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Intra-abdominal hypertension occurs in 50% of all patients admitted to the intensive care unit and is associated with significant morbidity and mortality. Intra-abdominal hypertension is defined as a sustained, pathologic rise in intra-abdominal pressure to 12 mm Hg or more. Patients with intra-abdominal hypertension may progress to abdominal compartment syndrome. Early identification and treatment of this condition will improve patient outcome. Patients at risk for intra-abdominal hypertension include those with major traumatic injury, major surgery, sepsis, burns, pancreatitis, ileus, and massive fluid resuscitation. Predisposing factors include decreased abdominal wall compliance, increased intraluminal contents, increased peritoneal cavity contents, and capillary leak/fluid resuscitation. [ABSTRACT FROM AUTHOR]

Initiate these best-practice interventions when your patient's critical illness or injury triggers this life-threatening pulmonary complication. [ABSTRACT FROM AUTHOR]

OBJECTIVE: : To present a clinical ethics case report that illustrates the benefits of using lip-reading interpreters for ventilated patients who are capable of mouthing words. DESIGN: : Case report. SETTING: : The burn unit of a university teaching hospital in New York City. PATIENT: : A 75-yr-old man was admitted to the burn unit with 50% total body surface area burns. He was awake, alert, ventilator-dependent via a tracheostomy, and able to mouth words. INTERVENTIONS: : A deaf lip-reading interpreter and a hearing American sign language interpreter worked together in a circuit formation to provide verbal voice for the patient. CONCLUSION: : For the ventilated patient who can mouth words, lip-reading interpretation offers an opportunity for communication. It is time we routinely provide lip-reading interpreters as well as recognize the need for prospective studies examining the role of lip-reading in medical settings. [ABSTRACT FROM AUTHOR]

Objective: Increasingly, medical schools integrate clinical skills into early didactic coursework. The Stop the Bleed® Campaign emphasizes prehospital hemorrhage control to reduce preventable deaths; however, this course overlooks team interactions. We assessed the impact of high-fidelity simulation during medical student orientation on identification and treatment of life-threatening hemorrhage in a team setting., Design: In this mixed method, prospective pre-, post-, and follow-up survey analysis assessing student knowledge and attitudes, student teams encountered a standardized patient in a prehospital environment with pulsatile bleeding from an extremity wound. Individual students completed surveys assessing previous experience, willingness and ability to assist bleeding person(s), and knowledge and attitudes about tourniquets. Postscenario, faculty preceptors made qualitative observations on teamwork., Setting: Medical student orientation at a tertiary care academic medical center with long-term follow-up., Participants: Medical students (N = 150)., Results: Ninety students (60%) completed both pre- and postsimulation questionnaires. Sixteen (17%) students had previous tourniquet training experience although none had applied a tourniquet outside of training. Postsimulation, students reported increased likelihood of providing treatment until additional help arrived (p = 0.035), improved ability to identify life-threatening hemorrhage (p < 0.001), and more favorable opinions about tourniquet use (p < 0.001) and potential for limb-salvage (p = 0.018). Long-term follow-up respondents (n = 34, 23%) reported increased ability to identify life-threatening hemorrhage (p = 0.010) and universal willingness to intervene until additional help arrived. Follow-up survey responses elicited themes in hemorrhage control including recognition of the importance of continuous pressure, appropriate use of tourniquets, a desire for repeated team training, and the recognition of clerkship rotations as an optimal setting for skill reinforcement. Preceptors noted variable team responses but uniformly endorsed the exercise., Conclusions: High-fidelity bleeding simulation during medical student orientation improved students' knowledge and attitudes about treating life-threatening hemorrhage and served as an introduction to team-based emergency care. Future studies should further explore team training and hemorrhage control education., (Copyright © 2024 Association of Program Directors in Surgery. All rights reserved.)

Ayurveda, an ancient holistic and personalized healing system originating from the Indian subcontinent, has been gaining increasing attention as a complementary and alternative medical practice for treating various health conditions, including those related to women's reproductive well-being. This comprehensive literature review examines a wide array of experimental and clinical studies exploring the diverse facets of Ayurvedic interventions in addressing issues such as menstrual irregularities, polycystic ovary syndrome (PCOS), infertility, and menopausal symptoms. The paper specifically focuses on discussing the available data regarding the efficacy of Tulsi ( Ocimum tenuiflorum ), ashwagandha ( Withania somnifera ), ginger ( Zingiber officinale ), cardamom ( Elettaria cardamomum ), turmeric ( Curcuma longa ), and Shatavari ( Asparagus racemosus ) , which have traditionally been used in Ayurvedic medicine for centuries. The synthesis of literature not only highlights the potential benefits of these Ayurvedic interventions, but also critically assesses the methodological rigor of existing studies, identifying research gaps, and proposing directions for future investigations. While acknowledging the need for further rigorous research and clinical trials, the review emphasizes the benefits of collaborative and integrative healthcare. This review aims to serve as a valuable resource for healthcare practitioners, researchers, and individuals seeking holistic and natural alternatives for female reproductive health management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Patibandla et al.)

