Interactions of Truncated Menaquinones in Lipid Monolayers and Bilayers.

Menaquinones (MK) are hydrophobic molecules that consist of a naphthoquinone headgroup and a repeating isoprenyl side chain and are cofactors used in bacterial electron transport systems to generate cellular energy. We have previously demonstrated that the folded conformation of truncated MK homologues, MK-1 and MK-2, in both solution and reverse micelle microemulsions depended on environment. There is little information on how MKs associate with phospholipids in a model membrane system and how MKs affect phospholipid organization. In this manuscript, we used a combination of Langmuir monolayer studies and molecular dynamics (MD) simulations to probe these questions on truncated MK homologues, MK-1 through MK-4 within a model membrane. We observed that truncated MKs reside farther away from the interfacial water than ubiquinones are are located closer to the phospholipid tails. We also observed that phospholipid packing does not change at physiological pressure in the presence of truncated MKs, though a difference in phospholipid packing has been observed in the presence of ubiquinones. We found through MD simulations that for truncated MKs, the folded conformation varied, but MKs location and association with the bilayer remained unchanged at physiological conditions regardless of side chain length. Combined, this manuscript provides fundamental information, both experimental and computational, on the location, association, and conformation of truncated MK homologues in model membrane environments relevant to bacterial energy production.

Structural Insights into the Recognition of Mono- and Diacetylated Histones by the ATAD2B Bromodomain.

Bromodomains exhibit preferences for specific patterns of post-translational modifications on core and variant histone proteins. We examined the ligand specificity of the ATAD2B bromodomain and compared it to its closely related paralogue in ATAD2. We show that the ATAD2B bromodomain recognizes mono- and diacetyllysine modifications on histones H4 and H2A. A structure-function approach was used to identify key residues in the acetyllysine-binding pocket that dictate the molecular recognition process, and we examined the binding of an ATAD2 bromodomain inhibitor by ATAD2B. Our analysis demonstrated that critical contacts required for bromodomain inhibitor coordination are conserved between the ATAD2/B bromodomains, with many residues playing a dual role in acetyllysine recognition. We further characterized an alternative splice variant of ATAD2B that results in a loss of function. Our results outline the structural and functional features of the ATAD2B bromodomain and identify a novel mechanism regulating the interaction of the ATAD2B protein with chromatin.

Management of Multi-Casualty Incidents in Mountain Rescue: Evidence-Based Guidelines of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).

Blancher, Marc, François Albasini, Fidel Elsensohn, Ken Zafren, Natalie Hölzl, Kyle McLaughlin, Albert R. Wheeler III, Steven Roy, Hermann Brugger, Mike Greene, and Peter Paal. Management of multi-casualty incidents in mountain rescue: Evidence-based guidelines of the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). High Alt Med Biol. 19:131-140, 2018. INTRODUCTION: Multi-Casualty Incidents (MCI) occur in mountain areas. Little is known about the incidence and character of such events, and the kind of rescue response. Therefore, the International Commission for Mountain Emergency Medicine (ICAR MEDCOM) set out to provide recommendations for the management of MCI in mountain areas. MATERIALS AND METHODS: Details of MCI occurring in mountain areas related to mountaineering activities and involving organized mountain rescue were collected. A literature search using (1) PubMed, (2) national mountain rescue registries, and (3) lay press articles on the internet was performed. The results were analyzed with respect to specific aspects of mountain rescue. RESULTS: We identified 198 MCIs that have occurred in mountain areas since 1956: 137 avalanches, 38 ski lift accidents, and 23 other events, including lightning injuries, landslides, volcanic eruptions, lost groups of people, and water-related accidents. DISCUSSION: General knowledge on MCI management is required. Due to specific aspects of triage and management, the approach to MCIs may differ between those in mountain areas and those in urban settings. CONCLUSIONS: Mountain rescue teams should be prepared to manage MCIs. Knowledge should be reviewed and training performed regularly. Cooperation between terrestrial rescue services, avalanche safety authorities, and helicopter crews is critical to successful management of MCIs in mountain areas.

Use of prehospital ultrasound in North America: a survey of emergency medical services medical directors.

BACKGROUND: Advances in ultrasound imaging technology have made it more accessible to prehospital providers. Little is known about how ultrasound is being used in the prehospital environment and we suspect that it is not widely used in North America at this time. We believe that EMS system characteristics such as provider training, system size, population served, and type of transport will be associated with use or non-use of ultrasound. Our study objective was to describe the current use of prehospital ultrasound in North America. METHODS: This study was a cross-sectional survey distributed to EMS directors on the National Association of EMS Physicians (NAEMSP) mailing list. Respondents had the option to complete a paper or electronic survey. RESULTS: Of the 755 deliverable surveys we received 255 responses from across Canada and the United states for an overall response rate of 30%. Of respondents, 4.1% of EMS systems (95% CI 1.9, 6.3) reported currently using ultrasound and an additional 21.7% (95% CI 17, 26.4) are considering implementing ultrasound. EMS services using ultrasound have a higher proportion of physicians (p < 0.001) as their highest trained prehospital providers when compared to the survey group as a whole. The most commonly cited current and projected applications are Focused Abdominal Sonography for Trauma (FAST) and assessment of pulseless electrical activity (PEA) arrest. The cost of equipment and training are the most significant barriers to implementation of ultrasound. Most medical directors want evidence that prehospital ultrasound improves patient outcomes prior to implementation. CONCLUSIONS: Prehospital ultrasound is infrequently used in North America and there are a number of barriers to its implementation, including costs of equipment and training and limited evidence demonstrating improved outcomes. A research agenda for prehospital ultrasound should focus on patient-important outcomes such as morbidity and mortality. Two commonly used indications that could be a focus of standardized training programs are the FAST exam, and assessment of PEA arrest.

