A comprehensive guide to MEGA-PRESS for GABA measurement.

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

Profiling of how nociceptor neurons detect danger - new and old foes.

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro-immune interplay is still ill-defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH 1-mediated immunity but also as drivers of TH 2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide-ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

Posterior cingulate metabolic changes occur in Parkinson's disease patients without dementia.

The basis for cognitive deficits in Parkinson's disease (PD) is unknown. Hippocampal atrophy has been shown in Alzheimer's disease (AD) and PD. N-Acetyl aspartate (NAA)/creatine (Cr) ratio in the posterior cingulate gyrus (PCG) is decreased in AD, but unknown in PD. Volumetric magnetic resonance (MR) imaging (at 1.5 T) determined corrected HC volume and MR spectroscopy (MRS) PCG metabolites in 12 non-demented mild to moderately affected PD patients (six male, six female) and ten controls (five male, five female). Age (PD=60.6 years, control=62.2; P=0.62), education (PD=14.1 years, controls=13.8; P=0.89) and global cognition (Mini-Mental State Exam score: PD=28.7, controls=29.6; P=0.14) did not differ. Only recall (CVLT-II, P=0.046) and NAA/Cr (PD=1.53, controls=1.78; P=0.03) were decreased in PD. Memory correlated with NAA/Cr (r=0.65, P=0.02) in PD. In conclusion, cingulate metabolic changes occur in PD.

Elevated iron status increases bacterial invasion and survival and alters cytokine/chemokine mRNA expression in Caco-2 human intestinal cells.

Iron status affects both microbial growth and immune function. Mammalian iron homeostasis is maintained primarily by regulating the absorption of the micronutrient in the proximal small intestine. The iron concentration of the enterocyte can fluctuate widely in response to both dietary and whole body iron status, as well as in response to infections. The possibility that an enterocyte with an elevated iron concentration is more susceptible to invasion by enteric pathogens is not known. Therefore, we examined the impact of enterocyte iron status on the invasion and survival of an enteric pathogen, as well as on the levels of several cytokine and chemokine mRNAs by the host cell. The enterocyte-like Caco-2 human intestinal cell line and Salmonella enteritidis served as the models to examine the effect of iron on the host-parasite interaction. Iron status of Caco-2 cells was altered by incubation in serum-free medium supplemented with varying levels of iron. Elevated iron status of Caco-2 cells increased the efficiency of the invasion and the number of bacteria surviving in the intracellular environment. Caco-2 cells constitutively expressed transforming growth factor-beta1, interleukin-8, monocyte chemotactic protein-1, tumor necrosis factor-alpha and interleukin-1beta, and infection with S. enteritidis increased the relative quantities of all cytokine/chemokine mRNAs except interleukin-1beta. Elevated iron status of Caco-2 cells decreased the levels of cytokine/chemokine mRNAs by 25-45% in uninfected cells. In contrast, bacterial infection was associated with a 21-95% increase in cytokine/chemokine mRNAs levels in Caco-2 cells with higher iron concentration compared with infected cells with lower iron concentration. These data support the hypothesis that elevated enterocyte iron status increases susceptibility to infection and exacerbates the mucosal inflammatory response initiated by microbial invasion by increasing cytokine/chemokine expression.

Exporting analogue behavioral observation from research to clinical practice: useful or cost-defective?

The special section on analogue behavioral observation (ABO) provided an in-depth review of various ABO assessment procedures. Despite their availability, however, these procedures are rarely used in clinical practice. This may result in part from the traditions on which most ABO assessments are based, from distinctions between clinical and research assessment environments, and from the need for more information about the cost-effectiveness of ABO strategies for meeting specific needs of clinicians in applied settings. Suggestions for bridging the research-clinical gap involve investigating more thoroughly when ABO does and does not provide useful information for various purposes in applied settings and increasing accessibility and cost-effectiveness of ABO procedures for practitioners.

Adolescent and family predictors of physical aggression, communication, and satisfaction in young adult couples: a prospective analysis.