Background: The heart failure (HF) virtual consultation (VC) is an eHealth tool for delivery of peer-to-peer specialist advice to general practitioners (GPs) to discuss HF diagnosis/management. We aim to investigate the impact of the VC service on onward referral rate and quality of assessment by GPs, as well as assess VC patient characteristics; Clinical Frailty Score (CSF), age and morbidity., Methods: This prospective observational study collected VC data on: demographics, comorbidity, frailty, referral indication, the impact of VC on clinical care and the GP response to the question 'what would you have done without the VC service'. We compared patient characteristics to a control population of patients attending the HF unit (HFU) (n=118)., Reults: Between 2015 and 2021, 1681 VC cases were discussed. The majority of cases were discussed from remote areas (75%). Rediscussion cases increased from 0% to 34%. VC patients were older (76.2 (±11.3) vs 73.1 (±12.5) years, p<0.05), more frail (CSF=3.8 (±1.7) vs 3 (±1.6), p<0.01) and multimorbid (number of comorbidities=7.1 (±3.4) vs 3.8 (±1.9), p<0.001) compared with patients attending the HFU. Without the VC, 93% of cases would have been referred to face-to-face hospital services. Instead, VC resulted in only 9% of cases being referred to hospital services. The remainder of cases were managed by the VC service, in a shared GP-specialist approach. GP use of natriuretic peptide (NP) increased from 0% in 2015-2016 to 63% in 2021 and use of TTE increased from 0% in 2015-2016 to 69% by 2021., Conclusions: The VC service provides a platform for case discussion in particular for older, frailer patients and reduces onward hospital referrals. This may facilitate early diagnosis and management of suspected HF in the current era of long outpatient waiting times. The quality of community HF assessment improved as indicated by increased use of NP/TTE by GPs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The conversion of CO2 to value-added products allows both capture and recycling of greenhouse gas emissions. While plants and other photosynthetic organisms play a key role in closing the global carbon cycle, their dependence on light to drive carbon fixation can be limiting for industrial chemical synthesis. Methanogenic archaea provide an alternative platform as an autotrophic microbial species capable of non-photosynthetic CO2 fixation, providing a potential route to engineered microbial fermentation to synthesize chemicals from CO2 without the need for light irradiation. One major challenge in this goal is to connect upstream carbon-fixation pathways with downstream biosynthetic pathways, given the distinct differences in metabolism between archaea and typical heterotrophs. We engineered the model methanogen, Methanococcus maripaludis, to divert acetyl-coenzyme A toward biosynthesis of value-added chemicals, including the bioplastic polyhydroxybutyrate (PHB). A number of studies implicated limitations in the redox pool, with NAD(P)(H) pools in M. maripaludis measured to be <15% of that of Escherichia coli, likely since methanogenic archaea utilize F420 and ferredoxins instead. Multiple engineering strategies were used to precisely target and increase the cofactor pool, including heterologous expression of a synthetic nicotinamide salvage pathway as well as an NAD+-dependent formate dehydrogenase from Candida boidinii. Engineered strains of M. maripaludis with improved NADH pools produced up to 171 ± 4 mg/L PHB and 24.0 ± 1.9% of dry cell weight. The metabolic engineering strategies presented in this study broaden the utility of M. maripaludis for sustainable chemical synthesis using CO2 and may be transferable to related archaeal species.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Introduction: Bacteraemia in pregnancy and the post-partum period can lead to maternal and newborn morbidly. The purpose of this study was to use machine learning tools to identify if bacteraemia in pregnant or post-partum women could be predicted by full blood count (FBC) parameters other than the white cell count., Methods: The study was performed on 129 women with a positive blood culture (BC) for a clinically significant organism, who had a FBC taken at the same time. They were matched with controls who had a negative BC taken at the same time as a FBC. The data were split in to a training (70%) and test (30%) data set. Machine learning techniques such as recursive partitioning and classification and regression trees were used., Results: A neutrophil/lymphocyte ratio (NLR) of >20 was found to be the most clinically relevant and interpretable construct of the FBC result to predict bacteraemia. The diagnostic accuracy of NLR >20 to predict bacteraemia was then examined. Thirty-six of the 129 bacteraemia patients had a NLR >20, while only 223 of the 3830 controls had a NLR >20. This gave a sensitivity of 27.9% (95% CI 20.3-36.4), specificity of 94.1% (93.3-94.8), positive predictive value of 13.9% (10.6-17.9) and a negative predictive value (NPV) of 97.4% (97.2-97.7) when the prevalence of bacteraemia was 3%., Conclusion: The NLR should be considered for use in routine clinical practice when assessing the FBC result in patients with suspected bacteraemia during pregnancy or in the post-partum period., (© 2020 John Wiley & Sons Ltd.)

Background: Race and socioeconomic status influence outcomes for adult and pediatric burn patients, yet the impact of these factors on elderly patients (Medicare eligible, 65 years of age) remains unknown., Methods: Data pooled from three verified burn centers from 2004 to 2014 were reviewed retrospectively. Age, race, gender, percent total body surface area (%TBSA) burn, mortality, length of stay (LOS), LOS per %TBSA burn, and zip code which provided Census data on race, poverty, and education levels within a community were collected. Data were analyzed using logistic and generalized linear models in SAS version 9.4 (SAS Institute, Cary, NC, USA)., Results: Our population was mainly Caucasian (63%), African American (18%), Hispanic (7.6%), and Asian (3.5%). Mean age was 76.3 ± 8.3 years, 52.5% were male. Mean %TBSA was 9 ± 13.8%; 15% of the patients sustained an inhalation injury. The mortality rate was 14.4%. Inhalation injury was significantly associated with mortality and discharge to a skilled nursing facility (SNF) (p < 0.05). Race was significantly associated with socioeconomic disparities and affected LOS/TBSA, but not discharge to SNF or mortality on univariate analysis. Poverty level, education level, and insurance status (others vs. public) independently predicted SNF discharge, while median income and insurance type independently predicted LOS/TBSA., Conclusion: In this elderly cohort, race did not predict standard markers of burn outcome (mortality and discharge to SNF). Socioeconomic status independently predicted LOS and discharge to SNF, suggesting a relationship between socioeconomic status and recovery from a burn injury. Better understanding of racial and socioeconomic disparities is necessary to provide equitable treatment of all patients., (Copyright © 2020. Published by Elsevier Ltd.)

