bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing PHYTOENE SYNTHASE activity fine-tunes the abundance of a cis-carotene-derived signal that regulates the PIF3/HY5 module and plastid biogenesis
Authors: Hou Xin , Alagoz Yagiz , Welsch Ralf , Mortimer Matthew D , Pogson Barry J , Cazzonelli Christopher I
Published: November 2023

PHYTOENE SYNTHASE (PSY) is a rate-limiting enzyme catalysing the first committed step of carotenoid biosynthesis, and changes in PSY gene expression and/or protein activity alter carotenoid composition and plastid differentiation in plants. Four genetic variants of PSY (psy-4, psy-90, psy-130, and psy-145) were identified using a forward genetics approach that rescued leaf virescence phenotypes and plastid abnormalities displayed by the Arabidopsis CAROTENOID ISOMERASE (CRTISO) mutant ccr2 (carotenoid and chloroplast regulation 2) when grown under a shorter photoperiod. The four non-lethal mutations affected alternative splicing, enzyme–substrate interactions, and PSY:ORANGE multi-enzyme complex binding, constituting the dynamic post-transcriptional fine-tuning of PSY levels and activity without changing localization to the stroma and protothylakoid membranes. psy genetic variants did not alter total xanthophyll or β-carotene accumulation in ccr2, yet they reduced specific acyclic linear cis-carotenes linked to the biosynthesis of a currently unidentified apocarotenoid signal regulating plastid biogenesis, chlorophyll biosynthesis, and photomorphogenic regulation. ccr2 psy variants modulated the PHYTOCHROME-INTERACTING FACTOR 3/ELONGATED HYPOCOTYL 5 (PIF3/HY5) ratio, and displayed a normal prolamellar body formation in etioplasts and chlorophyll accumulation during seedling photomorphogenesis. Thus, suppressing PSY activity and impairing PSY:ORANGE protein interactions revealed how cis-carotene abundance can be fine-tuned through holoenzyme–metabolon interactions to control plastid development.
Imaging Threading Dislocations and Surface Steps in Nitride Thin Films Using Electron Backscatter Diffraction
Authors: Hiller Kieran P , Winkelmann Aimo , Hourahine Ben , Starosta Bohdan , Alasmari Aeshah , Feng Peng , Wang Tao , Parbrook Peter J , Zubialevich Vitaly Z , Hagedorn Sylvia , Walde Sebastian , Weyers Markus , Coulon Pierre-Marie , Shields Philip A , Bruckbauer Jochen , Trager-Cowan Carol
Published: November 2023

Extended defects, like threading dislocations, are detrimental to the performance of optoelectronic devices. In the scanning electron microscope, dislocations are traditionally imaged using diodes to monitor changes in backscattered electron intensity as the electron beam is scanned over the sample, with the sample positioned so the electron beam is at, or close to the Bragg angle for a crystal plane/planes. Here, we use a pixelated detector instead of single diodes, specifically an electron backscatter diffraction (EBSD) detector. We present postprocessing techniques to extract images of dislocations and surface steps, for a nitride thin film, from measurements of backscattered electron intensities and intensity distributions in unprocessed EBSD patterns. In virtual diode (VD) imaging, the backscattered electron intensity is monitored for a selected segment of the unprocessed EBSD patterns. In center of mass (COM) imaging, the position of the center of the backscattered electron intensity distribution is monitored. Additionally, both methods can be combined (VDCOM). Using both VD and VDCOM, images of only threading dislocations, or dislocations and surface steps can be produced, with VDCOM images exhibiting better signal-to-noise. The applicability of VDCOM imaging is demonstrated across a range of nitride semiconductor thin films, with varying surface step and dislocation densities.
Antibacterial Efficacy of a Chitosan-Based Hydrogel Modified With Epsilon-Poly-l-Lysine Against Pseudomonas aeruginosa in a Murine-Infected Burn Wound Model
Authors: Moon Andrea Y , Bailey Emily J , Polanco Jonilee A , Kurata Wendy E , Pierce Lisa M
Published: November 2023

Introduction

Because antibiotic resistance is increasing worldwide and the leading cause of death in burn patients is an infection, an urgent need exists for nonantibiotic approaches to eliminate multidrug-resistant bacteria from burns to prevent their systemic dissemination and sepsis. We previously demonstrated the significant antibiofilm activity of a chitosan (CS) hydrogel containing the antimicrobial peptide epsilon-poly-l-lysine (EPL) against multidrug-resistant Pseudomonas aeruginosa using ex vivo porcine skin. In this study, we evaluated the in vivo antibacterial efficacy of a CS/EPL hydrogel against P. aeruginosa in a murine burn wound infection model.

Materials and Methods

Full-thickness burns were created on the dorsum using a heated brass rod and were inoculated with bioluminescent, biofilm-forming P. aeruginosa (Xen41). Mice were treated with CS/EPL, CS, or no hydrogel applied topically 2 or 24 hours after inoculation to assess the ability to prevent or eradicate existing biofilms, respectively. Dressing changes occurred daily for 3 days, and in vivo bioluminescence imaging was performed to detect and quantitate bacterial growth. Blood samples were cultured to determine systemic infection. In vitro antibacterial activity and cytotoxicity against human primary dermal fibroblasts, keratinocytes, and mesenchymal stem cells were also assessed.

