bluuebunny/crossref_metadata_2025 huggingface dataset:
PLEIOTROPIC REGULATORY LOCUS1 maintains actin microfilament integrity to regulate pavement cell morphogenesis
Authors: Gao Xiaowei , Yang Bo , Zhang Jingjing , Wang Chi , Ren Huibo , Fu Ying , Yang Zhenbiao
Published: January 2024

Actin dynamics are critical for plant cell morphogenesis, but the underlying signaling mechanisms regulating these dynamics are not well understood. Here, we established that PLEIOTROPIC REGULATORY LOCUS1 (PRL1) modulates leaf pavement cell (PC) morphogenesis in Arabidopsis (Arabidopsis thaliana) by maintaining the dynamic homeostasis of actin microfilaments (MF). Our previous studies indicated that PC shape was determined by antagonistic RHO-RELATED GTPase FROM PLANTS 2 (ROP2) and RHO-RELATED GTPase FROM PLANTS 6 (ROP6) signaling pathways that promote cortical MF and microtubule organization, respectively. Our genetic screen for additional components in ROP6-mediated signaling identified prl1 alleles. Genetic analysis confirmed that PRL1 plays a key role in PC morphogenesis. Mutations in PRL1 caused cortical MF depolymerization, resulting in defective PC morphogenesis. Further genetic analysis revealed that PRL1 is epistatic to ROP2 and ROP6 in PC morphogenesis. Mutations in PRL1 enhanced the effects of ROP2 and ROP6 in PC morphogenesis, leading to a synergistic phenotype in the PCs of ROP2 prl1 and ROP6 prl1. Furthermore, the activities of ROP2 and ROP6 were differentially altered in prl1 mutants, suggesting that ROP2 and ROP6 function downstream of PRL1. Additionally, cortical MF depolymerization in prl1 mutants occurred independently of ROP2 and ROP6, implying that these proteins impact PC morphogenesis in the prl1 mutant through other cellular processes. Our research indicates that PRL1 preserves the structural integrity of actin and facilitates pavement cell morphogenesis in Arabidopsis.
Automatic recording of rare behaviors of wild animals using video bio-loggers with on-board light-weight outlier detector
Authors: Tanigaki Kei , Otsuka Ryoma , Li Aiyi , Hatano Yota , Wei Yuanzhou , Koyama Shiho , Yoda Ken , Maekawa Takuya
Published: January 2024

Rare behaviors displayed by wild animals can generate new hypotheses; however, observing such behaviors may be challenging. While recent technological advancements, such as bio-loggers, may assist in documenting rare behaviors, the limited running time of battery-powered bio-loggers is insufficient to record rare behaviors when employing high-cost sensors (e.g. video cameras). In this study, we propose an artificial intelligence (AI)-enabled bio-logger that automatically detects outlier readings from always-on low-cost sensors, e.g. accelerometers, indicative of rare behaviors in target animals, without supervision by researchers, subsequently activating high-cost sensors to record only these behaviors. We implemented an on-board outlier detector via knowledge distillation by building a lightweight outlier classifier supervised by a high-cost outlier behavior detector trained in an unsupervised manner. The efficacy of AI bio-loggers has been demonstrated on seabirds, where videos and sensor data captured by the bio-loggers have enabled the identification of some rare behaviors, facilitating analyses of their frequency, and potential factors underlying these behaviors. This approach offers a means of documenting previously overlooked rare behaviors, augmenting our understanding of animal behavior.
Unexpected hydroxyl radical production in brewed tea under sunlight
Authors: Qin Linjun , Yang Lili , Shiraiwa Manabu , Faiola Francesco , Zhong Huan , Sonne Christian , Yang Yujue , Liu Shuting , Liu Guorui , Zheng Minghui , Jiang Guibin
Published: January 2024

