Capacities for theory of mind,metacognition, and neurocognitive function are independently related to emotional recognition in schizophrenia

While many with schizophrenia spectrum disorders experience difficulties understanding the feelings of others, little is known about the psychological antecedents of these deficits. To explore these issues we examined whether deficits in mental state decoding, mental state reasoning and metacognitive capacity predict performance on an emotion recognition task. Participants were 115 adults with a schizophrenia spectrum disorder and 58 adults with substance use disorders but no history of a diagnosis of psychosis who completed the Eyes and Hinting Test. Metacognitive capacity was assessed using the Metacognitive Assessment Scale Abbreviated and emotion recognition was assessed using the Bell Lysaker Emotion Recognition Test. Results revealed that the schizophrenia patients performed more poorly than controls on tests of emotion recognition, mental state decoding, mental state reasoning and metacognition. Lesser capacities for mental state decoding, mental state reasoning and metacognition were all uniquely related emotion recognition within the schizophrenia group even after controlling for neurocognition and symptoms in a stepwise multiple regression. Results suggest that deficits in emotion recognition in schizophrenia may partly result from a combination of impairments in the ability to judge the cognitive and affective states of others and difficulties forming complex representations of self and others.     

Erschwerte Anlage eines Pulmonaliskatheters durch eine persistierende linke V. cava superior

The incidental detection of a persistent left vena cava superior during insertion of a pulmonary artery catheter in a patient with acute respiratory distress syndrome (ARDS) prior to extracorporeal membrane oxygenation (ECMO) therapy is reported. A persistent left vena cava superior is the most frequent thoracic malformation and can be associated with other malformations such as congenital heart disease. Therefore, further diagnostic evaluation is needed especially in pulmonary hypertension and ARDS. Anaesthesiologists should be aware of the specific aspects associated with a persistent left vena cava superior.     

Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study

BACKGROUND AND PURPOSE:Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data.MATERIALS AND METHODS:Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization.RESULTS:Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes⁻¹ versus 14.3 ± 4.8 minutes⁻¹, P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes⁻¹, P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes⁻¹, P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes⁻¹, P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes⁻¹ versus 14.8 ± 3.4 minutes⁻¹, P = .38) or vary with mean arterial pressure (r = −0.08, [−0.10, 0.05]).CONCLUSIONS:Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.

Patients with intracerebral hemorrhage (ICH) most often present with elevated blood pressure (BP), but acute treatment remains controversial.^1,2 Despite the results of recent randomized controlled trials of BP management demonstrating no excess of adverse clinical events,^3,4 many physicians are reluctant to aggressively use antihypertensive agents in the acute phase of ICH. This relucence is primarily based on persisting theoretic concerns that there is a zone of tissue at risk for ischemic injury surrounding the acute hematoma.⁵ In addition, more recent MR imaging studies have suggested that subacute ischemic injury occurs in areas remote from the hematoma, including borderzone (BZ, also known as watershed) regions.^6–11 The etiology of these ischemic injuries has been postulated to be hemodynamic compromise secondary to BP reduction.¹⁰ Studies of CBF in the perihematoma region indicate that this region is relatively hypoperfused, but not severely enough to result in ischemia.^12–14 Previous PET studies have demonstrated that the perihematoma region is, in fact, hypometabolic, likely secondary to the primary brain injury, and that the oxygen extraction fraction is not elevated, indicating the absence of misery perfusion.^12,15 Nonetheless, it is possible that reduction of BP will result in a fall in cerebral perfusion pressure (CPP), subsequently precipitating ischemia.¹⁶ In the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), we demonstrated that acute BP reduction is not associated with a significant fall in CBF.¹⁷ It has been demonstrated, however, that CPP is more sensitive than CBF or CBV to changes in blood pressure.¹⁸ The relationship between CPP and BP reduction in patients with intracerebral hemorrhage is unknown.Global CPP is normally calculated as the difference between the mean arterial pressure and intracranial pressure, which requires insertion of an intraventricular manometer. Monitoring of intracranial pressure and CPP is generally reserved for patients with a decreased level of consciousness and/or obstructive hydrocephalus requiring ventricular drainage. In these cases, current consensus guidelines recommend that BP be titrated to ensure that CPP is between 50 and 70 mm Hg.^19,20 In addition, global CPP may not reflect local variations in intracranial pressure due to the mass effect of a hematoma, particularly in small hematomas.²¹ Measurements of regional CPP might inform clinical BP management decisions. With PET, it has been demonstrated that CPP can be calculated as a ratio of CBF to CBV.¹⁸ We adapted this technique by using CTP source data from ICH ADAPT to assess local CPP in acute ICH. We tested the hypothesis that aggressive antihypertensive therapy reduces CPP in the perihematoma and borderzone regions.     

