The role of immunoglobulin transport receptor, neonatal Fc receptor in mucosal infection and immunity and therapeutic intervention.

The neonatal Fc receptor (FcRn) can transport IgG and antigen-antibody complexes participating in mucosal immune responses that protect the host from most pathogens' invasion via the respiratory, digestive, and urogenital tracts. FcRn expression can be triggered upon stimulation with pathogenic invasion on mucosal surfaces, which may significantly modulate the innate immune response of the host. As an immunoglobulin transport receptor, FcRn is implicated in the pathophysiology of immune-related diseases such as infection and autoimmune disorders. In this review, we thoroughly summarize the recent advancement of FcRn in mucosal immunity and its therapeutic strategy. This includes insights into its regulation mechanisms of FcRn expression influenced by pathogens, its emerging role in mucosal immunity and its potential probability as a therapeutic target in infection and autoimmune diseases.

Ginsenoside Rg5, a potent agonist of Nrf2, inhibits HSV-1 infection-induced neuroinflammation by inhibiting oxidative stress and NF-κB activation.

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.

Manifestations of coronavirus infection disease-19 in anterior eye segment: An up-to-date review.

Coronavirus infection disease-19 (COVID-19) is a worldwide catastrophic emergency that first appeared in late 2019, in Wuhan, China. COVID-19 is a multitropism disease that first affects lung tissue. However, extrapulmonary manifestations have been suspected from the first COVID-19 cases. The ocular signs and symptoms were from the early changes that occur during the course of the disease. Changes in the anterior eye segment have a relatively higher incidence than the posterior eye segment. Of which, conjunctivitis, COVID-19 pharyngioceratoconjuctivitis, iridocyclitis, corneal punctate epitheliopathy, and pathomorphological changes in the physio-anatomy of the anterior eye segment. The potential pathogenesis includes direct penetration of the virus into the eye (conjunctiva, lumbus, and cornea) or due to a systemic pathway through viremia, as well as due to autoimmune antibodies against the ocular structure (immune privilege). The presence of ocular manifestations of the external anterior fibrous layer suggests a mild course of the disease.

Building citizen science intelligence for outbreak preparedness and response: a mixed-method study in nine countries to assess knowledge, readiness and feasibility.

INTRODUCTION: Citizen science (CS) is an emerging approach in public health to harness the collective intelligence of individuals to augment traditional scientific efforts. However, citizens' viewpoint, especially the hard-to-reach population, is lacking in current outbreak-related literature. We aim to understand the awareness, readiness and feasibility of outbreak-related CS, including digitally enabled CS, in low-income and middle-income countries. METHODS: This mixed-method study was conducted in nine countries between October 2022 and June 2023. Recruitment through civil society targeted the general population, marginalised/indigenous groups, youth and community health workers. Participants (aged ≥18 years) completed a quantitative survey, and a subset participated in focus group discussions (FGDs). RESULTS: 2912 participants completed the survey and 4 FGDs were conducted in each country. Incorporating participants' perspectives, CS is defined as the practice of active public participation, collaboration and communication in all aspects of scientific research to increase public knowledge, create awareness, build trust and facilitate information flow between citizens, governments and scientists. In Bangladesh, Indonesia, the Philippines, Cameroon and Kenya, majority were unaware of outbreak-related CS. In India and Uganda, majority were aware but unengaged, while in Nepal and Zimbabwe, majority participated in CS before. Engagement approaches should consider different social and cultural contexts, while addressing incentivisation, attitudes and practicality factors. Overall, 76.0% expressed interest in digital CS but needed training to build skills and confidence. Digital CS was perceived as convenient, safer for outbreak-related activities and producing better quality and quantity of data. However, there were concerns over non-inclusion of certain groups, data security and unclear communication. CONCLUSION: CS interventions need to be relatable and address context-specific factors influencing CS participation. Digital CS has the potential to facilitate collaboration, but capacity and access issues must be considered to ensure inclusive and sustainable engagement.

