Development and clinical utility of an ultra performance liquid chromatography - tandem mass spectrometry assay for monitoring omadacycline and tigecycline in severe bacterial infections.

Objective: We aimed to develop a rapid, simple, and precise ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) technique for simultaneous measurement of omadacycline (OMA) and tigecycline (TGC) in the bloodstream of individuals suffering from serious bacterial infections.

Methods: All analytes were extracted using a 0.2 % formic acid-water dilution and acetonitrile plasma protein precipitation.

RIPK1 inhibitors: A key to unlocking the potential of necroptosis in drug development.

Within the field of medical science, there is a great deal of interest in investigating cell death pathways in the hopes of discovering new drugs. Over the past two decades, pharmacological research has focused on necroptosis, a cell death process that has just been discovered. Receptor-interacting protein kinase 1 (RIPK1), an essential regulator in the cell death receptor signalling pathway, has been shown to be involved in the regulation of important events, including necrosis, inflammation, and apoptosis.

Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives.

In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC values in the low μM to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan.

Using the Fusion Proximal Area Method and Gravity Method to Identify Areas with Physician Shortages.

Objectives: This paper presents a geographic information system (GIS)-based proximal area method and gravity method for identifying areas with physician shortages. The innovation of this paper is that it uses the appropriate methods to discover each type of health resource and then integrates all these methods to assess spatial access to health resources using population distribution data. In this way, spatial access to health resources for an entire city can be visualized in one neat package, which can help health policy makers quickly comprehend realistic distributions of health resources at a macro level.

Design and synthesis of novel PEG-conjugated 20(S)-camptothecin sulfonylamidine derivatives with potent in vitro antitumor activity via Cu-catalyzed three-component reaction.

In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel structurally diverse PEG-based 20(S)-CPT sulfonylamidine derivatives were designed, synthesized via a Cu-multicomponent reaction (MCR), and evaluated for cytotoxicity against four human tumor cell lines (A-549, MDA-MB-231, KB, and KBvin). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Significantly, these derivatives exhibited comparable cytotoxicity against KBvin, while irinotecan was less active against this cell line.