Infection Process Research Articles

Histological Dissection of Fusarium-Banana Interaction Using a GFP-Tagged Subtropical Race 4 Strain of Fusarium oxysporum f. sp. cubense on Banana Cultivars with Differing Levels of Resistance

Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense (Foc), poses a significant threat to global banana production. This study used a GFP-tagged subtropical race 4 strain of Foc (GFP-Foc-STR4) to trace the pathogen’s movement in different banana cultivars. These include a race 4 resistant cultivar FHIA25 and the Cavendish somaclone ‘GCTCV119’, as well as susceptible cultivars including ‘Lady Finger’, ‘FHIA02’, and ‘Williams’ Cavendish. GFP localization revealed that GFP-Foc-STR4 was able to infect all tested cultivars, moving from the roots to the rhizome and aerial parts of the plant. Tyloses formation in root and rhizome vasculature, visualised with GFP autofluorescence and confirmed by scanning electron microscopy, was found to restrict Foc within the xylem vessels, slowing its spread but not fully preventing infection. This containment mechanism contributes to the host tolerance of ‘FHIA25’ and ‘GCTCV119’, though it does not confer complete immunity. The use of the fluorescently tagged Foc strain provides valuable insight into the infection process, and supports efforts in the integrated management of Fusarium wilt of banana.

Mesomycoplasma (Mycoplasma) ovipneumoniae dihydrolipoamide dehydrogenase is an immunogenic plasminogen binding protein and a putative adhesin

The interaction of Mesomycoplasma (Mycoplasma) ovipneumoniae (M. ovipneumoniae) with host cells is a pivotal step in the infection process, underlining the necessity to develop vaccines and therapeutic approaches targeting the pathogen's key invasion mechanisms. The bacterium's capacity for adherence, invasion, and subsequent evasion of the host immune response underpins its pathogenicity, rendering adherence genes feasible vaccine targets. This study focuses on pyruvate dehydrogenase complex component E3 (PdhD), a membrane-anchored surface protein implicated in these pathogenic processes. Bioinformatics analysis reveals the conservation of PdhD sequence within M. ovipneumoniae. Membrane protein extraction, immunoblotting and ELISA assay have confirmed the presence of PdhD on the M. ovipneumoniae surface and cytoplasm, suggesting its multifunctionality. Our research employed antibody inhibition assays to characterize the bacterial adhesion suppression by anti-PdhD antibodies, complemented by bactericidal complement assays, supporting its candidacy as a putative vaccine target. The ELISA binding assay substantiated that PdhD binded to plasminogen (Plg) in a dose-dependent manner. Notably, PdhD is also involved in biofilm formation. The inhibitory effect of anti-PdhD sera on biofilm formation is congruent with novel therapeutic strategies targeting related mycoplasmas. This study reports the characterization of the first virulence-associated protein PdhD of M. ovipneumoniae and suggests its potential as a vaccine target to combat M. ovipneumoniae infection.

Characterization of leukocytosis in patients with solid tumors with and without an infectious process

