ABSTRACT
Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ+ and interleukin-10+ regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases.
Subject(s)
Allergens , Food Hypersensitivity , Gastrointestinal Microbiome , Gels , Intestine, Small , Inulin , Animals , Food Hypersensitivity/immunology , Food Hypersensitivity/therapy , Gastrointestinal Microbiome/drug effects , Mice , Administration, Oral , Allergens/immunology , Intestine, Small/immunology , Intestine, Small/microbiology , Immunotherapy , Desensitization, Immunologic/methodsABSTRACT
Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Reference Values , Forced Expiratory Volume , Vital Capacity , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , SpirometryABSTRACT
Obstructive sleep apnea (OSA) has been linked to cancer in several clinical and community-based cohorts. The effect in community-based studies free of clinical referral bias needs to be replicated. In this observational prospective cohort study, we pooled data from three community-based prospective cohorts (Uppsala Sleep and Health in Men cohort [UMEN]; Sleep and health in women [SHE]; Men Androgen Inflammation Lifestyle Environment and Stress Cohort [MAILES]; nTotal = 1467). All cohorts had objective data on obstructive sleep apnea and registry linkage data on cancer and cancer mortality. Analyses for different obstructive sleep apnea measures (apnea-hypopnea index [AHI], oxygen desaturation index [ODI], and minimal saturation) as risk factors for cancer incidence (all cancers) were performed using Cox proportional hazards models (follow-up 5-16 years). We did not find an overall increased risk of cancer after adjustment for age, sex, and BMI (HRAHI [95% CI] = 1.00 [0.98; 1.01] and HRODI [95% CI] = 0.99 [0.97; 1.01]). Stratifying by daytime sleepiness did not influence the association. Cancer mortality was not significantly associated with obstructive sleep apnea. Taken together, we did not observe an overall increased risk of cancer or cancer mortality in relation to obstructive sleep apnea, however, our confidence limits remain wide for important diagnostic categories of sleep apnea severity. The relationship between obstructive sleep apnea and cancer needs further investigation in a comprehensive multi-cohort approach with greater statistical precision. For future studies we may need to find and then combine every community-based cohort study that can provide a definitive answer to the question on the risk of cancer from obstructive sleep apnea in the general population.
ABSTRACT
BACKGROUND: Appropriate malaria treatment-seeking behaviour (TSB) is critical for timely detecting malaria, prompt treatment, and prevention of onward transmission of the disease in a community. This study aimed to compare treatment-seeking behaviours between malaria patients and non-malaria febrile patients, and to analyse the factors associated with appropriate TSB along the China-Myanmar border. METHODS: A cross-sectional study was carried out to investigate the appropriate TSB of microscopy-confirmed malaria patients versus non-malaria febrile (NMF) patients. An unconditional logistic regression analysis (LRA) was used to identify factors associated with appropriate TSB. RESULTS: Among 223 malaria patients and 446 NMF patients, 129 (57.8%) of the malaria patients versus 163 (36.5%) of the NMF patients firstly sought treatment in health facilities without laboratory testing for malaria (P < 0.0001). A total of 85(38.1%) of the malaria patients versus 278 (62.3%) of the NMF patients had appropriate TSB, namely, seeking treatment in health facilities with laboratory testing for malaria within 48 h (P < 0.0001). Multivariate LRA identified that the malaria patients with Chinese nationality had less appropriate TSB compared to those with other nationalities (adjusted odds ratio [AOR]: 0.21, 95% confidence interval CI 0.07-0.68, P = 0.0097), and malaria patients residing in urban areas had more appropriate TSB compared to those living in rural areas (AOR: 2.16, 95%CI 1.06-4.39, P = 0.0337). CONCLUSIONS: TSB was not appropriate in malaria patients. Chinese citizenship and rural residence were two independent factors associated with inappropriate malaria TSB. It is urgently necessary to improve appropriate malaria TSB through effective campaigns of information, education, and communication for malaria control in Myanmar and preventing reestablishment of malaria transmission in Yunnan, China.
