QseC inhibition as a novel antivirulence strategy for the prevention of Acute Hepatopancreatic Necrosis Disease (AHPND)-causing Vibrio parahaemolyticus

Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus resulted in great economic losses in global shrimp aquaculture. There is an urgent need for development of novel strategies to combat AHPND-causing V. parahaemolyticus (Vp (AHPND)), given that one of the greatest challenges currently is the widespread use of antibiotics and subsequent emergence of multidrug-resistant bacteria. Here, we proposed a broad-spectrum antivirulence approach targeting a conserved histidine kinase, QseC, which has been demonstrated to activate virulence expression in several Gram-negative pathogens. Our results showed that QseC mediated the catecholamine stimulated effects on growth and flagellar motility of Vp (AHPND). Transcriptome analysis revealed that QseC was involved in the global regulation of the virulence of Vp (AHPND) as the Delta qseC mutant exhibited a decreased expression of genes related to type IV pilin, flagellar motility, and biofilm formation, while an overexpression of type VI secretion system and cell wall biosynthesis. Subsequently, the bacterial catecholamine receptor antagonist LED209 not only neutralized the stimulatory effects of host catecholamines on the growth and motility of Vp (AHPND) in vitro, but also attenuated the virulence of Vp (AHPND) towards brine shrimp larvae and white shrimp in vivo. Additionally, LED209 presented no interference with pathogen growth, nor the toxicity to the experimental animals. These results suggest that QseC can be an attractive antivirulence therapy target, and LED209 is a promising candidate for development of broad-spectrum antivirulence agents. This is the first study that demonstrated the role of QseC in the global regulation of Vp (AHPND) infection and demonstrated the antivirulence potential of LED209, which provides insight into the use of an antivirulence approach for targeting not only Vp (AHPND), but also a much larger collection of pathogenic bacteria

Relationship Between Reactive Astrocytes, by [18F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer’s Disease

Reactive astrocytes play an important role in the development of Alzheimer’s disease (AD). Here, we aimed to investigate the temporospatial relationships among monoamine oxidase-B, tau and amyloid-β (Aβ), translocator protein, and glucose metabolism by using multitracer imaging in AD transgenic mouse models. Positron emission tomography (PET) imaging with [18F]SMBT-1 (monoamine oxidase-B), [18F]florbetapir (Aβ), [18F]PM-PBB3 (tau), [18F]fluorodeoxyglucose (FDG), and [18F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3×Tg mice, and aged-matched wild-type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as the reference region. Immunofluorescence staining was performed on mouse brain tissue slices. [18F]SMBT-1 and [18F]florbetapir SUVRs were greater in the cortex and hippocampus of 10-month-old APP/PS1 mice than in those of 5-month-old APP/PS1 mice and wild-type mice. No significant difference in the regional [18F]FDG or [18F]DPA-714 SUVRs was observed in the brains of 5- or 10-month-old APP/PS1 mice or wild-type mice. No significant difference in the SUVRs of any tracer was observed between 11-month-old 3×Tg mice and age-matched wild-type mice. A positive correlation between the SUVRs of [18F]florbetapir and [18F]DPA-714 in the cortex and hippocampus was observed among the transgenic mice. Immunostaining validated the distribution of MAO-B and limited Aβ and tau pathology in 11-month-old 3×Tg mice; and Aβ deposits in brain tissue from 10-month-old APP/PS1 mice. In summary, these findings provide in vivo evidence that an increase in astrocyte [18F]SMBT-1 accompanies Aβ accumulation in APP/PS1 models of AD amyloidosis

Factors associated with loss to follow-up before and after treatment initiation among patients with tuberculosis: A 5-year observation in China

