Background
Bacterial flagellin, a Toll‐like receptor 5 agonist, is used as an adjuvant for immunomodulation. In this study, we aimed to evaluate the effect and its mechanism following intralymphatic ...administration of OVA‐flagellin (FlaB) mixture in the mouse model of allergic rhinitis.
Materials and Methods
BALB/c mice were sensitized with OVA and treated with an OVA‐FlaB mixture via intranasal, sublingual, and intralymphatic routes to evaluate the effect of each treatment. Several parameters for allergic inflammation and its underlying mechanisms were then evaluated.
Results
Intralymphatic injection of the OVA‐FlaB mixture reduced symptom scores, eosinophil infiltration in the nasal mucosa, and total and OVA‐specific IgE levels more significantly than intranasal and sublingual administration. Systemic cytokine (IL‐4, IL‐5, IL‐6, IL‐17, and IFN‐γ) production and local cytokine (IL‐4 and IL‐5) production were also reduced significantly after intralymphatic injection with OVA‐FlaB. Double intralymphatic injection of the mixture was more effective than single injection. Moreover, the expression of innate cytokines such as IL‐25 and IL‐33 in nasal epithelial cells was reduced, and the expression of chemokines such as CCL24 (eotaxin‐2), CXCL1, and CXCL2 was decreased in the nasal mucosa, suggesting the underlying mechanism for intralymphatic administration of the OVA‐FlaB mixture.
Conclusion
Intralymphatic administration of an OVA‐FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in a mouse model of allergic rhinitis. This effect may be attributed to the reduced expression of innate cytokines and chemokines. This treatment modality can be considered as a new therapeutic method and agent.
: Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by excessive collagen deposition, vascular dysfunction, and fibrosis of cutaneous and visceral organs. ...Current therapeutic options are limited and provide only modest benefit.
: This review summarizes investigational agents in recent Phase I and II clinical trials evaluated for the treatment of SSc with a focus on skin in patients with early diffuse disease and interstitial lung disease. We performed a search on Pubmed and https://clinicaltrials.gov with keywords systemic sclerosis, Phase I clinical trial, and Phase II clinical trial to identify relevant studies from 2015 to 2019.
: Therapeutic interventions in SSc should be guided by the level of disease activity and the degree of organ involvement. While most novel agents have failed to meet the primary endpoints of reducing skin thickening as measured by the modified Rodnan skin score, some have shown promise in improving the Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis (CRISS), reducing lung function decline, or improving patient-reported outcomes. However, most of the current evidence is based on small or open-label clinical trials. Well-designed, large, randomized, Phase III clinical trials are necessary to define the roles of investigational agents in treating SSc.
Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical ...antipsychotic drugs, which have largely replaced the older agents in clinical practice.
We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs).
Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval CI, 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score.
Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death.
Summary
Current bibliometric analyses of the evolving trends in research scope category across different time periods using the H‐classics method in implantology are considerably limited. The purpose ...of this study was to identify the classic articles in implantology to analyse bibliometric characteristics and associated factors in implantology for the past four decades. H‐Classics in implantology were identified within four time periods between 1977 and 2016, based on the h‐index from the Scopus® database. For each article, the principal bibliometric parameters of authorship, geographic origin, country origin, and institute origin, collaboration, centralisation, article type, scope of study and other associated factors were analysed in four time periods. A significant increase in mean numbers of authors per H‐Classics was found across time. Both Europe and North America were the most productive region/country and steadily dominated this field in each time period. Collaborations of author, internationally and inter‐institutionally had significantly increased across time. A significant decentralisation in authorships, institutes and journals was noted in past four decades. The journal of Clinical Oral Implant Researches has raised its importance for almost 30 years (1987‐2016). Research on Complications, peri‐implant infection/pathology/therapy had been increasing in production throughout each period. This is the first study to evaluate research trends in implantology in the past 40 years using the H‐classics method, which through analysing via principle bibliometric characteristics reflected a historical perspective on evolutionary mainstream in the field. Prominence of research regarding complications may forecast innovative advancements in future.
•Microplastics were analyzed in different water types and their treatment plants.•Wastewater was determined to contain the most abundant quantity of microplastics.•Ultrafiltration appears to be an ...excellent process for microplastics removal.•The quantity of microplastics in the tested waters in France is relatively high.
