Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells.

Developing B cells generate DNA double-stranded breaks (DSBs) to assemble immunoglobulin receptor (Ig) genes necessary for the expression of a mature B cell receptor. These physiologic DSBs are made by the RAG endonuclease, which is comprised of the RAG1 and RAG2 proteins. In pre-B cells, RAG-mediated DSBs activate the ATM kinase to coordinate canonical and non-canonical DNA damage responses (DDR) that trigger DSB repair and B cell developmental signals, respectively. Whether this broad cellular response is distinctive to RAG DSBs is poorly understood. To delineate the factors that direct DDR signaling in B cells, we express a tetracycline-inducible Cas9 nuclease in Rag1-deficient pre-B cells. Both RAG- and Cas9-mediated DSBs at Ig genes activate canonical DDR. In contrast, RAG DSBs, but not Cas9 DSBs, induce the non-canonical DDR-dependent developmental program. This unique response to RAG DSBs is, in part, regulated by non-core regions of RAG1. Thus, B cells trigger distinct cellular responses to RAG DSBs through unique properties of the RAG endonuclease that promotes activation of B cell developmental programs.

MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated. OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation. METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB generation, DSB repair, and termination of DDRs. RESULTS: Genetic testing in a newborn with abnormal screen for severe combined immune deficiency, T-cell lymphopenia, and near absence of B cells identified a novel splice variant in MYSM1 that results in nearly absent protein expression. Radiosensitivity testing in patient's peripheral blood lymphocytes showed constitutive γH2AX, a marker of DNA damage, in B cells in the absence of irradiation, suggesting a role for MYSM1 in response to DSBs generated during Ig recombination. Suppression of MYSM1 in pre-B cells did not alter generation or repair of Ig DSBs. Rather, loss of MYSM1 resulted in persistent DNA damage foci and prolonged DDR signaling. Loss of MYSM1 also led to protracted DDRs in U2OS cells with irradiation induced DSBs. CONCLUSIONS: MYSM1 regulates termination of DNA damage responses but does not function in DNA break generation and repair.

Reliability and Validity of the State-Trait Hopelessness Scale in a Primarily Rural Population of Adults With Ischemic Heart Disease in the US Great Plains.

PURPOSE: Hopelessness and rurality are each independently associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining hopelessness in rural patients with IHD. The authors of this study evaluated the reliability and validity of the State-Trait Hopelessness Scale (STHS) in a primarily rural population of adults with IHD living in West North Central United States (US Great Plains). METHODS: Reliability, concurrent validity, and convergent validity were evaluated for 115 adults hospitalized for IHD. Rural-Urban Commuting Area codes were used to stratify participants by rurality level, with 66% categorized as rural. Principal component analysis was used to examine potential factor structure of the STHS. FINDINGS: Cronbach α for the State and Trait Hopelessness subscales were 0.884 and 0.903, respectively. Concurrent validity was supported for the State and Trait subscales using the Patient Health Questionnaire-8 (State: r = 0.50, P < .001; Trait: r = 0.35, P < .001). Convergent validity was supported for the State subscale using the Duke Activity Status Index ( r = -0.23, P = .013). Principal component analysis showed 2 factors (hopelessness present and hopelessness absent) for the State and Trait subscales, accounting for 63% and 58% of variance, respectively. CONCLUSIONS: Findings support the reliability and validity of the STHS for evaluation of hopelessness in rural adults with IHD in clinical and research settings. Results replicated the same factor structure found in testing of the STHS in a primarily urban sample. Because of the prevalence of hopelessness in rural adults with IHD and association with increased mortality, hopelessness should be assessed during hospitalization and in the recovery period.

The impact of COVID-19 on incidence and outcomes from out-of-hospital cardiac arrest (OHCA) in Texas.