Introducción: La leucocitosis en el paciente oncológico con tumores sólidos constituye el segundo motivo de interconsulta y de forma general se indica la antibioticoterapia, si bien la leucocitosis es un signo común de las infecciones, particularmente bacterianas, existen otros estresores capaces de provocar una leucocitosis aguda que incluyen cirugías, ejercicio intenso, traumas, estrés emocional, neoplasias, entre otras, por lo cual la antibioticoterapia no debería generalizarse. Objetivo: Caracterizar de la leucocitosis en pacientes con tumores sólidos con y sin proceso infeccioso para quienes se solicitó, de enero de 2021 a agosto de 2023, interconsulta con Infectología del Instituto Nacional del Cáncer. Materiales y métodos: Diseño descriptivo, observacional, de corte transversal, con datos secundarios. Se procesaron datos de 144 casos de pacientes internados diagnosticados con tumores sólidos oncológicos o en espera de resultados confirmatorios, que solicitaron interconsulta con el especialista en infectología por presencia de leucocitosis en el hemograma en ausencia de clínica infecciosa o persistencia de la leucocitosis a pesar de un tratamiento antibiótico exitoso según parámetros clínicos. Se empleó la estadística descriptiva para el procesamiento de datos y se contó con aprobación del Comité de Ética del INCAN. Resultado: De los 144 pacientes, 44 (30,5%) presentaron algún proceso infeccioso evidenciable por clínica o métodos diagnósticos auxiliares. En 100 pacientes, (69,5%) no pudo evidenciarse la presencia de proceso infeccioso alguno con base en parámetros clínicos y métodos auxiliares diagnósticos. El fenómeno de leucocitosis y neutrofilia se observó en todos los casos en ambos grupos de pacientes, aun después del tratamiento con antibióticos en aquellos que lo precisaron. La trombocitosis se observó en 23/100 pacientes sin diagnóstico infeccioso (23%), versus 23/44 (52,2%) pacientes con proceso infeccioso activo. Conclusión: La reactividad leucocitaria es un fenómeno hematológico común en los procesos neoplásicos y persiste aún después de un tratamiento antibiótico exitoso. Los procesos infecciosos fueron evidentes, específicos, diversos y sin predominio significativo de alguna entidad en particular por lo que la antibioticoterapia empírica debe ser postergada.

Host-specific patterns of virulence and gene expression profiles of the broad-host-range entomopathogenic fungus Metarhizium anisopliae

Generalist pathogens with a broad host range encounter many different host environments. Such generalist pathogens are often highly versatile and adjust their expressed phenotype to the host being infected. Species in the fungal genus Metarhizium (Hypocreales: Clavicipitaceae) occupy various ecological niches, including plant rhizosphere symbionts, soil saprophytes, and insect pathogens with applications in biological control of pests. The species M. anisopliae is highly diverse combining the capability of association with plant roots and infection of a broad range of arachnid and insect hosts, from agricultural pests to vectors of human disease. It is among the most studied and applied biological control agents worldwide. Here, we investigate the phenotypic plasticity and differential gene expression of M. anisopliae blastospores during infection of different insect hosts. First, the virulence of M. anisopliae blastospores was evaluated against Tenebrio molitor (Coleoptera: Tenebrionidae), Spodoptera frugiperda (Lepidoptera: Noctuidae), Gryllus assimilis (Orthoptera: Gryllidae), and Apis mellifera (Hymenoptera: Apidae). Second, the percentage of appressorium formation on the membranous wings of the four hosts was determined, and third, the fungal transcriptome profile during penetration on the hosts was analyzed. Our findings reveal that M. anisopliae blastospores exhibit high virulence against Tenebrio molitor, with significantly higher appressorium formation on beetle wings compared to the other three tested insects. We also document distinct gene expression patterns in M. anisopliae blastospores during insect infection of T. molitor, S. frugiperda, and A. mellifera, with notable variations observed in G. assimilis. These differences are associated with the expression of enzymes involved in the degradation of specific compounds present in each insect wing, as well as hydrophobins, destruxins, and specialized metabolites related to virulence. The study emphasizes the differences in fungal gene expression during infection of the four insect orders and highlights the virulence-related genes specific to each infective process.

Spontaneous resolution of a giant bulla in a patient presenting with COVID-19 with presumed superadded bacterial infection.

