Activity in orbitofrontal neuronal ensembles reflects inhibitory control

Stopping, or inhibition, is a form of self‐control that is a core element of flexible and adaptive behavior. Its neural origins remain unclear. Some views hold that inhibition decisions reflect the aggregation of widespread and diverse pieces of information, including information arising in ostensible core reward regions (i.e., outside the canonical executive system). We recorded activity of single neurons in the orbitofrontal cortex (OFC) of macaques, a region associated with economic decisions, and whose role in inhibition is debated. Subjects performed a classic inhibition task known as the stop signal task. Ensemble decoding analyses reveal a clear firing rate pattern that distinguishes successful from failed inhibition and that begins after the stop signal and before the stop signal reaction time (SSRT). We also found a different and orthogonal ensemble pattern that distinguishes successful from failed stopping before the beginning of the trial. These signals were distinct from, and orthogonal to, value encoding, which was also observed in these neurons. The timing of the early and late signals was, respectively, consistent with the idea that neuronal activity in OFC encodes inhibition both proactively and reactively.     

Accuracy and User Performance of a New Blood Glucose Monitoring System

Introduction:Self-monitoring of blood glucose (BG) is important in diabetes management, allowing people with diabetes (PWD) to assess responses to diabetes therapy and to inform if they are attaining their glycemic targets. This study assessed the accuracy and user performance (UP) of a new blood glucose monitoring system (BGMS), CONTOUR®PLUS ELITE, according to International Organization for Standardization (ISO) 15197:2013 criteria and also more stringent criteria.Methods:In laboratory Study 1, capillary fingertip blood samples from 100 PWD were evaluated using the new BGMS. In clinical Study 2, 130 PWD had Yellow Springs Instrument (YSI) analyzer reference measurements against subject-obtained fingertip and palm blood, and trial staff-obtained venous blood. The new BGMS was tested with test strips from three different lots. A UP questionnaire assessed ease of use.Results:Study 1: 100% of combined accuracy results fulfilled ISO criteria (±15 mg/dL at BG <100 mg/dL; ±15% at BG ≥100 mg/dL); 99.8% fulfilled more stringent criteria (±10 mg/dL at BG <100 mg/dL; ±10% at BG ≥100 mg/dL). Error grid analysis showed that 100% of results were within zone A. Study 2: >98% of subject- and 100% of trial staff-obtained performance results met ISO criteria. Most subjects (>96%) found the BGMS easy to use.Conclusion:The new BGMS exceeded minimum ISO 15197:2013-specified standards for both accuracy and UP criteria, along with the more stringent accuracy criteria. These data show that this new BGMS can be a useful tool in managing glycemic control for PWD.     

Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis

Background/aims: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied.

Methods: All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated.

Results: Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD?=?0.98, p?=?.01) and the PE group (SMD?=?0.94, p?p?Conclusions: This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.     

Prenatal care reduces the impact of illicit drug use on perinatal outcomes.

OBJECTIVE: To estimate the extent that prenatal care (PNC) retains its protective influence against prematurity, low birth weight (LBW), and small for gestational age (SGA) status in infants exposed to illicit drug use (IDU) in pregnancy. STUDY DESIGN: This was a prospective cohort analysis including 6673 women residents of the District of Columbia (Washington, DC, USA) delivering at four city hospitals. Women were screened in the immediate postpartum period. Levels of PNC were established according to American College of Obstetrics and Gynecology guidelines and the Kotelchuck index. PNC and IDU were compared between subgroups. Adjusted relative risks for prematurity, LBW and SGA, controlling for maternal and gestational ages, were calculated in different groups according to IDU and level of PNC. RESULTS: IDU was identified in 13% of mothers screened. PNC was classified as none (6%), inadequate (10%), intermediate (20%), and adequate (64%). The highest risk for prematurity, LBW, or SGA occurred in infants born to mothers with no PNC and positive IDU in pregnancy (prematurity OR=12.05, 95% CI: 8.99 to 16.16; LBW OR=14.76, 95% CI: 11.03 to 19.75; SGA OR=9.20, 95% CI: 5.32 to 15.92). As PNC levels increased, significant reductions in risk for prematurity and LBW (not for SGA) in IDU-exposed infants were observed. Risk for SGA in IDU-exposed infants reduced significantly when PNC was introduced. CONCLUSIONS: In infants exposed to IDU, a reduction in risk for prematurity, LBW, and SGA, was consistently demonstrated with improved levels of PNC. In high-risk populations, health care should seek to reach mothers early, especially those identified at risk for IDU, and deliver PNC to them effectively.     