This study tested a model wherein the family conflict, depression, and antisocial behavior of 254 adolescents (mean age = 17 years; 63% female) are prospectively related to functioning within a marital (51%) or dating relationship in young adulthood (mean age = 23 years). Family aversive communication in adolescence and adolescent antisocial behavior predicted couple physical aggression. Family aversive communication predicted dyadic satisfaction and aversive couple communication for married women and dating men. Among those with partners who reported little antisocial behavior, adolescent antisocial behavior inversely predicted couple satisfaction and facilitative behavior. Partner antisocial behavior did not mediate the relation between adolescent characteristics and couple functioning. Findings emphasize the importance of the early family environment and psychopathology of the adolescent in the development of adaptive couple relationships.

Assessing social validity in clinical treatment research: issues and procedures.

Social validity is a term coined by behavior analysts to refer to the social importance and acceptability of treatment goals, procedures, and outcomes. This article discusses dimensions of social validity, methods used to evaluate various aspects of social validity, and the applicability of these concepts and methods in clinical treatment research.

MR imaging of dysplasia epiphysealis hemimelica: bony and soft-tissue abnormalities.

OBJECTIVE: The purpose of this study is to describe the bony and, to our knowledge, previously unreported associated soft-tissue abnormalities seen on MR imaging of dysplasia epiphysealis hemimelica. CONCLUSION: MR imaging accurately depicted bony and cartilagenous structural abnormalities in multiple planes and revealed previously undescribed secondary changes in menisci, tendons, ligaments, and muscle. MR imaging is of value in the assessment of patients with this disorder.

Patient consultation in a managed care setting: guiding pharmacy into the future.

Managed care organizations are excellent environments for pharmaceutical care programs to demonstrate their impact on patient care outcomes and to decrease costs. Patient consultation is the cornerstone in implementing pharmaceutical care because it increases patient contact with the pharmacists while improving patient compliance with drug therapy (adherence). Implementation of a patient consultation program that verifies patients' understanding of their disease and therapy gives the pharmacist information necessary to monitor drug therapy. Use of strategic planning to overcome barriers, followed by the development of local standards of practice, will refocus the practice philosophy to one of improving patient outcomes. Pharmacy managers must demonstrate and document the value that patient consultation brings to the patient and the healthcare system. Then, they must integrate their counseling effort with other health education efforts of the managed care system. Pharmacists will gain the support of other disciplines by reinforcing their efforts. Together they can work to decrease the problems that are inherent with drug therapy. These goals can be accomplished with minimal expense and have the potential to produce significant savings in healthcare costs.

Assessing acceptance and social skills with peers in childhood. Current issues.

This article reviews current strategies for assessing social skills with peers in childhood, highlighting contemporary unresolved issues in identifying children who need intervention, selecting target behaviors, and assessing treatment outcome. Sociometric measures of peer acceptance are also considered. Although many current measures of social skills have adequate evidence of reliability and convergent validity, assessment could benefit from (a) increased documentation that the content of measures assesses important skills in relating to peers, (b) improved methods for assessing social behavior in specific interpersonal situations, and (c) more empirical evidence that indirect assessment methods (self-report, peer assessment, and teacher report) and analogue observations reflect in vivo behavior.

Assessing violent offending in serious juvenile offenders.

The convergent validity of the two most frequently used methods for assessing violent offending in juveniles (i.e., self-reports and arrests) was evaluated. Participants were 87 serious juvenile offenders and their maternal figures, primarily from disadvantaged families. Validation measures tapped established behavioral, family, and peer correlates of delinquency. Results failed to support the ability of either arrests for violent crimes or self-reported violent offenses to index violent criminal behavior accurately. Several methodological features of the study support our hypothesis that the findings were not spurious. Procedural and conceptual implications of the findings are discussed.

Impact of social problem-solving training on aggressive boys: skill acquisition, behavior change, and generalization.

This study examined the impact of social problem-solving training on the behavior of five aggressive boys. Acquisition of problem-solving skills and changes in classroom behavior were evaluated using multiple-baseline designs within and across subjects. A generalization-programming procedure to promote the use of problem-solving skills in the natural environment was introduced across children in multiple-baseline fashion. Direct observation and behavior ratings were used to evaluate the treatment. Results indicated that each subject acquired the problem-solving skills at levels comparable to well-adjusted peers. Only one child showed behavioral improvement coincident with problem-solving skill acquisition. Three others showed moderate behavior change after the generalization-programming procedure was introduced. Only one child's gains on teacher ratings were maintained at the 6-month followup. The results suggest that cognitive-behavioral treatment of childrens' aggressive behavior may produce changes of limited magnitude and durability.

