Investigation of Electrical Transitions in the First Steps of Spark Plasma Sintering: Effects of Pre-Oxidation and Mechanical Loading within Copper Granular Media

Spark Plasma Sintering (SPS) has become a conventional and promising sintering method for powder consolidation. This study aims to well understand the mechanisms of densification encountered during SPS treatments, especially in the early stages of sintering. The direct current (DC) electrical behavior of copper granular medium is characterized. Their properties are correlated with their microstructural evolutions through post-mortem scanning electron microscope (SEM) observations to allow a thorough understanding of the involved Branly effect that is suspected to occur in SPS. The electrical response is studied by modifying the initial thickness of the oxide layer on particles surfaces and applying various mechanical loads on the granular medium. Without load and at low current, the measured quasi-reversible behavior is connected to the formation of spots at the microcontacts between the particles. By increasing the current, the Branly transition from an insulating to a conductive state suddenly occurs. The insulating oxide layer is destroyed, and micro-bridges are created. The application of a mechanical pressure strongly modifies the DC Branly effect. Increasing low stress leads to a strong decrease in the breakdown field. For high-applied pressure, successive drops in the electric field are detected during the electrical transition. These successive drops are induced by microcracking of the insulating oxide layer.     

Inhibition of In Vitro TNF-α Production by Anisomeles malabarica R.Br. Reinforces Its Anti-Rheumatic and Immunomodulatory Properties

In-vivo studies have suggested the anti-rheumatic and immunomodulatory properties of the methanolic extract of the plant Anisomeles malabarica R.Br. However, the mechanism of action of this plant in the modulation of inflammation using the various in vitro models has not been explored earlier. Hence, the current investigation was undertaken to study the anti-rheumatic and immunomodulatory role of aerial parts, leaves and roots in lipopolysaccharide (LPS) mediated signaling in macrophage and mouse connective tissue cell cultures. It was observed from the present study that by employing tumor necrosis factor-α (TNF-α) bioassay, all the three extracts viz., aerial parts, leaves and roots inhibited TNF-α production in LPS (1 μg/mL) stimulated RAW-32 cells. 38.75 % inhibition of TNF-α was observed at 200 μg extracts of the aerial parts of the plant followed by 17.64 and 14.94 % by the roots and leaves respectively. Taken together, these findings from the present in vitro studies suggest the anti-rheumatic and immunomodulatory properties of the methanolic extracts of A. malabarica.     

Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells

Introduction: There is a high expression of receptor tyrosine kinase like orphan receptor-1 (ROR-1), a tyrosine kinase receptor, in various tumor-cell types. ROR-1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR-1 is an attractive and promising therapeutic target. There are many therapeutic approaches that target ROR-1 and these include specific monoclonal antibodies (mAbs), modified T cells (CART cell), miRNAs and tyrosine kinase inhibitors (TKI).

Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.

Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1⁺ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment.     

Radio Frequency Ablation and Pulsed Radiofrequency for Treating Peripheral Neuralgias

Purpose of Review

Peripheral nerve pain is common among patients with typical management including the use of pain medications, neuropathic agents, steroid injections, and nerve blocks. Additionally, the use of pulsed radiofrequency (PRF) and radiofrequency ablation (RFA) can be used in the management of chronic peripheral nerve pain. Previous studies investigating the effectiveness of RFA and PRF, typically case reports, have demonstrated that peripheral nerve RFA and PRF have the potential to provide relief of chronic pain for long duration. Our study aimed at testing efficacy of RFA/PRF for treating peripheral neuralgia. This was a retrospective review. We identified 16 patients who received 17 RFAs/PRFs. Outcomes of interest collected included pain scores before and after procedures, percent improvement in pain after each procedure, and duration of improvement until the time of data collection. In addition, demographic data including age, sex, and nerves involved were collected.

Recent Findings

Eleven patients (12 RFAs/PRFs) (80%) reported improvement after their procedure. Pain scores improved significantly from 6.3?±?2.3 before each procedure to 3.6?±?2.7 after each procedure (p?=?0.003). Eleven patients (12 RFAs/PRFs) reported an average improvement of 60.8%?±?35% after their procedure with an average duration of improvement of 128.8?±?106.8 days.

Summary

RFA and PRF can be used to treat chronic peripheral pain after conservative methods fail to do so. Large clinical trials are needed to confirm our finding.

     

Decarboxylative cross-coupling reactions for P(O)–C bond formation

Phosphorus-containing compounds are one of the most important classes of organic compounds, which have wide applications in organic chemistry, medicinal chemistry, agricultural chemistry, and materials chemistry. In particular, organophosphorus compounds bearing a P(O)–C bond have attracted significant attention in recent decades due to their widespread biological and pharmacological activities. In this review, we will highlight the most important developments in the construction of P(O)–C bonds through decarboxylative C–P cross-coupling reactions. The literature has been surveyed from 2011 to May 2018.

Phosphorus-containing compounds are one of the most important classes of organic compounds, which have wide applications in organic chemistry, medicinal chemistry, agricultural chemistry, and materials chemistry.     

Excessive carotid in-stent neointimal formation predicts late cardiovascular events.

PURPOSE: To examine if excessive in-stent neointimal formation causing a subcritical stenosis may indicate enhanced vascular reactivity in response to injury, thus predicting late cardiovascular events. METHODS: One hundred consecutive patients (64 men; median age 71 years) with high-grade internal carotid artery stenoses (68 asymptomatic, 32 symptomatic) underwent carotid artery stenting (CAS). High-sensitivity C-reactive protein (hs-CRP) was measured before CAS. Patients were monitored with duplex ultrasound for excessive in-stent neointimal formation (flow-compromising lumen diameter reduction >/=50%), critical restenosis (>/=70%), or the occurrence of late major adverse cardiovascular events (MACE) defined as myocardial infarction (MI), stroke, and death occurring later than 30 days poststenting. RESULTS: Over a median 23-month follow-up, excessive neointimal formation was observed in 14 (14%) patients, restenosis in 2 (2%), and 30 late MACE in 25 [25%: 4 MIs, 2 ipsilateral strokes (in the patients with restenosis), 8 contralateral strokes, and 16 cardiovascular deaths]. Cumulative MACE-free survival rates at 6, 12, and 24 months were 92%, 84%, and 77%, respectively. Baseline hs-CRP levels were associated both with neointimal hyperplasia (p=0.024) and MACE (p=0.021). Patients with excessive neointimal formation exhibited a significantly increased adjusted risk for MACE (hazard ratio 3.56, p=0.010). CONCLUSIONS: Excessive in-stent neointimal formation after CAS indicates an increased risk for late MACE, potentially reflecting a state of exaggerated vascular reactivity in response to injury. Inflammation, which is associated both with neointimal hyperplasia and MACE, seems a common characteristic of different vascular pathologies.