Heart rate variability in human immunodeficiency virus-positive individuals

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Congenital causes of prolonged QT interval occur in individuals with genetic mutations in genes that control expression of potassium and sodium channels and acquired causes are numerous, predominantly drugs causing prolonged QT interval by blockade of potassium channels. Among the drugs, antiarrhythmic agents most notably quinidine, sotalol, dofetilide and ibutilide have the potential to induce the fatal torsade de pointes. Many non-antiarrhythmic drugs can also cause torsade de pointes. Although it is important to distinguish between the congenital and the acquired forms of long QT syndrome as the later can often be reversed by correction of the underlying disorder or discontinuation of the offending drug, both forms are not mutually exclusive. Clinical considerations and management of torsade de pointes are described.     

CD18-dependent and L-selectin-dependent neutrophil emigration is diminished in neonatal rabbits

Human neonatal neutrophils manifest decreases in mobility, adherence, and emigration compared with adult neutrophils that may contribute to the increased susceptibility of neonates to infection. In a developmental rabbit model, we show a reduced ability of neutrophils from 1-day-old rabbit pups to emigrate to inflamed peritoneium (3.7 +/- 0.35 x 10(6) neutrophils/mL peritoneal exudate) compared with 14-day- old (8.5 +/- 0.7 x 10(6)/mL) and adult rabbits (9.4 +/- 1.4 x 10(6) mL, P < .05) despite significantly increased blood neutrophil counts. Because the reductions in functional Mac-1 (CD11b/CD18) as well as the amount of surface L-selectin are hypothesized to be primarily responsible for the differences in human neonatal neutrophil mobility, we examined CD11b/CD18 and L-selectin in our model. Using flow cytometric analysis we found that similar to human neonates, neutrophils from 1-day-old rabbit pups had 57% of adult rabbit levels of L-selectin and, in contrast with adults, failed to show significant decreases in L-selectin after chemotactic stimulation. In addition, neutrophils from 1-day-old pups compared with adults showed a significantly diminished capacity to upregulate CD11b/CD18 after chemotactic stimulation in vitro, or after emigration to the inflamed peritoneum. Systemic administration of anti-L-selectin monoclonal antibody (MoAb) resulted in significant reduction in peritoneal neutrophils in adult (47%, P < .05) and 14-day-old rabbits (47%, P < .05), but was without effect in 1-day-old rabbits. Administration of anti-CD18 MoAb resulted in significant reduction in peritoneal neutrophil accumulation in all age groups though less in 1 day and 14 day (58% and 65%, respectively) than in adults (91%, P < .05). Only in the 14-day-old rabbits was there an additive effect of anti-L-selectin and anti-CD18 MoAbs compared with anti-CD18 alone (84% v 65%, P < .05). The findings in this in vivo rabbit model support the hypothesis that the previously described in vitro defects in human neonatal L-selectin and CD11b/CD18 may be major contributors to human neonatal inflammatory deficits.     

Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies

To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain.     

Trust in government and support for governmental regulation: the case of electronic health records

Background

This paper presents results from a public engagement effort in Nebraska, USA, which measured public opinions about governmental involvement in encouraging the use of electronic health records (EHRs).

Objective

We examine the role of trust in government in contributing to public support for government involvement in the development of EHR technologies. We hypothesize that trust in government will lead to support for federal and state governmental encouragement of the use of EHRs among doctors and insurance companies. Further, because individual experiences with health‐care professionals will reduce perceptions of risk, we expect that support for governmental involvement will be tempered by greater personal experience with the health‐care industry.

Design and Results

Examining a small survey of individuals on the issue, we find general support for both of our hypotheses. The findings suggest that trust in government does have a positive relationship with support for government involvement in the policy domain, but that the frequency of personal experiences with health‐care providers reduces the extent to which the public supports governmental involvement in the development of EHR technology.

Discussion and Conclusion

This inquiry contributes to our understanding of public attitudes towards government involvement in EHRs in the United States specifically and contributes to social science examining links between trust in government and support for governmental activity in the emerging policy domain regarding electronic health records systems.     

Repetition-related reductions in neural activity reveal component processes of mental simulation

In everyday life, people adaptively prepare for the future by simulating dynamic events about impending interactions with people, objects and locations. Previous research has consistently demonstrated that a distributed network of frontal–parietal–temporal brain regions supports this ubiquitous mental activity. Nonetheless, little is known about the manner in which specific regions of this network contribute to component features of future simulation. In two experiments, we used a functional magnetic resonance (fMR)-repetition suppression paradigm to demonstrate that distinct frontal–parietal–temporal regions are sensitive to processing the scenarios or what participants imagined was happening in an event (e.g. medial prefrontal, posterior cingulate, temporal–parietal and middle temporal cortices are sensitive to the scenarios associated with future social events), people (medial prefrontal cortex), objects (inferior frontal and premotor cortices) and locations (posterior cingulate/retrosplenial, parahippocampal and posterior parietal cortices) that typically constitute simulations of personal future events. This pattern of results demonstrates that the neural substrates of these component features of event simulations can be reliably identified in the context of a task that requires participants to simulate complex, everyday future experiences.     

Rationing Limited Healthcare Resources in the COVID-19 Era and Beyond: Ethical Considerations Regarding Older Adults

Coronavirus disease 2019 (COVID-19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age-Related Considerations in the COVID-19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.