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Aim: Prone posture is often recommended for symptomatic gastroesophageal reflux in young infants, but prone positioning has been associated with sudden infant death. The aim of this study was thus to establish the optimal alternative posture for reducing reflux.Methods: 24 infants (< 5 months) with symptomatic gastro-oesophageal reflux were studied prospectively with 48 h pH monitoring. They were randomly assigned to one of the 24 permutations of the four positions (supine, prone, right, left). During the first 24 hours the infant was held horizontally, and then the permutation was repeated at 30 degrees head elevation, giving a total of eight study segments for each infant. Data were edited to remove all time when the infants were not in the prescribed positions. Results were evaluated using analysis of covariance.Results: Gastro-oesophageal reflux expressed as reflux index (mean % (SEM)) was significantly less in the prone and left lateral positions (6.72 (1.06) and 7.69 (1.03) respectively) than in the supine and right lateral positions (15.33 (2.33) and 12.02 (1.38); p < 0.001). Head elevation did not affect any variables significantly.Conclusions: Head elevation may not always be of clinical value. The left lateral position is a suitable alternative to prone for the postural management of infants with symptomatic gastro-oesophageal reflux. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in the UK. The Department of Health set up an opportunistic screening programme for genital chlamydia infection, focusing on sexually active 16-24-year-old women and some men. This study identified those patients re-attending the genitourinary medicine (GUM) clinic and followed them up until September 2002. We examined the reasons for attendance and re-infection with chlamydia. Two hundred and eighty-five patients re-attended the clinic. Two-thirds of these had changed their sexual partners in the follow-up period. Fifty-six patients were diagnosed with genital chlamydia infection in subsequent clinic visits. The majority of them had changed their sexual partners, suggesting new acquisition of infection. This suggests that in this age group re-screening should be offered at a year interval. Patients diagnosed with genital chlamydia infection should be referred to the GUM clinic for further STI screening and partner notification. [ABSTRACT FROM AUTHOR]

Drowning is the third leading cause of death from unintentional injury worldwide, accounting for 7% of all injury-related deaths. The World Health Organization estimates that there are ≈236 000 deaths due to drowning worldwide each year. Significant efforts have focused on creating systems to prevent drowning, but an average of 4000 fatal and 8000 nonfatal drownings still occur annually in the United States-likely an underestimate. Drowning generally progresses from initial respiratory arrest due to submersion-related hypoxia to cardiac arrest; thus, it can be challenging to distinguish respiratory arrest from cardiac arrest because pulses are difficult to accurately palpate within the recommended 10-second window. Therefore, resuscitation from cardiac arrest attributable to this specific circumstance must focus on restoring breathing as much as it does circulation. Resuscitation from drowning may begin with in-water rescue breathing when safely provided by rescuers trained in the technique and should continue with chest compressions, in keeping with basic life support guidelines, once the drowned individual and the rescuer are in a safe environment (eg, dry land, a boat). This focused update incorporates systematic reviews from 2021 to 2023 performed by the International Liaison Committee on Resuscitation related to the resuscitation of drowning. These clinical guidelines are the product of a committee of experts representing the American Heart Association and the American Academy of Pediatrics. The writing group reviewed the recent International Liaison Committee on Resuscitation systematic reviews, including updated literature searches, prior guidelines related to resuscitation from cardiac arrest following drowning, and other drowning-related publications from the American Heart Association and American Academy of Pediatrics. The writing group used these reviews to update its recommendations aimed at resuscitation of cardiac arrest following drowning in adults and children.

Drowning is the third leading cause of death from unintentional injury worldwide, accounting for 7% of all injury-related deaths. In the United States, drowning is the leading cause of death in children 1 to 4 years of age and second leading cause of death due to unintentional injury in those aged 5 to 14 years. Drowning generally progresses from initial respiratory arrest due to submersion-related hypoxia to cardiac arrest; thus, it can be challenging to distinguish respiratory arrest from cardiac arrest because pulses are difficult to accurately palpate within the recommended 10-second window. Therefore, resuscitation from cardiac arrest due to this specific circumstance must focus on restoring breathing as much as it does circulation. Resuscitation from drowning may begin with in-water rescue breathing when safely provided by rescuers trained in the technique and should continue with chest compressions, in keeping with basic life support guidelines, once the drowned individual and the rescuer are in a safe environment (eg, dry land, boat). This focused update incorporates systematic reviews from 2021 to 2023 performed by the International Liaison Committee on Resuscitation related to the resuscitation of drowning. These clinical guidelines are the product of a committee of experts representing the American Academy of Pediatrics and the American Heart Association. The writing group reviewed the recent International Liaison Committee on Resuscitation systematic reviews, including updated literature searches, prior guidelines related to resuscitation from cardiac arrest following drowning, and other drowning-related publications from the American Academy of Pediatrics and the American Heart Association. The writing group used these reviews to update its recommendations aimed at resuscitation from cardiac arrest following drowning in children., (Copyright © 2024 by the American Academy of Pediatrics and American Heart Association, Inc.)