Early Biofilm Formation on the Drain Tip after Total Knee Arthroplasty Is Not Associated with Prosthetic Joint Infection: A Pilot Prospective Case Series Study of a Single Center.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication of arthroplasties that could occur during the surgery. The purpose of this study was to analyze the biofilm formation through microbiological culture tests and scanning electron microscopy (SEM) on the tip of surgical drainage removed 24 h after arthroplasty surgery. METHODS: A total of 50 consecutive patients were included in the present prospective observational study. Drains were removed under total aseptic conditions twenty-four hours after surgery. The drain tip was cut in three equal parts of approximately 2-3 cm in length and sent for culture, culture after sonication, and SEM analysis. The degree of biofilm formation was determined using a SEM semi-quantitative scale. RESULTS: From the microbiological analysis, the cultures of four samples were positive. The semi-quantitative SEM analysis showed that no patient had grade 4 of biofilm formation. A total of 8 patients (16%) had grade 3, and 14 patients (28%) had grade 2. Grade 1, scattered cocci with immature biofilm, was contemplated in 16 patients (32%). Finally, 12 patients (24%) had grade 0 with a total absence of bacteria. During the follow-up (up to 36 months), no patient showed short- or long-term infectious complications. CONCLUSIONS: Most of the patients who underwent primary total knee arthroplasty (TKA) showed biofilm formation on the tip of surgical drain 24 h after surgery even though none showed a mature biofilm formation (grade 4). Furthermore, 8% of patients were characterized by a positivity of culture analysis. However, none of the patients included in the study showed signs of PJI up to 3 years of follow-up.

Assessing the effectiveness of the expanded hepatitis A vaccination program in China: an interrupted time series design.

INTRODUCTION: China initialised the expanded hepatitis A vaccination programme (EHAP) in 2008. However, the effectiveness of the programme remains unclear. We aimed to comprehensively evaluate the effectiveness of EHAP in the country. METHODS: Based on the provincial data on the incidence of hepatitis A (HepA), the population and meteorological variables in China, we developed interrupted time series (ITS) models to estimate the effectiveness of EHAP with the autocorrelation, seasonality and the meteorological confounders being controlled. Results were also stratified by economic zones, age groups and provinces. RESULTS: We found a 0.9% reduction (RR=0.991, 95% CI: 0.990 to 0.991) in monthly HepA incidence after EHAP, which was 0.3% greater than the reduction rate before EHAP in China. Across the three economic regions, we found a 1.1% reduction in HepA incidence in both central and western regions after EHAP, which were 0.3% and 1.2% greater than the reduction rates before EHAP, respectively. We found a decreased reduction rate for the eastern region. In addition, we found generally increased reduction rate after EHAP for age groups of 0-4, 5-14 and 15-24 years. However, we found decreased reduction rate among the 25-64 and ≥65 years groups. We found a slight increased rate after EHAP in Shanxi Province but not elsewhere. CONCLUSION: Our finding provides comprehensive evidence on the effectiveness of EHAP in China, particularly in the central and western regions, and among the population aged 0-24 years old. This study has important implications for the adjustment of vaccination strategies for other regions and populations.

Understanding the factors affecting global political priority for controlling sexually transmitted infections: a qualitative policy analysis.

INTRODUCTION: Sexually transmitted infections (STIs) are a significant public health challenge, but there is a perceived lack of political priority in addressing STIs as a global health issue. Our study aimed to understand the determinants of global political priority for STIs since the 1980s and to discern implications for future prioritisation. METHODS: Through semistructured interviews from July 2021 to February 2022, we engaged 20 key stakeholders (8 women, 12 men) from academia, United Nations agencies, international non-governmental organisations, philanthropic organisations and national public health agencies. A published policy framework was employed for thematic analysis, and findings triangulated with relevant literature and policy documents. We examined issue characteristics, prevailing ideas, actor power dynamics and political contexts. RESULTS: A contrast in perspectives before and after the year 2000 emerged. STI control was high on the global health agenda during the late 1980s and 1990s, as a means to control HIV. A strong policy community agreed on evidence about the high burden of STIs and that STI management could reduce the incidence of HIV. The level of importance decreased when further research evidence did not find an impact of STI control interventions on HIV incidence. Since 2000, cohesion in the STI community has decreased. New framing for broad STI control has not emerged. Interventions that have been funded, such as human papillomavirus vaccination and congenital syphilis elimination have been framed as cancer control or improving newborn survival, rather than as STI control. CONCLUSION: Globally, the perceived decline in STI control priority might stem from discrepancies between investment choices and experts' views on STI priorities. Addressing STIs requires understanding the intertwined nature of politics and empirical evidence in resource allocation. The ascent of universal health coverage presents an opportunity for integrated STI strategies but high-quality care, sustainable funding and strategic coordination are essential.

COVID-19 epidemic in Panama.