Preparing for disasters both natural and anthropogenic requires assessment of risk through hazard vulnerability analysis and formulation of facility and critical care-specific disaster plans. Disaster surge conditions often require movement from conventional to contingency or crisis-level operations to meet the needs of the many under our care. Predisaster planning for modification of critical care space, staffing, and supplies is essential to successful execution of operations during a surge. Expansion of intensive care unit beds to nonconventional units such as perioperative areas, general care units, and even external temporary units may be necessary. Creative, tiered staffing models as well as just-in-time education of noncritical care clinicians and support staff are important to multiply capable personnel under surge conditions. Finally, anticipation of demand for key equipment and supplies is essential to maintain stockpiles, establish supply chains, and sustain operations under prolonged disaster scenarios., (©2021 American Association of Critical-Care Nurses.)

Objectives: In New York City, a multi-disciplinary Mass Casualty Consultation team is proposed to support prioritization of patients for coordinated inter-facility transfer after a large-scale mass casualty event. This study examines factors that influence consultation team prioritization decisions., Methods: As part of a multi-hospital functional exercise, 2 teams prioritized the same set of 69 patient profiles. Prioritization decisions were compared between teams. Agreement between teams was assessed based on patient profile demographics and injury severity. An investigator interviewed team leaders to determine reasons for discordant transfer decisions., Results: The 2 teams differed significantly in the total number of transfers recommended (49 vs 36; P = 0.003). However, there was substantial agreement when recommending transfer to burn centers, with 85.5% agreement and inter-rater reliability of 0.67 (confidence interval: 0.49-0.85). There was better agreement for patients with a higher acuity of injuries. Based on interviews, the most common reason for discordance was insider knowledge of the local community hospital and its capabilities., Conclusions: A multi-disciplinary Mass Casualty Consultation team was able to rapidly prioritize patients for coordinated secondary transfer using limited clinical information. Training for consultation teams should emphasize guidelines for transfer based on existing services at sending and receiving hospitals, as knowledge of local community hospital capabilities influence physician decision-making.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a low-frequency, high-acuity intervention. We hypothesized that REBOA-specific knowledge and comfort deteriorate significantly within 6 months of a formal training course if REBOA is not performed in the interim., Methods: A comprehensive REBOA course was developed including didactics and hands-on practical simulation training. Baseline knowledge and comfort were assessed with a precourse objective test and a subjective self-assessment. REBOA knowledge and comfort were then re-assessed immediately postcourse and again at 6 months and 1 year. Performance trends were measured using paired Student's t and Wilcoxon signed-rank tests., Results: Thirteen participants were evaluated including trauma faculty (n = 10) and fellows (n = 3). Test scores improved significantly from precourse (72% ± 10% correct) to postcourse (88% ± 8%, p < 0.001). At 6 months, scores remained no different from postcourse (p = 0.126); at 1 year, scores decreased back to baseline (p = 0.024 from postcourse; 0.285 from precourse). Subjective comfort with femoral arterial line placement and REBOA improved with training (p = 0.044 and 0.003, respectively). Femoral arterial line comfort remained unchanged from postcourse at 6 months (p = 0.898) and 1 year (p = 0.158). However, subjective comfort with REBOA decreased relative to postcourse levels at 6 months (p = 0.009), driven primarily by participants with no clinical REBOA cases in the interim., Conclusions: A formal REBOA curriculum improves knowledge and comfort with critical aspects of this procedure. This knowledge persists at 6 months, though subjective comfort deteriorated among those without REBOA placement in the interim. REBOA refresher training should be considered at 6-month intervals in the absence of clinical REBOA cases., Level of Evidence/study Type: Level III, prognostic., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