Identification of monogenic causes of immune dysregulation provides insight into human immune response and signaling pathways associated with autoimmunity. Here, Jeanpierre et al. (https://doi.org/10.1084/jem.20232337) identify new germline variants in the gene encoding PTPN2 associated with loss of regulatory function, enhanced JAK/STAT signaling, and early-onset autoimmunity., (© 2024 Tobin and Cooper.)

Introduction: Prolonged Casualty Care (PCC) is a military adaptation aimed at providing pre-hospital care in austere settings when evacuation is delayed or even impossible. Current lack of standardized medical equipment and size/weight restrictions of military packs during dismounted operations hinder effective PCC. We sought to design a standardized, practical, and effective prolonged field care kit (PFAK) to enable widespread implementation of PCC., Materials and Methods: We reviewed Joint Trauma System Clinical Practice Guidelines to generate a list of potential contents of the PFAK. We obtained Institutional Review Board (IRB) exemption and then conducted stakeholder surveys of combat casualty care experts across the Joint Trauma System using a modified Delphi survey approach. We established a civil-military working group that provided in-depth qualitative feedback on the PFAK contents and provided an initial design of a long-range medical rucksack (LMR) to house it. Responses were analyzed using mean rank scores to help determine initial components of the PFAK. Tactical subject-matter experts tested and evaluated the PFAK and LMR prototype in austere conditions to refine the design., Results: Review of the PCC Clinical Practice Guidelines generated 49 medications and 301 potential supplies as potential PFAK contents. The first Delphi survey was sent to 100 stakeholders (overall response rate of 60%). After the first survey, contents were narrowed to a list of the most essential 27 medications and 105 other components. Iterative prototypes of the PFAK and LMR were tested to determine ergonomics, portability, flexibility, and equipment compartmentalization to facilitate use in emergencies. The prototype was optimized to address the clinical, logistical, and tactical requirements of PCC across a variety of platforms and environmental conditions., Conclusions: Given the changing battlefield environment, efficient and effective PCC will play an increasingly important role in the management of combat trauma. The PFAK can meet this need by providing a practical and standardized resuscitation kit generated by expert military and trauma personnel consensus, carried conveniently in the LMR., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

With increasing computing power, artificial intelligence (AI) and machine learning (ML) have prospered, which facilitate the analysis of large datasets, especially those found in critical care. It is important to define these terminologies, to inform a standardized approach to critical care research. This manuscript hopes to clarify these terms with examples from medical literature. Three major components that are required for a successful ML implementation: (i) reliable dataset, (ii) ML algorithm, and (iii) unbiased model evaluation, are discussed. A reliable dataset can be structured or unstructured with limited noise, outliers, and missing values. ML, a subset of AI, is typically focused on supervised or unsupervised learning tasks in which the output is based on inputs and derived from iterative pattern recognition algorithms, while AI is the overall ability of a machine to "think" or mimic human behavior; and to analyze data free from human influence. Even with successful implementation, advanced AI and ML algorithms have faced challenges in adoption into practice, mainly due to their lack of interpretability, which hinders trust, buy-in, and engagement from clinicians. Consequently, traditional algorithms, such as linear and logistic regression, that may have reduced predictive power but are highly interpretable, continue to be widely used., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Prehospital blood transfusion has been widely practiced in the military and is drawing renewed scrutiny after many years of civilian use., Objective: The objective of this article is to quantify the benefit derived from prehospital transfusion of blood products., Methods: Deidentified data were extracted retrospectively from the flight records of a critical care transportation program between April 2018 and January 2020. Patients who were transported before a prehospital blood transfusion protocol were compared with patients after initiation of the blood transfusion protocol. Demographic data, vital signs, laboratory analytics, and other outcome measures were analyzed., Results: Nine scene transport patients who met the transfusion criteria before a blood transfusion protocol were compared with 11 patients transported after initiation of the protocol. Identical outcome measures were analyzed. Patients who received prehospital blood transfusions had a statistically significantly longer hospital length of stay (16.5 vs 3.7 days, P = .03) and were more often taken directly to the operating room (80% vs 28%, P = .04). No statistically significant difference was identified when comparing mean arterial pressure, heart rate, respiratory rate, hemoglobin, hematocrit, or survival to hospital discharge., Conclusions: Trauma patients who received prehospital blood transfusion had a longer hospital length of stay and were more often taken directly to the operating room, but without improvement in survival., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Porous organic polymers (POPs) have been prepared via a novel metal free polycondensation between a tritopic indole-based monomer and squaric, croconic and rhodizonic acids. Each of the three POPs exhibited high BET surface areas (331-667 m 2 g -1 ) and zwitterionic structures. Impedance measurements revealed that the intrinsic POPs were relatively weak proton conductors, with a positive correlation between the density of oxo-groups and the proton conduction. Doping the materials with LiCl vastly improved the proton conductivity up to a value of 0.54 S cm -1 at 90 °C and 90% relative humidity., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