Emergency physician-performed ultrasound to diagnose cholelithiasis: a systematic review.

OBJECTIVES: The authors sought to determine the diagnostic test characteristics of bedside emergency physician (EP)-performed ultrasound (US) for cholelithiasis in symptomatic emergency department (ED) patients. METHODS: A search was conducted of MEDLINE, EMBASE, the Cochrane Library, bibliographies of previous systematic reviews, and abstracts from major emergency medicine conference proceedings. We included studies that prospectively assessed the diagnostic accuracy of emergency US (EUS) for cholelithiasis, compared to a criterion reference standard of radiology-performed ultrasound (RADUS), computed tomography (CT), magnetic resonance imaging (MRI), or surgical findings. Two authors independently performed relevance screening of titles and abstracts, extracted data, and performed the quality analysis. Disagreements were resolved by conference between the two reviewers. EUS performance was assessed with summary receiver operator characteristics curve (SROC) analysis, with independently pooled sensitivity and specificity values across included studies. RESULTS: The electronic search yielded 917 titles; eight studies met the inclusion criteria, yielding a sample of 710 subjects. All included studies used appropriate selection criteria and reference standards, but only one study reported uninterpretable or indeterminate results. The pooled estimates for sensitivity and specificity were 89.8% (95% confidence interval [CI] = 86.4% to 92.5%) and 88.0% (95% CI = 83.7% to 91.4%), respectively. CONCLUSIONS: This study suggests that in patients presenting to the ED with pain consistent with biliary colic, a positive EUS scan may be used to arrange for appropriate outpatient follow-up if symptoms have resolved. In patients with a low pretest probability, a negative EUS scan should prompt the clinician to consider an alternative diagnosis.

Triaging multiple victims in an avalanche setting: the Avalanche Survival Optimizing Rescue Triage algorithmic approach.

As winter backcountry activity increases, so does exposure to avalanche danger. A complicated situation arises when multiple victims are caught in an avalanche and where medical and other rescue demands overwhelm resources in the field. These mass casualty incidents carry a high risk of morbidity and mortality, and there is no recommended approach to patient care specific to this setting other than basic first aid principles. The literature is limited with regard to triaging systems applicable to avalanche incidents. In conjunction with the development of an electronic avalanche rescue training module by the Canadian Avalanche Association, we have designed the Avalanche Survival Optimizing Rescue Triage algorithm to address the triaging of multiple avalanche victims to optimize survival and disposition decisions.

Pattern of injury and illness during expedition-length adventure races.

OBJECTIVE: To describe injuries and illnesses treated during an expedition-length adventure race and combine the results with those from previous studies to identify common patterns of injury and illness during these events. METHODS: The 2003 Subaru Primal Quest Expedition Length Adventure Race was held in Lake Tahoe, CA, from September 5 to 14, 2003. Eighty teams of 4 individuals participated. During the event, medical volunteers providing on-site medical care recorded each medical encounter on a medical encounter form. This information was used to describe the injuries and illnesses treated and was combined with previous investigations to identify common patterns of injury and illness during these events. RESULTS: During the 10-day study period, 356 patient encounters and 406 injuries and illnesses were recorded. The most frequent reason to require on-site medical care was injury of the skin and soft tissue (70.4%), with blisters the single most common of these injuries (45.6%). Other reasons were orthopedic injury (14.8%), respiratory illness (3.7%), and heat illness or dehydration (3.7%). CONCLUSIONS: The results of this and previous studies demonstrate a common pattern of injury and illness that includes a high frequency of skin and soft tissue injury, especially blisters. Injuries and illnesses such as altitude illness, contact dermatitis, and respiratory illness varied considerably among events. The number of patient encounters per athlete is similar among the studies, providing an approximation of the number of medical encounters expected given the number of participants. These results should assist medical providers for future events; however, it is imperative to carefully review the individual event to best predict the frequency of injury and illness.

Comparative fixation of tibial plateau fractures using alpha-BSM, a calcium phosphate cement, versus cancellous bone graft.

OBJECTIVES: To compare the compressive strength of a bone substitute material (alpha-BSM) to cancellous bone when used to fill a defect void in a cadaver model of a Schatzker II split depression fracture of the lateral tibial plateau. DESIGN: Randomized, paired design. SETTING: Biomedical engineering laboratory. PATIENTS: Twenty-six human tibias were harvested from 13 cadavers. Three pairs of tibia fractured during preparation and were excluded. The remaining 10 matched pairs were randomized to fixation by using the bone substitute material or cancellous bone. INTERVENTION: A split depression fracture of the lateral tibial plateau was created in each tibia by using reproducible methods. This fracture was stabilized with a stainless steel L-plate and screws and either alpha-BSM or cancellous bone to fill the defect void. MAIN OUTCOME MEASUREMENTS: Stiffness of the elevated fragment in compression, total depression of the joint at 1000 N. RESULTS: The alpha-BSM bone substitute displayed significantly greater stiffness than cancellous bone constructs in Schatzker II split depression fractures of the lateral tibial plateau (P < 0.0001). Plateau defects displaced significantly less at 1000 N when using alpha-BSM in comparison to cancellous bone (P < 0.0001). CONCLUSIONS: In this cadaveric study, alpha-BSM is an effective bone substitute compared with cancellous bone graft for stabilizing split depression fractures of the lateral tibial plateau.