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1.
Math Biosci Eng ; 21(2): 1979-2003, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38454671

RESUMO

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.


Assuntos
Reinfecção , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Suscetibilidade a Doenças
2.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473717

RESUMO

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.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Serotonina , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Catalepsia , Fotoperíodo , Suscetibilidade a Doenças , Plasticidade Neuronal
3.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473993

RESUMO

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.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Peixe-Zebra , Amoxicilina/metabolismo , Larva , Suscetibilidade a Doenças/metabolismo , Fígado/metabolismo
4.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474271

RESUMO

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.


Assuntos
Proteoma , Resiliência Psicológica , Ratos , Animais , Proteoma/metabolismo , Córtex Pré-Frontal/metabolismo , Isolamento Social , Fenótipo , Suscetibilidade a Doenças/metabolismo , Estresse Psicológico/metabolismo
5.
BMC Infect Dis ; 24(1): 337, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515037

RESUMO

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).


Assuntos
Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Borrelia , Doença de Lyme , Humanos , Estudo de Associação Genômica Ampla , Estudos Prospectivos , Leucócitos Mononucleares , Suscetibilidade a Doenças , Doença de Lyme/genética , Doença de Lyme/diagnóstico , Borrelia burgdorferi/genética , Citocinas/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/uso terapêutico , Grupo Borrelia Burgdorferi/genética , Secretoglobinas/genética
6.
HLA ; 103(3): e15424, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38516926

RESUMO

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.


Assuntos
Nanoporos , Humanos , Suscetibilidade a Doenças , Estudos Retrospectivos , Teste de Histocompatibilidade/métodos , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , Haplótipos , Frequência do Gene
7.
Behav Res Ther ; 176: 104503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518395

RESUMO

Given that emotion regulation difficulties confer risk for poor responses to stress, they may predict who is at risk for adverse psychological reactions to major, chronic stressors such as the COVID-19 pandemic. Specific adverse reactions to the pandemic may include more severe traumatic stress, anxiety, and excessive safety behavior use (i.e., hand washing). While emotion regulation difficulties may be a diathesis for adverse reactions to chronic stressors, the context(s) by which they may confer elevated risk is unclear. Accordingly, the present longitudinal study examined the interaction between pre-pandemic emotion regulation difficulties and early pandemic perceived stress in predicting subsequent COVID-related traumatic stress, anxiety, and safety behavior use over 32 weeks of the pandemic. Community adults (N = 145) who completed a measure of emotion regulation in 2016 as part of a larger study were recontacted at the start of the pandemic (March 2020) and assessed every two weeks for 32 weeks. Consistent with a diathesis-stress model, the interaction between difficulties in emotion regulation and perceived stress was significant in predicting COVID-19 anxiety (p = 0.003, d = 0.52) such that at high, but not low, levels of perceived stress, difficulties in emotion regulation in 2016 significantly predicted higher COVID-19 anxiety in 2020. The interaction between difficulties in emotion regulation in 2016 and perceived stress early in 2020 approached significance in predicting COVID-19 traumatic stress (p = 0.073, d = 0.31) and safety behavior use (p = 0.069, d = 0.31). These findings highlight that current perceived stress is an important context that potentiates the effects of preexisting emotion regulation difficulties on the emergence of anxiety-related symptoms during COVID-19, which has important implications for diathesis-stress models of adverse reactions to chronic stressors.


Assuntos
COVID-19 , Regulação Emocional , Adulto , Humanos , Estudos Prospectivos , Suscetibilidade a Doenças , Pandemias , Estudos Longitudinais , Ansiedade/psicologia , Estresse Psicológico/psicologia
8.
Front Immunol ; 15: 1333967, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482010

