Vacuum-assisted closure device enhances recovery of critically ill patients following emergency surgical procedures

Introduction: Critically ill surgical patients frequently develop intra-abdominal hypertension (IAH) leading to abdominal compartment syndrome (ACS) with subsequent high mortality. We compared two temporary abdominal closure systems (Bogota bag and vacuum-assisted closure (VAC) device) in intra-abdominal pressure (IAP) control. Methods: This prospective study with a historical control included 66 patients admitted to a medical and surgical intensive care unit (ICU) of a tertiary care referral center (Careggi Hospital, Florence, Italy) from January 2006 to April 2009. The control group included patients consecutively treated with the Bogota bag (Jan 2006-Oct 2007), whereas the prospective group was comprised of patients treated with a VAC. All patients underwent abdominal decompressive surgery. Groups were compared based upon their IAP, SOFA score, serial arterial lactates, the duration of having their abdomen open, the need for mechanical ventilation (MV) along with length of ICU and hospital stay and mortality. Data were collected from the time of abdominal decompression until the end of pressure monitoring. Results: The Bogota and VAC groups were similar with regards to demography, admission diagnosis, severity of illness, and IAH grading. The VAC system was more effective in controlling IAP (P < 0.01) and normalizing serum lactates (P < 0.001) as compared to the Bogota bag during the first 24 hours after surgical decompression. There was no significant difference between the SOFA scores. When compared to the Bogota, the VAC group had a faster abdominal closure time (4.4 vs 6.6 days, P = 0.025), shorter duration of MV (7.1 vs 9.9 days, P = 0.039), decreased ICU length of stay (LOS) (13.3 vs 19.2 days, P = 0.024) and hospital LOS (28.5 vs 34.9 days; P = 0.019). Mortality rate did not differ significantly between the two groups. Conclusions: Patients with abdominal compartment syndrome who were treated with VAC decompression had a faster abdominal closure rate and earlier discharge from the ICU as compared to similar patients treated with the Bogota bag

DRONE TECHNOLOGY EDUCATION IN RURAL, ISOLATED, TRIBAL AND INDIGENOUS (RITI) COMMUNITIES

Transportation and traffic safety is a primary concern within Rural, Isolated, Tribal and Indigenous (RITI) communities in Washington State. Emerging technologies such as connected and autonomous vehicles, sensors and drones have been tested and developed to improve traffic safety, but these advances have largely been limited to urban areas. This project identified opportunities and challenges of adopting drone technologies in RITI communities, and explored context-sensitive applications to traffic safety and related goals. In three phases, the team conducted community workshops, online surveys and other outreach activities with state and county agencies responsible for emergency management and crisis response in coastal Tribal and non-tribal communities; a planning studio and Comprehensive Plan Update for the City of Westport and its surrounding South Beach community straddling two rural counties and including the Shoalwater Bay Indian Tribe; and a pilot educational program with the School District that serves it. To be effective in rural contexts, adoption of drone technology depends on a broadening of local skill development and needs to target diverse community goals. In short, it needs to be broadly embedded in the community. Taking this sociotechnical approach, we focused on long-term workforce development and designed and implemented an after-school program (October 2021 – June 2022) for Ocosta Junior High School students. The course taught students how to assemble and pilot drones and apply them to a variety of practical needs including public works inspection, search and rescue, and environmental monitoring of coastal flooding

Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol

Members of the GHL ATPase superfamily, including type II topoisomerases, Hsp90-class chaperones, and MutL, all share a common GHKL-type ATP-binding fold and act as nucleotide-controlled ‘molecular clamps’. These enzymes' ATP-binding sites have proven to be rich drug targets, and certain inhibitors of type II topoisomerases and Hsp90 bind to this region and competitively inhibit these enzymes. Recently, it was found that radicicol, a drug known to block Hsp90 function, also inhibits the archaeal type IIB topoisomerase topo VI. Here, we use X-ray crystallography to show that despite low sequence identity (∼10–12%) between topo VI and Hsp90, radicicol binds to the ATPase sites of these two enzymes in an equivalent manner. We further demonstrate that radicicol inhibits both the dimerization of the topo VI ATPase domains and ATP hydrolysis, two critical steps in the enzyme's strand passage reaction. This work contributes to a growing set of structures detailing the interactions between GHL-family proteins and various drugs, and reveals radicicol as a versatile scaffold for targeting distantly related GHL enzymes

Mortality after emergency department intubation

Introduction The purpose of this study is to identify the rate of emergency department (ED) intubation and the mortality associated with ED intubation. Methods We conducted a retrospective chart review of all patients intubated in the ED between 1 January 2004 an

The Fragmented Mitochondrial Ribosomal RNAs of Plasmodium falciparum

The mitochondrial genome in the human malaria parasite Plasmodium falciparum is most unusual. Over half the genome is composed of the genes for three classic mitochondrial proteins: cytochrome oxidase subunits I and III and apocytochrome b. The remainder encodes numerous small RNAs, ranging in size from 23 to 190 nt. Previous analysis revealed that some of these transcripts have significant sequence identity with highly conserved regions of large and small subunit rRNAs, and can form the expected secondary structures. However, these rRNA fragments are not encoded in linear order; instead, they are intermixed with one another and the protein coding genes, and are coded on both strands of the genome. This unorthodox arrangement hindered the identification of transcripts corresponding to other regions of rRNA that are highly conserved and/or are known to participate directly in protein synthesis.The identification of 14 additional small mitochondrial transcripts from P. falciparum and the assignment of 27 small RNAs (12 SSU RNAs totaling 804 nt, 15 LSU RNAs totaling 1233 nt) to specific regions of rRNA are supported by multiple lines of evidence. The regions now represented are highly similar to those of the small but contiguous mitochondrial rRNAs of Caenorhabditis elegans. The P. falciparum rRNA fragments cluster on the interfaces of the two ribosomal subunits in the three-dimensional structure of the ribosome.All of the rRNA fragments are now presumed to have been identified with experimental methods, and nearly all of these have been mapped onto the SSU and LSU rRNAs. Conversely, all regions of the rRNAs that are known to be directly associated with protein synthesis have been identified in the P. falciparum mitochondrial genome and RNA transcripts. The fragmentation of the rRNA in the P. falciparum mitochondrion is the most extreme example of any rRNA fragmentation discovered

Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

Finite-time destruction of entanglement and non-locality by environmental influences

Entanglement and non-locality are non-classical global characteristics of quantum states important to the foundations of quantum mechanics. Recent investigations have shown that environmental noise, even when it is entirely local in influence, can destroy both of these properties in finite time despite giving rise to full quantum state decoherence only in the infinite time limit. These investigations, which have been carried out in a range of theoretical and experimental situations, are reviewed here.Comment: 27 pages, 6 figures, review article to appear in Foundations of Physic