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Human Vaccines & Immunotherapeutics Dec 2024Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective... (Review)
Review
Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective strategy for preventing disease. Mucosally administered vaccines have the potential to induce protective immune responses at mucosal sites. This manuscript delves into some of the latest developments in mucosal vaccination, particularly focusing on advancements in adjuvant technologies and the role of these adjuvants in enhancing vaccine efficacy against respiratory pathogens. It highlights the anatomical and immunological complexities of the respiratory mucosal immune system, emphasizing the significance of mucosal secretory IgA and tissue-resident memory T cells in local immune responses. We further discuss the differences between immune responses induced through traditional parenteral vaccination approaches vs. mucosal administration strategies, and explore the protective advantages offered by immunization through mucosal routes.
Topics: Humans; Immunity, Mucosal; Respiratory Mucosa; Animals; Vaccines; Administration, Mucosal; Adjuvants, Vaccine; Vaccination; Adjuvants, Immunologic; Respiratory Tract Infections; Memory T Cells; Immunoglobulin A, Secretory
PubMed: 38953250
DOI: 10.1080/21645515.2024.2368288 -
Circulation. Genomic and Precision... Jul 2024Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in . Interpreting the pathogenicity of missense variants...
BACKGROUND
Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in . Interpreting the pathogenicity of missense variants is challenging, and ≈79% of missense variants in ClinVar are currently classified as variants of uncertain significance. Automated patch clamp technology enables high-throughput functional studies of ion channel variants and can provide evidence for variant reclassification.
METHODS
An in vitro -Brugada syndrome automated patch clamp assay was generated and independently studied at Vanderbilt University Medical Center and Victor Chang Cardiac Research Institute. The assay was calibrated according to ClinGen Sequence Variant Interpretation recommendations using high-confidence variant controls (n=49). Normal and abnormal ranges of function were established based on the distribution of benign variant assay results. Odds of pathogenicity values were derived from the experimental results according to ClinGen Sequence Variant Interpretation recommendations. The calibrated assay was then used to study variants of uncertain significance observed in 4 families with Brugada syndrome and other arrhythmia phenotypes associated with loss-of-function.
RESULTS
Variant channel parameters generated independently at the 2 research sites showed strong correlations, including peak density (=0.86). The assay accurately distinguished benign controls (24/25 concordant variants) from pathogenic controls (23/24 concordant variants). Odds of pathogenicity values yielded 0.042 for normal function and 24.0 for abnormal function, corresponding to strong evidence for both American College of Medical Genetics and Genomics/Association for Molecular Pathology benign and pathogenic functional criteria (BS3 and PS3, respectively). Application of the assay to 4 clinical variants of uncertain significance revealed loss-of-function for 3/4 variants, enabling reclassification to likely pathogenic.
CONCLUSIONS
This validated high-throughput assay provides clinical-grade functional evidence to aid the classification of current and future -Brugada syndrome variants of uncertain significance.
PubMed: 38953211
DOI: 10.1161/CIRCGEN.124.004569 -
Journal of Fish Diseases Jul 2024The aquaculture sector plays a vital role in global food security, yet it grapples with significant challenges posed by infectious diseases. Piscine lactococcosis is one...
The aquaculture sector plays a vital role in global food security, yet it grapples with significant challenges posed by infectious diseases. Piscine lactococcosis is one of the significant threats in rainbow trout aquaculture due to its potential to cause severe economic losses through mortalities, reduced growth rates, and increased susceptibility to other pathogens. It poses challenges in disease management strategies, impacting the sustainability and profitability of rainbow trout farming. The current study focuses on the variations in serum blood parameters of farmed rainbow trout Oncorhynchus mykiss during a lactococcosis outbreak caused by Lactococcus garvieae. Blood samples were collected for biochemical analysis, fish were examined for parasites and bacteria, and DNA from bacterial colonies was PCR-amplified and sequenced for identification. Overall, 13 biochemical parameters, including proteins, enzymes, lipids, chemicals, and minerals, were measured in serum blood samples from both diseased and healthy fish. The results indicate significant alterations in the levels of these parameters during the outbreak, highlighting the impact of infections on the blood profile of farmed rainbow trout. Urea levels were significantly higher in diseased fish compared to controls, and creatinine, phosphorus, and magnesium also showed similar trends. Alanine aminotransferase and total protein levels were higher in control fish. Chloride levels differed significantly between groups. Iron levels were higher in controls and lower in diseased fish. No significant differences were found in other parameters. This study reveals significant changes in serum blood parameters of rainbow trout during a lactococcosis outbreak caused by L. garvieae. These changes highlight the potential of these parameters as tools for monitoring health status, stress, and aquaculture management. Continuous monitoring can provide valuable insights into disease severity and overall fish health, aiding in the development of improved management practices. The presented data contribute to understanding the pathophysiology of piscine lactococcosis and developing effective mitigation strategies for farmed rainbow trout.
