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Genome mining revealed the presence of two cdps-p450 operons in Saccharopolyspora antimicrobica. Heterologous expression, biochemical characterisation and structure elucidation proved that the two P450 enzymes catalyse distinct regio- and stereospecific dimerizations of cyclo-(l-Trp-l-Trp), which significantly expands the repertoire of diketopiperazine-tailoring enzymes. TtpB1 connects the monomers via C3-C3', both from the opposite side of H-11/H-11', while TtpB2 is characterised as the first P450 to mainly catalyse the unusual linkage between N1' and C3 from the H-11 side.

We have observed that critically ill patients with COVID-19 are in an extreme hypermetabolic state. This may be a major contributing factor to the extraordinary ventilatory and oxygenation demands seen in these patients. We aimed to quantify the extent of the hypermetabolic state and report the clinical effect of the use of hypothermia to decrease the metabolic demand in these patients.

Mild hypothermia was applied on four critically ill patients with COVID-19 for 48h. Metabolic rates, carbon dioxide production and oxygen consumption were measured by indirect calorimetry.

The average resting energy expenditure (REE) was 299% of predicted. Mild hypothermia decreased the REE on average of 27.0% with resultant declines in CO

production (VCO

) and oxygen consumption (VO

) by 29.2% and 25.7%, respectively. QNZ in VCO

and VO

was clinically manifested as improvements in hypercapnia (average of 19.1% decrease in pCO

levels) and oxygenation (average of 50.4% increase in pO

).

Our case series demonstrates the extent of hypermetabolism in COVID-19 critical illness and suggests that mild hypothermia reduces the metabolic rate, improves hypercapnia and hypoxia in critically ill patients with COVID-19.

Our case series demonstrates the extent of hypermetabolism in COVID-19 critical illness and suggests that mild hypothermia reduces the metabolic rate, improves hypercapnia and hypoxia in critically ill patients with COVID-19.The present study analyzes the importance of the inflammasome that involves the NLRP3 complex in the state of hypercytokinemia observed in patients with COVID-19, significantly increasing IL-1β, IL18, IL-6, and TNF. Unfortunately, improving the immune response can sometimes worsen the outcome of the disease. Studies show that colchicine, among other actions, inhibits the assembly of NLRP3 complex that is responsible for generating the active form of Caspase-1 that will convert Pro-IL-1β and Pro-IL-18 into their active forms. We suggest using colchicine, a class of drugs with low-cost, extensively tested, well-tolerated medicine as a complementary treatment for patients with COVID-19, in early stages of the disease based on knowledge of its immunomodulatory properties.

Modern smartphones contain sophisticated high-end hardware features, offering high computational capabilities at extremely manageable costs and have undoubtedly become an integral part in users' daily life. Additionally, smartphones offer a well-established ecosystem that is easily discoverable and accessible via the marketplaces of differing mobile platforms, thus encouraging the development of many smartphone apps. Such apps are not exclusively used for entertainment purposes but are also commonplace in health care and medical use. A variety of those health and medical apps exist within the context of tinnitus, a phantom sound perception in the absence of any physical external source.

In this paper, we shed light on existing smartphone apps addressing tinnitus by providing an up-to-date overview.

Based on PRISMA guidelines, we systematically searched and identified existing smartphone apps on the most prominent app markets, namely Google Play Store and Apple App Store. In addition, we applied the Mobiggesting the need for stringent clinical validation of smartphone apps in future. To the best of our knowledge, this work is the first to systematically identify and evaluate smartphone apps within the context of tinnitus.

This work demonstrated that there exists a plethora of smartphone apps for tinnitus. All of the apps received MARS scores higher than 2, suggesting that they all have some technical functional value. However, nearly all identified apps were lacking in terms of scientific evidence, suggesting the need for stringent clinical validation of smartphone apps in future. To the best of our knowledge, this work is the first to systematically identify and evaluate smartphone apps within the context of tinnitus.

Hospitals worldwide are developing ambitious digital transformation programs as part of broader efforts to create digitally advanced health care systems. However, there is as yet no consensus on how best to characterize and assess digital excellence in hospitals.

Our aim was to develop an international agreement on a defined set of technological capabilities to assess digital excellence in hospitals.

We conducted a two-stage international modified electronic Delphi (eDelphi) consensus-building exercise, which included a qualitative analysis of free-text responses. In total, 31 international health informatics experts participated, representing clinical, academic, public, and vendor organizations.

We identified 35 technological capabilities that indicate digital excellence in hospitals. These are divided into two categories (a) capabilities within a hospital (n=20) and (b) capabilities enabling communication with other parts of the health and social care system, and with patients and carers (n=15). The analysis of free-text responses pointed to the importance of nontechnological aspects of digitally enabled change, including social and organizational factors. Examples included an institutional culture characterized by a willingness to transform established ways of working and openness to risk-taking. #link# The availability of a range of skills within digitization teams, including technological, project management and business expertise, and availability of resources to support hospital staff, were also highlighted.

We have identified a set of criteria for assessing digital excellence in hospitals. Our findings highlight the need to broaden the focus from technical functionalities to wider digital transformation capabilities.

We have identified a set of criteria for assessing digital excellence in hospitals. Our findings highlight the need to broaden the focus from technical functionalities to wider digital transformation capabilities.

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