RESUMO

Introduction: The incidence of the autoimmune disease, type 1 diabetes (T1D), has been increasing worldwide and recent studies have shown that the gut microbiota are associated with modulating susceptibility to T1D. Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and is widely expressed on many cells, including dendritic cells (DCs), which are potent antigen-presenting cells (APCs). TLR5 modulates susceptibility to obesity and alters metabolism through gut microbiota; however, little is known about the role TLR5 plays in autoimmunity, especially in T1D. Methods: To fill this knowledge gap, we generated a TLR5-deficient non-obese diabetic (NOD) mouse, an animal model of human T1D, for study. Results: We found that TLR5-deficiency led to a reduction in CD11c+ DC development in utero, prior to microbial colonization, which was maintained into adulthood. This was associated with a bias in the DC populations expressing CD103, with or without CD8α co-expression, and hyper-secretion of different cytokines, both in vitro (after stimulation) and directly ex vivo. We also found that TLR5-deficient DCs were able to promote polyclonal and islet antigen-specific CD4+ T cell proliferation and proinflammatory cytokine secretion. Interestingly, only older TLR5-deficient NOD mice had a greater risk of developing spontaneous T1D compared to wild-type mice. Discussion: In summary, our data show that TLR5 modulates DC development and enhances cytokine secretion and diabetogenic CD4+ T cell responses. Further investigation into the role of TLR5 in DC development and autoimmune diabetes may give additional insights into the pathogenesis of Type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Animais , Humanos , Camundongos , Citocinas/metabolismo , Células Dendríticas , Suscetibilidade a Doenças/metabolismo , Camundongos Endogâmicos NOD , Receptor 5 Toll-Like/metabolismo
9.
J Math Biol ; 88(5): 51, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551684

RESUMO

Communities are commonly not isolated but interact asymmetrically with each other, allowing the propagation of infectious diseases within the same community and between different communities. To reveal the impact of asymmetrical interactions and contact heterogeneity on disease transmission, we formulate a two-community SIR epidemic model, in which each community has its contact structure while communication between communities occurs through temporary commuters. We derive an explicit formula for the basic reproduction number R 0 , give an implicit equation for the final epidemic size z, and analyze the relationship between them. Unlike the typical positive correlation between R 0 and z in the classic SIR model, we find a negatively correlated relationship between counterparts of our model deviating from homogeneous populations. Moreover, we investigate the impact of asymmetric coupling mechanisms on R 0 . The results suggest that, in scenarios with restricted movement of susceptible individuals within a community, R 0 does not follow a simple monotonous relationship, indicating that an unbending decrease in the movement of susceptible individuals may increase R 0 . We further demonstrate that network contacts within communities have a greater effect on R 0 than casual contacts between communities. Finally, we develop an epidemic model without restriction on the movement of susceptible individuals, and the numerical simulations suggest that the increase in human flow between communities leads to a larger R 0 .


Assuntos
Doenças Transmissíveis , Epidemias , Humanos , Modelos Epidemiológicos , Modelos Biológicos , Doenças Transmissíveis/epidemiologia , Número Básico de Reprodução , Suscetibilidade a Doenças/epidemiologia
11.
Sci Rep ; 14(1): 5973, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472283

RESUMO

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.


Assuntos
Doenças Transmissíveis , Epidemias , Humanos , Doenças Transmissíveis/epidemiologia , Surtos de Doenças/prevenção & controle , Suscetibilidade a Doenças/epidemiologia , Rede Social
12.
Sensors (Basel) ; 24(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38544259

RESUMO

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.


Assuntos
Movimento , Postura , Humanos , Idoso , Mãos , Movimento (Física) , Suscetibilidade a Doenças , Equilíbrio Postural , Cognição
13.
Sci Rep ; 14(1): 7260, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538683

RESUMO

External signs of disease are frequently used as indicators of disease susceptibility. However, immune profiling can be a more effective indicator to understand how host responses to infection may be shaped by host, pathogen and environmental factors. To better inform wildlife health assessment and research directions, we investigated the utility of a novel multivariate immunophenotyping approach examining innate and adaptive immune responses in differing climatic, pathogen co-infection and demographic contexts across two koala (Phascolarctos cinereus) populations in New South Wales: the Liverpool Plains (LP), and Southern Highlands to South-west Sydney (SHSWS). Relative to the comparatively healthy SHSWS, the LP had greater and more variable innate immune gene expression (IL-1ß, IL-6), and KoRV transcription. During extreme heat and drought, koalas from the LP displayed upregulation of a stress pathway gene and reduced adaptive immune genes expression, haematocrit and plasma protein, suggesting the possibility of environmental impacts through multiple pathways. In those koalas, KoRV transcription status, Chlamydia pecorum infection loads, and visible urogenital inflammation were not associated with immune variation, suggesting that immune markers were more sensitive indicators of real-time impacts than observed disease outcomes.


