Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

Protein and Long-Chain n-3 Polyunsaturated Fatty Acids Recovered from Herring Brines upon Flocculation and Flotation─A Case Study

A novel integrated process for recovery of protein-enriched biomasses from 5% presalting brines and spice brines of herring (Clupea harengus) was investigated by combining carrageenan- and/or acid-driven flocculation (F) plus dissolved air flotation (DAF). The F-DAF technique with carrageenan resulted in protein and lipid recoveries from 5% presalting brine of 78 and 38%, respectively. Without flocculation or with only acidification, protein and lipid recoveries in DAF were only 13 and 10%, respectively. Low protein and lipid recoveries, 8-12 and 1.8-8.2%, respectively, were also obtained when spice brine was subjected to only acidification and DAF. The protein content in dry biomasses from 5% presalting brine and spice brine was 36-43 and 13-16%, respectively. The corresponding lipid levels were 23-31 and 9-18%, respectively, with ash levels of 11-20 and 38-45%, respectively. Biomass proteins contained ≤45% essential amino acids, and the lipids had ≤16% long-chain n-3 polyunsaturated fatty acids. Freeze-dried spice brine biomasses were characterized by anchovy- and spice-related sensory attributes. 5% presalting brine biomasses were connected to fish and seafood attributes and showed gel forming capacity. The outlined F-DAF recovery system can thus recover both nutrients and interesting flavors from the herring process waters, which are currently lost from the food chain

Uterine Artery Embolization in a Patient With Large Uterine Fibroids

A woman in her 20s with no past medical history presented to the emergency department with a 4-day history of abdominal pain. Imaging revealed several large uterine fibroids that compressed various intra-abdominal structures. Options of observation, medical management, surgical management with abdominal myomectomy, and uterine artery embolization (UAE) were discussed. The patient was counseled about the associated risks of UAE and myomectomy. Since both procedures have a risk of infertility, the patient elected to proceed with uterine artery embolization due to the less invasive nature of the procedure. She was discharged after one day in the hospital following the procedure and readmitted three days later for suspected endometritis. The patient was treated with antibiotics for five days and discharged home. Eleven months post-procedure, the patient became pregnant. The patient had achieved a full-term delivery at 39 weeks and two days via a cesarean section secondary to a breech presentation

HISTO-ANATOMICAL AND PRELIMINARY CHROMATOGRAPHIC ANALYSIS ON POLYGALA VULGARIS L. (POLYGALACEAE) SPECIES

The paper highlights the histo-anatomical investigation of root, rhizome, aboveground stem and leaf of Polygala vulgaris L. (Polygalaceae) species, harvested in August 2016, from southern Romania, as well as the preliminary thin-layer chromatographic analysis of the polyphenols content of the aerial parts (Polygalae vulgaris herba). Rutin was identified and quantified starting from the 11 TLC fingerprint bands

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

External validation of the DHAKA score and comparison with the current IMCI algorithm for the assessment of dehydration in children with diarrhoea: a prospective cohort study