Bullous emphysema is a chronic disease characterized by bullae, or air spaces in the lungs. Giant bullae exceed one-third of the hemithorax volume and are usually treated via bullectomy. We present the case of a 35-year-old man who presented to hospital with a history of COVID-19 infection and seven days of chest pain and dyspnoea. A giant left upper lobe fluid-filled bulla was identified on computed tomography. He was discharged with a course of antibiotics. A radiograph performed one month after presentation revealed an unchanged giant bulla. However, a chest radiograph and computed tomography nine months after initial presentation showed complete spontaneous resolution of the bulla. Bullectomy was deemed unnecessary. Cases of spontaneous bullae resolution, or autobullectomy, are rare. Our case implicates the role of infectious processes in autobullectomy. Serial imaging monitoring and delayed cardiothoracic assessment may be prudent to assess bullectomy necessity.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort

IntroductionBiological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. MethodsMulticenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included.Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients’ colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). ResultsA total of 1090 patients were included. After induction, at approximately 12–14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response.At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab – 9 patients (37.5%) – compared to the other biological treatments analyzed.With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments.As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. ConclusionsBiological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy.In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

Structure-function mapping and mechanistic insights on the SARS CoV2 Nsp1.

Non-structural protein 1 (Nsp1) is a key component of the infectious process caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), responsible for the COVID-19 pandemic. Our previous data demonstrated that Nsp1 can degrade both RNA and DNA in the absence of the ribosome, a process dependent on the metal ions Mn2+, Ca2+, or Mg2+ (Salgueiro et al., SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease. Biometals. 2024;37:1127-1146). The protein is composed of two structural domains: the N-terminal domain (NTD) and C-terminal domain (CTD), connected by a loop. To elucidate the function of each structural domain, we generated four truncated versions of Nsp1 containing either the NTD or the CTD. Our results indicate that the Nsp1SARS-CoV2 domains play distinct functional roles. Specifically, the NTD is involved in nucleotide binding and regulation, while the CTD acts as the catalytic domain. Moreover, a tyrosyl radical was detected during the nuclease activity, and an in-depth analysis of the different constructs suggested that Y136 could be involved in this process. Indeed, our results show that Y136F Nsp1 variant lacks DNA nuclease activity but retains its RNA nuclease activity. Furthermore, we observed that the CTD has a propensity to associate with hydrophobic environments, suggesting that it might associate with cell membranes. However, the cellular function of this association requires further investigation. This study sheds light on the functions of the individual domains of Nsp1, providing valuable insights into its mechanism of action in Coronaviruses.

Renormalisation group methods for effective epidemiological models

Epidemiological models describe the spread of an infectious disease within a population. They capture microscopic details on how the disease is passed on among individuals in various different ways, while making predictions about the state of the entirety of the population. However, the type and structure of the specific model considered typically depend on the size of the population under consideration. To analyse this effect, we study a family of effective epidemiological models in space and time that are related to each other through scaling transformations. Inspired by a similar treatment of diffusion processes, we interpret the latter as renormalisation group transformations, both at the level of the underlying differential equations and their solutions. We show that in the large scale limit, the microscopic details of the infection process become irrelevant, safe for a simple real number, which plays the role of the infection rate in a basic compartmental model.

Evaluation of Certification Board of Infection Control and Epidemiology, Inc. Certification in Infection Control (CIC) Examination Rates

BackgroundInfection Prevention professionals develop through training and certification practices, with the Certified in Infection Control and Epidemiology (CIC®) exam being the industry standard for infection prevention and control expertise. MethodsThis study conducted a secondary analysis of Certification Board of Infection Control and Epidemiology, Inc. (CBIC) exam scores from 2013-2022. Reliability coefficients, Spearman-Brown coefficients, and Standard Error Measurement (SEM) averages were calculated for the CIC® exam’s eight objective areas from 2016-2022. ResultsOver the past decade, pass rates varied from 57.30% to 85.40%, with a mean of 69.7%. The number of exam participants ranged from 574 to 1,392. Despite the variability, the highest reliability, Spearman-Brown, and SEM averages were consistently observed in areas such as identifying infectious disease processes, surveillance, epidemiological investigation, and controlling transmission of infectious agents. ConclusionAs more facilities push for certification, the number of CIC® exam takers has increased. However, the evolving nature of infection prevention and the lack of a standardized training track contribute to variations in reliability coefficients across the exam's objective areas.

