bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Kidney Injury: Iterative Development of an Audit Tool for Trauma Patients
Authors: Holt Andrew , Rahm Jordan , Hopper H. Andrew , Hunt Darrell L.
Published: March 2023

BACKGROUND:

Acute kidney injury is a low-volume, high-risk complication in trauma patients and is associated with prolonged hospital length of stay and increased mortality. Yet, no audit tools exist to evaluate acute kidney injury in trauma patients.

OBJECTIVE:

This study aimed to describe the iterative development of an audit tool to evaluate acute kidney injury following trauma.

METHODS:

Our performance improvement nurses developed an audit tool to evaluate acute kidney injury in trauma patients using an iterative, multiphase process conducted from 2017 to 2021, which included a review of our Trauma Quality Improvement Program data, trauma registry data, literature review, multidisciplinary consensus approach, retrospective and concurrent review, and continuous audit and feedback for piloted and finalized versions of the tool.

RESULTS:

The final acute kidney injury audit tool can be completed within 30 min using data obtained from the electronic medical record and consists of six sections, including identification criteria, source potential causes, source treatment, acute kidney injury treatment, dialysis indications, and outcome status.

CONCLUSION:

The iterative development and testing of an acute kidney injury audit tool improved the uniform data collection, documentation, audit, and feedback of best practices to positively impact patient outcomes.
ATTAC! Development of a Novel Advanced Trauma Team Application Course
Authors: Orr Lanny , Stevens Lisa , McCotter Elizabeth , Peterson Alexa , Brant Jeannine M. , Thompson Simon J.
Published: March 2023

BACKGROUND:

Although existing trauma nurse courses provide basic education, advanced courses with simulation experiences that enhance team leadership, communication, and workflows are lacking.

OBJECTIVE:

To design and implement the Advanced Trauma Team Application Course (ATTAC) to promote advanced skills for nurses and respiratory therapists with varied experience and skill levels.

METHODS:

Trauma nurses and respiratory therapists were selected to participate based on years of experience and the novice to expert nurse model. Two nurses from each level (excluding novice) participated, ensuring a diverse cohort to promote development and mentorship. The 11-module course was presented over 12 months. A five-question survey was employed at the end of each module to self-evaluate assessment skills, communication skills, and comfort for trauma patient care. Participants rated skills and comfort on a “0–10” scale, with 0 being “not at all” to 10 being “extensively.”

RESULTS:

The pilot course was conducted from May 2019 to May 2020 at a Level II trauma center in the Northwest United States. Nurses reported ATTAC improved assessment skills, team communication, and comfort in caring for trauma patients (mean = 9.4; 95% CI [9.0, 9.8]; scale of 0–10). Participants indicated scenarios closely mimicked real-world situations; concept application commenced directly following each session.

CONCLUSION:

This novel approach to advanced trauma education promotes development of advanced skills that enable nurses to anticipate needs rather than being reactive, engage in critical thinking, and adapt to rapidly changing patient conditions.
In Vitro Investigation of the Effect of the Timing of Left Ventricular Assist Device Speed Modulation on Intraventricular Flow Patterns
Authors: Chassagne Fanette , Beckman Jennifer A. , Li Song , Mahr Claudius , Aliseda Alberto
Published: March 2023

Thromboembolic events remain a common complication for left ventricular assist device (LVAD) patients. To prevent in-pump thrombosis, third-generation LVADs use speed modulation, which is not synchronized with the native left ventricle (LV) contractility. This study aims to investigate the effect of speed modulation on intraventricular flow patterns, and specifically, the impact of timing relative to pressure variations in the LV. Stereo-particle image velocimetry measurements were performed in a patient-derived LV implanted with an LVAD, for different timings of the speed modulation and speed. Speed modulation has a strong effect on instantaneous afterload and flowrate (–16% and +20%). The different timings of the speed modulation resulted in different flowrate waveforms, exhibiting different maxima (5.3–5.9 L/min, at constant average flowrate). Moreover, the timing of the speed modulation was found to strongly influence intraventricular flow patterns, specifically, stagnation areas within the LV. These experiments highlight, once more, the complex relationship between LVAD speed, hemodynamic resistance, and intraventricular pressure. Overall, this study demonstrates the importance of considering native LV contractility in future LVAD controls, to improve hemocompatibility and reduce the risk of thromboembolic complications.
Seeking Common Ground
Authors: Maloney Kristen W.
Published: March 2023

Background

The nurse-patient relationship represents a valuable connection in cancer care. Largely studied within inpatient settings, the nature and influence of this central relationship in ambulatory settings remain relatively unexamined. The notable shift to ambulatory settings like infusion centers warrants examination of the nurse-patient relationship in this context.

Objective

The aim of this study was to develop a grounded theory of the nurse-patient relationship in ambulatory cancer infusion care.

Interventions/Methods

Using grounded theory methodology, 11 nurses were interviewed using a semistructured interview guide. Data collection continued until data saturation occurred with the primary concepts.

