An Introduction to Clinical Informatics for Early Medical Learners Using Colorectal Cancer Screening.

Introduction: Clinical informatics is an important component of the AMA-endorsed third pillar of undergraduate medical education, health systems science. Discrete educational opportunities for clinical informatics and health systems science among early learners are lacking in medical school curricula. Methods: We developed and evaluated a multistep, 2.5-hour activity during the gastroenterology module to introduce these topics to preclerkship medical students. A didactic session introducing clinical informatics and clinical decision support and reviewing health promotion and screening concepts was followed by small-group activities. Students worked through a series of exercises culminating in the generation of a clinical decision support tool based on the United States Preventive Services Task Force (USPSTF) colorectal cancer screening recommendations. Results: Between 2022 and 2023, 326 first-year medical students participated in this workshop. Feedback was predictably mixed. In 2022, 88% of postclass survey respondents confirmed having a better clinical informatics understanding after the workshop. In 2023, students reported a statistically significant increase in their self-reported understanding of the role of clinical informatics, clinical decision support, and USPSTF colorectal cancer recommendations. Discussion: Clinical decision support is a viable pathway for introduction of clinical informatics, health systems science, and public health/prevention topics. Our educational approach offers an interactive introduction to this group of topics that can benefit future physicians. While colon cancer provides a robust option for the clinical situation, this activity could be modified to fit into many different clinical scenarios, allowing for interdisciplinary education during either undergraduate or graduate medical education.

Air-Stable Cu(I) Metal-Organic Framework for Hydrogen Storage.

Metal-organic frameworks (MOFs) that contain open metal sites have the potential for storing hydrogen (H2) at ambient temperatures. In particular, Cu(I)-based MOFs demonstrate very high isosteric heats of adsorption for hydrogen relative to other reported MOFs with open metal sites. However, most of these Cu(I)-based MOFs are not stable in ambient conditions since the Cu(I) species display sensitivity toward moisture and can rapidly oxidize in air. As a result, researchers have focused on the synthesis of new air-stable Cu(I)-based materials for H2 storage. Here, we have developed a de novo synthetic strategy to generate a robust Cu(I)-based MOF, denoted as NU-2100, using a mixture of Cu/Zn precursors in which zinc acts as a catalyst to transform an intermediate MOF into NU-2100 without getting incorporated into the final MOF structure. NU-2100 is air-stable and displays one of the initial highest isosteric heats of adsorption (32 kJ/mol) with good hydrogen storage capability under ambient conditions (10.4 g/L, 233 K/100 bar to 296 K/5 bar). We further elucidated the H2 storage performance of NU-2100 using a combination of spectroscopic analysis and computational modeling studies. Overall, this new synthetic route may enable the design of additional stable Cu(I)-MOFs for next-generation hydrogen storage adsorbents at ambient temperatures.

REVISITING THE EBOLA EPIDEMIC IN WEST AFRICA: THE ROLE OF EMOTIONAL DETERMINANTS IN PUBLIC RESPONSES.

Background: The 2014-2016 Ebola epidemic was largely restricted to the three nations of Guinea, Liberia and Sierra Leone, yet it tested the world's ability to address a potential global pandemic. This study provides an in-depth examination of the role of emotions in the response to the outbreak and engagement with public health measures, and the contextual factors which influenced them. Methods: Historical research methods were utilised in the examination of primary and secondary sources. A multi-faceted SPEECH (Society and Politics, Economy, Epidemiology, Culture, Healthcare and Public Health) framework was developed to aid data synthesis and analysis. Results: The outbreak occurred in a region still reeling from years of civil war, where poverty was widespread and healthcare severely underfunded. Internationally, global health security had been politically neglected. After a slow start, the international response to the outbreak was strong, yet the lack of community engagement and inadequate consideration of local culture and traditional beliefs, fueled fear and hindered engagement with professionals and uptake of public health measures. Improved collaboration and communication with rural communities in the latter phases of the response was crucial in effectively addressing the outbreak. Conclusion: This study illustrates the importance of effective collaboration between international crisis responders, in-country public health practitioners and local communities in addressing public emotional responses to the Ebola outbreak. It highlights how community engagement and communications tactics can effectively be utilised to soothe and educate the public, abating counterproductive extreme emotional responses, and in turn improving uptake of public health measures.

