bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fresh whole blood resuscitation does not exacerbate skeletal muscle edema and long-term functional deficit after ischemic injury and hemorrhagic shock
Authors: Aurora Amit , Roe Janet L. , Umoh Nsini A. , Dubick Michael , Wenke Joseph C. , Walters Thomas J. 
Published: January 2018

BACKGROUND
Hemorrhagic shock caused by extremity vascular injuries is common in combat injuries. Fluid resuscitation is the standard treatment for severe hemorrhage (HEM). Tourniquets (TKs) used for HEM control cause ischemia-reperfusion (I/R) injury that induces edema formation in the injured muscle. Resuscitation fluids affect edema formation; however, its effect on long-term functional response remains unknown. The objectives of this study are to (1) compare acute muscle damage; (2) determine long-term functional recovery of ischemic muscle; and (3) compare local and systemic inflammatory response including the expression of junctional proteins following early resuscitation with Hextend and fresh whole blood using a rodent model of combined HEM and TK-induced limb I/R.

METHODS
Anesthetized Sprague-Dawley rats underwent 42.5% arterial HEM, followed by 3 hours of TK application. Animals were either not resuscitated or resuscitated with Hextend or fresh whole blood. Two time points were evaluated, 2 and 28 days. Plasma cytokine concentrations were determined at baseline and end resuscitation. At 2 days, edema formation, expression of junctional proteins, and tissue level cytokines concentrations were evaluated. At 28 days, in vivo muscle contractile properties were determined. At both time points, routine histology was performed and graded using a semiquantitative grading system.

RESULTS
All animals developed hemorrhagic hypovolemia; the mortality rate was 100% in nonresuscitated rats. Hextend resuscitation exacerbated muscle edema (~11%) and muscle strength deficit (~20%). Fresh whole blood resuscitation presented edema and muscle strength akin to TK only. Fresh whole blood resuscitation upregulated expression of junctional proteins including proangiogenic factors and dampened the inflammatory response.

CONCLUSION
Fresh whole blood resuscitation does not exacerbate either TK-induced edema or muscle strength deficit. Fresh whole blood resuscitation may reduce both acute and long-term morbidity associated with extremity trauma. To our knowledge, this is the first study to demonstrate the nature of the resuscitation fluid administered following HEM impacts short- and long-term indices of I/R in skeletal muscle.
Staff officers as blood suppliers: Effects of repeated donations and autologous reinfusions of untransfused units
Authors: Strandenes Geir , Sivertsen Joar , Eliassen Håkon , Braathen Hanne , Hervig Tor A. 
Published: January 2018

BACKGROUND
Limited blood inventory and resupply chains in combat settings can result in preventable deaths from traumatic hemorrhage. One way of mitigating this could be to establish donor pools where blood is collected in advance of high-risk missions and then reinfused back to the donor if not needed to treat casualties.

METHODS
Four hundred fifty milliliters plus 56 mL of blood was collected, rested for 2 hours in room temperature, and stored at 4°C. The blood was reinfused 22 to 24 hours after donation and the donor observed for adverse reactions. Samples were collected before and 20 minutes after each donation for hematology, immunoglobulin G, ferritin, C-reactive protein, total protein, lactate dehydrogenase, bilirubin, haptoglobin, and activated partial thromboplastin time.

RESULTS
Nine participants went through a total of 36 donation and reinfusion procedures. Four donors participated in five rounds, two in four rounds, two in three rounds, and one in two rounds. A significant drop was seen in hemoglobin (14.6 ± 0.9 to 13.9 ± 0.9) and ferritin (179 ± 70 to 149 ± 78) from before the first donation to after the last reinfusion (p < 0.05). Other parameters were unaffected.

CONCLUSION
This small pilot study suggests that repeated donations and reinfusions may be both feasible and safe. Blood collected in this way should be labeled with the donor’s full name and social security number (or similar) and the identity visually verified by the donor immediately before both donation and reinfusion. To further reduce risk, this form of donation should be restricted to scenarios where there is no other option for making blood available.