Tea is one of the world's most popular and widely consumed beverages. It is a common pastime to enjoy a cup of tea in the sunshine. However, little attention has been given to understanding the possible photochemical reactions occurring beneath the calm surface of brewed tea. Epigallocatechin gallate (EGCG), which is widely used in food and beverages, is the most significant active ingredient found in tea. In this study, we investigated the presence of free radicals in both an aqueous EGCG solution and brewed tea under simulated sunlight conditions. To our surprise, we unexpectedly observed the production of hydroxyl radicals (•OH) in brewed tea. It was found that sunlight irradiation played a critical role in the formation of •OH, independent of the presence of metal ions. Furthermore, we demonstrated that the •OH generated from the EGCG aqueous solution induced cell cytotoxicity and DNA damage in vitro. Considering the crucial role of •OH in various fields, including human health and the environment, it is important to further explore the practical implications of •OH production in brewed tea under sunlight. In summary, our study unveils the unexpected formation of •OH in brewed tea and emphasizes the significance of sunlight-induced reactions. The observed cytotoxic and DNA-damaging effects of •OH emphasize the importance of understanding the potential health consequences associated with tea consumption. Further research in this area will contribute to a better understanding of the broader implications of •OH production in brewed tea under sunlight.
Simultaneous measurements of radon, thoron and thoron progeny and induced cancer risk assessment in Djeno, Pointe-Noire, Republic of Congo
Authors: Sondzo Jucit Sem , Dallou Guy Blanchard , Meye Philippe Ondo , Diahou Russel Rolphe Caroll Moubakou , Biona Clobite Bouka , Kranrod Chutima , Omori Yasutaka , Hosoda Masahiro , Saïdou  , Tokonami Shinji
Published: January 2024

In this study, the activity concentrations of radon (222Rn), thoron (220Rn) and thoron progeny were measured simultaneously in Djeno (Pointe-Noire, Republic of Congo) using RADUET detectors to evaluate the air quality and the radiological risks due to the inhalation of these radionuclides. Activity concentrations of radon progeny were calculated from those of radon. Indoor radon, thoron and progenies followed a lognormal distribution ranging between 20 and 40, 6 and 62, 8 and 17.6 and 0.4 and 19.6 Bq m−3 for radon, thoron, radon progeny and thoron progeny, respectively. Mean values for radon were lower than the worldwide values estimated by the United Nation Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), which are 40 Bq m−3 (arithmetic mean) and 45 Bq m−3 (geometric mean). Radon concentrations in the dwellings under study were below the World Health Organization and the International Commission on Radiological Protection recommended reference levels, which are, respectively, 100 and 300 Bq m−3. The mean concentration of thoron was twice the world average value of 10 Bq m−3 estimated by UNSCEAR. Thoron progeny mean concentration was sharply greater than the typical value (0.3 Bq m−3) for indoor atmosphere provided by UNSCEAR. Annual effective dose ranges were 0.40–0.87 mSv (arithmetic mean, 0.57 ± 0.11 mSv) for radon and 0.10–4.14 mSv (arithmetic mean, 0.55 ± 0.77 mSv) for thoron. The mean value for radon was lower than the value (1.15 mSv) estimated by UNSCEAR, while the mean value for thoron was five times higher than the UNSCEAR value (0.10 mSv). The study showed that the use of the typical equilibrium factor value given by UNSCEAR to compute effective dose led to an error above 80%. Finally, the results of this study showed that the excess relative risk of radon-induced cancer was low, below 2% for the population under 55 y. The results presented in the present study prove that the population of Djeno is exposed to a relatively low potential risk of radon- and thoron-induced cancer.
Multimodal neuroimaging correlates of spectral power in NREM sleep delta sub-bands in cognitively unimpaired older adults
Authors: Champetier Pierre , André Claire , Rehel Stéphane , Ourry Valentin , Landeau Brigitte , Mézenge Florence , Roquet Daniel , Vivien Denis , de La Sayette Vincent , Chételat Gaël , Rauchs Géraldine ,   the Medit-Ageing Research Group, Bejanin Alexandre , Chauveau Léa , Chocat Anne , Collette Fabienne , Dautricourt Sophie , De Flores Robin , Delarue Marion , Demnitz-King Harriet , Espérou Hélène , Fauvel Séverine , Felisatti Francesca , Ferrand Devouge Eglantine , Frison Eric , Gonneaud Julie , Haudry Sacha , Hébert Oriane , Klimecki Olga , Kuhn Elizabeth , Landeau Brigitte , Lefranc Valérie , Marchant Natalie , Mezenge Florence , Palix Cassandre , Quillard Anne , Requier Florence , Salmon Eric , Touron Edelweiss , Turpin Anne-Laure , Vuilleumier Patrik , Whitfield Tim , Wirth Miranka
Published: January 2024

Study Objectives

In aging, reduced delta power (0.5–4 Hz) during N2 and N3 sleep has been associated with gray matter (GM) atrophy and hypometabolism within frontal regions. Some studies have also reported associations between N2 and N3 sleep delta power in specific sub-bands and amyloid pathology. Our objective was to better understand the relationships between spectral power in delta sub-bands during N2–N3 sleep and brain integrity using multimodal neuroimaging.