This Clinical Practice Guideline (CPG) provides a brief summary of the scientific literature for prehospital blood use, with an emphasis on the en route care environment. Updates include the importance of calcium administration to counteract the deleterious effects of hypocalcemia, minimal to no use of crystalloid, and stresses the importance of involved and educated en route care medical directors alongside at a competent prehospital and en route care providers (see Table 1). With the paradigm shift to use FDA-approved cold stored low titer group O whole blood (CS-LTOWB) along with the operational need for continued use of walking blood banks (WBB) and point of injury (POI) transfusion, there must be focused, deliberate training incorporating the different whole blood options. Appropriate supervision of autologous blood transfusion training is important for execution of this task in support of deployed combat operations as well as other operations in which traumatic injuries will occur. Command emphasis on the importance of this effort as well as appropriate logistical support are essential elements of a prehospital blood program as part of a prehospital/en route combat casualty care system., (2021.)

Current quantitative descriptions of the cardiovascular system in hemorrhagic shock focus on pressure based metrics. This approach is often incomplete; overlooking the important role of tissue perfusion. Electrical analogs to the cardiovascular system may offer a more complete description of hemorrhage. Application of fundamental concepts in electrical circuit theory (i.e.; Kirchhoff's Voltage Law and Ohm's Law) to analogs of the cardiovascular system offers a more refined description of this complex process. This manuscript hopes to serve as a starting point for a more mathematically robust, and clinically relevant description of hemorrhagic shock., (© 2021. Biomedical Engineering Society.)

Introduction: Studies assessing early trauma resuscitation have used long-term endpoints, such as 28- or 30-day mortality or Glasgow Outcomes Scores at 6-months. These endpoints are convenient but may not accurately reflect the effect of early resuscitation. We sought expert opinion and consensus on endpoints and definitions of variables needed to conduct a Department of Defense- (DoD) funded study to epidemiologically assess combat-relevant mortality and morbidity due to timeliness of resuscitation among critically injured civilians internationally., Methods: We conducted an online modified Delphi process with an international panel of civilian and US military experts. In several iterative rounds, experts reviewed background information, appraised relevant scientific evidence, provided comments, and rendered a vote on each variable. A-priori, we set consensus at ≥80% concordant votes., Results: Twenty panelists participated with a 100% response rate. Eight items were presented, with the following outputs for the epidemiologic study: Assess mortality within 7-days of injury; assess multi-organ failure using SOFA scores measured early (at day 3) and late (at day 7); assess traumatic brain injury mortality early (≤7-days) and late (28-days); hybrid (anatomic and physiologic) injury severity scoring is optimal; capture comorbidities per the US National Trauma Data Standard list with specific additions; assign resuscitative interventions to one of five standardized phases of trauma care; and, use a novel trauma death categorization system., Conclusions: A modified Delphi process yielded expert-ratified definitions and endpoints of variables necessary to conduct a combat-relevant epidemiologic study assessing outcomes due to early trauma resuscitation. Outputs may also benefit other groups conducting trauma resuscitation research.

