bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Postanesthesia Care Unit Delirium Is Associated with Differences in Aperiodic and Periodic Alpha Parameters of the Electroencephalogram during Emergence from General Anesthesia: Results from a Prospective Observational Cohort Study
Authors: Ostertag Julian , Engelhard Antonia , Nuttall Rachel , Aydin Duygu , Schneider Gerhard , García Paul S. , Hinzmann Dominik , Sleigh Jamie W. , Kratzer Stephan , Kreuzer Matthias
Published: October 2023

Background

Intraoperative alpha-band power in frontal electrodes may provide helpful information about the balance of hypnosis and analgesia and has been associated with reduced occurrence of delirium in the postanesthesia care unit. Recent studies suggest that narrow-band power computations from neural power spectra can benefit from separating periodic and aperiodic components of the electroencephalogram. This study investigates whether such techniques are more useful in separating patients with and without delirium in the postanesthesia care unit at the group level as opposed to conventional power spectra.

Methods

Intraoperative electroencephalography recordings of 32 patients who developed perioperative neurocognitive disorders and 137 patients who did not were considered in this post hoc secondary analysis. The power spectra were calculated using conventional methods and the “fitting oscillations and one over f” algorithm was applied to separate aperiodic and periodic components to see whether the electroencephalography signature is different between groups.

Results

At the group level, patients who did not develop perioperative neurocognitive disorders presented with significantly higher alpha-band power and a broadband increase in power, allowing a “fair” separation based on conventional power spectra. Within the first third of emergence, the difference in median absolute alpha-band power amounted to 8.53 decibels (area under the receiver operator characteristics curve, 0.74 [0.65; 0.82]), reaching its highest value. In relative terms, the best separation was achieved in the second third of emergence, with a difference in medians of 7.71% (area under the receiver operator characteristics curve, 0.70 [0.61; 0.79]). The area under the receiver operator characteristics curve values were generally lower toward the end of emergence with increasing arousal.

Conclusions

Increased alpha-band power during emergence in patients who did not develop perioperative neurocognitive disorders can be traced back to an increase in oscillatory alpha activity and an overall increase in aperiodic broadband power. Although the differences between patients with and without perioperative neurocognitive disorders can be detected relying on traditional methods, the separation of the signal allows a more detailed analysis. This may enable clinicians to detect patients at risk for developing perioperative neurocognitive disorders in the postanesthesia care unit early in the emergence phase.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Impact of Coronavirus Disease–era Clinical Trial Reform on Cancer Trial Access in Rural/Underserved Regions of the Mid-West
Authors: Gordon Elizabeth A. , Gordon Joshua W.
Published: October 2023

Objectives:

The coronavirus disease 2019 pandemic refocused the cancer community on bringing clinical trials closer to patients and increasing access for traditionally underserved communities. Pandemic-era deregulation increased flexibility with telemedicine visits, less frequent testing, and the ability to have tests done locally. This study evaluates the impact of 2020 cancer clinical trial reform on trial accessibility in rural/underserved regions of the mid-West.

Methods:

Publicly available clinicaltrials.gov data was accessed from January 1, 2018 to September 30, 2022 for the 3 leading causes of new cancer cases in Kentucky, Tennessee, Illinois, and Indiana. Interventional trials were categorized based on location using corresponding “Rural-Urban Commuting Area” codes (urban/metropolitan, suburban/micropolitan, small town/rural, and isolated/rural) and categorized as pre versus postpandemic (using March 15, 2020, when national regulatory guidelines were modified). Locations of trial offerings from pre and postpandemic dates were analyzed by paired t test. Comparison of trial location category by state and cancer type was analyzed by 1-way analysis of variance with pairwise multiple comparisons made using the Tukey-Kramer method.

Results:

Pandemic-era deregulation had no impact on increasing trial availability in suburban and small-town/rural locales (P = 0.1259). Only 18% of trials were offered outside of urban areas, with 15% in suburban and 3% in small town/rural areas. Results varied by state (P < 0.0001) with Illinois offering the most suburban and small-town trial availability (27%) compared with Kentucky, Indiana, and Tennessee (18%, 6%, and 2%, respectively). Trial availability in rural versus urban areas did not differ by cancer type (P = 0.07197).

Conclusions:

More work must be done to increase access to cancer clinical trials in rural and suburban areas of the United States.
Safety and Efficacy of Topical Vitamin D in the Management of Dry Eye Disease Associated With Meibomian Gland Dysfunction: A Placebo-Controlled Double-Blind Randomized Controlled Trial
Authors: Hassanpour Kiana , Langari Farideh , Akbarzadeh Amir Rezaeian , Kanavi Mozhgan Rezaei , Barani Maryam , Kheiri Bahareh , Karimian Farid , Ahmadieh Hamid , Sadoughi Mohammad-Mehdi
Published: October 2023

Purpose:

The aim of this study was to investigate the safety and efficacy of topical vitamin D in the management of dry eye disease associated with meibomian gland dysfunction (MGD).