The distribution and fate of microplastics in different water sources and their treatment plants (seawater, three municipal wastewaters, a pharmaceutical factory wastewater, and three drinking waters) in France were studied. Currently, research in this field is still under exploration since almost no relevant standards or policies have been introduced for the detection, the removal, or the discharge of microplastics. This study used an improved quantitative and qualitative analytical methodology for microplastic detection by μ-FTIR carried out with siMPle analytical software. By investigation, wastewater was determined to contain the most abundant microplastics in quantity (4,203–42,000 MP·L−1), then followed by surface water/groundwater (153–19,836 MP·L−1) and seawater (around 420 MP·L−1). Polyethylene was the dominant material in almost all water types followed by polypropylene, polystyrene, and polyethylene terephthalate. Almost all treatment technologies could remove microplastics whatever the feed water types and concentration of microplastics, though some treatment processes or transport pipes could cause additional contamination from microplastics. The four WWTPs, three DWTPs, and SWTP in France provided, respectively, 87.8–99.8%, 82.3–99.9%, 69.0–96.0% removal/retention of MPs in quantity, and provided 97.3–100%, 91.9–99.9%, 92.2–98.1% removal/retention of MPs in surface area. Moreover, ultrafiltration was confirmed to be an effective technology for microplastic retention and control of dimensions of microplastics in smaller ranges both in field-scale and lab-scale experiments. The 200 kDa ultrafiltration membrane could retain 70–100% and 80–100% of microplastics in quantity and in surface area, respectively.
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Long-term culture and monitoring of individual multicellular spheroids and embryoid bodies (EBs) remains a challenge for in vitro cell propagation. Here, we used a continuous 3D projection printing ...approach - with an important modification of nonlinear exposure - to generate concave hydrogel microstructures that permit spheroid growth and long-term maintenance, without the need for spheroid transfer. Breast cancer spheroids grown to 10 d in the concave structures showed hypoxic cores and signs of necrosis using immunofluorescent and histochemical staining, key features of the tumor microenvironment in vivo. EBs consisting of induced pluripotent stem cells (iPSCs) grown on the hydrogels demonstrated narrow size distribution and undifferentiated markers at 3 d, followed by signs of differentiation by the presence of cavities and staining of the three germ layers at 10 d. These findings demonstrate a new method for long-term (e.g. beyond spheroid formation at day 2, and with media exchange) 3D cell culture that should be able to assist in cancer spheroid studies as well as embryogenesis and patient-derived disease modeling with iPSC EBs.
Background
This study aimed to assess long‐term survival after liver resection for huge hepatocellular carcinoma (HCC).
Methods
Patients with stage I–III HCC who underwent hepatectomy from 2002 to ...2010 were identified retrospectively from prospective national databases and followed until December 2012. Patients were assigned into four groups according to tumour size: less than 3·0 cm (small), 3·0–4·9 cm (medium), 5·0–10·0 cm (large) and over 10·0 cm (huge). The primary endpoint was overall survival. The Kaplan–Meier method and Cox proportional hazards model were used for survival analysis.
Results
A total of 11 079 patients with HCC (mean(s.d.) age 59·7 (12·0) years) were eligible for this study. Median follow‐up was 72·5 months. Patients with huge HCC had the worst prognosis; overall survival rates for patients with small, medium, large and huge HCC were 72·0, 62·1, 50·8 and 35·0 per cent respectively at 5 years, and 52·6, 41·8, 35·8 and less than 20·0 per cent at 10 years (P < 0·001). Multivariable analysis showed that tumour size affected long‐term survival (hazard ratio (HR) 1·31, 1·55 and 2·38 for medium, large and huge HCC respectively versus small HCC). Prognostic factors for huge HCC were surgical margin larger than 0·2 cm (HR 0·70; P = 0·025), poor differentiation (HR 1·34; P = 0·004), multiple tumours (HR 1·64; P < 0·001), vascular invasion (HR 1·52; P = 0·008), cirrhosis (HR 1·37; P = 0·013) and the use of nucleoside analogues (HR 0·69; P = 0·004).
Conclusion
Huge HCCs have a worse prognosis than smaller HCCs after liver resection. A wide resection margin and antiviral therapy with nucleoside analogues may be associated with favourable long‐term survival.
Bigger not necessarily better
•An approach for microplastics analysis in real waters was developed using μ-FTIR.•Selection of appropriate rinsing water and digestion protocols was evaluated.•Digestion methods were not only ...related to the components of water samples.•Reliability of the methodology approach was evaluated through nine criteria.
Microplastics of millimeter dimensions have been widely investigated in environmental compartments and today, studies are mainly focused on particles of smaller dimensions (< 500 µm). However, as there are no relevant standards or policies for the preparation and analysis of complex water samples containing such particles, the results may be questionable. Therefore, a methodological approach for 10 µm to 500 µm microplastic analysis was developed using μ-FTIR spectroscopy coupled with the siMPle analytical software. This was undertaken on different water samples (sea, fresh, and wastewater) taking into consideration rinsing water, digestion protocols, collection of microplastics, and sample characteristics. Ultrapure water was the optimal rinsing water and ethanol was also proposed with a mandatory previous filtration. Although water quality could give some guidelines for the selection of digestion protocols, it is not the only decisive factor. The methodology approach by μ-FTIR spectroscopy was finally assessed to be effective and reliable. This improved quantitative and qualitative analytical methodology for microplastic detection can then be used to assess the removal efficiency of conventional and membrane treatment processes in different water treatment plants.
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