striking similarities, and involve a hub and spoke model. This model has a central major trauma centre, surrounded by a co-ordinated trauma network with trauma units. Concentration of major trauma into high volume centres is key, but these centres must be adequately resourced to deliver a high quality service. Investment in and co-ordination of prehospital care is essential to overcome geographical impediments to centralising trauma care. Funding of rehabilitation infrastructure and resources is also an integral part of a well-functioning trauma system. Trauma outcome data is key to informing trauma system design, with dissemination of this data and public engagement critical for change. CONCLUSION: International models of trauma care provide valuable lessons for countries currently in process of reconfiguring trauma services.

Is the post-disturbance composition of a plant population determined by selection for outcrossed seedlings or by the composition of the seedbank?

Seedbanks are expected to buffer populations against disturbances, such as fire, that could alter the genetic composition of smaller, ephemeral adult populations. However, seedling genotypes may be influenced by the spatially heterogeneous nature of both the seedbank and the disturbance (for example, germination may vary with local disturbance) and also by selection acting on germination and post-germination performance. We used microsatellite-DNA surveys of seedlings emerging from the soil-stored seedbanks of Grevillea macleayana after wildfire to compare diversity and spatial structure in seedlings and adults, and through resampling of the seedling data set, to determine whether the resultant adult population reflected the effects of selection or random seedling mortality. The large post-fire seedling cohorts captured the full allelic diversity of the pre-fire adult population. However, we found a mismatch in the genotypic structure of adults and seedlings. Seedlings displayed larger heterozygous deficits than adults; however, over the ensuing 11 years, seedling heterozygosity eventually matched values for the pre-fire adults. Increasing heterozygosity among adults has generally been attributed to heterosis and/or reduction in Wahlund effects via self-thinning. Resampling of early post-fire seedlings to generate samples of equivalent size to survivors at 11 years showed that increases in heterozygosity must be driven by selection favouring outcrossed seed. This finding is important in an evolutionary context but also has implications for the restoration of natural or managed populations where a seedbank is a viable source of recruits.

Defining optimal dietary starch, oil, and amino acid inclusion levels for broilers experiencing a coccidiosis challenge.

Alternative methods to alleviate coccidiosis in broilers are of interest to producers, including dietary strategies to minimize disruptions in growth rate and efficiency when faced with health challenges. Our objective was to determine optimal combinations of dietary starch, amino acids (AA), and oil to benefit productivity of broilers experiencing Eimeria-induced immune activation. Two trials were conducted using 1,536 male Ross 308 broiler chicks in floor pens randomly assigned to 1 of 17 experimental treatments. All birds received common starter (d 0-10) and finisher (d 24-35) diets, and only differed based on their assigned experimental grower diet (d 10-24). Trial 1 experimental grower diets ranged from 2,700 to 3,300 kcal/kg AME. Trial 2 included 10 experimental grower diets following a simplex lattice design consisting of 3 basal lots formulated to have the highest starch (45.4%), oil (10.2%), or AA density (120, 1.33% digestible Lys) and mixed in 4 equally spaced levels for each component (0, 0.33, 0.67, 1). These mixtures enabled varying densities of AA (80-120% of recommendation), starch:oil (4:1-20:1), and AME (2,940-3,450 kcal/kg). Bird and feeder weights were collected on d 0, 10, 24, and 35, and birds were exposed to an Eimeria challenge on d 11 or 12. In trial 2, excreta samples were collected for AME determination and carcasses were processed on d 36. Data were analyzed using ANOVA, t test, or regression. In Trial 1, BW gain and feed conversion were improved (P < 0.05) by increasing dietary AME. In Trial 2, birds receiving diets containing AA at 93 to 107% of recommendations and higher oil exhibited improved (P < 0.05) performance, but increased starch at the expense of oil reduced performance (P < 0.05). Relative breast and fat pad weights were not influenced by diet in Trial 2. We determined that broilers mildly challenged with Eimeria would exhibit highest BW gain when receiving diets containing 35.8% starch, 8.9% oil, and 101.3% of AA recommendations, which can be utilized by producers to maintain productivity under health-challenged conditions.

