Heterogeneous risk attitudes and waves of infection.

Many countries have experienced multiple waves of infection during the COVID-19 pandemic. We propose a novel but parsimonious extension of the SIR model, a CSIR model, that can endogenously generate waves. In the model, cautious individuals take appropriate prevention measures against the virus and are not exposed to infection risk. Incautious individuals do not take any measures and are susceptible to the risk of infection. Depending on the size of incautious and susceptible population, some cautious people lower their guard and become incautious-thus susceptible to the virus. When the virus spreads sufficiently, the population reaches "temporary" herd immunity and infection subsides thereafter. Yet, the inflow from the cautious to the susceptible eventually expands the susceptible population and leads to the next wave. We also show that the CSIR model is isomorphic to the SIR model with time-varying parameters.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study.

BACKGROUND: Households are considered ideal settings for studying the transmission dynamics of an infectious disease. METHODS: A prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. RESULTS: We enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0-18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4-45.5) and fatigue (aOR, 9.3; 95% CI, 3.8-22.7) were associated with SARS-CoV-2 transmission. CONCLUSIONS: We observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

The impact of within-host coinfection interactions on between-host parasite transmission dynamics varies with spatial scale.

Within-host interactions among coinfecting parasites can have major consequences for individual infection risk and disease severity. However, the impact of these within-host interactions on between-host parasite transmission, and the spatial scales over which they occur, remain unknown. We developed and apply a novel spatially explicit analysis to parasite infection data from a wild wood mouse (Apodemus sylvaticus) population. We previously demonstrated a strong within-host negative interaction between two wood mouse gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the coccidian Eimeria hungaryensis, using drug-treatment experiments. Here, we show this negative within-host interaction can significantly alter the between-host transmission dynamics of E. hungaryensis, but only within spatially restricted neighbourhoods around each host. However, for the closely related species E. apionodes, which experiments show does not interact strongly with H. polygyrus, we did not find any effect on transmission over any spatial scale. Our results demonstrate that the effects of within-host coinfection interactions can ripple out beyond each host to alter the transmission dynamics of the parasites, but only over local scales that likely reflect the spatial dimension of transmission. Hence there may be knock-on consequences of drug treatments impacting the transmission of non-target parasites, altering infection risks even for non-treated individuals in the wider neighbourhood.

Susceptibility to stress and nature exposure: Unveiling differential susceptibility to physical environments; a randomized controlled trial.

BACKGROUND: Emerging epidemiological evidence indicates nature exposure could be associated with greater health benefits among groups in lower versus higher socioeconomic positions. One possible mechanism underpinning this evidence is described by our framework: (susceptibility) adults in low socioeconomic positions face higher exposure to persistent psychosocial stressors in early life, inducing a pro-inflammatory phenotype as a lifelong susceptibility to stress; (differential susceptibility) susceptible adults are more sensitive to the health risks of adverse (stress-promoting) environments, but also to the health benefits of protective (stress-buffering) environments. OBJECTIVE: Experimental investigation of a pro-inflammatory phenotype as a mechanism facilitating greater stress recovery from nature exposure. METHODS: We determined differences in stress recovery (via heart rate variability) caused by exposure to a nature or office virtual reality environment (10 min) after an acute stressor among 64 healthy college-age males with varying levels of susceptibility (socioeconomic status, early life stress, and a pro-inflammatory state [inflammatory reactivity and glucocorticoid resistance to an in vitro bacterial challenge]). RESULTS: Findings for inflammatory reactivity and glucocorticoid resistance were modest but consistently trended towards better recovery in the nature condition. Differences in recovery were not observed for socioeconomic status or early life stress. DISCUSSION: Among healthy college-age males, we observed expected trends according to their differential susceptibility when assessed as inflammatory reactivity and glucocorticoid resistance, suggesting these biological correlates of susceptibility could be more proximal indicators than self-reported assessments of socioeconomic status and early life stress. If future research in more diverse populations aligns with these trends, this could support an alternative conceptualization of susceptibility as increased environmental sensitivity, reflecting heightened responses to adverse, but also protective environments. With this knowledge, future investigators could examine how individual differences in environmental sensitivity could provide an opportunity for those who are the most susceptible to experience the greatest health benefits from nature exposure.