Results

CS/EPL treatment initiated at early or delayed time points showed a significant reduction in bioluminescence imaging signal compared to CS on days 2 and 3 of treatment. Mice administered CS/EPL had fewer bloodstream infections, lower weight loss, and greater activity than the untreated and CS groups. CS/EPL reduced bacterial burden by two orders of magnitude in vitro and exhibited low cytotoxicity against human cells.

Conclusion

A topical hydrogel delivering the antimicrobial peptide EPL demonstrates in vivo efficacy to reduce but not eradicate established P. aeruginosa biofilms in infected burn wounds. This biocompatible hydrogel shows promise as an antimicrobial barrier dressing for the sustained protection of burn wounds from external bacterial contamination.
Early Enteral Nutrition in Aeromedically Evacuated Critically Ill/Injured Patients With a Resultant Validation Algorithm for the Theater Validating Flight Surgeon
Authors: Butler William P , Woody Sarah K , Huffman Sarah L , Harding Charles J , Brown Kayla N , Smith Danny E , Noe Todd C , Gholson Andre D
Published: November 2023

Introduction

Early enteral feeding in critically ill/injured patients promotes gut integrity and immunocompetence and reduces infections and intensive care unit/hospital stays. Aeromedical evacuation (AE) often takes place concurrently. As a result, AE and early enteral feeding should be inseparable.

Materials and Methods

This retrospective descriptive study employed AE enteral nutrition (EN) data (2007–2019) collected from patients who were U.S. citizens and mechanically ventilated. The dataset was created from the En Route Critical Care, Transportation Command Regulating and Command and Control Evacuation System, and Theater Medical Data Store databases. Comparisons were performed between patients extracted and patients not extracted, patients treated with EN and patients treated without EN, and within the EN group, between AE Fed and AE Withheld. The impact of the nutrition support in the Joint Trauma System Clinical Practice Guidelines (CPG) was assessed using the ‘before’ and ‘after’ methodology.

Results

An uptick in feeding rates was found after the 2010 CPG, 15% → 17%. With the next two CPG iterations, rates rose significantly, 17% → 48%. Concurrently, AE feeding holds rose significantly, 10% → 24%, later dropping to 17%. In addition, little difference was found between those patients not enterally fed preflight and those enterally fed across collected demographic, mission, and clinical parameters. Likewise, no difference was found between those enterally fed during AE and those withheld. Yet, 83% of the study’s patients were not fed, and 18% of those that were fed had feeding withheld for AE.

Conclusions

It appeared that the Clinical Practice Guidelines (CPGs) reinforced the value of feeding, but may well have sensitized to the threat of aspiration. It also appeared that early enteral feeding was underprescribed and AE feeding withholds were overprescribed. Consequently, an algorithm was devised for the Theater Validating Flight Surgeon, bearing in mind relevant preflight/inflight/clinical issues, with prescriptions designed to boost feeding, diminish AE withholding, and minimize complications.
Exposomic Signatures of Cervical Pain
Authors: Maldonado Carlos J , White-Phillip Jessica A , Liu Yuliang , Choi Y Sammy
Published: November 2023

Introduction

We evaluated risk factors associated with cervical pain (CP) among officers and enlisted members of the U.S. Army and Marine Aviation community using an exposomic approach. Specifically, we aimed to determine the factors associated with reported CP.

Materials and Methods

This is a retrospective cohort study that utilized the Medical Assessment and Readiness System housed at Womack Army Medical Center to evaluate the longitudinal data taken from medical and workforce resources. This study included 77,864 active duty AMAC members during October 2015-December 2019. Multivariable mixed-effects logistic regression was used to assess the relationship between the independent variables of rank, service time, deployment, Armed Forces Qualification Test score, tobacco use, alcohol use, age, gender, race, ethnicity, body mass index, marital status, and education level and the dependent variable, incidence occurrence of CP.

Results

The total analysis included 77,864 individuals with 218,180 person-years of observations. The incidence rate of CP was 18.8 per 100 person-years, with a 12% period prevalence. Cervical pain was independently associated with rank, service time, Armed Forces Qualification Test score, and alcohol use (all P < .05).

Conclusions

Our longitudinal exposomic signatures–based approach aims to complement the outcomes of data science and analytics from Medical Assessment and Readiness System with validations of objective biochemical indicator species observed in Army and Marine Aviation community members suffering from CP. This initial approach using parallel track complementarity has the potential of substantiating the underlying mechanisms foundational to design prospective personalized algorithms that can be used as a predictive model. Finally, a specific evaluation of occupational risk factors may provide insight into factors not readily ascertained from the civilian literature.
Improving Pre-exposure Prophylaxis Counseling at a Military Women’s Health Care Clinic to Champion CDC and Defense Health Agency Recommendations
Authors: Boedeker David , Zerpa Ethan , Drayer Sara M
Published: November 2023

Introduction

The CDC updated their guidelines in 2021 to recommend all doctors speak about pre-exposure prophylaxis (PrEP) against human immunodeficiency virus infection with all sexually active patients. In addition, there is a demonstrated need for physicians to counsel patients on PrEP to achieve military readiness. Results from the 2018 Health Related Behaviors Survey indicate 21.8% of U.S. service members were at high risk for human immunodeficiency virus. This improvement project aimed to assess deficiencies in providers’ knowledge before and after an educational intervention and describe policies clinics can adopt to adhere to CDC recommendations.

