The Behavioral Inhibition System and Engagement With, and Influence By, COVID-19 and Election-Based Misinformation.

The negative impact of misinformation on public discourse and public safety is increasingly a focus of attention. From the COVID-19 pandemic to national elections, exposure to misinformation has been linked to conflicting perceptions of social, economic, and political issues, which has been found to lead to polarization, radicalization, and acts of violence at the individual and group level. While a large body of research has emerged examining the development and spread of misinformation, little has been done to examine the human processes of being exposed to, and influenced by, misinformation material online. This article uses reinforcement sensitivity theory to examine the effect of individual differences in the Behavioral Inhibition System (BIS) on the behavioral and cognitive intentions to engage in violence after exposure to misinformation online. Using an online panel sample (Mechanical Turk), and a behavioral study that involved exposure to, and interaction with, misinformation, this study found that trait BIS score impacted how much individuals engaged with misinformation, as well as their ensuing activism and radicalism toward the narratives that were depicted. This study identified that engagement with misinformation impacted intentions for activism and radicalism, as did trait BIS. However, these effects were present for both misinformation and correct information conditions. These findings highlight the importance of BIS-related processes and raise important questions about the degree to which we need to think about online influence as a general process versus specific processes that directly relate to the effect of misinformation.

Comparison of glycoprotein separation reveals greater impact of carbohydrates and disulfides on electrophoretic mobility for CE-SDS versus SDS-PAGE.

Capillary electrophoresis sodium dodecyl sulfate (CE-SDS) has emerged as an indispensable tool in biopharmaceutical analysis to supersede the conventional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Despite the comparable migration behaviors of native proteins on the two platforms, the correlation has not been evaluated systematically for biotherapeutic proteins, which are often confounded by the presence of glycans and disulfides. Here we studied various mammalian glycoproteins using the two techniques under both reduced and non-reduced conditions. The results revealed substantial reduction in electrophoretic mobility under the capillary mode. Moreover, the migration order was found to be reversed between the reduced and nonreduced runs compared to SDS-PAGE. Such effects appeared to be independent of the content of sialylation. Our work unveiled complex interplays between the gel matrix, proteins and glycans which provide important guidance to biopharmaceutical analysis.

Hydrogen deuterium exchange reveals changes to protein dynamics of recombinant human erythropoietin upon N- and O- desialylation.

Recombinant human erythropoietin (EPO) is a therapeutic glycoprotein widely used for treating anemia. EPO glycans carry extensive sialylation and the level of the modification is known to affect receptor binding, protein stability and pharmacokinetics. Nonetheless, a detailed understanding of the effects of sialylation on EPO conformation and dynamics is still lacking. Here we investigate the changes to EPO dynamics following enzymatic trimming of terminal sialic acid by amide hydrogen deuterium exchange mass spectrometry (HDX-MS). The results revealed that desialylation enhances structural flexibility near the glycosylation sites, with greater effects observed around the O-glycosylation site relative to the N-glycosylation sites. The affected regions are surface-exposed loops connecting the helix bundle, which do not appear to reduce the thermostability of the molecule as revealed from melting measurement. Our findings demonstrate the feasibility of HDX-MS technique in deciphering the function of specific type of glycosylation that can provide novel insights into the role of sialylation on protein therapeutics.

Points to consider when establishing drug product specifications for parenteral microspheres.

Drug product specifications are a critical element of a good control strategy. Parenteral microsphere products are complex dosage forms, requiring careful development of test methods and acceptance criteria for the specifications. In particular, the in vitro release test method and acceptance criteria require rigorous scientific consideration and should be developed with an eye toward understanding the mechanisms of drug release. The final specifications need to ensure the safety, identity, strength, performance, and quality of the drug product at release and during storage through the end of its shelf-life. The specification limits are typically established based upon regulatory guidance, available data from the manufacturing process (process capability), from non-clinical, clinical, and stability studies.

A multistate outbreak of Serratia marcescens bloodstream infection associated with contaminated intravenous magnesium sulfate from a compounding pharmacy.

