Bringing COVID-19 vaccine to medically underserved populations utilizing a community-guided mobile vaccine program.

Between March 23, 2021, and December 31, 2022, the Mobile Vaccine Program (MVP) vaccinated 5044 individuals from medically-underserved communities in Middle Tennessee identified through and guided by a collaboration of local community agencies. The primary objective of the MVP was to vaccinate individuals for COVID-19 who had barriers to traditional mass vaccine strategies through community-guided strategies and partnerships. Three strategies were developed and implemented with community partners and their affiliated community health workers (CHWs). The strategies included pop-up vaccination clinics at community partner events, CHW-guided door-to-door in-home vaccination, and community partner-initiated homebound referrals for vaccination.

Chemical stability of naloxone products beyond their labeled expiration dates.

OBJECTIVE: The purpose of this study was to evaluate the chemical stability of previously dispensed, expired naloxone products. SETTING: When properly stored, certain products maintain stable, defined as within compendia acceptability, beyond their manufacturer's expiration date. Stockpiling life-saving medications such as the opioid overdose reversing agent naloxone nasal spray (NNS) or injection (NIJ) is of utmost importance to ensure public health emergency preparedness and response. Design/interventions/methods: After each naloxone product was stored at room temperature for several months (6-19) past their labeled expiration date, the level of active therapeutic content and the presence of degradation impurity, 2,29'-bisnaloxone, were evaluated via chromatographic separation with waters higher performance liquid chromatography integrated using the Waters X-Select CSHC-18. The effluent was detected at 229 nm. MAIN OUTCOME MEASURE: Active naloxone presence and the presence of degradation impurity, 2,29'-bisnaloxone, were evaluated. RESULTS: The mean potency of naloxone in both NNS and NIJ, up to 10 and 19 months post-expiration, respectively, is within the 90-110 percent United States Pharmacopeia acceptance limit (NNS: 102.8 ± 2.6 percent and NIJ: 106.0 ± 1.3 percent). No impurity was detected in any chromatogram of the expired products. CONCLUSION: In summary, since both NNS and NIJ were found to be chemically stable beyond 10 months of the expiration date, shelf-life extension of climate controlled, commercially available naloxone products should be further investigated as a potential cost savings measure for national strategic stockpiles, emergency medical services, hospitals, and public responders.

Predictors of medical students' ethical decision-making: A pilot study using the Theory of Interpersonal Behavior.

OBJECTIVE: To understand medical students' (MS) ethical decision-making using the Theory of Interpersonal Behavior (TIB). METHODS: We conducted two rounds of focus groups to develop a TIB-based questionnaire by eliciting students' perspectives on an ethical dilemma they will encounter in a standardized patient (SP) station, in which an SP "surgeon" asked them to intubate a sedated patient whom the student knew had requested no student involvement. We administrated questionnaires to 241 third-year MS following this SP station, asking for their decisions in the SP station and if a surgeon made the same request in their clerkship. Confirmatory factor analysis (CFA) was used to test whether observed data fit the proposed TIB-based model. RESULTS: The CFA provided an acceptable fit to the a priori proposed model. Fifty-five percent of students indicated they would intubate in an actual situation versus 18% in the SP station (p < 0.05). Using logistic regression, TIB domains affect and facilitating factors reported significant association with students' decisions in both the SP and hypothesized actual situations. CONCLUSIONS: The TIB appears to be an effective theoretical framework for explaining students' ethical decision-making. PRACTICE IMPLICATIONS: The TIB may guide design and assessment of educational programs for professional formation.

Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis.

Transgenesis has been a mainstay of mouse genetics for over 30 yr, providing numerous models of human disease and critical genetic tools in widespread use today. Generated through the random integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a coding gene or an essential element is disrupted, and there is evidence that larger scale structural variation can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic lines in existence have been discovered and reported, due in part to limitations in the discovery tools. Targeted locus amplification (TLA) provides a robust and efficient means to identify both the insertion site and content of transgenes through deep sequencing of genomic loci linked to specific known transgene cassettes. Here, we report the first large-scale analysis of transgene insertion sites from 40 highly used transgenic mouse lines. We show that the transgenes disrupt the coding sequence of endogenous genes in half of the lines, frequently involving large deletions and/or structural variations at the insertion site. Furthermore, we identify a number of unexpected sequences in some of the transgenes, including undocumented cassettes and contaminating DNA fragments. We demonstrate that these transgene insertions can have phenotypic consequences, which could confound certain experiments, emphasizing the need for careful attention to control strategies. Together, these data show that transgenic alleles display a high rate of potentially confounding genetic events and highlight the need for careful characterization of each line to assure interpretable and reproducible experiments.