Concurrent Supra-Postural Auditory-Hand Coordination Task Affects Postural Control: Using Sonification to Explore Environmental Unpredictability in Factors Affecting Fall Risk.

Clinical screening tests for balance and mobility often fall short of predicting fall risk. Cognitive distractors and unpredictable external stimuli, common in busy natural environments, contribute to this risk, especially in older adults. Less is known about the effects of upper sensory-motor coordination, such as coordinating one's hand with an external stimulus. We combined movement sonification and affordable inertial motion sensors to develop a task for the precise measurement and manipulation of full-body interaction with stimuli in the environment. In a double-task design, we studied how a supra-postural activity affected quiet stance. The supra-postural task consisted of rhythmic synchronization with a repetitive auditory stimulus. The stimulus was attentionally demanding because it was being modulated continuously. The participant's hand movement was sonified in real time, and their goal was to synchronize their hand movement with the stimulus. In the unpredictable condition, the tempo changed at random points in the trial. A separate sensor recorded postural fluctuations. Young healthy adults were compared to older adult (OA) participants without known risk of falling. The results supported the hypothesis that supra-postural coordination would entrain postural control. The effect was stronger in OAs, supporting the idea that diminished reserve capacities reduce the ability to isolate postural control from sensory-motor and cognitive activity.

Stability analysis of a SAIR epidemic model on scale-free community networks.

The presence of asymptomatic carriers, often unrecognized as infectious disease vectors, complicates epidemic management, particularly when inter-community migrations are involved. We introduced a SAIR (susceptible-asymptomatic-infected-recovered) infectious disease model within a network framework to explore the dynamics of disease transmission amid asymptomatic carriers. This model facilitated an in-depth analysis of outbreak control strategies in scenarios with active community migrations. Key contributions included determining the basic reproduction number, $ R_0 $, and analyzing two equilibrium states. Local asymptotic stability of the disease-free equilibrium is confirmed through characteristic equation analysis, while its global asymptotic stability is investigated using the decomposition theorem. Additionally, the global stability of the endemic equilibrium is established using the Lyapunov functional theory.

IL-4 regulates neutrophilic pulmonary inflammation in a mouse model of bronchial asthma.

Neutrophilic pulmonary inflammation in asthmatics substantially exacerbates the severity of the disease leading to resistance to conventional corticosteroid therapy. Many studies established the involvement of Th1- and Th17-cells and cytokines produced by them (IFNg, IL-17A, IL-17F etc.) in neutrophilic pulmonary inflammation. Recent studies revealed that IL-4 - a Th2-cytokine regulates neutrophil effector functions and migration. It was showed that IL-4 substantially reduces neutrophilic inflammation of the skin in a mouse model of cutaneous bacterial infection and blood neutrophilia in a mouse model systemic bacterial infection. However, there are no data available regarding the influence of IL-4 on non-infectious pulmonary inflammation. In the current study we investigated the effects of IL-4 in a previously developed mouse model of neutrophilic bronchial asthma. We showed that systemic administration of IL-4 significantly restricts neutrophilic inflammation of the respiratory tract probably through the suppression of Th1-/Th17-immune responses and downregulation of CXCR2. Additionally, pulmonary neutrophilic inflammation could be alleviated by IL-4-dependant polarization of N2 neutrophils and M2 macrophages, expressing anti-inflammatory TGFß. Considering these, IL-4 might be used for reduction of exaggerated pulmonary neutrophilic inflammation and overcoming corticosteroid insensitivity of asthma patients.

General protocol for predicting outbreaks of infectious diseases in social networks.

