Seasonal occurrence of multiple classes of antibiotics in East China rivers and their association with suspended particulate matter.

Understanding the occurrence and fate of antibiotics from different categories is vital to predict their environmental exposure and risks. This study presents the spatiotemporal occurrence of 45 multi-class antibiotics and their associations with suspended particulate matter (SPM) in Xiaoqing River (XRB) and Yellow River (YRB) via 10-month monitoring in East China. Thirty-five and 31 antibiotics were detected in XRB and YRB, respectively. Among them, fluoroquinolones (FQs) had the highest total mean concentration (up to 24.8 µg/L in XRB and 15.4 µg/L in YRB), followed by sulfonamides (SAs) (14.0 µg/L and 15.4 µg/L) and macrolides (MLs) (1.1 µg/L and 1.6 µg/L). Significant spatial-temporal variations were found in both rivers where higher concentrations of antibiotics were observed in urban and densely populated areas during winter and spring. Hydrological factors such as river flow and water volume, instream attenuation and antibiotic usage may cause the observed variabilities in the seasonal patterns of antibiotic pollution. Using linear regression analysis, for the first time, this study confirmed that the total concentrations of MLs (p < 0.05), FQs (p < 0.001) and SAs (p < 0.001) were strongly correlated with the turbidity/total suspended solids in the studied rivers (except MLs in YRB). It is thus suggested that partitioning processes onto SPM might affect the distribution of detected antibiotics in rivers, which are largely dependent on SPM composition and characteristics. The risk quotient (RQ) determined for up to 87 % of individual compound was below 0.1 in both rivers; however, the high joint toxicity reflected by the mixed RQs of detected antibiotics may rise risk alarm for aquatic species. Further aspects regarding active mechanisms of SPM-antibiotic interactions and ecological risks of coexistence of multiple antibiotics need to be investigated.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cytotoxicity in PC12 cells.

Alpinia oxyphylla, a traditional herb, is widely used for its neuroprotective, antioxidant and memory-improving effects. However, the neuroprotective mechanisms of action of its active ingredients are unclear. In this study, we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro. Alpinia oxyphylla was extracted three times with 95% ethanol (representing extracts 1-3). The third 95% ethanol extract was dried and resuspended in water, and then extracted successively with petroleum ether, ethyl acetate and n-butanol (representing extracts 4-6). The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells. The protective effect of the three ethanol extracts (at tested concentrations of 50, 100 and 200 µg/mL) against cytotoxicity to PC12 cells increased in a concentration-dependent manner. The ethyl acetate, petroleum ether and n-butanol extracts (each tested at 100, 150 and 200 µg/mL) had neuroprotective effects as well. The optimum effective concentration ranged from 50-200 µg/mL, and the protective effect of the ethyl acetate extract was comparatively robust. These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide. Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

Influential factors for visit time for tracheobronchial foreign bodies in pediatrics.

PURPOSE: This study aims to investigate the inflential factors for visit time for tracheobronchial foreign bodies in pediatrics, and to shorten the time of diagnosis and reduce complications. METHODS: A questionnaire survey was designed and conducted among the caretakers of children with tracheobronchial foreign bodies, and the related inflential factors for visit time were analyzed. RESULTS: The visit time for tracheobronchial foreign body was correlated with the age of the child, the type of foreign body, the educational level of the caretaker, a history of foreign body aspiration were provided, an examination was performed during the visit, the anti-inflammatory and anti-allergic treatment, and transfer to a higher level hospital. Age, history of foreign body aspiration were provided, and anti-inflammatory and anti-allergic treatment were the independent inflential factors for the time of diagnosis (P < 0.05). CONCLUSION: The visit time for tracheobronchial foreign bodies was affected by many factors. It is necessary to strengthen the publicity scope and intensity on health education for tracheobronchial foreign bodies in community doctors and parents, to shorten the time of diagnosis and reduce complications.

Peptide-MHC-based nanomedicines for autoimmunity function as T-cell receptor microclustering devices.

We have shown that nanoparticles (NPs) can be used as ligand-multimerization platforms to activate specific cellular receptors in vivo. Nanoparticles coated with autoimmune disease-relevant peptide-major histocompatibility complexes (pMHC) blunted autoimmune responses by triggering the differentiation and expansion of antigen-specific regulatory T cells in vivo. Here, we define the engineering principles impacting biological activity, detail a synthesis process yielding safe and stable compounds, and visualize how these nanomedicines interact with cognate T cells. We find that the triggering properties of pMHC-NPs are a function of pMHC intermolecular distance and involve the sustained assembly of large antigen receptor microclusters on murine and human cognate T cells. These compounds show no off-target toxicity in zebrafish embryos, do not cause haematological, biochemical or histological abnormalities, and are rapidly captured by phagocytes or processed by the hepatobiliary system. This work lays the groundwork for the design of ligand-based NP formulations to re-program in vivo cellular responses using nanotechnology.

Jagunal homolog 1 is a critical regulator of neutrophil function in fungal host defense.