Evaluation of adjustment methods used to determine prevalence of low birth-weight babies at a rural hospital in Andhra Pradesh, India.

Accurate reporting of prevalence of low birth weight (LBW) is important for monitoring health of a population. LBW is often underestimated in developing countries due to heaping of the data at 2.5 kg. UNICEF uses an average adjustment factor of 25% to re-classify babies listed as exactly 2.5 kg into the LBW category. From October 2009 to February 2010, we weighed 859 consecutive live births at a rural hospital in Andhra Pradesh, India, using analog and digital scales to evaluate the relative validity of the adjustment factor. Significantly more babies weighed exactly 2.5 kg on analog (13.4%) versus digital (2.2%) scales, showing heaping. Percentage of LBW by digital method (29.5%) was significantly higher compared to the analog method (23%) and with adjustment factors (26.4%). Conventional methods of adjusting birth-weight data underestimate the prevalence of LBW. Sensitive digital weighing machines or better adjustment methods are needed to monitor LBW in developing countries.

Dietary Tyrosine Intake (FFQ) Is Associated with Locus Coeruleus, Attention and Grey Matter Maintenance: An MRI Structural Study on 398 Healthy Individuals of the Berlin Aging Study-II.

BACKGROUND AND OBJECTIVE: It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus-Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer's disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC signal intensity 2) whether LC mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test - TMT), and 3) whether LC signal intensity relates to an objective measure of brain maintenance (BrainPAD). METHODS: The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC signal intensity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA - measured with Food Frequency Questionnaire - FFQ). As a control procedure, the same analyses were repeated on other main seeds of the neuromodulators' subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. RESULTS: Results show that HD-Tyr-IDA is positively associated with LC signal intensity. Similarly, LC disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. CONCLUSIONS: These findings provide the first evidence linking tyrosine intake with LC-NA system signal intensity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Neural correlates of oddball detection in self-motion heading: a high-density event-related potential study of vestibular integration.

The perception of self-motion is a product of the integration of information from both visual and non-visual cues, to which the vestibular system is a central contributor. It is well documented that vestibular dysfunction leads to impaired movement and balance, dizziness and falls, and yet our knowledge of the neuronal processing of vestibular signals remains relatively sparse. In this study, high-density electroencephalographic recordings were deployed to investigate the neural processes associated with vestibular detection of changes in heading. To this end, a self-motion oddball paradigm was designed. Participants were translated linearly 7.8 cm on a motion platform using a one second motion profile, at a 45° angle leftward or rightward of straight ahead. These headings were presented with a stimulus probability of 80-20 %. Participants responded when they detected the infrequent direction change via button-press. Event-related potentials (ERPs) were calculated in response to the standard (80 %) and target (20 %) movement directions. Statistical parametric mapping showed that ERPs to standard and target movements differed significantly from 490 to 950 ms post-stimulus. Topographic analysis showed that this difference had a typical P3 topography. Individual participant bootstrap analysis revealed that 93.3 % of participants exhibited a clear P3 component. These results indicate that a perceived change in vestibular heading can readily elicit a P3 response, wholly similar to that evoked by oddball stimuli presented in other sensory modalities. This vestibular-evoked P3 response may provide a readily and robustly detectable objective measure for the evaluation of vestibular integrity in various disease models.

Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review.

