CELEBRATE Feeding: A Responsive Approach to Food and Feeding in Early Learning Settings.

Early learning and child care (ELCC) settings in Canada follow nutrition standards that outline food provisions, with many also encouraging responsive feeding practices that help to create a supportive environment for children. Caregivers who lack confidence in children's ability to regulate their own intake, or those who feel stressed about mealtime, may unknowingly engage in less responsive feeding practices. The CELEBRATE Feeding Approach is a flexible framework, driven by behaviour change theory, that builds on previous definitions and concepts of responsive feeding in ELCC environments. Through this approach, there is an intentional focus on supporting early childhood educators to implement feeding practices that are more responsive. The approach incorporates 13 target educator behaviours related to the three overlapping categories of CELEBRATE language, CELEBRATE Mealtime, and CELEBRATE Play. These practices recognize and support the development of a child's sense of autonomy, confidence, and self-regulation not only at mealtimes but also through play-based exploration and language that is used throughout the day around food and feeding. The goal is that children will be open to a wide variety of food, develop their self-regulation skills, and build the foundation for a positive relationship with food throughout their lifetime.

Quantifying quality: The impact of measures of school quality on children's academic achievement across diverse societies.

Recent decades have seen a rapid acceleration in global participation in formal education, due to worldwide initiatives aimed to provide school access to all children. Research in high income countries has shown that school quality indicators have a significant, positive impact on numeracy and literacy-skills required to participate in the increasingly globalized economy. Schools vary enormously in kind, resources, and teacher training around the world, however, and the validity of using diverse school quality measures in populations with diverse educational profiles remains unclear. First, we assessed whether children's numeracy and literacy performance across populations improves with age, as evidence of general school-related learning effects. Next, we examined whether several school quality measures related to classroom experience and composition, and to educational resources, were correlated with one another. Finally, we examined whether they were associated with children's (4-12-year-olds, N = 889) numeracy and literacy performance in 10 culturally and geographically diverse populations which vary in historical engagement with formal schooling. Across populations, age was a strong positive predictor of academic achievement. Measures related to classroom experience and composition were correlated with one another, as were measures of access to educational resources and classroom experience and composition. The number of teachers per class and access to writing materials were key predictors of numeracy and literacy, while the number of students per classroom, often linked to academic achievement, was not. We discuss these results in the context of maximising children's learning environments and highlight study limitations to motivate future research. RESEARCH HIGHLIGHTS: We examined the extent to which four measures of school quality were associated with one another, and whether they predicted children's academic achievement in 10 culturally and geographically diverse societies. Across populations, measures related to classroom experience and composition were correlated with one another as were measures of access to educational resources to classroom experience and composition. Age, the number of teachers per class, and access to writing materials were key predictors of academic achievement across populations. Our data have implications for designing efficacious educational initiatives to improve school quality globally.

Creation and initial validation of a genetic counseling supervisory self-efficacy scale.

Fieldwork supervision is the "signature pedagogy" for training genetic counseling students, ensuring that students have the experience necessary to become minimally competent genetic counselors. According to the National Society of Genetic Counselors 2022 Professional Status Survey, roughly 40% of genetic counselors serve as supervisors for genetic counseling graduate students. Despite fieldwork supervision being essential for training, there are currently no validated supervision skill assessment tools for genetic counseling fieldwork supervisors to use for professional development. While a self-efficacy scale for genetic counselors currently exists, a comprehensive self-efficacy scale for genetic counseling supervision skills does not. The purpose of the study was to develop and validate a genetic counseling supervisory self-efficacy scale (GCSSES). This study was comparative, quantitative, and cross-sectional, with data collected via an online questionnaire which assessed supervision self-efficacy (95 items), derived from 154 published GC supervision competencies, demographics (5), experience (9), and supervisory development (18), using the Psychotherapy Supervisory Development Scale (PSDS). A total of 119 board-certified genetic counselors completed the survey. Factor analysis eliminated 40 items due to insufficient factor loading, and item-item correlation eliminated one item with elevated inter-item correlation, leaving 54 items on the finalized GCSSES. Exploratory factor analysis derived four GCSSES factors, which accounted for 65% of the variance in the scale: (a) Goal Setting, Feedback, and Evaluation; (b) Complex Aspects of Supervision; (c) Conflict Resolution; and (d) Working Alliance. Preliminary analyses show the GCSSES has high reliability and internal consistency (Cronbach's alpha = 0.99). Positive correlations between experience variables and supervisory self-efficacy were identified. A 54 item GCSSES was developed by this study. The GCSSES may serve as a tool for genetic counseling supervisors and graduate programs to assess skills, monitor professional development, and target training. A genetic counseling supervisory self-efficacy scale can also be used in future studies regarding training of genetic counseling supervisors.