Materials and Methods

A pre-intervention survey was distributed to providers at the Walter Reed National Military Medical Center Gynecologic Surgery and Obstetrics clinic. Based on results, an educational lecture and standardized intake form were developed. Following the intervention, a post-survey was distributed to providers. A chart review was performed to determine whether PrEP counseling increased following the intervention.

Results

Forty-seven gynecologic providers were sent a pre- and post-intervention survey. Thirty-seven individuals completed the pre-intervention survey (response rate 78.72%), whereas 18 people completed the post-intervention survey (response rate 38.30%). Descriptive analysis suggested comfort counseling on PrEP, comfort with Defense Health Agency guidance on PrEP, and knowledge of PrEP all increased. In terms of the chart review, 81 charts were reviewed pre- and post-intervention. Although we failed to meet our target counseling rate of 70%, the number of patients who were counseled on or prescribed PrEP following our intervention was statistically significant (P = .013).

Conclusions

This improvement project increased provider knowledge and comfort with PrEP, but only marginally affected behavior changes among providers. This failure may be related to the specific clinic in which the study was implemented. Further research is needed to facilitate routine counseling of PrEP among military women’s health care providers.
Provider Perceptions of Oxygenation Strategies for Critically Ill Trauma Patients With and Without Moderate-to-Severe Traumatic Brain Injury
Authors: Dylla Layne , Douin David J , Cwik Jessica E , Steinwand Aimee , Rice John D , Jackson Conner L , Anderson Erin L , Higgins Hannah M , Monte Andrew A , Ginde Adit A
Published: November 2023

Background

Hypoxia and hyperoxia (pulse oximetry [SpO2] > 96%) are associated with increased mortality in critically ill patients. However, provider practices regarding oxygenation in traumatic brain injury (TBI) patients are unknown. This study assesses views on oxygenation of critically ill trauma patients with and without TBI and how this varies between Neurological ICU (NeuroICU) and Surgical-Trauma ICU (STICU) providers.

Methods

This is a cross-sectional survey of Level I trauma center’s NeuroICU and STICU providers. We used Likert scales, yes–no questions, and multiple-choice case-based scenarios to characterize provider views on oxygenation with descriptive statistics to characterize responses. Significant differences regarding TBI and non-TBI patients or NeuroICU and STICU providers were determined using Fisher’s exact test and a P-value of .05.

Results

A total of 83 providers initiated the survey, and 53 providers completed it. Most providers identified a threshold SpO2 < 92% for the administration of supplemental oxygen in critically ill TBI patients. A total of 9% of providers “somewhat or completely agreed” that they were more likely to give supplemental oxygen to a critically ill trauma patient with TBI than one without TBI and the same SpO2. A total of 48% of providers selected an SpO2 < 90% as the point at which supplemental oxygen should be initiated in patients without TBI, compared to 27% of providers in patients with TBI (P < .01). This threshold for supplemental oxygen use varied by provider type for non-TBI patients, but not for TBI patients (30% NeuroICU and 69% STICU providers selected SpO2 < 90% in non-TBI, P < .05; 30% NeuroICU and 35% STICU providers selected SpO2 < 90% in TBI, P = .85).

Conclusions

Critical care providers at UCHealth University of Colorado Hospital approach the oxygenation of critically ill trauma patients with and without TBI differently. Specifically, critical care respondents accepted a different lower oxygen saturation threshold for TBI and non-TBI patients. NeuroICU and STICU respondents differed in their threshold for the down-titration of supplemental oxygen. Targeted education for critical care providers may reduce these discrepancies and optimize oxygen use.
Association of Prehospital Neck Wound Survivability and Battlefield Medical Evacuation Time in Afghanistan
Authors: Paulson Matthew W , Rossetto Marika , McKay Jerome T , Bebarta Vikhyat S , Flarity Kathleen , Keenan Sean , Schauer Steven G
Published: November 2023

Introduction

The U.S. Military’s Golden Hour policy led to improved warfighter survivability during the Global War on Terror. The policy’s success is well-documented, but a categorical evaluation and stratification of medical evacuation (MEDEVAC) times based on combat injury is lacking.

Methods

We queried the Department of Defense Joint Trauma System Prehospital Trauma Registry for casualties with documented penetrating neck trauma in Afghanistan requiring battlefield MEDEVAC from June 15, 2009, through February 1, 2021. Casualties were excluded if the time from the point of injury to reach higher level medical care was not documented, listed as zero, or exceeded 4 hours. They were also excluded if demographic data were incomplete or deemed unreliable or if their injuries occurred outside of Afghanistan.

We designed a logistic regression model to test for associations in survivability, adjusting for composite injury severity score, patient age group, and type of next higher level of care reached. We then used our model to interpolate MEDEVAC times associated with 0.1%, 1%, and 10% increased risk of death for an incapacitated casualty with penetrating neck trauma.

Results

Of 1,147 encounters, 444 casualties met inclusion criteria. Of these casualties, 430 (96.9%) survived to discharge. Interpolative analysis of our multivariable logistic regression model showed that MEDEVAC times ≥8 minutes, ≥53 minutes, and ≥196 minutes are associated with a 0.1%, 1%, and 10% increased risk of mortality from baseline, respectively.