National Multicenter Study on the Prevalence of Carbapenemase-Producing Enterobacteriaceae in the Post-COVID-19 Era in Argentina: The RECAPT-AR Study

The COVID-19 pandemic has exacerbated the global antimicrobial resistance (AMR) crisis. Consequently, it is more urgent than ever to prioritize AMR containment and support countries in improving the detection, characterization, and rapid response to emerging AMR threats. We conducted a prospective, multicenter study to assess the prevalence of carbapenemase-producing Enterobacterales in infectious processes in Argentina during the post-COVID-19 pandemic period and explore therapeutic alternatives for their treatment (RECAPT-AR study). Methods: A total of 182 hospitals participated by submitting Enterobacterales clinical isolates to the National Reference Laboratory (NRL) during the first three weeks of November 2021. Inclusion criteria were defined as an ertapenem MIC ≥ 0.5 mg/L, a zone diameter ≤ 22 mm. Carbapenemase genes and those coding for major extended-spectrum β-lactamases were molecularly characterized using multiplex PCR at the NRL. Antibiotic susceptibility testing followed international standards (CLSI and EUCAST). Results: The NRL analyzed 821 Enterobacterales isolates. Metallo-β-lactamase (MBL, 42.0%) and KPC (39.8%) accounted for 81.8% of carbapenemases, followed by OXA-163 (7.4%), a variant of OXA-48 with additional activity against extended-spectrum cephalosporins, and enzyme combinations (8.3%). These combinations included NDM plus KPC (3.4%), OXA-163 plus KPC (2.4%), and OXA-163 plus NDM (2.1%). Klebsiella pneumoniae was the main species recovered, representing 76% of the isolates. According to the carbapenemase classes or combinations, tigecycline exhibited a susceptibility range of 33–83%, fosfomycin 59–81%, colistin 27–78%, and amikacin 17–81%. Ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) showed 92% and 98% susceptibility against serine carbapenemases, respectively. Meanwhile, aztreonam-avibactam (AZA) exhibited 96–98% susceptibility against all carbapenemase classes. Conclusions: A new epidemiological landscape has emerged, characterized by the equivalent circulation of NDM and KPC. K. pneumoniae remains the primary species responsible for their dissemination. The co-production of carbapenemase combinations, particularly KPC plus NDM, was confirmed, mainly in K. pneumoniae. High activity was observed for AZA against MBLs and for CZA and IMR against KPC and OXA-163 carbapenemases.

Coronavirus nucleocapsid protein enhances the binding of p-PKCα to RACK1: Implications for inhibition of nucleocytoplasmic trafficking and suppression of the innate immune response.

The hallmark of coronavirus infection lies in its ability to evade host immune defenses, a process intricately linked to the nuclear entry of transcription factors crucial for initiating the expression of antiviral genes. Central to this evasion strategy is the manipulation of the nucleocytoplasmic trafficking system, which serves as an effective target for the virus to modulate the expression of immune response-related genes. In this investigation, we discovered that infection with the infectious bronchitis virus (IBV) dynamically impedes the nuclear translocation of several transcription factors such as IRF3, STAT1, STAT2, NF-κB p65, and the p38 MAPK, leading to compromised transcriptional induction of key antiviral genes such as IFNβ, IFITM3, and IL-8. Further examination revealed that during the infection process, components of the nuclear pore complex (NPC), particularly FG-Nups (such as NUP62, NUP153, NUP42, and TPR), undergo cytosolic dispersion from the nuclear envelope; NUP62 undergoes phosphorylation, and NUP42 exhibits a mobility shift in size. These observations suggest a disruption in nucleocytoplasmic trafficking. Screening efforts identified the IBV nucleocapsid (N) protein as the agent responsible for the cytoplasmic distribution of FG-Nups, subsequently hindering the nuclear entry of transcription factors and suppressing the expression of antiviral genes. Interactome analysis further revealed that the IBV N protein interacts with the scaffold protein RACK1, facilitating the recruitment of activated protein kinase C alpha (p-PKCα) to RACK1 and relocating the p-PKCα-RACK1 complex to the cytoplasm. These observations are conserved across diverse coronaviruses N proteins. Concurrently, the presence of both RACK1 and PKCα/β proved essential for the phosphorylation and cytoplasmic dispersion of NUP62, the suppression of antiviral cytokine expression, and efficient virus replication. These findings unveil a novel, highly effective, and evolutionarily conserved mechanism.