Subject(s)
Malaria , Humans , Cross-Sectional Studies , Myanmar/epidemiology , China/epidemiology , Malaria/prevention & control , Patient Acceptance of Health Care , Fever/diagnosisABSTRACT
Diabetic wound treatment faces significant challenges in clinical settings. Alternative treatment approaches are needed. Continuous bleeding, disordered inflammatory regulation, obstruction of cell proliferation, and disturbance of tissue remodeling are the main characteristics of diabetic wound healing. Hydrogels made of either naturally derived or synthetic materials can potentially be designed with a variety of functions for managing the healing process of chronic wounds. Here, a hemostatic and anti-inflammatory hydrogel patch is designed for promoting diabetic wound healing. The hydrogel patch is derived from dual-cross-linked methacryloyl-substituted Bletilla Striata polysaccharide (B) and gelatin (G) via ultraviolet (UV) light. It is demonstrated that the B-G hydrogel can effectively regulate the M1/M2 phenotype of macrophages, significantly promote the proliferation and migration of fibroblasts in vitro, and accelerate angiogenesis. It can boost wound closure by normalizing epidermal tissue regeneration and depositing collagen appropriately in vivo without exogenous cytokine supplementation. Overall, the B-G bioactive hydrogel can promote diabetic wound healing in a simple, economical, effective, and safe manner.
Subject(s)
Diabetes Mellitus , Hydrogels , Collagen , Gelatin , Humans , Wound HealingABSTRACT
Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) is combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers can be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibit enhanced growth, proliferation, vascular endothelial growth factor production, and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds can greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis-related immunofluorescence staining indicate SG7 scaffolds demonstrate enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.
Subject(s)
Fibroins , Mesenchymal Stem Cells , Nanofibers , Cell Proliferation , Gelatin , Mesenchymal Stem Cells/metabolism , Methacrylates , Silk , Tendons , Tissue Engineering , Tissue Scaffolds , Vascular Endothelial Growth Factor A/metabolismABSTRACT
To search for colorectal cancer (CRC) risk loci, Swedish samples were used for a genome-wide haplotype analysis. A logistic regression model was employed in 2663 CRC cases and 1642 controls in the discovery analysis. Three analyses were done, on all, familial-, and nonfamilial CRC samples and only results with odds ratio (OR) > 1 were analyzed. single nucleotide polymorphism (SNP) analysis did not generate any statistically significant results. Haplotype analysis suggested novel loci, on chromosome 2q36.1 (OR = 1.71, p value = 5.6924 × 10-8 ) in all CRC samples, chromosome 1q43 (OR = 4.04 p value = 3.24 × 10-8 ) in familial CRC samples, and two hits in nonfamilial CRC samples, chromosomes 2q36.1 (OR = 1.71 p value = 5.69 × 10-8 ) and 3p24.3 (OR = 1.62 p value = 6.21 × 10-9 ). Moreover, one locus on chromosome 20q13.33 was suggested in analyses of all samples, and five more novel loci were suggested on chromosomes 10q25.3, 15q,22.31, 17p11.2, 1p34.2, and 3q24. The haplotypes from the analysis of all samples were replicated in a second study of CRC cases and controls from the same part of Sweden. In summary, using haplotype analysis in Swedish CRC samples, the best hits were novel loci and the locus on chromosomes 2q36.1 and 20q13.33 suggested in the analysis of all samples were confirmed in a second cohort. The ORs were often higher than ORs from published genome-wide association study (GWAS). The study suggested it was possible that a risk locus could involve more than one gene, and that haplotypes could give information on the gene or genes possibly involved in the risk at specific locus.
Subject(s)
Colorectal Neoplasms , Genome-Wide Association Study , Case-Control Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study/methods , Humans , Polymorphism, Single Nucleotide , Sweden/epidemiologyABSTRACT
BACKGROUND: The World Health Organization (WHO) has certificated China malaria free, but imported malaria is a continuous challenge in preventing reintroduction of malaria in the border area of China. Understanding risk factors of malaria along China-Myanmar border is benefit for preventing reintroduction of malaria in China and achieving the WHO's malaria elimination goal in the Greater Mekong Subregion (GMS). METHODS: This is a case-control study with one malaria case matched to two controls, in which cases were microscopy-confirmed malaria patients and controls were feverish people with microscopy-excluded malaria. A matched logistic regression analysis (LRA) was used to identify risk factors associated with malaria infection. RESULTS: From May 2016 through October 2017, the study recruited 223 malaria cases (152 in China and 71 in Myanmar) and 446 controls (304 in China and 142 in Myanmar). All the 152 cases recruited in China were imported malaria. Independent factors associated with malaria infection were overnight out of home in one month prior to attendance of health facilities (adjusted odd ratio [AOR] 13.37, 95% confidence interval [CI]: 6.32-28.28, P < 0.0001), staying overnight in rural lowland and foothill (AOR 2.73, 95% CI: 1.45-5.14, P = 0.0019), staying overnight at altitude < 500 m (AOR 5.66, 95% CI: 3.01-10.71, P < 0.0001) and streamlets ≤ 100 m (AOR9.98, 95% CI: 4.96-20.09, P < 0.0001) in the border areas of Myanmar; and people lacking of knowledge of malaria transmission (AOR 2.17, 95% CI: 1.42-3.32, P = 0.0004). CONCLUSIONS: Malaria transmission is highly focalized in lowland and foothill in the border areas of Myanmar. The risk factors associated with malaria infection are overnight staying out of home, at low altitude areas, proximity to streamlets and lack of knowledge of malaria transmission. To prevent reintroduction of malaria transmission in China and achieve the WHO goal of malaria elimination in the GMS, cross-border collaboration is continuously necessary, and health education is sorely needed for people in China to maintain their malaria knowledge and vigilance, and in Myanmar to improve their ability of personal protection.