The effects of a positive behavioral context on the social impact of aggressive behavior.

The hypothesis is experimentally examined that a positive behavioral repertoire can ameliorate the negative social impact of aggressive behavior. Sixty-six fourth- through sixth-grade girls viewed and rated a series of videotaped interactions between two female confederates. The proportion of positive to aggressive behavior viewed by each subject was manipulated across six experimental conditions by varying the number of positive behaviors exhibited by one of the confederates (target) while the number of aggressive behaviors displayed by her remained constant (i.e., 0%, 20%, 43%, 60%, 80%, and 100% positive). Each subject provided sociometric ratings of the target and selected trait descriptors that best described her from a checklist. The results indicated that positive behavior exhibited in high rates (80% or more, compared to aggressive behavior) offset the negative effects of aggression on both sociometric ratings and positive and negative descriptors.

A participatory learning module: asepsis and universal precautions.

Mastery of medical and surgical asepsis principles is mandatory for nurses in today's health care environment. The authors report on the development, implementation, and evaluation of a multimedia asepsis module incorporating universal precautions. Practical application of the content, using graphics, medical supplies, and video, occurs in the four-station participatory learning module. Student evaluations of this learning module are positive.

Team management: an alternative to acting directorship.

A sudden absence of leadership due to unexpected illness, death, or resignation can seriously weaken an organization. Orderly administrative transition was believed to be necessary by those confronting a sudden leadership void. A team management administrative approach was proposed in response to an urgent and complex problem. Results of an evaluation of the team at the end of 1 year of leadership are presented. Team management is documented as a viable alternative to a one person acting director in an academic setting.

Differences in children's peer sociometric and attribution ratings due to context and type of aggressive behavior.

Sociometric and attribution (internality and responsibility) ratings of boys performing different kinds of aggression (hostile and instrumental hitting and pushing) and of neutral behavior occurring in two contexts (provoked and unprovoked) were investigated in an analogue fashion. Thirty fifth- and sixth-grade boys viewed and rated 12 brief videotaped scenes of two unfamiliar male peers interacting, presented in one of six random orders. Provoked aggression resulted in less dislike, less worthiness of punishment, and greater attribution to external causes than unprovoked aggression. Instrumental and hostile aggression produced lower liking ratings and were viewed as more deserving of punishment than neutral behavior but did not differ from each other. Results support distinctions between provoked and unprovoked aggression but not between hostile and instrumental aggression, at least in terms of their functional impact on peer judgements.

Decreased production of suppressive-B-cell factor by synovial membrane B-lymphocytes in rheumatoid arthritis.

Suppressive-B-cell factor (SBF) is an autoregulatory B-cell lymphokine produced by heat-aggregated-IgG stimulated B-lymphocytes which suppresses polyclonal immunoglobulin production. SBF production by rheumatoid arthritis (RA) patients' peripheral blood B-lymphocytes inversely correlates with disease activity and in vitro rheumatoid factor production. To further define the role of SBF in the pathogenesis of RA, the present study measured SBF production by surgically-obtained synovial membrane mononuclear leukocytes. SBF production by RA synovial leukocytes was similar to the levels previously described for RA peripheral blood leukocytes. Both RA and osteoarthritis (OA) synovial leukocytes produced significantly less SBF than leukocytes obtained from otherwise healthy patients with plica. OA patients produced less SBF than RA patients, but the difference was not statistically significant. SBF values for combined RA patients and controls with OA or plica correlated with the degree of histological plasma cell infiltration providing further evidence for SBF production by cells of the B-lymphocyte lineage. Depletion studies also demonstrated that synovial SBF was produced by B-lymphocytes. The molecular weight (34,000) of synovial SBF was similar to the molecular weight of peripheral blood SBF. Decreased SBF production by RA synovial B-lymphocytes is a functional abnormality in RA which may contribute to the perpetuation of synovial rheumatoid factor production and chronic synovial inflammation.