Unilateral hamstrings static stretching can impair the affected and contralateral knee extension force but improve unilateral drop jump height.

PURPOSE: Prolonged static stretching (SS) in isolation (no dynamic warm-up) can impair muscle performance. There are conflicting reports whether impairments are present in antagonist and contralateral muscles. The objective of this study was to assess the effect of unilateral hamstrings SS on ipsilateral stretched and contralateral limbs' strength and jump power. METHODS: The SS (four repetitions of 30-s) and control sessions involved unilateral testing of the stretched leg and contralateral leg for knee extension (KE) maximum voluntary isometric contraction (MVIC) force and electromyography (EMG), drop jump (DJ) height and contact time at 1-min post-stretching. RESULTS: There were significant KE MVIC force impairments for both the SS (p = 0.006, d = 0.3, - 8.1%) and contralateral (p = 0.02, d = 0.20, - 4.2%) leg. With normalized data, there was a near-significant (p = 0.1), small magnitude (d = 0.29), greater force impairment with the ipsilateral (93.0 ± 12.8% of pre-test) versus the contralateral (96.2 ± 9.1% of pre-test) KE MVIC force. DJ height significantly improved for the stretched leg (p = 0.03, d = 0.18, + 9.2%) with near-significant, improvements for the contralateral leg (p = 0.06, d = 0.22, + 12.1%). For the stretched leg, DJ contact time was significantly (p = 0.04, d = 0.18, + 3.4%) prolonged, but there was no significant change with the contralateral leg. CONCLUSIONS: Unilateral hamstrings SS induced strength deficits in the ipsilateral and contralateral knee extension MVIC and a prolongation of the stretched leg DJ contact period. In anticipation of maximal force outputs, prolonged SS in isolation (no dynamic warm-up included) can have negative consequences on antagonist and contralateral muscle performance.

Cross Education Training Effects are Evident with Twice Daily, Self-Administered Band Stretch Training.

Currently there are recommendations for stretching type, repetitions and duration within a training session to improve flexibility. It is, however, unclear whether multiple daily stretch training sessions provide greater flexibility than single daily sessions. The objective was to investigate the effectiveness of single (1×day) versus twice daily (2×day) unilateral stretch training sessions on hip flexion range of motion (ROM), agonist and antagonist force and jump performance of the stretched and contralateral, non-stretched legs. Groups included a control, 1×day and 2×day stretch training groups. Static stretching (SS) involved self-administered (stretch band), unilateral, hamstrings and quadriceps stretching for 2-weeks. Pre- and post-testing involved hip flexion ROM, knee extension and flexion maximal voluntary isometric contraction (MVIC) forces and unilateral drop jumps (DJ). The 2×day group showed a 12.8% (p = 0.08) greater active ROM versus Control. The 1×day group showed a 7.5% (p=0.1) ballistic ROM increase with no significant changes with the 2×day and Control groups. The stretched leg experienced a 5.01% (p = 0.1) hip flexion ballistic ROM increase contrasting with a 2.3% increase for the contralateral leg. Twice daily training provided 7.1% (p = 0.07) and 6.6% (p = 0.01) quadriceps MVC force increases of the stretched trained and contralateral legs respectively. Contralateral DJ height improved 22.6% (p = 0.002) with 2×day training. In conclusion, 1xday and 2×day stretch training tended to improved ballistic and active ROM respectively, whereas 2×day training improved MVIC force and DJ height. The findings may apply to fitness enthusiasts and rehabilitation as unilateral stretching may retain performance and active ROM of the stretched and contralateral limbs.