Subject(s)
Malaria , Case-Control Studies , China/epidemiology , Humans , Malaria/epidemiology , Malaria/prevention & control , Myanmar/epidemiology , Risk FactorsABSTRACT
Grid management is a grassroots governance strategy widely implemented in China since 2004 to improve the government's efficiency to actively find and solve problems among populated regions. A grid-based strategy surveillancing high-risk groups, including mobile and migrant populations (MMPs), in the China-Myanmar border region has played an indispensable role in promoting and consolidating the malaria elimination efforts by tracking and timely identification of potential importation or re-establishment of malaria among MMPs. A sequential mixed methods was implementated to explore the operational mechanism and best practices of the grid-based strategy including through the focus group discussions (FGDs), comparison of before and after the implementation of a grid-based strategy in the field sites, and data collection from the local health system.This paper distills the implementation mechanism and highlights the role of the grid-based strategy in the elimination and prevention of re-establishment of malaria transmission.
Subject(s)
Malaria , Transients and Migrants , China/epidemiology , Computer Systems , Humans , Malaria/epidemiology , Malaria/prevention & control , MyanmarABSTRACT
Cancer immunotherapies, including immune checkpoint inhibitor (ICI)-based therapies, have revolutionized cancer treatment. However, patient response to ICIs is highly variable, necessitating the development of methods to quickly assess efficacy. In this study, an array of miniaturized bioreactors has been developed to model tumor-immune interactions. This immunotherapeutic high-throughput observation chamber (iHOC) is designed to test the effect of anti-PD-1 antibodies on cancer spheroid (MDA-MB-231, PD-L1+) and T cell (Jurkat) interactions. This system facilitates facile monitoring of T cell inhibition and reactivation using metrics such as tumor infiltration and interleukin-2 (IL-2) secretion. Status of the tumor-immune interactions can be easily captured within the iHOC by measuring IL-2 concentration using a micropillar array where sensitive, quantitative detection is allowed after antibody coating on the surface of array. The iHOC is a platform that can be used to model and monitor cancer-immune interactions in response to immunotherapy in a high-throughput manner.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Immunotherapy , Lab-On-A-Chip Devices , Neoplasms/drug therapyABSTRACT
Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, we present a detachable hybrid microneedle depot (d-HMND) for cell delivery. Our system consists of an array of microneedles with an outer poly(lactic-co-glycolic) acid (PLGA) shell and an internal gelatin methacryloyl (GelMA)-MSC mixture (GMM). The GMM was characterized and optimized for cell viability and mechanical strength of the d-HMND required to penetrate mouse skin tissue was also determined. MSC viability and function within the d-HMND was characterized in vitro and the regenerative efficacy of the d-HMND was demonstrated in vivo using a mouse skin wound model.
ABSTRACT
The Global Lung Function Initiative (GLI) has recently published international reference values for diffusing capacity of the lung for carbon monoxide (D LCO). Lower limit of normal (LLN), i.e. the 5th percentile, usually defines impaired D LCO We examined if the GLI LLN for D LCO differs from the LLN in a Swedish population of healthy, never-smoking individuals and how any such differences affect identification of subjects with respiratory burden.Spirometry, D LCO, chest high-resolution computed tomography (HRCT) and questionnaires were obtained from the first 15â040 participants, aged 50-64â
years, of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Both GLI reference values and the lambda-mu-sigma (LMS) method were used to define the LLN in asymptomatic never-smokers without respiratory disease (n=4903, of which 2329 were women).Both the median and LLN for D LCO from SCAPIS were above the median and LLN from the GLI (p<0.05). The prevalence of D LCO
Subject(s)
Lung , Adult , Female , Forced Expiratory Volume , Humans , Lung/diagnostic imaging , Male , Middle Aged , Reference Values , Spirometry , Sweden/epidemiology , Vital CapacityABSTRACT
The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.
