Supply-side and demand-side factors influencing uptake of malaria testing services in the community: lessons for scale-up from a post-hoc analysis of a cluster randomised, community-based trial in western Kenya.

OBJECTIVES: Maximising the impact of community-based programmes requires understanding how supply of, and demand for, the intervention interact at the point of delivery. DESIGN: Post-hoc analysis from a large-scale community health worker (CHW) study designed to increase the uptake of malaria diagnostic testing. SETTING: Respondents were identified during a household survey in western Kenya between July 2016 and April 2017. PARTICIPANTS: Household members with fever in the last 4 weeks were interviewed at 12 and 18 months post-implementation. We collected monthly testing data from 244 participating CHWs and conducted semistructured interviews with a random sample of 70 CHWs. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was diagnostic testing before treatment for a recent fever. The secondary outcomes were receiving a test from a CHW and tests done per month by each CHW. RESULTS: 55% (n=948 of 1738) reported having a malaria diagnostic test for their recent illness, of which 38.4% were tested by a CHW. Being aware of a local CHW (adjusted OR=1.50, 95% CI: 1.10 to 2.04) and belonging to the wealthiest households (vs least wealthy) were associated with higher testing (adjusted OR=1.53, 95% CI: 1.14 to 2.06). Wealthier households were less likely to receive their test from a CHW compared with poorer households (adjusted OR=0.32, 95% CI: 0.17 to 0.62). Confidence in artemether-lumefantrine to cure malaria (adjusted OR=2.75, 95% CI: 1.54 to 4.92) and perceived accuracy of a malaria rapid diagnostic test (adjusted OR=2.43, 95% CI: 1.12 to 5.27) were positively associated with testing by a CHW. Specific CHW attributes were associated with performing a higher monthly number of tests including formal employment, serving more than 50 households (vs <50) and serving areas with a higher test positivity. On demand side, confidence of the respondent in a test performed by a CHW was strongly associated with seeking a test from a CHW. CONCLUSION: Scale-up of community-based malaria testing is feasible and effective in increasing uptake among the poorest households. To maximise impact, it is important to recognise factors that may restrict delivery and demand for such services. TRIAL REGISTRATION NUMBER: NCT02461628; Post-results.

The World Health Organization's Disease Outbreak News: A retrospective database.

The World Health Organization (WHO) notifies the global community about disease outbreaks through the Disease Outbreak News (DON). These online reports tell important stories about both outbreaks themselves and the high-level decision making that governs information sharing during public health emergencies. However, they have been used only minimally in global health scholarship to date. Here, we collate all 2,789 of these reports from their first use through the start of the Covid-19 pandemic (January 1996 to December 2019), and develop an annotated database of the subjective and often inconsistent information they contain. We find that these reports are dominated by a mix of persistent worldwide threats (particularly influenza and cholera) and persistent epidemics (like Ebola virus disease in Africa or MERS-CoV in the Middle East), but also document important periods in history like the anthrax bioterrorist attacks at the turn of the century, the spread of chikungunya and Zika virus to the Americas, or even recent lapses in progress towards polio elimination. We present three simple vignettes that show how researchers can use these data to answer both qualitative and quantitative questions about global outbreak dynamics and public health response. However, we also find that the retrospective value of these reports is visibly limited by inconsistent reporting (e.g., of disease names, case totals, mortality, and actions taken to curtail spread). We conclude that sharing a transparent rubric for which outbreaks are considered reportable, and adopting more standardized formats for sharing epidemiological metadata, might help make the DON more useful to researchers and policymakers.

Identifying xenobiotic metabolites with in silico prediction tools and LCMS suspect screening analysis.