Natural killer (NK) cell effector functions are dependent on metabolic regulation of cellular function; however, less is known about in vivo metabolic pathways required for NK cell antiviral function. Mice with an inducible NK-specific deletion of Cox10, which encodes a component of electron transport chain complex IV, were generated to investigate the role of oxidative phosphorylation in NK cells during murine cytomegalovirus (MCMV) infection. Ncr1-Cox10 Δ/Δ mice had normal numbers of NK cells but impaired expansion of antigen-specific Ly49H + NK cells and impaired NK cell memory formation. Proliferation in vitro and homeostatic expansion were intact, indicating a specific metabolic requirement for antigen-driven proliferation. Cox10-deficient NK cells upregulated glycolysis, associated with increased AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) activation, although this was insufficient to protect the host. These data demonstrate that oxidative metabolism is required for NK cell antiviral responses in vivo., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Drowning results in more than 360,000 deaths annually, making it the 3rd leading cause of unintentional injury death worldwide. Prior studies have examined airway interventions affecting patient outcomes in cardiac arrest, but less is known about drowning patients in arrest. This study evaluated the outcomes of drowning patients in the Cardiac Arrest Registry to Enhance Survival (CARES) who received advanced airway management., Methods: A retrospective analysis of the CARES database identified cases of drowning etiology between 2013 and 2018. Patients were stratified by airway intervention performed by EMS personnel. Demographics, sustained return of spontaneous circulation [ROSC], survival to hospital admission, survival to hospital discharge, and neurological outcomes were compared between airway groups using chi-squared tests and logistic regression., Results: Among 2388 drowning patients, 70.4% were male, 41.8% white, and 13.1% survived to hospital discharge. Patients that received supraglottic airways [SGA] had statistically significantly lower odds of survival to hospital admission compared to endotracheal tube [ETT] use (adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI] 0.42-0.76) as well as lower odds of survival to discharge compared to bag valve mask [BVM] use (aOR = 0.40, 95% CI 0.19-0.86) when accounting for relative ROSC timing., Conclusion: In this national cohort of drowning patients in cardiac arrest, SGA use was associated with significantly lower odds of survival to hospital admission and discharge. However, survival to discharge with favorable neurological outcome did not differ significantly between airway management techniques. Further studies will need to examine if airway intervention order or time to intervention affects outcomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study reports for the first time the preparation of an electrospun microfibrous mat of PIM-EA-TB. The electrospinning was carried out using a chloroform/ n -Propyl-lactate (n-PL) binary solvent system with different chloroform/nPL ratios, in order to control the morphology of the microfibres. With pure chloroform, porous and dumbbell shape fibres were obtained whereas, with the addition on n-PL, circular and thinner fibres have been produced due to the higher boiling point and the higher conductivity of n-PL. The electrospinning process conditions were investigated to evaluate their impact on the fibres' morphology. These microfibrous mats presented potential to be used as breathable/waterproof materials, with a pore diameter of 11 μm, an air resistance of 25.10 -7 m -1 and water breakthrough pressure of 50 mBar.

This Role 1, prolonged field care (PFC) clinical practice guideline (CPG) is intended to be used after Tactical Combat Casualty Care (TCCC) Guidelines, when evacuation to higher level of care is not immediately possible. A provider must first and foremost be an expert in TCCC, the Department of Defense standard of care for first responders. The intent of this PFC CPG is to provide evidence and experience-based solutions to those who manage airways in an austere environment. An emphasis is placed on utilizing the tools and adjuncts most familiar to a Role 1 provider. The PFC capability of airway is addressed to reflect the reality of managing an airway in a Role 1 resource-constrained environment. A separate Joint Trauma System CPG will address mechanical ventilation. This PFC CPG also introduces an acronym to assist providers and their teams in preparing for advanced procedures, to include airway management., (2020.)

Background: Surgical management of trauma in the last 20 years has evolved in parallel with the military's experience in the current conflicts. Therapies such as widespread tourniquet use, empiric administration of fresh frozen plasma, and airborne intensive care units had been viewed skeptically but are now common practice. There is an opportunity to expand the envelope of care even further through similarly innovative approaches and varied avenues of research., Results: As the molecular biology of trauma is elucidated, research methodologies must also be developed to capitalize on innovative approaches to resuscitation. Blood component therapy and control of bleeding remain as the fundamental concepts in trauma care. The inflammo-immune response to injury, however, plays an increasingly recognized role in recovery of organ function. Perhaps the inflammatory cascade of trauma can be manipulated to extend the treatment envelope of at risk trauma patients.In trauma, the additional challenge of delivering effective treatment, often required very early after injury, necessitates the development of treatments to be implemented on the front lines of trauma care that are cost-effective, portable, and environmentally stable. Future conflicts may not offer ready access to high-level surgical care; therefore, resuscitative therapies will be needed for wounded service members because they are evacuated to the surgeon. Manipulation of the inflammatory response to trauma may offer a solution. As our understanding of the immune response continues to develop, the potential for improved outcomes for the wounded expands., Conclusion: A review of basic concepts in immunology is necessary to appreciate any potential impact of immunotherapeutic approaches to trauma and inflammation. An overview of current options will focus on outcome benefits of available therapies and suggest possible areas for future investigation. Quantitative approaches will leverage basic science to identify high-yield strategies to improve care of the injured combatant., Level of Evidence: Review, level III.