Visualizing the Internalization of Marburg Viruslike Particles into Living Cells.

Viral entry into cells is a pivotal stage of the infection process and, therefore, a prime target for the development of antiviral therapeutics. Here, we describe a system to monitor the internalization of lipophilic dye-labeled Marburg viruslike particles (VLPs) into living cells. Using cells stably expressing fluorescent protein-fused markers for specific cell organelles, the VLP entry process can be visualized. This procedure enables the characterization of the entry process by visualizing individual steps using specific bio-probes. Additionally, when combined with image analysis, this method allows for the quantification of the efficiencies of individual entry steps including particle adsorption, uptake by endocytosis, and membrane fusion. Finally, this method can be used for antiviral drug screening.

Role of UeMsb2 in Filamentous Growth and Pathogenicity of Ustilago esculenta

Ustilago esculenta is a dimorphic fungus that specifically infects Zizania latifolia, causing stem swelling and the formation of an edible fleshy stem known as jiaobai. The pathogenicity of U. esculenta is closely associated with the development of jiaobai and phenotypic differentiation. Msb2 acts as a key upstream sensor in the MAPK (mitogen-activated protein kinase) signaling pathway, playing critical roles in fungal hyphal growth, osmotic regulation, maintenance of cell wall integrity, temperature adaptation, and pathogenicity. In this study, we cloned the UeMsb2 gene from U. esculenta (GenBank No. MW768949). The open reading frame of UeMsb2 is 3015 bp in length, lacks introns, encodes a 1004-amino-acid protein with a conserved serine-rich domain, and is localized to the vacuole. Expression analysis revealed that UeMsb2 is inducibly expressed during both hyphal growth and infection processes. Deletion of UeMsb2 did not affect haploid morphology or growth rate in vitro but significantly impaired the strain’s mating ability, suppressed filamentous growth, slowed host infection progression, and downregulated the expression of b signaling pathway genes associated with pathogenicity. Notably, the deletion of UeMsb2 did not influence the in vitro growth of U. esculenta under hyperosmotic, thermal, or oxidative stress conditions. These findings underscore the critical role of UeMsb2 in regulating the pathogenicity of U. esculenta. This study provides insights into the interaction between U. esculenta and Z. latifolia, particularly the mechanisms that drive host stem swelling.

Hyaluronan Scaffold Decorated with Bifunctional Peptide Promotes Wound Healing via Antibacterial and Anti-Inflammatory.

The invasion of bacteria and inflammation impeded infected wounds heal. Here, a hyaluronan-based scaffold (HAG-g-C) was designed by cross-linking with gallic acid-modified gelatin to provide a protein microenvironment and decorated with cathelicidin-BF (CBF), a natural antimicrobial peptide, to remove bacterial infections and reverse the inflammatory environment. In vitro, HAG-g-C presented an antibacterial effect on Staphylococcus aureus and Escherichia coli. Meanwhile, it could drive the phenotypic switch of macrophage from M1 to M2 to accelerate tissue remodeling. In a mouse model of S. aureus-infected total skin defects, HAG-g-C inhibited the process of infection at the beginning of the wound and then regulated the M1 macrophage transformed to M2 phenotype on day 12. In addition, HAG-g-C induced collagen deposition, and reduced the expression of TNF-α, thereby significantly accelerating the reconstruction of infected wounds.