BACKGROUND: In contrast to pharmaceutical manufacturers, compounding pharmacies adhere to different quality-control standards, which may increase the likelihood of undetected outbreaks. In 2005, the Centers for Disease Control and Prevention received reports of cases of Serratia marcescens bloodstream infection occurring in patients who underwent cardiac surgical procedures in Los Angeles, California, and in New Jersey. An investigation was initiated to determine whether there was a common underlying cause. METHODS: A matched case-control study was conducted in Los Angeles. Case record review and environmental testing were conducted in New Jersey. The Centers for Disease Control and Prevention performed a multistate case-finding investigation; isolates were compared using pulsed-field gel electrophoresis analysis. RESULTS: Nationally distributed magnesium sulfate solution (MgSO(4)) from compounding pharmacy X was the only significant risk factor for S. marcescens bloodstream infection (odds ratio, 6.4; 95% confidence interval, 1.1-38.3) among 6 Los Angeles case patients and 18 control subjects. Five New Jersey case patients received MgSO(4) from a single lot produced by compounding pharmacy X; culture of samples from open and unopened 50-mL bags in this lot yielded S. marcescens. Seven additional case patients from 3 different states were identified. Isolates from all 18 case patients and from samples of MgSO(4) demonstrated indistinguishable pulsed-field gel electrophoresis patterns. Compounding pharmacy X voluntarily recalled the product. Neither the pharmacy nor the US Food and Drug Administration could identify a source of contamination in their investigations of compounding pharmacy X. CONCLUSIONS: A multistate outbreak of S. marcescens bloodstream infection was linked to contaminated MgSO(4) distributed nationally by a compounding pharmacy. Health care personnel should take into account the different quality standards and regulation of compounded parenteral medications distributed in large quantities during investigations of outbreaks of bloodstream infection.

Liver transplantation is not curative for methylmalonic acidopathy caused by methylmalonyl-CoA mutase deficiency.

Methylmalonic acidopathy resulting from severe methylmalonyl-CoA mutase deficiency causes acute, potentially lethal ketoacidotic episodes, renal failure, and acute and chronic neurologic disease. As dietary and alkali therapy is suboptimal, liver transplantation during infancy has been touted as a potential cure. However, reports in liver transplant recipients about new onset neurologic disease, in the absence of ketoacidosis, and progressive renal insufficiency have cast doubt about its effectiveness. We report the long-term (9 years) outcome for the first patient with severe methylmalonic acidopathy transplanted in the USA and provide new biochemical data that indicate why transplanted patients are still susceptible to "metabolic strokes". In our 10-year-old male patient, there is clear evidence that the de novo synthesis of propionyl-CoA within the CNS leads to brain methylmalonate (MMA) accumulation that is largely unaffected by transplantation. Liver replacement is not a cure for methylmalonic acidopathy.

Concurrent validity of the College Adjustment scales using comparison with the MMPI College Maladjustment Scale.

The concurrent validity of the College Adjustment Scales was assessed using comparison to the College Maladjustment Scale of the Minnesota Multiphasic Inventory-2. Undergraduate students (N=56, 40 women, M age = 21.3 yr., 87.5% white, non-Hispanic) completed both tests. Analysis indicated scores on 8 of 9 College Adjustment Scales correlated significantly in the predicted direction with those on the College Maladjustment Scale, thereby providing some additional support for convergent validity. While the conclusions are limited significantly by the small sample, this report provides an incremental contribution to the validity of the College Adjustment Scales.

In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency.

We present a unique finding of an elevated level of pyruvate at 2.37 ppm revealed by in vivo MR spectroscopy of a female neonate. Low fibroblast pyruvate dehydrogenase (PDH) complex activity subsequently confirmed a diagnosis of PDH deficiency. Abnormalities of brain development consistent with PDH deficiency were also evident on fetal and postnatal MR images. To our knowledge, this is the first report of pyruvate being shown in vivo in a child and the first report of MR spectroscopy aiding in the diagnosis of inborn error in pyruvate metabolism before confirmation by conventional enzymatic testing. This finding has potential implications for earlier diagnosis in patients with defects in mitochondrial metabolism.

Erythrocyte galactose 1-phosphate quantified by isotope-dilution gas chromatography-mass spectrometry.

BACKGROUND: Measurements of alpha-D-galactose 1-phosphate (Gal-1-P) in erythrocytes are used to monitor the adequacy of dietary therapy in the treatment of galactosemia. We have devised a gas chromatography-mass spectrometry (GC/MS) isotope-dilution method for quantification of Gal-1-P. METHODS: We prepared trimethylsilyl (TMS) derivatives and used alpha-D-[2-(13)C]Gal-1-P as the internal standard for GC/MS. Results obtained with this method were compared with those determined by the established enzymatic method for samples from 23 healthy individuals (11 children and 12 adults), 9 suspected patients with galactosemia, 12 galactosemic patients on diet therapy, and 2 newly diagnosed toxic neonates. RESULTS: The method was linear up to 2.5 mmol/L with a lower limit of detection of 2.1 nmol (0.55 mg/L). Intra- and interassay imprecision (CVs) was 2.2-8.8%. In the 23 healthy individuals, values ranged from nondetectable to 9.2 micromol/L (2.4 mg/L of packed erythrocytes). Galactosemic patients on diet therapy had values of 10.9-45 mg/L of packed erythrocytes, whereas the newly identified patients had values of 166 and 373 mg/L. CONCLUSIONS: The GC/MS method is precise and useful over the wide range of concentrations needed to assess the galactose burden in patients with galactosemia.