In 2018, the World Health Organization (WHO) launched the Global Burn Registry (GBR). Its purpose is to help improve the understanding of burn injury worldwide. The purpose of this study was to identify early findings from this database. The GBR was accessed on January 5, 2020. Cases from centers in low income (LIC) and low-middle-income countries (LMIC) were combined into a low resource (LR) group, and cases in high income (HIC) and upper-middle-income countries (UMIC) were combined into a high resource (HR) group. Statistical analysis was performed with SAS 9.4. Data are expressed as mean ± SEM. Logistic regression was used to identify risk factors for death. Revised Baux Score (RBS) was calculated. Odds ratios are expressed as mean (95% confidence interval). The LA50 was calculated from the regression of death and total burn size (TBSA) for different age groups. At the time of analysis, there were 4307 cases in the GBR treated at 28 facilities in 17 countries (5 HIC, 5 UMIC, 4 LMIC, and 3 LIC). There were 2945 cases (68%) from HR countries and 1362 (32%) from LR countries. The mean age of patients in both LR and HR was similar (24.5 ± 0.5 vs 24.2 ± 0.4 years, P = .58), but LR had larger TBSA burns (30.5 ± 0.7% vs 19.8 ± 0.4% TBSA, P < .0001). There were fewer scald burns and more flame injuries in the LR countries (28.4 ± 1.3% vs 43.3 ± 1.0% and 55.2 ± 1.4% vs 39.0 ± 0.9%, P < .0001). Case fatality and RBS were greater in LR (31.9 ± 1.3% vs 9.4 ± 0.5% and 59.4 ± 1.1% vs 45.3 ± 0.6%, P < .0001). In regression analysis, LR was an independent risk factor for death with an odds ratio of 4.2 (3.2-5.4). The LA50 for HR countries was similar to that calculated from cases in the National Burn Repository of the American Burn Association (ABA NBR). For LR countries, the LA50 was lower for all ages except those 65 and older, ranging from 30% to 43% TBSA. Only a few facilities have contributed data to the GBR so far, with LR countries less represented than HR ones. The proportion of cases in the pediatric age group is much less represented in LR countries than in HR, possibly because many burned children in LR countries do not get burn care at specialized centers. Survival in HR countries is similar to that in North America. The GBR provides early insights into global burn care. Opportunities for improvement are greatest in LR countries. New Innovations may be necessary to increase participation from burn centers in LR countries. This report provides an early look at burn care across the globe based on cases in the GBR. It may inform further efforts to characterize and improve burn care in LR countries., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intra-abdominal hypertension has been identified as an independent risk factor for death in critically ill patients. Known risk factors for intra-abdominal hypertension indicate that intra-abdominal pressures should be measured and monitored. The Abdominal Compartment Society has identified medical and surgical interventions to relieve intra-abdominal hypertension or to manage the open abdomen if abdominal compartment syndrome occurs. The purpose of this article is to describe assessments and interventions for managing intra-abdominal hypertension and open abdomen that are within the scope of practice for direct-care nurses. These guidelines provide direction to critical care nurses caring for these patients., (©2020 American Association of Critical-Care Nurses.)

Modern mechanical ventilators are more complex than those first developed in the 1950s. Newer ventilation modes can be difficult to understand and implement clinically, although they provide more treatment options than traditional modes. These newer modes, which can be considered alternative or nontraditional, generally are classified as either volume controlled or pressure controlled. Dual-control modes incorporate qualities of pressure-controlled and volume-controlled modes. Some ventilation modes provide variable ventilatory support depending on patient effort and may be classified as closed-loop ventilation modes. Alternative modes of ventilation are tools for lung protection, alveolar recruitment, and ventilator liberation. Understanding the function and application of these alternative modes prior to implementation is essential and is most beneficial for the patient., (©2018 American Association of Critical-Care Nurses.)

Procedural sedation is used to alleviate pain and anxiety associated with diagnostic procedures in the acute care setting. Although commonly used, procedural sedation is not without risk. Key to reducing this risk is early identification of risk factors through presedation screening and monitoring during the procedure. Electrocardiogram, respiratory rate, blood pressure, and pulse oximetry commonly are monitored. These parameters do not reliably identify airway and ventilation compromise. Capnography measures exhaled carbon dioxide and provides early identification of airway obstruction and hypoventilation. Capnography is useful in patients receiving supplemental oxygen. In these patients, oxygen desaturation reported by pulse oximetry may lag during episodes of respiratory depression and apnea. Capnography indicates partial pressure of end-tidal carbon dioxide and provides information regarding airway integrity and patterns of ventilation compromise. Implementation of this technology may provide an additional layer of safety, reducing risk of respiratory compromise in patients receiving procedural sedation., (©2018 American Association of Critical-Care Nurses.)

Objective: To determine if an innovative extracorporeal electrohydraulic shock wave (SW) device (sparker array [SPA]) can effectively fracture artificial stones in vitro and in vivo, and if SPA treatment produces a renal lesion in our pig model of lithotripsy injury. Results of these experiments will be used to help evaluate the suitability of this device as a clinical lithotripter., Materials and Methods: Ultracal-30 artificial stones were placed in a holder at the focus of the SPA and treated with 600 SWs (21.6 kV, 60 shocks/min). Stone fragments were collected, dried, and weighed to determine stone breakage. In vivo stone breakage entailed implanting stones into pigs. These stones were treated with 600 or 1200 SWs and the fragments were collected for analysis. Lesion analysis consisted of treating the left kidney of pigs with 1200 or 2400 SWs and quantitating the hemorrhagic lesion., Results: In vitro, 71% ± 2% of each artificial stone was fractured to <2 mm in size. In vivo stone breakage averaged 63%. Renal injury analysis revealed that only 1 of 7 kidneys showed evidence of hemorrhagic injury in the treated area., Conclusion: The SPA consistently comminuted artificial stones demonstrating its ability to fracture stones like other lithotripters. Also, the SPA caused little to no renal injury at the settings used in this study. These findings suggest further research is warranted to determine the potential of this device as a clinical lithotripter., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this paper, an extracorporeal shock wave source composed of small ellipsoidal sparker units is described. The sparker units were arranged in an array designed to produce a coherent shock wave of sufficient strength to fracture kidney stones. The objective of this paper was to measure the acoustical output of this array of 18 individual sparker units and compare this array to commercial lithotripters. Representative waveforms acquired with a fiber-optic probe hydrophone at the geometric focus of the sparker array indicated that the sparker array produces a shock wave (P + ∼40-47 MPa, P - ∼2.5-5.0 MPa) similar to shock waves produced by a Dornier HM-3 or Dornier Compact S. The sparker array's pressure field map also appeared similar to the measurements from a HM-3 and Compact S. Compared to the HM-3, the electrohydraulic technology of the sparker array produced a more consistent SW pulse (shot-to-shot positive pressure value standard deviation of ±4.7 MPa vs ±3.3 MPa).