Hypovolaemia after overnight fasting is believed to exacerbate postoperative nausea and vomiting (PONV). However, data on the efficacy of supplemental i.v. crystalloids for PONV prophylaxis are conflicting. We performed a literature search using CENTRAL, MEDLINE, EMBASE, CINAHL, and Web of Science. We included prospective randomized controlled trials that reported PONV event rates in patients receiving supplemental i.v. crystalloids or a conservative fluid regimen after elective surgery under general anaesthesia. Studies were evaluated with regard to random sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessment, incomplete outcome data, and selective reporting. We identified 15 trials (n=787 crystalloids; n=783 conservative fluids). Compared with conservative fluids, i.v. crystalloids reduced the risk of early postoperative nausea (PON) (relative risk 0.73, 95% confidence interval 0.59-0.89; P=0.003), late PON (0.41, 0.22-0.76; P=0.004), and overall PON (0.66, 0.46-0.95; P=0.02). I.V. crystalloids did not reduce the risk of early postoperative vomiting (POV) (0.66, 0.37-1.16; P=0.16) or late POV (0.52, 0.25-1.11; P=0.09), but did reduce overall POV (0.48, 0.29-0.79; P=0.004). I.V. crystalloids did not reduce the risk of early PONV (0.74, 0.49-1.12; P=0.16), but did reduce the risk of late PONV (0.27, 0.13-0.54; P<0.001) and overall PONV (0.59, 0.42-0.84; P=0.003). I.V. crystalloids reduced the need for antiemetic rescue treatment (0.56, 0.45-0.68; P<0.001). In summary, supplemental i.v. crystalloids were associated with a lower incidence of several PONV outcomes. However, a number of PONV outcomes failed to reach statistical significance, perhaps due to the lack of power. Thus, studies sufficiently powered for the less frequent outcomes (e.g. POV) are required.

Evidence-based analysis of risk factors for postoperative nausea and vomiting.

BACKGROUND: /st> In assessing a patient's risk for postoperative nausea and vomiting (PONV), it is important to know which risk factors are independent predictors, and which factors are not relevant for predicting PONV. METHODS: /st> We conducted a systematic review of prospective studies (n>500 patients) that applied multivariate logistic regression analyses to identify independent predictors of PONV. Odds ratios (ORs) of individual studies were pooled to calculate a more accurate overall point estimate for each predictor. RESULTS: /st> We identified 22 studies (n=95 154). Female gender was the strongest patient-specific predictor (OR 2.57, 95% confidence interval 2.32-2.84), followed by the history of PONV/motion sickness (2.09, 1.90-2.29), non-smoking status (1.82, 1.68-1.98), history of motion sickness (1.77, 1.55-2.04), and age (0.88 per decade, 0.84-0.92). The use of volatile anaesthetics was the strongest anaesthesia-related predictor (1.82, 1.56-2.13), followed by the duration of anaesthesia (1.46 h(-1), 1.30-1.63), postoperative opioid use (1.39, 1.20-1.60), and nitrous oxide (1.45, 1.06-1.98). Evidence for the effect of type of surgery is conflicting as reference groups differed widely and funnel plots suggested significant publication bias. Evidence for other potential risk factors was insufficient (e.g. preoperative fasting) or negative (e.g. menstrual cycle). CONCLUSIONS: /st> The most reliable independent predictors of PONV were female gender, history of PONV or motion sickness, non-smoker, younger age, duration of anaesthesia with volatile anaesthetics, and postoperative opioids. There is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patient's risk for PONV.

Patterns of hybridization and asymmetrical gene flow in hybrid zones of the rare Eucalyptus aggregata and common E. rubida.

The patterns of hybridization and asymmetrical gene flow among species are important for understanding the processes that maintain distinct species. We examined the potential for asymmetrical gene flow in sympatric populations of Eucalyptus aggregata and Eucalyptus rubida, both long-lived trees of southern Australia. A total of 421 adults from three hybrid zones were genotyped with six microsatellite markers. We used genealogical assignments, admixture analysis and analyses of spatial genetic structure and spatial distribution of individuals, to assess patterns of interspecific gene flow within populations. A high number of admixed individuals were detected (13.9-40% of individuals), with hybrid populations consisting of F(1) and F(2) hybrids and backcrosses in both parental directions. Across the three sites, admixture proportions were skewed towards the E. aggregata genetic cluster (x=0.56-0.65), indicating that backcrossing towards E. aggregata is more frequent. Estimates of long-term migration rates also indicate asymmetric gene flow, with higher migration rates from E. aggregata to hybrids compared with E. rubida. Taken together, these results indicate a greater genetic input from E. aggregata into the hybrid populations. This asymmetry probably reflects differences in style lengths (E. rubida: ~7 mm, E. aggregata: ~4 mm), which can prevent pollen tubes of smaller-flowered species from fertilizing larger-flowered species. However, analyses of fine-scale genetic structure suggest that localized seed dispersal (<40 m) and greater clustering between hybrid and E. aggregata individuals may also contribute to directional gene flow. Our study highlights that floral traits and the spatial distributions of individuals can be useful predictors of the directionality of interspecific gene flow in plant populations.