Results

The grounded theory, entitled Seeking Common Ground, includes 6 primary concepts. The concepts “we are all human”; “we work in a busy, complex environment”; “we seek common ground with patients”; “we use connections to support meaningful encounters”; “we find meaning in the relationships created”; and “we are governed by the push and pull of time” abstract the nurse-patient relationship from the nurses’ perspective, emphasizing fundamental human connections.

Conclusions

The grounded theory Seeking Common Ground depicts the profound connection that nurses form with their patients in the ambulatory infusion setting. Underscoring the value of the nurse-patient relationship as foundational to the nursing profession must be driven through practice, education, and policy.

Implications for Practice

Consideration of educational aspects within nursing across all levels to influence clinical practice will remain key.
The Predictive Role of Illness Perception on Lymphedema Risk-Management Behaviors in Women After Breast Cancer Surgery
Authors: Luo Xia , Zhang Lijuan , Chen Jing , Zhang Yue , Yan Jun
Published: March 2023

Background

Illness perception affects lymphedema risk-management behaviors. However, little is known about these behavioral changes within 6 months after surgery and how illness perception predicts behavioral trajectories.

Objective

The aim of this study was to explore the trajectories of lymphedema risk-management behaviors in breast cancer survivors within 6 months after surgery and the predictive role of illness perception.

Methods

Participants were recruited from a cancer hospital in China and completed a baseline survey (Revised Illness Perception Questionnaire) and follow-up assessments (Lymphedema Risk-Management Behavior Questionnaire and the physical exercise compliance dimension of the Functional Exercise Adherence Scale) at the first, third, and sixth months postoperatively.

Results

A total of 251 women were analyzed. Regarding the Lymphedema Risk-Management Behavior Questionnaire, the total scores were stable. The scores of the “lifestyle” and “skin care” dimensions showed upward trends; the scores of the “avoiding compression and injury” and “other matters needing attention” dimensions showed downward trends. For “physical exercise compliance,” scores remained stable. Furthermore, key illness perceptions (especially “personal control” and “causes”) at baseline could predict the starting levels of and changes in behavioral trajectories.

Conclusion

Different lymphedema risk-management behaviors exhibited different trajectories and could be predicted by illness perception.

Implications for Practice

Oncology nurses should focus on the early development of behaviors related to “lifestyle” and “skin care” and the later maintenance of “avoiding compression and injury” and “other matters needing attention” during follow-up, as well as help women strengthen their personal control beliefs and correctly understand the causes of lymphedema during hospitalization.
The Impact of a Culturally Meaningful Storytelling Intervention on Stigma and Attitudes About Mental Health Treatment
Authors: Conner Kyaien O. , Kosyluk Kristin , Tran Jennifer T. , Anderson Erica , Davis-Cotton Denise , Hill Angela M.
Published: March 2023

The fear of being devalued or discriminated against is a salient deterrent to seeking mental health care, especially in communities of color where racial stigma also impacts mental health and perceptions of service utilization. To address this issue, our research team partnered with This Is My Brave Inc to develop and evaluate a virtual storytelling intervention to highlight and amplify the voices of Black and Brown Americans living with mental illness and/or addiction. We utilized a pretest-posttest survey design administered electronically to viewers of the series (n = 100 Black, indigenous, people of color and n = 144 non-Hispanic White). Results indicated that postintervention, scores on public stigma and perceived discrimination measures were significantly reduced. We identified significant interaction effects, such that Black, indigenous, people of color viewers showed a greater rate of improvement on outcomes. This study provides strong preliminary evidence of the impact of a culturally meaningful virtual approach to addressing stigma and improving attitudes about mental health treatment.
Survey of the Faculty Status of Optometrists at Academic Medical Centers in the United States
Authors: Quan Steven C. , Song Sunah , Koepf Beverly , Saroufim Paola , Kaufman Evan , Day Sherry , Louie Derek , St. Clair Bryce , Stokkermans Thomas
Published: March 2023

Significance

This is the first study of the prevalence and faculty status of optometrists practicing at academic medical centers in the United States.

Purpose

To quantify the number of optometrists at academic medical centers, along with faculty rank and postdoctoral training programs.

Methods

The official websites of academic medical centers and schools of medicine in the United States were examined during the 2021-22 academic year to identify departments of ophthalmology and collect faculty profiles of employed optometrists. Institutional data was cross-referenced and analyzed by geographic distribution. Data was gathered from the Association of Schools and Colleges of Optometry and Accreditation Council on Optometry Education to identify post-graduate training programs in optometry.

Results

192 academic medical centers were identified, of which 121 (63.02%) had a residency or fellowship program in ophthalmology and/or optometry. 125 (65.10%) of these institutions had at least one staff optometrist. 718 optometrists were found at these institutions, representing 1.83% of the 39,205 practicing optometrists estimated in the United States. Of the 718 optometrists, 369 (51.39%) held an academic appointment at a medical school. The most common academic rank was Assistant Professor (184; 25.63%), followed by Instructor (138; 19.22%), Associate Professor (34; 4.74%), and Full Professor (13; 1.81%). The distribution of academic rank was similar across all regions, but varied between institutions as to whether all, some, or none of the optometric faculty were appointed by a medical school. Of 296 optometry residency programs in the United States, 21 (7.09%) were at an academic medical center. Of 15 optometric fellowship programs in the United States, 3 (20%) were at an academic medical center. Of the 192 institutions in this study, 22 (11.46%) had a post-doctoral optometric training program.