Methods:

In this randomized controlled trial, patients with symptomatic MGD were divided into 2 groups to receive topical vitamin D drops or placebo in their randomized eyes. The exclusion criteria consisted of patients with vitamin D deficiency, previous ocular surgery, and patients with ocular diseases affecting the tear film. Patients and researchers were masked to the study groups. The outcomes included the score of Dry Eye Questionnaire (DEQ) 5 and Ocular Surface Disease Index (OSDI), corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer, and MG expressibility score evaluated at baseline and weeks 4 and 8.

Results:

Twenty-eight eyes of 28 patients were recruited in each group. In addition to the improvement of subjective parameters in both groups, there was a statistically significantly greater improvement in the vitamin D group compared with control for average scores of OSDI (13.38 ± 7.32 vs. 27.94 ± 7.49) and DEQ5 (9.67 ± 1.86 vs. 14.14 ± 2.45) at week 8 (Ps <0.001). In addition, a significant improvement in TBUT and Schirmer test was observed in both groups in weeks 4 and 8 (P value <0.05). There was a significant difference between the treatment and control groups after 8 weeks for OSDI, DEQ5, Schirmer, TBUT, corneal fluorescein staining, and MG expressibility score (P value <0.05).

Conclusions:

The preliminary results of this randomized controlled trial suggested that use of topical vitamin D drops with a lipid vehicle could be safe and might significantly improve the symptoms and signs of dry eye associated with MGD.
Treatment of geographic atrophy: an update on data related to pegcetacoplan
Authors: Patel Sagar B. , Heier Jeffrey S. , Chaudhary Varun , Wykoff Charles C.
Published: October 2023

Purpose of review

Geographic atrophy is an advanced and currently untreatable form of age-related macular degeneration (AMD), which leads to significant compromise of visual function and quality of life. Dysregulation of the complement cascade has been directly implicated in AMD pathogenesis. Pegcetacoplan is a pegylated highly selective bicyclic peptide that inhibits the cleavage of complement component 3 (C3), which represents a key step in propagation of the complement cascade. The phase 2 FILLY trial as well as the phase 3 OAKS and DERBY trials have evaluated the safety and efficacy of pegcetacoplan for the treatment of GA.

Recent findings

The FILLY, OAKS and DERBY trials have demonstrated that local inhibition of C3 cleavage with pegcetacoplan can reduce geographic atrophy lesion growth compared with sham with an effect size of approximately 11–35% depending on the specific trial and specific geographic atrophy phenotype considered. Overall pegcetacoplan has appeared to be well tolerated with the notable side effect of a dose-dependent increase in the rate of exudative AMD development in treated eyes.

The FILLY, OAKS and DERBY trials have demonstrated that pegcetacoplan is a potentially viable treatment for geographic atrophy. Additional data from the 2-year outcomes of DERBY and OAKS as well as data from the ongoing 3-year GALE extension study will provide additional insights into the potential therapeutic benefit of pegcetacoplan. Future studies assessing complement inhibition at earlier stages of AMD, with the goal of preventing geographic atrophy formation, are warranted.
Rapid Diagnosis of Bartonella-Induced Hemophagocytic Lymphohistiocytosis Using Next-Generation Sequencing of Plasma
Authors: Mondy Kristin E. , Thyagarajan Rama , Han H. Stephen , Lee Brian
Published: October 2023

Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled activation of macrophages and phagocytosis of hematopoietic cells. Recognition and treatment are often delayed in infectious triggers of HLH because of lack of rapid and reliable diagnostic modalities, as well as the need for invasive tissue sampling. We report a rare case of Bartonella-induced HLH in a kidney transplant patient who presented with fever of unknown origin. The diagnosis was expedited with next-generation sequencing of microbial cell-free DNA. We also describe the successful treatment outcome with antibiotics alone and the promising utility of this newer diagnostic method.
Peritoneal Tuberculosis
Authors: Ozturk Nazli Begum , Tsagkaris Christos , Iliaz Raim
Published: October 2023

Peritoneal tuberculosis (PT) is the most common form of abdominal tuberculosis. Diagnosis of PT can be difficult because of vague clinical symptoms, insidious onset, limitations of available diagnostic tests, and variable imaging findings. Early and timely diagnosis and treatment are important in preventing morbidity and mortality in PT. In this review, we summarize the current literature on presentation, diagnosis, and management of PT.
A Retrospective Analysis of Ischemic Stroke Patients Supports That Very Early Mobilization Within 24 Hours After Intravenous Alteplase Is Safe and Possibly Beneficial
Authors: Yanase Lisa , Clark Diane , Baraban Elizabeth , Stuchiner Tamela
Published: October 2023

