Dielectric properties of human macrophages are altered by Mycobacterium tuberculosis infection.

The analysis of cell electrophysiology for pathogenic samples at BSL3 can be problematic. It is virtually impossible to isolate infected from uninfected without a label, for example green fluorescent protein, which can potentially alter the cell electrical properties. Furthermore, the measurement of highly pathogenic organisms often requires equipment dedicated only for use with these organisms due to safety considerations. To address this, we have used dielectrophoresis to study the electrical properties of the human THP-1 cell line and monocyte-derived macrophages before and after infection with non-labelled Mycobacterium tuberculosis. Infection with these highly pathogenic bacilli resulted in changes including a raised surface conductance (associated with reduced zeta potential) and increased capacitance, suggesting an increase in surface roughness. We have also investigated the effect of fixation on THP-1 cells as a means to enable study on fixed samples in BSL1 or 2 laboratories, which suggests that the properties of these cells are largely unaffected by the fixation process. This advance results in a novel technique enabling the isolation of infected and non-infected cells in a sample without labelling.

A Qualitative Analysis of Barriers to Accessing HIV Prevention Services During an HIV Outbreak among Persons who Inject Drugs in West Virginia.

In response to an increase in HIV diagnoses among persons who inject drugs (PWID) in Kanawha County, West Virginia, West Virginia Bureau for Public Health and CDC conducted a qualitative assessment in Kanawha County to inform HIV outbreak response activities. Interviews with 26 PWID and 45 community partners were completed. Transcribed interviews were analyzed to identify barriers to accessing HIV prevention services among PWID using the risk environment framework. Participants identified numerous political, physical, social, and economic community-level barriers that influenced access to HIV prevention services among PWID. Political factors included low community support for syringe services programs (SSPs); physical factors included low SSP coverage, low coverage of HIV testing outreach events, low HIV preexposure prophylaxis availability, and homelessness; social factors included stigma and discrimination; economic factors included community beliefs that SSPs negatively affect economic investments and limited resources for HIV screening in clinical settings. Individual-level barriers included co-occurring acute medical conditions and mental illness. Community-level interventions, such as low-barrier one-stop shop models, are needed to increase access to sterile syringes through comprehensive harm reduction services.

Were Needles Everywhere?: Differing Views on Syringe Waste and Disposal Associated With Needs-Based Syringe Services Programs Among Community Partners and Persons Who Inject Drugs.

BACKGROUND: Community concerns surrounding syringe waste are a common barrier to syringe services program (SSP) implementation. In Kanawha County, West Virginia, community opposition to SSPs resulted in the closure of needs-based SSPs prior to and during an HIV outbreak among persons who inject drugs (PWID). This qualitative analysis examines views of PWID and community partners on syringe waste and disposal associated with needs-based SSPs. METHODS: Qualitative interviews with 26 PWID and 45 community partners (medical and social service providers, law enforcement personnel, policymakers, and religious leaders) were conducted. Interviews were recorded, transcribed, and coded. Code summaries described participants' views on syringe waste and disposal and needs-based SSPs. RESULTS: Community partners and PWID who favored needs-based SSPs reported that needs-based SSPs had not affected or reduced syringe waste. Conversely, community partners who favored one-to-one exchange models and/or barcoded syringes described needs-based SSPs increasing syringe waste. Community partners often cited pervasive community beliefs that SSPs increased syringe waste, risk of needlesticks, drug use, and crime. Community partners were unsure how to address syringe waste concerns and emphasized that contradictory views on syringe waste posed barriers to discussing and implementing SSPs. CONCLUSIONS: Participants' views on whether syringe waste was associated with needs-based SSPs often aligned with their support or opposition for needs-based SSPs. These differing views resulted in challenges finding common ground to discuss SSP operations amid an HIV outbreak among PWID. SSPs might consider addressing syringe waste concerns by expanding syringe disposal efforts and implementing community engagement and stigma reduction activities.