Understanding the metabolic fate of a xenobiotic substance can help inform its potential health risks and allow for the identification of signature metabolites associated with exposure. The need to characterize metabolites of poorly studied or novel substances has shifted exposure studies towards non-targeted analysis (NTA), which often aims to profile many compounds within a sample using high-resolution liquid-chromatography mass-spectrometry (LCMS). Here we evaluate the suitability of suspect screening analysis (SSA) liquid-chromatography mass-spectrometry to inform xenobiotic chemical metabolism. Given a lack of knowledge of true metabolites for most chemicals, predictive tools were used to generate potential metabolites as suspect screening lists to guide the identification of selected xenobiotic substances and their associated metabolites. Thirty-three substances were selected to represent a diverse array of pharmaceutical, agrochemical, and industrial chemicals from Environmental Protection Agency's ToxCast chemical library. The compounds were incubated in a metabolically-active in vitro assay using primary hepatocytes and the resulting supernatant and lysate fractions were analyzed with high-resolution LCMS. Metabolites were simulated for each compound structure using software and then combined to serve as the suspect screening list. The exact masses of the predicted metabolites were then used to select LCMS features for fragmentation via tandem mass spectrometry (MS/MS). Of the starting chemicals, 12 were measured in at least one sample in either positive or negative ion mode and a subset of these were used to develop the analysis workflow. We implemented a screening level workflow for background subtraction and the incorporation of time-varying kinetics into the identification of likely metabolites. We used haloperidol as a case study to perform an in-depth analysis, which resulted in identifying five known metabolites and five molecular features that represent potential novel metabolites, two of which were assigned discrete structures based on in silico predictions. This workflow was applied to five additional test chemicals, and 15 molecular features were selected as either reported metabolites, predicted metabolites, or potential metabolites without a structural assignment. This study demonstrates that in some-but not all-cases, suspect screening analysis methods provide a means to rapidly identify and characterize metabolites of xenobiotic chemicals.

An early analysis of the World Bank's Pandemic Fund: a new fund for pandemic prevention, preparedness and response.

In response to shortcomings in epidemic preparedness and response that were revealed by the COVID-19 pandemic, there have been numerous proposals for ways to improve preparedness and response financing. Included among these is the World Bank's Pandemic Fund, formerly known as the Financial Intermediary Fund for Pandemic Prevention, Preparedness, and Response, which was launched in September 2022. This analysis piece examines the Pandemic Fund, where it fits into ongoing discussions surrounding financing for preparedness and response efforts and discusses emerging apprehensions about the new financing mechanism. Briefly, the Pandemic Fund is not the first time that the World Bank has hosted a financing mechanism to provide support for pandemic response. Notably the Pandemic Emergency Financing Facility (PEF)-which was launched in 2017 and closed in 2021-was criticised for generally failing to realise its potential. However, the Pandemic Fund seems to be addressing several of these critiques by placing a greater emphasis on prevention and preparedness financing, as opposed to response financing. Still, there is an important need for response funding mechanisms, and concerningly, the Pandemic Fund seems to support response efforts in name only. While it is clearly desirable to prepare for and prevent outbreaks for a multitude of reasons, it is also naive to assume that strengthening preparedness capacities will eliminate outbreaks and the need for response financing altogether. Accordingly, there is a need to complement this new financing mechanism with dedicated funding for responding to infectious disease outbreaks and to closely link this response financing with health security frameworks and instruments.

Cellular Invasion Assay for the Real-Time Tracking of Individual Cells in Spheroid or Tumor-like Mimics.

Cellular invasion is the gateway to metastasis, with cells moving from a primary tumor into neighboring regions of healthy tissue. Invasion assays provide a tractable experimental platform to quantitatively assess cellular movement in the presence of potential chemokines or inhibitors. Many such assays involve cellular movement from high cell densities to cell-free regions. To improve the physiological relevance of such assays, we developed an assay format to track cellular movement throughout a uniform density of cells. This assay format imparts diffusion-dominated environments along the channel, resulting in oxygen and nutrient gradients found in spheroids or poorly vascularized tumors. By incorporating oxygen- and pH-sensing films, we quantified spatial and temporal changes in the extracellular environment while simultaneously tracking the movement of a subset of cells engineered to express fluorescent proteins constitutively. Our results show the successful invasion into neighboring tissues likely arises from a small population with a highly invasive phenotype. These highly invasive cells continued to move throughout the 48 h experiment, suggesting they have stem-like or persister properties. Surprisingly, the distance these persister cells invaded was unaffected by the density of cells in the channel or the presence or absence of an oxygen gradient. While these datasets cannot determine if the invasive cells are inherent to the population or if diffusion-dominated environments promote them, they highlight the need for further study.

State-level public health preparedness indices as predictors of COVID-19 mortality outcomes: results from the United States of America in 2020.