Subject(s)
Extracellular Fluid , Gelatin , Hydrogels , Needles/classification , Skin , HumansSubject(s)
Reference Values , Adult , Humans , Oscillometry , Reproducibility of Results , Respiratory Function Tests , Spirometry , Sweden/epidemiologyABSTRACT
Objective: To assess the malaria transmission risk in the border area of Yunnan Province and provide evidence for adjustment of malaria intervention and elimination strategies. Method: Data concerning malaria prevalence, vector distribution, and institutional intervention capacity were collected in 197 towns of 20 counties in the border area of Yunnan Province during 2012-2014. The malaria transmission potential index ï¼TPIï¼, intervention capacity index (ICI) and malaria risk index (MRI) were calculated for each town, based on the criteria formulated by a professional committee. The towns were categorized according to the indices aforementioned. The risk map was created with GIS software. Results: Based on the TPI, the 197 towns comprised of 2 grade-I towns (including Nabang in Yingjiang and Banlao in Cangyuan) with high transmission potential, 11 grade-II towns with moderate transmission potential and 184 grade-III towns with low transmission potential. Based on the ICI, the 197 towns comprised of 4 grade-III towns (including Zhongke in Ximen, Zhonghe and Diantan in Tengchong, and Menghan in Jinghong) with a weak control capacity, 20 grade-II towns with a moderate control capacity and 173 grade-I towns with a strong control capacity. Based on the MRI, the 197 towns comprised of 2 grade-I towns (including Nabang in Yingjiang, and Banlao in Cangyuan) with a high transmission risk level, 12 grade-II towns with a moderate level and 183 grade-III towns with a low level distributed in 20 counties. Conclusion: The grade I or II towns with moderate and high transmission risk constitute <5% of the 197 towns in the border area, suggesting a relatively low level of malaria transmission risk in most counties.
Subject(s)
Malaria/transmission , Risk Assessment , Animals , China , Disease Vectors , Humans , PrevalenceABSTRACT
The capture and ligation probe-PCRï¼CLIP-PCRï¼ with pooling strategy method and microscopy were applied on 100 clinical samplesï¼7 positive and 93 negative samplesï¼ from the malaria reference laboratory in Yunnan Province. By calculating the detection rate, sensitivity, specificity, detection time and detection cost, the efficacy of the CLIP-PCR with pooling strategy method in detecting Plasmodium spp. was evaluated. The CLIP-PCR with matrix pooling strategy successfully detected Plasmodium spp. in all the 7 positive samples. Its sensitivity and specificity relative to the microscopy as a gold standard were both 100%. The detection time for all the samples by CLIP-PCR was 5.0 h, 85.0% shorter than that by microscopyï¼33.3 hï¼, and the detection cost was 300 yuan, 75.0% less than that by microscopy ï¼1 000 yuanï¼.
Subject(s)
Plasmodium , China , DNA, Protozoan , Humans , Malaria , Microscopy , Polymerase Chain ReactionABSTRACT
AIM: Chronotropic incompetence and impaired heart rate (HR) recovery are related to mortality. Guidelines lack specific reference values for HR recovery. We defined normal values and studied blunted HR response and recovery, and mortality risk. METHODS: We included 9,917 subjects (45% females) aged 18-85 years who performed a cycle exercise test. We defined normal values for peak HR, HR reserve, and HR recovery at 1 and 2 minutes (HRR1 and HRR2) based on individuals apparently healthy (N=2,242). Associations between blunted HR indices (<5th percentile) and mortality over a median follow-up of 8.6 years were analysed using Cox regression and competing risk analysis. RESULTS: All HR indices were age-dependent and independent predictors of all-cause and CV mortality. The 5th percentiles of HR reserve, HRR1, and HRR2 correlated weakly with existing reference values. HR recovery variables were the strongest predictors of all-cause mortality (HRR1, hazard ratio 1.70 [95% confidence interval, 1.49-1.94] and HRR2, 1.57 [1.37-1.79]), including in subjects with normal exercise capacity (HRR1, 1.96 [1.61-2.39] and HRR2, 1.76 [1.46-2.12]). Combining HR indices appeared to increase the risk of all-cause (HRR1 and HRR2, 1.96 [1.68-2.29] and peak HR and HRR1, 1.87 [1.56-2.23]) and CV mortality, although no specific combination was superior for predicting CV mortality. CONCLUSIONS: All HR variables were age-dependent and associated with all-cause and CV mortality. Blunted HR recovery variables were the strongest predictors of all-cause mortality, even in subjects with normal exercise capacity. Combined blunted HR indices appeared to add prognostic value.