A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ 1-42 peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occur in vivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Multiple reaction monitoring-MS analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes, including Lipid 654, an agonist for human and mouse Toll-like receptor (TLR)2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes and human serum and brain samples from healthy adults. The median Lipid 430/Lipid 654 ratio observed in carotid endarterectomy samples was significantly higher than the median ratio in lipid extracts of common oral and intestinal Bacteroidetes bacteria, and serum and brain samples from healthy subjects. More importantly, the median Lipid 430/Lipid 654 ratio was significantly elevated in carotid endarterectomies when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)

Communicating service-specific practice patterns, guidelines, and provider information to a new team of learners that rotate frequently can be challenging. Leveraging individual and healthcare electronic resources, a mobile device platform was implemented into a newly revised resident onboarding process. We hypothesized that offering an easy-to-use mobile application would improve communication across multiple disciplines as well as improve provider experiences when transitioning to a new rotation. A mobile platform was created and deployed to assist with enhancing communication within a trauma service and its resident onboarding process. The platform had resource materials such as: divisional policies, Clinical Practice Guidelines (CMGs), and onboarding manuals along with allowing for the posting of divisional events, a divisional directory that linked to direct dialing, text or email messaging, as well as on-call schedules. A mixed-methods study, including an anonymous survey, aimed at providing information on team member's impressions and usage of the mobile application was performed. Usage statistics over a 3-month period were analyzed on those providers who completed the survey. After rotation on the trauma service, trainees were asked to complete an anonymous, online survey addressing both the experience with, as well as the utility of, the mobile app. Thirty of the 37 (81%) residents and medical students completed the survey. Twenty-five (83%) trainees stated that this was their first experience rotating on the trauma service and 6 (20%) were from outside of the health system. According to those surveyed, the most useful function of the app were access to the directory (15, 50%), the divisional calendar (4, 13.3%), and the on-call schedules (3, 10%). Overall, the app was felt to be easy to use (27, 90%) and was accessed an average of 7 times per day (1-50, SD 9.67). Over half the survey respondents felt that the mobile app was helpful in completing their everyday tasks (16, 53.3%). Fifteen (50%) of the respondents stated that the app made the transition to the trauma service easier. Twenty-five (83.3%) stated it was valuable knowing about departmental events and announcements, and 17 (56.7%) felt more connected to the division. The evolution of mobile technology is rapidly becoming fundamental in medical education and training. We found that integrating a service-specific mobile application improved the learner's experience when transitioning to a new service and was a valuable onboarding instrument. Level of evidence IV., Competing Interests: Competing interests: None declared.

Little is known about the outcomes of pediatric burn patients in resource-limited and rural locations of the developing world. In March 2013, our pediatric burn unit existing in this setting established an electronic registry of all patients. The authors analyzed the registry to determine overall mortality rates and predictors of mortality, including that of underweight status and body part burned. The secure electronic database of all admissions was reviewed for age, gender, weight, burn percentage (TBSA%), body part burned, cause/place of injury, length of stay, underweight status, surgery performed, reason for discharge, and mortality. Univariable and multivariable logistic regression was used to determine the variables associated with mortality. Kaplan-Meier curves were also analyzed. A total of 211 cases (59.7% male) admitted from March 2013 to June 2014 were reviewed. The median age, %TBSA, and length of stay were 2.0 years (1.3-3.3), 8.0% (5.0-13.4), and 8.5 days (4-14). The overall mortality rate was 15/211 (7.1%). Most injuries were unintentional (93.8%) scalds (85.3%) occurring in the home (98.1%). Two factors were significantly associated with mortality in the final multivariable model: %TBSA (odds ratio = 1.31 for 1% increase in %TBSA; 95% confidence interval = 1.17-1.46) and younger age (odds ratio = 0.20; 0.07-0.63). This study characterizes mortality among patients at a pediatric burn unit serving a rural population in the developing world. The majority of pediatric burns were unintentional scalds occurring in the home. %TBSA and lower age were the strongest predictors of mortality. Burn location and underweight status were not independent predictors of mortality. Overall mortality was 7.1%. These data are applicable to improving outcomes for patients in this burn unit and similar settings of its kind.

Natural photosynthesis harnesses solar energy to convert CO2 and water to value-added chemical products for sustaining life. We present a hybrid bioinorganic approach to solar-to-chemical conversion in which sustainable electrical and/or solar input drives production of hydrogen from water splitting using biocompatible inorganic catalysts. The hydrogen is then used by living cells as a source of reducing equivalents for conversion of CO2 to the value-added chemical product methane. Using platinum or an earth-abundant substitute, α-NiS, as biocompatible hydrogen evolution reaction (HER) electrocatalysts and Methanosarcina barkeri as a biocatalyst for CO2 fixation, we demonstrate robust and efficient electrochemical CO2 to CH4 conversion at up to 86% overall Faradaic efficiency for ≥ 7 d. Introduction of indium phosphide photocathodes and titanium dioxide photoanodes affords a fully solar-driven system for methane generation from water and CO2, establishing that compatible inorganic and biological components can synergistically couple light-harvesting and catalytic functions for solar-to-chemical conversion.