This study evaluates associations between state-level preparedness indices and reported COVID-19-related mortality outcomes in all 50 states and the District of Columbia in the United States of America during three distinct time periods throughout the first year of the COVID-19 pandemic. State-level preparedness data for the year 2019 were gathered from the National Health Security Preparedness and Trust for America's Health Indices, and COVID-19-related mortality data for March-December 2020 (i.e., excess mortality and reported COVID-19 mortality rates) were collected in May 2022. Linear regression analyses were conducted to examine associations during three distinct time periods. Statistically significant positive associations were observed between both indices and reported COVID-19 mortality rates during the first time period. A statistically significant negative association was observed between one preparedness index and excess mortality during the second time period. No other significant associations existed for the outcomes or time periods considered in this analysis. These results demonstrate that state-level preparedness indices were not well attuned to COVID-19-related mortality outcomes during the first year of the pandemic. This suggests that current measures of state-level preparedness may be underinclusive and require a reconceptualization to improve their utility for public health practice.

Examining the Use of Mobile Technology to Deliver Tailored Sexual Assault Prevention in a Classroom Environment in the Military: Development and Usability Study.

BACKGROUND: Advances in mobile technology over the last 10 years have expanded its use in scientific research. However, there are challenges in creating a reliable system for intervention content delivery and data collection in an environment with limited internet connectivity and limited staffing capacity. The Sexual Communication and Consent (SCC) study used tablets to provide individualized Sexual Assault Prevention and Response training in a classroom environment that was both technologically and support staff limited. OBJECTIVE: We developed the SCC Basic Military Training app and a separate Sexual Assault Response Coordinator app to support individualized training within the new SCC program. This paper presents the functionality, protocols, challenges, and feasibility of deploying mobile technology in an educational environment in the military with limited resources. METHODS: We developed both mobile apps targeting the Apple iOS ecosystem. The Basic Military Training app provided a screening instrument that routed the trainee into 1 of 5 specific intervention programs. Over 2 days of basic military training set 2 weeks apart, trainees received a combined 6 hours of program-specific tablet training, combined with universal, interactive classroom training, led by qualified instructors. The Sexual Assault Response Coordinator app, used to deliver supplemental content to a subgroup of trainees, was made available for voluntary and private use at the Sexual Assault Response Coordinator's office on base. All anonymous data were manually transferred onto laptops, where the data were aggregated into files and securely transferred to the project staff for analysis. The study was conducted at the Lackland Air Force Base, Joint Base San Antonio, with 9196 trainees providing the data. RESULTS: A total of 7742 trainees completed both the sessions of the SCC program and a series of evaluative assessments. Some trainees did not receive day 2 training, and only received day 1 training because the COVID-19 pandemic shortened the study period. Of the 190 SCC classes taught, only one class was unable to complete tablet training because of Apple licensing-related technology failure. The 360 study tablets were distributed across 3 classrooms (120 per classroom) and were handled at least 16,938 times with no reports of breakage or requiring replacement. Wi-Fi access limitations exacerbated the complexity of Apple licensing revalidation and the secure transfer of data from the classroom to project personnel. The instructor staff's limited technical knowledge to perform certain technical tasks was challenging. CONCLUSIONS: The results demonstrated the feasibility of deploying a mobile app for tablet-based training in a military educational environment. Although successful, the study was not without technical challenges. This paper gives examples of technical lessons learned and recommendations for conducting the study differently, with the aim that the knowledge gained may be helpful to other researchers encountering similar requirements.

Comparing the performance and coverage of selected in silico (liver) metabolism tools relative to reported studies in the literature to inform analogue selection in read-across: A case study.