Evaluation of the relative potential for contact and doffing transmission of SARS-CoV-2 by a range of personal protective equipment materials.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the causative agent of coronavirus disease 2019 (COVID-19)-has caused a global public health emergency. Personal protective equipment (PPE) is the primary defence against viral exposure in healthcare and community settings. However, the surfaces of PPE materials may trap virus for contact transmission or through laden aerosols generated during removal of PPE, through cleaning or during movement. In this study, the relative efficacy of current PPE materials in terms of virion adsorption to materials and their antiviral potency, has been evaluated on a wide range of PPE for the first time, including four polymer glove types, two types of scrubs, apron material, a mask, visor and a selection of other commercial polymers and products. Although differences in virion adsorption to the test materials were observed, none of the existing polymer-based PPE resulted in more than tenfold reduction in the SARS-CoV-2 titre within either 10 min or 30 min contact period. The wettability and surface chemistry of the test materials were analysed to investigate any correlations with their surface physicochemical properties. While no correlation was found between wettability and viral retention under air flow challenge, one secondary ion of m/z 101.03 (+) and three secondary ions of m/z 31.98 (-), 196.93 (-) and 394.33 (+) in ToF-SIMS data of the test materials showed positive and negative correlations with the viral retention, respectively, which was identified by PLS regression model, suggesting that the surface chemistry plays a role in determining the extent of virion adsorption. Our findings outline the material aspects that influence the efficacy of current PPE against SARS-CoV-2 transmission and give suggestions on the development of novel simple polymer-based PPE for better infection protection.

Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein­specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

Child witchcraft confessions as an idiom of distress in Sierra Leone; results of a rapid qualitative inquiry and recommendations for mental health interventions.

BACKGROUND: Reports about child witchcraft are not uncommon in sub-Saharan Africa. In this study we approach child witchcraft as an idiom of distress. In an environment that may prohibit children from openly expressing distress, the shared imagery of witchcraft can provide a cultural idiom to communicate about psychosocial suffering. We used an ecological approach to study how some children in distressing circumstances come to a witchcraft confession, with the aim to set out pathways for mental health interventions. METHODS: We employed rapid qualitative inquiry methodology, with an inductive and iterative approach, combining emic and etic perspectives. We conducted 37 interviews and 12 focus group discussions with a total of 127 participants in Freetown, Sierra Leone. Inductive analysis was used to identify risk and protective factors related to witchcraft accusations and confessions. RESULTS: We identified risk and protective factors related to the individual child, the family, peer relations, teachers and other professionals in a child's life, traditional healers, pastors and the wider society. We found that in the context of a macrosystem that supports witchcraft, suspicions of witchcraft are formed at the mesosystem level, where actors from the microsystem interact with each other and the child. The involvement of a traditional healer or pastor often forms a tipping point that leads to a confession of witchcraft. CONCLUSIONS: Child witchcraft is an idiom of distress, not so much owned by the individual child as well as by the systems around the child. Mental health interventions should be systemic and multi-sectoral, to prevent accusations and confessions, and address the suffering of both the child and the systems surrounding the child. Interventions should be contextually relevant and service providers should be helped to address conscious and subconscious fears related to witchcraft. Beyond mental health interventions, advocacy, peacebuilding and legislation is needed to address the deeper systemic issues of poverty, conflict and abuse.

Correction: A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C.

[This corrects the article DOI: 10.1371/journal.pntd.0008459.].

A proactive approach: Examples for integrating disaster risk reduction and mental health and psychosocial support programming.