BACKGROUND: Stroke care guidelines recommend early mobilization of acute ischemic stroke patients, but there are sparse data regarding early mobilization of stroke patients receiving thrombolytic therapy. We developed the Providence Early Mobility for Stroke (PEMS) protocol to mobilize patients to their highest individual tolerance within 24 hours of stroke admission in 2010, and it has been in continuous use at our primary and comprehensive stroke centers for over a decade. In this study, we evaluated the PEMS protocol in all patients treated with intravenous alteplase without endovascular treatment. METHODS: This retrospective study includes 318 acute ischemic stroke patients treated with alteplase who were admitted to 2 urban stroke centers between January 2013 and December of 2017 and were mobilized with the PEMS protocol within 24 hours of receiving alteplase. Safety of PEMS was assessed by change in National Institutes of Health Stroke Scale at 24 hours by time first mobilized. Using multivariate and logistic regression models, we analyzed time first mobilized and 90-day modified Rankin scale (mRS). RESULTS: Median time first mobilized was 9 hours from administration of alteplase. For every hour delay in mobilization, the odds of being slightly or moderately disabled (mRS, 2-3) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .004), and the odds of being severely disabled or dead (mRS, 4-6) at 90 days increased by 7% (adjusted odds ratio, 1.07; P = .02). In addition, for every hour delay in mobilization, 24-hour National Institutes of Health Stroke Scale increased by 1.8%. DISCUSSION: Our results support that the PEMS protocol is safe, and possibly beneficial, for acute ischemic stroke patients treated with intravenous alteplase. Our protocol differs from other very early mobility protocols because it does not prescribe a “dose” of activity. Instead, each patient was mobilized to his/her individual highest degree as soon as it was safe to do so.
Associations of Delirium to Posthospital Outcomes After Acute Stroke: A Scoping Review
Authors: Young Bethany C. , Rhoten Bethany A.
Published: October 2023

Background: Delirium is a common and distressing manifestation of acute brain dysfunction that is associated with poor outcomes in various critically ill patient populations. Although patients with acute stroke experience delirium, understanding of delirium in this population is limited. The purpose of this scoping review is to describe existing evidence about delirium and associations with posthospital outcomes after acute stroke. Methods: Arksey and O'Malley's 5-stage framework was used to perform a scoping review. PubMed, CINAHL, and EMBASE electronic databases were searched. Outcome domains of interest included mortality, cognitive function, physical function, mental health, and quality of life. Full-text, peer-reviewed articles with adult stroke sample populations (acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage) were included. Results: Nineteen articles, involving 5611 unique patients, were included. Most sample populations included patients with either acute ischemic stroke or intracerebral hemorrhage. Heterogeneous research aims, methods, and outcome measures limit the ability to compare specific findings across studies. However, included studies suggest higher mortality at 12 months, worse cognition, and greater functional impairment in patients who have experienced acute stroke and delirium. Limited information regarding associations of delirium with posthospital mental health outcomes and quality of life precluded the ability to analyze these relationships and warrants further investigation. Conclusion: This review suggests concerning findings about associations of delirium to posthospital outcomes after acute stroke. Better characterization of delirium after acute stroke and analysis of its impact on long-term outcomes are needed.
The Impact of Primary Care Practice Structural Capabilities on Nurse Practitioner Burnout, Job Satisfaction, and Intent to Leave
Authors: Schlak Amelia , Poghosyan Lusine , Rosa William E. , Mathew Shiyon , Liu Jianfang , Martsolf Grant , Flandrick Kathleen , Chen Julius L.
Published: October 2023

Background:

Lack of structure for care delivery (ie, structural capabilities) has been linked to lower quality of care and negative patient outcomes. However, little research examines the relationship between practice structural capabilities and nurse practitioner (NP) job outcomes.

Objectives:

We investigated the association between structural capabilities and primary care NP job outcomes (ie, burnout, job dissatisfaction, and intent to leave).

Research Design:

Secondary analysis of 2018-2019 cross-sectional data.

Subjects:

A total of 1110 NPs across 1002 primary care practices in 6 states.

Measures:

We estimated linear probability models to assess the association between structural capabilities and NP job outcomes, controlling for NP work environment, demographics, and practice features.

Results:

The average structural capabilities score (measured on a scale of 0–1) across practices was 0.6 (higher score indicates more structural capabilities). After controlling for potential confounders, we found that a 10-percentage point increase in the structural capabilities score was associated with a 3-percentage point decrease in burnout (P<0.001), a 2-percentage point decrease in job dissatisfaction (P<0.001), and a 3-percentage point decrease in intent to leave (P<0.001).

Conclusions:

Primary care NPs report lower burnout, job dissatisfaction, and intent to leave when working in practices with greater structural capabilities for care delivery. These findings suggest that efforts to improve structural capabilities not only facilitate effective care delivery and benefit patients but they also support NPs and strengthen their workforce participation. Practice leaders should further invest in structural capabilities to improve primary care provider job outcomes.
Intensive Case Management to Reduce Hospital Readmissions
Authors: Shade Kate , Hidalgo Paulina , Arteaga Manuel , Rowland Janet , Huang Winnie
Published: October 2023

Purpose of Study:

Hospital readmissions burden the U.S. health care system, and they have negative effects on patients and their families. The primary aim of this study was to pilot an intensive case management (ICM) intervention to reduce 30-day hospital readmissions. A secondary aim was to obtain patient- and caregiver-reported reasons for readmission.

Primary Practice Setting:

The setting was a vertically integrated health care system located in Northern California.

Methodology and Sample:

This pilot quality improvement project occurred over a 4-month period. The intervention was delivered by master's degree students in nurse case management through an academic–clinical partnership. Patients hospitalized with a 30-day readmission were offered the ICM intervention. A total of 36 patients were identified and 20 accepted. Patient and/or caregiver was interviewed to identify reasons for their readmission. Data were collected about pre–/post–health care utilization including subsequent 30-day readmission. Mixed methods were used to analyze the findings.