Changes in the regulatory landscape of chemical safety assessment call for the use of New Approach Methodologies (NAMs) including read-across to fill data gaps. One critical aspect of analogue evaluation is the extent to which target and source analogues are metabolically similar. In this study, a set of 37 structurally diverse chemicals were compiled from the EPA ToxCast inventory to compare and contrast a selection of metabolism in silico tools, in terms of their coverage and performance relative to metabolism information reported in the literature. The aim was to build understanding of the scope and capabilities of these tools and how they could be utilised in a read-across assessment. The tools were Systematic Generation of Metabolites (SyGMa), Meteor Nexus, BioTransformer, Tissue Metabolism Simulator (TIMES), OECD Toolbox, and Chemical Transformation Simulator (CTS). Performance was characterised by sensitivity and precision determined by comparing predictions against literature reported metabolites (from 44 publications). A coverage score was derived to provide a relative quantitative comparison between the tools. Meteor, TIMES, Toolbox, and CTS predictions were run in batch mode, using default settings. SyGMa and BioTransformer were run with user-defined settings, (two passes of phase I and one pass of phase II). Hierarchical clustering revealed high similarity between TIMES and Toolbox. SyGMa had the highest coverage, matching an average of 38.63% of predictions generated by the other tools though was prone to significant overprediction. It generated 5,125 metabolites, which represented 54.67% of all predictions. Precision and sensitivity values ranged from 1.1-29% and 14.7-28.3% respectively. The Toolbox had the highest performance overall. A case study was presented for 3,4-Toluenediamine (3,4-TDA), assessed for the derivation of screening-level Provisional Peer Reviewed Toxicity Values (PPRTVs), was used to demonstrate the practical role in silico metabolism information can play in analogue evaluation as part of a read-across approach.

Financial Assistance for Health Security: Effects of International Financial Assistance on Capacities for Preventing, Detecting, and Responding to Public Health Emergencies.

BACKGROUND: Health security funding is intended to improve capacities for preventing, detecting, and responding to public health emergencies. Recent years have witnessed substantial increases in the amounts of donor financial assistance to health security from countries, philanthropies, and other development partners. To date, no work has examined the effects of assistance on health security capacity development over time. This paper presents an analysis of the time-lagged effects of assistance for health security (AHS) on levels of capacity. METHODS: We collected publicly available health security assessment scores published between 2010 and 2019 and data relating to financial AHS. Using validated methods, we rescaled assessment scores on analogous scales to enable comparison and binned them in quartiles. We then used a distributed lag model (DLM) in a Bayesian ordinal regression framework to assess the effects of AHS on capacity development over time. RESULTS: Strong evidence exists for associations between financial assistance and select capacities on a variety of lagged time intervals. Financial assistance had positive effects on zoonotic disease capacities in the year it was disbursed, and positive effects on legislation, laboratory, workforce, and risk communication capacities one year after disbursal. Financial assistance had negative effects on laboratory and emergency response capacities two years after it was disbursed. Financial assistance did not have measurable effects on coordination, antimicrobial resistance (AMR), food safety, biosafety, surveillance, or response preparedness capacities over the timeframe considered. CONCLUSION: Financial AHS is associated with positive effects for several core health security capacities. However, for the majority of capacities, levels of funding were not significantly associated with capacity level, though we cannot fully exclude endogeneity. Future work should continue to investigate these relationships in different contexts and examine other factors that may contribute to capacity development.

How do local-level authorities engage in epidemic and pandemic preparedness activities and coordinate with higher levels of government? Survey results from 33 cities.

The COVID-19 pandemic suggests that there are opportunities to improve preparedness for infectious disease outbreaks. While much attention has been given to understanding national-level preparedness, relatively little attention has been given to understanding preparedness at the local-level. We, therefore, aim to describe (1) how local governments in urban environments were engaged in epidemic preparedness efforts before the COVID-19 pandemic and (2) how they were coordinating with authorities at higher levels of governance before COVID-19. We developed a survey and distributed it to 50 cities around the world involved in the Partnership for Healthy Cities. The survey included several question formats including free-response, matrices, and multiple-choice questions. RACI matrices, a project management tool that helps explain coordination structures, were used to understand the level of government responsible, accountable, consulted, and informed regarding select preparedness activities. We used descriptive statistics to summarize local-level engagement in preparedness. Local authorities from 33 cities completed the survey. Prior to the COVID-19 pandemic, 20 of the cities had completed infectious disease risk assessments, 10 completed all-hazards risk assessments, 11 completed simulation exercises, 10 completed after-action reviews, 19 developed preparedness and response plans, three reported involvement in their country's Joint External Evaluation of the International Health Regulations, and eight cities reported involvement in the development of their countries' National Action Plan for Health Security. RACI matrices revealed various models of epidemic preparedness, with responsibility often shared across levels, and national governments accountable for the most activities, compared to other governance levels. In conclusion, national governments maintain the largest role in epidemic and pandemic preparedness but the role of subnational and local governments is not negligible. Local-level actors engage in a variety of preparedness activities and future efforts should strive to better include these actors in preparedness as a means of bolstering local, national, and global health security.

