Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long-term control of infection while also preventing an over-zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro- and anti-inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying the signals, cells, cytokines, and other immune response factors that mediate this balance over time has been difficult using traditional research strategies. Computational modeling studies based on data from traditional systems can identify how this balance contributes to immunity. Here we provide evidence from both experimental and mathematical/computational studies to support the concept of a dynamic balance operating during persistent and other infection scenarios. We focus mainly on tuberculosis, currently the leading cause of death due to infectious disease in the world, and also provide evidence for other infections. A better understanding of the dynamically balanced immune response can help shape treatment strategies that utilize both drugs and host-directed therapies.

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The goal of this study was to evaluate the effects of a 6-week forgiveness intervention on three outcomes: (a) offense-specific forgiveness, (b) forgiveness-likelihood in new situations, and (c) health-related psychosocial variables, such as perceived stress and trait-anger. Participants were 259 adults who had experienced a hurtful interpersonal transgression from which they still felt negative consequences. They were randomized to a forgiveness-training program or a no-treatment control group. The intervention reduced negative thoughts and feelings about the target transgression 2 to 3 times more effectively than the control condition, and it produced significantly greater increases in positive thoughts and feelings toward the transgressor. Significant treatment effects were also found for forgiveness self-efficacy, forgiveness generalized to new situations, perceived stress, and trait-anger.

Background: Quantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer's disease (AD) will provide a template for understanding the underlying aetiology of the clinical syndrome and, concomitantly, for improving early diagnosis, clinical trial recruitment and treatment assessment. This study aims to characterise continuous changes of such markers and determine their rate of change and temporal order throughout the AD continuum. Methods: The methodology is founded on the development of stochastic models to estimate the expected time to reach different clinical disease states, for different risk groups, and synchronise short-term individual biomarker data onto a disease progression timeline. Twenty-seven markers are considered, including a range of cognitive scores, cerebrospinal (CSF) and plasma fluid proteins, and brain structural and molecular imaging measures. Data from 2014 participants in the Alzheimer's Disease Neuroimaging Initiative database is utilised. Results: The model suggests that detectable memory dysfunction could occur up to three decades prior to the onset of dementia due to AD (ADem). This is closely followed by changes in amyloid-β CSF levels and the first cognitive decline, as assessed by sensitive measures. Hippocampal atrophy could be observed as early as the initial amyloid-β accumulation. Brain hypometabolism starts later, about 14 years before onset, along with changes in the levels of total and phosphorylated tau proteins. Loss of functional abilities occurs rapidly around ADem onset. Neurofilament light is the only protein with notable early changes in plasma levels. The rate of change varies, with CSF, memory, amyloid PET and brain structural measures exhibiting the highest rate before the onset of ADem, followed by a decline. The probability of progressing to a more severe clinical state increases almost exponentially with age. In accordance with previous studies, the presence of apolipoprotein E4 alleles and amyloid-β accumulation can be associated with an increased risk of developing the disease, but their influence depends on age and clinical state. Conclusions: Despite the limited longitudinal data at the individual level and the high variability observed in such data, the study elucidates the link between the long asynchronous pathophysiological processes and the preclinical and clinical stages of AD.

Nosocomial transmission of SARS-CoV-2 is a key concern, and evaluating the effect of testing and infection prevention and control strategies is essential for guiding policy in this area. Using a within-hospital SEIR transition model of SARS-CoV-2 in a typical English hospital, we estimate that between 9 March 2020 and 17 July 2020 approximately 20% of infections in inpatients, and 73% of infections in healthcare workers (HCWs) were due to nosocomial transmission. Model results suggest that placing suspected COVID-19 patients in single rooms or bays has the potential to reduce hospital-acquired infections in patients by up to 35%. Periodic testing of HCWs has a smaller effect on the number of hospital-acquired COVID-19 cases in patients, but reduces infection in HCWs by as much as 37% and results in only a small proportion of staff absences (approx. 0.3% per day). This is considerably less than the 20–25% of staff that have been reported to be absent from work owing to suspected COVID-19 and self-isolation. Model-based evaluations of interventions, informed by data collected so far, can help to inform policy as the pandemic progresses and help prevent transmission in the vulnerable hospital population. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.

Objective. To evaluate whether the Geriatric Medication Game increases understanding, awareness, and empathy towards geriatric patients and the challenges they encounter in our health care system, especially as those challenges relate to medication use. Design. One hundred two students from the St. Louis College of Pharmacy participated in the game and 96 students completed a pretest and posttest questionnaire that assessed their attitudes and experiences. The players were asked to rate the level of emotions they experienced and their awareness of geriatric needs. Assessment. Students' perceptions changed significantly for the majority of the items assessed. Frustration was the highest emotion experienced (median=4). Over 70% of students stated the game increased empathy and understanding toward patients. Conclusion. The Geriatric Medication Game serves as a resource for increasing pharmacy students' awareness of the perceptions and experiences of geriatric patients.

Nosocomial transmission of SARS-CoV-2 is a key concern and evaluating the effect of testing and infection prevention control strategies is essential for guiding policy in this area. Using a within-hospital SEIR transition model of SARS-CoV-2 in a typical UK hospital, we predict that approximately 20% of infections in inpatients, and 89% of infections in HCWs were due to nosocomial transmission. Placing suspected COVID-19 patients in single rooms or bays has the potential to reduce hospital-acquired infections in patients by up to 80%. Periodic testing of HCWs has a smaller effect on the patient-burden of COVID-19 but would considerably reduce infection in HCWs by as much as 64% and result in only a small proportion of staff absences (approximately 1% per day). This is considerably fewer than currently observed due to suspected COVID-19 and self-isolation.

Health promoters have been unable to reach and engage people on social media (SM) to the extent that food industry brands and lifestyle personalities have. The objective of this study was to identify the SM post strategies associated with higher engagement in nutrition and food-related posts using a retrospective content analysis. The six most engaging posts from both Facebook and Instagram’s 10 most successful nutrition and food-related accounts were analysed across four fields. Subjective and objective post strategies were coded on 736 posts, and associations with engagement were explored using the Least Absolute Shrinkage and Selection Operator (LASSO). Lifestyle personalities recorded the highest absolute engagement, while health promoters recorded the highest engagement relative to follower count. Strategies associated with higher Facebook engagement included using hashtags and prompting engagement through announcements, while on Instagram, higher engagement was associated with higher caption counts, providing health information links, prompting engagement through strategies that require an action, and using humorous strategies. Strategies associated with lower Instagram engagement included reposted content, general encouragement to eat strategies, encouragement to exercise strategies, not inducing any emotion/hedonic sensations, and providing a negative tone. Health promoters should adapt SM posts to the different SM platforms and utilise strategies associated with higher engagement to engage with their audience on SM.