A foundational skill in burn surgery is tangential excision (TE). The purpose of this study was to develop a simulation model for TE, hypothesizing that simulation could be used in surgical training. TE simulation was created using the TE knife, foam, mineral oil, and base. Subjects, surgeons, or surgeons in training, were given a pre- and post-task questionnaire about experience with TE. Subjects were divided into three TE experience groups: novice--none, intermediate--some, and expert--TE in current or past practice. The task was to excise pre-marked rectangles, generating four excisional products (EPs). Evaluators blindly assessed performance by EP analysis using a novel scoring tool and reviewed videos using a modified objective structured assessment of technical skill (OSATS) rubric. Inter-rater reliabilities and P values were obtained, comparing Novice and Intermediate with Expert scores. Forty subjects completed the study: 16 were identified as TE novices, 17 as intermediates, and seven as experts. All EPs and videos were reviewed blindly by two evaluators using the EP scoring tool and OSATS methodology, respectively. Intraclass correlation coefficients were calculated to measure inter-rater reliabilities, which were acceptable (ICC => 0.42) for OSATS, time, and EP analysis: border and texture. Statistical differences between Novice and Expert scores were found (P < .0100, P < .0200, P < .0025, and P < .0005, respectively). Statistical differences between Intermediate and Expert scores were also found (P < .0100, P < .0200, P < .0100, and P < .0025, respectively). Post-simulation survey results showed experts 86% of the time agreeing or strongly agreeing that the simulation was similar to the clinical skin and 100% felt it would be a useful for training before clinical performance. Simulation for TE was successfully created to blindly discern level of TE experience. Participants agreed that simulation could play an essential role in burn surgical training.

Direct solar-powered production of value-added chemicals from CO2 and H2O, a process that mimics natural photosynthesis, is of fundamental and practical interest. In natural photosynthesis, CO2 is first reduced to common biochemical building blocks using solar energy, which are subsequently used for the synthesis of the complex mixture of molecular products that form biomass. Here we report an artificial photosynthetic scheme that functions via a similar two-step process by developing a biocompatible light-capturing nanowire array that enables a direct interface with microbial systems. As a proof of principle, we demonstrate that a hybrid semiconductor nanowire-bacteria system can reduce CO2 at neutral pH to a wide array of chemical targets, such as fuels, polymers, and complex pharmaceutical precursors, using only solar energy input. The high-surface-area silicon nanowire array harvests light energy to provide reducing equivalents to the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production of acetic acid under aerobic conditions (21% O2) with low overpotential (η < 200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200 h). The resulting acetate (∼6 g/L) can be activated to acetyl coenzyme A (acetyl-CoA) by genetically engineered Escherichia coli and used as a building block for a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB) polymer, and three different isoprenoid natural products. As such, interfacing biocompatible solid-state nanodevices with living systems provides a starting point for developing a programmable system of chemical synthesis entirely powered by sunlight.

Thoracic injuries account for 25% of all civilian deaths. Blunt force injuries are a subset of thoracic injuries and include injuries of the tracheobronchial tree, pleural space, and lung parenchyma. Early identification of these injuries during initial assessment and resuscitation is essential to reduce associated morbidity and mortality rates. Management of airway injuries includes definitive airway control with identification and repair of tracheobronchial injuries. Management of pneumothorax and hemothorax includes pleural space drainage and control of ongoing hemorrhage, along with monitoring for complications such as empyema and chylothorax. Injuries of the lung parenchyma, such as pulmonary contusion, may require support of oxygenation and ventilation through both conventional and nonconventional mechanical ventilation strategies. General strategies to improve pulmonary function and gas exchange include balanced fluid resuscitation to targeted volume-based resuscitation end points, positioning therapy, and pain management.

Maternal infection during pregnancy increases the risk for schizophrenia in offspring. In rodent models, maternal immune activation (MIA) yields offspring with schizophrenia-like behaviors. None of these behaviors are, however, specific to schizophrenia. The presence of hallucinations is a key diagnostic symptom of schizophrenia. In mice, this symptom can be defined as brain activation in the absence of external stimuli, which can be mimicked by administration of hallucinogens. We find that, compared with controls, adult MIA offspring display an increased stereotypical behavioral response to the hallucinogen 2,5-dimethoxy-4-iodoamphetamine (DOI), an agonist for serotonin receptor 2A (5-HT2AR). This may be explained by increased levels of 5-HT2AR and downstream signaling molecules in unstimulated MIA prefrontal cortex (PFC). Using manganese-enhanced magnetic resonance imaging to identify neuronal activation elicited by DOI administration, we find that, compared with controls, MIA offspring exhibit a greater manganese (Mn(2+)) accumulation in several brain areas, including the PFC, thalamus, and striatum. The parafascicular thalamic nucleus, which plays the role in the pathogenesis of hallucinations, is activated by DOI in MIA offspring only. Additionally, compared with controls, MIA offspring demonstrate higher DOI-induced expression of early growth response protein 1, cyclooxygenase-2, and brain-derived neurotrophic factor in the PFC. Chronic treatment with the 5-HT2AR antagonist ketanserin reduces DOI-induced head twitching in MIA offspring. Thus, the MIA mouse model can be successfully used to investigate activity induced by DOI in awake, behaving mice. Moreover, manganese-enhanced magnetic resonance imaging is a useful, noninvasive method for accurately measuring this type of activity.