BACKGROUND: Dehydration due to diarrhoea is a leading cause of child death worldwide, yet no clinical tools for assessing dehydration have been validated in resource-limited settings. The Dehydration: Assessing Kids Accurately (DHAKA) score was derived for assessing dehydration in children with diarrhoea in a low-income country setting. In this study, we aimed to externally validate the DHAKA score in a new population of children and compare its accuracy and reliability to the current Integrated Management of Childhood Illness (IMCI) algorithm. METHODS: DHAKA was a prospective cohort study done in children younger than 60 months presenting to the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute diarrhoea (defined by WHO as three or more loose stools per day for less than 14 days). Local nurses assessed children and classified their dehydration status using both the DHAKA score and the IMCI algorithm. Serial weights were obtained and dehydration status was established by percentage weight change with rehydration. We did regression analyses to validate the DHAKA score and compared the accuracy and reliability of the DHAKA score and IMCI algorithm with receiver operator characteristic (ROC) curves and the weighted kappa statistic. This study was registered with ClinicalTrials.gov, number NCT02007733. FINDINGS: Between March 22, 2015, and May 15, 2015, 496 patients were included in our primary analyses. On the basis of our criterion standard, 242 (49%) of 496 children had no dehydration, 184 (37%) of 496 had some dehydration, and 70 (14%) of 496 had severe dehydration. In multivariable regression analyses, each 1-point increase in the DHAKA score predicted an increase of 0.6% in the percentage dehydration of the child and increased the odds of both some and severe dehydration by a factor of 1.4. Both the accuracy and reliability of the DHAKA score were significantly greater than those of the IMCI algorithm. INTERPRETATION: The DHAKA score is the first clinical tool for assessing dehydration in children with acute diarrhoea to be externally validated in a low-income country. Further validation studies in a diverse range of settings and paediatric populations are warranted. FUNDING: National Institutes of Health Fogarty International Center

Influence of Substrate Temperature on Structural and Morphological Properties of SnO2 Nanostructured Thin Films

SnO2 nanostructures thin films with thickness of 500 nm were prepared by electron beam-physical vapor deposition on glass substrate at temperature of 300, 373, 443, and 583 K. Structural and morphological properties of these nanostructured thin films were studied by Scanning and Transmission Electron Microscopy (SEM, TEM) and Atomic Force Microscope (AFM) methods. The changes in structural and morphological properties are found at different temperatures. Increase temperature causes important change of the structural and morphological properties. The sample prepared at 300 K has crystalline structure and the sample prepared at 583 K has amorphous structure. Roughness parameters have low values at 300, 373, 443 K as opposed to the values obtained at 583 K. This different behavior may be due to the amorphous structure of the sample that was observed in the TEM analysis

External validation of the DHAKA score and comparison with the current IMCI algorithm for the assessment of dehydration in children with diarrhoea: a prospective cohort study

Background Dehydration due to diarrhoea is a leading cause of child death worldwide, yet no clinical tools for assessing dehydration have been validated in resource-limited settings. The Dehydration: Assessing Kids Accurately (DHAKA) score was derived for assessing dehydration in children with diarrhoea in a low-income country setting. In this study, we aimed to externally validate the DHAKA score in a new population of children and compare its accuracy and reliability to the current Integrated Management of Childhood Illness (IMCI) algorithm. Methods DHAKA was a prospective cohort study done in children younger than 60 months presenting to the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute diarrhoea (defi ned by WHO as three or more loose stools per day for less than 14 days). Local nurses assessed children and classifi ed their dehydration status using both the DHAKA score and the IMCI algorithm. Serial weights were obtained and dehydration status was established by percentage weight change with rehydration. We did regression analyses to validate the DHAKA score and compared the accuracy and reliability of the DHAKA score and IMCI algorithm with receiver operator characteristic (ROC) curves and the weighted κ statistic. This study was registered with ClinicalTrials.gov, number NCT02007733. Findings Between March 22, 2015, and May 15, 2015, 496 patients were included in our primary analyses. On the basis of our criterion standard, 242 (49%) of 496 children had no dehydration, 184 (37%) of 496 had some dehydration, and 70 (14%) of 496 had severe dehydration. In multivariable regression analyses, each 1-point increase in the DHAKA score predicted an increase of 0·6% in the percentage dehydration of the child and increased the odds of both some and severe dehydration by a factor of 1·4. Both the accuracy and reliability of the DHAKA score were signifi cantly greater than those of the IMCI algorithm. Interpretation The DHAKA score is the fi rst clinical tool for assessing dehydration in children with acute diarrhoea to be externally validated in a low-income country. Further validation studies in a diverse range of settings and paediatric populations are warranted

Dietary replacement of fishmeal with marine proteins recovered from shrimp and herring process waters promising in Atlantic salmon aquaculture