LEVEL OF EVIDENCE
Therapeutic/Care management study, level V.
The history and promising future of phage therapy in the military service
Authors: Gelman Daniel , Eisenkraft Arik , Chanishvili Nina , Nachman Dean , Coppenhagem Glazer Shunit , Hazan Ronen 
Published: January 2018

ABSTRACT
The continuous evolvement of bacterial resistance to most, if not all, available antibiotics is a worldwide problem. These strains, frequently isolated from military-associated environments, have created an urgent need to develop supplementary anti-infective modalities. One of the leading directions is phage therapy, which includes the administration of bacteriophages, viruses that specifically target bacteria, as biotherapies. Although neglected in the West until recent years, bacteriophages have been widely studied and clinically administered in the former Soviet Union and Eastern Europe for over a century, where they were found to be incredibly efficient at battling numerous infectious diseases.
In this review, we discuss the high potential of phage therapy as a solution for resistant bacterial infectious diseases relating to military medicine. By describing the historical development and knowledge acquired on phage therapy, we define the advantages of bacteriophages for combating resistant bacteria in multiple settings, such as trauma injuries and foodborne illnesses, as a preventive tool and therapy against biological warfare agents, and more. We also present the most recent successful clinical applications of bacteriophages in military settings worldwide.
We believe that augmenting military medicine by integrating phage therapy is an important and required step in preparedness for the rapidly approaching post–antibiotic era.
Analysis of isolated transverse process fractures sustained during blast-related events
Authors: Newell Nicolas , Pearce A. Phillip , Spurrier Edward , Gibb Iain , Webster Claire E. , Clasper Jonathan C. , Masouros Spyros D. 
Published: January 2018

BACKGROUND
Personnel have sustained a range of devastating blast injuries during recent conflicts. Previous studies have focused on severe injuries, including to the spine; however, no study has specifically focused on the most common spinal injury—transverse process (TP) fractures. Although their treatment usually requires limited intervention, analysis of TP fractures may help determine injury mechanisms.

METHODS
Data were collected from victims with spinal fractures who were injured in improvised explosive device attacks, from the UK’s Joint Theatre Trauma Registry. The level and side of each TP fracture were recorded, as well as associated injuries, whether they were mounted or dismounted, and outcome (survivor or fatality).

RESULTS
Most (80%) of the TP fractures were lumbar. More bilateral (both left and right fractures at the same level), and L5 TP fractures, were seen in fatalities than survivors. In the mounted group, lumbar TP fractures were statistically significantly associated with fatality, head injury, noncompressible torso hemorrhage, pelvic injury, and other spinal injuries. In the dismounted group, thoracic TP fractures were associated with head, chest wall, and other spinal injuries; and lumbar TP fractures were associated with pelvic and other spinal injuries.

CONCLUSIONS
Different injury mechanisms of the TP in the mounted and dismounted groups are likely. Inertial forces acting within the torso due to rapid loading being transferred through the seat, or high intra-abdominal pressures causing the tensile forces acting through the lumbar fascia to avulse the TPs are likely mechanisms in the mounted group. Blunt trauma, violent lateral flexion-extension forces, or rapid flail of the lower extremities causing tension of the psoas muscle, avulsing the TP, are likely causes in the dismounted group. Isolated lumbar TP fractures can be used as markers for more severe injuries, and fatality, in mounted blast casualties.

LEVEL OF EVIDENCE
Prognostic and epidemiological, level III.
Permissive hypotension versus conventional resuscitation strategies in adult trauma patients with hemorrhagic shock: A systematic review and meta-analysis of randomized controlled trials
Authors: Tran Alexandre , Yates Jeffrey , Lau Aaron , Lampron Jacinthe , Matar Maher 
Published: January 2018

BACKGROUND
Aggressive fluid resuscitation in trauma promotes deleterious effects such as clot disruption, dilutional coagulopathy and hypothermia. Animal studies suggest that permissive hypotension maintains appropriate organ perfusion, reduces bleeding and improves mortality. This review assesses the efficacy and safety of permissive hypotension in adult trauma patients with hemorrhagic shock.