Analysis of the incidence of influenza and acute upper respiratory tract infections under conditions of routine influenza vaccination

Background. Acute upper respiratory tract infections and influenza, while maintaining high epidemiological, social and economic significance, have a major effect on the public health of countries and individual regions.The aim. To study the impact of influenza vaccination on the manifestations of the epidemic process of influenza and acute upper respiratory tract infections in the Irkutsk region.Materials and methods. Epidemiological analysis of the incidence of acute upper respiratory tract infections and influenza, analysis of influenza mortality and the impact of vaccination on these infections were performed using continuous samples of statistical data from the Directorate of Rospotrebnadzor in the Irkutsk Region for the period of 2003–2022 (forms 2, 5).Results. The intensity of the epidemic process of acute upper respiratory tract infections among the general population, children and adults during the observation period was characterized by an uneven course with a tendency towards increase. The dynamics of the incidence of acute upper respiratory tract infections in children and adults demonstrates multidirectional trends over the compared periods. The incidence of influenza in the general population had a steady downward trend, the decrease rate was –8.4 %. At the same time, there are significant changes in the intensity of the epidemic process in the compared periods. The proportion of adults increased in the structure of cases of acute upper respiratory tract infections, and the proportion of children increased in the structure of cases of influenza. Significant changes in the epidemic seasons of influenza are shown. Since the beginning of routine influenza vaccination in the region, the number of vaccinated people has increased annually – from 23.6 to 61.7 % of the population. Against the background of the influenza vaccination campaign, a statistically significant decrease in the incidence of acute upper respiratory tract infections among the general population and children under 14 years of age was registered (p &lt; 0.01).Conclusion. In the Irkutsk region, the epidemiological disadvantage for the studied infections persists. Increasing the regulated indicators of population coverage with preventive influenza vaccinations (75 % and more) will help reduce the incidence rate.

MiR-PC-3p-241582_34 Contributes to the Infection of Athetis lepigone by Regulating the Expression of HSWP4 in Nosema bombycis.

Athetis lepigone is a recurring pest in the maize seedling stage under the wheat-maize no-tillage direct seeding system in China's summer maize region. Our previous research identified a highly pathogenic Nosema bombycis to A. lepigone, which spore wall protein plays an important role in the infection process. However, the regulatory mechanism of this spore wall protein is still unclear. In this study, we explored the regulatory mechanism of miRNAs on spore wall proteins. Transcriptome sequencing results showed that expression of the spore wall protein, HSWP4, significantly increased in the germination group compared to dormancy group. Silencing of HSWP4 reduced the number of microsporidian spores breaking through the midgut wall cells of A. lepigone. Association analysis of small RNA and mRNA revealed that the targeting site of miR-PC-3p-241582_34 on HSWP4 was located in the CDS region, and miR-PC-3p-241582_34 had a significant negative regulatory relationship with HSWP4. The dual luciferase reporter assay demonstrated that miR-PC-3p-241582_34 significantly affected the luciferase activity of the HSWP4-3'UTR expression vector (P < 0.05). Delivery of miRNA mimics decreased the expression of HSWP4 and inhibited the behavior of microsporidian spores breaking through the midgut wall of A. lepigone. On the other hand, delivery of inhibitors produced opposite results, indicating that the miR-HSWP4 pathway plays an important role in microsporidian infection of A. lepigone. This study provides a new theoretical basis for understanding the pathogenic mechanism and gene regulation of microsporidia, as well as for the green control of A. lepigone.

Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni.

Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC). Herein, we reanalyzed the transcriptomic data from PBMC obtained from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination and Day 7 post-challenge). In addition, we generated new data on PBMC collected 35days after infection. Deconvolution analysis was performed to estimate immune cell composition by CIBERSORTx. Gene co-expression networks and over-representation analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING, and the hub proteins for each module were identified using Cytoscape. Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to a Th2 immune response, and a second module (M6) associated with the vaccination process, displaying pathways related to a Th1 response, CD8 + T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2 as hubs, while module M6, associated with vaccination, disclosed Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21 as hub proteins. Our data point to the potentiald role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21).