Results:

Thirteen of 20 enrolled patients received the weekly ICM intervention for at least 30 days. Seven declined further contact before 30 days. Patient-reported reasons for readmission included being discharged too soon, poor communication among providers and with patients/families, lack of understanding about disease management and/or treatment options, and inadequate support. Several patients believed that their readmission was unavoidable due to the complexity of their illnesses. We compared 30-day readmissions for those who participated in and those who declined the ICM intervention, finding that those who received the ICM intervention had a lower readmission rate than those who did not receive the intervention (35% vs. 37.5%).
Research on the balanced geographic allocation of medical facilities in Shenzhen City based on the hierarchical medical system
Authors: Yang Xiaochun , Zhuang Haobin , Miao Wenjie , Hong Wuyang , Zhang Li
Published: October 2023

Objective:

Based on the hierarchical medical system, this study evaluated the accessibility of medical facilities (MFs), analyzed their geographic allocation, and put forward suggestions for the balanced allocation of MFs in Shenzhen.

Methods:

This study implemented a 2-step floating catchment area method to evaluate the accessibility of MFs. Statistical and spatial analysis methods were used to analyze the spatial characteristics and service equity of accessibility in Shenzhen.

Results:

The spatial allocation of the accessibility of low-level MFs in Shenzhen was characterized by the emergence of point-like high-accessibility areas in a large low-accessibility area. Here, there is the problem of insufficient service capacity, which limits the implementation of the hierarchical medical system. The spatial characteristics of the accessibility of high-level MFs in Shenzhen included a high degree of agglomeration, large differences inside and outside the original special economic zone, and large areas with weak accessibility. There was a spatial imbalance in the overall accessibility of MFs, wherein individuals with higher incomes typically have better and more equitable accessibility.

Conclusions:

A balanced geographic allocation of MFs can ensure the implementation of the hierarchical medical system and enhance the equity of medical services. Strategies for balanced geographic allocation of MFs are proposed as follows: comprehensively improving the service capacity and construction standards of community healthcare centers; promoting the construction of primary hospitals and community hospitals in areas with a high population density; establishing additional secondary hospitals and tertiary hospitals in areas with low accessibility to high-level MFs; and encouraging coordinated urban development and MFs construction.
Point-of-Care Ultrasound of a Pediatric Gastric Trichobezoar
Authors: Chiang Elaine , Balasubramanian Shriman , Rabiner Joni E.
Published: October 2023

This case report describes a previously healthy pediatric patient with acute onset of abdominal pain and distention who was found to have an epigastric mass on physical examination. Point-of-care ultrasound (POCUS) demonstrated a large gastric mass with ultrasonographic features consistent with a trichobezoar. After POCUS was performed, trichophagia was confirmed on history, and the patient went to the operating room for removal of a large trichobezoar. We conclude POCUS may be helpful for evaluation of epigastric masses and diagnosis of gastric trichobezoars. We review the ultrasound technique, sonographic findings, and literature regarding ultrasound diagnosis of trichobezoars.
Rehabilitation improves persistent symptoms of COVID-19: a non-randomized, controlled, open study in Brazil
Authors: Campos Maria Cristine , Nery Tatyana , Speck Ana Elisa , Arpini Maiqueli , Antunes Moisés Moraes , de Bem Alves Ana Cristina , de Souza Santos Naiara , Matos Maria Paula Pereira , Schmidt Nelson , Bicca Letícia Roehe , Panisson Camila Mascarelo , Freitas Mariana Alves , Diefenthaeler Fernando , Kuriki Heloyse Uliam , Damin Vanessa , Da Rosa Rodrigo Oliveira , Gress Josiane Bueno , Schneider Ione Jayce Ceola , Vieira Danielle Soares Rocha , Arcêncio Livia , Aguiar Aderbal S.
Published: October 2023

Objective

This study aimed to investigate the effects of an 8-week face-to-face rehabilitation program on subjects with persistent symptoms of COVID-19 compared to a remote monitoring group.

Design

Clinical, non-randomized, controlled, and open study. The face-to-face supervised rehabilitation lasted eight consecutive weeks, twice a week. The remote monitoring group received health guidance. The allocation was carried out by preference due to the emergency period without vaccination during the pandemic. Fatigue, dyspnea (Pulmonary Functional Status and Dyspnea Questionnaire), and exercise capacity (Incremental Shuttle Walk Test) were the primary outcome measures. Lung function, functional status (Post-COVID-19 Functional Status), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale), attention (d2-R), memory (Rey's Auditory-Verbal Learning Test), handgrip strength, and knee extensor strength were secondary outcome measures.

Results

37 subjects (24.3% hospitalized) completed the baseline and final assessment, rehabilitation [n = 22, 40.8 (SD 10.0) years, 54.5% female], or remote guidance [n = 15, 45.4 (SD 10.5) years, 40% female]. Both groups showed improved fatigue and exercise capacity. Exercise rehabilitation improved dyspnea, anxiety, attention, and short-term memory.