Conclusions

This study shows the distribution of academic rank and postdoctoral training programs for optometrists at academic medical centers.
Case Series: Unbiased Deep Sequencing Analysis of Acute Infectious Conjunctivitis in an Ambulatory Eye Center in Berkeley, California
Authors: Kanai Kuniyoshi , Whiteside Meredith , Wong Michael , La Tammy , Nassiri Maryam , Lee Sam , Yeung Sze Kei , Coulter Adrienne , Roufail Mareena , Ruder Kevin , Chen Cindi , Liu David , Abraham Thomas , Hinterwirth Armin , Lietman Thomas M. , Doan Thuy , Seitzman Gerami D. ,   on behalf of the Seasonal Conjunctivitis Outbreak Reporting for Prevention and Improved Outcomes (SCORPIO) Study Group
Published: March 2023

SIGNIFICANCE

Acute infectious conjunctivitis poses significant challenges to eye care providers. It can be highly transmissible, and because etiology is often presumed, correct treatment and management can be difficult. This study uses unbiased deep sequencing to identify causative pathogens of infectious conjunctivitis, potentially allowing for improved approaches to diagnosis and management.

PURPOSES

This study aimed to identify associated pathogens of acute infectious conjunctivitis in a single ambulatory eye care center.

CASE REPORTS

This study included patients who presented to the University of California Berkeley eye center with signs and symptoms suggestive of infectious conjunctivitis. From December 2021 to July 2021, samples were collected from seven subjects (ages ranging from 18 to 38). Deep sequencing identified associated pathogens in five of seven samples, including human adenovirus D, Haemophilus influenzae, Chlamydia trachomatis, and human coronavirus 229E.

CONCLUSIONS

Unbiased deep sequencing identified some unexpected pathogens in subjects with acute infectious conjunctivitis. Human adenovirus D was recovered from only one patient in this series. Although all samples were obtained during the COVID-19 pandemic, only one case of human coronavirus 229E and no SARS-CoV-2 were identified.
Tenofovir Concentration Is Not Enough in Intraocular Tissues of Patients With HIV infection
Authors: Qian Yiwen , Wang Luoziyi , Xing Yaru , Yin Lin , Jiang Jing , Suo Jinshan , Che Xin , Zhang Lijun , Wang Zhiliang
Published: March 2023

Objective:

To determine tenofovir (TFV) penetration into intraocular tissues using ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS).

Methods:

Nineteen participants taking tenofovir in combination antiretroviral therapy (cART) regimen who underwent pars plana vitrectomy (PPV) surgery were enrolled in the observational retrospective study between January 2019 and August 2021. The participants were divided into mild, moderate, and severe groups according to retinal manifestations. Basic information was recorded during PPV surgery. Paired blood plasma and vitreous humor samples (n = 19) were collected for UHPLC-MS/MS.

Results:

The median plasma and vitreous tenofovir concentrations were 106.00 ng/mL (interquartile range[IQR], 54.6–142.5) and 41.40 ng/mL (IQR 9.4–91.6), respectively. The median vitreous/plasma concentration ratio from the paired samples was 0.42 (IQR 0.16–0.84). The plasma and vitreous tenofovir concentrations were significantly correlated (r = 0.483, P = 0.036). The median vitreous tenofovir concentration was the lowest in the mild group (4.58 ng/mL). Six vitreous samples were below 50% inhibitory concentration (IC50) (11.5 ng/mL), and 2 of them were undetectable. Significant differences were noted in vitreous/plasma and vitreous tenofovir concentrations (P = 0.035 and P = 0.045, respectively) among the 3 groups but not in plasma tenofovir concentration (P = 0.577). No correlation was noted between vitreous HIV-1 RNA and vitreous tenofovir concentrations (r = 0.049, P = 0.845).

Conclusion:

Vitreous tenofovir did not reliably or consistently achieve concentrations sufficient to inhibit viral replication in intraocular tissues due to poor penetration of the blood–retinal barrier (BRB). The higher vitreous tenofovir concentrations were associated with moderate or severe disease compared with mild disease, indicating an association with the severity of BRB disruption.
Brief Report: Interruptions in HIV Prevention and Treatment During the COVID-19 Pandemic: A Cross-Sectional Study of Transgender and Gender Nonbinary Adults in the United States
Authors: Poteat Tonia C. , Wirtz Andrea L. , Adams Dee , Linton Sabriya L. , Gutierrez Carmen , Brown Carter , Miller Marissa , Rich Ashleigh J. , Williams Jennifer , Nguyen Trang Q. , Reisner Sari L.
Published: March 2023

Background:

Transgender and gender nonbinary (TNB) people have been disproportionately affected by HIV and the COVID-19 pandemic. This study explored the prevalence of HIV prevention and treatment (HPT) interruptions during the pandemic and identified factors associated with these interruptions.

