The stroke exercise preference inventory is feasible to use in a community rehabilitation setting.

Exploring exercise preferences may help people to adhere to exercise programs by promoting customized programs to suit the person's choices and concerns. We investigated if the Stroke Exercise Preference Inventory, a questionnaire designed to explore stroke survivors' preferences for exercise and potential barriers, was feasible to use, and whether it assisted physiotherapists to design ongoing exercise programs in a mixed diagnostic convenience sample attending community rehabilitation. Physiotherapy staff interviewed 42 participants, and sought feedback about the questionnaire. Participant responses for exercise preferences and perceived barriers were then summarized. The questionnaire was quick to administer, readily understood, and considered relevant to consider when discussing options for exercise. Clinicians reported the questionnaire was useful for 48% (20/42) of participants, as it engaged the participant, clarified their preferences and allowed problem solving of potential barriers to exercise. Participants expressed strong preferences to be challenged, and to receive supervision and support. Preferences regarding environmental and social context of exercise varied widely. Difficulty getting started was the most common barrier reported. The Stroke Exercise Preference Inventory was feasible to use with a mixed diagnostic group during community rehabilitation, and provides structure to explore preferences and barriers to exercise. It remains to be tested whether use of the questionnaire promotes adherence to exercise programs.

Synchronous Multifocal Canalicular Adenomas.

Canalicular adenoma (CAD) is an uncommon benign tumor of minor salivary glands with predilection for the upper labial mucosa. An 80-year-old female presented with nine submucosal nodules of the upper labial mucosa and bilateral buccal mucosa. Histopathologic examination revealed multifocal circumscribed tumor islands with a tubular growth pattern within a loose hypocellular myxoid background stroma. Interconnecting rows of columnar tumor cells imparted a canalicular morphology. In addition to the characteristic histopathologic findings, a comprehensive immunohistochemical panel supported a final diagnosis of multifocal CAD. Synchronous multifocality in CAD is an infrequent finding and this sine qua non clinicopathologic correlation article exemplifies such a case.

Exploring relevance, public perceptions, and business models for establishment of private well water quality monitoring service.

Existing public policies mostly focus on public water systems, leaving aside the quality issues regarding private wells in small and rural locations. Establishment of affordable and accessible water quality monitoring services may ensure acceptable levels of all the parameters. This paper aims to explore (a) health risk because of chemical contaminants of private wells, (b) population perspective on well water quality and monitoring, and (c) to create a business model of a centralized water quality monitoring service. The results show potential problems with toxic levels of arsenic, barium, cadmium, chromium, lead, mercury, and selenium. About 5% of the province's population is at risk for potential exposure to contaminated private well water. The survey reinforces that the successful implementation of water testing laboratories for private wells is a shared responsibility between well owners and the government organizations, and almost three-fourths respondents were willing to share the cost up to certain limit. A business model including financial projections for a centralized water testing laboratory is presented. Drinking of unmonitored private well water is putting population health at risk. Either strong regulation with mandatory water testing or voluntary water testing with adequate government subsidy can ensure sustainable function of a centralized water testing laboratory.

Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model.

Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol(®)) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor NaB (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level, arguing against a DAAO-mediated effect. However, NaB reduced plasma L-serine and based on reports that NaB also elevates various plasma metabolites, for example aminoisobutyric acid (AIB), a potential effect via the System A amino acid carrier may be involved in the regulation of synaptic glycine level to modulate NMDAR function needs to be investigated. Acute ascorbic acid (300 mg/kg) also inhibited PCP-induced locomotor activity, which was further attenuated in the presence of D-serine (600 mg/kg). Ascorbic acid may have an action at the dopamine membrane carrier and/or altering redox mechanisms that modulate NMDARs, but this needs to be further investigated. The findings support an effect of D-serine on PCP-induced hyperactivity. They also offer suggestions on an interaction of NaB via an unknown mechanism, other than DAAO inhibition, perhaps through metabolomic changes, and find unexpected synergy between D-serine and ascorbic acid that supports combined NMDA glycine- and redox-site intervention. Although mechanisms of these specific agents need to be determined, overall it supports continued glutamatergic drug development.

A biological basis for depression in pancreatic cancer.

BACKGROUND: Patients with pancreatic adenocarcinoma frequently present with depression the symptoms of which may precede cancer diagnosis, suggesting that the pathophysiology of depression in pancreatic adenocarcinoma may result from biological changes that are induced by the presence of the tumour itself. The present study was conducted to test a hypothesized relationship with the kynurenine pathway, which has been implicated in both depression and tumour-induced immunosuppression. METHODS: 17 patients with pancreatic adenocarcinoma were recruited and completed mood questionnaires (Functional Assessment of Cancer Therapy -Pancreatic Cancer, Beck Depression Inventory and the Beck Anxiety Inventory) and blood testing for serum levels of tryptophan, kynurenine, kynurenic acid and quinolinic acid. Tumour burden was determined from pathology reports (tumour size and nodal involvement). RESULTS: Findings indicated a negative correlation between mood scores and the plasma kynurenic acid : tryptophan ratio in plasma, and a positive correlation between tumour burden and plasma kynurenine level. CONCLUSIONS: This study suggests that pancreatic cancer may influence mood via the kynurenine pathway. The relationship of the kynurenine pathway with pancreatic tumour burden should be explored further in large multicentre studies because a better understanding of this physiology might have significant clinical benefit.