Viable Mice with Extensive Gene Humanization (25-kbp) Created Using Embryonic Stem Cell/Blastocyst and CRISPR/Zygote Injection Approaches.

Here, we describe an expansion of the typical DNA size limitations associated with CRISPR knock-in technology, more specifically, the physical extent to which mouse genomic DNA can be replaced with donor (in this case, human) DNA at an orthologous locus by zygotic injection. Driving our efforts was the desire to create a whole animal model that would replace 17 kilobase pairs (kbp) of the mouse Bcl2l11 gene with the corresponding 25-kbp segment of human BCL2L11, including a conditionally removable segment (2.9-kbp) of intron 2, a cryptic human exon immediately 3' of this, and a native human exon some 20 kbp downstream. Using two methods, we first carried out the replacement by employing a combination of bacterial artificial chromosome recombineering, classic embryonic stem cell (ESC) targeting, dual selection, and recombinase-driven cassette removal (ESC/Blastocyst Approach). Using a unique second method, we employed the same vector (devoid of its selectable marker cassettes), microinjecting it along with redundant single guide RNAs (sgRNAs) and Cas9 mRNA into mouse zygotes (CRISPR/Zygote Approach). In both instances, we were able to achieve humanization of Bcl2l11 to the extent designed, remove all selection cassettes, and demonstrate the functionality of the conditionally removable, loxP-flanked, 2.9-kbp intronic segment.

Residents' and standardized patients' perspectives on empathy: issues of agreement.

OBJECTIVE: We investigated correlations between residents' scores on the Jefferson Scale of Empathy (JSE), residents' perceptions of their empathy during standardized-patient encounters, and the perceptions of standardized patients. METHODS: Participants were 214 first-year residents in internal medicine or family medicine from 13 residency programs taking standardized patient-based clinical skills assessment in 2011. We analyzed correlations between residents' JSE scores; standardized patients' perspectives on residents' empathy during OSCE encounters, using the Jefferson Scale of Patient Perceptions of Physician Empathy; and residents' perspectives on their own empathy, using a modified version of this scale. RESULTS: Residents' JSE scores correlated with their perceptions of their own empathy during encounters but correlated poorly with patients' assessments of resident empathy. CONCLUSION: The poor correlation between residents' and standardized patients' assessments of residents' empathy raises questions about residents' abilities to gauge the effectiveness of their empathic communications. The study also points to a lack of congruence between the assessment of empathy by standardized patients and residents as receivers and conveyors of empathy, respectively. PRACTICE IMPLICATIONS: This study adds to the literature on empathy as a teachable skill set and raises questions about use of OSCEs to assess trainee empathy.

Distraction and pedestrian safety: how talking on the phone, texting, and listening to music impact crossing the street.

As use of handheld multimedia devices has exploded globally, safety experts have begun to consider the impact of distraction while talking, text-messaging, or listening to music on traffic safety. This study was designed to test how talking on the phone, texting, and listening to music may influence pedestrian safety. 138 college students crossed an interactive, semi-immersive virtual pedestrian street. They were randomly assigned to one of four groups: crossing while talking on the phone, crossing while texting, crossing while listening to a personal music device, or crossing while undistracted. Participants distracted by music or texting were more likely to be hit by a vehicle in the virtual pedestrian environment than were undistracted participants. Participants in all three distracted groups were more likely to look away from the street environment (and look toward other places, such as their telephone or music device) than were undistracted participants. Findings were maintained after controlling for demographics, walking frequency, and media use frequency. Distraction from multimedia devices has a small but meaningful impact on college students' pedestrian safety. Future research should consider the cognitive demands of pedestrian safety, and how those processes may be impacted by distraction. Policymakers might consider ways to protect distracted pedestrians from harm and to reduce the number of individuals crossing streets while distracted.

