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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 -
Journal of Paediatrics and Child Health Jul 2024The World Health Organization (WHO) estimates that 3.5% of the population live with hepatitis B virus (HBV); migrants to Europe are disproportionately affected. UK birth...
AIMS
The World Health Organization (WHO) estimates that 3.5% of the population live with hepatitis B virus (HBV); migrants to Europe are disproportionately affected. UK birth dose HBV vaccination is limited to infants born to those living with HBV (LWHBV). High-risk infants (high maternal infectivity, low birthweight) also receive HBV immunoglobulin (HBIG). The Family Hepatitis Clinic follows infants and those LWHBV working towards WHO goals of combating viral hepatitis by 2030.
METHODS
A trust-wide electronic note review of outcomes for infants born to those LWHBV (2016-2020).
RESULTS
Two hundred and eighty-three infants, 134 (47%) females, born to those LWHBV were referred. Two hundred and thirty-one (82%) attended follow-up with a vertical transmission rate of 0%. Twenty (7%) individuals LWHBV received tenofovir disoproxil fumerate in pregnancy; median viral load (VL) at initiation 125 416 376 DNA IU/mL, one having birth VL. Twenty-eight (10%) infants were stratified as high risk and all received HBIG and birth dose vaccination with 9 (32%) subsequently lost to follow-up, compared to 48 (19%) low-risk infants. 267/283 (94%) had birth dose vaccination documented and 206/283 (73%) received at least four vaccine doses. 215/283 (76%) infants had serology by 24 months; 17 (6%) with suboptimal vaccine responses: hepatitis B surface antibody <100 IU/mL. Serology before 18 months resulted in higher rates of maternal hepatitis B core antibody detection (15% vs. 3%).
CONCLUSION
Prevention of vertical transmission of HBV was universal in those attending, although high-risk infants were more likely lost to follow up. HBV post-vaccine serological protection was comparable with national data from 2021 (77% >4 doses, 77% HBsAb >100).
PubMed: 38953228
DOI: 10.1111/jpc.16609 -
ACS Applied Materials & Interfaces Jul 2024In recent years, flexible strain sensors have gradually come into our lives due to their superiority in the field of biomonitoring. However, these sensors still suffer...
In recent years, flexible strain sensors have gradually come into our lives due to their superiority in the field of biomonitoring. However, these sensors still suffer from poor durability, high hysteresis, and difficulty in calibration, resulting in great hindrance of practical application. Herein, starting with interfacial interaction regulation and structure-induced cracking, flexible strain sensors with high performance are successfully fabricated. In this strategy, dopamine treatment is used to enhance the bonding between flexible substrates and carbon nanotubes (CNT). The combination within the conductive networks is then controlled by substituting the CNT type. Braid-like fibers are employed to achieve controllable expansion of the conductive layer cracks. Finally, we obtain strain sensors that possess high linearity ( = 0.997) with low hysteresis (5%), high sensitivity (GF = 60) and wide sensing range (0-50%), short response time (62 ms), outstanding stability, and repeatability (>10,000 cycles). Flexible strain sensors with all performances good are rarely reported. Static and dynamic respiration and pulse signal monitoring by the fiber sensor are demonstrated. Moreover, a knee joint monitoring system is constructed for the monitoring of various walking stances, which is of great value to the diagnosis and rehabilitation of many diseases.
PubMed: 38953185
DOI: 10.1021/acsami.4c07016 -
Journal of Leukocyte Biology Jul 2024Sepsis is a dysregulated systemic inflammatory response to an infection, which can lead to multiple organ dysfunction syndrome that includes the kidney. Leukocyte...