Methods

In-home polysomnography was performed in 127 cognitively unimpaired older adults (mean age ± SD: 69.0 ± 3.8 years). N2–N3 sleep EEG power was calculated in delta (0.5–4 Hz), slow delta (0.5–1 Hz), and fast delta (1–4 Hz) frequency bands. Participants also underwent magnetic resonance imaging and Florbetapir-PET (early and late acquisitions) scans to assess GM volume, brain perfusion, and amyloid burden. Amyloid accumulation over ~21 months was also quantified.

Results

Higher delta power was associated with higher GM volume mainly in fronto-cingular regions. Specifically, slow delta power was positively correlated with GM volume and perfusion in these regions, while the inverse association was observed with fast delta power. Delta power was neither associated with amyloid burden at baseline nor its accumulation over time, whatever the frequency band considered.

Conclusions

Our results show that slow delta is particularly associated with preserved brain structure, and highlight the importance of analyzing delta power sub-bands to better understand the associations between delta power and brain integrity. Further longitudinal investigations with long follow-ups are needed to disentangle the associations among sleep, amyloid pathology, and dementia risk in older populations.

Clinical Trial Information

Name: Study in Cognitively Intact Seniors Aiming to Assess the Effects of Meditation Training (Age-Well). URL: https://clinicaltrials.gov/ct2/show/NCT02977819?term=Age-Well&draw=2&rank=1. See STROBE_statement_AGEWELL in supplemental materials.

Registration

EudraCT: 2016-002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819.
Adolescent Simulation in a Health Assessment Course for Advanced Practice Nursing Students
Authors: Edgar Carly , Young Cara C. , Cuevas Heather
Published: January 2024

Advanced practice registered nurse (APRN) students face challenges transitioning to practice. They benefit greatly from simulated learning experiences that build confidence and increase competence in the skills needed to perform in an APRN role. The purpose of this quality improvement project was to evaluate the effectiveness of a simulated adolescent well visit in an advanced health assessment course. Using a pretest/posttest design, qualitative and quantitative data were collected from participants. Results included high learner satisfaction, an increase in both self-reported competence and confidence, and an appreciation for the “safe space” of learning.
Exploring the Effectiveness of a Prenursing Introductory Course: Experiences of Culturally Diverse Nursing Students
Authors: Griffin Miriam L.
Published: January 2024

Greater ethnic and racial diversity in the nursing profession is needed to reduce health care disparities and provide culturally competent health care to an increasingly diverse patient population. Prenursing preparation and early intervention programs have been developed to reduce attrition among culturally diverse students. A basic qualitative study was conducted to answer how culturally diverse students describe their experiences in a prenursing introductory course, part of a rigorous bachelor of nursing program at a historically Black university. An inductive thematic analysis revealed that students considered the course too easy; the course contributed to first-semester success.
Improvements in Objective and Patient-Reported Measures of Physical Function Following an 8-Week Exercise Oncology Program
Authors: Brooks Alexander M. , Fairman Ciaran M. , Harrington Shana E.
Published: January 2024

Background:

Physical function is often impaired because of cancer and its treatment. Despite this, it is not common to comprehensively assess physical function in clinical practice. The purpose of this study was to examine the changes in objective and patient-reported physical function in adults with a history of cancer who completed an exercise program.

Methods:

The program was offered 2 d/wk for 8 weeks at an outpatient physical therapy clinic and consisted of resistance and aerobic exercises that were individualized to each participant. Objective physical function was assessed using the Bellarmine Norton Assessment Tool consisting of self-reported physical activity frequency, 2-minute step test, 30-second sit to stand, timed arm curl, Timed Up and Go, and scaled total score. Patient-reported physical function was assessed using the PROMIS-Physical Function (PF) Computerized Adaptive Test (CAT).

Results:

Significant differences (P < .001) were found for all outcomes demonstrating improvements in objective and patient-reported physical function. Changes in raw and scaled total score for objective physical function displayed large Cohen d effect sizes (ES), physical activity (ES = 0.82), 2-minute step test (ES = 1.00), 30-second sit to stand (ES = 1.01), arm curl (ES = 1.01), Timed Up and Go (ES = 0.85), and scaled total score (ES = 1.31). Changes in PROMIS-PF CAT demonstrated a medium-large effect (ES = 0.78).

