Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses.

Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and can modify recipient cell function. To determine how the composition and cellular sources of exRNAs and the extracellular vesicles (EVs) that carry them change in vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before and after lung allergen challenge. In the lung, extracellular microRNAs (ex-miRNAs) had a composition that was highly correlated with airway-lining epithelium. Using cell type-specific membrane tagging and single vesicle flow, we also found that 80% of detected vesicles were of epithelial origin. After the induction of allergic airway inflammation, miRNAs selectively expressed by immune cells, including miR-223 and miR-142a, increased and hematopoietic-cell-derived EVs also increased >2-fold. These data demonstrate that infiltrating immune cells release ex-miRNAs and EVs in inflamed tissues to alter the local extracellular environment

MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation.

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92-deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses

Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons

Cymantrene–Triazole "Click" Products: Structural Characterization and Electrochemical Properties

We report the first known examples of triazole-derivatized cymantrene complexes (η5-[4-substituted triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I), obtained via a “click” chemical synthesis, bearing a phenyl, 3-aminophenyl, or 4-aminophenyl moiety at the 4-position of the triazole ring. Structural characterization data using multinuclear NMR, UV–vis, ATR-IR, and mass spectrometric methods are provided, as well as crystallographic data for (η5-[4-phenyltriazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I) and (η5-[4-(3-aminophenyl)triazol-1-yl]cyclopentadienyl)tricarbonylmanganese(I). Cyclic voltammetric characterization of the redox behavior of each of the three cymantrene–triazole complexes is presented together with digital simulations, in situ infrared spectroelectrochemistry, and DFT calculations to extract the associated kinetic and thermodynamic parameters. The trypanocidal activity of each cymantrene–triazole complex is also examined, and these complexes are found to be more active than cymantrene alone

Hospitalization and emergency department visits among seniors receiving homecare: a pilot study

BACKGROUND: Despite the recent growth in home health services, data on clinical outcomes and acute health care utilization among older adults receiving homecare services are sparse. Obtaining such data is particularly relevant in Ontario where an increasing number of frail seniors receiving homecare are awaiting placement in long-term care facilities. In order to determine the feasibility of a large-scale study, we conducted a pilot study to assess utilization of acute health care services among seniors receiving homecare to determine associated clinical outcomes. METHODS: This prospective cohort study followed forty-seven seniors admitted to homecare by two homecare agencies in Hamilton, Ontario over a 12-month period. Demographic information and medical history were collected at baseline, and patients were followed until either termination of homecare services, death, or end of study. The primary outcome was hospitalization. Secondary outcomes included emergency department visits that did not result in hospitalization and death. Rates of hospitalization and emergency department visits without admission were calculated, and univariate analyses were performed to test for potential risk factors. Survival curves for accumulative rates of hospitalization and emergency department visits were created. RESULTS: 312 seniors were eligible for the study, of which 123 (39%) agreed to participate initially. After communicating with the research nurse, of the 123 who agreed to participate initially, 47 (38%) were enrolled in the study. Eleven seniors were hospitalized during 3,660 days of follow-up for a rate of 3.0 incident hospitalizations per 1,000 homecare-days. Eleven seniors had emergency department visits that did not result in hospitalization, for a rate of 3.3 incident emergency department visits per 1,000 homecare-days. There were no factors significantly associated with hospitalization or emergency department visits when adjustment was made for multiple comparisons. CONCLUSION: The incidence of hospitalization and visits to the emergency department among seniors receiving homecare services is high. Getting satisfactory levels of enrolment will be a major challenge for larger prospective studies

The Global COVID-19 Observatory and Resource Center for Childhood Cancer: A response for the pediatric oncology community by SIOP and St. Jude Global

The COVID-19 pandemic quickly led to an abundance of publications and recommendations, despite a paucity of information on how COVID-19 affects children with cancer. This created a dire need for a trusted resource with curated information and a space for the pediatric oncology community to share experiences. The Global COVID-19 Observatory and Resource Center for Childhood Cancer was developed, launched, and maintained by the International Society of Pediatric Oncology and St. Jude Children's Research Hospital. The three components (Resource Library, Global Registry, and Collaboration Space) complement each other, establishing a mechanism to generate and transfer knowledge rapidly throughout the community

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

ChemBank: a small-molecule screening and cheminformatics resource database

ChemBank (http://chembank.broad.harvard.edu/) is a public, web-based informatics environment developed through a collaboration between the Chemical Biology Program and Platform at the Broad Institute of Harvard and MIT. This knowledge environment includes freely available data derived from small molecules and small-molecule screens and resources for studying these data. ChemBank is unique among small-molecule databases in its dedication to the storage of raw screening data, its rigorous definition of screening experiments in terms of statistical hypothesis testing, and its metadata-based organization of screening experiments into projects involving collections of related assays. ChemBank stores an increasingly varied set of measurements derived from cells and other biological assay systems treated with small molecules. Analysis tools are available and are continuously being developed that allow the relationships between small molecules, cell measurements, and cell states to be studied. Currently, ChemBank stores information on hundreds of thousands of small molecules and hundreds of biomedically relevant assays that have been performed at the Broad Institute by collaborators from the worldwide research community. The goal of ChemBank is to provide life scientists unfettered access to biomedically relevant data and tools heretofore available primarily in the private sector

The impact of a brief lifestyle intervention delivered by generalist community nurses (CN SNAP trial)

BackgroundThe risk factors for chronic disease, smoking, poor nutrition, hazardous alcohol consumption, physical inactivity and weight (SNAPW) are common in primary health care (PHC) affording opportunity for preventive interventions. Community nurses are an important component of PHC in Australia. However there has been little research evaluating the effectiveness of lifestyle interventions in routine community nursing practice. This study aimed to address this gap in our knowledge.MethodsThe study was a quasi-experimental trial involving four generalist community nursing (CN) services in New South Wales, Australia. Two services were randomly allocated to an ‘early intervention’ and two to a ‘late intervention’ group. Nurses in the early intervention group received training and support in identifying risk factors and offering brief lifestyle intervention for clients. Those in the late intervention group provided usual care for the first 6 months and then received training. Clients aged 30–80 years who were referred to the services between September 2009 and September 2010 were recruited prior to being seen by the nurse and baseline self-reported data collected. Data on their SNAPW risk factors, readiness to change these behaviours and advice and referral received about their risk factors in the previous 3 months were collected at baseline, 3 and 6 months. Analysis compared changes using univariate and multilevel regression techniques.Results804 participants were recruited from 2361 (34.1%) eligible clients. The proportion of clients who recalled receiving dietary or physical activity advice increased between baseline and 3 months in the early intervention group (from 12.9 to 23.3% and 12.3 to 19.1% respectively) as did the proportion who recalled being referred for dietary or physical activity interventions (from 9.5 to 15.6% and 5.8 to 21.0% respectively). There was no change in the late intervention group. There a shift towards greater readiness to change in those who were physically inactive in the early but not the comparison group. Clients in both groups reported being more physically active and eating more fruit and vegetables but there were no significant differences between groups at 6 months.ConclusionThe study demonstrated that although the intervention was associated with increases in advice and referral for diet or physical activity and readiness for change in physical activity, this did not translate into significant changes in lifestyle behaviours or weight. This suggests a need to facilitate referral to more intensive long-term interventions for clients with risk factors identified by primary health care nurses