Aspergillus fumigatus is an environmental fungus that can cause invasive pulmonary aspergillosis when spores are inhaled into the respiratory tract and invade airway or lung tissue. Influenza is a common respiratory virus that can cause severe respiratory disease, and postinfluenza invasive pulmonary aspergillosis, which is becoming a well-recognized clinical problem, typically occurs in critically ill patients. Mice challenged with influenza A PR/8/34 H1N1 and subsequently challenged with A. fumigatus had increased fungal burden, viral burden, inflammation, and mortality compared with single infected mice. Neutrophil recruitment in the lung of superinfected mice was decreased; however, mice were not neutropenic, and there was no difference in absolute blood neutrophils between groups. Additionally, CXCL1 and CXCL2 were decreased in lungs of superinfected mice compared with controls. IFN levels were increased in mice that received influenza, and deletion of STAT1 resulted in decreased fungal burden, increased airway and lung neutrophils, and increased CXCL1 compared with wild-type mice, whereas deletion of STAT2 did not change fungal burden or airway neutrophilia compared with wild-type mice. These data demonstrate a mechanism by which influenza A-induced STAT1 signaling inhibits neutrophil recruitment and increases susceptibility to postinfluenza invasive pulmonary aspergillosis., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Introduction: The concept of compressions only cardiopulmonary resuscitation (CO-CPR) evolved from a perception that lay rescuers may be less likely to perform mouth-to-mouth ventilations during an emergency. This study hopes to describe the efficacy of bystander compressions and ventilations cardiopulmonary resuscitation (CV-CPR) in cardiac arrest following drowning., Hypothesis/problem: The aim of this investigation is to test the hypothesis that bystander cardiopulmonary resuscitation (CPR) utilizing compressions and ventilations results in improved survival for cases of cardiac arrest following drowning compared to CPR involving compressions only., Methods: The Cardiac Arrest Registry for Enhanced Survival (CARES) was queried for patients who suffered cardiac arrest following drowning from January 1, 2013 through December 31, 2017, and in whom data were available on type of bystander CPR delivered (ie, CV-CPR CO-CPR). The primary outcome of interest was neurologically favorable survival, as defined by cerebral performance category (CPC)., Results: Neurologically favorable survival was statistically significantly associated with CV-CPR in pediatric patients aged five to 15 years (aOR = 2.68; 95% CI, 1.10-6.77; P = .03), as well as all age group survival to hospital discharge (aOR = 1.54; 95% CI, 1.01-2.36; P = .046). There was a trend with CV-CPR toward neurologically favorable survival in all age groups (aOR = 1.35; 95% CI, 0.86-2.10; P = .19) and all age group survival to hospital admission (aOR = 1.29; 95% CI, 0.91-1.84; P = .157)., Conclusion: In cases of cardiac arrest following drowning, bystander CV-CPR was statistically significantly associated with neurologically favorable survival in children aged five to 15 years and survival to hospital discharge.

Background: Persistent crying in infancy is common and may be associated with gastroesophageal reflux disease (GERD) and/or non-IgE-mediated cow's milk protein allergy (CMPA). We aimed to document upper gastrointestinal motility events in infants with CMPA and compare these to findings in infants with functional GERD., Methods: Infants aged 2 to 26 weeks with persistent crying, GERD symptoms and possible CMPA were included. Symptoms were recorded by 48-hour cry-fuss chart and validated reflux questionnaire (infant GERD questionnaire [IGERDQ]). Infants underwent a blinded milk elimination-challenge sequence to diagnose CMPA. GERD parameters and mucosal integrity were assessed by 24-hour pH-impedance monitoring before and after cow's milk protein (CMP) elimination. C-octanoate breath testing for gastric emptying dynamics, dual-sugar intestinal permeability, fecal calprotectin, and serum vitamin D were also measured., Results: Fifty infants (mean age 13 ± 7 weeks; 27 boys) were enrolled. On the basis of CMP elimination-challenge outcomes, 14 (28%) were categorized as non-IgE-mediated CMPA, and 17 (34%) were not allergic to milk; 12 infants with equivocal findings, and 7 with incomplete data were excluded. There were no baseline differences in GERD parameters between infants with and without CMPA. In the CMPA group, CMP elimination resulted in a significant reduction in reflux symptoms, esophageal acid exposure (reflux index), acid clearance time, and an increase in esophageal mucosal impedance., Conclusions: In infants with persistent crying, upper gastrointestinal motility parameters did not reliably differentiate between non-IgE-mediated CMPA and functional GERD. In the group with non-IgE-mediated CMPA, elimination of CMP significantly improved GERD symptoms, esophageal peristaltic function, and mucosal integrity.

Background: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants., Methods: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens., Results: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups., Conclusion: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