Preliminary evidence for correlation between PASAT performance and P3a and P3b amplitudes in progressive multiple sclerosis.

BACKGROUND: The no-go P3a event-related potential (ERP) is a measure of attentional engagement and the P3b is a measure of context updating. The aim of this study was to compare ERP topographies: (i) to Paced Auditory Serial Addition Test (PASAT) results, (ii) of visual and auditory P3a and P3b of patients with primary progressive multiple sclerosis (PPMS) versus patients with secondary-progressive multiple sclerosis (SPMS) and (iii) of both progressive subtypes to healthy controls. METHODS: Thirty subjects (10 PPMS, 10 SPMS and 10 age-matched controls) completed visual and auditory no-go P3a and P3b tasks whilst data were recorded from a 128-scalp channel electroencephalography (EEG) array. Data from scalp channels were converted into continuous interpolated images (incorporating the entire scalp and time). Topographical differences and correlations were then tested using statistical parametric mapping. RESULTS: For the patients with multiple sclerosis (MS), PASAT score correlated significantly with parietal regions in the auditory P3b, auditory P3a and visual P3b conditions, and with central regions in the visual P3a condition. Patients with PPMS had significantly lower amplitude than patients with SPMS in the auditory P3b condition over the parietal area. The control group had greater amplitude than the patients with MS in all the P3 tasks, with the exception of the auditory P3b. CONCLUSIONS: These data suggest that PASAT performance and P3 ERPs correlate for MS progressive subtypes and that PPMS and SPMS differ in electrophysiological responses during auditory P3b tasks.

Outcomes of point-of-care testing for influenza in the emergency department of a tertiary referral hospital in Ireland.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality, and represents a recurring financial burden for community- and hospital-based treatment. Nosocomial outbreaks exacerbate the impact of influenza. Rapid diagnosis of influenza has been shown to reduce transmission. However, point-of-care testing (POCT) in emergency departments and prudent direction of patients with the virus to reduce hospital-acquired infection (HAI) have not been evaluated widely. AIM: To assess performance characteristics of the Abbott ID NOW™ Influenza A & B 2 system, impact on incidence of hospital-acquired influenza, and admission rate ratio for patients who have POCT compared with laboratory testing. POCT was introduced in the 2018-2019 influenza season. Data from then were compared with preceding and subsequent seasons. METHODS: Records of POCT and laboratory testing for the 2017-2018, 2018-2019, and 2019-2020 influenza seasons were analysed. Sensitivity and specificity of POCT were compared pairwise with Xpert Flu A/B/RSV. Patient admission rates and time of waiting for admission were compared. FINDINGS: Compared to laboratory assay, POCT demonstrated sensitivity of 90.6% (95% confidence interval (CI): 78.6-96.5) and specificity of 99.2% (95.2-100) for influenza A, with 51.4% and 41.9% reductions in numbers of HAIs observed in the two seasons when POCT was available, respectively. The admission rate ratio for influenza cases diagnosed by POCT compared with laboratory diagnosis was 0.72 (95% CI: 0.53-0.97; P = 0.031). CONCLUSION: POCT for influenza appears a feasible strategy for testing of patients during peak influenza virus season, with potential to reduce HAI. The relatively rapid turnaround time may also benefit clinical management of patients presenting at emergency departments with suspected influenza.

Verbal intelligence is a more robust cross-sectional measure of cognitive reserve than level of education in healthy older adults.