Neutrophils are key innate immune effector cells that are essential to fighting bacterial and fungal pathogens. Here we report that mice carrying a hematopoietic lineage-specific deletion of Jagn1 (encoding Jagunal homolog 1) cannot mount an efficient neutrophil-dependent immune response to the human fungal pathogen Candida albicans. Global glycobiome analysis identified marked alterations in the glycosylation of proteins involved in cell adhesion and cytotoxicity in Jagn1-deficient neutrophils. Functional analysis confirmed marked defects in neutrophil migration in response to Candida albicans infection and impaired formation of cytotoxic granules, as well as defective myeloperoxidase release and killing of Candida albicans. Treatment with granulocyte/macrophage colony-stimulating factor (GM-CSF) protected mutant mice from increased weight loss and accelerated mortality after Candida albicans challenge. Notably, GM-CSF also restored the defective fungicidal activity of bone marrow cells from humans with JAGN1 mutations. These data directly identify Jagn1 (JAGN1 in humans) as a new regulator of neutrophil function in microbial pathogenesis and uncover a potential treatment option for humans.

Autoimmune responses in T1DM: quantitative methods to understand onset, progression, and prevention of disease.

Understanding the physiological processes that underlie autoimmune disorders and identifying biomarkers to predict their onset are two pressing issues that need to be thoroughly sorted out by careful thought when analyzing these diseases. Type 1 diabetes (T1D) is a typical example of such diseases. It is mediated by autoreactive cytotoxic CD4⁺ and CD8⁺ T-cells that infiltrate the pancreatic islets of Langerhans and destroy insulin-secreting ß-cells, leading to abnormal levels of glucose in affected individuals. The disease is also associated with a series of islet-specific autoantibodies that appear in high-risk subjects (HRS) several years prior to the onset of diabetes-related symptoms. It has been suggested that T1D is relapsing-remitting in nature and that islet-specific autoantibodies released by lymphocytic B-cells are detectable at different stages of the disease, depending on their binding affinity (the higher, the earlier they appear). The multifaceted nature of this disease and its intrinsic complexity make this disease very difficult to analyze experimentally as a whole. The use of quantitative methods, in the form of mathematical models and computational tools, to examine the disease has been a very powerful tool in providing predictions and insights about the underlying mechanism(s) regulating its onset and development. Furthermore, the models developed may have prognostic implications by aiding in the enrollment of HRS into trials for T1D prevention. In this review, we summarize recent advances made in determining T- and B-cell involvement in T1D using these quantitative approaches and delineate areas where mathematical modeling can make further contributions in unraveling certain aspect of this disease.

[Prevention and nursing care of central line-associated bloodstream infections in critically ill patients].

Catheter-related bloodstream infections are associated with significantly increased morbidity, mortality, and expenditures. Such infections are a serious threat to patient safety in the intensive care unit. This review describes the latest protocols related to preventing and treating central venous catheter-associated bloodstream infections in critically ill patients. According to 2011 Center for Disease Control (CDC) guidelines and central line care bundles by the institute for healthcare improvement (IHI), prevention measures for catheter-related bloodstream infections include the following: hand hygiene, maximal barrier precautions insertion, chlorhexidine skin antisepsis, optimal catheter site selection, proper catheter maintenance, insertion site care, and daily review of line necessity, with prompt removal of unnecessary lines. These are important and effective infection prevention measures. Guidelines and care bundles also recommend organizing care modules based on unit characteristics; integrating resources and empirical measures; education and training to promote comprehensive implementation; and auditing and monitoring to ensure staff continue to follow procedures. Effectively preventing central venous catheter-related bloodstream infections can enhance care quality and move healthcare closer to achieving the goal of zero tolerance.

Stroke subtype classification: a comparative study of ASCO and modified TOAST.

BACKGROUND AND PURPOSE: The ASCO stroke classification may be an improvement over the modified TOAST for etiological diagnoses. We aimed to compare the differences in stroke subtype classification between these two classification system. METHODS: Selected for this study were 425 first-time acute ischemic stroke patients. For each, the cause of ischemic stroke was classified according to both the ASCO and modified TOAST criteria. The κ statistic and McNemar test were used to compare the similarities and differences, respectively, between the two approaches. RESULTS: More patients were classified as having an atherosclerotic etiology under the ASCO 1 category than the modified TOAST system (60.2% vs. 57.9%; P=0.132). There was no significant difference between the proportion of patients with undetermined etiology as defined by the ASCO 1 and the modified TOAST (15.5% vs. 16.2%; P=0.795). Both the modified TOAST and ASCO-1 correctly identified all patients with etiology "other cause". Agreement between the two classification systems was high in every subtype category except 'undetermined' (κ>0.81 for atherosclerosis, κ=0.61 to κ=0.8 for cardiac disease, and κ=0.480 for undetermined). When ASCO-1 to ASCO 3 were applied, atherosclerosis was identified as the cause in 76.0% of patients, small artery disease in 46.4%, and cardiac disease in 11.3%. CONCLUSION: There is a moderately high agreement between the ASCO and modified TOAST classification schemes in all subtypes except that of "undetermined" etiology. Application of ASCO-1 did not reduce the proportion of patients 'undetermined' etiology compared to modified TOAST.