The Relationship Between the Supervisory Working Alliance and Student Self-Efficacy in Genetic Counseling Training.

The purpose of this study was to determine if a genetic counseling student's perception of the supervisory working alliance (SWA) is related to their self-efficacy on select clinical practice-based competencies (PBCs), evaluating the second tenet of the Reciprocal Engagement Model of Supervision (REM-S) from a student perspective. Second year genetic counseling students (N = 168) completed a survey containing demographic and clinical rotation experience questions, the Supervisory Working Alliance Inventory-Trainee Form (SWAI-T), and the Genetic Counseling Self-Efficacy Scale (GCSES). Overall, the SWAI-T was significantly associated with all factors of the GCSES. Additionally, the relationship between the SWAI-T and self-efficacy was specific to those who had only one supervisor, thus highlighting the SWA may be most important under these circumstances. This serves as an important step in being able to guide supervisors toward effective methods in supervision, which may include encouraging supervisors to build a strong relationship with their supervisee in order to help strengthen the student's confidence in their clinical skills.

Development and Validation of the Genetic Counseling Self-Efficacy Scale (GCSES).

This study describes the development of a self-efficacy scale that is specific to genetic counseling and based both on Bandura's self-efficacy theory (2006) and the Accreditation Council for Genetic Counseling practice-based competencies (2013). The phase 1 validation compared genetic counseling students (n = 20) and genetic counselors (n = 18). Nine items were removed from the scale at this point for lack of discrimination or redundancy. The phase 2 validation included a larger cohort of genetic counseling students (n = 168). Factor analysis identified six factors accounting for 58% of the total variance. Cronbach's alpha as well as the inter-item correlations and item-total correlations of both the full scale items and underlying factors indicated that the items and factors of the scale are sufficiently related, but not redundant. The newly developed Genetic Counseling Self-Efficacy Scale (GCSES) has the potential to be used as an outcome measure in research related to training or professional development of genetic counselors as well as for a training tool.

Advancing assessment of responsive feeding environments and practices in child care.

Child care environments offer an ideal setting for feeding interventions. CELEBRATE Feeding is an approach implemented in child care environments in two Maritime Provinces in Canada to support responsive feeding (RF) to foster children's self-efficacy, self-regulation, and healthy relationships with food. This study aimed to describe RF in child care using established and enhanced scoring frameworks. The Environment and Policy Assessment and Observation (EPAO) was modified to reflect RF environments and practices, resulting in our modified EPAO and a CELEBRATE scale. Observations were conducted in 18 child care rooms. Behaviours and environments were scored on both scales, creating 21 RF scores, with a score of '3' indicating the most responsiveness. Descriptive analyses of the scores were conducted. The overall room averages were Mean (M) = 41.00, Standard Deviation (SD) = 7.07 (EPAO), and M = 37.92 SD = 6.50 (CELEBRATE). Most responsive scores among rooms within our EPAO and CELEBRATE scales, respectively, were 'educators not using food to calm or encourage behaviour' (M = 2.94, SD = 0.24; M = 2.98, SD = 0.06) and 'not requiring children to sit at the table until finished' (M = 2.89, SD = 0.47; M = 2.97, SD = 0.12). The least responsive scores within the EPAO were 'educator prompts for children to drink water' (M = 0.78, SD = 0.94) and 'children self-serving' (M = 0.83, SD = 0.38). The least responsive in the CELEBRATE scale were 'enthusiastic role modelling during mealtime' (M = 0.70, SD = 0.68) and 'praise of mealtime behaviour unrelated to food intake' (M = 0.74, SD = 0.55). The CELEBRATE scale captured unique observation information about RF to allow documenting change over time with detailed measurement to inform and support nutrition interventions within child care environments.

Variability and harshness shape flexible strategy-use in support of the constrained flexibility framework.