BACKGROUND: Cognitive reserve is most commonly measured using socio-behavioural proxy variables. These variables are easy to collect, have a straightforward interpretation, and are widely associated with reduced risk of dementia and cognitive decline in epidemiological studies. However, the specific proxies vary across studies and have rarely been assessed in complete models of cognitive reserve (i.e. alongside both a measure of cognitive outcome and a measure of brain structure). Complete models can test independent associations between proxies and cognitive function in addition to the moderation effect of proxies on the brain-cognition relationship. Consequently, there is insufficient empirical evidence guiding the choice of proxy measures of cognitive reserve and poor comparability across studies. METHOD: In a cross-sectional study, we assessed the validity of 5 common proxies (education, occupational complexity, verbal intelligence, leisure activities, and exercise) and all possible combinations of these proxies in 2 separate community-dwelling older adult cohorts: The Irish Longitudinal Study on Ageing (TILDA; N = 313, mean age = 68.9 years, range = 54-88) and the Cognitive Reserve/Reference Ability Neural Network Study (CR/RANN; N = 234, mean age = 64.49 years, range = 50-80). Fifteen models were created with 3 brain structure variables (grey matter volume, hippocampal volume, and mean cortical thickness) and 5 cognitive variables (verbal fluency, processing speed, executive function, episodic memory, and global cognition). RESULTS: No moderation effects were observed. There were robust positive associations with cognitive function, independent of brain structure, for 2 individual proxies (verbal intelligence and education) and 16 composites (i.e. combinations of proxies). Verbal intelligence was statistically significant in all models. Education was significant only in models with executive function as the cognitive outcome variable. Three robust composites were observed in more than two-thirds of brain-cognition models: the composites of (1) occupational complexity and verbal intelligence, (2) education and verbal intelligence, and (3) education, occupational complexity, and verbal intelligence. However, no composite had larger average effects nor was more robust than verbal intelligence alone. CONCLUSION: These results support the use of verbal intelligence as a proxy measure of CR in cross-sectional studies of cognitively healthy older adults.

Brain event-related potentials predict individual differences in inhibitory control.

Stop-signal reaction time (SSRT), the time needed to cancel an already-initiated motor response, quantifies individual differences in inhibitory control. Electrophysiological correlates of SSRT have primarily focused on late event-related potential (ERP) components over midline scalp regions from successfully inhibited stop trials. SSRT is robustly associated with the P300, there is mixed evidence for N200 involvement, and there is little information on the role of early ERP components. Here, machine learning was first used to interrogate ERPs during both successful and failed stop trials from 64 scalp electrodes at 4 ms resolution (n = 148). The most predictive model included data from both successful and failed stop trials, with a cross-validated Pearson's r of 0.32 between measured and predicted SSRT, significantly higher than null models. From successful stop trials, spatio-temporal features overlapping the N200 in right frontal areas and the P300 in frontocentral areas predicted SSRT, as did early ERP activity (<200 ms). As a demonstration of the reproducibility of these findings, the application of this model to a separate dataset of 97 participants was also significant (r = 0.29). These results show that ERPs during failed stops are relevant to SSRT, and that both early and late ERP activity contribute to individual differences in SSRT. Notably, the right lateralized N200, which predicted SSRT here, is not often observed in neurotypical adults. Both the ascending slope and peak of the P300 component predicted SSRT. These results were replicable, both within the training sample and when applied to ERPs from a separate dataset.

Window of opportunity: an episode of recruitment in a Banksia hybrid zone demonstrates continuing hybridization and phenotypic plasticity.