INTRODUCTION: Emerging research demonstrates lower rates of bystander cardiopulmonary resuscitation (BCPR), public AED (PAD), worse outcomes, and higher incidence of OHCA during the COVID-19 pandemic. We aim to characterize the incidence of OHCA during the early pandemic period and the subsequent long-term period while describing changes in OHCA outcomes and survival. METHODS: We analyzed adult OHCAs in Texas from the Cardiac Arrest Registry to Enhance Survival (CARES) during March 11-December 31 of 2019 and 2020. We stratified cases into pre-COVID-19 and COVID-19 periods. Our prehospital outcomes were bystander cardiopulmonary resuscitation (BCPR), public AED use (PAD), sustained ROSC, and prehospital termination of resuscitation (TOR). Our hospital survival outcomes were survival to hospital admission, survival to hospital discharge, good neurological outcomes (CPC Score of 1 or 2) and Utstein bystander survival. We created a mixed effects logistic regression model analyzing the association between the pandemic on outcomes, using EMS agency as the random intercept. RESULTS: There were 3619 OHCAs (45.0% of overall study population) in 2019 compared to 4418 (55.0% of overall study population) in 2020. Rates of BCPR (46.2% in 2019 to 42.2% in 2020, P < 0.01) and PAD (13.0% to 7.3%, p < 0.01) decreased. Patient survival to hospital admission decreased from 27.2% in 2019 to 21.0% in 2020 (p < 0.01) and survival to hospital discharge decreased from 10.0% in 2019 to 7.4% in 2020 (p < 0.01). OHCA patients were less likely to receive PAD (aOR = 0.5, 95% CI [0.4, 0.8]) and the odds of field termination increased (aOR = 1.5, 95% CI [1.4, 1.7]). CONCLUSIONS: Our study adds state-wide evidence to the national phenomenon of long-term increased OHCA incidence during COVID-19, worsening rates of BCPR, PAD use and survival outcomes.

Changes in Field Termination of Resuscitation and Survival Rates After an Educational Intervention to Promote on Scene Resuscitation for Out-of-Hospital Cardiac Arrest.

BACKGROUND: Emergency medical services (EMS) agencies with higher field termination-of-resuscitation (TOR) rates tend to have higher survival rates from out-of-hospital cardiac arrest (OHCA). Whether EMS agencies can improve survival rates through efforts to focus on resuscitation on scene and optimize TOR rates is unknown. OBJECTIVE: The goal of this study was to determine if an EMS agency's efforts to enhance on-scene resuscitation were associated with increased TOR and OHCA survival with favorable neurologic outcome. METHODS: A single-city, retrospective analysis of prospectively collected 2017 quality assurance data was conducted. Patient demographics, process, and outcome measures were compared before and after an educational intervention to increase field TOR. The primary outcome measure was survival to hospital discharge with favorable neurologic status. RESULTS: There were 320 cases that met inclusion criteria. No differences in age, gender, location, witnessed arrest, bystander cardiopulmonary resuscitation, initial shockable rhythm, or presumed cardiac etiology were found. After the intervention, overall TOR rate increased from 39.6% to 51.1% (p = 0.06). Among subjects transported without return of spontaneous circulation (ROSC), average time on scene increased from 26.4 to 34.2 min (p = 0.02). Rates of sustained ROSC and survival to hospital admission were similar between periods. After intervention, there was a trend toward increased survival to hospital discharge rate (relative risk [RR] 2.09; 95% confidence interval [CI] 0.74-5.91) and an increase in survival with favorable neurologic status rate (RR 5.96; 95% CI 0.80-44.47). CONCLUSION: This study described the association between an educational intervention focusing on optimization of resuscitation on scene and OHCA process and outcome measures. Field termination has the potential to serve as a surrogate marker for aggressively treating OHCA patients on scene.

Evaluation of Physiologic Alterations during Prehospital Paramedic-Performed Rapid Sequence Intubation.