Hepatitis C Virus Infection Preceding an Outbreak of Human Immunodeficiency Virus Among Persons Who Inject Drugs-Kanawha County, West Virginia, 2019-2021.

Of 65 cases during a human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in West Virginia (2019-2021), 61 (94%) had hepatitis C diagnosed a median of 46 months prior to HIV diagnosis. Hepatitis C diagnosis among PWID should trigger improved access to prevention and treatment services.

Loss of phenotypic inheritance associated with ydcI mutation leads to increased frequency of small, slow persisters in Escherichia coli.

Whenever a genetically homogenous population of bacterial cells is exposed to antibiotics, a tiny fraction of cells survives the treatment, the phenomenon known as bacterial persistence [G.L. Hobby et al., Exp. Biol. Med. 50, 281-285 (1942); J. Bigger, The Lancet 244, 497-500 (1944)]. Despite its biomedical relevance, the origin of the phenomenon is still unknown, and as a rare, phenotypically resistant subpopulation, persisters are notoriously hard to study and define. Using computerized tracking we show that persisters are small at birth and slowly replicating. We also determine that the high-persister mutant strain of Escherichia coli, HipQ, is associated with the phenotype of reduced phenotypic inheritance (RPI). We identify the gene responsible for RPI, ydcI, which encodes a transcription factor, and propose a mechanism whereby loss of phenotypic inheritance causes increased frequency of persisters. These results provide insight into the generation and maintenance of phenotypic variation and provide potential targets for the development of therapeutic strategies that tackle persistence in bacterial infections.

Notes from the Field: HIV Outbreak During the COVID-19 Pandemic Among Persons Who Inject Drugs - Kanawha County, West Virginia, 2019-2021.

During October 2019, the West Virginia Bureau for Public Health (WVBPH) noted that an increasing number of persons who inject drugs (PWID) in Kanawha County received a diagnosis of HIV. The number of HIV diagnoses among PWID increased from less than five annually during 2016-2018 to 11 during January-October 2019 (Figure). Kanawha County (with an approximate population of 180,000*) has high rates of opioid use disorder and overdose deaths, which have been increasing since 2016,† and the county is located near Cabell County, which experienced an HIV outbreak among PWID during 2018-2019 (1,2). In response to the increase in HIV diagnoses among PWID in 2019, WVBPH released a Health Advisory§; and WVBPH and Kanawha-Charleston Health Department (KCHD) convened an HIV task force, conducted care coordination meetings, received CDC remote assistance to support response activities, and expanded HIV testing and outreach.

Prevalence and predictors of post-traumatic stress symptoms in 2200 hospitalised and non-hospitalised injured New Zealanders.

OBJECTIVE: Post-traumatic stress disorder following injuries unrelated to mass casualty events has received little research attention in New Zealand. Internationally, most studies investigating predictors of post-injury post-traumatic stress disorder focus on hospitalised patients although most survivors are not hospitalised. We compared the prevalence and predictors of symptoms suggestive of post-traumatic stress disorder 12 months following injury among hospitalised and non-hospitalised entitlement claimants in New Zealand's Accident Compensation Corporation. This government-funded universal no-fault insurance scheme replaced tort-based compensation for injuries in 1974 since when civil litigation (which can bias post-traumatic stress disorder estimates) has been rare. METHODS: A total of 2220 Accident Compensation Corporation claimants aged 18-64 years recruited to the Prospective Outcomes of Injury Study were interviewed at 12 months post-injury to identify symptoms suggestive of post-traumatic stress disorder using the Impact of Events Scale. Multivariable models examined the extent to which baseline sociodemographic, injury, health status and service interaction factors predicted the risk of post-traumatic stress disorder symptoms among hospitalised and non-hospitalised groups. RESULTS: Symptoms suggestive of post-traumatic stress disorder were reported by 17% of hospitalised and 12% of non-hospitalised participants. Perceived threat to life at the time of the injury doubled this risk among hospitalised (adjusted relative risk: 2.0; 95% confidence interval: 1.2-3.2) and non-hospitalised (relative risk: 1.8; 95% confidence interval: 1.2-2.8) participants. Among hospitalised participants, other predictors included female gender, Pacific and 'other' minority ethnic groups, pre-injury depressive symptoms, financial insecurity and perceived inadequacies in healthcare interactions, specifically information and time to discuss problems. Among non-hospitalised survivors, predictors included smoking, hazardous drinking, assault and poor expectations of recovery. CONCLUSION: One in six hospitalised and one in eight non-hospitalised people reported post-traumatic stress disorder symptoms 12 months following injury. Perceived threat to life was a strong predictor of this risk in both groups. Identifying early predictors of post-traumatic stress disorder, regardless of whether the injury required hospitalisation, could help target tailored interventions that can reduce longer-term psychosocial morbidity.