Human cognition is incredibly flexible, allowing us to thrive within diverse environments. However, humans also tend to stick to familiar strategies, even when there are better solutions available. How do we exhibit flexibility in some contexts, yet inflexibility in others? The constrained flexibility framework (CFF) proposes that cognitive flexibility is shaped by variability, predictability, and harshness within decision-making environments. The CFF asserts that high elective switching (switching away from a working strategy) is maladaptive in stable or predictably variable environments, but adaptive in unpredictable environments, so long as harshness is low. Here we provide evidence for the CFF using a decision-making task completed across two studies with a total of 299 English-speaking adults. In line with the CFF, we found that elective switching was suppressed by harshness, using both within- and between-subjects harshness manipulations. Our results highlight the need to study how cognitive flexibility adapts to diverse contexts.

Immuno-phenotypic and functional characterization of rabbit pulmonary intravascular macrophages.

Pulmonary intravascular macrophages (PIMs) are present in species such as cattle, sheep and horse and promote acute lung inflammation (ALI). Rabbits are often used as a model of ALI but there is controversy about the presence of PIMs in these species. Rabbits were treated with 10 mg/kg of gadolinium chloride intravenously (GC; n = 6) or saline (n = 6) followed by euthanasia at 48 h post-treatment to determine the presence of PIMs. In a subsequent study, rabbits were pre-treated with GC or 0.9 % saline followed by 100 µg/kg of E. coli lipopolysaccharide intravenously 48 h later. Rabbits were euthanized 24 h post-LPS treatment. Light and electron microscopy showed that PIMs attached to the capillary endothelium and were positive for RAM-11 anti-macrophage antibody. While GC treatment induced apoptotic PIMs, there was no difference in the PIM number between control and GC-treated rabbits. Rabbits administered with LPS were 3.5 times more likely to die before the end of the 24-h period than those pre-treated with GC. Lung heterophil accumulation and IL-1ß, TNFα and IL-6 mRNA expression were significantly higher in rabbits administered with LPS compared to those administered with GC before the LPS injection. PIMs from the LPS-treated rabbits were positive for TNFα. Lung, BAL and serum IL-8 and MCP-1 expression was not different between LPS rabbits with or without pre-treatment with GC. We conclude that rabbit lungs contain PIMs and that their depletion reduces endotoxin-induced lung inflammation. The presence of PIMs in rabbit lungs may need to be considered while using rabbit to model acute lung injury.

Expression of Toll-like receptor 9 in mouse and human lungs.

Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms, and constitute an important part of the innate immune system. Numerous studies have shown the importance of these receptors, including TLR9, in establishing effective immune responses to a broad range of infections, and in disorders such as COPD. TLR9 detects unmethylated DNA and is expressed in a wide range of immune cells in mice and humans, as well as other species. Most TLR9 expression studies have been done on cultured or isolated cells, but none that we know of on intact lung. Because cell-specific expression of TLR9 is important to understand its precise role in lung physiology, we tested mouse and human lung tissues for expression of TLR9 mRNA and protein with in situ hybridization and immunohistochemistry, respectively. We found TLR9 mRNA and protein expression in bronchial epithelium, vascular endothelium, alveolar septal cells and alveolar macrophages in both species. Immuno-electron microscopy delineated TLR9 expression in plasma membrane, cytoplasm and the nucleus of various lung cells. Lungs from human cases of COPD had significantly increased numbers of TLR9-positive cells. These are the first data showing TLR9 mRNA and protein expression in intact human and mouse lungs. The data may be useful for clarifying the role of TLR9 in the contributions of specific cells to lung physiology.

ErbB2 requires integrin alpha5 for anoikis resistance via Src regulation of receptor activity in human mammary epithelial cells.