PubMed: 38953153
DOI: 10.1111/jfd.13994 -
Journal of Materials Chemistry. B Jul 2024In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by (), a common opportunistic pathogen. Infections...
In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by (), a common opportunistic pathogen. Infections caused by during surgical procedures highlight the need for effective strategies to inhibit its adhesion, growth, and colonization, particularly on the surfaces of invasive medical devices. Until now, most existing research has focused on nanopillar structures (positive topographies). Uniform nanopillar arrays have been shown to control bacterial behavior based on the spacing between nanopillars. However, nanopillar structures are susceptible to external friction, impact, and force, making it challenging to maintain their antibacterial properties. Therefore, in this study, we investigate the antibacterial behavior of nanohole structures, which offer relatively superior mechanical robustness compared to nanopillars. Moreover, for applications in medical devices such as laparoscopes, there is a pressing need for surfaces that are not only transparent and flexible (or curved) but are also equipped with antibacterial properties. Our study introduces a scalable multi-functional surface that synergistically combines antibacterial and anti-fog properties. This is achieved by fabricating thin films with variously sized holes (ranging from 0.3 μm to 4 μm) using polyurethane acrylate (PUA). We assessed the activity of on these surfaces and found that a 1 μm-diameter-hole pattern significantly reduced the presence of live , without any detection of dead . This bacteriostatic effect is attributed to the restricted proliferation due to the confined area provided by the hole pattern. However, the persistence of some live on the surface necessitates further measures to minimize bacterial adhesion and enhance antibacterial effectiveness. To address this challenge, we coated the zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the nanohole pattern surface to reduce adhesion. Moreover, in long-term experiments on surfaces, the MPC-coated effectively inhibited the colonization of (18 h; 82%, 7 days; 83%, and 14 days; 68% antibacterial rate). By integrating PUA, MPC, and nanohole architectures into a single, flexible platform, we achieved a multi-functional surface catering to transparency, anti-fogging, and anti-biofouling requirements. This innovative approach marks a significant advancement in surface engineering, offering a versatile solution applicable in various fields, particularly in preventing contamination in invasive medical devices like laparoscopes. The resultant surface, characterized by its transparency, flexibility, and antibacterial functionality, stands out as a promising candidate for mitigating -related risks in medical applications.
PubMed: 38953113
DOI: 10.1039/d4tb00434e -
Infection and Drug Resistance 2024The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world....
BACKGROUND
The occurrence and dissemination of hypermucoviscous and hypervirulent (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.
METHODS
In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.
RESULTS
The overall prevalence of hm isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv . The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of /. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.
CONCLUSION
Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.
PubMed: 38953096
DOI: 10.2147/IDR.S468482 -
Cureus May 2024Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study...
Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study employs advanced molecular techniques, specifically polymerase chain reaction (PCR) profiling, to comprehensively characterize the genetic landscape of XDR pathogenic bacteria in patients diagnosed with pulmonary TB. The objective of the study is to elucidate the genes that are associated with drug resistance in pulmonary TB strains through the application of PCR and analyze specific genetic loci that contribute to the development of resistance against multiple drugs. Materials and methods A total of 116 clinical samples suspected of TB were collected from the tertiary healthcare setting of Saveetha Medical College and Hospitals for the identification of MTB, which includes sputum (n = 35), nasal swabs (n = 17), blood (n = 44), and bronchoalveolar lavage (BAL) (n = 20). The collected specimens were processed and subjected to DNA extraction. As per the protocol, reconstitution of the DNA pellet was carried out. The reconstituted DNA was stored at -20 °C for the PCR assay. From the obtained positive sample specimens, XDR pulmonary TB specimens were focused on the targeted genes, specifically the gene for rifampicin resistance, , and gene for thepromoter region for isoniazid resistance. Results Out of a total of 116 samples obtained, 53 tested positive for pulmonary TB, indicative of a mycobacterial infection. Among these positive cases, 43 patients underwent treatment at a tertiary healthcare facility. Subsequently, a PCR assay was performed with the extracted DNA for the target genes , , and . Specifically, 22 sputum samples exhibited gene expression for , , and , while nine nasal swabs showed expression of the and genes. Additionally, gene expression was detected in seven blood specimens, and both and genes were expressed in five BAL samples. Conclusion The swift diagnosis and efficient treatment of XDR-TB can be facilitated by employing advanced and rapid molecular tests and oral medication regimens. Utilizing both newly developed and repurposed anti-TB drugs like pretomanid, bedaquiline, linezolid, and ethionamide. Adhering to these current recommendations holds promise for managing XDR-TB effectively. Nevertheless, it is significant to conduct well-designed clinical trials and studies to further evaluate the efficacy of new agents and shorter treatment regimens, thus ensuring continuous improvement in the management of this challenging condition.