Conclusion

Rehabilitation is essential for dyspnoea in subjects with persistent symptoms of COVID-19 while fatigue naturally reverses.
Efficacy of a Decision Aid in Breast Cancer Patients Considering Immediate Reconstruction: Results of a Randomized Controlled Trial
Authors: ter Stege Jacqueline A. , Woerdeman Leonie A. E. , Kieffer Jacobien M. , Sherman Kerry A. , Agelink van Rentergem Joost A. , van Duijnhoven Frederieke H. , van Huizum Martine A. , Gerritsma Miranda A. , Kuenen Marianne , Corten Eveline M. L. , Kimmings Nikola (A. N.) , Ruhé Quinten (P. Q.) , Krabbe-Timmerman Irene S. , van’t Riet Martijne , Hahn Daniela E. E. , Witkamp Arjen J. , Oldenburg Hester S. A. , Bleiker Eveline M. A.
Published: October 2023

Background:

Breast cancer patients face complex decisions about immediate breast reconstruction (BR) after mastectomy. The authors evaluated the efficacy of an online decision aid in improving the decision-making process, decision quality, and health outcomes in breast cancer patients considering immediate BR.

Methods:

In a multicenter, randomized, controlled trial, patients were allocated to either the intervention group, receiving care as usual with access to an online decision aid, or the control group, receiving care as usual with an information leaflet. The primary outcome was decisional conflict. Secondary outcomes assessed the process of decision-making (eg, preparation for decision-making, satisfaction with information), decision quality (decision regret, knowledge), and health outcomes (eg, satisfaction with BR outcomes, body image). Patients completed questionnaires at time (T) 0 (baseline); T1 (1 week after consultation with a plastic surgeon); and T2 (3 months) and T3 (12 months) after surgery.

Results:

The authors included 250 patients. Decisional conflict decreased over time in both groups, with no between-group differences. Intervention participants felt better prepared for decision-making than controls (P = 0.002). At T2, 87% of intervention participants were very satisfied with the information about BR, compared with 73% of control participants (P = 0.011). No significant between-group differences were observed in any other outcome.

Conclusions:

The authors’ online decision aid was as effective in reducing decisional conflict as an information leaflet about immediate BR after mastectomy. However, the decision aid substantially improved the decision-making process by better preparing breast cancer patients for decisions about immediate BR.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Outcomes of the Use of Fresh-Frozen Costal Cartilage in Rhinoplasty
Authors: Hanna Steven A. , Mattos David , Datta Shaishav , Reish Richard G.
Published: October 2023

Background:

Rhinoplasty is made more challenging when there is insufficient septal cartilage for use as graft material. Several autologous and homologous graft options have been used in the past, although each comes with its own set of challenges. Fresh-frozen costal cartilage (FFCC) is an increasingly popular alternative that yields the benefits of homologous tissue while having a lower theoretical risk profile. Given the relatively novel nature of this option, the authors analyzed the complication rates of Musculoskeletal Transplant Foundation FFCC.

Methods:

A retrospective chart review of the use of FFCC in rhinoplasty in the senior author’s (R.G.R.) practice was conducted between March of 2018 to December of 2021. A total of 282 cases were reviewed and analyzed for rates of infection, warping, and resorption. Patients with a minimum of 12 months of follow-up were included.

Results:

The mean age of the study group was 35.8 years, and 27 male and 255 female patients were included. Forty cases were primary rhinoplasties; the remaining 242 were revisions. The mean follow-up period was 20.3 months. Six patients (2.1%) required empiric antibiotics postoperatively; no patient had clinical signs of warping, resorption, or displacement, and 6 patients (2.1%) required operative revision unrelated to the FFCC.

Conclusions:

This study provides follow-up data on the complication profile of FFCC in rhinoplasty. Acute infection, warping, and resorption rates were found to be no greater than rhinoplasty complication rates when autologous or homologous tissue is used. FFCC is a safe, convenient, and patient-centered option for graft tissue in rhinoplasty.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Synergistic Effect of Full-Spectrum Light Therapy and Transient Immunosuppressants Prolonged Allotransplant Survival
Authors: Liu Keng-Fan , Ramachandran Savitha , Chang Chao-Wei , Chen Rong-Fu , Huang Chao-hsin , Huang Han-Ting , Lee Chia-Chun , Li Yun-Ting , Kuo Yur-Ren
Published: October 2023

Background:

The lifelong administration of immunosuppressants remains the largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model.

Methods:

Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term antilymphocyte serum (ALS) and cyclosporine A (CsA). Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis.

Results:

The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared with the control (group 1). However, in group 4, FBLT combined with short-term ALS/CsA, median composite tissue allograft survival time (266 days) was significantly prolonged compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (P < 0.01). Group 4 also showed a significant increase in regulatory T cells (P = 0.04) and transforming growth factor-β1 levels (P = 0.02), and a trend toward a decrease in interleukin-1β levels (P = 0.03) at 16 weeks after transplantation as compared with control (group 1).

Conclusions:

FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and antiinflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Clinical Relevance Statement:

Full-spectrum light therapy could be a potential strategy to increase vascularized composite allotransplant survival.
Predictors of Postoperative Diplopia following Orbital Fracture Repair in Adults
Authors: Hassan Bashar , Yoon Joshua , Er Seray , Resnick Eric , Yusuf Cynthia , Liang Fan , Yang Robin , Grant Michael
Published: October 2023

Background:

Postoperative diplopia is reported in up to 52% of orbital bone fracture (OBF) repair. Evidence on these risk factors is based on low-quality data, single-institution studies, and small sample sizes. Our study is the largest and first multicenter study to determine the predictors of postoperative diplopia following OBF repair.