Setting:

Data were drawn from LITE Connect, a US-based, nationwide, online, self-administered survey designed to examine the experiences of TNB adults during the COVID-19 pandemic. A convenience sample of 2134 participants were recruited between June 14, 2021, and May 1, 2022.

Methods:

The analytic sample was restricted to participants taking antiretroviral medications to prevent or treat HIV before the onset of the pandemic (n = 153). We calculated descriptive statistics as well as Pearson χ2 bivariate tests and multivariable models to identify factors associated with HPT interruptions during the pandemic.

Results:

Thirty-nine percent of participants experienced an HPT interruption. We found a lower odds of HPT interruptions among participants living with HIV [adjusted odds ratios (aOR) 0.45; 95% Confidence Intervals (CI): 0.22, 0.92; P = 0.02] and essential workers [aOR 0.49; 95% CI: 0.23, 1.0; P = 0.06] and higher odds among people with chronic mental health conditions [aOR 2.6; 95% CI: 1.1, 6.2; P = 0.03]. When sex and education were included, we found a lower odds of interruptions among people with higher education. CI widened, but the magnitude and direction of effects did not change for the other variables.

Conclusions:

Focused strategies to address longstanding psychosocial and structural inequities are needed to mitigate HPT treatment interruptions in TNB people and prevent similar challenges during future pandemics.
Complications Following Alloplastic Chin Augmentation
Authors: Liao Christopher D. , Rodriguez Ezequiel , Zhao Kelley , Kunda Nicholas , George Finny
Published: March 2023

Background

Alloplastic implantation has become a popular method of chin augmentation. Historically, silicone was the most commonly used implant, but porous materials have grown in favor due to improved fibrovascularization and stability. Nevertheless, it is unclear which implant type has the most favorable complication profile. This systematic review aims to compare the complications of published chin implants and surgical approaches to provide data-driven recommendations for optimizing chin augmentation outcomes.

Methods

The PubMed® database was queried on March 14, 2021. We selected studies reporting data on alloplastic chin augmentation excluding additional procedures such as osseous genioplasty, fat grafting, autologous grafting, and fillers. The following complications were extracted from each article: malposition, infection, extrusion, revision, removal, paresthesias, and asymmetry.

Results

Among the 39 articles analyzed, the year of publication ranged from 1982 to 2020; additionally, 31 were retrospective case series, 5 were retrospective cohort or comparative studies, 2 were case reports, and 1 was a prospective case series. More than 3104 patients were included. Among the 11 implants reported, the 3 implants with the highest number of publications were silicone, high-density porous polyethylene (HDPE), and expanded polytetrafluoroethylene (ePTFE). Silicone demonstrated the lowest rates of paresthesias (0.4%) compared to HDPE (20.1%, P < 0.01) and ePTFE (3.2%, P < 0.05). In contrast, there were no statistically significant differences in rates of implant malposition, infection, extrusion, revision, removal, or asymmetry when stratified by implant type. Various surgical approaches were also documented. Compared with subperiosteal implant placement, the dual-plane technique demonstrated higher rates of implant malposition (2.8% vs 0.5%, P < 0.04), revision (4.7% vs 1.0%, P < 0.001), and removal (4.7% vs 1.1%, P < 0.01), but a lower incidence of paresthesias (1.9% vs. 10.8%, P < 0.01). Compared with extraoral incisions, intraoral incisions resulted in higher rates of implant removal (1.5% vs 0.5%, P < 0.05) but lower rates of asymmetry (0.7% vs 7.5%, P < 0.01).

Conclusion

Silicone, HDPE, and ePTFE had low overall complication rates, demonstrating an acceptable safety profile regardless of implant selection. Surgical approach was found to significantly influence complications. Additional comparative studies on surgical approach while controlling for implant type would be beneficial for optimizing alloplastic chin augmentation practices.
Tracking Symptoms of Patients With Lymphedema Before and After Power-Assisted Liposuction Surgery
Authors: Bustos Valeria P. , Friedman Rosie , Pardo Jaime A. , Granoff Melisa , Fu Mei R. , Singhal Dhruv
Published: March 2023

Purpose

Lymphedema negatively impacts patients from a psychosocial standpoint and consequently affects patient's quality of life. Debulking procedures using power-assisted liposuction (PAL) are currently deemed an effective treatment for fat-dominant lymphedema and improves anthropometric measurements as well as quality of life. However, there have been no studies specifically evaluating changes in symptoms related to lymphedema after PAL. An understanding of how symptoms change after this procedure would be valuable for preoperative counseling and to guide patient expectations.

Methods

A cross-sectional study was performed in patients with extremity lymphedema who underwent PAL from January 2018 to December 2020 at a tertiary care facility. A retrospective chart review and follow-up phone survey were conducted to compare signs and symptoms related to lymphedema before and after PAL.