OBJECTIVE: Physiologic alterations during rapid sequence intubation (RSI) have been studied in several emergency airway management settings, but few data exist to describe physiologic alterations during prehospital RSI performed by ground-based paramedics. To address this evidence gap and provide guidance for future quality improvement initiatives in our EMS system, we collected electronic monitoring data to evaluate peri-intubation vital signs changes occurring during prehospital RSI. METHODS: Electronic patient monitor data files from cases in which paramedic RSI was attempted were prospectively collected over a 15-month study period to supplement the standard EMS patient care documentation. Cases were analyzed to identify peri-intubation changes in oxygen saturation, heart rate, and blood pressure. RESULTS: Data from 134 RSI cases were available for analysis. Paramedic-assigned prehospital diagnostic impression categories included neurologic (42%), respiratory (26%), toxicologic (22%), trauma (9%), and cardiac (1%). The overall intubation success rate (95%) and first-attempt success rate (82%) did not differ across diagnostic impression categories. Peri-intubation desaturation (SpO2 decrease to below 90%) occurred in 43% of cases, and 70% of desaturation episodes occurred on first-attempt success. The incidence of desaturation varied among patient categories, with a respiratory diagnostic impression associated with more frequent, more severe, and more prolonged desaturations, as well as a higher incidence of accompanying cardiovascular instability. Bradycardia (HR decrease to below 60 bpm) occurred in 13% of cases, and 60% of bradycardia episodes occurred on first-attempt success. Hypotension (systolic blood pressure decrease to below 90 mmHg) occurred in 7% of cases, and 63% of hypotension episodes occurred on first-attempt success. Peri-intubation cardiac arrest occurred in 2 cases, one of which was on first-attempt success. Only 11% of desaturations and no instances of bradycardia were reflected in the standard EMS patient care documentation. CONCLUSIONS: In this study, the majority of peri-intubation physiologic alterations occurred on first-attempt success, highlighting that first-attempt success is an incomplete and potentially deceptive measure of intubation quality. Supplementing the standard patient care documentation with electronic monitoring data can identify unrecognized physiologic instability during prehospital RSI and provide valuable guidance for quality improvement interventions.

Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival.

Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing demonstrated that multiple SI stem cell populations, marked by Lgr5, Bmi1, or HopX expression, contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double-strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy.

Survivors Perceptions of Recovery following Air Medical Transport Accidents.

Abstract Objective: Air medical transport (AMT) teams play an essential role in the care of the critically ill and injured. Their work, however, is not without risk. Since the inception of the industry numerous AMT accidents have been reported. The objective of this research is to gain a better understanding of the post-accident sequelae for professionals who have survived AMT accidents. The hope is that this understanding will empower the industry to better support survivors and plan for the contingencies of post-accident recovery. Methods: Qualitative methods were used to explore the experience of flight crew members who have survived an AMT accident. "Accident" was defined using criteria established by the National Transportation Safety Board. Traditional focus group methodology explored the survivors' experiences following the accident. Results: Seven survivors participated in the focus group. Content analysis revealed themes in four major domains that described the experience of survivors: Physical, Psychological, Relational and Financial. Across the themes survivors reported that industry and company response varied greatly, ranging from generous support, understanding and action to make safety improvements, to little response or action and lack of attention to survivor needs. Conclusion: Planning for AMT post-accident response was identified to be lacking in scope and quality. More focused efforts are needed to assist and support the survivors as they regain both their personal and professional lives following the accident. This planning should include all stakeholders in safe transport; the individual crewmember, air medical transport companies, and the industry at large.

Forkhead box O1 (FOXO1) protein, but not p53, contributes to robust induction of p21 expression in fasted mice.