Objective: It is necessary to establish the evolution that the pandemic has had in Panama by weeks and months and to clearly establish the existence of surges or peaks, according to cases and deaths and the relationship with age groups. Methodology: We conducted a retrospective cohort study of all confirmed COVID-19 cases reported by the Ministry of Health of Panama during the first 3 years of the epidemic (March 9, 2020, March 11, 2023). All cases were obtained from information provided by the Ministry of Health. We obtained daily information of the population at the national level reported as new cases, deaths, admission to hospitals, admission to intensive care units and by age groups. The information is classified by epidemiological week and by month from the diagnosis of the first case until March 2023. Results: During the three years of the study, 1,032,316 cases of COVID-19 were registered in the Republic of Panama, and the number of deaths reported was 8,621, for a fatality rate of 0.83 % throughout that period. The number of deaths decreased over the 3 years of the pandemic; however, similar to the cases, there were periods of surges (peaks) per year in June/July and in December/January. The lethality progressively increased according to the age of the affected patients. During the first year, the lethality in those under 20 years of age was 0.05 %, and in those over 80 years old, it was 17.54 %. This pattern was maintained during the second year; however, there was a large decrease in all age groups. Conclusion: the highest lethality rate in Panama occurred in the first year of the pandemic, with a great decrease in the third year; the impact of lethality is proportional to the age of the individual, with a high possibility of death in those over 80 years of age. During each pandemic year, there are two peaks (surges of new cases and deaths) per year, which are important times to take into account to generate strategies aimed at reducing the impact.

Effects of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans on Modeling Subgingival Microbiome and Impairment of Oral Epithelial Barrier.

Periodontitis is an exemplar of dysbiosis associated with the coordinated action of multiple members within the microbial consortium. The polymicrobial synergy and dysbiosis hypothesis proposes a dynamic host-microbiome balance, with certain modulators capable of disrupting eubiosis and driving shifts towards dysbiosis within the community. However, these factors remain to be explored. We established a Porphyromonas gingivalis- or Aggregatibacter actinomycetemcomitans-modified subgingival microbiome model and 16S rRNA sequencing revealed that P. gingivalis and A. actinomycetemcomitans altered the microbiome structure and composition indicated by α and ß diversity metrics. P. gingivalis increased the subgingival dysbiosis index (SDI), while A. actinomycetemcomitans resulted in a lower SDI. Furthermore, P. gingivalis-stimulated microbiomes compromised epithelium function and reduced expression of tight junction proteins, whereas A. actinomycetemcomitans yielded mild effects. In conclusion, by inoculating P. gingivalis, we created dysbiotic microcosm biofilms in vitro resembling periodontitis-related subgingival microbiota, exhibiting enhanced dysbiosis and impaired epithelium integrity.

Microbially produced fertilizer provides rhizobacteria to hydroponic tomato roots by forming beneficial biofilms.

Hydroponic cultivation of Solanum lycopersicum (tomato) is important, and high tomato production depends on the use of nitrogen and phosphate fertilizers. We had developed a microbial fertilizer (MF), which is mainly composed of nitrate. To investigate the effect of MF on plant growth, hydroponic tomato was grown with MF or commercial inorganic fertilizer (IF), and the microbiomes of the rhizosphere and the liquid phase were analyzed by confocal microscopy and high-throughput sequencing. Plant biomass and biofilm formation were increased by growth in MF compared to IF. The microbial community structures of tomato roots and hydroponic water differed between the two conditions, and three operational taxonomic units (OTUs) dominated in plants grown with MF. The three OTUs were related to Rudaea spp., Chitinophaga spp., and Stenotrophobacter terrae, which are reported to be disease-suppressive epiphytic or endophytic microbes of plant roots. Because these three OTUs also predominated in the MF itself, they were likely provided to the rhizosphere or endophytic environments of tomato roots via hydroponic water. KEY POINTS: • Microbial fertilizer for hydroponic growth enhanced biofilm formation on tomato root. • Microbial fertilizer contains tomato-root epiphytic or endophytic microbes. • Microbial fertilizer provided beneficial microbes to the rhizosphere and endophytic environments of tomato roots via hydroponic water.

Genotypic characteristics of Uropathogenic Escherichia coli isolated from complicated urinary tract infection (cUTI) and asymptomatic bacteriuria-a relational analysis.