Epidemic spreading on social networks with quenched connections is strongly influenced by dynamic correlations between connected nodes, posing theoretical challenges in predicting outbreaks of infectious diseases. The quenched connections introduce dynamic correlations, indicating that the infection of one node increases the likelihood of infection among its neighboring nodes. These dynamic correlations pose significant difficulties in developing comprehensive theories for threshold determination. Determining the precise epidemic threshold is pivotal for diseases control. In this study, we propose a general protocol for accurately determining epidemic thresholds by introducing a new set of fundamental conditions, where the number of connections between individuals of each type remains constant in the stationary state, and by devising a rescaling method for infection rates. Our general protocol is applicable to diverse epidemic models, regardless of the number of stages and transmission modes. To validate our protocol's effectiveness, we apply it to two widely recognized standard models, the susceptible-infected-recovered-susceptible model and the contact process model, both of which have eluded precise threshold determination using existing sophisticated theories. Our results offer essential tools to enhance disease control strategies and preparedness in an ever-evolving landscape of infectious diseases.

Effect of Short Photoperiod on Behavior and Brain Plasticity in Mice Differing in Predisposition to Catalepsy: The Role of BDNF and Serotonin System.

Seasonal affective disorder is characterized by depression during fall/winter as a result of shorter daylight. Catalepsy is a syndrome of some grave mental diseases. Both the neurotransmitter serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are involved in the pathophysiological mechanisms underlying catalepsy and depressive disorders. The aim was to compare the response of behavior and brain plasticity to photoperiod alterations in catalepsy-resistant C57BL/6J and catalepsy-prone CBA/Lac male mice. Mice of both strains were exposed for six weeks to standard-day (14 h light/10 h darkness) or short-day (4 h light/20 h darkness) conditions. Short photoperiod increased depressive-like behavior in both strains. Only treated CBA/Lac mice demonstrated increased cataleptic immobility, decreased brain 5-HT level, and the expression of Tph2 gene encoding the key enzyme for 5-HT biosynthesis. Mice of both strains maintained under short-day conditions, compared to those under standard-day conditions, showed a region-specific decrease in the brain transcription of the Htr1a, Htr4, and Htr7 genes. After a short photoperiod exposure, the mRNA levels of the BDNF-related genes were reduced in CBA/Lac mice and were increased in the C57BL/6J mice. Thus, the predisposition to catalepsy considerably influences the photoperiodic changes in neuroplasticity, wherein both C57BL/6J and CBA/Lac mice can serve as a powerful tool for investigating the link between seasons and mood.

Embryonic Amoxicillin Exposure Has Limited Impact on Liver Development but Increases Susceptibility to NAFLD in Zebrafish Larvae.

Amoxicillin is commonly used in clinical settings to target bacterial infection and is frequently prescribed during pregnancy. Investigations into its developmental toxicity and effects on disease susceptibility are not comprehensive. Our present study examined the effects of embryonic amoxicillin exposure on liver development and function, especially the effects on susceptibility to non-alcoholic fatty liver disease (NAFLD) using zebrafish as an animal model. We discovered that embryonic amoxicillin exposure did not compromise liver development, nor did it induce liver toxicity. However, co-treatment of amoxicillin and clavulanic acid diminished BESP expression, caused bile stasis and induced liver toxicity. Embryonic amoxicillin exposure resulted in elevated expression of lipid synthesis genes and exacerbated hepatic steatosis in a fructose-induced NAFLD model, indicating embryonic amoxicillin exposure increased susceptibility to NAFLD in zebrafish larvae. In summary, this research broadens our understanding of the risks of amoxicillin usage during pregnancy and provides evidence for the impact of embryonic amoxicillin exposure on disease susceptibility in offspring.

Prefrontal Cortex Cytosolic Proteome and Machine Learning-Based Predictors of Resilience toward Chronic Social Isolation in Rats.

