Sylvian fissure asymmetries in nonhuman primates revisited: a comparative mri study

Magnetic resonance images (MRI) were collected in a sample of 28 apes, 16 Old World monkeys and 8 New World monkeys. The length of the sylvian fissure (SF) and the superior temporal sulcus (STS) was traced in each hemisphere from three regions of the cerebral cortex. These three regions were labeled according to their position on the sagittal plane as lateral, medial and insular. It was hypothesized that the length and asymmetry of these fissures would be dependent on the region of measurement and that a leftward asymmetry in the SF and STS would be more robust in the great ape sample than for the monkeys. The results indicated within the ape sample a population-level leftward asymmetry in the medial and insular regions of the SF. Within the Old and New World monkey samples, the SF was leftward in the medial region at the population level, but not at the insular region. Additionally, the Old World monkeys exhibited a population-level rightward lateral SF and a rightward lateral STS. No other families exhibited population-level asymmetries in the lateral region of the SF or in any region of the STS. These results are consistent with findings reported in apes and, to a lesser extent, monkeys. MRI has excellent potential for comparing neuroanatomy across taxonomic families that will help future investigations.     

Pharmacokinetics of dopamine in healthy male subjects

BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.     

Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure

Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neu^hi), but low levels of CD8⁺ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neu^hi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients.     

Chemical emissions from residential dryer vents during use of fragranced laundry products

Common laundry products, used in washing and drying machines, can contribute to outdoor emissions through dryer vents. However, the types and amounts of chemicals emitted are largely unknown. To investigate these emissions, we analyzed the volatile organic compounds (VOCs) both in the headspace of fragranced laundry products and in the air emitted from dryer vents during use of these products. In a controlled study of washing and drying laundry, we sampled emissions from two residential dryer vents during the use of no products, fragranced detergent, and fragranced detergent plus fragranced dryer sheet. Our analyses found more than 25 VOCs emitted from dryer vents, with the highest concentrations of acetaldehyde, acetone, and ethanol. Seven of these VOCs are classified as hazardous air pollutants (HAPs) and two as carcinogenic HAPs (acetaldehyde and benzene) with no safe exposure level, according to the US Environmental Protection Agency. As context for significance, the acetaldehyde emissions during use of one brand of laundry detergent would represent 3% of total acetaldehyde emissions from automobiles in the study area. Our study points to the need for additional research on this source of emissions and the potential impacts on human and environmental health.     

Brief Report: Mambalgin-3 potentiates human acid-sensing ion channel 1b under mild to moderate acidosis: Implications as an analgesic lead

Acid-sensing ion channels (ASICs) are expressed in the nervous system, activated by acidosis, and implicated in pain pathways. Mambalgins are peptide inhibitors of ASIC1 and analgesic in rodents via inhibition of centrally expressed ASIC1a and peripheral ASIC1b. This activity has generated interest in mambalgins as potential therapeutics. However, most mechanism and structure–activity relationship work on mambalgins has focused on ASIC1a, and neglected the peripheral analgesic target ASIC1b. Here, we compare mambalgin potency and mechanism of action at heterologously expressed rat and human ASIC1 variants. Unlike the nanomolar inhibition at ASIC1a and rodent ASIC1b, we find mambalgin-3 only weakly inhibits human ASIC1b and ASIC1b/3 under severe acidosis, but potentiates currents under mild/moderate acidosis. Our data highlight the importance of understanding the activity of potential ASIC-targeting pharmaceuticals at human channels.     

Plasma atrial natriuretic peptide in essential hypertension. Comparison with normotensive subjects and effects of changes in dietary sodium intake

Plasma levels of atrial natriuretic peptide (ANP) in 106 patients with essential hypertension with a supine mean blood pressure (mean +/- SEM) of 128.9 +/- 1.6 mmHg and not on treatment were significantly higher than those in 47 normotensive subjects (supine mean blood pressure 93.9 +/- 1.2 mmHg) with mean values of 17.2 +/- 1.1 and 8.6 +/- 0.6 pg/ml, respectively (P less than 0.001). Similar results were found in a subgroup of 35 hypertensive patients identically matched in terms of age, sex, and race with 35 normotensive subjects. Plasma levels of ANP were correlated significantly with age in normotensive subjects and with age and blood pressure in the hypertensive patients. In 12 hypertensive patients studied on a low (10 mmol sodium/day), on their usual sodium intake (around 120 mmol sodium/24 hr) and on a high (350 mmol sodium/day) intake, plasma ANP increased approximately twofold by the fifth day of the high sodium intake, but there was no significant difference between the plasma levels on their usual sodium intake and those on the fifth day of the low sodium intake. Supine mean blood pressure on the patients' usual sodium intake was 119.3 +/- 2.7 mmHg and was reduced to 110.0 +/- 3 mmHg by the fifth day of the low sodium intake (P less than 0.005). However, there was no significant difference between the blood pressure levels on their usual and high sodium intake (118.3 +/- 3.0 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Medical scribes have no impact on the patient experience of an emergency department

Objective

We aimed to evaluate patient perceptions of medical scribes in the ED and to test for scribe impacts on ED Net Promoter Scores, Press Ganey Surveys and other patient‐centred topics.

Methods

Exploratory semi‐structured interviews were conducted in the ED during wait times after scribed consultations. Interview results were used to derive topics relating to scribes. Items addressing these topics from validated surveys were combined with items from widely used patient satisfaction questionnaires. Questionnaires were administered in the ED by face‐to‐face approach while patients were waiting for admission/discharge or test results. Patients and doctors were blinded to the purpose of the questionnaire. The survey evaluated for non‐inferiority of scribed consultations, using Net Promoter Scores, Press Ganey questions and questions specific to the presence of the scribe.

Results

Patient interviews did not identify any negative views regarding the presence of scribes during consultations. Thematic saturation was achieved after seven interviews. Two hundred and fifty‐eight patients were approached to complete the questionnaire, and 215 participated (83%); 95 and 118 participants in the scribed and non‐scribed groups, respectively. There was no difference between scribed and non‐scribed consultations on the following measures of satisfaction: the Net Promoter Score, Press Ganey questions, quality of information received from doctors, communication, privacy concerns or inhibition about revealing private information and room crowding.

Conclusion

We found no evidence that scribes reduce patient satisfaction during emergency consultations, nor prompt discomfort that might cause a patient to withhold information.