There is a general agreement that fish meal (FM) and fish oil (FO) are valuable resources for aquafeed, but that the production cannot keep the same pace as the current growth of the aquaculture industry. Therefore, there is a need to find alternative sources for lipids and protein. This study examines the possibility of using proteins recovered from seafood industry side stream waters as a complement to FM in feed for Atlantic salmon. To recover the proteins, herring and shrimp process side streams waters were flocculated then treated with dissolved air flotation (DAF), which is considered a gentle technology. Shrimp steam water was used to obtain shrimp protein (SP) and herring salt brine to obtain herring protein (HP). The recovered semi-solid protein fraction was spray dried and formulated into experimental diets at inclusion levels of 1.9–10% (dw/dw). Two feeding trials were conducted to investigate; 1) the properties of different flocculants to recover SP from shrimp steam water, alginate (Alg; 1.9% inclusion), carrageenan (Carr; 2.0% inclusion) and a synthetic flocculant from Kemira (Kem; 3.8% inclusion). 2) total or partial replacement of FM with SP-Alg (10% and no FM) and HP-Alg (3% and 8% FM). For both feeding trials each diet was provided to triplicate tanks (n = 31 and 30/tank) of Atlantic salmon with a start weight of 193 g (duration 10 weeks) and 304 g (duration 7 weeks) respectively. All fish showed similar feed intake, feed conversion ratio (on tank basis) and weight gain. The inclusion of SP or HP as total or partial replacement of FM did neither influence adiposity of the fish, as measured by condition factor, nor heposomatic index (HSI). No negative effect of the alternative protein could be found through histological examination of the intestine. In feeding trial two, diets did not affect the adaptive immune indicators CD8α and MHC II. The SP-Alg diet did not affect intestinal barrier and transporting functions, assessed using Ussing-chamber technology. However, HP-Alg affected the trans-epithelial resistance, which indicate that the intestinal barrier function could be affected by low inclusions. We conclude that from a biological perspective, SP recovered from shrimp steaming waters using Alg and DAF technology represents a new marine biomass with potential as a replacement for FM in Atlantic salmon feed. To diversify the possibility of using flocculants to retrieve proteins we also suggest further investigation of the potential to use Carr in larger inclusions

Endovascular Thrombectomy for Mild Strokes: How Low Should We Go? A Multicenter Cohort Study

Background and Purpose:Endovascular thrombectomy (EVT) is effective for acute ischemic stroke with large vessel occlusion (LVO) and NIHSS ≥6. However, EVT benefit for mild deficits LVOs (NIHSS Methods: A retrospective cohort of patients with anterior circulation LVO and NIHSSoutcome; mRS=0–2 was the secondary. Symptomatic intracerebral hemorrhage (sICH) was the safety outcome. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, presentation NIHSS, time-last-seen-normal-to-presentation, center, IV-alteplase, ASPECTS, and thrombus location. We then performed propensity score matching as a sensitivity analysis. Results were also stratified by thrombus location. Results: 214 patients (EVT-124, medical management-90) were included from 8 US and Spain centers between January/2012 and March/2017. The groups were similar in age, ASPECTS, IValteplase rate and time-last-seen-normal-to-presentation. There was no difference in mRS=0–1 between EVT and medical management (55.7% versus 54.4%, respectively, aOR=1.3, 95%CI=0.64–2.64, p=0.47). Similar results were seen for mRS=0–2 (63.3% EVT versus 67.8% medical management, aOR=0.9, 95%CI=0.43–1.88, p=0.77). In a propensity matching analysis, there was no treatment effect in 62 matched pairs (53.5%EVT, 48.4% medical management; OR=1.17, 95%CI=0.54–2.52, p=0.69). There was no statistically significant difference when stratified by any thrombus location; M1 approached significance (p=0.07). sICH rates were higher with thrombectomy (5.8% EVT versus 0% medical management, p=0.02). Conclusions: Our retrospective multicenter cohort study showed no improvement in excellent and independent functional outcomes in mild strokes (NIHS