BACKGROUND AND AIMS: In perennial plants (especially post-fire resprouters), extant populations may reflect recruitment events in the distant past. This is true of hybrid zones formed by two Banksia species of swamps and woodlands in south-eastern Australia, Banksia robur and B. oblongifolia. Both resprout after fire but recruitment is dependent on periodic fires. Although plants of intermediate morphology have also been identified as hybrids using allozyme markers, the extent of ongoing hybridization is unknown. This study investigates whether both microsatellite markers and morphological measurements can be used to distinguish between the two species and their hybrids. A recent recruitment event and microsatellite markers allow the frequency of ongoing hybridization to be estimated, and also the effects of environmental variation on the morphology of plants and seedlings to be tested. METHODS: Variation at seven microsatellite loci was scored and seven leaf characteristics within putatively pure stands and mixed stands of both species were measured, revealing that the two species were genetically and morphologically distinct and that mixed stands also contained genetically and sometimes morphologically distinct hybrids. An opportunity created by wildfires was used to analyse the genetics and morphometrics of adults and seedlings from two hybrid zones. KEY RESULTS: Approximately 9 % of adults and 21 % of seedlings were identified as genetic hybrids in both hybrid zones. Within these sites, the genotype of mature plants correlated well with morphology, except for some hybrid plants that had parental morphology. However, seedling morphology was highly variable and insufficient to describe the composition of the hybrid zone in this cohort. Greater phenotypic plasticity was evident among seedlings growing within the hybrid zones than seedlings growing in pots. CONCLUSIONS: The hybrid zones are complex and the range of genotypes detected in seedlings reveals both continuing hybridization and introgression.

Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.

Minimally invasive colon resection for malignant colonic conditions is associated with a transient early increase in plasma sVEGFR1 and a decrease in sVEGFR2 levels after surgery.

INTRODUCTION: Plasma VEGF levels increase after minimally invasive colorectal resection (MICR) and remain elevated for 2-4 weeks. VEGF induces physiologic and pathologic angiogenesis by binding to endothelial cell (EC) bound VEGF-Receptor-1 (VEGFR1) and VEGFR2. Soluble forms of these receptors sequester plasma VEGF, decreasing the amount available to bind to EC-bound receptors. Ramifications of surgery-related plasma VEGF changes partially depend on plasma levels of sVEGFR1 and sVEGFR2. This study assessed perioperative sVEGFR1 and sVEGFR2 levels after MICR in patients with colorectal cancer. METHODS: Forty-five patients were studied; blood samples were taken from all patients preoperatively (preop) and on postoperative days (POD) 1 and 3; in most a fourth sample was drawn between POD 7-30. Late samples were bundled into two time points: POD 7-13 and POD 14-30. sVEGFR1 and sVEGFR2 levels were measured via ELISA. sVEGFR2 data are reported as mean +/- SD and were assessed with the paired samples t test. sVEGFR1 data were not normally distributed. They are reported as median and 95% confidence interval (CI) and were assessed with the Wilcoxon signed-Rank test (p < 0.05). RESULTS: Preoperatively, the mean plasma sVEGFR2 level (7583.9 pg/ml) was greater than the sVEGFR1 result (98.3 pg/ml). Compared with preop levels, sVEGFR2 levels were significantly lower on POD 1 (6068.2 pg/ml, +/-2034.5) and POD 3 (6227.6 pg/ml, +/-2007.0), whereas sVEGFR1 levels were significantly greater on POD 1 (237.5 pg/ml; 95% CI, 89.6-103.5), POD 3 (200.2 pg/ml; 95% CI, 159-253), and POD 7-13 (102.9 pg/ml; 95% CI, 189.7-253). No differences were found on POD 7-13 for sVEGFR2 or POD 14-30 for either protein. CONCLUSIONS: sVEGFR2 values decreased and sVEGFR1 levels increased early after MICR; sVEGFR2 changes dominate due to their much larger magnitude. The net result is less plasma VEGF bound by soluble receptors and more plasma VEGF available to bind to ECs early after surgery.

Effect of Bacillus subtilis DSM 32315 under Different Necrotic Enteritis Models in Broiler Chickens: A Meta-Analysis of Five Independent Research Trials.