A diagnostic test accuracy meta-analysis of maternal serum ischemia-modified albumin for detection of preeclampsia

Background/aims: Ischemia-modified albumin (IMA) has been widely accepted as a serological biomarker. IMA has been proposed as a simple and novel marker of oxidative stress in preeclampsia (PE). This systematic review and diagnostic test accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel serological biomarker, IMA to detect PE.

Methods: A systematic search of major databases was performed to identify all published diagnostic accuracy studies on IMA. Risk of bias and applicability concerns were assessed for included studies. Summary estimates; the pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects models. The overall test performance was summarized using summary receiver operating characteristic (SROC) curve analysis.

Results: Six articles were included in this meta-analysis. The overall estimates of IMA in detecting PE were pooled sensitivity; 0.80 (95%CI 0.73–0.86), pooled specificity; 0.76 (95%CI 0.70–0.81), DOR; 14.32 (95%CI 5.06–40.57), and area under curve (AUC); 0.860. There was no between-study heterogeneity due to threshold effect.

Conclusions: This meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy (AUC?=?0.860). However, further research is needed for re-evaluation and clinical validation of fairly promising results of this meta-analysis.     

Covert Cryptococcal Meningitis in a Patient With Systemic Lupus Erythematous

Background: Cryptococcal meningitis is a rare but well-recognized illness with a high mortality rate in immunosuppressed patients with systemic lupus erythematosus (SLE). The diagnosis of cryptococcal meningitis in these patients can be challenging, especially in the emergency department (ED), as the clinical presentation may be non-specific, which can lead to delayed treatment. Objective: To recognize risk factors associated with the development of cryptococcal meningitis infection in patients with SLE and to provide an update on the clinical presentation, prognosis, and therapeutic options. Case Report: A 21-year-old man with SLE presented with a 4-day history of headache, fever, nausea, and vomiting after being discharged from the ED 1 day before this visit, after lumbar puncture showed normal values. One week before, he had completed 7-day pulse therapy with intravenous cyclophosphamide and intravenous methylprednisone for lupus nephritis. The patient was febrile, but the remainder of the examination was normal. Laboratory data showed lymphopenia. Given his immunocompromised state, a cryptococcal antigen was added to cerebrospinal fluid (CSF) sent from the prior ED visit and was positive at a titer of 1:8. The patient was treated with amphotericin B and 5-flucytosine for 6 weeks. Ten months later the patient remained free of infection. Conclusion: Normal neurological and CSF examination do not exclude cryptococcal meningitis in immunocompromised patients with SLE. India ink or, preferably, latex agglutination test and CSF fungal culture are recommended. A high level of suspicion is the key in the diagnosis of cryptococcal meningitis and will help avoid delays in treatment.     

Antihypertensive effect of ragaglitazar: a novel PPARalpha and gamma dual activator.