Environmental lead exposure, maternal thyroid function, and childhood growth.

Prenatal and early-life exposure to lead is hypothesized to have a range of adverse effects on childhood health. Drawing on data collected from a population-based prospective cohort study of a highly exposed town and a low exposed town in Kosovo, Yugoslavia we assessed whether elevated maternal blood lead (BPb) concentrations during pregnancy were associated with reduced childhood measures of attained height and BMI or growth rate, and whether the associations, if any, were mediated by maternal thyroid hormone concentration at mid-pregnancy. There was no association between blood lead levels and height or BMI in either town. However, increased maternal thyroid hormone was unexpectedly associated with reduced attained childhood height, and growth rate of height from 6.5 to 10 years, in the low-exposure town. We examine potential reasons for this unexpected inverse association.

Ghrelin and leptin response to oral glucose challenge among antipsychotic drug-treated children.

We investigated ghrelin, leptin, glucose, and insulin response to an oral glucose tolerance test among children receiving antipsychotics. Hormone concentrations were assayed at fasting, 30, 60, and 120 minutes. The sample was composed of 9 obese (defined as at or above the 95th percentile for age) and 10 overweight/normal children (defined as less than the 95th percentile in weight) based on National Institutes of Health criteria. Ages of the obese (10.7 +/- 3.4 years) and the overweight/normal (13.1 +/- 1.6 years) did not differ. Leptin was significantly higher among the obese group and did not change consequent to glucose. Ghrelin did not differ between the groups, and when the values were combined, ghrelin decreased at 30 minutes and approached fasting concentrations at 120 minutes. To further explore our data, we constituted separate groups based upon z score changes. When weight gain defined as an increase in z score (X = 0.4), the nongainers showed leptin concentrations to decrease over time. Findings encourage further oral glucose tolerance test studies to explain the leptin response to weight gain seen among children receiving antipsychotic medication.

Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD.

OBJECTIVE: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). METHOD: The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale. RESULTS: Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD. CONCLUSIONS: MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.

gamma-Aminobutyric acid-serotonin interactions in healthy men: implications for network models of psychosis and dissociation.

BACKGROUND: This study tested the hypothesis that deficits in gamma-aminobutyric acid type A (GABA(A)) receptor function might create a vulnerability to the psychotogenic and perceptual altering effects of serotonergic (5-HT(2A/2C)) receptor stimulation. The interactive effects of iomazenil, an antagonist and partial inverse agonist of the benzodiazepine site of the GABA(A) receptor complex, and m-chlorophenylpiperazine (m-CPP), a partial agonist of 5-HT(2A/2C) receptors, were studied in 23 healthy male subjects. METHODS: Subjects underwent 4 days of testing, during which they received intravenous infusions of iomazenil/placebo followed by m-CPP/placebo in a double-blind, randomized crossover design. Behavioral, cognitive, and hormonal data were collected before drug infusions and periodically for 200 min after. RESULTS: Iomazenil and m-CPP interacted in a synergistic manner to produce mild psychotic symptoms and perceptual disturbances without impairing cognition. Iomazenil and m-CPP increased anxiety in an additive fashion. Iomazenil and m-CPP interacted in a synergistic manner to increase serum cortisol. CONCLUSIONS: Gamma-aminobutyric acid-ergic deficits might increase the vulnerability to the psychotomimetic and perceptual altering effects of serotonergic agents. These data suggest that interactions between GABA(A) and 5-HT systems might contribute to the pathophysiology of psychosis and dissociative-like perceptual states.

Treatment of rats with antipsychotic drugs: lack of an effect on brain N-acetyl aspartate levels.

BACKGROUND: Proton magnetic resonance spectroscopy (1H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in the rat the effect of antipsychotic drugs on NAA in several brain regions where NAA reductions have been reported in chronically medicated patients with schizophrenia. METHODS: Three groups of nine rats each were treated with haloperidol (6 mg/kg/day), clozapine (70 mg/kg/day) and vehicle for 6 weeks and were sacrificed. Concentrations of NAA were determined by high-performance liquid chromatography (HPLC) from the following brain regions: cortex, striatum, thalamus, hippocampus and cerebellum. RESULTS: Mixed-factorial ANOVA of NAA concentrations revealed no significant effect of drug group [F(2, 24) = 0.034; p = 0.966] or a group by brain region interaction [F(8, 44) = 0.841; p = 0.572]. There was a significant main effect of region [F(4, 21) = 6.104; p = 0.002] with higher NAA in the cortex. CONCLUSIONS: These results are consistent with the only other study of the effect of typical and atypical antipsychotic drugs on NAA in the rat brain. The well-documented lower NAA in chronically treated schizophrenia patients is probably not a simple effect of antipsychotic medications.