Conclusions

Our data characterize the maximum MEDEVAC times associated with 0.1%, 1%, and 10% increased risk of death from baseline survivability for penetrating battlefield neck trauma in Afghanistan.
The Impact of Lifetime Traumatic Brain Injury (TBI) on Mental Health Symptoms among Service Members in Interdisciplinary TBI Programs
Authors: Remigio-Baker Rosemay A , Bailie Jason M , Ettenhofer Mark L , Cordero Evelyn , Hungerford Lars D
Published: November 2023

Introduction

Traumatic brain injury (TBI) is highly prevalent among active duty service members (ADSMs) and imposes a significant health burden, particularly on mental health (e.g., post-traumatic stress disorder [PTSD] and depressive symptoms). Little is known about how TBI setting characteristics impact PTSD and depressive symptom expression in service members undergoing interdisciplinary TBI care.

Materials and Methods

The study included 455 patients enrolled in interdisciplinary, outpatient TBI programs within the military health system. Using Poisson regression with robust error variance, TBI injury setting characteristics (i.e., before military service, during military training, and during noncombat/combat deployment) were evaluated against clinically-elevated PTSD (PTSD Checklist, DSM-5 score ≥ 33) and depressive (Patient Health Questionnaire-8 score ≥ 15) symptoms.

Results

In adjusted models, TBI sustained before military service was associated with less likelihood for clinically-elevated PTSD symptoms at pretreatment (prevalence ratio [PR] = 0.76, confidence interval [CI] = 0.60-0.96) and post-treatment (PR = 0.67, CI = 0.52-0.87). TBI sustained during combat deployment, however, resulted in the greatest impact on clinically-elevated pretreatment PTSD (PR = 1.49, CI = 1.16-1.91) and depressive (PR = 1.47, CI = 1.06-2.03) symptoms. Null results were found between military training/noncombat deployment and mental health symptoms. Regardless of the TBI setting, following TBI treatment, there remained 37.5% (n = 180) and 24.8% (n = 108) with clinically-elevated PTSD and depressive symptoms, respectively.

Conclusions

There was a differential impact of TBI settings, particularly between TBI sustained before military service and that from combat deployment among ADSMs enrolled in outpatient TBI programs. This may be indicative of differences in the characteristics of these environments (e.g., injury severity) or the impact of such an event during recovery from current TBIs. The large percentage of ADSMs who present with clinically-elevated mental health symptoms after treatment may suggest the need for additional resources to address mental health needs before, during, and after treatment in TBI programs.
Efficacy of Medical Device Alarm Integration into a Simulated H-60 Integrated Communication System
Authors: Kroening Laura R , Kinsler Rachel E , Molles Jeffrey J , Lloyd Amy L
Published: November 2023

Introduction

This study sought to examine the efficacy of integrating medical device alarms into the intercommunication set of a simulated HH-60, allowing medics to hear the alarms over the ambient noise of the aeromedical environment.

Materials and Methods

U.S. Army critical care flight paramedics were recruited as subjects for this study. Subjects participated in two testing scenarios: One with patient monitor alarms integrated into their communication lines and one without integrated alarms (the control condition). Testing took place in a simulated HH-60 interior with two priority-level patients per testing scenario, one on either side of the interior. Subjects provided care to these two patients for 30 minutes per scenario. After both scenarios were complete, the subjects were given a questionnaire to obtain their feedback on alarm integration.

Results

Six subjects took part in this study, so the results do not have sufficient power to represent the population. No statistically significant results were found. Looking at the trends in the data, implementing alarm integration showed the indications of reducing reaction time to alarms, decreasing or matching the amount of time spent with the patient monitor, and equivalent amounts of time dedicated to patient treatment when compared to the nonintegrated scenario.

The feedback obtained from the subjects provided a list of perceived benefits, drawbacks, and improvements related to the integration of medical device alarms into the intercommunication set.

Conclusions

Although the study was underpowered, the trends in the data indicate a benefit to the medics when integrating medical device alarms. When coupled with strongly favorable end-user feedback, the results provide justification for pursuing the effort of integrating alarms and performing future studies with improved integration systems to optimize the potential of the system.
Effectiveness of Negative Pressure Wound Therapy During Aeromedical Evacuation Following Soft Tissue Injury and Infection
Authors: Baucom Matthew R , Wallen Taylor E , Youngs Jaclyn , Singer Kathleen E , Delman Aaron M , Schuster Rebecca M , Blakeman Thomas C , Strilka Richard , Pritts Timothy A , Goodman Michael D
Published: November 2023

Introduction

Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied. We hypothesized that instillation NPWT during simulated AE would decrease bacterial colonization within simple and complex soft tissue wounds.