Sepsis is a dysregulated systemic inflammatory response to an infection, which can lead to multiple organ dysfunction syndrome that includes the kidney. Leukocyte recruitment is an important process of the host immune defense in response to sepsis. Endothelial cells (EC) actively regulate leukocyte recruitment by expressing adhesion molecules following the activation of dedicated intracellular signal transduction pathways. Previous studies reported that the expression of adhesion molecules was associated with the activation of endothelial NF-κB p65 and MAPK c-Jun pathways in vitro in response to conditions that mimic processes that occur in inflammation. This study aimed to investigate the spatiotemporal patterns of leukocyte recruitment, expression of adhesion molecules, and endothelial nuclear p65 and c-Jun localization in renal microvascular beds of septic mice. Here, we used a cecal ligation and puncture (CLP) sepsis mouse model and RT-qPCR and immunohistochemical staining. We showed that neutrophils, macrophages, and T lymphocytes were all present in the kidney, yet only neutrophils accumulated in a spatiotemporally discernible pattern, mainly in glomeruli at 4 hours after CLP-sepsis initiation. E-selectin, not VCAM-1, was expressed in glomeruli at the same time point. In a subset of mice at 72 hours after CLP-sepsis started, VCAM-1 expression was prominent in glomerular EC, which was not related to changes in mmu-microRNA(miR)-126a-3p levels, a short noncoding microRNA previously shown to inhibit the translation of VCAM-1 mRNA into protein. Nuclear localization of p65 and c-Jun occurred in EC of all microvascular segments at 4 and 7 hours after CLP-sepsis initiation. In summary, sepsis-induced recruitment of neutrophils, E-selectin expression, and NF-κB p65 and MAPK c-Jun pathway activation coincided in glomeruli at the early stage of the disease. In the other microvascular beds, sepsis led to NF-κB p65 and MAPK c-Jun pathway activation with limited expression of E-selectin and no association with VCAM-1 expression or leukocyte recruitment.
PubMed: 38953175
DOI: 10.1093/jleuko/qiae146 -
Journal of Leukocyte Biology Jul 2024Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory...
Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining we hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren's syndrome (pSS), a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren's syndrome (ESS) that we previously established for YPF formula treatment. YPF therapy ameliorated the ESS pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using co-culture assay and adoptive transfer models, we demonstrated that YPF formula directly restrained effector/memory T cell expansion and differentiation into Th17 and T follicular helper (Tfh) cells, the key subsets in ESS pathogenesis. Importantly, we recruited 20 pSS patients and conducted a pilot study of 8-week therapy of YPF formula. YPF treatment effectively improved fatigue symptoms, exocrine gland functions and reduced serum IgG/IgA levels, while effector T and B cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggested a novel approach to assess the immunomodulatory effects of YPF formula, which may be favorable for patients with autoimmune disorders.
PubMed: 38953166
DOI: 10.1093/jleuko/qiae155 -
Indian Journal of Ophthalmology Jul 2024To evaluate the appropriateness of responses generated by an online chat-based artificial intelligence (AI) model for diabetic retinopathy (DR) related questions.
OBJECTIVE
To evaluate the appropriateness of responses generated by an online chat-based artificial intelligence (AI) model for diabetic retinopathy (DR) related questions.
DESIGN
Cross-sectional study.
METHODS
A set of 20 questions framed from the patient's perspective addressing DR-related queries, such as the definition of disease, symptoms, prevention methods, treatment options, diagnostic methods, visual impact, and complications, were formulated for input into ChatGPT-4. Peer-reviewed, literature-based answers were collected from popular search engines for the selected questions and three retinal experts reviewed the responses. An inter-human agreement was analyzed for consensus expert responses and also between experts. The answers generated by the AI model were compared with those provided by the experts. The experts rated the response generated by ChatGPT-4 on a scale of 0-5 for appropriateness and completeness.
RESULTS
The answers provided by ChatGPT-4 were appropriate and complete for most of the DR-related questions. The response to questions on the adverse effects of laser photocoagulation therapy and compliance to treatment was not perfectly complete. The average rating given by the three retina expert evaluators was 4.84 for appropriateness and 4.38 for completeness of answers provided by the AI model. This corresponds to an overall 96.8% agreement among the experts for appropriateness and 87.6% for completeness regarding AI-generated answers.