METHODS
We searched the MEDLINE and EMBASE databases from inception to May 2017 for randomized controlled trials comparing permissive hypotension vs. conventional resuscitation following traumatic injury. We included preoperative and intraoperative resuscitation strategies. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included blood product utilization, estimated blood loss and in-hospital complications. Pooling was performed with a random-effects model.

RESULTS
We screened 722 abstracts, from which five randomized trials evaluating 1,158 patients were included. Blood pressure targets in the intervention arms varied from systolic BP 50 mm Hg to 70 mm Hg or mean arterial pressure of 50 mm Hg or higher as compared to systolic BP 65 mm Hg to 100 mm Hg or mean arterial pressure of 65 or higher in the control arms. Two studies evaluated only patients with penetrating injury while the remaining three additionally included blunt injuries. Four trials suggested a survival benefit for 30-day or in-hospital mortality with hypotensive resuscitation, although three studies were insufficiently powered to find statistical significance. Studies were of poor to moderate quality due to poor protocol reporting and lack of blinding. The pooled odds ratio was 0.70 (95% confidence interval, 0.53–0.92), suggesting a survival benefit for permissive hypotension. Those patients received fewer blood products and had lesser estimated blood loss.

CONCLUSION
Permissive hypotension may offer a survival benefit over conventional resuscitation for patients with hemorrhagic injury. It may additionally reduce blood loss and blood product utilization. However, the majority of studies were underpowered, thus reflecting a need for high quality, adequately powered trials.

PROSPERO REGISTRATION
Systematic Review, level II.
CRD42017070526.
Socioeconomic Inequalities in the Kidney Transplantation Process: A Registry-Based Study in Sweden
Authors: Zhang Ye , Gerdtham Ulf-G. , Rydell Helena , Jarl Johan 
Published: January 2018

Background
Few studies have examined the association between individual-level socioeconomic status and access to kidney transplantation. This study aims to investigate the association between predialysis income and education, and access to (i) the kidney waitlist (first listing), and (ii) kidney transplantation conditional on waitlist placement. Adjustment will be made for a number of medical and nonmedical factors.

Methods
The Swedish Renal Register was linked to national registers for adult patients in Sweden who started dialysis during 1995 to 2013. We employed Cox proportional hazards models.

Results
Nineteen per cent of patients were placed on the waitlist. Once on the waitlist, 80% received kidney transplantation. After adjusting for covariates, patients in the highest income quintile were found to have higher access to both the waitlist (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.53-1.96) and kidney transplantation (HR, 1.33; 95% CI, 1.16-1.53) compared with patients in the lowest income quintile. Patients with higher education also had better access to the waitlist and kidney transplantation (HR, 2.16; 95% CI, 1.94-2.40; and HR, 1.16; 95% CI, 1.03-1.30, respectively) compared with patients with mandatory education.

Conclusions
Socioeconomic status-related inequalities exist with regard to both access to the waitlist, and kidney transplantation conditional on listing. However, the former inequality is substantially larger and is therefore expected to contribute more to societal inequalities. Further studies are needed to explore the potential mechanisms and strategies to reduce these inequalities.
Function of BriC Peptide in the Pneumococcal Competence and Virulence Portfolio
Authors: Aggarwal Surya D. , Eutsey Rory , West-Roberts Jacob , Domenech Arnau , Xu Wenjie , Abdullah Iman Tajer , Mitchell Aaron P. , Veening Jan-Willem , Yesilkaya Hasan , Hiller N. Luisa 
Published: January 2018

AbstractStreptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pathway influences the structure and stability of biofilms. However, the molecules that link the competence pathway to biofilm formation are unknown. Here, we describe a new competence-induced gene, called briC, and demonstrate that its product promotes biofilm development and stimulates colonization in a murine model. We show that expression of briC is induced by the master regulator of competence, ComE. Whereas briC does not substantially influence early biofilm development on abiotic surfaces, it significantly impacts later stages of biofilm development. Specifically, briC expression leads to increases in biofilm biomass and thickness at 72h. Consistent with the role of biofilms in colonization, briC promotes nasopharyngeal colonization in the murine model. The function of BriC appears to be conserved across pneumococci, as comparative genomics reveal that briC is widespread across isolates. Surprisingly, many isolates, including strains from clinically important PMEN1 and PMEN14 lineages, which are widely associated with colonization, encode a long briC promoter. This long form captures an instance of genomic plasticity and functions as a competence-independent expression enhancer that may serve as a precocious point of entry into this otherwise competence-regulated pathway. Moreover, overexpression of briC by the long promoter fully rescues the comE-deletion induced biofilm defect in vitro, and partially in vivo. These findings indicate that BriC may bypass the influence of competence in biofilm development and that such a pathway may be active in a subset of pneumococcal lineages. In conclusion, BriC is a part of the complex molecular network that connects signaling of the competence pathway to biofilm development and colonization.
Endotoxin Tolerance Induced by Different TLR Ligands
Authors: Butcher Suzanne K. , O’Carroll Christine , Wells Christine A. , Carmody Ruaidhrí J. 
Published: January 2018

AbstractEndotoxin tolerance is a long-recognised property of macrophages that leads to an altered response to repeated or chronic exposure to Toll-like receptor (TLR) ligands. The physiological role of tolerance is to limit the potential damage to host tissue that may otherwise result from prolonged production of pro-inflammatory cytokines. Endotoxin tolerance is induced by all TLRs tested to date, however, tolerance induced by the TLR4 ligand lipopolysaccharide (LPS) is by far the best studied. LPS tolerance involves a global transcriptional shift from a pro-inflammatory response toward one characterised by the expression of anti-inflammatory and pro-resolution factors. Although largely reversible, LPS-tolerance leads to a hybrid macrophage activation state that is pro-inflammatory in nature but possesses distinct regulatory anti-inflammatory features. Remarkably, a comparative transcriptomic analysis of tolerance induced by different TLR ligands has not previously been reported. Here we describe the transcriptomic profiles of mouse macrophages tolerised with ligands for TLR2, TLR3, TLR4 and TLR 9. While we identified TLR-specific transcriptional profiles in macrophages tolerised with each ligand, tolerance induced by TLR4 was the most comprehensive state, such that each gene tolerised by any of the TLRs tested was also found to be tolerised by TLR4. Pro-inflammatory cytokines are not universally supressed in all tolerant cells but distinct patterns of cytokine expression distinguished TLR-specific tolerance. Analysis of gene regulatory regions revealed specific DNA sequence motifs associated with distinct states of TLR tolerance, implicating previously identified as well as novel transcriptional regulators of tolerance in macrophages. These data provide a basis for the future exploitation of TLR-specific tolerant states to achieve therapeutic re-programming of the innate immune response.
Structural variability of EspG chaperones from mycobacterial ESX-1, ESX-3 and ESX-5 type VII secretion systems
Authors: Tuukkanen Anne T. , Freire Diana , Chan Sum , Arbing Mark A. , Reed Robert W. , Evans Timothy J. , Zenkeviciutė Grasilda , Kim Jennifer , Kahng Sara , Sawaya Michael R. , Chaton Catherine T. , Wilmanns Matthias , Eisenberg David , Parret Annabel H. A. , Korotkov Konstantin V. 
Published: January 2018

