Effects of Autism-associated mutations on structure and function of Epigenetic Regulator KMT5B

[Abstract Not Available

Constraints and opportunities of the Tamil Nadu industrial cassava value chain and market

Cassava (ManihotesculentaCrantz), a tuber crop, known to support rural communities for its caloric value and vast industrial applications, supports over 10,000 smallholder farmers in Tamil Nadu, India. Using quantitative and qualitative data collected from key informants along the industrial cassava market chain in Tamil Nadu, this paper analyses the market structure, supply, demand and market trends for industrially utilized cassava. This analysis is used to identify market constraints and opportunities amongst the value chain actors to support marketgrowth, with the goal of ultimately improving the livelihoods of smallholder farmers in Tamil Nadu. Clear constraints were observed influencing market functions and actors. The industrial cassava industry is undergoing continual transition amidst pressurein an unregulated and fluctuating marketplace, additionally impacting demand trends. The market, composed of diverse production units relative to size and economical value, has become highly competitive resulting in constraints related to product quality and production methods. These constraints have direct impacts on farmers, who often take the greatest economical risk along the value chain. Key recommendations resulting from this research include further exploration of a regulated market, establishing industrial production standards, improving quality standards, and further development of marketing methods. Essential to these recommendations is a collaborative effort towards innovation along the entire value chain, as growth needs to be collectively pursued to ensure sustainable market function and fair distribution of rents

SYNTHESIS AND CHARACTERIZATION OF POLY D-L LACTIDE (PLA) NANOPARTICLES FOR THE DELIVERY OF QUERCETIN

Objectives: Synthesis and optimization of Poly D-L Lactide (PLA) nanoparticles for the delivery of an antioxidant molecule quercetin.Methods: The quercetin was encapsulated by PLA nanoparticles by nanoprecipitation method. The average particle size and the electric charge for different formulations were measured by particle size and zeta potential analyzer. The quercetin loaded PLA nanoparticles (Q-PLAN) was characterized by differential scanning calorimetry & Fourier transform-Infra red spectroscopy, Scanning electron microscopy and Atomic force microscopy. The average drug content, encapsulation efficiency and drug release studies were carried out for different formulations of Q-PLAN. The antioxidant activity of the formulated Q-PLAN nanoparticles was tested using DPPH assay.Results: The formulation F3 (Quercetin 75 mg: PLA 200 mg) was found to be optimized formulation based on particle size analysis, Zeta potential, drug content, encapsulation efficiency and drug release studies. The mean diameter and zeta potential of optimized Q-PLAN and PLA nanoparticles were found to be 242±20 nm, 185±10 nm and-22.5±1.5 mV,-20.5±1.0 mV. The F3 formulation showed encapsulation efficiency of 73.3% and 5.5±0.06 mg/ml of actual drug loading. The F3 formulations showed 99.7% of drug release. The optimized Q-PLAN showed better scavenging effects when compared to the free quercetin.Conclusions: The poor aqueous solubility and stability of the antioxidant molecule quercetin have been improved by entrapping the quercetin molecules into the PLA nanoparticles.Â

Neoadjuvant Pembrolizumab and High-Dose IFNα-2b in Resectable Regionally Advanced Melanoma

PurposeNeoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.Patients and methodsPatients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.v. every 3 weeks and HDI 20 MU/m2/day i.v., 5 days per week for 4 weeks, then 10 MU/m2/day subcutaneously 3 days per week for 2 weeks. Definitive surgery followed, as did adjuvant combination immunotherapy, completing a year of treatment. Primary endpoint was safety of the combination. Secondary endpoints included overall response rate (ORR), pathologic complete response (pCR), recurrence-free survival (RFS), and overall survival (OS). Blood samples for correlative studies were collected throughout. Tumor tissue was assessed by IHC and flow cytometry at baseline and at surgery.ResultsA total of 31 patients were enrolled, and 30 were evaluable. At data cutoff (October 2, 2019), median follow-up for OS was 37.87 months (range, 33.2-43.47). Median OS and RFS were not reached. Radiographic ORR was 73.3% [95% confidence interval (CI): 55.5-85.8], with a 43% (95% CI: 27.3-60.1) pCR rate. None of the patients with a pCR have had a recurrence. HDI and pembrolizumab were discontinued in 73% and 43% of patients, respectively. Correlative analyses suggested that intratumoral PD-1/PD-L1 interaction and HLA-DR expression are associated with pCR (P = 0.002 and P = 0.008, respectively).ConclusionsNeoadjuvant concurrent HDI and pembrolizumab demonstrated promising clinical activity despite high rates of treatment discontinuation. pCR is a prognostic indicator.See related commentary by Menzies et al., p. 4133