Urban pandemic response: Survey results describing the experiences from twenty-five cities during the COVID-19 pandemic.

Since first being detected in Wuhan, China in late December 2019, COVID-19 has demanded a response from all levels of government. While the role of local governments in routine public health functions is well understood-and the response to the pandemic has highlighted the importance of involving local governments in the response to and management of large, multifaceted challenges-their role in pandemic response remains more undefined. Accordingly, to better understand how local governments in cities were involved in the response to the COVID-19 pandemic, we conducted a survey involving cities in the Partnership for Healthy Cities to: (i) understand which levels of government were responsible, accountable, consulted, and informed regarding select pandemic response activities; (ii) document when response activities were implemented; (iii) characterize how challenging response activities were; and (iv) query about future engagement in pandemic and epidemic preparedness. Twenty-five cities from around the world completed the survey and we used descriptive statistics to summarize the urban experience in pandemic response. Our results show that national authorities were responsible and accountable for a majority of the activities considered, but that local governments were also responsible and accountable for key activities-especially risk communication and coordinating with community-based organizations and civil society organizations. Further, most response activities were implemented after COVID-19 had been confirmed in a city, many pandemic response activities proved to be challenging for local authorities, and nearly all local authorities envisioned being more engaged in pandemic preparedness and response following the COVID-19 pandemic. This descriptive research represents an important contribution to an expanding evidence base focused on improving the response to the ongoing COVID-19 pandemic, as well as future outbreaks.

Global Fund contributions to health security in ten countries, 2014-20: mapping synergies between vertical disease programmes and capacities for preventing, detecting, and responding to public health emergencies.

BACKGROUND: The Global Fund to Fight AIDS, Tuberculosis and Malaria is a robust vertical global health programme. The extent to which vertical programmes financially support health security has not been investigated. We, therefore, endeavoured to quantify the extent to which the budgets of this vertical programme support health security. We believe this is a crucial area of work as the global community works to combine resources for COVID-19 response and future pandemic preparedness. METHODS: We examined budgets for work in Kenya, Uganda, Vietnam, Democratic Republic of the Congo, Guatemala, Guinea, India, Indonesia, Nigeria, and Sierra Leone from January, 2014 to December, 2020. These ten countries were selected because of the robustness of investments and the availability of data. Using the International Health Regulations Joint External Evaluation (JEE) tool as a framework, we mapped budget line items to health security capacities. Two researchers independently reviewed each budget and mapped items to the JEE. Budgets were then jointly reviewed until a consensus was reached regarding if an item supported health security directly, indirectly, or not at all. The budgets for the study countries were inputted into a single Microsoft Excel spreadsheet and line items that mapped to JEE indicators were scaled up to their respective JEE capacity. Descriptive analyses were then done to determine the total amount of money budgeted for activities that support health security, how much was budgeted for each JEE capacity, and how much of the support was direct or indirect. FINDINGS: The research team reviewed 37 budgets. Budgets totalled US$6 927 284 966, and $2 562 063 054 (37·0%) of this mapped to JEE capacities. $1 330 942 712 (19·2%) mapped directly to JEE capacities and $1 231 120 342 (17·8%) mapped indirectly to JEE capacities. Laboratory systems, antimicrobial resistance, and the deployment of medical countermeasures and personnel received the most overall budgetary support; laboratory systems, antimicrobial resistance, and workforce development received the greatest amount of direct budgetary support. INTERPRETATION: Over one-third of the Global Fund's work also supports health security and the organisation has budgeted more than $2 500 000 000 for activities that support health security in ten countries since 2014. Although these funds were not budgeted specifically for health security purposes, recognising how vertical programmes can synergistically support other global health efforts has important implications for policy related to health systems strengthening. FUNDING: Resolve to Save Lives: An Initiative of Vital Strategies.

COVID-19 and the proliferation of urban networks for health security.