Results

Forty-five patients were included in this study. Of these, 27 patients (60%) underwent upper extremity PAL and 18 patients (40%) underwent lower extremity PAL. The mean follow-up time was 15.5±7.9 months. After PAL, patients with upper extremity lymphedema reported having resolved heaviness (44%), as well as improved achiness (79%) and swelling (78%). In patients with lower extremity lymphedema, they reported having improved all signs and symptoms, particularly swelling (78%), tightness (72%), and achiness (71%).

Conclusions

In patients with fat-dominant lymphedema, PAL positively impacts patient-reported outcomes in a sustained fashion over time. Continuous surveillance of postoperative studies is required to elucidate factors independently associated with the outcomes found in our study. Moreover, further studies using a mixed method approach will help us better understand patient's expectations to achieve informed decision and adequate treatment goals.
Satisfaction With Information Predicts Satisfaction With Outcome and Surgeon in Black and Hispanic Patients Undergoing Breast Reconstruction
Authors: Zong Amanda M. , Leibl Kayla E. , Weichman Katie E.
Published: March 2023

Background

Racial disparities in American healthcare contribute to worse outcomes among minority patients. Minority patients undergoing breast reconstruction are more likely to report dissatisfaction with their reconstruction process as compared with White patients, yet there is limited research exploring contributory factors. This study investigates which process-of-care, clinical, and surgical variables are most strongly correlated with Black and Hispanic patients' reported satisfaction.

Methods

A retrospective review of all patients who underwent postmastectomy breast reconstruction at a single academic center from 2015 to 2021 was performed. Patients were included for analysis if they identified as Black or Hispanic and completed preoperative, less than 1-year postoperative, and 1- to 3-year postoperative BREAST-Q surveys. At both postoperative time points, the association between satisfaction with outcome and surgeon and selected independent variables was determined using regression analysis.

Results

One hundred eighteen Black and Hispanic patients were included for analysis, with average age 49.59 ± 9.51 years and body mass index 30.11 ± 5.00 kg/m2. In the multivariate model for predicting satisfaction with outcome, only satisfaction with preoperative information (P< 0.001) was a statistically significant predictor during early and late postoperative evaluations. For predicting satisfaction with surgeon, satisfaction with information (P< 0.001) remained a significant predictor in the early and late postoperative evaluations, with lower body mass index as an additionally significant predictor during the late postoperative period.

Conclusions

Patient satisfaction with preoperative information received is the single most significant factor associated with Black and Hispanic patient satisfaction with outcome and plastic surgeon. This finding encourages further research on effective and culturally inclusive information delivery so as to both improve patient satisfaction and reduce healthcare disparities.
Plastic Surgery Roles in Wound Centers in the Northeastern United States
Authors: Lin Andrea , Lu Stephen
Published: March 2023

Introduction

Wound care is a substantial industry costing nearly $19 billion USD, and dedicated wound care centers play a critical role via a multidisciplinary team-based approach. At the same time, plastic surgeons are often considered experts in evaluation and management of wounds, particularly chronic and complex wounds. However, the extent of direct involvement of plastic surgeons in wound care centers is unclear. In this study, we sought to evaluate the presence of plastic surgeons and other specialties in wound care centers across all Northeastern states Connecticut, Delaware, District of Columbia, Maine, Maryland, Massachusetts, New Jersey, New York, New Hampshire, Pennsylvania, Rhode Island, Virginia, West Virginia, and Vermont.

Methods

A comprehensive list of wound care clinics in northeastern United States was obtained from the Healogics website. For each site, information was gathered via website listings, including number of providers and the professional certification/specialization for each provider. Providers were those with qualifications including Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Doctor of Physical Therapy (DPT), Doctor of Podiatric Medicine (DPM), Certified Registered Nurse Anesthetist (CRNA), Certified Registered Nurse Practitioner (CRNP), Physician Associate (PA), and Physical Therapist (PT).

Results

A total of 118 Healogics wound care clinics and 492 providers were located across 14 northeastern states including District of Columbia. After researching each location, updated in November 2022, plastic surgeons were only 3.7% (18 of 492) providers employed. Specialties such as internal medicine (90 of 492 [18%]), general surgery (76 of 492 [15%]), podiatry (68 of 292 [13.8% ]), and other midlevel providers such as nurse practitioners (35 of 492 [7.1%]) were more frequently employed over plastic surgery. All plastic surgeons were board certified the American Board of Plastic Surgery.