Survivors' perceptions of support following a parent's suicide.

Children who experience a parent's suicide are vulnerable to an increased risk for mental health disorders and suicide attempts. In this study, 17 adults, each a child survivor of their parent's suicide, shared their perceptions of support following the suicide. Helpful experiences included opening communication about suicide and offering individualized support. Unhelpful experiences included judgment and blame, silence regarding suicide, and a heightened awareness of the surviving parent's challenges. Individuals most helpful in meeting the child's needs included those with preexisting relationships. In particular, our findings emphasize the critical need for honest, open, and age-appropriate communication about the parent's suicide.

Health literacy: The role of NHS library and knowledge services.

Health literacy is key to person-centred, preventative healthcare and is both a societal and individual responsibility. This feature describes work undertaken by Health Education England, the Community Health and Learning Foundation and NHS Library and Knowledge Services to raise awareness among NHS staff and other key partners of the impact of low health literacy. It highlights a range of health literacy resources and ideas for developing and adapting these tools for remote delivery during and post-pandemic. D.I.

Introducing Porosity in Colloidal Biocoatings to Increase Bacterial Viability.

A biocoating confines nongrowing, metabolically active bacteria within a synthetic colloidal polymer (i.e., latex) film. Bacteria encapsulated inside biocoatings can perform useful functions, such as a biocatalyst in wastewater treatment. A biocoating needs to have a high permeability to allow a high rate of mass transfer for rehydration and the transport of both nutrients and metabolic products. It therefore requires an interconnected porous structure. Tuning the porosity architecture is a challenge. Here, we exploited rigid tubular nanoclays (halloysite) and nontoxic latex particles (with a relatively high glass transition temperature) as the colloidal "building blocks" to tailor the porosity inside biocoatings containing Escherichia coli bacteria as a model organism. Electron microscope images revealed inefficient packing of the rigid nanotubes and proved the existence of nanovoids along the halloysite/polymer interfaces. Single-cell observations using confocal laser scanning microscopy provided evidence for metabolic activity of the E. coli within the biocoatings through the expression of a yellow fluorescent protein. A custom-built apparatus was used to measure the permeability of a fluorescein sodium salt in the biocoatings. Whereas there was no measurable permeability in a coating made from only latex particles, the permeability coefficient of the composite biocoatings increased with increasing halloysite content up to a value of 1 × 10-4 m h-1. The effects of this increase in permeability was demonstrated through a specially developed resazurin reduction assay. Bacteria encapsulated in halloysite composite biocoatings had statistically significant higher metabolic activities in comparison to bacteria encapsulated in a nonoptimized coating made from latex particles alone.

Impact of further injury on participation in work and activities among those previously injured: results from a New Zealand prospective cohort study.