AbstractType VII secretion systems (ESX) are responsible for transport of multiple proteins in mycobacteria. How different ESX systems achieve specific secretion of cognate substrates remains elusive. In the ESX systems, the cytoplasmic chaperone EspG forms complexes with heterodimeric PE-PPE substrates that are secreted from the cells or remain associated with the cell surface. Here we report the crystal structure of the EspG1 chaperone from the ESX-1 system determined using a fusion strategy with T4 lysozyme. EspG1 adopts a quasi 2-fold symmetric structure that consists of a central β-sheet and two α-helical bundles. Additionally, we describe the structures of EspG3 chaperones from four different crystal forms. Alternate conformations of the putative PE-PPE binding site are revealed by comparison of the available EspG3 structures. Analysis of EspG1, EspG3 and EspG5 chaperones using small-angle X-ray scattering (SAXS) reveals that EspG1 and EspG3 chaperones form dimers in solution, which we observed in several of our crystal forms. Finally, we propose a model of the ESX-3 specific EspG3-PE5-PPE4 complex based on the SAXS analysis.HighlightsThe crystal structure of EspG1 reveals the common architecture of the type VII secretion system chaperonesStructures of EspG3 chaperones display a number of conformations that could reflect alternative substrate binding modesEspG3 chaperones dimerize in solutionA model of EspG3 in complex with its substrate PE-PPE dimer is proposed based on SAXS data
Whole genome sequencing for predicting clarithromycin resistance in Mycobacterium abscessus
Authors: Lipworth Samuel , Hough Natasha , Leach Laura , Morgan Marcus , Jeffery Katie , Andersson Monique , Robinson Esther , Smith E. Grace , Crook Derrick , Peto Tim , Walker Timothy 
Published: January 2018

AbstractMycobacterium abscessus is emerging as an important pathogen in chronic lung diseases with concern regarding patient to patient transmission. The recent introduction of routine whole genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterise the genetic determinants of resistance. We conducted a systematic review to catalogue all known resistance determining mutations. This knowledge was used to construct a predictive algorithm based on mutations in the erm(41) and rrl genes which was tested on a collection of 203 sequentially acquired clinical isolates for which there was paired genotype/phenotype data. A search for novel resistance determining mutations was conducted using an heuristic algorithm.The sensitivity of existing knowledge for predicting resistance in clarithromycin was 95% (95% CI 89 – 98%) and the specificity was 66% (95% CI 54 – 76%). Subspecies alone was a poor predictor of resistance to clarithromycin. Eight potential new resistance conferring SNPs were identified. WGS demonstrates probable resistance determining SNPs in regions the NTM-DR line probe cannot detect. These mutations are potentially clinically important as they all occurred in samples predicted to be inducibly resistant, and for which a macrolide would therefore currently be indicated. We were unable to explain all resistance, raising the possibility of the involvement of other as yet unidentified genes.
Canopy cover and structural complexity affect the phylogenetic composition of a pond-dwelling Neotropical anuran metacommunity
Authors: Provete Diogo B. 
Published: January 2018

AbstractPhylogenetic information has been increasingly included into (meta)community assembly studies. However, recent studies have challenged the framework commonly used to infer processes from phylogenetic structure. Amphibians are good model organisms to study processes promoting structure in metacommunities, since they are subjected to different environmental and spatial processes throughout their biphasic life cycle. Pond canopy cover is one of these environmental factors that strongly influence the distribution of species and traits of several freshwater taxa, including larval amphibians (e.g., behavior, color, fin height, and length of intestine). Here, I tested the influence of pond canopy cover, floating vegetation, and pond morphology on the phylogenetic structure of an anuran metacommunity in the Atlantic Forest of Southeastern Brazil. I sampled tadpoles in 13 ponds and marshes from June 2008 and July 2009 in the Serra da Bocaina National Park, São Paulo. After building a metacommunity phylogeny, I used an eigenvector-based technique to describe the metacommunity phylogenetic composition (Principal Coordinates of Phylogenetic Structure, PCPS). I then run a db-RDA to evalute whether a subset of these eigenvectors can be explained by environmental variables. I found that pond canopy cover and floating vegetation were the main variables influencing lineage sorting in this metacommunity. Canopy cover separated hylid lineages from other families that were associated with open areas. Floating vegetation separated two hylid tribes (Cophomantini and Dendropsophini). Our results mainly suggest that the effect of canopy cover and floating vegetation on the structure of anuran metacommunity may affect not only species, but also entire lineages.