Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting‐state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19–37 years) underwent a randomized, three‐way, cross‐over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long‐distance (seed‐based and dual‐regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10^?3), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia‐related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = ?.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.     

Oral lichenoid reactions related to mercury sensitivity

Lichen planus is a common disorder of unknown aetiology. It has been proposed that in some cases it represents a form of allergic reaction to the metals contained in dental amalgam, particularly mercury. Twenty-nine consecutive dentate patients who had lichen planus of the oral mucosa were patch-tested to the range of metals contained in dental amalgam. Ten out of 29 (34%) showed an allergic reaction to mercury and all of these patients had amalgams greater than 5 years old. The amalgams were poorly contoured and had corroded, resulting in continued release of mercury ions. Six patients had their amalgams replaced with composite or glass ionomer materials resulting in resolution of ulcerated lesions. In a follow-up of 3-24 months, one patient had a recurrence of ulcerated areas and another, despite resolution of the oral lesions had persistent discomfort.     

Measurement Properties of a Client Self-report for Treatment Planning and Documenting Therapy Outcomes

The purpose of this study was to validate the Occupational Self Assessment (OSA). The Occupational Self Assessment is an evaluation tool and an outcome measure based on the Model of Human Occupation and concepts of client-centered practice. It is a two-part rating form that elicits client's perceptions and values concerning their own occupational competence, values, and the impact of the environment on their occupational behavior. Data were collected from 302 clients which included physically disabled, psychiatrically disabled and non-disabled adults. Rasch analysis was used to analyze the data. Results supported the preliminary validity and reliability of the OSA and recommendations are given for further improvement of the tool.     

Effect of Computer-Assisted Interviewing on Self-Reported Sexual Behavior Data in a Microbicide Clinical Trial

In a microbicide safety and effectiveness trial (HPTN 035) in Malawi, 585 women completed the same questionnaire through a face-to-face interview (FTFI) and an audio computer-assisted self-interview (ACASI). Concordance between FTFI and ACASI responses ranged from 72.0 % for frequency of sex in the past week to 95.2 % for anal intercourse (AI) in the past 3 months. Reported gel and condom use at last sex act were marginally lower with ACASI than FTFI (73.5 % vs. 77.2 %, p = 0.11 and 60.9 % vs. 65.5 %, p = 0.05, respectively). More women reported AI with ACASI than FTFI (5.0 % vs. 0.2 %, p < 0.001). Analyses of consistency of responses within ACASI revealed that 15.0 % of participants in the condom-only arm and 28.7 % in the gel arm provided at least one discrepant answer regarding total sex acts and sex acts where condom and gel were used (19.2 % reported one inconsistent answer, 8.1 % reported two inconsistent answers, and 1.4 % reported three inconsistent answers). While ACASI may provide more accurate assessments of sensitive behaviors in HIV prevention trials, it also results in a high level of internally inconsistent responses.     

A panel of monoclonal antibodies to ovine placental lactogen

A panel of 11 rat monoclonal antibodies (mAbs) has been raised to ovine placental lactogen (PL). By competitive enzyme-linked immunoabsorbent assay (ELISA), confirmed by two-site ELISA, the antibodies were shown to recognize six antigenic determinants on the ovine PL molecule, two of which overlap. One antigenic determinant (designated 1) was shared by other members of the prolactin/growth hormone (GH)/PL family in ruminants, humans and rodents. The binding of (125)I-labelled ovine PL to crude receptor preparations from sheep liver (somatotrophic) or rabbit mammary gland (lactogenic) was inhibited by mAbs recognizing antigenic determinants 2-6. Both types of receptor preparation were affected similarly. In the local in vivo pigeon crop sac assay, mAbs directed against determinants 3 and 6 enhanced the biological activity of ovine PL.     

Effects of varying protein and energy intakes on growth and metabolic response in low birth weight infants

Growth (weight, length, head circumference, and skinfold thickness), retention of major nutrients (nitrogen, sodium, potassium, chloride, calcium, and phosphorus), and chemical indices of protein adequacy (plasma albumin and transthyretin concentrations) and excess (blood urea nitrogen concentration and acid-base status; plasma amino acid concentrations) were determined serially from the time desired intake was tolerated until discharge weight (2200 gm) was reached in low birth weight infants (birth weight 900 to 1750 gm) fed one of three formulas, which provided protein and energy intakes, respectively, of 2.24 gm/kg/day and 115 kcal/kg/day (group 1), 3.6 gm/kg/day and 115 kcal/kg/day (group 2), and 3.5 gm/kg/day and 149 kcal/kg/day (group 3). Weight gain and rate of increase in length and head circumference were less in group 1 than in groups 2 and 3. Retention of most major nutrients also was less in group 1, as was blood urea nitrogen concentration, plasma albumin and transthyretin concentrations, and plasma concentrations of several amino acids. The rate of weight gain was not significantly greater in group 3 than in group 2, but the rate of increase in skinfold thickness was greater in this group. Neither nutrient retention nor metabolic indices differed between groups 2 and 3. These results suggest that a protein intake of 2.24 gm/kg/day is inadequate for the type of LBW infants studied, that the higher protein intakes are well tolerated, and that an energy intake of 149 vs 115 kcal/kg/day does not enhance utilization of the higher protein intakes studied.     

Genetic aberrations defined by comparative genomic hybridization distinguish long-term from typical survivors of glioblastoma

Glioblastoma (GBM) remains a highly lethal neoplasm, refractory to current therapies. The molecular genetic aberrations most closely related to clinical aggressiveness in GBM have been difficult to identify, perhaps due in part to the short survival range observed in cohorts of GBM patients. To address this, we characterized 39 tumors from rare patients (2-5% of all GBM cases) who experienced long-term survival (>3 years) using comparative genomic hybridization as a genome-wide screen. We then compared the frequency and type of aberrations with those in tumors from 24 typical or short-term survivors [STSs (<1.5 years)]. Losses of 9p and 10 and simple gains of chromosome 7 showed at least trends toward increased frequency in the STS group. Additional aberrations, including loss of 6q and gains of 19q and 20q, were significantly more frequent in the STS group. The presence of 19q loss was exclusive to the long-term survivor (LTS) group. Multivariate analyses indicated that 6q loss, 10q loss, and 19q gain were associated with short-term survival (all P < 0.01). The combination of any two of these three aberrations was seen in 16 of 24 STSs but only 1 of 39 LTSs. This comparison of rare LTSs with STSs (typical GBM survivors) identified 6q loss, 10q loss, and 19q gain, particularly when two or more of these were present, as most closely associated with aggressive clinical behavior in GBM. Loss of 19q may be a marker of long-term survival.     

How often are nonenhancing supratentorial gliomas malignant? A population study

The presence of contrast enhancement in a brain tumor is often regarded as a sign of malignancy. The authors identified 314 patients with malignant and low-grade supratentorial glial neoplasms in an unselected population, 58 of which lacked contrast enhancement on preoperative neuroimaging. Nonenhancing gliomas were malignant in approximately one third of cases, especially in older patients. Histologic confirmation of the diagnosis is therefore important in all patients suspected of harboring a primary glial neoplasm.