Natural disasters and humanitarian emergencies exert devastating impacts globally. Among these effects are disruptions in mental health and psychosocial well-being. Traditionally, mental health and psychosocial support (MHPSS) interventions have been implemented in response and recovery phases. Yet, the field of disaster management has demonstrated a shift towards disaster risk reduction (DRR). The degree to which the MHPSS field has followed this trend has been limited by several factors, including a lack of consensus-based guidance for MHPSS and DRR integration. However, examples from the field exist and demonstrate the feasibility of taking proactive approaches to supporting mental health and well-being and building better before emergencies occur. The following article outlines two case examples, one project in Sierra Leone and another in India, integrating MHPSS and DRR approaches and principles. Lessons learned from these cases and specific challenges in each context are highlighted and discussed.

Polymer microarrays rapidly identify competitive adsorbents of virus-like particles.

The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable the rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for example, to aid in the purification of vaccine components or in the design of a more effective PPE. Here, we show that an adaption of a polymer microarray method for screening bacterial-surface interactions allows for the screening of polymers for desirable material-virion interactions. Nonpathogenic virus-like particles including fluorophores are exposed to the arrays in an aqueous buffer as a simple model of virions carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella virus-like particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for the discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus, which we propose would be part of a material scale up step carried out in high containment facilities, alongside the use of more complex media to represent biological fluids.

Stakeholder perspectives of Community Mental Health Forums: a qualitative study in Sierra Leone.

BACKGROUND: Mental health is the leading cause of disability worldwide. In the wake of both a civil war and an Ebola outbreak, Sierra Leone ranks as one of the lowest ranked countries on the Human Development Index (UNDP. Human Development Report 2015, Work for Human Development. The United Nations Development Programme; 2015). The WHO identified Sierra Leone among its priority countries for the piloting of its Mental Health Gap Action Programme (mhGAP). Aligned to these efforts, CBM and their affiliated partners employed the use of Community Mental Health Forums (CMHFs), facilitated by Mental Health Nurses (MHNs), as a sensitive and practical way of engaging key community stakeholders to discuss and address issues of mental health. This study sought firstly, to identify factors that affect the successful implementation of CMHFs, as identified by programme participants. Second, the study sought to identify what changes participants perceived as having taken place as a result of their participation in CMHFs. METHODS: 10 MHNs and 52 forum participants were purposely selected to take part in key informant interviews and focus group discussions, conducted across eight districts in Sierra Leone. Interview transcripts were analysed across four rounds of coding, using a mixture of deductive and inductive approaches. RESULTS: Results identified three themes, Traditional Beliefs and Culture; Health System; and Inclusive Approaches as affecting the implementation of CMHFs in their districts. Participants further perceived that their participation in the Community Mental Health Forums resulted in changes taking place across the themes of Awareness and beliefs, Behaviours towards people experiencing psychological distress, and as leading to greater Collaboration and cooperation between formal and informal mental health practitioners. CONCLUSIONS: Results are discussed in the context of the extant literature and a novel framework, that incorporates multiple best practice recommendations and factors which influence the successful implementation of CMHFs is put forward.

A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C.

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs.

Hepatitis C Virus Vaccine: Challenges and Prospects.

The hepatitis C virus (HCV) causes both acute and chronic infection and continues to be a global problem despite advances in antiviral therapeutics. Current treatments fail to prevent reinfection and remain expensive, limiting their use to developed countries, and the asymptomatic nature of acute infection can result in individuals not receiving treatment and unknowingly spreading HCV. A prophylactic vaccine is therefore needed to control this virus. Thirty years since the discovery of HCV, there have been major gains in understanding the molecular biology and elucidating the immunological mechanisms that underpin spontaneous viral clearance, aiding rational vaccine design. This review discusses the challenges facing HCV vaccine design and the most recent and promising candidates being investigated.

Purification of native Sigma class glutathione transferase from Fasciola hepatica.