Reporter mice that enable the activity of the endogenous p21 promoter to be dynamically monitored in real time in vivo and under a variety of experimental conditions revealed ubiquitous p21 expression in mouse organs including the brain. Low light bioluminescence microscopy was employed to localize p21 expression to specific regions of the brain. Interestingly, p21 expression was observed in the paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus, regions that detect nutrient levels in the blood stream and signal metabolic actions throughout the body. These results suggested a link between p21 expression and metabolic regulation. We found that short-term food deprivation (fasting) potently induced p21 expression in tissues involved in metabolic regulation including liver, pancreas and hypothalamic nuclei. Conditional reporter mice were generated that enabled hepatocyte-specific expression of p21 to be monitored in vivo. Bioluminescence imaging demonstrated that fasting induced a 7-fold increase in p21 expression in livers of reporter mice and Western blotting demonstrated an increase in protein levels as well. The ability of fasting to induce p21 expression was found to be independent of p53 but dependent on FOXO1. Finally, occupancy of the endogenous p21 promoter by FOXO1 was observed in the livers of fasted but not fed mice. Thus, fasting promotes loading of FOXO1 onto the p21 promoter to induce p21 expression in hepatocytes.

An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.

This report describes the development of an evidence-based guideline for external hemorrhage control in the prehospital setting. This project included a systematic review of the literature regarding the use of tourniquets and hemostatic agents for management of life-threatening extremity and junctional hemorrhage. Using the GRADE methodology to define the key clinical questions, an expert panel then reviewed the results of the literature review, established the quality of the evidence and made recommendations for EMS care. A clinical care guideline is proposed for adoption by EMS systems. Key words: tourniquet; hemostatic agents; external hemorrhage.

Orientation of New Graduate Registered Nurses Postpandemic: A Follow-up Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has increased the rate of nurses leaving practice, which has highlighted the importance of new graduate nurse orientation. The literature has limited recommendations for orientation strategies. METHOD: The goal of this study was to determine what changes have occurred in orientation processes for new graduate nurses since the COVID-19 pandemic. A survey of nurse leaders was used to examine changes and opportunities. RESULTS: Leaders are more intentional with orientation processes, including frequent check-ins and increased discussion of time management, difficult conversations, and workplace violence. Individualized orientation plans are used, along with a stronger focus on nurse wellness. CONCLUSION: Recommendations include continuing support after orientation is completed and partnering with academia to provide content on stress management and wellness. Innovative and cost-effective transition to practice programs are needed to meet the needs of new nurses. [J Contin Educ Nurs. 2024;55(7):345-350.].

FEA-Based Stress-Strain Barometers as Forecasters for Corneal Refractive Power Change in Orthokeratology.

PURPOSE: To improve the effectivity of patient-specific finite element analysis (FEA) to predict refractive power change (RPC) in rigid Ortho-K contact lens fitting. Novel eyelid boundary detection is introduced to the FEA model to better model the effects of the lid on lens performance, and stress and strain outcomes are investigated to identify the most effective FEA components to use in modelling. METHODS: The current study utilises fully anonymised records of 249 eyes, 132 right eyes, and 117 left eyes from subjects aged 14.1 ± 4.0 years on average (range 9 to 38 years), which were selected for secondary analysis processing. A set of custom-built MATLAB codes was built to automate the process from reading Medmont E300 height and distance files to processing and displaying FEA stress and strain outcomes. Measurements from before and after contact lens wear were handled to obtain the corneal surface change in shape and power. Tangential refractive power maps were constructed from which changes in refractive power pre- and post-Ortho-K wear were determined as the refractive power change (RPC). A total of 249 patient-specific FEA with innovative eyelid boundary detection and 3D construction analyses were automatically built and run for every anterior eye and lens combination while the lens was located in its clinically detected position. Maps of four stress components: contact pressure, Mises stress, pressure, and maximum principal stress were created in addition to maximum principal logarithmic strain maps. Stress and strain components were compared to the clinical RPC maps using the two-dimensional (2D) normalised cross-correlation and structural similarity (SSIM) index measure. RESULTS: On the one hand, the maximum principal logarithmic strain recorded the highest moderate 2D cross-correlation area of 8.6 ± 10.3%, and contact pressure recorded the lowest area of 6.6 ± 9%. Mises stress recorded the second highest moderate 2D cross-correlation area with 8.3 ± 10.4%. On the other hand, when the SSIM index was used to compare the areas that were most similar to the clinical RPC, maximum principal stress was the most similar, with an average strong similarity percentage area of 26.5 ± 3.3%, and contact pressure was the least strong similarity area of 10.3 ± 7.3%. Regarding the moderate similarity areas, all components were recorded at around 34.4% similarity area except the contact pressure, which was down to 32.7 ± 5.8%. CONCLUSIONS: FEA is an increasingly effective tool in being able to predict the refractive outcome of Ortho-K treatment. Its accuracy depends on identifying which clinical and modelling metrics contribute to the most accurate prediction of RPC with minimal ocular complications. In terms of clinical metrics, age, Intra-ocular pressure (IOP), central corneal thickness (CCT), surface topography, lens decentration and the 3D eyelid effect are all important for effective modelling. In terms of FEA components, maximum principal stress was found to be the best FEA barometer that can be used to predict the performance of Ortho-K lenses. In contrast, contact pressure provided the worst stress performance. In terms of strain, the maximum principal logarithmic strain was an effective strain barometer.