Chronic social isolation (CSIS) generates two stress-related phenotypes: resilience and susceptibility. However, the molecular mechanisms underlying CSIS resilience remain unclear. We identified altered proteome components and biochemical pathways and processes in the prefrontal cortex cytosolic fraction in CSIS-resilient rats compared to CSIS-susceptible and control rats using liquid chromatography coupled with tandem mass spectrometry followed by label-free quantification and STRING bioinformatics. A sucrose preference test was performed to distinguish rat phenotypes. Potential predictive proteins discriminating between the CSIS-resilient and CSIS-susceptible groups were identified using machine learning (ML) algorithms: support vector machine-based sequential feature selection and random forest-based feature importance scores. Predominantly, decreased levels of some glycolytic enzymes, G protein-coupled receptor proteins, the Ras subfamily of GTPases proteins, and antioxidant proteins were found in the CSIS-resilient vs. CSIS-susceptible groups. Altered levels of Gapdh, microtubular, cytoskeletal, and calcium-binding proteins were identified between the two phenotypes. Increased levels of proteins involved in GABA synthesis, the proteasome system, nitrogen metabolism, and chaperone-mediated protein folding were identified. Predictive proteins make CSIS-resilient vs. CSIS-susceptible groups linearly separable, whereby a 100% validation accuracy was achieved by ML models. The overall ratio of significantly up- and downregulated cytosolic proteins suggests adaptive cellular alterations as part of the stress-coping process specific for the CSIS-resilient phenotype.

Genome-wide analyses in Lyme borreliosis: identification of a genetic variant associated with disease susceptibility and its immunological implications.

BACKGROUND: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. METHODS: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients-divided into a discovery and validation cohort-were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. RESULTS: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. CONCLUSIONS: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. TRIAL REGISTRATION: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015-02-13).

Single locus HLA sequencing with the nanopore technology for HLA disease association diagnosis.

Associations between HLA genotype and disease susceptibility encompass almost all the classic HLA loci. The level of typing resolution enabling a correct identification of an HLA disease susceptibility gene depends on the disease itself and/or on the accumulated knowledge about the molecular involvement of the HLA allele(s) engaged. Therefore, the application of Next Generation Sequencing technologies to HLA disease association, which would improve typing resolution, could prove useful to better understand disease severity. In the present study, we tested a nanopore sequencing approach developed by Omixon Biocomputing Ltd, dedicated to on-demand locus typing for HLA and disease, as an alternative to the conventional widely used sequence specific oligoprobe (SSO) approach. A total of 145 DNA samples used in routine diagnosis by SSO were retrospectively analyzed with nanopore technology, for HLA-A*02 immunotherapy decision for A*29, B*27, B*51, B*57 identification in class I, and DRB1, DQA1, and DQB1 for bullous dermatosis, rheumatoid arthritis, diabetes, and celiac disease requests in class II. Each locus was typed in a separate experiment, except for DQB1 and DQA1, which were analyzed together. Concordance between typings reached 100% for all the loci tested. Ambiguities by nanopore were only found for missing exon coverage. This approach was found to be very well adapted to the routine flow imposed by the SSO technique. This study illustrates the use of the new NanoTYPE MONO kit for single locus HLA sequencing for HLA and disease association diagnosis.

Waning immunity can drive repeated waves of infections.

In infectious disease models, it is known that mechanisms such as births, seasonality in transmission and pathogen evolution can generate oscillations in infection numbers. We show how waning immunity is also a mechanism that is sufficient on its own to enable sustained oscillations. When previously infected or vaccinated individuals lose full protective immunity, they become partially susceptible to reinfections. This partial immunity subsequently wanes over time, making individuals more susceptible to reinfections and potentially more infectious if infected. Losses of full and partial immunity lead to a surge in infections, which is the precursor of oscillations. We present a discrete-time Susceptible-Infectious-Immune-Waned-Infectious (SIRWY) model that features the waning of fully immune individuals (as a distribution of time at which individuals lose fully immunity) and the gradual loss of partial immunity (as increases in susceptibility and potential infectiousness over time). A special case of SIRWY is the discrete-time SIRS model with geometric distributions for waning and recovery. Its continuous-time analogue is the classic SIRS with exponential distributions, which does not produce sustained oscillations for any choice of parameters. We show that the discrete-time version can produce sustained oscillations and that the oscillatory regime disappears as discrete-time tends to continuous-time. A different special case of SIRWY is one with fixed times for waning and recovery. We show that this simpler model can also produce sustained oscillations. In conclusion, under certain feature and parameter choices relating to how exactly immunity wanes, fluctuations in infection numbers can be sustained without the need for any additional mechanisms.

