Simple Cannulation Procedure for Serial Blood Sampling Through Cutaneous Ulnar Vein in Chickens

The objective of the study was to collect repeated, low-stress blood samples from the ulnar vein of chickens required for pharmacokinetic studies or hormonal assays. The study used 5 apparently healthy, unsexed, commercial broiler chickens about 6 weeks old and weighing 1.7–1.9 kg for serial sampling of blood. The study prepared the birds prior to cannulation and penetrated the catheter through the skin and into the lumen of the ulnar vein. The study successfully carried out serial blood samplings in 4 of 5 cannulated birds. Heparin (10%) solution maintained patency and prevented blood clot formation inside the cannula. However, the study found repeated clotting occurring in 1 bird. Cannula failed to maintain patency; the study could not carry out blood sampling properly, which was attributed to air embolism that might have occurred during catheter manipulation or repeated filling of cannula with heparin solution. The study observed no hematoma or inflammation at the site of cannulation. Owing to the advantages and to facilitate compliance with nonhuman animal welfare, this technique seems simple and efficient, allowing adoption for serial blood collection in chickens.     

Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment.

Objective

To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment.

Methods

We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies'' web sites electronically up to Dec 30^th, 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates.

Results

We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin.

Conclusions

Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment.     

The Efficacy of Resiliency Training Programs: A Systematic Review and Meta-Analysis of Randomized Trials

Importance

Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders.

Objectives

To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases.

Data Sources

Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts.

Study Selection

Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used.

Data Extraction and Synthesis

Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups.

Main Outcomes

The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety.

Results

We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I² = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I² = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I² = 61%].

Conclusions

We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it.

Registration Number

PROSPERO #CRD42014007185     

Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.     

Metabolic Reprogramming in Mutant IDH1 Glioma Cells

BackgroundMutations in isocitrate dehydrogenase (IDH) 1 have been reported in over 70% of low-grade gliomas and secondary glioblastomas. IDH1 is the enzyme that catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate while mutant IDH1 catalyzes the conversion of α-ketoglutarate into 2-hydroxyglutarate. These mutations are associated with the accumulation of 2-hydroxyglutarate within the tumor and are believed to be one of the earliest events in the development of low-grade gliomas. The goal of this work was to determine whether the IDH1 mutation leads to additional magnetic resonance spectroscopy (MRS)–detectable changes in the cellular metabolome.MethodsTwo genetically engineered cell models were investigated, a U87-based model and an E6/E7/hTERT immortalized normal human astrocyte (NHA)-based model. For both models, wild-type IDH1 cells were generated by transduction with a lentiviral vector coding for the wild-type IDH1 gene while mutant IDH1 cells were generated by transduction with a lentiviral vector coding for the R132H IDH1 mutant gene. Metabolites were extracted from the cells using the dual-phase extraction method and analyzed by ¹H-MRS. Principal Component Analysis was used to analyze the MRS data.ResultsPrincipal Component Analysis clearly discriminated between wild-type and mutant IDH1 cells. Analysis of the loading plots revealed significant metabolic changes associated with the IDH1 mutation. Specifically, a significant drop in the concentration of glutamate, lactate and phosphocholine as well as the expected elevation in 2-hydroxyglutarate were observed in mutant IDH1 cells when compared to their wild-type counterparts.ConclusionThe IDH1 mutation leads to several, potentially translatable MRS-detectable metabolic changes beyond the production of 2-hydroxyglutarate.     

MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes

The mechanisms regulating the disassembly of branched actin networks formed by the Arp2/3 complex still remain to be fully elucidated. In addition, the impact of Arp3 isoforms on the properties of Arp2/3 are also unexplored. We now demonstrate that Arp3 and Arp3B isocomplexes promote actin assembly equally efficiently but generate branched actin networks with different disassembly rates. Arp3B dissociates significantly faster than Arp3 from the network, and its depletion increases actin stability. This difference is due to the oxidation of Arp3B, but not Arp3, by the methionine monooxygenase MICAL2, which is recruited to the actin network by coronin 1C. Substitution of Arp3B Met293 by threonine, the corresponding residue in Arp3, increases actin network stability. Conversely, replacing Arp3 Thr293 with glutamine to mimic Met oxidation promotes disassembly. The ability of MICAL2 to enhance network disassembly also depends on cortactin. Our observations demonstrate that coronin 1C, cortactin, and MICAL2 act together to promote disassembly of branched actin networks by oxidizing Arp3B-containing Arp2/3 complexes.