Methods

The porcine models were anesthetized before any experiments. For the simple tissue wound model, two 4-cm dorsal wounds were created in 34.9 ± 0.6 kg pigs and were inoculated with Acinetobacter baumannii (AB) or Staphylococcus aureus 24 hours before a 4-hour simulated AE or ground control. During AE, animals were randomized to one of the five groups: wet-to-dry (WTD) dressing, NPWT, instillation NPWT with normal saline (NS-NPWT), instillation NPWT with Normosol-R® (NM-NPWT), and RX-4-NPWT with the RX-4 system. For the complex musculoskeletal wound, hind-limb wounds in the skin, subcutaneous tissue, peroneus tertius muscle, and tibia were created and inoculated with AB 24 hours before simulated AE with WTD or RX-4-NPWT dressings. Blood samples were collected at baseline, pre-flight, and 72 hours post-flight for inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor alpha. Wound biopsies were obtained at 24 hours and 72 hours post-flight, and the bacteria were quantified. Vital signs were measured continuously during simulated AE and at each wound reassessment.

Results

No significant differences in hemodynamics or serum cytokines were noted between ground or simulated flight groups or over time in either wound model. Simulated AE alone did not affect bacterial proliferation compared to ground controls. The simple tissue wound arm demonstrated a significant decrease in Staphylococcus aureus and AB colony-forming units at 72 hours after simulated AE using RX-4-NPWT. NS-NPWT during AE more effectively prevented bacterial proliferation than the WTD dressing. There was no difference in colony-forming units among the various treatment groups at the ground level.

Conclusion

The hypoxic, hypobaric environment of AE did not independently affect the bacterial growth after simple tissue wound or complex musculoskeletal wound. RX-4-NPWT provided the most effective bacterial reduction following simulated AE, followed by NS-NPWT. Future research will be necessary to determine ideal instillation fluids, negative pressure settings, and dressing change frequency before and during AE.
Factors Associated With Chronic Pain Intensity in U.S. Army Soldiers
Authors: Ee Juliana S , Dogbey Godwin Y , Fitzpatrick John K , Agnello Robert N , Skelly Stephanie K , Chang Min Ho , Frost Landon S
Published: November 2023

Introduction

Chronic pain is prevalent among U.S. military personnel and veterans. The effectiveness of evidence-based pain treatments can be boosted with knowledge of factors associated with chronic pain perception. This study examined the factors that influence soldiers’ self-rating of their chronic pain intensity.

Materials and Methods

The study design was a retrospective review of the intake questionnaire from 203 soldiers seen at an Interdisciplinary Pain Management Center. The intake covered various aspects of soldiers’ chronic pain experience, including pain intensity, interference in functioning, emotional sequelae, and pain-related catastrophic thinking. Pain intensity and impact were measured using the Defense and Veterans Pain Rating Scale. The mood was measured using the depression (Patient Health Questionnaire [PHQ]-9) and the anxiety (Generalized Anxiety Disorder-7) scales from the PHQ. Pain-related catastrophic thinking was measured using the Pain Catastrophizing Scale (PCS). Pain interference was assessed using a five-item scale that inquired about concentration, life and recreation enjoyment, task performance, and socializing. Data were analyzed using descriptive statistics and linear regression analyses.

Results

The mean duration of pain was 34.73 ± 38.66 months. Regression analysis using scores from the PHQ-9, Generalized Anxiety Disorder-7, three PCS subscales (rumination, magnification, and helplessness), and pain interference scale as predictors showed that pain interference and PCS helplessness factors were significant predictors of average pain rating (R2 = 24%, P < .001).

Conclusions

Pain interference in functioning and pain-related thoughts of helplessness accounted for a significant degree of the variance in soldiers’ self-rating of their chronic pain. The findings suggest that added attention should be directed at helping patients boost their self-efficacy in using pain-coping methods to improve their functioning and address the perception of helplessness about their pain.
Continued Development and Testing of a Novel Steerable Chest Tube, Extendable Infusion Cannula, and Portable Suction–Infusion Pump for Use in Austere and Transport Environments to Prevent Retained Hemothorax
Authors: Fortune John B , Tiller Kimberley
Published: November 2023

With blunt and penetrating trauma to the chest, warfighters frequently suffer from hemothorax. Optimal management requires the placement of a chest tube to evacuate the blood. Malposition of the tube may be a causative factor of inadequate drainage (retained hemothorax). As a potential solution, we developed a previously reported steerable chest tube allowing accurate placement into a desired location to enhance effectiveness. To provide assisted aspiration, we developed a portable, battery-operated suction device capable of simultaneous or sequential infusion. This report details the ongoing progress of this project. Updated steerable tube and pump prototypes were designed and produced. The tubes were tested for feasibility in two pigs and one cadaver by fluoroscopically comparing tip positions after insertion by a number of providers. Measured drainage volumes comparing standard vs. steerable tubes after pleural infusion of 1,000 mL of saline in two pigs were compared. Testing of the pump focused on the accuracy of suction and volume functions. The steerable tube prototype consists of sequentially bonded segments of differing flexibility and an ergonomic tensioning handle. The portable suction pump accurately provides up to 80 cmH2O of suction, an infusion capability of up to 10 mL/min, and a 950 mL removable reservoir canister. After minimal training, providers easily and repeatedly placed the tip of the steerable tube in the lateral diaphragmatic sulcus in animals and cadavers. Arc was limited to the distal segment. Compared to a standard tube, the steerable tube placed along the diaphragm improved pleural fluid drainage volumes by 17%, although this did not reach statistical significance in six trials. These new prototypes represent substantial improvements and were performed according to expectations. We believe that this steerable chest tube and portable suction–infusion pump can be effectively used for warfighters with chest injuries in austere environments.
Association of Chronic Pain With Alcohol Consumption and Tobacco Use in Active Duty Soldiers
Authors: Skelly Stephanie K , Ee Juliana S , Dogbey Godwin Y , Agnello Robert N
Published: November 2023

Introduction

Chronic pain and lifestyle habits, namely alcohol consumption and tobacco use, impact soldier readiness. This study examines the relationship between chronic pain and these lifestyle habits in soldiers seen at the Interdisciplinary Pain Management Center (IPMC).