Methods:

The authors conducted a retrospective review of patients who underwent OBF repair at 2 centers from 2015 to 2019. The authors’ primary outcome was the incidence or persistence of postoperative diplopia at least 2 weeks after OBF repair. Descriptive statistics were calculated. Multivariable logistic regression was performed to determine significant predictors of postoperative diplopia.

Results:

Of 254 patients, the median age was 36.1 years (interquartile range, 27.8 to 50.7 years), and the median follow-up was 79.5 days (interquartile range, 40.3 to 157.3 days). The most common postoperative ocular symptom was diplopia (51 of 254 [20.1%]). Patients who had preoperative limited ocular motility or enophthalmos had greater odds of developing postoperative diplopia, compared with patients who did not have these preoperative symptoms (adjusted ORs, 2.33 [95% CI, 1.03 to 5.24] and 2.35 [95% CI, 1.06 to 5.24], respectively). Patients who had combined orbital floor and medial wall and moderate OBF (>2-cm2 defect or >3-mm displacement) on preoperative computed tomographic scan had greater odds (adjusted ORs, 2.16 [95% CI, 1.04 to 4.46] and 3.77 [95% CI, 1.44 to 9.83], respectively) of developing postoperative diplopia, compared with patients without these preoperative computed tomographic findings.

Conclusion:

During primary assessment of the patient with OBF, preoperative ocular signs and symptoms, fracture severity, and location of OBF are key predictors of postoperative diplopia.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
LITERATURE REVIEW ON INTERVENTIONS FOR PREVENTION OF UNPLANNED EXTUBATION IN NICU PICU: A PHILOSOPHY OF NURSING SCIENCE
Authors: Mariyam Mariyam , Rumambo Pandin Moses Glorino , Fitriani Netty Prasetiya
Published: October 2023

Introduction

One of the complications of endotracheal tube (ETT) installation is unplanned extubation (UE). UE is an initial inappropriate removal of an ETT by a patient or medical personnel. This literature review are to describe interventions to prevent unplanned extubation in NICU and PICU.

Method

Literature review searches using Sciencedirect, Google Scholar and Pubmed. The keywords used in searching articles were unplanned extubation PICU NICU. The search criteria were publication year 2017-2023, quasi-experimental design and full text.

Result

The results show that actions that can reduce the incidence of UE are standardization interventions for ETT safety, protocols for moving patients (patient transportation), and collaborative interventions for providing sedation.

Conclusion

standardization of ETT safety, protocols for moving patients (patient transport), and collaboration in providing sedation can be used to reduce unplanned extubation.
Organic compounds drive growth in phytoplankton taxa from different functional groups
Authors: Martens Nele , Ehlert Emilia , Putri Widhi , Sibbertsen Martje , Schaum C.-Elisa
Published: October 2023

Phytoplankton are usually considered autotrophs by default, but an increasing number of studies shows that many taxa are able to also utilise organic carbon. Acquiring nutrients and energy from different sources might enable an efficient uptake of required substances and provide a strategy to deal with a varying resource availability, especially in highly dynamic ecosystems such as estuaries. In our study we investigated the effects of 31 organic carbon sources on the growth of 17 phytoplankton strains from the Elbe estuary spanning four functional groups. All of our strains were able to make use of at least 1 and up to 26 organic compounds for growth. Pico-sized green algae such asMychonastes, ChoricystisandChlorella, as well as nano-sized green algae from the genusMonoraphidiumin particular were positively affected by a high variety of substances. Reduced light availability, typically appearing in turbid estuaries and similar habitats, resulted in an overall poorer ability to utilise organic substances for growth, indicating that organic carbon acquisition was not primarily a specific strategy to deal with darkness. Our results give further evidence for mixotrophy being an ubiquitous ability of phytoplankton and highlight the importance to consider this trophic strategy in research.
Reduced nephron endowment in the commonSix2-TGCtgmouse line is due toSix3misexpression by aberrant enhancer-promoter interactions in the transgene
Authors: Perl Alison J. , Liu Han , Hass Matthew , Adhikari Nirpesh , Chaturvedi Praneet , Hu Yueh-Chiang , Jiang Rulang , Liu Yaping , Kopan Raphael
Published: October 2023

Lifelong kidney function relies on the complement of nephrons generated during mammalian development from a mesenchymal nephron progenitor cell (NPC) population. Low nephron endowment confers increased susceptibility to chronic kidney disease. We asked whether reduced nephron numbers in the popularSix2TGCtransgenic mouse line1was due to disruption of a regulatory gene at the integration site or to ectopic expression of a gene(s) contained within the transgene. Targeted locus amplification identified integration of theSix2TGCtransgene within an intron ofCntnap5aon chr1. We generated Hi-C datasets from NPCs isolated from theSix2TGCtg/+mice, theCited1CreERT2/+control mice, and theSix2TGCtg/+;Tsc1+/Flox,2mice that exhibited restored nephron number compared withSix2TGCtg/+mice, and mapped the precise integration ofSix2TGCandCited1CreERT2transgenes to chr1 and chr14, respectively. No changes in topology, accessibility, or expression were observed within the 50-megabase region centered onCntnap5ainSix2TGCtg/+mice compared with control mice. By contrast, we identified an aberrant regulatory interaction between aSix2distal enhancer and theSix3promoter contained within the transgene. Increasing theSix2TGCtgtoSix2locus ratio or removing oneSix2allele inSix2TGCtg/+mice, caused severe renal hypoplasia. Furthermore, CRISPR disruption ofSix3within the transgene (Six2TGCΔSix3CT) restored nephron endowment to wildtype levels and abolished the stoichiometric effect. Data from genetic and biochemical studies together suggest that inSix2TGC,SIX3 interferes with SIX2 function in NPC renewal through its C-terminal domain.