Your business in court and at federal agencies: 2010 - 2011.

This year the government aggressively pursued Manufacturers under the enhanced provisions of the False Claims Act (FCA), as well as under the provisions of the Food, Drug and Cosmetics Act (FDCA). In addition, the government pursued actions against individual executives under the Responsible Corporate Officer Doctrine ("RCO Doctrine") because it does not believe sanctions against the companies provide sufficient deterrence to inappropriate behavior. Companies need to focus on implementing effective compliance programs in order to prevent the occurrence of allegedly improper activity. It should be noted that the existence of an effective program will not protect executives from liability under the RCO Doctrine if improper behavior takes place. The Food and Drug Administration's (FDA's) has undertaken a number of initiatives during the past year in an attempt to counter claims that its review processes for domestic products is driving the development of drugs and devices to overseas markets. The Agency also has improved its capacity to review products imported from overseas by undertaking initiatives with foreign agencies and stationing more FDA employees in foreign countries. The FDA increased the number of warning letters and other enforcement actions. The FDA added two new topics of enhanced authority during the year. One was an expansion of its regulatory authority over foods, and the second was new authority to regulate certain tobacco products. The former is being subjected to some review by the courts, and the scope of its authority over tobacco is the subject of ongoing major litigation. The Federal Trade Commission (FTC) and Securities and Exchange Commission (SEC) are unlikely to experience significant change regarding their regulation of Manufacturers. The FTC, as it has for many years, continues to try to prevent "reverse" payments to generic drug manufacturers by Innovator Manufacturers to diminish generic drug competition, and proposed legislation is before Congress. The SEC still appears focused on the Foreign Corporate Practices Act with respect to enforcement against pharmaceutical and device manufacturers. Federal preemption of State law continues to be a topic of concern, with Court's taking different positions on the effect of the various Supreme Court decisions made in the last two years.

Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission.

BACKGROUND: HIV-1 envelope gp41 is a transmembrane protein that promotes fusion of the virus with the plasma membrane of the host cells required for virus entry. In addition, gp41 is an important target for the immune response and development of antiviral and vaccine strategies, especially when targeting the highly variable envelope gp120 has not met with resounding success. Mutations in gp41 may affect HIV-1 entry, replication, pathogenesis, and transmission. We, therefore, characterized the molecular properties of gp41, including genetic diversity, functional motifs, and evolutionary dynamics from five mother-infant pairs following perinatal transmission. RESULTS: The gp41 open reading frame (ORF) was maintained with a frequency of 84.17% in five mother-infant pairs' sequences following perinatal transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in gp41 sequences. Both mother and infant gp41 sequences were under positive selection pressure, as determined by ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 157 mother-infant gp41 sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked sequences. The functional domains of gp41, including fusion peptide, heptad repeats, glycosylation sites and lentiviral lytic peptides were mostly conserved in gp41 sequences analyzed in this study. The CTL recognition epitopes and motifs recognized by fusion inhibitors were also conserved in the five mother-infant pairs. CONCLUSION: The maintenance of an intact envelope gp41 ORF with conserved functional domains and a low degree of genetic variability as well as positive selection pressure for adaptive evolution following perinatal transmission is consistent with an indispensable role of envelope gp41 in HIV-1 replication and pathogenesis.

Alcohol's actions on neuronal nicotinic acetylcholine receptors.

Although it has been known for many years that alcoholism and tobacco addiction often co-occur, relatively little information is available on the biological factors that regulate the co-use and abuse of nicotine and alcohol. In the brain, nicotine acts at several different types of receptors collectively known as nicotinic acetylcholine receptors (nAChRs). Alcohol also acts on at least some of these receptors, enhancing the function of some nAChR subtypes and inhibiting the activity of others. Chronic alcohol and nicotine administration also lead to changes in the numbers of nAChRs. Natural variations (i.e., polymorphisms) in the genes encoding different nAChR subunits may be associated with individual differences in the sensitivity to some of alcohol's and nicotine's effects. Finally, at least one subtype of nAChR may help protect cells against alcohol-induced neurotoxicity.