1,3,4-Oxadiazoles are a common motif in pharmaceutical chemistry, but few convenient methods for their modification exist. A fast, convenient, high yielding and general α-substitution of 1,3,4-oxadiazoles has been developed using a metalation-electrophilic trapping protocol both in batch and under continuous flow conditions in contradiction to previous reports which suggest that α-metalation of this ring system results in ring fragmentation. In batch, lithiation is accomplished at an industrially convenient temperature, -30 °C, with subsequent trapping giving isolated yields of up to 91 %. Under continuous flow conditions, metalation is carried out at room temperature, and subsequent in flow electrophilic trapping gave up to quantitative isolated yields. Notably, lithiation in batch at room temperature results only in ring fragmentation and we propose that the superior mixing in flow allows interception and exploitation of an unstable intermediate before decomposition can occur., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptides and is inhibited by the soluble decoy receptor IL-22-binding protein (IL-22BP). Little is known about the effect of the IL-22/IL-22BP regulatory pathway on lung infection, and it has not been studied in the setting of super-infection. We exposed wild-type and IL-22BP -/- mice to influenza A/PR/8/34 for 6 days prior to infection with S. aureus (USA300) S. pneumoniae. Super-infected IL-22BP -/- mice had decreased bacterial burden and improved survival compared to controls. IL-22BP -/- mice exhibited decreased inflammation, increased lipocalin 2 expression, and deletion of IL-22BP was associated with preserved epithelial barrier function with evidence of improved tight junction stability. Human bronchial epithelial cells treated with IL-22Fc showed evidence of improved tight junctions compared to untreated cells. This study revealed that IL-22BP -/- mice are protected during influenza, bacterial super-infection, suggesting that IL-22BP has a pro-inflammatory role and impairs epithelial barrier function likely through interaction with IL-22.

Postinfluenza bacterial superinfections cause increased morbidity and mortality compared with singular infection with influenza during both pandemics and seasonal epidemics. Vaccines and current treatments provide limited benefit, a rationale to conduct studies utilizing alternative therapies. FY1 and an optimized version, MEDI8852, anti-influenza HA mAbs, have been shown to neutralize influenza virus during singular influenza infection. MEDI4893*, an anti-Staphylococcus aureus α-toxin mAb, has been shown to improve survival when administered prophylactically prior to S. aureus pneumonia. Our objective was to determine if mAbs can improve survival during postinfluenza bacterial pneumonia. We administered FY1 in a murine model of postinfluenza methicillin-resistant S. aureus (MRSA) pneumonia and observed improved survival rates when given early during the course of influenza infection. Our findings indicate decreased lung injury and increased uptake and binding of bacteria by macrophages in the mice that received FY1 earlier in the course of influenza infection, corresponding to decreased bacterial burden. We also observed improved survival when mice were treated with a combination of FY1 and MEDI4893* late during the course of postinfluenza MRSA pneumonia. In conclusion, both FY1 and MEDI4893* prolong survival when used in a murine model of postinfluenza MRSA pneumonia, suggesting pathogen-specific mAbs as a possible therapeutic in the context of bacterial superinfection.

Objective: Given the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics ( Lactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis ) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks' gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition., Research Design and Methods: This was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia., Results: The study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm ( P = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) ( P = 0.049). One- and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm ( P = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) ( P = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) ( P = 0.042). There were no differences in other secondary outcomes., Conclusions: The probiotics used in this study did not prevent GDM in overweight and obese pregnant women., (© 2019 by the American Diabetes Association.)

Introduction:: Limited options exist for cardiovascular support of the trauma patient in extremis. This patient population offers challenges that are often considered insurmountable. This article identifies a heterogeneous group of trauma patients in extremis who may benefit from extracorporeal membrane oxygenation., Methods:: Data were sourced from the medical records of all patients placed on extracorporeal membrane oxygenation following trauma at a Level I Trauma Center between 1 December 2016 and 1 December 2017., Results:: All patients were male (N = 7), mostly with blunt injuries (n = 5), with an average age of 41 years and with an average Injury Severity Scores of 33 (median = 34). Two out of seven patients survived (28.5%). Survivors tended to have a longer duration on extracorporeal membrane oxygenation (13.5 vs 3.8 days), had extracorporeal membrane oxygenation initiated later (15 vs 7.8 days), and had suffered a blunt injury. Two patients were initiated on veno-arterial extracorporeal membrane oxygenation (both non-survivors) and five were initiated on veno-venous extracorporeal membrane oxygenation (two survivors, three non-survivors). Five patients were heparinized immediately (one survivor, four non-survivors), and two patients were heparinized after clotting was noted in the circuit (one survivor, one non-survivor). Three of the seven (42.8%) patients suffered cardiac arrest either prior to, or during, the initiation of extracorporeal membrane oxygenation (all non-survivors)., Discussion:: Extracorporeal membrane oxygenation use in the trauma patient in extremis is not standard; however, this article demonstrates that extracorporeal membrane oxygenation is feasible in a complex, heterogeneous patient population when treated at designated centers.