Significance

Using high-resolution chromatin conformation and accessibility datasets we mapped the integration site of two popular transgenes used in studies of nephron progenitor cells and kidney development. Aberrant enhancer-promoter interactions drive ectopic expression ofSix3in theSix2TGCtgline which was correlated with disruption of nephrogenesis. Disruption ofSix3within the transgene restored nephron numbers to control levels; further genetic and biochemical studies suggest thatSix3interferes withSix2-mediated regulation of NPC renewal.
Reverse Correlation Characterizes More Complete Tinnitus Spectra in Patients
Authors: Barnett Nelson V. , Hoyland Alec , Chari Divya A. , Parrell Benjamin , Lammert Adam C.
Published: October 2023

Goal

We validate a recent reverse correlation approach to tinnitus characterization by applying it to individuals with clinically-diagnosed tinnitus.

Methods

Two tinnitus patients assessed the subjective similarity of their non-tonal tinnitus percepts and random auditory stimuli. Regression of the responses onto the stimuli yielded reconstructions which were evaluated qualitatively by playing back resynthesized waveforms to the subjects and quantitatively by response prediction analysis.

Results

Subject 1 preferred their resynthesis to white noise; subject 2 did not. Response prediction balanced accuracies were significantly higher than chance across subjects: subject 1: 0.5963, subject 2: 0.6922.

Conclusion

Reverse correlation can provide the foundation for reconstructing accurate representations of complex, non-tonal tinnitus in clinically diagnosed subjects. Further refinements may yield highly similar waveforms to individualized tinnitus percepts.

Impact Statement

Characterization of tinnitus sounds can help clarify the heterogeneous nature of the condition and link etiology to subtypes and treatments.
FORMATION OF MALIGNANT, METASTATIC SMALL CELL LUNG CANCERS THROUGH OVERPRODUCTION OF cMYC PROTEIN IN TP53 AND RB1 DEPLETED PULMONARY NEUROENDOCRINE CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS
Authors: Chen Huanhuan Joyce , Gardner Eric E. , Shah Yajas , Zhang Kui , Thakur Abhimanyu , Zhang Chen , Elemento Olivier , Varmus Harold
Published: October 2023

We recently described our initial efforts to develop a model for small cell lung cancer (SCLC) derived from human embryonic stem cells (hESCs) that were differentiated to form pulmonary neuroendocrine cells (PNECs), a putative cell of origin for neuroendocrine-positive SCLC. Although reduced expression of the tumor suppressor genesTP53andRB1allowed the induced PNECs to form subcutaneous growths in immune-deficient mice, the tumors did not display the aggressive characteristics of SCLC seen in human patients. Here we report that the additional, doxycycline-regulated expression of a transgene encoding wild-type or mutant cMYC protein promotes rapid growth, invasion, and metastasis of these hESC-derived cells after injection into the renal capsule. Similar to others, we find that the addition of cMYC encourages the formation of the SCLC-N subtype, marked by high levels ofNEUROD1RNA. Using paired primary and metastatic samples for RNA sequencing, we observe that the subtype of SCLC does not change upon metastatic spread and that production of NEUROD1 is maintained. We also describe histological features of these malignant, SCLC-like tumors derived from hESCs and discuss potential uses of this model in efforts to control and better understand this recalcitrant neoplasm.
Aboveground enemy release increases seedling survival in grasslands
Authors: Brian Joshua I. , Shepherd Harry E. R. , Pérez-Navarro María Ángeles , Catford Jane A.
Published: October 2023

The enemy release hypothesis is a popular hypothesis to explain the success of invasive plants. Enemy release studies typically focus on single species or types of communities, feature indirect experimental manipulations that apply pesticides to whole communities not individual species, and only examine responses of established plants or plant populations, limiting their generality. Using a novel species-specific approach, we examine whether enemy release can enhance seedling survival and recruitment of 16 grassland species by experimentally linking enemy release with enhanced plant performance.

We planted seedlings of 16 native grassland species from two functional groups (C4 grasses and non-legume forbs) into two grassland sites (early and mid succession). We hand-painted 1,548 individual seedlings with pesticides (insecticide and fungicide) over the course of a growing season to enforce aboveground species-specific enemy release, and tested whether it enhanced survival relative to untreated controls. Using native species enabled us to directly test effects of enemy release, while avoiding confounding factors like unknown invasion histories. Of the 16 native study species, 13 are naturalised/invasive outside of their native ranges.