ErbB2, a receptor tyrosine kinase highly expressed in many tumors, is known to inhibit apoptotic signals. Overexpression of ErbB2 causes anoikis resistance that contributes to luminal filling in three-dimensional mammary epithelial acinar structures in vitro. Given that integrins and growth factor receptors are highly interdependent for function, we examined the role of integrin subunits in ErbB2-mediated survival signaling. Here, we show that MCF-10A cells overexpressing ErbB2 upregulate integrin alpha5 via the MAP-kinase pathway in three-dimensional acini and found elevated integrin alpha5 levels associated with ErbB2 status in human breast cancer. Integrin alpha5 is required for ErbB2-mediated anoikis resistance and for optimal ErbB2 signaling to the Mek-Erk-Bim axis as depletion of integrin alpha5 reverses anoikis resistance and Bim inhibition. Integrin alpha5 is required for full activation of ErbB2 tyrosine phosphorylation on Y877 and ErbB2 phosphorylation is associated with increased activity of Src in the absence of adhesion. Indeed, we show that blocking elevated Src activity during cell detachment reverses ErbB2-mediated survival and Bim repression. Thus, integrin alpha5 serves as a key mediator of Src and ErbB2-survival signaling in low adhesion states, which are necessary to block the pro-anoikis mediator Bim, and we suggest that this pathway represents a potential novel therapeutic target in ErbB2-positive tumors.

Studying policy implementation using a macro, meso and micro frame analysis: the case of the Collaboration for Leadership in Applied Health Research & Care (CLAHRC) programme nationally and in North West London.

BACKGROUND: The publication of Best research for best health in 2006 and the "ring-fencing" of health research funding in England marked the start of a period of change for health research governance and the structure of research funding in England. One response to bridging the 'second translational gap' between research knowledge and clinical practice was the establishment of nine Collaborations for Leadership in Applied Health Research and Care (CLAHRCs). The goal of this paper is to assess how national-level understanding of the aims and objectives of the CLAHRCs translated into local implementation and practice in North West London. METHODS: This study uses a variation of Goffman's frame analysis to trace the development of the initial national CLAHRC policy to its implementation at three levels. Data collection and analysis were qualitative through interviews, document analysis and embedded research. RESULTS: Analysis at the macro (national policy), meso (national programme) and micro (North West London) levels shows a significant common understanding of the aims and objectives of the policy and programme. Local level implementation in North West London was also consistent with these. CONCLUSIONS: The macro-meso-micro frame analysis is a useful way of studying the transition of a policy from high-level idea to programme in action. It could be used to identify differences at a local (micro) level in the implementation of multi-site programmes that would help understand differences in programme effectiveness.

Regulation of TLR10 Expression and Its Role in Chemotaxis of Human Neutrophils.

Toll-like receptors are innate immune receptors that play a critical role in pathogen-associated molecular pattern recognition. TLR10 was recently identified and very limited data are available on its expression, mechanisms that regulate its expression, and its role in primary immune cells. To study the expression pattern of TLR10 in primary immune cells, we examined TLR10 protein expression in naive and Escherichia coli lipopolysaccharide (LPS)-activated human neutrophils. Human neutrophils challenged with LPS showed a decrease in total and surface TLR10 expression at 90 min. TLR10 in LPS-activated neutrophils colocalized with flotallin-1, a lipid raft marker, and EEA-1, an early endosomal marker, to suggest its endocytosis. There was increased colocalization of TLR10 with TLR4 at LPS 60 min followed by decrease at later LPS treatment times. Treatment with TLR4 neutralizing antibody decreased cytoplasmic localization of TLR10 in LPS-treated neutrophils. Reactive oxygen species (ROS) depletion and neutralization of p65 subunit of NF-κB in LPS-treated neutrophils decreased TLR10 expression. Live cell imaging of LPS-activated neutrophils showed TLR10 translocation in the leading edge and TLR10 knockdown in neutrophils reduced their fMLP-induced chemotaxis and the number of neutrophils with pseudopodia but without affecting the expression of key proteins of actin nucleation process, ARP-3 and Diap1. Taken together, our findings show that neutrophil activation alters TLR10 expression through ROS production and NF-κB regulation, and TLR10 knockdown reduced neutrophil chemotaxis.

Retinoid receptors are expressed in mouse and human lungs.