We provide a detailed description on the physiologic HR response and recovery kinetics in a population apparently CV risk-free referred for cycle exercise testing. When assessed in a larger population, blunted HR response and recovery were associated with increased mortality. HR response and recovery are age-dependent. We provide novel reference values.All blunted HR indices (peak HR, HR reserve, HRR1 and HRR2) are strong predictors of all-cause and CV mortality, and combined HR indices appeared to add prognostic value in all the analyses.Blunted HRR1 followed by HRR2 are the strongest predictor of all-cause mortality even in subjects with normal exercise capacity, highlighting the importance of their assessment in standard exercise testing.
ABSTRACT
Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies. By examining how metal ions modulate the innate and adaptive immune systems, as well as host-microbiota interactions, we discuss strategies for the development of such metalloimmunotherapies for the treatment of cancer and other immune-related diseases.
Subject(s)
Immunotherapy , Neoplasms , Humans , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , Animals , Metals , Immunity, Innate , Adaptive ImmunityABSTRACT
Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults with a 5-year survival rate of 30.5%. These poor patient outcomes are attributed to tumor relapse, stemming from ineffective innate immune activation, T cell tolerance, and a lack of immunological memory. Thus, new strategies are needed to activate innate and effector immune cells and evoke long-term immunity against AML. One approach to address these issues is through Stimulator of Interferon Genes (STING) pathway activation, which produces Type I Interferons (Type I IFN) critical for innate and adaptive immune activation. Here, we report that systemic immunotherapy with a lipid-based nanoparticle platform (CMP) carrying Mn2+ and STING agonist c-di-AMP (CDA) exhibited robust anti-tumor efficacy in a mouse model of disseminated AML. Moreover, CMP immunotherapy combined with immune checkpoint blockade against cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) elicited robust innate and adaptive immune activation with enhanced cytotoxic potential against AML, leading to extended animal survival after re-challenge with AML. Overall, this CMP combination immunotherapy may be a promising approach against AML and other disseminated cancer.
Subject(s)
Antineoplastic Agents , Leukemia, Myeloid, Acute , Nanoparticles , Neoplasms , Mice , Adult , Animals , Humans , Manganese , Leukemia, Myeloid, Acute/drug therapy , T-Lymphocytes , Immunotherapy , Immunity, InnateABSTRACT
This study aimed to determine whether the EQ-5D-5L tool captures the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, in patients with post-COVID-19 conditions while also investigating if adding these symptoms improves the explained variance of the health-related quality of life (HRQoL). In this exploratory cross-sectional study, two cohorts of Swedish patients (n = 177) with a history of COVID-19 infection answered a questionnaire covering sociodemographic characteristics and clinical factors, and their HRQoL was assessed using EQ-5D-5L with the Visual Analogue Scale (EQ-VAS). Spearman rank correlation and multiple regression analyses were employed to investigate the extent to which the most common persistent symptoms, such as fatigue, memory/concentration problems and dyspnea, were explained by the EQ-5D-5L. The explanatory power of EQ-5D-5L for EQ-VAS was also analyzed, both with and without including symptom(s). We found that the EQ-5D-5L dimensions partly captured fatigue and memory/concentration problems but performed poorly in regard to capturing dyspnea. Specifically, the EQ-5D-5L explained 55% of the variance in memory/concentration problems, 47% in regard to fatigue and only 14% in regard to dyspnea. Adding fatigue to the EQ-5D-5L increased the explained variance of the EQ-VAS by 5.7%, while adding memory/concentration problems and dyspnea had a comparatively smaller impact on the explained variance. Our study highlights the EQ-5D-5L's strength in capturing fatigue and memory/concentration problems in post-COVID-19 patients. However, it also underscores the challenges in assessing dyspnea in this group. Fatigue emerged as a notably influential symptom, significantly enhancing the EQ-5D-5L's predictive ability for these patients' EQ-VAS scores.