Background: Uropathogenic Escherichia coli (UPEC) is the predominant agent causing various categories of complicated urinary tract infections (cUTI). Although existing data reveals that UPEC harboured numerous virulence determinants to aid its survival in the urinary tract, the reason behind the occurrence of differences in the clinical severity of uninary tract infections (UTI) demonstrated by the UPEC infection is poorly understood. Therefore, the present study aims to determine the distribution of virulence determinants and antimicrobial resistance among different phylogroups of UPEC isolated from various clinical categories of cUTI and asymptomatic bacteriuria (ASB) E. coli isolates. The study will also attempt a relational analysis of the genotypic characteristics of cUTI UPEC and ASB E. coli isolates. Methods: A total of 141 UPEC isolates from cUTI and 160 ASB E. coli isolates were obtained from Universiti Malaya Medical Centre (UMMC). Phylogrouping and the occurrence of virulence genes were investigated using polymerase chain reaction (PCR). Antimicrobial susceptibility of the isolates to different classes of antibiotics was determined using the Kirby Bauer Disc Diffusion method. Results: The cUTI isolates were distributed differentially among both Extraintestinal Pathogenic E. coli (ExPEC) and non-ExPEC phylogroups. Phylogroup B2 isolates were observed to possess the highest average aggregative virulence score (7.17), a probable representation of the capability to cause severe disease. Approximately 50% of the cUTI isolates tested in this study were multidrug resistant against common antibiotics used to treat UTI. Analysis of the occurrence of virulence genes among different cUTI categories demonstrated that UPEC isolates of pyelonephritis and urosepsis were highly virulent and had the highest average aggregative virulence scores of 7.80 and 6.89 respectively, compared to other clinical categories. Relational analysis of the occurrence of phylogroups and virulence determinants of UPEC and ASB E. coli isolates showed that 46.1% of UPEC and 34.3% of ASB E. coli from both categories were distributed in phylogroup B2 and had the highest average aggregative virulence score of 7.17 and 5.37, respectively. The data suggest that UPEC isolates which carry virulence genes from all four virulence genes groups studied (adhesions, iron uptake systems, toxins and capsule synthesis) and isolates from phylogroup B2 specifically could predispose to severe UTI involving the upper urinary tract. Therefore, specific analysis of the genotypic characteristics of UPEC could be further explored by incorporating the combination of virulence genes as a prognostic marker for predicting disease severity, in an attempt to propose a more evidence driven treatment decision-making for all UTI patients. This will go a long way in enhancing favourable therapeutic outcomes and reducing the antimicrobial resistance burden among UTI patients.

Role of phytocompounds as the potential anti-viral agent: an overview.

Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.

Molecular mechanisms and cellular functions of liquid-liquid phase separation during antiviral immune responses.

Spatiotemporal separation of cellular components is vital to ensure biochemical processes. Membrane-bound organelles such as mitochondria and nuclei play a major role in isolating intracellular components, while membraneless organelles (MLOs) are accumulatively uncovered via liquid-liquid phase separation (LLPS) to mediate cellular spatiotemporal organization. MLOs orchestrate various key cellular processes, including protein localization, supramolecular assembly, gene expression, and signal transduction. During viral infection, LLPS not only participates in viral replication but also contributes to host antiviral immune responses. Therefore, a more comprehensive understanding of the roles of LLPS in virus infection may open up new avenues for treating viral infectious diseases. In this review, we focus on the antiviral defense mechanisms of LLPS in innate immunity and discuss the involvement of LLPS during viral replication and immune evasion escape, as well as the strategy of targeting LLPS to treat viral infectious diseases.

Does obesity related eating behaviors only affect chronic diseases? A nationwide study of university students in China.

The primary aims of this study are to examine associations between obesity-related eating behaviors (OEB) and chronic and infectious diseases, and mental disorders. A representative nationwide survey was used to collect information among 11,659 medical students from 31 universities in China. Multiple variable logistic regression analysis was conducted to examine the associations between OEB and the diseases. The multiple variable logistic regression model found that OEB was significantly associated with chronic disease (OR (Odds Ratio): 1.74 < 95 % C.I (Confidence Interval): 1.45, 2.65 > ), infectious disease (OR: 3.37 < 95 % C.I: 1.04, 1.81 > ), and mental disorder (OR: 1.87(<95 % C.I: 1.55, 2.25 > ). These findings underscore the importance of addressing OEB in programs and policies to promote health and prevent disease among university students.

COVID-19, stigma, and habituation: evidence from mobility data.