Retinoid receptors are members of nuclear receptor superfamily consisting of two distinct families: RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each family contains three receptor subtypes α, ß, and γ. Retinoids transduce their effects through binding to retinoid receptors and inhibit transcription factors such as activator protein-1 and nuclear factor-κB (NF-κB) both of which regulate the transcription of several inflammatory genes. Considering the role of retinoid receptors in lung physiology, we need a precise understanding of their expression in normal and inflamed lungs. We used light and electron microscopic immunohistochemistry and Western blot to determine the expression of retinoid receptors in a murine model of endotoxin-induced (E. coli; 055:B5, 80 µg intranasal) acute lung inflammation and normal human lungs. Western blot showed expression of all six retinoid receptor subtypes in normal and inflamed mouse lungs. Immunohistology localized differential expression of retinoid receptors in airway epithelium, alveolar/septal macrophages, vascular endothelium, and alveolar septum in mouse lungs. Intranasal LPS challenge in mice resulted in increased expression of RXRα in airway epithelium compared to control animals. All six retinoid receptor subtypes were expressed in normal human lungs. Immunoelectron microscopy further confirmed the localization of all the receptors in various lung cells including the nucleus of these cells. The basal and altered expression of retinoid receptors in normal and inflamed lungs, respectively, may suggest their roles in lung pathophysiology.

Overcoming cognitive set bias requires more than seeing an alternative strategy.

Determining when to switch from one strategy to another is at the heart of adaptive decision-making. Previous research shows that humans exhibit a 'cognitive set' bias, which occurs when a familiar strategy occludes-even much better-alternatives. Here we examined the mechanisms underlying cognitive set by investigating whether better solutions are visually overlooked, or fixated on but disregarded. We analyzed gaze data from 67 American undergraduates (91% female) while they completed the learned strategy-direct strategy (LS-DS) task, which measures their ability to switch from a learned strategy (LS) to a more efficient direct strategy (DS or shortcut). We found that, in the first trial block, participants fixated on the location of the shortcut more when it was available but most (89.6%) did not adopt it. Next, participants watched a video demonstrating either the DS (N = 34 Informed participants) or the familiar LS (N = 33 Controls). In post-video trials, Informed participants used the DS more than pre-video trials and compared to Controls. Notably, 29.4% of Informed participants continued to use the LS despite watching the DS video. We suggest that cognitive set in the LS-DS task does not stem from an inability to see the shortcut but rather a failure to try it.

The social learning and development of intra- and inter-ethnic sharing norms in the Congo Basin: A registered report protocol.

Compared to other species, the extent of human cooperation is unparalleled. Such cooperation is coordinated between community members via social norms. Developmental research has demonstrated that very young children are sensitive to social norms, and that social norms are internalized by middle childhood. Most research on social norm acquisition has focused on norms that modulated intra-group cooperation. Yet around the world, multi-ethnic communities also cooperate, and this cooperation is often shaped by distinct inter-group social norms. In the present study, we will investigate whether inter-ethnic and intra-ethnic social norm acquisition follows the same, or distinct, developmental trajectories. Specifically, we will work with BaYaka foragers and Bandongo fisher-farmers who inhabit multi-ethnic villages in the Republic of the Congo. In these villages, inter-ethnic cooperation is regulated by sharing norms. Through interviews with adult participants, we will provide the first descriptive account of the timing and mechanism by which BaYaka and Bandongo learn to share with out-group members. Children (5-17 years) and adults (17+ years) will also participate in a modified Dictator Game to investigate the developmental trajectories of children's intra- and inter-ethnic sharing choices. Based on our ethnographic knowledge of the participating communities, we predict that children's intra-ethnic sharing choices in the Dictator Game will match those of adults at an earlier age than their inter-ethnic sharing choices. We will analyze our data using logistic Bayesian modelling.

Expression of toll-like receptor 9 in lungs of pigs, dogs and cattle.