Conclusions

Wound care requires collaboration between specialties, with significant repercussions on health care costs and patient outcomes. Plastic surgery provides unique surgical services for the healing of wounds, and the natural expectation would be that plastic surgery should be heavily involved at wound care centers. However, the data do not reflect significant involvement at an official level. Further studies will investigate causes and the societal, financial, and patient impacts of this lack of direct engagement. Although many plastic surgeons may not desire the majority of their practice to be wound care management, it stands to reason that some affiliation, at least for patient awareness and referral, may be warranted.
Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma
Authors: Gabbe Belinda J. , Reeder Sandra , Ekegren Christina L. , Mather Anne , Kimmel Lara , Cameron Peter A. , Higgins Alisa M.
Published: March 2023

BACKGROUND

Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

METHODS

The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

RESULTS

Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5–17) at baseline, 10 (5–19) in the new ward phase, and 17 (9–23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

CONCLUSION

The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

LEVEL OF EVIDENCE

Economic and Value-based Evaluations; Level III.
Paeoniflorin protects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mice by inhibiting oxidative stress and neuronal apoptosis through activating the Nrf2/HO-1 signaling pathway
Authors: Zhang Jingyan , Bai Qingyang , Wen Qiuting , Han Lijun , Shi Yan , Zhang Xiaojie
Published: March 2023

Objectives

This study aimed to explore the neuroprotective effects of paeoniflorin on oxidative stress and apoptosis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mice.

Methods

The effects of paeoniflorin on motor function in mice were evaluated by behavioral test. Then substantia nigra of mice were collected and neuronal damage was assessed using Nissl staining. Positive expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry. Levels of malondialdehyde, superoxide dismutase (SOD) and glutathione were measured by biochemical method. terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect apoptosis of dopaminergic neurons. Western blotting and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1), B-cell lymphoma-2(Bcl-2), Bax and cleaved caspase-3.

Results

Paeoniflorin treatment significantly ameliorated the motor performance impairment in MPTP-induced PD mice. Moreover, it notably increased the positive expression rate of TH and reduced the damage and apoptosis of dopaminergic neurons in the substantia nigra. Furthermore, paeoniflorin increased the levels of SOD and glutathione and decreased the malondialdehyde content. It also promoted Nrf2 nuclear translocation, increased the protein and mRNA expressions of HO-1 and Bcl-2 and reduced the protein and mRNA expressions of BCL2-Associated X2 (Bax) and cleaved caspase-3. Treatment with the Nrf2 inhibitor, ML385, notably reduced the effects of paeoniflorin in MPTP-induced PD mice.

Conclusions

Neuroprotective effects of paeoniflorin in MPTP-induced PD mice may be mediated via inhibition of oxidative stress and apoptosis of dopaminergic neurons in substantia nigra through activation of the Nrf2/HO-1 signaling pathway.
Metagenome-assembled genomes of three Hepatoplasmataceae provide insights into isopod-mollicute symbiosis
Authors: Kawato Satoshi , Nozaki Reiko , Kondo Hidehiro , Hirono Ikuo
Published: March 2023

The digestive organs of terrestrial isopods harbor bacteria of the recently proposedmollicute family Hepatoplasmataceae. The only complete genome available for Hepatoplasmataceae is that of “Candidatus Hepatoplasma crinochetorum”. The scarcity of genome sequences has hampered our understanding of the symbiotic relationship between isopods and mollicutes. Here, we present four complete metagenome-assembled genomes (MAGs) of uncultured Hepatoplasmataceae members identified from shotgun sequencing data of isopods. We propose three novel species “Candidatus Tyloplasma littoralis” identified from the semiterrestrial isopod Tylos granuliferus, “Candidatus Hepatoplasma vulgare” identified from the common pill bug Armadillidium vulgare, and “Candidatus Hepatoplasma scaber” identified from the common rough woodlouse Porcellio scaber. Phylogenetic analysis of 16S ribosomal RNA sequences showed that “Candidatus Tyloplasma littoralis” and other semiterrestrial isopod-associated mollicutes form a sister clade to terrestrial Hepatoplasma members, justifying their assignment to a novel genus. Phylogenomic analysis of 151 mollicutes confirmed that Hepatoplasmataceae is a sister clade of Metamycoplasmataceae in the order Mycoplasmoidales. Our analysis also revealed that that Hepatoplasmataceae lack major metabolic pathways but has a likely intact type IIA CRISPR-Cas9 machinery, indicating that these mollicutes have an ectosymbiotic lifestyle with high nutritional dependence on their host. We did not find any evidence that Hepatoplasmataceae encode digestive enzymes that could provide nutritional benefits to the host, which suggests that they may act as defensive symbionts.
Melanotransferrin Functions as a Pro-Oncogenic WNT Agonist: A Yin-Yang Relationship in Melanoma with the WNT Antagonist and Metastasis Suppressor, NDRG1
Authors: Paluncic J. , Gholam Azad M. , Lane D.J.R , Skoda J. , Park K.C. , Chiang S. , Bae D.H. , Scolyer R. , Afroz R. , Babu G. , Wilmott J. , Loh K. , Jansson P.J. , Dharmasivam M. , Huang M.L. , Zhao X. , Kovacevic Z. , Richardson D.R.
Published: March 2023

