Goal‐directed behaviors in patients with schizophrenia: Concept relevance and updated model

Goal‐directed behaviors are formulated to pursue a given objective by constructing a plan and selecting actions that lead to the intended goal, either immediately or over an extended period. This concept is important to the study of human behavior because of its involvement in the majority of complex or novel situations that an individual may encounter, regardless of the cognitive, affective, or social abilities required. In this paper, we aim to demonstrate the relevance of goal‐directed behaviors to our understanding of the cognitive deficits and other symptoms associated with schizophrenia. A systematic analysis of this relation may allow us to develop integrative hypotheses regarding positive, negative, and disorganized symptoms of schizophrenia rather than consider them to be distinct issues. In this article, we review previous studies of goal‐directed actions in patients with schizophrenia in order to clarify the relevant concepts and provide a theoretical basis for the integration of existing results. Based on available theoretical models and data, we propose an updated model to facilitate further investigation of schizophrenia‐related impairments in goal‐directed behaviors.     

Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD)

OBJECTIVE

Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population.

RESEARCH DESIGN AND METHODS

We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[³H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR_i= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR_i= fasting FFA × FPI).

RESULTS

Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01–0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001).

CONCLUSIONS

Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease in industrialized countries (1). NAFLD is strongly correlated with insulin-resistant states such as obesity, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM). Cross-sectional studies have associated T2DM with worse histology in NAFLD (2) and possibly with a greater risk of progression and more aggressive disease. For instance, patients with diabetes have a higher risk of developing fibrosis and cirrhosis (2–5), although the natural history of the disease in patients with T2DM remains unclear. Compared with nondiabetic subjects, subjects with T2DM are believed to have an increased risk of developing NAFLD (3,6), but the true prevalence of prediabetes and T2DM has never been systematically assessed by means of an oral glucose tolerance test (OGTT) among patients with NAFLD. The magnitude of the problem is large: an estimated 25.8 million people, or 8.3% of the U.S. population, have type 1 and type 2 diabetes (7). Even more worrisome is that 35% of adults and ∼50% of those aged >60 years have prediabetes, a condition that puts them at higher risk for developing T2DM. Whether NAFLD, a condition associated with insulin resistance (IR), increases the risk of developing T2DM remains unclear.The purpose of our study was to determine the prevalence of abnormal glucose metabolism and understand how hyperglycemia and NAFLD impact the metabolic profile of these subjects.     

Age-specific thyroid hormone and thyrotropin reference intervals for a pediatric and adolescent population

Abstract Background: Establishment of reliable reference intervals remains valuable for confirming validity and advancing standardization across methods and populations. Moreover, knowledge of the measurement uncertainty (U) and of the reference change value (RCV) has important applications in clinical chemistry. Methods: Starting from the information available in the laboratory data base (29,901 subjects) an initial selection was carried out by eliminating all subjects with a clinical or laboratory pathological report; data from 7581 0- to 20-year-old subjects (53.87% girls) remained in the study. These subjects, divided into nine age groups, were used to define reference distribution percentiles (2.5th, 50th and 97.5th) of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), and free T4 (fT4), as well as U and RCV of these assays. Results: In early infancy, T4 and fT4 values were higher than in the older age groups. Serum T4 95th percentile reference value, useful for the diagnosis of hyperthyroidism, was 142.9 in 20-year-old boys and 230.4 nmol/L in early infants and serum T3 95th percentile was 2.6 and 3.5 nmol/L, respectively, while fT4 2.5th percentile reference value, useful for the diagnosis of hypothyroidism, was 9.6 and 13.0 pmol/L, respectively. Serum TSH 97.5th percentile showed less age variation, 4.38-4.88 mIU/L. Performance of the four assays resulted in approximately 20% Us, reflecting simple and complex imprecision, trueness, analytical and functional sensitivity. RCV of serum TSH (58.6%) was larger than for thyroid hormones (28.3%-34.7%), probably due to the high biological variation of this hormone. Conclusions: We have established reference interval for TSH and thyroid hormones, as well as Us for assessing reliability of measurements, and RCVs to alert users on the presence of clinical significant changes.     

Testing the reliability and efficiency of the pilot Mixed Methods Appraisal Tool (MMAT) for systematic mixed studies review

BackgroundSystematic literature reviews identify, select, appraise, and synthesize relevant literature on a particular topic. Typically, these reviews examine primary studies based on similar methods, e.g., experimental trials. In contrast, interest in a new form of review, known as mixed studies review (MSR), which includes qualitative, quantitative, and mixed methods studies, is growing. In MSRs, reviewers appraise studies that use different methods allowing them to obtain in-depth answers to complex research questions. However, appraising the quality of studies with different methods remains challenging. To facilitate systematic MSRs, a pilot Mixed Methods Appraisal Tool (MMAT) has been developed at McGill University (a checklist and a tutorial), which can be used to concurrently appraise the methodological quality of qualitative, quantitative, and mixed methods studies.ObjectivesThe purpose of the present study is to test the reliability and efficiency of a pilot version of the MMAT.MethodsThe Center for Participatory Research at McGill conducted a systematic MSR on the benefits of Participatory Research (PR). Thirty-two PR evaluation studies were appraised by two independent reviewers using the pilot MMAT. Among these, 11 (34%) involved nurses as researchers or research partners. Appraisal time was measured to assess efficiency. Inter-rater reliability was assessed by calculating a kappa statistic based on dichotomized responses for each criterion. An appraisal score was determined for each study, which allowed the calculation of an overall intra-class correlation.ResultsOn average, it took 14 min to appraise a study (excluding the initial reading of articles). Agreement between reviewers was moderate to perfect with regards to MMAT criteria, and substantial with respect to the overall quality score of appraised studies.ConclusionThe MMAT is unique, thus the reliability of the pilot MMAT is promising, and encourages further development.     

Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1

Prostaglandins (PG) are known to induce pain perception indirectly by sensitizing nociceptors. Accordingly, the analgesic action of nonsteroidal anti-inflammatory drugs (NSAIDs) results from inhibition of cyclooxygenases and blockade of PG biosynthesis. Cyclopentenone PGs, 15-d-PGJ(2), PGA(2), and PGA(1), formed by dehydration of their respective parent PGs, PGD(2), PGE(2), and PGE(1), possess a highly reactive alpha,beta-unsaturated carbonyl group that has been proposed to gate the irritant transient receptor potential A1 (TRPA1) channel. Here, by using TRPA1 wild-type (TRPA1(+/+)) or deficient (TRPA1(-/-)) mice, we show that cyclopentenone PGs produce pain by direct stimulation of nociceptors via TRPA1 activation. Cyclopentenone PGs caused a robust calcium response in dorsal root ganglion (DRG) neurons of TRPA1(+/+), but not of TRPA1(-/-) mice, and a calcium-dependent release of sensory neuropeptides from the rat dorsal spinal cord. Intraplantar injection of cyclopentenone PGs stimulated c-fos expression in spinal neurons of the dorsal horn and evoked an instantaneous, robust, and transient nociceptive response in TRPA1(+/+) but not in TRPA1(-/-) mice. The classical proalgesic PG, PGE(2), caused a slight calcium response in DRG neurons, increased c-fos expression in spinal neurons, and induced a delayed and sustained nociceptive response in both TRPA1(+/+) and TRPA1(-/-) mice. These results expand the mechanism of NSAID analgesia from blockade of indirect nociceptor sensitization by classical PGs to inhibition of direct TRPA1-dependent nociceptor activation by cyclopentenone PGs. Thus, TRPA1 antagonism may contribute to suppress pain evoked by PG metabolites without the adverse effects of inhibiting cyclooxygenases.