Assuntos
Infecções por Chlamydia , Chlamydia , Coinfecção , Phascolarctidae , Animais , Phascolarctidae/genética , Coinfecção/veterinária , Chlamydia/genética , Animais Selvagens , Suscetibilidade a Doenças
15.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542460

RESUMO

Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity. In this study, we applied a transcriptomic approach to investigate the genome-wide gene expression in MH-susceptible cases using muscle biopsies taken for diagnostic testing. Baseline comparisons between muscle from MH-susceptible individuals (MHS, n = 8) and non-susceptible controls (MHN, n = 4) identified 822 differentially expressed genes (203 upregulated and 619 downregulated) with significant enrichment in genes associated with oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Investigations of 10 OXPHOS target genes in a larger cohort (MHN: n = 36; MHS: n = 36) validated the reduced expression of ATP5MD and COQ6 in MHS samples, but the remaining 8 selected were not statistically significant. Further analysis also identified evidence of a sex-linked effect in SDHB and UQCC3 expression, and a difference in ATP5MD expression across individuals with MH sub-phenotypes (trigger from in vitro halothane exposure only, MHSh (n = 4); trigger to both in vitro halothane and caffeine exposure, MHShc (n = 4)). Our data support a link between MH-susceptibility and dysregulated gene expression associated with mitochondrial bioenergetics, which we speculate plays a role in the phenotypic variability observed within MH.


Assuntos
Hipertermia Maligna , Humanos , Hipertermia Maligna/genética , Hipertermia Maligna/metabolismo , Halotano/farmacologia , Halotano/metabolismo , Fosforilação Oxidativa , Cálcio/metabolismo , Músculo Esquelético/metabolismo , Suscetibilidade a Doenças/metabolismo , Biópsia , Expressão Gênica , Contração Muscular , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Proteínas de Transporte/metabolismo
16.
Math Biosci Eng ; 21(3): 4648-4668, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38549343

RESUMO

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.


Assuntos
Doenças Transmissíveis , Redes Comunitárias , Humanos , Modelos Biológicos , Doenças Transmissíveis/epidemiologia , Número Básico de Reprodução , Suscetibilidade a Doenças
17.
Methods Mol Biol ; 2756: 317-326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427302

RESUMO

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.


Assuntos
Solanum lycopersicum , Tylenchoidea , Animais , Solanum lycopersicum/genética , Tylenchoidea/genética , Raízes de Plantas/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Suscetibilidade a Doenças/metabolismo
18.
PLoS One ; 19(3): e0298932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427619

RESUMO

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.


Assuntos
Doenças Transmissíveis , Vacinas , Humanos , Doenças Transmissíveis/epidemiologia , Pandemias/prevenção & controle , Saúde Pública , Suscetibilidade a Doenças
19.
Medicine (Baltimore) ; 103(9): e37360, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38428906

RESUMO

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.


Assuntos
Eritrócitos , Estresse Oxidativo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Oxirredução , Eritrócitos/metabolismo , Suscetibilidade a Doenças
20.
Neurobiol Dis ; 193: 106457, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38423191

RESUMO

Epilepsy is a brain disorder affecting up to 1 in 26 individuals. Despite its clinical importance, the molecular mechanisms of epileptogenesis are still far from clarified. Our previous study showed that disruption of Clock in excitatory neurons alters cortical circuits and leads to generation of focal epilepsy. In this study, a GAD-Cre;Clockflox/flox mouse line with conditional Clock gene knockout in inhibitory neurons was established. We observed that seizure latency was prolonged, the severity and mortality of pilocarpine-induced seizure were significantly reduced, and memory was improved in GAD-Cre;Clockflox/flox mice. We hypothesize that mice with CLOCK knockout in inhibitory neurons have increased threshold for seizure, opposite from mice with CLOCK knockout in excitatory neurons. Further investigation showed Clock knockout in inhibitory neurons upregulated the basal protein level of ARC, a synaptic plasticity-associated immediate-early gene product, likely through the BDNF-ERK pathway. Altered basal levels of ARC may play an important role in epileptogenesis after Clock deletion in inhibitory neurons. Although sEPSCs and intrinsic properties of layer 5 pyramidal neurons in the somatosensory cortex exhibit no changes, the spine density increased in apical dendrite of pyramidal neurons in CLOCK knockout group. Our results suggest an underlying mechanism by which the circadian protein CLOCK in inhibitory neurons participates in neuronal activity and regulates the predisposition to epilepsy.


Assuntos
Epilepsia , Animais , Camundongos , Ansiedade , Suscetibilidade a Doenças/metabolismo , Epilepsia/genética , Epilepsia/metabolismo , Camundongos Knockout , Neurônios/metabolismo , Convulsões/metabolismo
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