Challenge models are needed to understand the pathogenesis of necrotic enteritis (NE) and provide the basis of evaluating nonantibiotic feed-additive interventions. In the category of nonantibiotic feed additives, the application of probiotics to improve intestinal health and growth performance of broiler chickens in the face of an NE challenge has been well described. However, it is crucial to evaluate the consistency of specific probiotics for mitigating the disease challenge and improving performance. Therefore, a meta-analysis of five independent research trials was conducted with the objective of evaluating the effect of Bacillus subtilis DSM 32315 (probiotic) on body weight gain (BWG), feed conversion ratio (FCR), NE mortality, and lesion score (LS) of broiler chickens challenged with NE. These independent studies were conducted in three countries (the United States, Thailand, and Finland). The statistical analysis used fixed and random effects to estimate the mean effect size (MES) of the difference between NE-challenged birds (control) and NE-challenged probiotic-fed birds and the 95% confidence interval of MES. A meta-regression was performed to evaluate heterogeneity (MES variance) among studies. The statistical analysis was performed using a robust variance estimation strategy with a SAS macro. Probiotic-supplemented birds had a significantly higher BWG (MES = 1.04, P = 0.009) and a significantly lower FCR (MES = -1.39, P = 0.020), NE mortality (MES = -1.15, P = 0.012), and LS (MES = -1.29, P = 0.045). Response variables of BWG (Q = 2.81, P = 0.560) and NE mortality (Q = 5.60, P = 0.354) did not present heterogeneity. Heterogeneity was found for FCR (Q = 10.34, P = 0.035) and LS (Q = 16.13, P = 0.001). Overall, dietary supplementation of B. subtilis DSM 32315 significantly improved BWG and reduced FCR, mortality, and LS in a repeatable large-scale manner.

Dietary methylsulfonylmethane supplementation and oxidative stress in broiler chickens.

Methylsulfonylmethane (MSM) is an organic, sulfur-containing compound widely used as a dietary supplement to improve joint health and treat arthritic pain. An experiment was conducted to study the effects of feeding 0.05% MSM to broilers exposed to diet-induced oxidative stress on tissue MSM distribution, growth performance, oxidative stress biomarkers, and immune responsivity. A total of 528 birds were allocated to 4 dietary treatments (fresh oil-no MSM, fresh oil-MSM, oxidized oil-no MSM, oxidized oil-MSM) as provided ad libitum to 11 replicate cages of 12 birds per treatment. Blood and tissue samples were collected to analyze MSM concentrations, and oxidative stress biomarkers including concentrations of thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), total glutathione, and glutathione peroxidase (GPx) and reductase (GR) activities. Additionally, blood samples collected at day 25 were used to quantify T-cell (TC) populations using flow cytometry. Overall, MSM was quantified in all tissues and plasma samples of MSM-treated groups at all time points. Oxidized oil reduced (P = 0.006) feed intake over the 21-d feeding period, but MSM did not affect growth equally across time points. No effects (P > 0.2) of MSM or oil type were observed on TC populations. In the presence of oxidized oil, MSM reduced (P = 0.013) plasma TBARS and increased (P = 0.02) liver GPx at day 21, and increased (P = 0.06) liver GR at day 7. Irrespective of dietary oil type, groups supplemented with MSM showed higher plasma TAC at day 7 (P = 0.023), liver GPx activity at day 21 (P = 0.003), and liver GR activity at day 7 (P = 0.004) compared with groups not receiving MSM. In conclusion, 0.05% dietary MSM supplementation partially protected birds from oxidative stress but did not affect immune cell profiles.

Abdominal wall dimensions and umbilical position vary widely with BMI and should be taken into account when choosing port locations.

BACKGROUND: Many surgeons rely on the umbilicus when determining the location of ports for laparoscopic procedures and falsely assume that it is located in the vertical midline. The purpose of this study was to assess the degree of variation in umbilical position and abdominal dimensions in the general population. METHODS: Torso length, abdominal girth, weight, and height were recorded for 259 patients over a 9-month period. Body mass index (BMI) was calculated and used to classify patients into four groups: underweight, normal, overweight, and obese. RESULTS: Average umbilical position for all BMI groups was below the true vertical midpoint and dropped further caudally as BMI increased. In addition, average abdominal dimensions increased with increasing BMI. There was no statistical difference between males and females in each BMI group regarding umbilical position or abdominal dimensions. CONCLUSION: There is a clear relationship between increasing BMI and a drop in umbilical position as well as an increase in abdominal dimensions. We recommend determining umbilical position and abdominal dimensions prior to placing ports and shifting port positions toward target quadrants.