BackgroundLoss to follow-up (LTFU) is a significant barrier to the completion of anti-tuberculosis (TB) treatment and a major predictor of TB-associated deaths. Currently, research on LTFU-related factors in China is both scarce and inconsistent.MethodsWe collected information from the TB observation database of the National Clinical Research Center for Infectious Diseases. The data of all patients who were documented as LTFU were assessed retrospectively and compared with those of patients who were not LTFU. Descriptive epidemiology and multivariable logistic regression analyses were conducted to identify the factors associated with LTFU.ResultsA total of 24,265 TB patients were included in the analysis. Of them, 3,046 were categorized as LTFU, including 678 who were lost before treatment initiation and 2,368 who were lost afterwards. The previous history of TB was independently associated with LTFU before treatment initiation. Having medical insurance, chronic hepatitis or cirrhosis, and providing an alternative contact were independent predictive factors for LTFU after treatment initiation.ConclusionLoss to follow-up is frequent in the management of patients with TB and can be predicted using patients’ treatment history, clinical characteristics, and socioeconomic factors. Our research illustrates the importance of early assessment and intervention after diagnosis. Targeted measures can improve patient engagement and ultimately treatment adherence, leading to better health outcomes and disease control

Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Abstract Background The current therapies of thyroid-associated ophthalmopathy (TAO) were still a challenging matter. In this study, we aimed to contrast the impact of before- after rituximab (RTX) therapy in the patients with TAO. Methods We searched the PubMed, EMBASE, and SCOPUS databases for articles published up to July 3, 2017. Fixed- or random-effects meta-analysis was used to provide pooled estimates of standard mean difference (SMD) both the primary outcome from clinical activity score (CAS), and secondary outcomes from thyrotropin receptor antibody (TRAb), proptosis, thyroid stimulating hormone (TSH), and interleukin-6 (IL-6) levels. In addition, the quality and each study was assessed using either the Newcastle Ottawa Scale (NOS) or the Cochrane Risk of Bias tool, and reliability of the meta-analytic result using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results Of the 839 articles initially searched, 11 studies were finally eligible for inclusion. Subgroup analysis results showed that comparing with initial value, there was a decline in CAS at 1,3,6,12 month after RTX treatment, decreased TRAbs level at 6,12 month, proptosis improvement at least 1 month, unchanged IL-6 level at 6 month, decreased TSH level at 3 month but unchanged at 12 month. All included studies were classified as good quality. Conclusions The pooled data suggested that the preliminary effects of RTX treatment on TAO might be promising. However, more large-sample and high-quality studies targeting RTX use during this disease and long-term surveillance of prognosis are urgently needed

Associations between e-health literacy and chronic disease self-management in older Chinese patients with chronic non-communicable diseases: a mediation analysis

Abstract Background Chronic non-communicable diseases (CNCDs) are an urgent public health issue in China, especially among older adults. Hence, self-management is crucial for disease progression and treatment. Electronic health (e-health) literacy and self-efficacy positively correlate with self-management. However, we know little about their underlying mechanisms in older adults with CNCDs. Objective To explore the factors that influence chronic disease self-management (CDSM) and verify self-efficacy as the mediator between e-health literacy and self-management behavior in older patients with CNCDs. Methods This cross-sectional study included 289 older patients with CNCDs from Hunan province, China, between July and November 2021. E-health literacy, self-efficacy, social support, and CDSM data were collected through questionnaires. The influence of each factor on CDSM was explored with multiple linear regression analysis. Intermediary effects were computed via a structural equation model. Results The total CDSM score in the patients was 29.39 ± 9.60 and only 46 (15.92%) patients used smart healthcare devices. The regression analysis showed e-health literacy, self-efficacy, and social support were the factors that affected CDSM. Furthermore, the structural equation model revealed that self-efficacy directly affected CDSM (β = 0.45, P < 0.01), whereas e-health literacy affected it directly (β = 0.42, P < 0.01) and indirectly (β = 0.429, P < 0.01) through self-efficacy. Conclusions This study revealed that self-management among older patients with CNCDs is at a low level, and few of them use smart healthcare devices. Self-efficacy plays a partial intermediary role between e-health literacy and self-management in older patients with CNCDs. Thus, efforts to improve their CDSM by targeting e-health literacy may be more effective when considering self-efficacy

Additional file 5: Figure S2. of Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Judgements about each risk of bias item for each included study. (TIFF 24 kb

Additional file 2: Table S1. of Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Quality evaluation of included studies using GRADE criteria. (DOC 70 kb

Additional file 3: Table S2. of Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Quality evaluation of included studies using NOS. (DOC 38 kb

Additional file 6: Table S3. of Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Mean changes for subgroup during RTX for the treatment of TAO. (DOC 46 kb

Additional file 1: of Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis

Data collection forms. (DOC 70 kb