Investigation of How Corneal Densitometry Artefacts Affect the Imaging of Normal and Keratoconic Corneas.

PURPOSE: To investigate corneal densitometry artefacts found in Pentacam Scheimpflug scans and their potential effect on assessing keratoconic (KC) corneas compared to normal (N) corneas. METHODS: The current study utilises Pentacam data of 458 N eyes, aged 35.6 ± 15.8 (range 10-87), referred to as the "N group", and 314 KC eyes, aged 31.6 ± 10.8 (range 10-72), referred to as the "KC group", where densitometry data were extracted and analysed via a custom-built MATLAB code. Radial summations of the densitometry were calculated at diameters ranging from 0.5 mm to 5.0 mm. The minimum normalised radial summation of densitometry (NRSD) value and angle were determined at each diameter and then linked. KC cone locations and areas of pathology were determined, and a comparison between N and KC groups was carried out both within the averaged area of pathology and over the corneal surface. RESULTS: Joining minimum NRSD trajectory points marked a clear distortion line pointing to the nasal-superior direction at 65° from the nasal meridian. The findings were found to be independent of eye laterality or ocular condition. Consistency was detected in the right and left eyes among both the N and KC groups. The location of the KC cone centre and the area of pathology were determined, and the densitometry output was compared both within the area of pathology and over the whole cornea. When the average densitometry was compared between N and KC eyes within the KC area of pathology, the N group recorded a 16.37 ± 3.15 normalised grey-scale unit (NGSU), and the KC group recorded 17.74 ± 3.4 NGSU (p = 0.0001). However, when the whole cornea was considered, the N group recorded 16.71 ± 5.5 NGSU, and the KC group recorded 15.72 ± 3.98 NGSU (p = 0.0467). A weak correlation was found between the Bad D index and NGSU when the whole measured cornea was considered (R = -0.01); however, a better correlation was recorded within the KC area of pathology (R = 0.21). CONCLUSIONS: Nasal-superior artefacts are observed in the densitometry Pentacam maps, and analysis shows no significant differences in their appearance between N or KC corneas. When analysing KC corneas, it was found that the cone positions are mostly on the temporal-inferior side of the cornea, opposite to the densitometry artefact NRSD trajectory. The analysis suggests that the corneal densitometry artefacts do not interfere with the KC area of pathology as it reaches its extreme in the opposite direction; therefore, weighting the densitometry map to increase the contribution of the inferior-temporal cornea and decreasing that of the superior-nasal area would improve the classification or identification of KC if densitometry is to be used as a KC metric.

A blueprint for critical care transport research.