PURPOSE: To examine participation in paid work, unpaid work and activities 12 months after a sentinel (initial) injury, and to determine the impact of sustaining a subsequent injury (SI) on these participation outcomes. METHODS: Participants were recruited to the Prospective Outcomes of Injury Study following an Accident Compensation Corporation (ACC; New Zealand's no-fault injury insurer) entitlement claim injury. Outcomes were whether participants reported reduced paid work hours, reduced unpaid work (e.g. housework, gardening) or reduced activities (e.g. socialising, leisure pursuits) at 12 months compared to before the sentinel injury event. SIs were ACC claims of any type. Using multivariable models, characteristics of SIs were examined as potential predictors of reduced participation. RESULTS: At 12 months, 30% had reduced paid work hours, 12% had reduced unpaid work and 25% had reduced activities. Sustaining a SI predicted reduced paid work (RR 1.5; 95% CI 1.2, 1.8), but not unpaid work or activities. Participants who had sustained intracranial SIs were at highest risk of reduced paid work (RR 3.2, 95% CI 1.9, 5.2). Those sustaining SIs at work were less likely to have reduced paid work (RR 0.7; 95% CI 0.6, 1.0) than those with only non-work SIs. Participants sustaining assaultive SIs had higher risk of reduced unpaid work (RR 2.6, 95% CI 1.0, 6.8). CONCLUSIONS: Reduced participation is prevalent after a substantive sentinel injury, and sustaining a SI impacts on return to paid work. Identification of SI characteristics that put people at high risk of participation restriction may be useful for focusing on rehabilitative attention.

Developing a framework to evaluate knowledge into action interventions.

BACKGROUND: There are many challenges in delivering and evaluating knowledge for healthcare, but the lack of clear routes from knowledge to practice is a root cause of failures in safety within healthcare. Various types and sources of knowledge are relevant at different levels within the healthcare system. These need to be delivered in a timely way that is useful and actionable for those providing services or developing policies. How knowledge is taken up and used through networks and relationships, and the difficulties in attributing change to knowledge-based interventions, present challenges to understanding how knowledge into action (K2A) work influences healthcare outcomes. This makes it difficult to demonstrate the importance of K2A work, and harness support for its development and resourcing. This paper presents the results from a project commissioned by NHS Education for Scotland (NES) and Healthcare Improvement Scotland (HIS) to create an evaluation framework to help understand the NHS Scotland Knowledge into Action model. METHODS: The team took a developmental approach to creating an evaluation framework that would be useful and practical. This included a literature review to ensure the evaluation was evidence-based; adaptation of contribution analysis for K2A project; action research with K2A project leads to refine the work and develop suitable measures. RESULTS: Principles for evaluation and an evaluation framework based on contribution analysis were developed and implemented on a trial project. An outcomes chain was developed for the K2A programme and specific projects. This was used to design, collect and collate evidence of the K2A intervention. Data collected routinely by the intervention was supplemented with specific feedback measures from K2A project users. CONCLUSIONS: The evaluation approach allowed for scrutiny of both processes and outcomes and was adaptable to projects on different scales. This framework has proved useful as a planning, reflecting and evaluation tool for K2A, and could be more widely used to evidence the ways in which knowledge to action work helps improve healthcare outcomes.

Two years after injury: prevalence and early post-injury predictors of ongoing injury-related problems.

PURPOSE: To determine, in a cohort with injuries classified anatomically as mainly minor or moderate and for which only 25% were hospitalised acutely, the prevalence of ongoing problems attributed by participants to their injury 2 years prior, and to examine whether three-month post-injury experiences and expectations predict such problems. METHODS: Participants (N = 2231; 18-64 years at injury) were those in the Prospective Outcomes of Injury Study who completed the initial three-month and final two-year interviews. The outcome measure was whether participants reported ongoing injury-related problems at 2 years. Possible early post-injury predictors were identified from the first interview; pre-injury and injury-related potential confounders from the first interview, insurer records and hospital discharge records. Multivariable models estimated relative risks. RESULTS: Almost half the participants reported injury-related problems at 2 years. Participants reporting non-recovery at 3 months were more likely than those reporting recovery to have ongoing problems at 2 years, ranging from participants expecting to get better soon [adjusted RR 2.2, 95% CI (1.7,2.8)) to those expecting to never get better (aRR 3.1, 95% CI (2.4,4.0)]. Several three-month post-injury experiences also predicted ongoing problems at 2 years. Participants at highest risk included those with extreme pain [aRR 2.1, 95% CI (1.7,2.5)], and less involvement in usual activities [aRR 1.7, 95% CI (1.5,1.9)]. CONCLUSIONS: Findings indicate that early post-injury characteristics predict longer-term recovery among this cohort, most of who were not classified as seriously injured, and provide guidance for future studies on interventions to reduce poor outcome prevalence, particularly focussing on pain management and enabling return to independence and social participation.