Grf10, a homeodomain-containing transcription factor, regulates adenylate and one-carbon metabolism and morphogenesis in the human fungal pathogen Candida albicans Here, we identified functional domains and key residues involved in transcription factor activity using one-hybrid and mutational analyses. We localized activation domains to the C-terminal half of the Grf10 protein by one-hybrid analysis and identified motifs using bioinformatic analyses; one of the characterized activation domains (AD1) responded to temperature. The LexA-Grf10 fusion protein activated the lexA op -HIS1 reporter in an adenine-dependent fashion, and this activation was independent of Bas1, showing that the adenine limitation signal is transmitted directly to Grf10. Overexpression of LexA-Grf10 led to filamentation, and this required a functioning homeodomain, consistent with Grf10 controlling the expression of key filamentation genes; filamentation induced by LexA-Grf10 overexpression was independent of adenine levels and Bas1. Alanine substitutions were made within the conserved interaction regions (IR) of LexA-Grf10 and Grf10 to investigate roles in transcription. In LexA-Grf10, the D302A mutation activated transcription constitutively, and the E305A mutation was regulated by adenine. When these mutations were introduced into the native gene locus, the D302A mutation was unable to complement the ADE phenotype and did not promote filamentation under hypha-inducing conditions; the E305A mutant behaved as the native gene with respect to the ADE phenotype and was partially defective in inducing hyphae. These results demonstrate allele-specific responses with respect to the different phenotypes, consistent with perturbations in the ability of Grf10 to interact with multiple partner proteins. IMPORTANCE Metabolic adaptation and morphogenesis are essential for Candida albicans , a major human fungal pathogen, to survive and infect diverse body sites in the mammalian host. C. albicans utilizes transcription factors to tightly control the transcription of metabolic genes and morphogenesis genes. Grf10, a critical homeodomain transcription factor, controls purine and one-carbon metabolism in response to adenine limitation, and Grf10 is necessary for the yeast-to-hypha morphological switching, a known virulence factor. Here, we carried out one-hybrid and mutational analyses to identify functional domains of Grf10. Our results show that Grf10 separately regulates metabolic and morphogenesis genes, and it contains a conserved protein domain for protein partner interaction, allowing Grf10 to control the transcription of multiple distinct pathways. Our findings contribute significantly to understanding the role and mechanism of transcription factors that control multiple pathogenic traits in C. albicans ., (Copyright © 2018 Wangsanut et al.)

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.

Trauma airway management is a critical skill for medical providers supporting combat casualties since it is an integral component of damage control resuscitation and surgery. This clinical practice guideline presents methods for optimizing the airway management of patients with traumatic injury in the operational medical treatment facility environment. The guidelines represent the knowledge and experience of 10 co-authors from 3 allied countries representing Emergency Medicine, Surgery and Anesthesia.

An improved understanding of the pathophysiology of combat trauma has evolved over the past decade and has helped guide the anesthetic care of the trauma patient requiring surgical intervention. Trauma anesthesia begins before patient arrival with warming of the operating room, preparation of anesthetic medications and routine anesthetic machine checks. Induction of anesthesia must account for potential hemodynamic instability and intubation must consider airway trauma. Maintenance of anesthesia is accomplished with anesthetic gas, intravenous infusions or a combination of both. Resuscitation must precede or be ongoing with the maintenance of anesthesia. Blood product transfusion, antibiotic administration, and use of pharmacologic adjuncts (e.g., tranexamic acid, calcium) all occur simultaneously. Ventilatory strategies to mitigate lung injury can be initiated in the operating room, and resuscitation must be effectively transitioned to the intensive care setting after the case. Good communication is vital to efficient patient movement along the continuum of care. The resuscitation that is undertaken before, during and after operative management must incorporate important changes in care of the trauma patient. This Clinical Practice Guideline hopes to provide a template for care of this patient population. It outlines a method of anesthesia that incorporates the induction and maintenance of anesthesia into an ongoing resuscitation during surgery for a trauma patient in extremis.

Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 min. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas were concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile.