Materials and Methods

This cross-sectional retrospective review utilized data from active duty soldiers receiving treatment at the IPMC. Soldiers (N = 203, 85% men) treated at the IPMC completed an intake questionnaire that included the Defense and Veterans Pain Rating Scale, the Alcohol Use Disorders Identification Test-Concise, and inquiries about tobacco use. Tobacco use was quantified as the amount and frequency of cigarettes smoked. Other tobacco products were converted to an equivalent number of cigarettes. Data were analyzed using descriptive statistics, Pearson’s correlation, and independent samples t-test analyses.

Results

The mean duration of pain reported was 34.73 ± 38.66 months (median = 24.00). Soldiers engaging in hazardous drinking reported significantly higher interference with sleep (mean = 6.53 versus 5.40, P = .03) and greater negative effect on mood (mean = 6.33 versus 5.30, P = .04) compared to the no hazardous drinking group. Nonsignificant differences were found between tobacco users and non-tobacco users regarding pain intensity and pain effect on activity, sleep, mood, and stress (all P > .05). Among tobacco users, a significant negative correlation was found between a daily number of cigarettes used and sleep interference (r = −0.29, P = .024) as well as effect on mood (r = −0.33, P = .010). Years of tobacco use showed a significant negative correlation with the average pain intensity (r = −0.32, P = .025).

Conclusions

The results suggest that addressing alcohol consumption is an essential part of chronic pain treatment. The finding of a negative association between years of nicotine use and pain intensity suggests that nicotine use may have served as a coping mechanism. Further research is needed.
Chronic Pain and Childhood Adversity Experiences Among U.S. Military Personnel
Authors: Ee Juliana S , Culp Phillip A , Bevis Zachary J , Dogbey Godwin Y , Agnello Robert N , Chang Min Ho
Published: November 2023

Introduction

Chronic pain in a military population is prevalent, is costly, and can limit daily activities and affect soldier readiness. It has been associated with childhood adversity (CA) within the veteran, adult, and pediatric populations. Given the need to maximize soldier resiliency, an examination of the link between CA and chronic pain in an active duty population for a better understanding that informs treatment options is warranted.

Materials and Methods

The analytic sample comprised 32 men and 8 women drawn from a retrospective review of 203 intake assessments at an interdisciplinary pain management center. We identified a group (CA) of 20 patients who reported a history of pre-adolescent sexual abuse or living in an “abusive” childhood home and compared it with a control group (no-CA) of 20 patients, matched for age, gender, pain history duration, and pain problem. Validated measures were used to assess pain intensity, interference in functioning and well-being, emotional sequelae of pain as reflected in symptoms of depression and anxiety, and pain-related catastrophic thinking. Data were analyzed using descriptive statistics and independent samples t-test analyses.

Results

Differences in current, worst, and average pain ratings were non-significant between groups. The CA group reported significantly greater effect of pain on mood (mean: 6.20 versus 4.25, P < .02) and showed a trend toward higher pain interference in functioning (mean: 17.70 versus 15.05, P = .053). The CA patients had significantly more serious depression (mean: 12.65 versus 4.50, P < .001) and anxiety symptoms (mean: 10.60 versus 2.35, P < .001) and significantly higher pain catastrophizing tendency (mean: 30.05 versus 20.50, P < .03).

Conclusions

Overall, the findings suggest that childhood trauma should be considered by providers when treating depression and anxiety in soldiers with chronic pain. Being mindful of trauma-informed care may have implications, perhaps, for cases perceived as treatment resistant.
Neuropathological Examination of Mice Chronically Exposed to Secondhand Smoke
Authors: Lopes Leilani A , Davenport Conor , Ramos Torres Estefania , Chlebowski Anna , Mikami Anna , Raber Jacob , Ruth Torres Eileen , Kisby Glen
Published: November 2023

Introduction

Around 21.6–35% of military personnel are smokers, while 12.26% of them have been regularly exposed to second-hand smoke (SHS). Second-hand smoke is considered an important risk factor for neurological diseases because it can induce oxidative stress, DNA damage, and disrupt DNA repair pathways.

Material and Methods

The brain of air (sham) or SHS exposed mice was cryoperserved, sectioned, and placed on a glass slide before immunoprobing them with antibodies to observe for oxidative DNA damage (8-oxoG), oxidative DNA repair (8-oxoguanine DNA glycosylase 1, Ogg1; apurinic/apyrimidinic endonuclease, Ape1), and inflammatory (glial fibrillary acidic protein) proteins.

Results

Nissl staining of the prefrontal cortex (PFCTX) revealed the presence of dark, shrunken cells, hippocampal thinning, and the presence of activated astrocytes in SHS exposed mice. 8-oxoG staining was also more prominent in the PFCTX and hippocampus (HIPP) of SHS exposed mice. Ogg1 staining was reduced in the PFCTX and CA3 hippocampal neurons of SHS exposed mice, whereas it was more prominent in CA1 and CA4 hippocampal neurons. In contrast, Ape1 staining was more prominent in the PFCTX and the HIPP of SHS exposed mice.

