Notes

How can the unity of prematurity and hereditary cardiovascular disease impact the creating mental faculties?
The mitochondrial contact site and cristae organizing system (MICOS) is a multi-protein interaction hub that helps define mitochondrial ultrastructure. While the functional importance of MICOS is mostly characterized in yeast and mammalian cells in culture, the contributions of MICOS to tissue homeostasis in vivo remain further elucidation. In this study, we examined how knocking down expression of Drosophila MICOS genes affects mitochondrial function and muscle tissue homeostasis. We found that CG5903/MIC26-MIC27 colocalizes and functions with Mitofilin/MIC60 and QIL1/MIC13 as a Drosophila MICOS component; knocking down expression of any of these three genes predictably altered mitochondrial morphology, causing loss of cristae junctions, and disruption of cristae packing. Furthermore, the knockdown flies exhibited low mitochondrial membrane potential, fusion/fission imbalances, increased mitophagy, and limited cell death. Reductions in climbing ability indicated deficits in muscle function. Knocking down MICOS genes also caused reduced mtDNA content and fragmented mitochondrial nucleoid structure in Drosophila Together, our data demonstrate an essential role of Drosophila MICOS in maintaining proper homeostasis of mitochondrial structure and function to promote the function of muscle tissue.Basidiomycota are a large and diverse phylum of fungi. They can make bioactive metabolites that are used or have inspired the synthesis of antibiotics and agrochemicals. Terpenoids are the most abundant class of natural products encountered in this taxon. Other natural product classes have been described, including polyketides, peptides, and indole alkaloids. The discovery and study of natural products made by basidiomycete fungi has so far been hampered by several factors, which include their slow growth and complex genome architecture. Recent developments of tools for genome and metabolome studies are allowing researchers to more easily tackle the secondary metabolome of basidiomycete fungi. Inexpensive long-read whole-genome sequencing enables the assembly of high-quality genomes, improving the scaffold upon which natural product gene clusters can be predicted. Thiazovivin nmr CRISPR/Cas9-based engineering of basidiomycete fungi has been described and will have an important role in linking natural products to their genetic determinants. Platforms for the heterologous expression of basidiomycete genes and gene clusters have been developed, enabling natural product biosynthesis studies. Molecular network analyses and publicly available natural product databases facilitate data dereplication and natural product characterisation. These technological advances combined are prompting a revived interest in natural product discovery from basidiomycete fungi.This article has an associated Future Leader to Watch interview with the first author of the paper.
The COVID-19 pandemic in the USA has been accompanied by high rates of mortality and an unprecedented need for palliative care delivery. Little is known about the use of palliative care services in intensive care unit (ICU) settings during the COVID-19 pandemic.

This is a retrospective cohort study of critically ill COVID-19 patients requiring ICU admission, between 7 March and 14 April 2020 to two academic teaching hospitals in New York City. Palliative care consultation included a one-time telemedicine consultation or continued telemedicine consultation and follow-up with multidisciplinary team involvement. Patient information was collected from the electronic health record and analyses were conducted with Stata V.15.1 (StataCorp) statistical software.

A total of 151 critically ill patients with COVID-19 pneumonia requiring ICU admission were identified, of whom 59 (39.07%) received an inpatient palliative care consultation. More than half of patients died (n=85/151, 56.29%), with 57.65% (n=49/85) of these patients receiving palliative care services during their hospitalisation. Patients who received palliative care consultation were more likely to be older, sicker and receive mechanical ventilation than their counterparts. Patients who died and did not receive palliative care were younger and required non-invasive ventilation support.

There is a lack of utilisation of palliative care in COVID-19 patients admitted to the ICU. Further research into predictors of poor outcomes in critically ill COVID-19 patients may help identify patients that would benefit from early palliative care involvement going forward.
There is a lack of utilisation of palliative care in COVID-19 patients admitted to the ICU. Further research into predictors of poor outcomes in critically ill COVID-19 patients may help identify patients that would benefit from early palliative care involvement going forward.
Insufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. We aimed to determine the most clinically pragmatic design of a future randominsed controlled trial (RCT), based on how NSAIDs are currently used and perceived efficacy.

An online survey was distributed to members of the Association for Palliative Medicine of Great Britain and Ireland examining NSAID use, indications and perceived efficacy, as well as duration of respondents' experience in palliative medicine.

23% of 968 members responded. A placebo-controlled trial of NSAIDs as a strong opioid adjunct in cancer-related bone pain was considered the most clinically pragmatic design. Concerning current practice, oral administration was the preferential route (79.4%), dosed regularly (79.5%). Selective cyclooxygenase-2 (COX-2) inhibitors and non-selective COX-2 inhibitors were considered similarly effective by 45% in cancer pain; ibuprofen being the first line oral NSAID of choice (42.6%). Treatment efficacy is generally determined within 1 week (94.3%). On a Likert scale, most physicians consider NSAIDs improve cancer pain either 'sometimes' (57.7%) or 'often' (40%). Years of specialist palliative care experience did not affect perception of efficacy (p=0.353).

A randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.
A randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.
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