INTRODUCTION: An estimated 500,000 critical care patient transports occur annually in the United States. Little research exists to inform optimal practices, promote safety, or encourage responsible, cost-effective use of this resource. Previous efforts to develop a research agenda have not yielded significant progress in producing much-needed scientific study. PURPOSE: Identify and characterize areas of research needed to direct the development of evidence-based guidelines METHODS: The study used a modified Delphi technique to develop a concept map of the research domains in critical care transport. Proprietary, internet-based software was used for both data collection and analysis. The study was conducted in 3 phases: brainstorming, categorizing, and prioritizing, using experts from all aspects of critical care transport. RESULTS: A total of 101 research questions were developed and ranked by 27 participants representing the transport community and stakeholders. An 8-cluster solution was developed with multidimensional scaling and hierarchical cluster analysis to identify the following research areas: clinical care, education/training, finance, human factors, patient outcomes, safety, team configuration, and utilization. A plot characterized each domain by urgency and feasibility. CONCLUSION: The content and concepts represented by the cluster map can help direct research planning in the critical care transport industry and prioritize funding decisions.

Assessing satisfaction and quality in the EMS/HEMS working relationship.

BACKGROUND/OBJECTIVE: Treatment provided to critically ill and injured patients during air medical transport bridges initial local emergency medical service (EMS) treatment and the care provided upon arrival to the emergency department. Transition of care from EMS to air medical service includes multiple elements, many of which have been previously undefined. These include operational details surrounding the handoff and attention to issues of continuity in patient care. The purpose of this study is to pilot the development of survey instrumentation to measure key elements of quality in the interaction between EMS and air medical crews. METHODS: A focus group of 12 individuals, including rural and urban EMS providers, medical directors, administrators, and air medical transport providers, defined the activities involved in the working relationship between EMS and air medical transport. Ideas were refined into statements and placed into a 16-item Likert scale questionnaire distributed to EMS agencies throughout Ohio. Exploratory factor analysis was performed to identify subscales within the questionnaire. RESULTS: 380 questionnaires were returned over 2009, 2010, and 2011. Factor analysis of the initial responses from 2009 revealed themes similar to those identified by the focus group: patient care, user-friendly helicopter EMS (HEMS) operations, response time accuracy, operational feedback, and general system issues. The measure had good internal reliability, with alphas for subscales in the 0.85-0.88 range. A modified questionnaire used in 2010 and 2011 actually performed as a single scale. CONCLUSION: Using qualitative and quantitative approaches, a survey instrument was developed to assess satisfaction with HEMS care from the EMS provider's perspective. Evaluating the EMS perspective on the working relationship with HEMS is a new field of discovery for the air medical transport industry and process improvement activities.

Prehospital factors associated with mortality in injured air medical patients.

BACKGROUND: Air medical transport provides rapid transport to definitive care. Overtriage and the expense and risk of transport may offset survival benefits. OBJECTIVE: We assessed the ability of prehospital factors to predict resource need for helicopter-transported patients. METHODS: We performed a prospective, observational cohort analysis of injured scene patients taken to one of two level I trauma centers from October 2009 to September 2010. Variables analyzed included patient demographics, diagnoses, and clinical outcomes (in-hospital mortality, emergent surgery within 24 hours, blood transfusion within 24 hours, and intensive care unit [ICU] admission ≥24 hours, as well as a combined outcome of all clinical outcomes). Prehospital variables were prospectively obtained from air medical providers at the time of transport and included past medical history, mechanism of injury, and clinical factors. We compared those variables with and without the outcomes of interest via χ(2) analysis and the Kruskal-Wallis test, where appropriate. Multivariate logistic regression identified factors associated with outcomes of interest with the intent of developing a clinical prediction tool. RESULTS: Five hundred fifty-seven patients were transported during the study period. The majority of the patients were male (67%) and white (95%) and had an injury that occurred in a rural location (58%). Most injuries were blunt (97%), and patients had a median Injury Severity Score (ISS) of 9. The overall mortality was 4%; 48% of the patients had one of the four outcomes. The most common reasons for requesting air transport were motor vehicle collision (MVC) with high-risk mechanism (18%), MVC at a speed greater than 20 mph (18%), Glasgow Coma Scale score (GCS) less than 14 (15%), and loss of consciousness (LOC) greater than 5 minutes (15%). Factors associated with mortality were age greater than 44 years, GCS less than 14, systolic blood pressure (SBP) less than 90 mmHg, and flail chest. This model had 100% sensitivity and 50% specificity and missed no deaths. The combined endpoint of all four outcomes (death, receipt of blood, surgery, ICU admission) included intubation by emergency medical services, two or more fractures of the humerus/femur, presence of a neurovascular injury, a crush injury to the head, failure to localize to pain on examination, GCS less than 14, or the presence of a penetrating head injury. This model had a sensitivity of 57% (53%-61%) and a specificity of 78% (75%-87%). CONCLUSIONS: Very few prehospital criteria were associated with clinically important outcomes in helicopter-transported patients. Evidence-based guidelines for the most appropriate utilization of air medical transport need to be further evaluated and developed for injured patients.