A persistent mystery in the melanoma field has been the function of one of the first melanoma tumor antigens characterized, namely p97 (melanotransferrin; MTf). While MTf expression increases melanoma cell proliferation, migration, and tumorigenesis, the molecular mechanism responsible is unknown. On the other hand, N-myc down-stream regulated gene 1 (NDRG1) is a potent metastasis suppressor and WNT antagonist. Expression of NDRG1 in melanoma cells suggests a role in inhibiting metastasis, with this study investigating MTf’s role in oncogenic signaling. We demonstrate MTf acts as a pro-oncogenic WNT agonist, which down-regulates NDRG1, while silencingMTfincreases NDRG1 expression. In contrast, silencingNDRG1increases MTf expression. These observations demonstrate a bidirectional negative feedback loop and “Yin-Yang” relationship between MTf and NDRG1. Mechanistically, MTf was directly associated with the WNT co-receptor, lipoprotein-receptor 6 (LRP6), and increased total LRP6 expression, activated p-LRP6 (Ser1490), β-catenin, and activated β-catenin (Ser552) levels, with MTf expression inducing their nuclear accumulation. Additionally, MTf expression increased downstream WNT targets, namely cyclin D1 and c-Myc, with c-Myc down-regulating NDRG1 expression. Silencingc-Mycprevented the Yin-Yang relationship between NDRG1 and MTf, indicating c-Myc played a key role in their inverse regulation. Melanoma patient specimens demonstrated that a low NDRG1/MTf ratio was significantly (p= 0.008) associated with lower survival and metastasis. Chemotherapeutic agents that up-regulated NDRG1 depressed MTf and nuclear LRP6 and potently inhibited melanoma xenograft growthin vivo. This study demonstrates MTf acts as a WNT agonist, with a Yin-Yang relationship being observed with the WNT antagonist, NDRG1.
Zbtb46coordinates angiogenesis and immunity to control tumor outcome
Authors: Kabir Ashraf Ul , Subramanian Madhav , Wu Jun , Kim Minseo , Krchma Karen , Wang Xiaoli , Halabi Carmen M. , Pan Hua , Wickline Samuel A. , Fremont Daved H. , Choi Kyunghee
Published: March 2023

Tumor-angiogenesis and -immunity play critical roles in cancer progression and outcome. An inverse correlation of these two1hints at common regulatory mechanism(s). Here, we report thatZbtb46, a repressive transcription factor and a widely accepted marker for classical dendritic cells (DCs)2, 3, constitutes one such regulatory mechanism.Zbtb46was downregulated in both DCs and endothelial cells (ECs) by tumor-derived factors to facilitate robust tumor growth.Zbtb46downregulation led to a hallmark pro-tumor microenvironment (TME), including dysfunctional vasculature and immunosuppressive cell accumulation. Analysis of cancer patient data revealed a similar association of lowZBTB46expression with an immunosuppressive TME and a worse prognosis. In contrast, enforcedZbtb46expression mitigated the pro-tumor TME features and restricted tumor growth. Mechanistically,Zbtb46-deficient ECs were highly angiogenic, andZbtb46-deficient bone-marrow progenitors upregulatedCebpband diverted the DC program to myeloid lineage output, potentially explaining the myeloid lineage skewing phenomenon in cancer4–7. Conversely, enforcedZbtb46expression normalized tumor vessels and, by suppressingCebpb, skewed bone-marrow precursors towards more DC generation over macrophages, leading to an immune-hot TME. Remarkably,Zbtb46mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in pre-clinical models. These findings identifyZbtb46as a common regulatory mechanism for angiogenesis and for myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.
A truncated HIV Tat demonstrates potent and specific latency reversal activity
Authors: Gulck Ellen Van , Pardons Marion , Nijs Erik , Verheyen Nick , Dockx Koen , Van den Eynde Christel , Battivelli Emilie , Vega Jerel , Florence Eric , Autran Brigitte , Archin Nancie M. , Margolis David M. , Katlama Kristine , Hamimi Chiraz , Van den Wyngaert Ilse , Eyassu Filmon , Vandekerckhove Linos , Boden Daniel
Published: March 2023

A major barrier to HIV-1 cure is caused by the pool of latently infected CD4 T-cells that persist under combination antiretroviral therapy (cART). This latent reservoir is capable of producing replication-competent infectious virus once prolonged suppressive cART is withdrawn. Inducing the reactivation of HIV-1 gene expression in T-cells harboring a latent provirus in people living with HIV-1 under cART will likely result in depletion of this latent reservoir due to cytopathic effects or immune clearance. Studies have investigated molecules that reactivate HIV-1 gene expression but to date no latency reversal agent has been identified to eliminate latently infected cells harboring replication-competent HIV in cART treated individuals. Stochastic fluctuations in HIV-1tatgene expression have been described and hypothesized to allow the progression into proviral latency. We hypothesized that exposing latently infected CD4+ T-cells to Tat would result in effective latency reversal. Our results indicate the capacity of a truncated Tat protein and mRNA to reactivate HIV-1 in latently infected T-cellsex vivoto a similar degree as the protein kinase C agonist: Phorbol 12-Myristate 13-Acetate, without T-cell activation nor any significant transcriptome perturbation.
Effectiveness of a multi-country implementation-focused network on quality of care: delivery of interventions and processes for improved maternal, newborn and child health outcomes
Authors: Djellouli Nehla , Shawar Yusra Ribhi , Mwaba Kasonde , Akter Kohenour , Seruwagi Gloria , Tufa Asebe Amenu , Gonfa Geremew , Mwandira Kondwani ,   QCN Evaluation Group, Kyamulabi Agnes , Shiffman Jeremy , English Mike , Colbourn Tim
Published: March 2023

