Thermophilic Fungi as the Microbial Agents of Choice for the Industrial Co-Fermentation of Wood Wastes and Nitrogen-Rich Organic Wastes to Bio-Methane.

The novel industrial approach of co-fermenting wood wastes with agricultural wastes that are rich in nitrogen such as animal manures to produce bio-methane (renewable natural gas) fuel via thermophilic anaerobic digestion mimics an analogous process occurring in lower termites, but it relies instead on thermophilic fungi along with other thermophilic microorganisms comprising suitable bacteria and archaea. Wood microbial hydrolysis under thermophilic temperatures (range of 55 °C to 70 °C) and aerobic or micro-aerobic conditions constitutes the first step of the two-step (hydrolysis and fermentation) dry thermophilic anaerobic digestion industrial process, designated as "W2M3+2", that relies on thermophilic fungi species, most of which grow naturally in wood piles. Eleven thermophilic fungi have been identified as likely agents of the industrial process, and their known growth habitats and conditions have been reviewed. Future research is proposed such that the optimal growth temperature of these thermophilic fungi could be increased to the higher thermophilic range approaching 70 °C, and a tolerance to partial anaerobic conditions can be obtained by modifying the fungal microbiome via a symbiotic existence with bacteria and/or viruses.

PEG: The Magic Bullet for Biophysical Analysis of Highly Aggregating Small Molecules in Aqueous Solutions.

Biophysical research plays a crucial role in drug discovery, but many druglike molecules are poorly soluble and prone to aggregation, making their analysis challenging and susceptible to artifacts. To address this issue, we propose an approach that uses poly(ethylene glycol) (PEG) as an excipient in aqueous buffers to reduce the propensity of small molecules to aggregate. We show how PEG allows us to measure the thermodynamics of a complex formed by a heterobifunctional Small Molecule (hSM) that brings two proteins together. Our model accounts for all of the equilibrium states of the small molecule in solution, resulting in more precise parameters for describing how the proteins and the ligand interact. These precise parameters are important for designing better lead molecules.

Observations on the Occurrence, Transmission and Management of the COVID-19 Pandemic Derived from Physics.

Three important observations derived from the ongoing COVID-19 pandemic could result in the development of novel approaches to deal with it and avoid or at least minimize the occurrence and impact of future outbreaks. First, the dramatic increase in pandemics in the past decade alone suggests that the current relationship of humans with the environment is quickly becoming unstable, with potentially catastrophic consequences. In order to reduce the toll in life and property, we would need to shift our emphasis from control of nature to a symbiosis with nature. This, then, can become the new framework for dealing effectively with environmental issues such as climate change, whereby properly applied medical science would provide the necessary impetus for action. Second, the existence of superspreaders of infection among populations in this pandemic requires that we develop objective tests, most likely of a genetic nature, to identify them rather than apply indiscriminate and draconian controls across the board. Not identifying superspreaders in a timely fashion could allow this pandemic to turn into a black swan event, with a catastrophic impact on society. Third, we need to refocus our efforts in dealing with this pandemic from the virus itself to the human hosts. An objective morbidity risk index can be developed such that most of us can go about our daily business without the fear of becoming seriously ill, while measures can be implemented to protect those who are most vulnerable to this virus. These observations point clearly to a need for a paradigm shift.

Implementation of Tele-Critical Care at General Leonard Wood Army Community Hospital.

INTRODUCTION: Tele-Intensive Care Unit (tele-ICU) is care provided to critically ill patients by remote clinicians using audio, and video communications and network resources to access real-time patient information from physiologic monitors and the electronic medical record. Tele-ICU has been demonstrated in civilian healthcare to reduce mortality, improve care quality and safety, decrease intensive care unit (ICU) length of stay (LOS) and ventilator days, and save money. General Leonard Wood Army Community Hospital (GLWACH) is a small medical treatment facility with limited resources with respect to subspecialists and ancillary services. MATERIALS AND METHODS: In 2012, GLWACH identified the lack of board-certified critical care physicians and limited baseline critical care capabilities as gaps that reduced surgical opportunities, challenged critical skill sustainment, exposed potential patient safety issues, and resulted in costly patient transfers to network hospitals. To address these gaps, GLWACH partnered with the Baptist Health Tele-ICU Service, located in Little Rock, AR, to provide Tele-ICU services to its four-bed intensive care unit. Video Teleconsultation (VTC) equipment was installed in the ICU as was a vendor specific solution for accessing real-time patient vital signs and an "emergency" button. The emergency button functioned by turning on the VTC equipment and calling the Tele-ICU center in Little Rock immediately when pushed. To assess impact, hospital and ICU volume, acuity, case mix index, purchased care costs were monitored before and after implementation of the system. Additionally, a Safety Attitudes Questionnaire (SAQ) was administered before and after implementation. RESULTS: The implementation of the tele-ICU program at GLWACH increased hospital and ICU patient volume, surgical patient volume, and patient complexity. Purchased care costs declined by 30% in the year following implementation and return on investment was $233,311 (19%). All measurements of the SAQ improved following implementation. CONCLUSIONS: These findings support the implementation of tele-ICU in the MHS as a cost-effective method to sustain readiness amongst critical care clinicians and improve safety culture in MHS hospitals.

Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1H-indol-1-yl)acetamides as Covalent Inhibitors of KRASG12C.

KRAS regulates many cellular processes including proliferation, survival, and differentiation. Point mutants of KRAS have long been known to be molecular drivers of cancer. KRAS p.G12C, which occurs in approximately 14% of lung adenocarcinomas, 3-5% of colorectal cancers, and low levels in other solid tumors, represents an attractive therapeutic target for covalent inhibitors. Herein, we disclose the discovery of a class of novel, potent, and selective covalent inhibitors of KRASG12C identified through a custom library synthesis and screening platform called Chemotype Evolution and structure-based design. Identification of a hidden surface groove bordered by H95/Y96/Q99 side chains was key to the optimization of this class of molecules. Best-in-series exemplars exhibit a rapid covalent reaction with cysteine 12 of GDP-KRASG12C with submicromolar inhibition of downstream signaling in a KRASG12C-specific manner.