Detection of Pathogenesis-Related (PR) Genes in Susceptible Tomato Plants Infected by Meloidogyne spp.

Meloidogyne species, as infective second-stage juveniles (J2s) larvae, are parasites able to attack host of relevant agronomic interest such as tomato plants. The identification of gene expression markers, useful to investigate the levels of root-knot nematode infection in the roots, is a fundamental tool in plant-pathogen interaction. The laboratory methods for analyzing the differential expression of pathogenesis-related (PR) genes constitute powerful tools for detecting the induced systemic acquired resistance defense response to M. incognita in infected plants and can be extended to all pathogen infection markers to obtain an early and sustainable control.

Multi-feature SEIR model for epidemic analysis and vaccine prioritization.

The SEIR (susceptible-exposed-infected-recovered) model has become a valuable tool for studying infectious disease dynamics and predicting the spread of diseases, particularly concerning the COVID pandemic. However, existing models often oversimplify population characteristics and fail to account for differences in disease sensitivity and social contact rates that can vary significantly among individuals. To address these limitations, we have developed a new multi-feature SEIR model that considers the heterogeneity of health conditions (disease sensitivity) and social activity levels (contact rates) among populations affected by infectious diseases. Our model has been validated using the data of the confirmed COVID cases in Allegheny County (Pennsylvania, USA) and Hamilton County (Ohio, USA). The results demonstrate that our model outperforms traditional SEIR models regarding predictive accuracy. In addition, we have used our multi-feature SEIR model to propose and evaluate different vaccine prioritization strategies tailored to the characteristics of heterogeneous populations. We have formulated optimization problems to determine effective vaccine distribution strategies. We have designed extensive numerical simulations to compare vaccine distribution strategies in different scenarios. Overall, our multi-feature SEIR model enhances the existing models and provides a more accurate picture of disease dynamics. It can help to inform public health interventions during pandemics/epidemics.

Oxidative stress's impact on red blood cells: Unveiling implications for health and disease.

Oxidative stress, a condition characterized by an imbalance between reactive oxygen species (ROS) production and the body's ability to detoxify them, has emerged as a pivotal factor in the pathophysiology of various diseases. Red blood cells (RBCs), essential components of the circulatory system, are particularly susceptible to oxidative damage due to their high oxygen-carrying capacity and the abundance of vulnerable biomolecules. This review comprehensively explores the intricate mechanisms underlying oxidative stress-induced damage to red blood cells and the subsequent implications for overall health and disease. We delve into the sources of ROS generation within RBCs, including metabolic processes and external factors, shedding light on the delicate redox balance that governs cellular homeostasis. The impact of oxidative stress on red blood cells extends beyond the confines of their primary physiological role, as these cells actively participate in immune responses, inflammation modulation, and nitric oxide metabolism. Consequently, understanding the implications of oxidative stress on RBCs provides valuable insights into the broader landscape of health and disease. In conclusion, this review underscores the critical role of oxidative stress in influencing red blood cell physiology and its far-reaching implications for human health. Elucidating the molecular intricacies of this relationship not only enhances our understanding of fundamental biological processes but also paves the way for the development of targeted therapeutic interventions to mitigate the adverse effects of oxidative stress on red blood cells and, by extension, on overall health.