Conclusion:

The effectiveness of the exercise program was supported by significant improvements in objective and patient-reported physical function. The use of such outcomes provides a useful method to understand changes in physical function and supports the development of effective exercise methods for survivors of cancer.
Prospective Single-Arm Feasibility of Supervised Virtual Exercise in Women Living with Ovarian Cancer: The BE-BALANCED Study
Authors: Fujita Rafael A. , Tinker Anna , Fujisawa Natalie , Holmes Andrea , Hanley Gillian E. , Mackey Dawn C. , Trinh Linda , Lesser Iris , Mackenzie Kelly A. , Larnder Ashley , Murphy Rachel A. , Smith Gillian V. H. , Lam Jee A. , Campbell Kristin L.
Published: January 2024

Background:

Access to exercise programming that addresses the unique needs of women living with and beyond ovarian cancer is limited. Feasible and accessible supportive care programs to enhance physical function and quality of life are needed. We aimed to assess the feasibility of a 12-week virtually delivered exercise program for women living with and beyond ovarian cancer.

Methods:

BE-BALANCED was a prospective single-arm feasibility pilot study. Women who had completed primary chemotherapy treatment of ovarian cancer within the past year were recruited through oncologist referrals or self-referral. The 12-week group exercise program targeting aerobic capacity, functional strength, balance, and range of motion was conducted virtually twice weekly using Zoom. Feasibility measures were accrual, attendance, adherence, and attrition. Physical function was evaluated using the Short Physical Performance Battery and selected components of the Senior Fitness Test.

Results:

Fourteen participants enrolled in the study (47% of the accrual target). Feasibility goals for the exercise sessions were met for attendance (84% ± 19%), adherence to virtual sessions (78% ± 19%), and fidelity of group belonging (18% ± 4%), and met for overall attrition (21%). Improvements were observed in gait speed, 30-second bicep curls, 6-minute walk, chair stand, and emotional well-being (P < .05). Participant satisfaction with the program was high (4.4/5).

Conclusion:

Our findings demonstrated the feasibility of a virtually delivered exercise program for women living with and beyond ovarian cancer, with favorable attendance, adherence, and safety data. The program showed potential in improving physical outcomes and quality of life for participants. However, recruitment was a challenge. Future interventions could consider different approaches to increase recruitment.
Evaluation and Management of Buprenorphine Extended-Release Injection Thrombophlebitis: A Case Report
Authors: Barrett John , Schapiro Rebecca , Casey Emily , Chertok Judy
Published: January 2024

Introduction

Buprenorphine extended-release subcutaneous injection (BUP-XR) is a medication used to treat opioid use disorder. It is a long-acting formulation of buprenorphine, which is a partial opioid agonist. Buprenorphine extended-release subcutaneous injection is injected into the subcutaneous space forming a depot that can last up to a month. The most common adverse effects of BUP-XR are injection site pain, erythema, and induration.

Case Report

A man in his late 30s presented to the emergency department 48 hours after BUP-XR injection with abdominal pain. He was found to have superficial venous thrombosis of an abdominal wall vessel extending near the deep venous system. He was subsequently started on apixaban for 30 days and cefadroxil for 7 days to reduce the risk of extension and infection. He fully recovered and has since restarted BUP-XR without further complications.

Conclusions

Venous thrombosis is a rare but potentially life-threatening complication of BUP-XR. It is important for emergency and outpatient clinicians to be aware of adverse reactions associated with this medication. The patient was successfully treated with a 30-day course of apixaban and able to resume taking BUP-XR without further complications. Clinicians may want to consider supplementing BUP-XR with sublingual film after injection-related complications due to possible lower serum levels.
Immunosuppressant Medications in Pregnancy
Authors: Saad Antonio F. , Pacheco Luis D. , Saade George R.
Published: January 2024