Stability and Bifurcation Analysis for the Transmission Dynamics of Skin Sores with Time Delay

Impetigo is a highly contagious skin infection that primarily affects children and communities in low-income regions and has become a significant public health issue impacting both individuals and healthcare systems. A nonlinear deterministic model based on the transmission dynamics of skin sores (impetigo) is developed with a specific emphasis on the time delay effects in the infection and recovery processes. To address this complexity, we introduce a delay differential equation (DDE) to describe the dynamic process. We analyzed the existence of Hopf bifurcations associated with the two equilibrium points and examined the mechanisms underlying the occurrence of these bifurcations as delays exceeded certain critical values. To obtain more comprehensive insights into this phenomenon, we applied the center manifold theory and the normal form method to determine the direction and stability of Hopf bifurcations near bifurcation curves. This research not only offers a novel theoretical perspective on the transmission of impetigo but also lays a significant mathematical foundation for developing clinical intervention strategies. Specifically, it suggests that an increased time delay between infection and isolation could lead to more severe outbreaks, further supporting the development of more effective intervention approaches.

Accuracy of Mentzer index for predicting iron deficiency anemia in adults

Background: It is of great clinical significance to differentiate between causes of microcytic, hypo chromatic anemias, iron deficiency anemia being one of them as it will improve with iron supplements. Complete blood picture is unable to differentiate. Iron studies and Hemoglobin electrophoresis are expensive tests. This necessitates the need of a cost-effective test and therefore we tried to determine the effectiveness of mentzer index in predicting iron deficiency anemia. Methods: It was an Observational, Cross-sectional study, conducted in Department of General Medicine, Federal government polyclinic hospital, Islamabad. Patients with microcytic hypochromic anemia, both from indoor and outdoor were included in study. Iron deficiency Anemia was diagnosed by iron studies (serum ferritin, Serum Iron, TIBC and transferrin saturation) and then mentzer index was calculated to check accuracy. Patient with normocytic or macrocytic anemia or other cell lines deficiency, patients with infectious diseases or inflammatory process were excluded from study. Results: A total of 155 patients were included in the study. Out of all the patients 145(93.5%) had mentzer index of &gt; 13 while 10(6.5%) had mentzer index of &lt;13. All of 150 patients (100%) had transferrin saturation lessthan 20 % indicating iron deficiency anemia against 93.5% picked up by Mentzer index. The receiver operator curves (ROC) showed that the MCV was the most important predictor of anemia while calculating mentzer index. The AUC value for MCV was 0.886(CI: 95%, 0.806-0.966, p value &lt;0.000). MCV value between 52.6 to 63.5 fl predicted that the Mentzer index would be above 13, thus suggesting iron deficiency anemia with a sensitivity of more than 86%. Conclusion: Study findings support the use of Mentzer index, particularly MCV, as a valuable tool for predicting iron deficiency anemia.

Skin fragility in autoimmune blistering diseases of the skin

In many disorders, skin and/or mucosal changes are dominated by blisters, wounds, or erosions. While these changes can be observed during infective, traumatic, metabolic, or inflammatory processes, these are normally clinical hallmarks of the disruption of the cytoarchitectural stability of the skin. Several proteins, such as those located in the dermal-epidermal junction zone and forming the hemidesmosomes, or those forming epidermal desmosomes are crucial for the maintenance of skin integrity. Defective function may be genetically determined due to impaired or absent production of specific proteins (i.e., epidermolysis bullosa) or due to autoimmune disorders that lead to the production of autoreactive antibodies targeting desmosomal or hemidesmosomal skin antigens. The latter group of diseases are classically named autoimmune blistering diseases of the skin. These can be divided in the pemphigoid group, where antigens are components of the hemidesmosomes, and pemphigus group, where desmosomal proteins are targeted. In this review, we provide ashort vademecum of autoimmune skin disorders that are associated with skin fragility.