BACKGROUND: The Japanese government has restricted people's going-out behavior by declaring a non-punitive state of emergency several times under COVID-19. This study aims to analyze how multiple policy interventions that impose non-legally binding restrictions on behavior associate with people's going-out. THEORY: This study models the stigma model of self-restraint behavior under the pandemic with habituation effects. The theoretical result indicates that the state of emergency's self-restraint effects weaken with the number of times. METHODS: The empirical analysis examines the impact of emergency declarations on going-out behavior using a prefecture-level daily panel dataset. The dataset includes Google's going-out behavior data, the Japanese government's policy interventions based on emergency declarations, and covariates that affect going-out behavior, such as weather and holidays. RESULTS: First, for multiple emergency declarations from the beginning of the pandemic to 2021, the negative association between emergency declarations and mobility was confirmed in a model that did not distinguish the number of emergency declarations. Second, in the model that considers the number of declarations, the negative association was found to decrease with the number of declarations. CONCLUSION: These empirical analyses are consistent with the results of theoretical analyses, which show that the negative association between people's going-out behavior and emergency declarations decreases in magnitude as the number of declarations increases.

Swollen hands and feet syndrome: An uncommon presentation of a common disease.

Leprosy is an infectious disease caused by M. leprae with predominant skin and neurological involvement. Although musculoskeletal involvement can occur in leprosy during the disease course, the first presentation of leprosy with musculoskeletal manifestation is relatively rare. Here we present a case that presented musculoskeletal manifestation as an initial feature.

Investigation ways of causes needle sticks injuries, risk factors affecting on health and ways to preventive.

Needle sticks injuries (NSIs) has caused many health concerns, including the widespread infection disease. Needle sticks injuries can have high threaten health human especially, all those who are in contact with health and medical centers. The purpose of this review study was the determination the effects of needle sticks injuries (NSIs) on health care worker and patents. In this a review study of literature studied conducted on international databases included Google Scholar, ISI/WOS (Web of Science), Springer, Scopus, Medline/PubMed. The literature signs a notable undesirable affect from potential needle sticks injuries related to ways to preventive and risks factors among patents and health care worker. The literature was shown needle stick injuries can cause with a variety of ways including needle recapping, non-standard safety boxes, thin gloves, and inadequate personal protective equipment. According to the result this study, needle stick injuries can transfer infectious disease (Human Immunodeficiency viruses [HIV], Hepatitis C virus [HCV]) and increase risk health on health care worker and patients. According to research related to the subject, the ways to prevent reduce needle sticks include personal protective equipment, holding retraining courses for medical staff in the direction to raise awareness can significantly reduce cases of needle sticks injuries. Further research using more sophisticated methodology is warranted.

Causal effects and immune cell mediators between prescription analgesic use and risk of infectious diseases: a Mendelian randomization study.

Introduction: Clinical observations have found that prolonged use of analgesics increases the incidence of infection. However, the direct causal relationship between prescription analgesic use (PAU) and risk of infection (ROI) remains unclear. Methods: This study used Mendelian randomization (MR) design to estimate the causal effect of PAU on ROI, as well as their mediating factors. Genetic data on prescription analgesics use and immune cells were obtained from published GWAS. Additionally, data on ROI were extracted from the FinnGen database. Two-sample MR analysis and multivariate MR (MVMR) analysis were performed using inverse variance weighting (IVW) to ascertain the causal association between PAU and ROI. Finally, 731 immune cell phenotypes were analyzed for their mediating role between analgesics and infection. Results: Using two-sample MR, IVW modeling showed that genetically predicted opioid use was associated with increased risk of pulmonary infection (PI) (OR = 1.13, 95% CI: 1.05-1.21, p< 0.001) and upper respiratory infection (URI) (OR = 1.18, 95% CI: 1.08-1.30, p< 0.001); non-steroidal anti-inflammatory drugs (NSAIDs) were related to increased risk of skin and subcutaneous tissue infection (OR = 1.21, 95% CI: 1.05-1.39, p = 0.007), and antimigraine preparations were linked to a reduced risk of virus hepatitis (OR = 0.79, 95% CI: 0.69-0.91, p< 0.001). In MVMR, the association of opioids with URI and PI remained after accounting for cancer conditions. Even with a stricter threshold (p< 0.05/30), we found a significant causal association between opioids and respiratory infections (URI/PI). Finally, mediation analyses found that analgesics influence the ROI through different phenotypes of immune cells as mediators. Conclusion: This MR study provides new genetic evidence for the causal relationship between PAU and ROI, and the mediating role of immune cells was demonstrated.