Pregnant patients are often on immunosuppressant medications, most commonly to manage transplantation or autoimmune disorders. Most immunosuppressant agents, including tacrolimus, corticosteroids, azathioprine, and calcineurin inhibitors, are safe during pregnancy and lactation. However, mycophenolic acid is associated with higher risks of birth defects and should be avoided in pregnancy. Tacrolimus, the commonly used drug in transplantation medicine and autoimmune disorders, requires monitoring of serum levels for dose adjustment, particularly during pregnancy. Although no pregnancy-specific therapeutic range exists, the general target range is 5–15 ng/mL, and pregnant patients may require higher doses to achieve therapeutic levels. Adherence to prescribed immunosuppressive regimens is crucial to prevent graft rejection and autoimmune disorder flare-ups. This review aims to provide essential information about the use of immunosuppressant medications in pregnant individuals. With a rising number of pregnant patients undergoing organ transplantations or having autoimmune disorders, it is important to understand the implications of the use of these medications during pregnancy.
Revisiting Post-ICU Admission Fluid Balance Across Pediatric Sepsis Mortality Risk Strata: A Secondary Analysis of a Prospective Observational Cohort Study
Authors: Atreya Mihir R. , Cvijanovich Natalie Z. , Fitzgerald Julie C. , Weiss Scott L. , Bigham Michael T. , Jain Parag N. , Abulebda Kamal , Lutfi Riad , Nowak Jeffrey , Thomas Neal J. , Baines Torrey , Quasney Michael , Haileselassie Bereketeab , Sahay Rashmi , Zhang Bin , Alder Matthew N. , Stanski Natalja L. , Goldstein Stuart L.
Published: January 2024

OBJECTIVES:

Post-ICU admission cumulative positive fluid balance (PFB) is associated with increased mortality among critically ill patients. We sought to test whether this risk varied across biomarker-based risk strata upon adjusting for illness severity, presence of severe acute kidney injury (acute kidney injury), and use of continuous renal replacement therapy (CRRT) in pediatric septic shock.

DESIGN:

Ongoing multicenter prospective observational cohort.

SETTING:

Thirteen PICUs in the United States (2003–2023).

PATIENTS:

Six hundred and eighty-one children with septic shock.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Cumulative percent PFB between days 1 and 7 (days 1–7 %PFB) was determined. Primary outcome of interest was complicated course defined as death or persistence of greater than or equal to two organ dysfunctions by day 7. Pediatric Sepsis Biomarker Risk Model (PERSEVERE)-II biomarkers were used to assign mortality probability and categorize patients into high mortality (n = 91), intermediate mortality (n = 134), and low mortality (n = 456) risk strata. Cox proportional hazard regression models with adjustment for PERSEVERE-II mortality probability, presence of sepsis-associated acute kidney injury on day 3, and use of CRRT, demonstrated that time-dependent variable days 1–7%PFB was independently associated with an increased hazard of complicated course. Risk-stratified analyses revealed that each 10% increase in days 1–7 %PFB was associated with increased hazard of complicated course only among patients with high mortality risk strata (adjusted hazard ratio 1.24 (95% CI, 1.08–1.43), p = 0.003). However, this association was not causally mediated by PERSEVERE-II biomarkers.

CONCLUSIONS:

Our data demonstrate the influence of cumulative %PFB on the risk of complicated course in pediatric septic shock. Contrary to our previous report, this risk was largely driven by patients categorized as having a high mortality risk based on PERSEVERE-II biomarkers. Incorporation of such prognostic enrichment tools in randomized trials of restrictive fluid management or early initiation of de-escalation strategies may inform targeted application of such interventions among at-risk patients.
Insertion Site Dilemma: Rethinking Radial Arterial Catheter Placement for Device Resilience
Authors: Spencer Timothy R. , Imbriaco Guglielmo
Published: January 2024

The study by Marie et al (2023) discusses their outcomes regarding the distance of radial arterial catheters from the radiocarpal joint and its association to device failure, although authors found no significant difference in failure rates between catheters inserted proximally or distally to the radiocarpal joint. However, other recent studies have reported that catheters inserted more distally are more likely to fail, with rates high as 25%. Factors that contribute to failure include poor site selection, infection, device occlusion, or dislodgement. With reliance on accurate hemodynamics from arterial catheters, providers should be aware of the risks and take steps to minimize them, as catheter failure is more than just associated infection, the inability to aspirate blood or a useable arterial waveform. Optimal insertion location, use of ultrasound-guided techniques, appropriate securement, and close monitoring of the catheter, along with accurate reporting of failure reasons, will help clarify future research outcomes.
Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein
Authors: Nakamura Mariko , Yoshimi Akira , Tokura Tatsuya , Kimura Hiroyuki , Kishi Shinichi , Miyauchi Tomoya , Iwamoto Kunihiro , Ito Mikiko , Sato-Boku Aiji , Mouri Akihiro , Nabeshima Toshitaka , Ozaki Norio , Noda Yukihiro
Published: January 2024

Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.
An improved conflict avoidance assay reveals modality-specific differences in pain hypersensitivity across sexes
Authors: Ferland Samuel , Wang Feng , De Koninck Yves , Ferrini Francesco
Published: January 2024