Toll-like receptors (TLRs) are important components of the innate immune system. Compared with other TLRs such as TLR4, there is less data on the expression and function of TLR9, which binds to unmethylated DNA. Because there is no data on the cell-specific protein expression of TLR9 in lungs of cattle, dog and pigs, and pulmonary diseases are the major cause of economic losses, we studied TLR9 expression in lungs using Western blotting, immunohistology and immuno-electron microscopy. We characterized a mouse TLR9 antibody to detect TLR9 in lung extracts from pigs, dogs, and cattle. The TLR9 peptide used to raise the mouse TLR9 antibody had significant homology with TLR9 amino acid sequences from these species. Light and electron microscopic immunostaining localized TLR9 in airway epithelium, vascular endothelium, alveolar macrophages, and pulmonary intravascular monocytes/macrophages in all three species. These data are of potential importance for the understanding of pulmonary immune responses in these veterinary species.

1H Magnetic Resonance Spectroscopy to Understand the Biological Basis of ALS, Diagnose Patients Earlier, and Monitor Disease Progression.

At present, limited biomarkers exist to reliably understand, diagnose, and monitor the progression of amyotrophic lateral sclerosis (ALS), a fatal neurological disease characterized by motor neuron death. Standard MRI technology can only be used to exclude a diagnosis of ALS, but 1H-MRS technology, which measures neurochemical composition, may provide the unique ability to reveal biomarkers that are specific to ALS and sensitive enough to diagnose patients at early stages in disease progression. In this review, we present a summary of current theories of how mitochondrial energetics and an altered glutamate/GABA neurotransmitter flux balance play a role in the pathogenesis of ALS. The theories are synthesized into a model that predicts how pathogenesis impacts glutamate and GABA concentrations. When compared with the results of all MRS studies published to date that measure the absolute concentrations of these neurochemicals in ALS patients, results were variable. However, when normalized for neuronal volume using the MRS biomarker N-acetyl aspartate (NAA), there is clear evidence for an elevation of neuronal glutamate in nine out of thirteen studies reviewed, an observation consistent with the predictions of the model of increased activity of glutamatergic neurons and excitotoxicity. We propose that this increase in neuronal glutamate concentration, in combination with decreased neuronal volume, is specific to the pathology of ALS. In addition, when normalized to glutamate levels, there is clear evidence for a decrease in neuronal GABA in three out of four possible studies reviewed, a finding consistent with a loss of inhibitory regulation contributing to excessive neuronal excitability. The combination of a decreased GABA/Glx ratio with an elevated Glx/NAA ratio may enhance the specificity for 1H-MRS detection of ALS and ability to monitor glutamatergic and GABAergic targeted therapeutics. Additional longitudinal studies calculating the exact value of these ratios are needed to test these hypotheses and understand how ratios may change over the course of disease progression. Proposed modifications to the experimental design of the reviewed 1H MRS studies may also increase the sensitivity of the technology to changes in these neurochemicals, particularly in early stages of disease progression.

Oral medication administration: implications caused by capsule splitting.

OBJECTIVE: To demonstrate that capsule splitting does not result in an equal quantity of drug in both parts of the capsule, affecting the dosage of the drug. DESIGN: Descriptive nonexperimental study. SETTING: Glen Burnie, MD, from May 2007 to May 2008. PARTICIPANTS: Not applicable. INTERVENTION: At varying times, three student pharmacists (two from the University of Maryland and one from Creighton University) filled and packed 62 capsules ranging in size from #4 to #000 using bulk powder. Each capsule was weighed and then split. The capsule split was also weighed, as well as the amount of powder found in each portion of the capsule. Statistical analyses were performed, including t test, standard error, and relative error. MAIN OUTCOME MEASURE: Whether after splitting a capsule the top of the capsule supplies less of the drug and the base of the capsule more of the drug, leading to non-weight uniformity of splitting capsules. RESULTS: The weight of the base of the capsule powder was always more than the weight of the top portion of the capsule. Capsule size #1 showed the most deviation and capsule size #4 the least deviation between the top and bottom of the capsule. CONCLUSION: Capsules should not be ordered to be split because the base of the capsule holds more of the drug powder than that of the top of the capsule. This study infers that the patient would receive approximately 75% of the dose when given the base of the capsule and about 25% of the dose when given the top of the capsule.