Background: CRPS is a painful, debilitating, and often-chronic condition characterized by various sensory, motor, and vascular disturbances. Despite many years of study, current treatments are limited by our understanding of the underlying mechanisms. Little is known on the molecular level concerning changes in gene expression supporting the nociceptive sensitization commonly observed in CRPS limbs, or how those changes might evolve over time., Results: We used a well-characterized mouse tibial fracture/cast immobilization model of CRPS to study molecular, vascular and nociceptive changes. We observed that the acute (3 weeks after fracture) and chronic (7 weeks after fracture) phases of CRPS-like changes in our model were accompanied by unique alterations in spinal gene expression corresponding to distinct canonical pathways. For the acute phase, top regulated pathways were: chemokine signaling, glycogen degradation, and cAMP-mediated signaling; while for the chronic phase, the associated pathways were: coagulation system, granzyme A signaling, and aryl hydrocarbon receptor signaling. We then focused on the role of CcL2, a chemokine that we showed to be upregulated at the mRNA and protein levels in spinal cord tissue in our model. We confirmed its association with the nociceptive sensitization displayed in this model by demonstrating that the spinal but not peripheral administration of a CCR2 antagonist (RS504393) in CRPS animals could decrease mechanical allodynia. The spinal administration of CcL2 itself resulted in mechanical allodynia in control mice., Conclusions: Our data provide a global look at the transcriptional changes in the spinal cord that accompany the acute and chronic phases of CRPS as modeled in mice. Furthermore, it follows up on one of the top-regulated genes coding for CcL2 and validates its role in regulating nociception in the fracture/cast model of CRPS.

Background: Alzheimer's disease (AD) is characterized by progressive neuronal loss and cognitive decline. Epidemiological studies suggest that the risk of AD is higher in women even when data are adjusted for age., Objective: We set out to compare changes in 9-month-old male and female mice which overexpress amyloid precursor protein (APP) with presenilin (PS1; APP/PS1 mice) and to evaluate whether any changes were coupled with deficits in spatial learning., Methods: APP/PS1 mice were assessed for their ability to learn in the Morris water maze and Aβ burden assessed by Congo Red and Aβ triple ultrasensitive assay. Neuroinflammatory changes were examined in brain tissue along with expression of Aβ-generating and Aβ-degrading enzymes., Results: A deficit in reversal phase learning in the Morris water maze was observed in female mice and was paralleled by evidence of increased accumulation of Aβ, microglial activation and expression of IL-1β. Accumulation of Aβ was coupled with an increase in expression of BACE-1 and a decrease in insulin-degrading enzyme (IDE)., Conclusion: The results indicate that the observed impairment in spatial memory in female APP/PS1 mice correlated with increased Aβ burden and the changes in Aβ may have occurred as a result of enhanced BACE-1 and decreased IDE expression., (Copyright © 2012 S. Karger AG, Basel.)

Synaptic levels of the monoamine neurotransmitters dopamine, serotonin, and norepinephrine are modulated by their respective plasma membrane transporters, albeit with a few exceptions. Monoamine transporters remove monoamines from the synaptic cleft and thus influence the degree and duration of signaling. Abnormal concentrations of these neuronal transmitters are implicated in a number of neurological and psychiatric disorders, including addiction, depression, and attention deficit/hyperactivity disorder. This work concentrates on the norepinephrine transporter (NET), using a battery of in vivo magnetic resonance imaging techniques and histological correlates to probe the effects of genetic deletion of the norepinephrine transporter on brain metabolism, anatomy and functional connectivity. MRS recorded in the striatum of NET knockout mice indicated a lower concentration of NAA that correlates with histological observations of subtle dysmorphisms in the striatum and internal capsule. As with DAT and SERT knockout mice, we detected minimal structural alterations in NET knockout mice by tensor-based morphometric analysis. In contrast, longitudinal imaging after stereotaxic prefrontal cortical injection of manganese, an established neuronal circuitry tracer, revealed that the reward circuit in the NET knockout mouse is biased toward anterior portions of the brain. This is similar to previous results observed for the dopamine transporter (DAT) knockout mouse, but dissimilar from work with serotonin transporter (SERT) knockout mice where Mn(2+) tracings extended to more posterior structures than in wildtype animals. These observations correlate with behavioral studies indicating that SERT knockout mice display anxiety-like phenotypes, while NET knockouts and to a lesser extent DAT knockout mice display antidepressant-like phenotypic features. Thus, the mainly anterior activity detected with manganese-enhanced MRI in the DAT and NET knockout mice is likely indicative of more robust connectivity in the frontal portion of the reward circuit of the DAT and NET knockout mice compared to the SERT knockout mice.

Background: To examine the effect of office-based duplex-guided balloon-assisted maturation (DG-BAM) on arteriovenous fistula (AVF), we retrospectively analyzed our experience., Methods: Over the past 10 months, we performed 185 DG-BAMs (range, 1-8 procedures; mean, 3.7) in 45 patients (29 male, 16 female; mean age, 68.2 ± 12.8 years) with 31 radial-cephalic, 7 brachial-cephalic, and 7 brachial-basilic AVFs. Balloon sizes (3-10 mm) were chosen based on duplex measurements (1-2 mm larger than minimal vein diameter). Forearm AVFs were dilated to 8 mm, and arm AVFs were dilated to 10 mm., Results: All cases but one (99.5%) were successfully dilated. This exception was a large AVF rupture that required surgical repair. AVFs failed to mature in seven of the remaining 44 patients (16%) despite DG-BAM because of proximal vein stenoses (PVS). Four patients had cephalic arch stenoses, and three had proximal subclavian vein stenoses. Arm AVFs were more commonly associated with PVS (6 of 14 patients, 43%) as compared with the ones placed in the forearm (1 of 30 patients, 3.3%), with a P value of 0.0024. All these seven AVFs subsequently matured after successful balloon angioplasty of the venous outflow., Conclusions: These data suggest that office-based DG-BAM of AVFs is feasible, safe, and averts nephrotoxic contrast and radiation. PVS appear to be the most common cause of failure for AVFs subjected to BAM. Because arm AVFs are at increased risk of PVS, we suggest that a careful duplex evaluation of the outflow be performed in these cases and in all AVFs that fail to mature., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Porcine bladder extracellular matrix (PBEM) is an innovative wound healing alternative to traditional wound closure and reconstruction. By stimulating blood vessel formation and chemotaxis of progenitor cells to the site of injury, it promotes a unique healing environment favouring regeneration of native tissue over scar formation. This is the first clinical report describing the novel use of PBEM scaffold material to close a large defect resulting from a burn contracture release. The benefits of this method are the improved functional and cosmetic result. PBEM-moderated tissue regeneration may serve a valuable role in burn reconstruction.