Subsequent Injury Study (SInS): Improving outcomes for injured New Zealanders.

BACKGROUND: Subsequent injury (SI) is a major contributor to disability and costs for individuals and society. AIM: To identify modifiable risk factors predictive of SI and SI health and disability outcomes and costs. OBJECTIVES: To (1) describe the nature of SIs reported to New Zealand's no-fault injury insurer (the Accident Compensation Corporation (ACC)); (2) identify characteristics of people underaccessing ACC for SI; (3) determine factors predicting or protecting against SI; and (4) investigate outcomes for individuals, and costs to society, in relation to SI. DESIGN: Prospective cohort study. METHODS: Previously collected data will be linked including data from interviews undertaken as part of the earlier Prospective Outcomes of Injury Study (POIS), ACC electronic data and national hospitalisation data about SI. POIS participants (N=2856, including 566 Maori) were recruited via ACC's injury register following an injury serious enough to warrant compensation entitlements. We will examine SI over the following 24 months for these participants using descriptive and inferential statistics including multivariable generalised linear models and Cox's proportional hazards regression. DISCUSSION: Subsequent Injury Study (SInS) will deliver information about the risks, protective factors and outcomes related to SI for New Zealanders. As a result of sourcing injury data from New Zealand's 'all injury' insurer ACC, SInS includes people who have been hospitalised and not hospitalised for injury. Consequently, SInS will provide insights that are novel internationally as other studies are usually confined to examining trauma registries, specific injuries or injured workers who are covered by a workplace insurer rather than a 'real-world' injury population.

Knowledge into action - supporting the implementation of evidence into practice in Scotland.

BACKGROUND: The knowledge into action model for NHS Scotland provides a framework for librarians and health care staff to support getting evidence into practice. Central to this model is the development of a network of knowledge brokers to facilitate identification, use, creation and sharing of knowledge. OBJECTIVE: To translate the concepts described in the model into tangible activities with the intention of supporting better use of evidence in health care and subsequently improving patient outcomes. METHODS: Four areas of activity were addressed by small working groups comprising knowledge services staff in local and national boards. The areas of activity were as follows: defining existing and required capabilities and developing learning opportunities for the knowledge broker network; establishing national search and summarising services; developing actionable knowledge tools; and supporting person-to-person knowledge sharing. CONCLUSION: This work presents the development of practical tools and support to translate a conceptual model for getting knowledge into action into a series of activities and outputs to support better use of evidence in health care and subsequently improved patient outcomes.

An evaluation of case completeness for New Zealand Coronial case files held on the Australasian National Coronial Information System (NCIS).

Large administrative databases provide powerful opportunities for examining the epidemiology of injury. The National Coronial Information System (NCIS) contains Coronial data from Australia and New Zealand (NZ); however, only closed cases are stored for NZ. This paper examines the completeness of NZ data within the NCIS and its impact upon the validity and utility of this database. A retrospective review of the capture of NZ cases of quad-related fatalities held in the NCIS was undertaken by identifying outstanding Coronial cases held on the NZ Coronial Management System (primary source of NZ Coronial data). NZ data held on the NCIS database were incomplete due to the non-capture of closed cases and the unavailability of open cases. Improvements to the information provided on the NCIS about the completeness of NZ data are needed to improve the validity of NCIS-derived findings and the overall utility of the NCIS for research.

Factors predictive of subsequent injury in a longitudinal cohort study.