A Pd II catalyst system has been used to successfully catalyse two mechanistically distinct reactions in a one-pot procedure: dehydrogenation of 2,2-disubstituted cyclopentane-1,3-diones and the subsequent oxidative Heck coupling. This auto-tandem catalytic reaction is applicable to both batch and continuous flow processes, with the latter being the first example of a tandem aerobic dehydrogenation/oxidative Heck in flow. In addition, a telescoped reaction involving enantioselective desymmetrisation of the all-C quaternary centre was successfully achieved., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The point-of-care ultrasound exam has become an essential tool for hemodynamic monitoring and resuscitation in the trauma bay as well as the intensive care unit. Transthoracic ultrasound provides a dynamic assessment of cardiac function, volume status, and fluid responsiveness that offers potential advantage over traditional methods of hemodynamic monitoring. More recently, a focused transthoracic echocardiography exam was described to improve immediate resuscitation of severely injured patients in the trauma bay. Transesophageal echocardiography (TEE) for trauma could expand upon the role of focused echocardiography. TEE offers improved visualization of cardiac anatomy and physiology, improved diagnostic accuracy, and real-time assessment of intraoperative resuscitation progress, particularly in the operating room. This review discusses the fundamental principles of echocardiography as well as different ultrasound modes with their respective strengths and limitations. It reviews the current literature on the use of TEE in trauma, and suggests views for a trauma resuscitation transesophageal echocardiography exam (TREE), including sample images and videos., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cardiac arrest associated with drowning is a major public health concern with limited research available on outcome. This investigation aims to define the population at risk, and identify factors associated with neurologically favourable survival., Methods: The Cardiac Arrest Registry for Enhanced Survival (CARES) database was queried for patients who had suffered cardiac arrest following drowning between January 1, 2013 and December 31, 2015. The primary outcomes of interest were for favourable or unfavourable neurological outcome at hospital discharge, as defined by Cerebral Performance Category (CPC)., Results: A total of 919 drowning patients were identified. Neurological outcome data was available in 908 patients. Neurologically favourable survival was significantly associated with bystander CPR (Odds Ratio (OR)=2.94; 95% Confidence Interval (CI) 1.86-4.64; p<0.001), witnessed drowning (OR=2.6; 95% CI 1.69-4.01; p<0.001) and younger age (OR=0.97, 95% CI 0.96-0.98; p<0.001). Public location of drowning (OR=1.17; 95% CI 0.77-1.79; p=0.47), male gender (OR=0.9, 95% CI 0.57-1.43; p=0.66), and shockable rhythm (OR=1.54; 95% CI 0.76-3.12; p=0.23), were not associated with favourable neurological survival. AED application prior to EMS was associated with a decreased likelihood of favourable neurological outcome (OR=0.38; 95% CI 0.28-0.66; p<0.001). In multivariate analysis, bystander CPR (adjusted OR 3.02, 95% CI 1.85-4.92, p<0.001), witnessed drowning (adjusted OR 3.27, 95% CI 2.0-5.36, p<0.001) and younger age (adjusted OR 0.97, 95% CI 0.96-0.98, p<0.001) remained associated with neurologically favourable survival., Conclusions: Neurologically favourable survival after drowning remains low but is improved by bystander CPR. Shockable rhythms were uncommon and not associated with improved outcomes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Despite mixed results regarding the clinical utility of checklists, the anesthesia community is increasingly interested in advancing research around this important topic. Although several checklists have been developed to address routine perioperative care, few checklists in the anesthesia literature specifically target the management of trauma patients. We adapted a recently published "trauma and emergency checklist" for the initial phase of resuscitation and anesthesia of critically ill trauma patients into an applicable perioperative cognitive aid in the form of a pictogram that can be downloaded by the medical community. The Ryder Cognitive Aid Checklist for Trauma Anesthesia is a letter-sized, full-color document consisting of 2 pages and 5 sections. This cognitive aid describes the essential steps to be performed: before patient arrival to the hospital, on patient arrival to the hospital, during the initial assessment and management, during the resuscitation phase, and for postoperative care. A brief online survey is also presented to obtain feedback for improvement of this tool. The variability in utility of cognitive aids may be because of the specific clinical task being performed, the skill level of the individuals using the cognitive aid, overall quality of the cognitive aid, or organizational challenges. Once optimized, future research should be focused at ensuring successful implementation and customization of this tool.

Objective: These data describe the critical care procedures performed on, and the resuscitation markers of, critically wounded personnel in Afghanistan following point of injury (POI) transports and intratheater transports. Providing this information may help inform discussion on the design of critical care transportation platforms for future conflicts., Methods: The Department of Defense Trauma Registry (DoDTR) was queried for descriptive data on combat casualties with Injury Severity Score (ISS) greater than 15 who were transported in Operation Enduring Freedom (OEF) from 1 January 2010 to 31 December 2010. Both POI transportation events and interfacility transportation events were reviewed. Base deficit (BD) was evaluated as a maker of resuscitation, and international normalized ratio (INR) was evaluated as a measure of coagulopathy., Results: There were 1198 transportation events that occurred during the study period--634 (53%) transports from the POI and 564 (47%) intratheater transports. Critical care interventions were performed during 147 (12.3%) transportation events, including intubation, cricothyrotomy, double-lumen endotracheal tube placement, needle or tube thoracostomy, central venous access placement, and cardiopulmonary resuscitation. The mean BD on arrival in the emergency department was -5.4 mEq/L for POI transports and 0.68 mEq/L intratheater transports (ρ<.001). The mean INR on arrival in the emergency department was 1.48 for POI transports and 1.21 for intratheater transports (ρ<.001)., Conclusions: Critical care interventions were needed frequently during evacuation of severely injured personnel. Furthermore, many troops arrived acidotic and coagulopathic following initial transport from POI. Together, these data suggest that a platform capable of damage control resuscitation and critical care interventions may be warranted on longer transports of more critically injured patients., (2015.)