Recent years have witnessed cities establishing themselves as major players in addressing global issues, often taking collective action through international city networks and organizations. These networks are important, as they amplify the voices of municipal officials, who are often excluded from high-level decision-making, and can also provide a platform for officials from low- or middle-income nations to participate in higher-level political forums. The global response to the COVID-19 pandemic has included traditional public health stakeholders-including supranational organizations, international non-governmental organizations and national authorities-but has also featured mayors and city networks, in an unprecedented fashion. Existing networks without an explicit focus on health have shifted their focuses to prioritize pandemic response and several new networks have been created. These developments are significant, not only because they represent a shift in health governance and policy, but also because cities and urban networks more broadly have exhibited a nimbleness and pragmatism unmatched by higher levels of governance. These characteristics could prove beneficial for addressing the current pandemic, as well as future health issues and emergencies. Furthermore, given the relative lack of engagement with health security issues before the COVID-19 pandemic, the drastic health and economic impacts associated with it, and the demonstrable value added by strong city leadership, there are an open policy window and a compelling case for continued city engagement in health security.

Ready or Not, Patients Will Present: Improving Urban Pandemic Preparedness.

Over the past century, society has achieved great gains in medicine, public health, and health-care infrastructure, particularly in the areas of vaccines, antibiotics, sanitation, intensive care and medical technology. Still, despite these developments, infectious diseases are emerging at unprecedented rates around the globe. Large urban centers are particularly vulnerable to communicable disease events, and must have well-prepared response systems, including on the front-line level. In November 2018, the United States' largest municipal health-care delivery system, New York City Health + Hospitals, hosted a half-day executive-level pandemic response workshop, which sought to illustrate the complexity of preparing for, responding to, and recovering from modern-day infectious diseases impacting urban environments. Attendees were subjected to a condensed, plausible, pandemic influenza scenario and asked to simulate the high-level strategic decisions made by leaders by internal (eg, Chief Medical Officer, Chief Nursing Officer, and Legal Affairs) and external (eg, city, state, and federal public health and emergency management entities) partners across an integrated system of acute, postacute, and ambulatory sites, challenging players to question their assumptions about managing the consequences of a highly pathogenic pandemic.

A One Health Approach for Guinea Worm Disease Control: Scope and Opportunities.

Guinea worm disease (GWD) is a neglected tropical disease that was targeted for eradication several decades ago because of its limited geographical distribution, predictable seasonality, straightforward diagnosis, and exclusive infection of humans. However, a growing body of evidence challenges this last attribute and suggests that GWD can affect both humans and animal populations. The One Health approach emphasizes the relatedness of human, animal, and environmental health. We reviewed epidemiological evidence that could support the utility of a One Health approach for GWD control in the six countries that have reported human GWD cases since 2015-Angola, Cameroon, Chad, Ethiopia, Mali, and South Sudan. Human GWD cases have dramatically declined, but recent years have seen a gradual increase in human case counts, cases in new geographies, and a rapidly growing number of animal infections. Taken together, these suggest a need for an adjusted approach for eradicating GWD using a framework rooted in One Health, dedicated to improving disease surveillance and in animals; pinpointing the dominant routes of infection in animals; elucidating the disease burden in animals; determining transmission risk factors among animals and from animals to humans; and identifying practical ways to foster horizontal and multidisciplinary approaches.

Rapid urban health security assessment tool: a new resource for evaluating local-level public health preparedness.

Urbanisation will be one of the defining demographic trends of the 21st century-creating unique opportunities for sustainable capacity development, as well as substantial risks and challenges for managing public health and health emergencies. Plans and policies for responding to public health emergencies are generally framed at higher levels of governance, but developing, improving and sustaining the capacities necessary for implementing these policies is a direct function of local-level authorities. Evaluating local-level public health capacities is an important process for identifying strengths and weaknesses that can impact the preparedness for, detection of and response to health security threats. However, while various evaluations and assessments exist for evaluating capacities at other levels, currently, there are no readily available health security assessments for the local-level. In this paper, we describe a tool-the Rapid Urban Health Security Assessment (RUHSA) Tool-that is based on a variety of other relevant assessments and guidance documents. Assessing capacities allow for local-level authorities to identify the strengths and weaknesses of their local health security systems, create multiyear action plans and prioritise opportunities for improving capacities, effectively engage with development partners to target resources effectively and develop compelling narratives and a legacy of leadership. While the RUHSA Tool was not designed to be used in the midst of a public health emergency, such as the ongoing COVID-19 pandemic, it may also be adapted to inform a checklist for prioritising what capacities and activities a city needs to rapidly develop or to help focus requests for assistance.