Synthesis and preclinical evaluation of an Al<Superscript>18</Superscript>F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand

Purpose

The aim of this study was to synthesize and preclinically evaluate an ¹⁸F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.

Methods

Several conditions for the labeling of ¹⁸F-PSMA-11 via ¹⁸F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.

Results

Quantitative labeling yields could be achieved with >97 % radiochemical purity. The ¹⁸F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4?±?3.3 %ID/g and 0.795?±?0.260 %ID/g, respectively; p?<?4.2e-5). Results were confirmed by ex vivo gamma counter analysis of tissues after the last imaging time point. The highest absorbed dose was reported for the kidneys. The maximum effective dose for an administered activity of 200 MBq was 1.72 mSv.

Conclusion

¹⁸F-PSMA-11 using direct labeling of chelate-attached peptide with aluminum-fluoride detected PSMA-expressing tumors with high tumor-to-liver ratios. The kidneys were the dose-limiting organs. Even by applying the most stringent dosimetric calculations, injected activities of up to 0.56 GBq are feasible.

     

Exposure to Environmental Tobacco Smoke and the Risk of Adverse Respiratory Events in Children Receiving General Anesthesia

Background: Exposure to environmental tobacco smoke is associated with detrimental effects on pulmonary function in children. The authors investigated the relation between airway complications in children receiving general anesthesia and the passive inhalation of tobacco smoke.

Methods: Six hundred two children scheduled to receive general anesthesia were enrolled in this prospective study. The anesthesiologist and the recovery room nurse, unaware of the smoke exposure history, recorded the occurrence of airway complications. A history of passive smoking was assessed by measuring the urinary concentration of the major nicotine metabolite cotinine and by questionnaire.

Results: Airway complications occurred in 42% of the patients with urinary concentrations of cotinine >or= to 40 ng/ml, in 33% of the patients with concentrations of cotinine between 10.0 and 39.9 ng/ml, and in 24% of the patients with concentrations of cotinine < 10 ng/ml (P = 0.01 for the trend among the three groups). The gender of the child (P = 0.001) and the educational level of the child's mother (P = 0.0008) significantly modified the effect of the concentration of cotinine on the incidence of adverse respiratory events.     

Molecular beacon genotyping for globoid cell leukodystrophy from hair roots in the twitcher mouse and rhesus macaque

Rapid and accurate genotype determination is ideal for the maintenance of breeding colonies of laboratory animal models of genetic disease. The rhesus macaque and murine (twitcher) models of globoid cell leukodystrophy have a dinucleotide deletion or single nucleotide substitution, respectively, which abolish ceramide beta-galactosidase activity and are authentic models of Krabbe disease. We report a molecular beacon PCR assay for each species which allows unambiguous determination of the genotype in under 4h. The assay works reliably with DNA extracted from hair roots using Chelex-100 in a 20 min, 100 degrees C incubation. We demonstrate that genotyping from hair roots is a preferred alternative to collecting blood or tissue for DNA extraction because it reduces animal distress, uses an inexpensive reagent, and is simpler and faster. Following amplification on a standard thermocycler with a 96-well plate format, these molecular beacon assays can be read on a standard laboratory fluorescent plate reader, eliminating the need to use a real-time thermocycler or to open the plate for subsequent restriction enzyme digestion and gel electrophoresis. The multiplexed ratio of fluorescence from wild-type- and mutant-specific beacons reporting at 560 nm and 535 nm wavelengths is distinct for each genotype.     

Perihematoma cerebral blood flow is unaffected by statin use in acute intracerebral hemorrhage patients

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting <24 hours from ICH onset were randomized to a systolic blood pressure target <150 or <180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P=0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P=0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume.