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[This corrects the article DOI: 10.1016/j.jesf.2024.07.002.].
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The Long Life Family Study (LLFS) enrolled 4953 participants in 539 pedigrees displaying exceptional longevity. To identify genetic mechanisms that affect cardiovascular risks in the LLFS population, we developed a multi-omics integration pipeline and applied it to 11 traits associated with cardiovascular risks. Using our pipeline, we aggregated gene-level statistics from rare-variant analysis, GWAS, and gene expression-trait association by Correlated Meta-Analysis (CMA). Across all traits, CMA identified 64 significant genes after Bonferroni correction (p ≤ 2.8 × 10-7), 29 of which replicated in the Framingham Heart Study (FHS) cohort. Notably, 20 of the 29 replicated genes do not have a previously known trait-associated variant in the GWAS Catalog within 50 kb. Thirteen modules in Protein-Protein Interaction (PPI) networks are significantly enriched in genes with low meta-analysis p-values for at least one trait, three of which are replicated in the FHS cohort. The functional annotation of genes in these modules showed a significant over-representation of trait-related biological processes including sterol transport, protein-lipid complex remodeling, and immune response regulation. Among major findings, our results suggest a role of triglyceride-associated and mast-cell functional genes FCER1A, MS4A2, GATA2, HDC, and HRH4 in atherosclerosis risks. Our findings also suggest that lower expression of ATG2A, a gene we found to be associated with BMI, may be both a cause and consequence of obesity. Finally, our results suggest that ENPP3 may play an intermediary role in triglyceride-induced inflammation. Our pipeline is freely available and implemented in the Nextflow workflow language, making it easily runnable on any compute platform ( https://nf-co.re/omicsgenetraitassociation ).
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BACKGROUND: Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown. METHODS: We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0. RESULTS: We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice. CONCLUSIONS: The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.
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Anticuerpos Antiprotozoarios , Proteínas Protozoarias , Vacunas Antiprotozoos , Toxoplasma , Toxoplasmosis Animal , Vacunas Atenuadas , Animales , Toxoplasma/inmunología , Toxoplasma/genética , Ratones , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Anticuerpos Antiprotozoarios/sangre , Femenino , Toxoplasmosis Animal/prevención & control , Toxoplasmosis Animal/inmunología , Citocinas/metabolismo , Virulencia , Carga de Parásitos , Modelos Animales de Enfermedad , Enfermedad Crónica , Toxoplasmosis/prevención & control , Toxoplasmosis/inmunología , Toxoplasmosis/parasitologíaRESUMEN
BACKGROUND: Carotid blowout syndrome is a serious complication of head and neck cancer (HNC) that may involve the intracranial or extracranial internal carotid artery (ICA). Although parent artery occlusion (PAO) is the major endovascular treatment for intracranial carotid blowout syndrome (iCBS), the efficacy of using a balloon-expandable coronary stent-graft (BES) remains unclear. METHODS: This was a quasi-randomized trial, prospective study that included patients with iCBS treated by BES or PAO between 2018 and 2024. Patients were allocated to either group based on the last digit of their chart number; even numbers went to the BES group and odd numbers to the PAO group. The inclusion criteria of iCBS included the pathological process of CBS involving petrous and/or cavernous ICA detected by both imaging and clinical features. The primary outcome was defined as rebleeding events after intervention. The secondary outcome was defined as neurological complication after intervention. RESULTS: Fifty-nine patients with 61 iCBS lesions were enrolled. Thirty-three iCBS lesions were treated with BES and 28 underwent PAO. The results for the BES group versus the PAO group, respectively, were: rebleeding events, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); neurological complication, 5/33 (15.1%) vs 5/28 (17.8%) (p=0.78); median hemostatic time (months), 10.0 vs 11.5 (p=0.22); and median survival time (months), 10.0 vs 11.5 (p=0.39). CONCLUSIONS: No significant difference in rebleeding risk or neurological complication was observed between the BES and PAO groups. Our study confirmed the safety and effectiveness of applying BES for iCBS in HNC patients.
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Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-ß, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.
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Infecciones por Coronavirus , Medicamentos Herbarios Chinos , Farmacología en Red , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Porcinos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Enfermedades de los Porcinos/tratamiento farmacológico , Enfermedades de los Porcinos/virología , Antivirales/farmacología , Replicación Viral/efectos de los fármacos , Línea Celular , Espectrometría de Masas en Tándem , Diarrea/tratamiento farmacológico , Diarrea/virología , Diarrea/veterinaria , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib-resistance. Liquid chromatography-mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD-9291, Tagrisso), H1975 cells were used to establish the osimertinib-resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and ß1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV-related signaling pathway in EGFR-mutated and osimertinib-resistant lung cancer cells.
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BACKGROUND: Multitasking, defined as performing two or more interventions simultaneously, increases the cognitive burden of clinicians. This may, in turn, lead to higher risk of medication and procedural errors. Time motion study (TMS) data for nurses in nursing homes revealed an extensive amount of multitasking while managing medications. Further investigation of multitasked nursing interventions will provide a foundation for optimizing medication management workflows. OBJECTIVES: Using a continuous observational TMS method, this study aimed to describe pairs of multitasked nursing interventions associated with medication management interventions, including preparing and administering medications, assessing medication effects, instructing on medications, and documenting medication administration. METHODS: An external nurse observer used 57 pre-defined Omaha System nursing interventions embedded within TimeCaT (version 3.9) TMS data recording software to collect observation data in a single nursing home. A total of 120 hours of time-stamped observation data from nine nurses was downloaded from TimeCaT and analyzed using descriptive and inferential statistics. RESULTS: The majority (74%) of medication management interventions were multitasked, resulting in 2,003 pairs of multitasked interventions. Of the 57 Omaha System nursing interventions, 35 were involved in these multitasking pairs. When nurses multitasked, the average duration of medication preparation was longer (non-multitasked: 81 seconds; multitasked: 162 seconds, p<0.05), while the average duration of medication administration record documentation was shorter (non-multitasked: 93 seconds; multitasked: 66 seconds, p<0.05). CONCLUSIONS: The findings reveal the complexity of medication management in nursing homes with numerous and diverse multitasking pairs. Findings provide a platform for in-depth study of medication management multitasking in the clinical context, and inform future efforts to create clinical and informatics solutions to optimize medication management workflow. This method may be also applied to examine medication management and multitasking in other clinical settings.
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INTRODUCTION: Herbal medicines (HMs) are commonly used during the postpartum period in South Korea. However, the safety concerns associated with these medicines remain unresolved. This study aims to establish a registry of patients receiving HM treatment during the postpartum period and collect clinical data on treatments and adverse reactions to build evidence evaluating the safety of HM use. METHODS AND ANALYSIS: This study will use a prospective observational registry, including patients admitted to the obstetrics and gynaecology department of the Woosuk University Korean Medicine Hospital's postpartum care centre. A total of 1000 eligible patients visiting the Korean medicine hospital to recover from various postchildbirth symptoms and opting for HM treatment will be enrolled in the registry. For safety assessment, demographic information, medical history, adverse events (AEs) and treatment details, including HM prescription and concomitant medication usage, will be collected throughout the patient's hospitalisation period at the postpartum care centre for analysis. Adverse reactions will be monitored daily during hospitalisation, and collected AEs will be analysed for causality using the WHO Uppsala Monitoring Centre causality assessment and the Naranjo Algorithm Score. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Woosuk University Korean Medicine Medical Center (WSOH IRB H2311-03-01). The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: KCT0009060.
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Periodo Posparto , Sistema de Registros , Humanos , Femenino , República de Corea , Estudios Prospectivos , Embarazo , Medicina Tradicional Coreana , Fitoterapia/efectos adversos , Adulto , Medicina de HierbasRESUMEN
BACKGROUND: As a relatively novel approach to enhancing skeletal muscle health, mixed protein supplementation has shown similar responses to whey protein. However, no previous studies have examined its impact on golf swing performance. This study aimed to examine the effect of mixed protein supplementation on the swing performance and muscle strength of casual golfers. METHODS: Sixty participants with a handicap of less than 20 were recruited and randomly assigned to a double-blind, placebo-controlled study design. The participants were divided into two groups: a mixed protein group (MG, n = 30), and a placebo control group (CG, n = 30). They were instructed to ingest either a supplement containing casein calcium, whey protein, and isolated pea protein, or a placebo, once daily for 8 weeks. Pre- and posttests consisted of anthropometric measurements, muscle strength (isokinetic knee and trunk strength, and handgrip strength), 2-minute push-ups, balance, and golf swing performance using a driver and 7-iron. RESULTS: After the 8-week supplementation period, ANCOVA, using baseline values as covariates, revealed significant differences for driver distance (p = .004) and driver ball speed (p < .001). MG significantly increased driver distance by 5.17 ± 12.8 m (p = .046), driver ball speed by 1.36 ± 2.87 m/s (p = .021). Additionally, significantly improvements were observed in hand grip strength (+2.12 ± 3.47 kg, p = .004), two-minute push-ups (+4.89 ± 8.14 reps, p = .004), and balance score (-0.37 ± 0.69 min, p = .009). No significant differences were observed in body composition parameters (p > .05). CONCLUSION: The intake of a mixed protein containing both animal and plant proteins had positive effects on golf performance and muscle function. Therefore, mixed proteins may represent a safe and effective approach to enhancing skeletal muscle health in golf players.
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Rendimiento Atlético , Suplementos Dietéticos , Golf , Fuerza Muscular , Músculo Esquelético , Proteína de Suero de Leche , Humanos , Golf/fisiología , Método Doble Ciego , Fuerza Muscular/efectos de los fármacos , Fuerza Muscular/fisiología , Masculino , Proteína de Suero de Leche/administración & dosificación , Proteína de Suero de Leche/farmacología , Rendimiento Atlético/fisiología , Músculo Esquelético/fisiología , Músculo Esquelético/efectos de los fármacos , Adulto , Caseínas/administración & dosificación , Caseínas/farmacología , Adulto Joven , Proteínas de Guisantes/administración & dosificación , Fenómenos Fisiológicos en la Nutrición Deportiva , Proteínas en la Dieta/administración & dosificación , Femenino , Fuerza de la Mano/fisiologíaRESUMEN
In the original publication [...].
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OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.
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Background: The rapid aging of Korea's population underscores the urgent need for effective programs to enhance the well-being and longevity of the elderly. This study presents preliminary results from the Korean project, examining the impact of cost-effective and accessible exercise programs on functional performance of older people and to determine the long-term maintenance of intervention. Methods: We randomized 90 older adults aged ≥65 years to the walking group (WG), resistance + walking (RWG), or active control (CG) group. We designed a 12-week main intervention (supervised resistance training 2 d/week and individual walking exercise) and a 12-week follow-up through self-directed exercise (same protocol but unsupervised). The participants' mini mental state examination, color-word Stroop test and 5-time sit to stand, timed up & go, handgrip strength, and knee extensor strength tests were assessed at pre, post, as well as follow-up. Results: For the RWG group, significant improvements were found in timed up & go (P < 0.001), and 5-time sit to stand (P < 0.001) compared to CG, with benefits maintained at follow-up. Both RWG and WG showed significant enhancements in knee extensor power (RWG: P < 0.0001; WG: P < 0.001) and flexor power (RWG: P < 0.01; WG: P = 0.018) compared to CG. Although cognitive performance did not show significant group-by-time interactions, RWG exhibited improvements in the Stroop Color and Color-Word tests at follow-up compared to baseline. Conclusion: A resistance training program combined with walking effectively enhanced functional performance in older adults, providing lasting benefits over 12 weeks on physical functions, such as strength and endurance. However, it showed limited benefits on cognitive performance.
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BACKGROUND: Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. PURPOSE: The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. METHODS: Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. RESULTS: We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. CONCLUSION: We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.
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Presión Sanguínea , Inflamasomas , Isoflavonas , Proteína con Dominio Pirina 3 de la Familia NLR , Núcleo Hipotalámico Paraventricular , Especies Reactivas de Oxígeno , Transducción de Señal , Receptor Toll-Like 4 , Animales , Masculino , Ratas , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Isoflavonas/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Prehipertensión/tratamiento farmacológico , Ratas Endogámicas Dahl , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Cloruro de Sodio Dietético , Receptor Toll-Like 4/metabolismoRESUMEN
We developed emulsion-filled calcium alginate gels (EF-CAG) as a novel thermoresponsive carrier for plant-based meat analogs (PBMA), designed to mimic the cooking-induced flavor release of real meat. Optimized to maximize flavor release upon heating, EF-CAG demonstrated a thermoresponsive release of 51% with a notable size reduction. Initial release profiles varied between media; a burst release of 43% occurred in water within the first 5 min, while <1% was released in air. EF-CAG consistently increased flavor release in PBMA during cooking, without adversely affecting appearance or flavor stability, maintaining flavor retention at 4 °C for 10 days. The sensory evaluation confirmed that EF-CAG successfully masked the beef flavor before cooking and enhanced its release afterward. Our findings suggest that EF-CAG can be effectively used as a flavoring agent for PBMA, offering similar flavor attributes to real meat during cooking.
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Alginatos , Culinaria , Emulsiones , Aromatizantes , Geles , Gusto , Alginatos/química , Aromatizantes/química , Emulsiones/química , Geles/química , Animales , Humanos , Bovinos , Carne/análisis , Calor , Sustitutos de la CarneRESUMEN
To evaluate the measurement accuracy of horizontal and vertical remote emission sensing (RES) equipment, a real-world dynamic test was carried out in Chengdu by using electric vehicles equipped with various concentrations of standard gases. In addition, a new Image-based Spectral Processing Algorithm (ISPA) for vertical remote sensing spectral data was developed to improve the measurement capability. The results showed that the ISPA provided a greater percentage of valid data and lower relative errors; thus, our new algorithm could more effectively analyze the spectral data to measure vehicle emission levels. The percentages of valid horizontal and vertical RES data were 71% and 84%, respectively. The mean relative errors of CO2, CO, HC and NO measured by the vertical RES were about 5%, 20%, 20% and 40%, respectively, and those of CO2, CO and NO measured by the horizontal RES were 3%, 13% and 15%, respectively. For the common vehicle emission concentration, the percentage of valid data for the two RES types increased with increasing gas concentration. As the vehicle speed increased, the relative errors of the horizontal RES equipment showed an increasing trend for the same concentration of gas. Furthermore, for the same speed segment, the relative errors of the horizontal RES equipment increased as the simulated emission concentration decreased. The vertical RES equipment did not exhibit a consistent trend in terms of changes. This study provides a data quality reference for further RES applications.
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Contaminantes Atmosféricos , Monitoreo del Ambiente , Tecnología de Sensores Remotos , Emisiones de Vehículos , Emisiones de Vehículos/análisis , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/instrumentación , Tecnología de Sensores Remotos/métodos , Contaminantes Atmosféricos/análisis , Dióxido de Carbono/análisis , Monóxido de Carbono/análisis , Algoritmos , Contaminación del Aire/estadística & datos numéricos , ChinaRESUMEN
AIMS: To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. METHODS: Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-ß1, TNF-ß, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. RESULTS: Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040â D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042â D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016â D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104â D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. CONCLUSIONS: Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.
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Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)-negative and early-stage RA are still to be improved. We aimed to screen autoantibodies in ACPA-negative patients and evaluated their diagnostic performance. The human genome-wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti-ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA-negative RA, including anti-ANAPC15, anti-LSP1, anti-APBB1, anti-parathymosin, and anti-UBL7. Anti-parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA-negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA-positive RA and 23.8% in ACPA-negative RA) in independent testing patients. Therefore, HuProt arrays identified RA-associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA-negative RA.
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Introduction: Fospropofol disodium is a novel prodrug that has improved pharmacokinetic and pharmacodynamic properties when compared with propofol. This trial aims to compare the efficacy and safety of fospropofol versus propofol sedation for same-day bidirectional endoscopy in elderly patients. Methods and analysis: This is a prospective, single-center, double-blind, randomized, propofol-controlled, non-inferiority trial. A total of 256 patients aged 65 years or older, who are scheduled for same-day bidirectional endoscopy under sedation, will be randomly allocated, in a 1:1 ratio, to either fospropofol group or propofol group (n = 128 in each group). All patients will receive analgesic pre-treatment with sufentanil 5 µg. Two minutes later, an initial bolus dose of fospropofol 6.5 mg/kg or 1.5 mg/kg propofol and supplemental doses of fospropofol 1.6 mg/kg or 0.5 mg/kg propofol will be titrated as needed to achieve target sedation levels during the procedures. The primary outcome is the success rate of same-day bidirectional endoscopy. Secondary outcomes include the time to successful induction of sedation, duration, time to being fully alert, time to patient discharge, endoscopist satisfaction, patient satisfaction, and the top-up frequency and dosage of sedative medications. The safety endpoints consist of adverse events concerning cough reflex, gag reflexes, body movement, muscular tremor, and pain on injection. Sedation-related AEs, including episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), and bradycardia, will also be recorded. Data will be analyzed on an intention-to-treat basis. Discussion: We hypothesize that the efficacy and safety of fospropofol sedation for elderly patients undergoing same-visit bidirectional endoscopy will not be inferior to that of propofol. Our findings will potentially provide a new sedation regimen for same-visit bidirectional endoscopy in elderly patients. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02875639.
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To date, more than 20 species in the genus Cyclospora have been reported. Among them, Cyclospora cayetanensis has been recognized as the causative agent of human cyclosporiasis, which is characterized by severe intestinal injury and prolonged diarrhea in patients with immune dysfunction. The presence of C. cayetanensis in cattle has been confirmed. To date, however, no surveillance data are available on the occurrence and prevalence of Cyclospora spp. in cattle in Shanxi Province, North China. In the present study, a total of 761 fecal samples collected from cattle in three representative counties (Qi, Jishan, and Shanyin) in this Province were examined for Cyclospora spp. by using a polymerase-chain-reaction-restriction-fragment-length polymorphism (PCR-RFLP) test based on the nuclear small subunit ribosomal RNA (SSU rRNA) gene. The prevalence of Cyclospora spp. in cattle was 2.1%, and region, age, sex, and breed were not identified to be risk factors. Molecular evolutionary analysis based on the SSU rRNA sequences revealed that all 12 of the isolates were relatively distant from the human pathogen C. cayetanensis; seven isolates were grouped with Cyclospora colobi, whereas the others were grouped with cattle Cyclospora spp. reported previously. Though C. cayetanensis was not detected in cattle in the present study, more investigations should be performed in human populations, other animal species, or cattle from other regions of Shanxi Province and other environmental sources from the One Health perspective.
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Background: The cGAS-STING axis-mediated type I interferon pathway is a crucial strategy for host defense against DNA virus infection. Numerous evasion strategies developed by the pseudorabies virus (PRV) counteract host antiviral immunity. To what extent PRV-encoded proteins evade the cGAS-STING signaling pathway is unknown. Methods: Using US2 stably expressing cell lines and US2-deficient PRV model, we revealed that the PRV tegument protein US2 reduces STING protein stability and downregulates STING-mediated antiviral signaling. Results: To promote K48-linked ubiquitination and STING degradation, US2 interacts with the LBD structural domain of STING and recruits the E3 ligase TRIM21. TRIM21 deficiency consistently strengthens the host antiviral immune response brought on by PRV infection. Additionally, US2-deficient PRV is less harmful in mice. Conclusions: Our study implies that PRV US2 inhibits IFN signaling by a new mechanism that selectively targets STING while successfully evading the host antiviral response. As a result, the present study reveals a novel strategy by which PRV evades host defense and offers explanations for why the Bartha-K61 classical vaccine strain failed to offer effective defense against PRV variant strains in China, indicating that US2 may be a key target for developing gene-deficient PRV vaccines.