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IRAK4 is an attractive therapeutic target for the treatment of inflammatory conditions. Structure guided optimization of a nicotinamide series of inhibitors has been expanded to explore the IRAK4 front pocket. This has resulted in the identification of compounds such as 12 with improved potency and selectivity. Additionally 12 demonstrated activity in a pharmacokinetics/pharmacodynamics (PK/PD) model. Further optimization efforts led to the identification of the highly kinome selective 21 , which demonstrated a robust PD effect and efficacy in a TLR7 driven model of murine psoriasis., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Late-life immigration among seniors for purposes of family reunification is a growing phenomenon in developed countries. Using the World Health Organization's Quality of Life instrument short form (WHOQOL-BREF) and other psychosocial measures related to the political/legal context of immigration, and personal and environmental autonomy (mastery, immigration status, access to transportation, and language barrier), this study examined quality of life (QoL) in Asian Indian seniors (N = 109), who immigrated to the United States to reunite with their adult children. The sample scores on Overall QoL and QoL domains (physical and psychological health, social relationships, and environment) were similar to established norms. Although all QoL domains correlated significantly with Overall QoL at the bivariate level, multivariate analysis showed that only environmental domain contributed significantly to Overall QoL. Linear regressions indicated: Mastery contributed significantly to Overall QoL and all QoL domains; access to transport contributed to Overall QoL, physical health, and environmental QoL; immigration status (a proxy for political/legal context) contributed to environmental QoL whereas language barrier contributed to none. Implications for improving perceptions of QoL, mastery, access to transport and other services are discussed.

Cancer is one of the leading causes of death in the world. American Cancer Society reported 12 million new cases of malignancy diagnosed worldwide in 2007, with 7.6 million people dying from the disease. Plant-derived molecules have played an important role in cancer chemotherapy. Many cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Flavonoids, a plant-derived molecule has shown to regulate proliferation and cell death pathways leading to cancer. Some Flavonoids have already entered in clinical trials, among them Quercetin is emerging as prospective anticancer drug candidates and its prodrug QC12 has entered in phase-I clinical studies. In this review authors have tried to cover in brief but comprehensive way, the chemistry related to synthesis and uses of "Quercetin & its derivatives" with special emphasis on the anticancer properties.

A case of Actinomycosis affecting the transverse colon masquerading as an abdominal neoplasm with perforation to abdominal parietal wall is presented. Abdominal actinomycosis lesions may present as a perforated abdominal neoplasm requiring emergency laparotomy. This case report highlights the diagnostic dilemma and the management algorithm for such infections.

Domesticated animals formed an important element of farming practices in prehistoric Britain, a fact revealed through the quantity and variety of animal bone typically found at archaeological sites. However, it is not known whether the ruminant animals were raised purely for their tissues (e.g., meat) or alternatively were exploited principally for their milk. Absorbed organic residues from pottery from 14 British prehistoric sites were investigated for evidence of the processing of dairy products. Our ability to detect dairy fats rests on the observation that the delta(13)C values of the C(18:0) fatty acids in ruminant dairy fats are approximately 2.3 per thousand lower than in ruminant adipose fats. This difference can be ascribed to (i) the inability of the mammary gland to biosynthesize C(18:0); (ii) the biohydrogenation of dietary unsaturated fatty acids in the rumen; and (iii) differences (i.e., 8.1 per thousand ) in the delta(13)C values of the plant dietary fatty acids and carbohydrates. The lipids from a total of 958 archaeological pottery vessels were extracted, and the compound-specific delta(13)C values of preserved fatty acids (C(16:0) and C(18:0)) were determined via gas chromatography-combustion-isotope ratio mass spectrometry. The results provide direct evidence for the exploitation of domesticated ruminant animals for dairy products at all Neolithic, Bronze Age, and Iron Age settlements in Britain. Most significantly, studies of pottery from a range of key early Neolithic sites confirmed that dairying was a widespread activity in this period and therefore probably well developed when farming was introduced into Britain in the fifth millennium B.C.