Conclusions

These studies demonstrate that oxidative DNA damage (8-oxoG) was elevated and oxidative DNA repair (Ape1 and Ogg1) was altered in the brain of SHS exposed mice. In addition, activated astrocytes (i.e., glial fibrillary acidic protein) were also observed in the brain of SHS exposed mice. Therefore, SHS induces both oxidative DNA damage and repair as well as inflammation as possible underlying mechanism(s) of the cognitive decline and metabolic changes that were observed in chronically exposed mice. A better understanding of how chronic exposure to SHS induces cognitive dysfunction among military personnel could help improve the combat readiness of U.S. soldiers as well as reduce the financial burden on the DOD and veterans’ families.
Does Cuff Design Impact Insertion and Removal Force of Tracheostomy Tubes? A Bench Model
Authors: Borg Ulf , Bolger Emmet , Morris Sean
Published: November 2023

Introduction

Percutaneous dilatational tracheostomy is a commonly performed procedure in intensive care units. Unrecognized tracheal ring fracture has been suggested as a possible factor for tracheal stenosis. The degree of tracheal compression relates to the amount of force required to cannulate the trachea. The objective of this study was to determine the force required to insert two types of tracheostomy tubes with different cuff designs.

Materials and Methods

This bench model measured the insertion and removal force of two tracheostomy tubes; one with a barrel-shaped, high-volume, low-pressure cuff (traditional Shiley tracheostomy tube) and another with a taper-shaped, low-volume, low-pressure cuff (Shiley flexible tracheostomy tube). Three sizes of tracheostomy tubes either with a barrel- or taper-shaped cuff were tested (Jackson sizes 4, 6, and 10, corresponding to 6.5-, 7.5-, and 10-mm ISO sizes, respectively). A model representing the tissue that the tube traverses to enter the tracheal lumen was designed, and the tracheostomy tube was mounted on a universal testing machine to measure the force necessary to insert and remove the tube.

Results

Across all tracheostomy tubes’ sizes tested, significantly less force was required to insert the Shiley flexible tracheostomy tube compared to the traditional Shiley tracheostomy tube. Significantly less force was also required to remove the flexible tracheostomy tube compared to the traditional tracheostomy tube.

Conclusions

This model suggests that less force is required to insert the Shiley flexible tracheostomy tube, which could result in less tracheal compression. This may be because of the smaller taper-shaped cuff that, when deflated, occupies less volume compared to the barrel-shaped cuff. As a result, less tracheal injury may occur when using the Shiley flexible tracheostomy tube during percutaneous tracheostomy procedures.
Autonomous Multi-modality Burn Wound Characterization using Artificial Intelligence
Authors: Jacobson Maxwell J , Masry Mohamed El , Arrubla Daniela Chanci , Tricas Maria Romeo , Gnyawali Surya C , Zhang Xinwei , Gordillo Gayle , Xue Yexiang , Sen Chandan K , Wachs Juan
Published: November 2023

Introduction

Between 5% and 20% of all combat-related casualties are attributed to burn wounds. A decrease in the mortality rate of burns by about 36% can be achieved with early treatment, but this is contingent upon accurate characterization of the burn. Precise burn injury classification is recognized as a crucial aspect of the medical artificial intelligence (AI) field. An autonomous AI system designed to analyze multiple characteristics of burns using modalities including ultrasound and RGB images is described.

Materials and Methods

A two-part dataset is created for the training and validation of the AI: in vivo B-mode ultrasound scans collected from porcine subjects (10,085 frames), and RGB images manually collected from web sources (338 images). The framework in use leverages an explanation system to corroborate and integrate burn expert’s knowledge, suggesting new features and ensuring the validity of the model. Through the utilization of this framework, it is discovered that B-mode ultrasound classifiers can be enhanced by supplying textural features. More specifically, it is confirmed that statistical texture features extracted from ultrasound frames can increase the accuracy of the burn depth classifier.

Results

The system, with all included features selected using explainable AI, is capable of classifying burn depth with accuracy and F1 average above 80%. Additionally, the segmentation module has been found capable of segmenting with a mean global accuracy greater than 84%, and a mean intersection-over-union score over 0.74.

Conclusions

This work demonstrates the feasibility of accurate and automated burn characterization for AI and indicates that these systems can be improved with additional features when a human expert is combined with explainable AI. This is demonstrated on real data (human for segmentation and porcine for depth classification) and establishes the groundwork for further deep-learning thrusts in the area of burn analysis.
Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model
Authors: da Silva Jacqueline Teixeira , Dantas de Sousa Paulo Henrique , Costa Adelaide Fernandes , de Menezes Liliana Borges , Alves Suzana Ferreira , Pellegrini Flavio , Amaral Andre Correa
Published: November 2023

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.
Ethyl caffeate combined with fluconazole exhibits efficacy against azole-resistant oropharyngeal candidiasis via the EFGR/JNK/c-JUN signaling pathway
Authors: Wang Tianming , Pan Min , Bao Mengyuan , Bu Qingru , Yang Ruotong , Yang Yue , Shao Jing , Wang Changzhong , Li Ning
Published: November 2023