CONCLUSION
ChatGPT-4 exhibits a high level of accuracy in generating appropriate responses for a range of questions in DR. However, there is a need to improvise the model to generate complete answers for certain DR-related topics.
Topics: Diabetic Retinopathy; Humans; Cross-Sectional Studies; Artificial Intelligence; Surveys and Questionnaires
PubMed: 38953134
DOI: 10.4103/IJO.IJO_2510_23 -
Zhonghua Yi Xue Za Zhi Jul 2024An effective infectious disease surveillance and early warning system is a crucial component of public health safety and is essential for preventing and controlling...
An effective infectious disease surveillance and early warning system is a crucial component of public health safety and is essential for preventing and controlling outbreaks of infectious diseases. Enhancing surveillance and early warning capabilities is an urgent priority for advancing high-quality disease prevention and control efforts. Combining the research findings and practical experiences of experts in epidemiology, clinical medicine, disease prevention and control, data science, and computer science, and following multiple rounds of expert discussions, we have developed a consensus on the key technologies for a multi-point trigger intelligent surveillance and early warning system for infectious diseases. This consensus primarily covers the related concepts and definitions of the multi-point trigger intelligent surveillance and early warning system for infectious diseases, the key technical framework, sources, acquisition, and governance of multi-channel warning data, classification of early warning methods, multi-point trigger intelligent surveillance and early warning paths, multi-point trigger warning and comprehensive assessment, response to warning signals, and evaluation of early warning effectiveness. It aims to provide technical references for the construction and application of a multi-point trigger intelligent surveillance and early warning system for infectious diseases.
PubMed: 38953126
DOI: 10.3760/cma.j.cn112137-20240612-01317 -
Cureus May 2024Deep brain stimulation (DBS) has emerged as an important therapeutic option for several movement disorders; however, the management of acute complications, such as acute...
Deep brain stimulation (DBS) has emerged as an important therapeutic option for several movement disorders; however, the management of acute complications, such as acute subdural hematoma (ASDH), remains challenging. This is the case of a 71-year-old woman with Parkinson's disease who developed ASDH 12 years after bilateral DBS placement. On admission with altered consciousness, imaging revealed significant displacement of the DBS electrodes because of the hematoma. Emergent craniotomy with endoscopic evacuation was performed with preservation of the DBS system. Postoperatively, complete evacuation of the hematoma was confirmed, and the patient experienced significant clinical improvement. ASDH causes significant electrode displacement in patients undergoing DBS. After hematoma evacuation, the electrodes were observed to return to their proper position, and the patient exhibited a favorable clinical response to stimulation. To preserve the DBS electrodes, endoscopic hematoma evacuation via a small craniotomy may be useful.
PubMed: 38953093
DOI: 10.7759/cureus.61469 -
The Lancet Regional Health. Western... Jun 2024In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As...
BACKGROUND
In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia.
METHODS
A comprehensive collection of HIV-1 sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale.
FINDINGS
Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers ( ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low values.
INTERPRETATION
This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia.
FUNDING
National Health and Medical Research Council, Australian Research Council.
PubMed: 38953059
DOI: 10.1016/j.lanwpc.2024.101103 -
Frontiers in Immunology 2024Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly... (Observational Study)
Observational Study
BACKGROUND
Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.
METHODS
Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.
RESULTS
The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38CD8T cells, PD-1NK cells, HLA-DRCD8T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1 NK cells, while cluster 2 featured higher proportions of naïve CD4T cells. Furthermore, the level of PD-1NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, <0.01). Moreover, the levels of PD1 NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1 NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1 NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; <0.001).
CONCLUSION
The study provides novel insights into the association between PD1NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.
Topics: Humans; Sepsis; Male; Female; Programmed Cell Death 1 Receptor; Middle Aged; Aged; Killer Cells, Natural; Retrospective Studies; Biomarkers; Prognosis; Immunophenotyping; ROC Curve; Machine Learning
PubMed: 38953031
DOI: 10.3389/fimmu.2024.1426064