Ragaglitazar is a novel and potent dual peroxisome proliferators activated receptor (PPAR) alpha and gamma activator. The aim of this study is to investigate the effect of ragaglitazar on blood pressure and endothelial function in insulin resistant animal model and non-insulin resistant hypertensive models. The effects ragaglitazar were tested in Zucker fa/fa, spontaneously hypertensive rats (SHR), 2 kidney 1clip rat (2K1C) and Wistar Kyoto rats (WKY). Pioglitazone was taken as a comparative standard. Ragaglitazar showed significant reduction (P<0.001) of systolic blood pressure (SBP) in insulin resistant fa/fa rats, with concomitant reduction in plasma triglycerides (TG) and insulin levels while pioglitazone (10 mg kg(-1)) showed significant (P<0.05) but comparatively less reduction. Ragaglitazar in contrast to pioglitazone showed significant reduction (P<0.05) of SBP in SHR, 2K1C while the same dose did not have any effect on normotensive WKY. Ragaglitazar also showed significant improvement in acetylcholine-induced relaxation in isolated aorta of Zucker fa/fa, SHR, 2K1C and also potentiated the insulin-induced vasorelaxation in Zucker fa/fa rats. These findings summarize that ragaglitazar shows significant reduction of BP and improvement in endothelial function not only in insulin resistant but also in non-insulin resistant hypertensive models where standard thiazolidinediones are ineffective. These data indicates that dual PPARalpha and gamma activator ragaglitazar can be beneficial for the treatment of hypertension and vascular disease commonly associated with type 2 diabetes.     

A radiotherapy technique to limit dose to neural progenitor cell niches without compromising tumor coverage

Radiation therapy (RT) for brain tumors is associated with neurocognitive toxicity which may be a result of damage to neural progenitor cells (NPCs). We present a novel technique to limit the radiation dose to NPC without compromising tumor coverage. A study was performed in mice to examine the rationale and another was conducted in humans to determine its feasibility. C57BL/6 mice received localized radiation using a dedicated animal irradiation system with on-board CT imaging with either: (1) Radiation which spared NPC containing regions; (2) Radiation which did not spare these niches; or (3) Sham irradiation. Mice were sacrificed 24 h later and the brains were processed for immunohistochemical Ki-67 staining. For the human component of the study, 33 patients with primary brain tumors were evaluated. Two intensity modulated radiotherapy (IMRT) plans were retrospectively compared: a standard clinical plan and a plan which spares NPC regions while maintaining the same dose coverage of the tumor. The change in radiation dose to the contralateral NPC-containing regions was recorded. In the mouse model, non-NPC-sparing radiation treatment resulted in a significant decrease in the number of Ki67⁺ cells in dentate gyrus (DG) (P = 0.008) and subventricular zone (SVZ) (P = 0.005) compared to NPC-sparing radiation treatment. In NPC-sparing clinical plans, NPC regions received significantly lower radiation dose with no clinically relevant changes in tumor coverage. This novel radiation technique should significantly reduce radiation doses to NPC containing regions of the brain which may reduce neurocognitive deficits following RT for brain tumors.     

Assessment of stereopsis in pediatric and adolescent spectacle-corrected refractive error – A cross-sectional study

Purpose:To assess the level of stereopsis in school children with spectacle-corrected refractive errors using Titmus fly and Randot stereo tests, evaluate the factors associated with the level of stereopsis, and determine the level of agreement between the two tests.Methods:A cross-sectional study was done on 5- to 18-year-old school-children wearing spectacles for at least 1-month duration. Visual acuity was assessed using Snellen’s visual acuity chart, and their spectacle correction being used currently was measured using an auto lensmeter. The level of stereopsis was assessed using Randot and Titmus fly stereo tests. Data were entered using Microsoft Excel and analyzed using IBM-SPSS version 20, Chicago, IL. The associations between stereopsis and type of refractive error, visual acuity, age, and gender were analyzed. An agreement between Randot and Titmus fly test was done using Kappa statistics.Results:A total of 222 children (101 boys and 121 girls; mean age 13 years) were assessed. Astigmatism was the most prevalent refractive error (60.4%), followed by myopia (24.8%) and hypermetropia (1.4%). Thirty children (13.5%) had anisometropia. All hyperopes had normal stereopsis. Children with spherical myopia had better stereopsis, followed by astigmatism and anisometropia in the same order (P = 0.036). Children with anisometropia ≤1.5 D had better stereopsis than anisometropia more than 1.5 D. Stereopsis was also found to have no correlation with the age and visual acuity at the time of testing or the age at which the child first started wearing spectacles. Stereopsis values obtained from Randot and Titmus fly stereo tests showed moderate agreement with Kappa value 0.581.Conclusion:Anisometropia and astigmatism are the most critical factors determining the level of stereopsis in refractive errors.