Response of small intestinal epithelial cells to acute disruption of cell division through CDC25 deletion.

The CDC25 protein phosphatases (CDC25A, B, and C) drive cell cycle transitions by activating key components of the cell cycle engine. CDC25A and CDC25B are frequently overproduced in human cancers. Disruption of Cdc25B or Cdc25C individually or in combination has no effect on mouse viability. Here we report that CDC25A is the only family member to provide an essential function during early embryonic development, and that other family members compensate for its loss in adult mice. In contrast, conditional disruption of the entire family is lethal in adults due to a loss of small intestinal epithelial cell proliferation in crypts of Lieberkühn. Cdc25 loss induced Wnt signaling, and overall crypt structures were preserved. In the face of continuous Wnt signaling, nearly all crypt epithelial progenitors differentiated into multiple cell lineages, including crypt base columnar cells, a proposed stem cell. A small population of Musashi/Dcamkl-1/nuclear beta-catenin-positive epithelial cells was retained in these crypts. These findings have implications for the development of novel, less cytotoxic cancer chemotherapeutic drugs that specifically target the cell cycle.

A primer for achieving glycemic control in the cardiac surgical patient.

Maintaining glycemic control (blood glucose <180 mg/dL) has been shown to reduce morbidity and enhance long-term survival in patients with diabetes mellitus following coronary artery bypass graft (CABG) surgery. In this review we present a management strategy to achieve perioperative glycemic control in all patients undergoing CABG surgery, with and without diabetes mellitus, designed to achieve compliance with current Surgical Care Improvement Project (SCIP) and Society of Thoracic Surgeons (STS) guidelines.

Assessing DNA Damage Responses Using B Lymphocyte Cultures.

Development of B cells requires the programmed generation and repair of double-stranded DNA breaks in antigen receptor genes. Investigation of the cellular responses to these DNA breaks has established important insights into B cell development and, more broadly, has provided fundamental advances into the molecular mechanisms of DNA damage response pathways. Abelson transformed pre-B cell lines and primary pre-B cell cultures are malleable experimental systems with diverse applications for studying DNA damage responses. This chapter describes methods for generating these cellular systems, inducing and quantifying DSBs, and assessing DNA damage programs.

The lived experience of nurses transitioning to professional practice during the COVID-19 pandemic.

As a result of the COVID-19 pandemic, newly graduating nurses have entered into rapidly changing clinical environments, experiencing healthcare in a manner for which they were not fully prepared. The purpose of this study is to describe the lived experience of these newly graduated registered nurses (RNs) who transitioned to practice during the COVID-19 pandemic, and to gain understanding of how to better prepare future graduates for similar situations. A multisite qualitative phenomenological design was used in this study of 12 frontline nurses that graduated in the spring of 2020 and transitioned into their new role as RNs. A trained research team conducted semistructured interviews and completed a thematic analysis of the data. The results were six themes that emerged from the study participants' interviews: (1) fear, (2) emotional conflict, (3) self-doubt, (4) alone, (5) communication barriers, and (6) finding the positive.