OBJECTIVES: The aims are to: (1) Determine the cumulative incidence of self-reported subsequent injury (of any anatomical site or injury type) occurring between 3 months and 12 months after a sentinel injury among participants in the Prospective Outcomes of Injury Study in New Zealand and (2) Examine the preinjury and injury-related predictors of subsequent injury. METHODS: Prospective Outcomes of Injury Study participants (n=2282) were interviewed 3 months, 5 months and 12 months after a sentinel injury event. Data were collected about a range of preinjury and injury-related factors at the 3-month interview and about subsequent injury at the 5-month and 12-month interviews. Poisson regression modelling was used to determine the preinjury and injury-related predictors of subsequent injury. RESULTS: Between the 3-month and 12 month interviews 28% of the participants reported at least one subsequent injury. Subsequent injury was 34% more likely among participants with a prior injury affecting them at the time of the sentinel injury compared with participants without a prior injury affecting them, and more likely among non-workers (31% more likely) and trade/manual workers (32% more likely) compared with professionals. Participants whose sentinel injury was due to assault were 43% more likely to report a subsequent injury compared with those whose sentinel injury was accidental. A subsequent injury was 23% less likely if the sentinel injury was a lower extremity fracture compared with other injuries, and 21% less likely if the sentinel injury event involved hospitalisation. CONCLUSIONS: Among general injury populations it may be possible to identify people at increased risk for subsequent injury.

Prevalence of poor outcomes soon after injury and their association with the severity of the injury.

Little is known of injury outcomes among non-hospitalised injured populations. This study examined the occurrence of poor outcomes 3 months after injury among the 2856 participants in the Prospective Outcomes of Injury Study, most of whom had sustained injuries considered of minor severity (by injury severity scoring) and had not received treatment at a hospital facility. The prevalence of poor outcomes was high across all health, physical functioning and social functioning domains and expectation characteristics examined, including for those participants with the 'least severe' injuries. Approximately half of the cohort reported experiencing moderate to high pain or psychological distress and reduced social participation, and three-quarters did not consider themselves recovered. Our findings demonstrate that, to obtain an accurate understanding of injury burden, injury outcome research should not focus only on those injured persons who are hospitalised.

Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection.

The 6-kDa early secretory antigenic target of Mycobacterium tuberculosis (ESAT-6) and the 10-kDa culture filtrate antigen (CFP-10), encoded in region of difference 1 (RD1) and secreted by the ESAT-6 system 1 (Esx-1) secretion system, are the most immunodominant and highly M. tuberculosis (MTB)-specific antigens. These attributes are responsible for their primary importance in tuberculosis (TB) immunodiagnosis and vaccine development. Rv3615c [Esx-1 substrate protein C (EspC)], encoded outside RD1, is similar in size and sequence homology to CFP-10 and ESAT-6, suggesting it might be a target of cellular immunity in TB. Using ex vivo enzyme-linked immunospot- and flow cytometry-based cytokine-secretion assay, we comprehensively assessed cellular immune responses to EspC in patients with active TB, latently infected persons, and uninfected bacillus Calmette-Guérin (BCG)-vaccinated controls. EspC was at least as immunodominant as ESAT-6 and CFP-10 in both active and latent TB infection. EspC contained broadly recognized CD4(+) and CD8(+) epitopes, inducing a predominantly CD4(+) T-cell response that comprised functional T-cell subsets secreting both IFN-γ and IL-2 as well as functional T-cell subsets secreting only IFN-γ. Surprisingly, T-cell responses to EspC were as highly specific (93%) for MTB infection as responses to ESAT-6 and CFP-10, with only 2 of 27 BCG-vaccinated controls responding to each antigen. Using quantitative proteomics and metabolically labeled mutant and genetically complemented MTB strains, we identified the mechanism of the specificity of anti-EspC immunity as the Esx-1 dependence of EspC secretion. The high immunodominance of EspC, equivalent to that of ESAT-6 and CFP-10, makes it a TB vaccine candidate, and its high specificity confers strong potential for T-cell-based immunodiagnosis.