PubMed: 38953074
DOI: 10.7759/cureus.61424 -
IJID Regions Jun 2024
PubMed: 38953056
DOI: 10.1016/j.ijregi.2024.100367 -
PeerJ 2024Potato farming is a vital component of food security and the economic stability especially in the under developing countries but it faces many challenges in production,...
Potato farming is a vital component of food security and the economic stability especially in the under developing countries but it faces many challenges in production, blackleg disease caused by () is one of the main reason for damaging crop yield of the potato. Effective management strategies are essential to control these losses and to get sustainable potato crop yield. This study was focused on characterizing the and the investigating new chemical options for its management. The research was involved a systematic survey across the three district of Punjab, Pakistan (Khanewal, Okara, and Multan) to collect samples exhibiting the black leg symptoms. These samples were analyzed in the laboratory where gram-negative bacteria were isolated and identified through biochemical and pathogenicity tests for . DNA sequencing further confirmed these isolates of strains. Six different chemicals were tested to control blackleg problem in both and at different concentrations. experiment, Cordate demonstrated the highest efficacy with a maximum inhibition zones of 17.139 mm, followed by Air One (13.778 mm), Profiler (10.167 mm), Blue Copper (7.7778 mm), Spot Fix (7.6689 mm), and Strider (7.0667 mm). , Cordate maintained its effectiveness with the lowest disease incidence of 14.76%, followed by Blue Copper (17.49%), Air One (16.98%), Spot Fix (20.67%), Profiler (21.45%), Strider (24.99%), and the control group (43.00%). The results highlight Cordate's potential as a most effective chemical against , offering promising role for managing blackleg disease in potato and to improve overall productivity.
Topics: Solanum tuberosum; Pectobacterium; Plant Diseases; Pakistan
PubMed: 38952990
DOI: 10.7717/peerj.17518 -
PeerJ 2024This study examined the effects of microbial agents on the enzyme activity, microbial community construction and potential functions of inter-root soil of aubergine ( ×...
BACKGROUND
This study examined the effects of microbial agents on the enzyme activity, microbial community construction and potential functions of inter-root soil of aubergine ( × Duch.). This study also sought to clarify the adaptability of inter-root microorganisms to environmental factors to provide a theoretical basis for the stability of the microbiology of inter-root soil of aubergine and for the ecological preservation of farmland soil.
METHODS
Eggplant inter-root soils treated with (QZ_T1), (QZ_T2), (QZ_T3), (QZ_T4) and (QZ_T5) were used to analyse the effects of different microbial agents on the inter-root soils of aubergine compared to the untreated control group (QZ_CK). The effects of different microbial agents on the characteristics and functions of inter-root soil microbial communities were analysed using 16S rRNA and ITS (internal transcribed spacer region) high-throughput sequencing techniques.
RESULTS
The bacterial diversity index and fungal diversity index of the aubergine inter-root soil increased significantly with the application of microbial fungicides; gas exchange parameters and soil enzyme activities also increased. The structural and functional composition of the bacterial and fungal communities in the aubergine inter-root soil changed after fungicide treatment compared to the control, with a decrease in the abundance of phytopathogenic fungi and an increase in the abundance of beneficial fungi in the soil. Enhancement of key community functions, reduction of pathogenic fungi, modulation of environmental factors and improved functional stability of microbial communities were important factors contributing to the microbial stability of fungicide-treated aubergine inter-root soils.
Topics: Soil Microbiology; Fungicides, Industrial; Photosynthesis; Microbiota; Solanum melongena; Plant Roots; Soil; RNA, Ribosomal, 16S
PubMed: 38952982
DOI: 10.7717/peerj.17620 -
Frontiers in Medicine 2024infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this...
BACKGROUND
infection is a rare condition primarily occurring in immunocompromised patients with extremely high mortality. Currently, there is no standard treatment for this condition, and successful treatment reports are scarce.
CASE PRESENTATION
We present a case of infection in a 63-year-old female patient with AIDS, who was admitted to our hospital with symptoms of fever, skin ulcers, subcutaneous nodules, and food regurgitation from the nose while eating. After initial empirical treatment failed, a biopsy of the subcutaneous nodule was performed, and metagenomic next-generation sequencing (mNGS) technology was used to detect pathogenic microorganisms in both the biopsy specimen and blood samples. The results revealed infection. Additionally, histopathological examination of the biopsy specimen and cytological examination of the secretions from the ulcer surface also confirmed this pathogenic infection. The patient's symptoms significantly improved upon discharge after adjusting the treatment regimen to a combination of anti-amebic therapy.
CONCLUSION
Immunocompromised patients presenting with unexplained fever and skin or sinus lesions should be evaluated for infection. Multi-drug combination therapy is required for this organism infection, and a standard treatment protocol still needs further research. Metagenomic next-generation sequencing is a valuable tool for early diagnosis of unknown pathogen infections.
PubMed: 38952864
DOI: 10.3389/fmed.2024.1377302