Release from insects increased seedling survival by 80% on average, with no additional benefit of release from fungal pathogens. This effect was consistent across functional groups and community successional stages, and was strongest in resource-acquisitive species. The size of species’ performance benefits from enemy release were positively correlated with the number of regions globally where each species has been introduced and naturalised.

Synthesis. Previous studies of enemy release have centred on adults and findings have varied among species. We found a positive effect of release from insect herbivores early in colonisation – a trend that held across functional groups and types of resident community. We posit that the consistent vulnerability of seedlings vis-à-vis later life stages leads to this more ubiquitous benefit of enemy release. Enemy release may therefore aid initial recruitment of most, if not all, plants during the invasion process, even if enemies rapidly accumulate. The positive correlations between the benefits of enemy release for seedlings, species’ life history strategies and global naturalisation patterns provide compelling hypotheses for future research.
On the contrast response function of adapted neural populations
Authors: Tring Elaine , Dipoppa Mario , Ringach Dario L.
Published: October 2023

The magnitude of neural responses in sensory cortex depends on the intensity of a stimulus and its probability of being observed within the environment. How these two variables combine to influence the overall response of cortical populations remains unknown. Here we show that, in primary visual cortex, the vector magnitude of the population response is described by a separable power-law that factors the intensity of a stimulus and its probability.
Cross-pathway integration of cAMP signals through cGMP and calcium-regulated phosphodiesterases in mouse striatal cholinergic interneurons
Authors: Bompierre Ségolène , Byelyayeva Yelyzaveta , Mota Elia , Lefevre Marion , Pumo Anna , Kehler Jan , Castro Liliana R.V. , Vincent Pierre
Published: October 2023

Acetylcholine plays a key role in striatal function, yet the intricate dynamics of cyclic nucleotide signaling which govern the firing properties of cholinergic interneurons (ChINs) have remained elusive. Since phosphodiesterases determine the dynamics of cyclic nucleotides, in this study, we used FRET biosensors and pharmacological compounds to examine phosphodiesterase activity in ChINs in mouse brain slices. Intriguingly, these neurons displayed strikingly low levels and slow cAMP responsiveness compared to medium-sized spiny neurons (MSNs). Our experiments revealed that PDE1, PDE3 and PDE4 are important regulators of cAMP level in ChINs. Notably, the induction of cGMP production by nitric oxide (NO) donors increases cAMP by inhibiting PDE3 - a mechanism hitherto unexplored in neuronal context. Furthermore, the activation of NMDA or metabotropic glutamate receptors increases intracellular calcium, consequently activating PDE1 and thereby decreasing both cAMP and cGMP. This interplay of phosphodiesterases enables the control of cAMP by the neuromodulatory influences of glutamate and NO. Remarkably, the NO/cGMP signal results in different effects: NO enhances cAMP in ChINs by inhibiting PDE3, whereas it reduces cAMP levels in MSNs by activating PDE2A. These findings underscore the specificity of intracellular signaling in ChINs compared to MSNs and show how the NO-cGMP pathway affects these various neuronal types differently. These observations have significant implications for understanding the regulation of the striatal network and the integration of dopaminergic signals and suggest innovative therapeutic strategies for addressing basal ganglia disorders with unmet medical need.
Exploration of the Tunability of BRD4 Degradation by DCAF16Trans-labelling Covalent Glues
Authors: Hassan Muhammad Murtaza , Li Yen-Der , Ma Michelle W. , Teng Mingxing , Byun Woong Sub , Puvar Kedar , Lumpkin Ryan , Sandoval Brittany , Rutter Justine C. , Jin Cyrus Y. , Wang Michelle Y. , Xu Shawn , Schmoker Anna M. , Cheong Hakyung , Groendyke Brian J. , Qi Jun , Fischer Eric S. , Ebert Benjamin L. , Gray Nathanael S.
Published: October 2023

Small molecules that can induce protein degradation by inducing proximity between a desired target and an E3 ligase have the potential to greatly expand the number of proteins that can be manipulated pharmacologically. Current strategies for targeted protein degradation are mostly limited in their target scope to proteins with preexisting ligands. Alternate modalities such as molecular glues, as exemplified by the glutarimide class of ligands for the CUL4CRBNligase, have been mostly discovered serendipitously. We recently reported atrans-labelling covalent glue mechanism which we named ‘Template-assisted covalent modification’, where an electrophile decorated small molecule binder of BRD4 was effectively delivered to a cysteine residue on an E3 ligase DCAF16 as a consequence of a BRD4-DCAF16 protein-protein interaction. Herein, we report our medicinal chemistry efforts to evaluate how various electrophilic modifications to the BRD4 binder, JQ1, affect DCAF16trans-labeling and subsequent BRD4 degradation efficiency. We discovered a decent correlation between the ability of the electrophilic small molecule to induce ternary complex formation between BRD4 and DCAF16 with its ability to induce BRD4 degradation. Moreover, we show that a more solvent-exposed warhead presentation is optimal for DCAF16 recruitment and subsequent BRD4 degradation. Unlike the sensitivity of CUL4CRBNglue degraders to chemical modifications, the diversity of covalent attachments in this class of BRD4 glue degraders suggests a high tolerance and tunability for the BRD4-DCAF16 interaction. This offers a potential new avenue for a rational design of covalent glue degraders by introducing covalent warheads to known binders.