Ethyl caffeate (EC) is a phenylpropanoid compound derived from Elephantopus scaber. In our previous work, EC was investigated to have a strong synergistic antifungal effect against azole-resistant strains of Candida albicans when combined with fluconazole (FLU). However, the protective effect and mechanism of EC + FLU on oropharyngeal candidiasis (OPC) caused by drug-resistant strains of C. albicans have not been investigated. This study aimed to investigate the protective effect and mechanism of EC combined with FLU against C. albicans-resistant strains that lead to OPC. An OPC mouse model revealed that EC + FLU treatment reduced fungal load and massive hyphal invasion of tongue tissues, and ameliorated the integrity of the tongue mucosa. Periodic acid-Schiff staining results showed more structural integrity of the tongue tissues and reduced inflammatory cell infiltration after EC + FLU treatment. Phosphorylation of EGFR (epidermal growth factor receptor) and other proteins in the EFGR/JNK (c-Jun N-terminal kinase)/c-JUN (transcription factor Jun) signaling pathway was significantly downregulated by EC + FLU. EGFR and S100A9 mRNA expression were also reduced. The above results were verified in FaDu cells. ELISA results showed that the concentration of inflammatory factors in the cell supernatant was significantly reduced after EC combined with FLU treatment. Molecular docking revealed that EC exhibited high binding energy to EGFR. In conclusion, EC enhances the susceptibility of azole-resistant C. albicans to FLU, and the underlying mechanism is related to the inhibition of the EGFR/JNK/c-JUN signaling pathway. This result suggests that EC has potential to be developed as an antifungal sensitizer to treat OPC caused by azole-resistant C. albicans.
Can the low-redshift Lyman alpha forest constrain AGN feedback models?
Authors: Khaire Vikram , Hu Teng , Hennawi Joseph F , Walther Michael , Davies Frederick
Published: November 2023

We investigate the potential of low-redshift Lyman alpha (Lyα) forest for constraining active galactic nuclei (AGNs) feedback models by analysing the Illustris and IllustrisTNG simulation at z = 0.1. These simulations are ideal for studying the impact of AGN feedback on the intergalactic medium (IGM) as they share initial conditions with significant differences in the feedback prescriptions. Both simulations reveal that the IGM is significantly impacted by AGN feedback. Specifically, feedback is stronger in Illustris and results in reducing cool baryon fraction to 23 per cent relative to 39 per cent in IllustrisTNG. However, when comparing various statistics of Lyα forest such as 2D and marginalized distributions of Doppler widths and H i column density, line density, and flux power spectrum with real data, we find that most of these statistics are largely insensitive to the differences in feedback models. This lack of sensitivity arises because of the fundamental degeneracy between the fraction of cool baryons and the H i photoionization rate (ΓHI) as their product determines the optical depth of the Lyα forest. Since the ΓHI cannot be precisely predicted from first principles, it needs to be treated as a nuisance parameter adjusted to match the observed Lyα line density. After adjusting ΓHI, the distinctions in the considered statistics essentially fade away. Only the Lyα flux power spectrum at small spatial scales exhibits potentially observable differences, although this may be specific to the relatively extreme feedback model employed in Illustris. Without independent constraints on either ΓHI or cool baryon fraction, constraining AGN feedback with low-redshift Lyα forest will be very challenging.
Machine learning-based photometric classification of galaxies, quasars, emission-line galaxies, and stars
Authors: Zeraatgari Fatemeh Zahra , Hafezianzadeh Fatemeh , Zhang Yanxia , Mei Liquan , Ayubinia Ashraf , Mosallanezhad Amin , Zhang Jingyi
Published: November 2023

This paper explores the application of machine learning methods for classifying astronomical sources using photometric data, including normal and emission line galaxies (ELGs; starforming, starburst, AGN, broad-line), quasars, and stars. We utilized samples from Sloan Digital Sky Survey (SDSS) Data Release 17 (DR17) and the ALLWISE catalogue, which contain spectroscopically labelled sources from SDSS. Our methodology comprises two parts. First, we conducted experiments, including three-class, four-class, and seven-class classifications, employing the Random Forest (RF) algorithm. This phase aimed to achieve optimal performance with balanced data sets. In the second part, we trained various machine learning methods, such as k-nearest neighbours (KNN), RF, XGBoost (XGB), voting, and artificial neural network (ANN), using all available data based on promising results from the first phase. Our results highlight the effectiveness of combining optical and infrared features, yielding the best performance across all classifiers. Specifically, in the three-class experiment, RF and XGB algorithms achieved identical average F1 scores of 98.93 per cent on both balanced and unbalanced data sets. In the seven-class experiment, our average F1 score was 73.57 per cent. Using the XGB method in the four-class experiment, we achieved F1 scores of 87.9 per cent for normal galaxies (NGs), 81.5 per cent for ELGs, 99.1 per cent for stars, and 98.5 per cent for quasars (QSOs). Unlike classical methods based on time-consuming spectroscopy, our experiments demonstrate the feasibility of using automated algorithms on carefully classified photometric data. With more data and ample training samples, detailed photometric classification becomes possible, aiding in the selection of follow-up observation candidates.