Generating linear oxygen gradients across 3D cell cultures with block-layered oxygen controlled chips (BLOCCs).

Oxygen is a transcriptional regulator responsible for tissue homeostasis and maintenance. Studies relating cellular phenotype with oxygen tension often use hypoxia chambers, which expose cells to a single, static oxygen tension. Despite their ease of use, these chambers are unable to replicate the oxygen gradients found in healthy and diseased tissues. Microfabricated devices capable of imposing an oxygen gradient across tissue-like structures are a promising tool for these studies, as they can provide a high density of information in a single experimental setup. We describe the fabrication and characterization of a modular device, which leverages the gas-permeability of silicone to impose gradients of oxygen across cell-containing regions, assembled by layering sheets of laser cut acrylic and silicone rubber. The silicone also acts as a barrier, separating the flowing gases from the cell culture medium, preventing evaporation or bubble formation in experiments that require prolonged periods of incubation. The acrylic components provide a rigid framework to provide a sterile culture environment. Using oxygen-sensing films, we show the device can support gradients of different ranges and steepness by simply changing the composition of the gases flowing through the silicone components of the BLOCC. Using a cell-based reporter assay, we demonstrate that cellular responses to hypoxia are proportional to oxygen tension.

Developing a Drug Screening Platform: MALDI-Mass Spectrometry Imaging of Paper-Based Cultures.

Many potential chemotherapeutics fail to reach patients. One of the key reasons is that compounds are tested during the drug discovery stage in two-dimensional (2D) cell cultures, which are often unable to accurately model in vivo outcomes. Three-dimensional (3D) in vitro tumor models are more predictive of chemotherapeutic effectiveness than 2D cultures, and thus, their implementation during the drug screening stage has the potential to more accurately evaluate compounds earlier, saving both time and money. Paper-based cultures (PBCs) are an emerging 3D culture platform in which cells suspended in Matrigel are seeded into paper scaffolds and cultured to generate a tissue-like environment. In this study, we demonstrate the potential of matrix-assisted laser desorption/ionization-mass spectrometry imaging with PBCs (MALDI-MSI-PBC) as a drug screening platform. This method discriminated regions of the PBCs with and without cells and/or drugs, indicating that coupling PBCs with MALDI-MSI has the potential to develop rapid, large-scale, and parallel mass spectrometric drug screens.

Risk Factors for Infectious Diseases in Urban Environments of Sub-Saharan Africa: A Systematic Review and Critical Appraisal of Evidence.

Our world is rapidly urbanizing. According to the United Nations, between 1990 and 2015, the percent of the world's population living in urban areas grew from 43% to 54%. Estimates suggest that this trend will continue and that over 68% of the world's population will call cities home by 2050, with the majority of urbanization occurring in African countries. This urbanization is already having a profound effect on global health and could significantly impact the epidemiology of infectious diseases. A better understanding of infectious disease risk factors specific to urban settings is needed to plan for and mitigate against future urban outbreaks. We conducted a systematic literature review of the Web of Science and PubMed databases to assess the risk factors for infectious diseases in the urban environments of sub-Saharan Africa. A search combining keywords associated with cities, migration, African countries, infectious disease, and risk were used to identify relevant studies. Original research and meta-analyses published between 2004 and 2019 investigating geographical and behavioral risk factors, changing disease distributions, or control programs were included in the study. The search yielded 3610 papers, and 106 met the criteria for inclusion in the analysis. Papers were categorized according to risk factors, geographic area, and study type. The papers covered 31 countries in sub-Saharan Africa with East Africa being the most represented sub-region. Malaria and HIV were the most frequent disease focuses of the studies. The results of this work can inform public health policy as it relates to capacity building and health systems strengthening in rapidly urbanizing areas, as well as highlight knowledge gaps that warrant additional research.