Fascioliasis is a parasitic disease of grazing livestock and a threat to global food security by significantly reducing the production value of sheep, goats and cattle. Moreover, the zoonotic parasite is also a re-emerging food borne threat to human populations. Driven by climate change, the prevalence of fascioliasis is set to increase. Efforts to control the main causative agent, Fasciola hepatica, are hampered by short lived chemotherapy approaches that are becoming increasingly obsolete due to therapeutic failure and resistance. A protective vaccine is urgently needed. A recombinant form of Sigma class glutathione transferase (Hematopoietic Prostaglandin D synthase) from F. hepatica (FhGSTS1) with confirmed prostaglandin synthase activity shows immune-modulation activity via suppression of Th17 responses in host dendritic cells. In vaccine trials recombinant FhGSTS1 reduces liver pathology but not worm burden. Native FhGSTS1 is yet to be tested for immune-modulation activities or for vaccine potential, primarily due to the technical difficulty in purifying FhGST-S1 away from the other more abundant GST members in F. hepatica cytosol. This paper reports a pipeline for the purification of native FhGSTS1 using a two-step process consisting of glutathione-agarose affinity and cationic exchange chromatography. The methodology allows for the isolation of purified and active FhGSTS1 or Sigma GSTs from other sources for analytical biochemical and immunological studies.

Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection.

BACKGROUND/OBJECTIVES: Infection with varicella zoster virus (VZV) produces lifelong immunity, but duration of post-vaccination immunity has not been established. The purpose of this study is to determine if a difference exists in the long-term seropositivity of anti-VZV antibodies in a cohort of young adults who were vaccinated against varicella as compared to a similar cohort with a history of chickenpox disease, and to determine which variables best predict waning seropositivity following varicella vaccination. METHODS: This retrospective cohort study captures immunization and serology data from approximately 10,000 recruits who entered basic military training between January 1, 2008, and December 31, 2015, and who have childhood immunization records in the Air Force Aeromedical Services Information Management System. Varicella vaccine immunogenicity was determined relative to the immunogenicity of chickenpox disease, as measured by multiplex flow immunoassay. Among vaccine recipients, waning seroimmunity was modeled and adjusted for several important covariates. RESULTS: Basic military trainees who received varicella vaccine in childhood were 24% less likely to be seropositive to VZV than trainees who were exempt from vaccine due to a history of chickenpox disease. There was no significant difference in seropositivity between male and female trainees. The odds of a vaccinated trainee being seropositive to VZV decreased by 8% with each year elapsed since vaccination. Seroprevalence declined below estimated herd immunity thresholds in vaccinated trainees born after 1994, and in the cohort as a whole for trainees born after 1995. CONCLUSION: Despite prior vaccination, seroimmunity in a large cohort of young adults unexposed to wild-type VZV failed to meet the estimated threshold for herd immunity. If vaccination in accordance with the current US VZV vaccination schedule is inadequate to maintain herd immunity, young adults not previously exposed to wild-type VZV may be at increased risk for varicella outbreaks.

Treatment of Pseudomonas Keratitis by Continuous Infusion of Topical Antibiotics With the Morgan Lens.

PURPOSE: Despite following standard treatment, Pseudomonas keratitis can continue to progress and result in loss of vision or of the eye. Our cases demonstrate that the Morgan Lens can be an effective topical antibiotic delivery vehicle in advanced keratitis. METHODS: Two patients (3 eyes) with Pseudomonas keratitis were included in this report after failing to respond to intense inpatient topical treatment. Because loss of the eyes was imminent, the Morgan Lenses were used for continuous lavage with ceftazidime (50 mg/mL), in conjunction with other conventional treatment. RESULTS: Three days after lavage, corneal cultures became negative in all eyes. Infusion was continued for at least a week to ensure sterilization of the infection before switching to standard topical therapy. The infection in both cases was promptly eradicated and the eyes were rescued. CONCLUSIONS: The Morgan Lens can be a viable alternative in treating severe and aggressive infectious keratitis or sclerokeratitis. Application of the Morgan Lens is noninvasive and requires minimal training. Intravenous tubing connectors allow for easy swapping between medications, simultaneous administration of multiple medications, and titration of dosing. Additionally, it is cost-effective as the low demand for nursing care essentially eliminates the need for intensive care unit admission.