Mounting evidence implicates axonal transport defects, typified by the presence of axonal varicosities with aberrant accumulations of cargo, as an early event in Alzheimer's disease (AD) pathogenesis. Work identifying amyloid precursor protein (APP) as a vesicular motor receptor for anterograde axonal transport further implicates axonal transport in AD. Manganese-enhanced MRI (MEMRI) detects axonal transport dynamics in preclinical studies. Here we pursue an understanding of the role of APP in axonal transport in the central nervous system by applying MEMRI to hippocampal circuitry and to the visual pathway in living mice homozygous for either wild type or a deletion in the APP gene (n=12 for each genotype). Following intra-ocular or stereotaxic hippocampal injection, we performed time-lapse MRI to detect Mn(2+) transport. Three dimensional whole brain datasets were compared on a voxel-wise basis using within-group pair-wise analysis. Quantification of transport to structures connected to injection sites via axonal fiber tracts was also performed. Histology confirmed consistent placement of hippocampal injections and no observable difference in glial-response to the injections. APP-/- mice had significantly reduced transport from the hippocampus to the septal nuclei and amygdala after 7h and reduced transport to the contralateral hippocampus after 25 h; axonal transport deficits in the APP-/- animals were also identified in the visual pathway. These data support a system-wide role for APP in axonal transport within the central nervous system and demonstrate the power of MEMRI for assessing neuronal circuitry involved in memory and learning., (Copyright © 2012 Elsevier Inc. All rights reserved.)

There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from AβPP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-β-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-β-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.

Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking.

Introduction: Harrison's class IV calvarial burns with greater than 75% exposure present a special problem in flame injury. This problem is compounded in small children and or those with a large total body surface area burn, thus limiting the possibility of local flaps and free tissue transfers for coverage and leaving only wound care and skin grafts as options for closure. The literature suggests trephination with a high speed drill until viable bone is reached, then autografting the subsequent granulation tissue. In the most severe cases when the calvarium is deeply thermally injured and drilling down to the level of the Dura does not yield any sign of viability; should the surgeon proceed with removal of the clearly compromised calvarium down to Dura or leave it in place?, Methods: At a pediatric burn center, we reviewed all Harrison's class IV flame burns to the head with more than 75% exposure of the calvarium for a 2.5-year period. Five cases fit our inclusion criteria., Results: All five patients had drilling of the calvarium to debride dead bone. Three of the children had drilling that reached viable bone and were treated with a combination of early grafting and allowing granulation tissue to form then grafting. Two of the patients had extreme flame burns to the head with large areas having no clinical evidence of viability down to the Dura. The photographic record and CT reconstructions of these two cases are presented. The figures show the progression of healing of the calvarium in each child. A persistent calvarial defect only in the area of complete removal of calvarium to Dura is seen in each child's record. The remaining areas demonstrate progressive wound closure with remodeling of the skull in long term follow-up., Conclusion: In deep massive calvarial burns to the head it is difficult to achieve wound closure. Trepanation with subsequent grafting and expectant management while awaiting granulation tissue bed is the current recommended treatment for this clinical problem. The aggressiveness of surgical debridement of dead bone is largely based on clinical appearance of the tissue. In the cases presented here, complete removal of clinically non-viable burned calvarium resulted in calvarial defects that were avoided when some deep calvarium was left in place despite its poor clinical appearance. The clinical challenge of closing calvarial defects in the reconstructive phase of care should not be underestimated. Therefore, avoidance of a defect if possible by allowing some bone to remain during trephination is recommended., (Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.)

Novel phosphorylated dihydroceramide (PDHC) lipids produced by the periodontal pathogen Porphyromonas gingivalis include phosphoethanolamine (PE DHC) and phosphoglycerol dihydroceramides (PG DHC) lipids. These PDHC lipids mediate cellular effects through Toll-like receptor 2 (TLR2) including promotion of IL-6 secretion from dendritic cells and inhibition of osteoblast differentiation and function in vitro and in vivo. The PE DHC lipids also enhance (TLR2)-dependent murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The unique non-mammalian structures of these lipids allows for their specific quantification in bacteria and human tissues using multiple reaction monitoring (MRM)-mass spectrometry (MS). Synthesis of these lipids by other common human bacteria and the presence of these lipids in human tissues have not yet been determined. We now report that synthesis of these lipids can be attributed to a small number of intestinal and oral organisms within the Bacteroides, Parabacteroides, Prevotella, Tannerella and Porphyromonas genera. Additionally, the PDHCs are not only present in gingival tissues, but are also present in human blood, vasculature tissues and brain. Finally, the distribution of these TLR2-activating lipids in human tissues varies with both the tissue site and disease status of the tissue suggesting a role for PDHCs in human disease.