The Network for Improving Quality of Care for Maternal, Newborn and Child Health (QCN) aims to work through learning, action, leadership and accountability. We aimed to evaluate the effectiveness of QCN in these four areas at the global level and in four QCN countries: Bangladesh, Ethiopia, Malawi and Uganda.

This mixed method evaluation comprised 2-4 iterative rounds of data collection between 2019-2022, involving stakeholder interviews, hospital observations, QCN members survey, and document review. Qualitative data was analysed using a coding framework developed from underlying theories on network effectiveness, behaviour change, and QCN proposed theory of change. Survey data capturing respondents’ perception of QCN was analysed with descriptive statistics.

The QCN global level, led by the WHO secretariat, was effective in bringing together network countries’ governments and global actors via providing online and in-person platforms for communication and learning. In-country, various interventions were delivered in ‘learning districts’, however often separately by different partners in different locations, and disrupted by the pandemic. Governance structures for quality of care were set-up, some preceding QCN, and were found to be stronger and better (though often externally) resourced at national than local levels. Awareness of operational plans and network activities was lower at local than national levels but increased from 2019 to 2022. Capacity building efforts were implemented – yet often dependent on implementing partners and donors. QCN stakeholders agreed 15 core monitoring indicators though data collection was challenging, especially for indicators requiring new or parallel systems including those on experience of care. Accountability through community engagement, scorecards, and ombudsmen was encouraged but these initiatives remained nascent in 2022.

Global and national leadership elements of QCN have been most effective to date, with action, learning and accountability more challenging, partner or donor dependent, remaining to be scaled-up, and pandemic-disrupted.
Brain-wide mapping of neuronal architecture controlling torpor
Authors: Yamaguchi Hiroshi , Murphy Keith R , Fukatsu Noriaki , Sato Kazuhide , Yamanaka Akihiro , de Lecea Luis
Published: March 2023

Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature during torpor is controlled by the brain, the underlying neural circuits remain largely unknown. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We found that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of body temperature and metabolic rate during torpor and identify critical nodes of the torpor-regulatory network.
Interaction Between HCN and Slack Channels Regulates mPFC Pyramidal Cell Excitability and Working Memory
Authors: Wu Jing , El-Hassar Lynda , Datta Dibyadeep , Thomas Merrilee , Zhang Yalan , David P. Jenkins , DeLuca Nicholas J. , Chatterjee Manavi , Gribkoff Valentin K. , Arnsten Amy F.T. , Kaczmarek Leonard K.
Published: March 2023

The ability of monkeys and rats to carry out spatial working memory tasks has been shown to depend on the persistent firing of pyramidal cells in the prefrontal cortex (PFC), arising from recurrent excitatory connections on dendritic spines. These spines express hyperpolarization-activated cyclic nucleotide-gated (HCN) channels whose open state is increased by cAMP signaling, and which markedly alter PFC network connectivity and neuronal firing. In traditional neural circuits, activation of these non-selective cation channels leads to neuronal depolarization and increased firing rate. Paradoxically, cAMP activation of HCN channels in PFC pyramidal cells reduces working memory-related neuronal firing. This suggests that activation of HCN channels may hyperpolarize rather than depolarize these neurons. The current study tested the hypothesis that Na+influx through HCN channels activates Na+-activated K+(KNaor Slack) channels to hyperpolarize the membrane. We have found that HCN and Slack KNachannels co-immunoprecipitate in cortical extracts and that, by immunoelectron microscopy, they colocalize at postsynaptic spines of PFC pyramidal neurons. A specific blocker of HCN channels, ZD7288, reduces KNacurrent in pyramidal cells that express both HCN and Slack channels, indicating that blockade of HCN channels reduced K+current indirectly by lowering Na+influx. In contrast, ZD7288 has no effect on KNacurrents in an HEK cell line stably expressing this Slack channels but no HCN channels, demonstrating that ZD7288 does not block Slack channels directly. Activation of HCN channels by cAMP in a cell line expressing a Ca2+reporter results in elevation of cytoplasmic Ca2+, but the effect of cAMP is completely reversed if the HCN channels are co-expressed with Slack channels. Finally, we have used a novel pharmacological blocker of Slack channels to show that inhibition of either Slack or HCN channels in rat PFC improves working memory performance, and that the actions of Slack and HCN channel blockers occlude each other in the memory task. Our results suggest that the regulation of working memory by HCN channels in PFC pyramidal neurons is mediated by an HCN-Slack channel complex that links activation HCN channels to suppression of neuronal excitability.