Abnormal encoding of somatosensory modalities (ie, mechanical, cold, and heat) are a critical part of pathological pain states. Detailed phenotyping of patients' responses to these modalities have raised hopes that analgesic treatments could one day be tailored to a patient's phenotype. Such precise treatment would require a profound understanding of the underlying mechanisms of specific pain phenotypes at molecular, cellular, and circuitry levels. Although preclinical pain models have helped in that regard, the lack of a unified assay quantifying detailed mechanical, cold, and heat pain responses on the same scale precludes comparing how analgesic compounds act on different sensory phenotypes. The conflict avoidance assay is promising in that regard, but testing conditions require validation for its use with multiple modalities. In this study, we improve upon the conflict avoidance assay to provide a validated and detailed assessment of all 3 modalities within the same animal, in mice. We first optimized testing conditions to minimize the necessary amount of training and to reduce sex differences in performances. We then tested what range of stimuli produce dynamic stimulus–response relationships for different outcome measures in naive mice. We finally used this assay to show that nerve injury produces modality-specific sex differences in pain behavior. Our improved assay opens new avenues to study the basis of modality-specific abnormalities in pain behavior.
Healthy women show more experimentally induced central sensitization compared with men
Authors: Guekos Alexandros , Saxer Janis , Salinas Gallegos Diego , Schweinhardt Petra
Published: January 2024

Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. In 66 subjects (33 women), a thermal CS induction protocol was applied to the dorsum of one foot and a sham protocol to the other. Spatial extent [cm2] of secondary mechanical hyperalgesia (SMH) and dynamic mechanical allodynia were assessed as subjective CS proxy measures, relying on verbal feedback. Changes in nociceptive withdrawal reflex magnitude (NWR-M) and response rate (NWR-RR) recorded through surface electromyography at the biceps and rectus femoris muscles were used as objective CS proxies. The effect of the CS induction protocol on SMH was higher in women than in men (effect size 2.11 vs 1.68). Nociceptive withdrawal reflex magnitude results were statistically meaningful for women (effect size 0.31-0.36) but not for men (effect size 0.12-0.29). Differences between men and women were not meaningful. Nociceptive withdrawal reflex response rate at the rectus femoris increased in women after CS induction and was statistically different from NWR-RR in men (median differences of 13.7 and 8.4% for 120 and 140% reflex threshold current). The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.
A Comparison of Functional Luminal Imaging Probe With High-resolution Manometry, Timed Barium Esophagram, and pH Impedance Testing to Evaluate Functional Luminal Imaging Probe’s Diagnostic Capabilities
Authors: Miller James D. , Kemple Brendan P. , Evans Joni K. , Clayton Steven B.
Published: January 2024

Objective:

The aims of this study are to determine the functional luminal imaging probe’s (FLIP) diagnostic utility by comparing FLIP measurements with results from other esophageal evaluation standards.

Background:

The FLIP is an esophageal evaluation technique performed at the time of endoscopy. Few studies have evaluated FLIP diagnostic capabilities compared with the established testing techniques, including high-resolution manometry (HRIM), time barium esophagram (TBE), and 24-hour impedance-pH monitoring.

Patients and Methods:

A retrospective review was performed for 413 preintervention patients who underwent FLIP testing during endoscopy. Data from HRIM, 24-hour pH monitoring, and TBE were compared.

Results:

Abnormal Distensibility Index (DI) was associated with abnormal integrated relaxation pressure (IRP; P = 0.003). Average DI was higher in patients with abnormal IRP (>15 mm Hg) when a hiatal hernia was present (P = 0.025). The total agreement between correlated diagnoses from FLIP and HRIM was 33.5%. DI was not associated with acid exposure time on pH monitoring. Agreement between FLIP and TBE was 49% with a sensitivity of 98.1% and a specificity of 36.5%. A 60 mL distension had a significantly lower detection rate than 40 mL and 50 mL for active peristalsis and was unaffected by pressure (P < 0.05).

Conclusions:

FLIP as an adjunct to HRIM is supported by strong metric correlation. FLIP was not correlated to pH monitoring findings, suggesting FLIP is not useful in reflux assessment. The agreement between FLIP and TBE was lower than in previous studies. Hiatal hernia impacted the normality between DI and IRP, not between FLIP and TBE. We suggest analyzing peristaltic patterns on panometry at all fill volumes to optimize detection.
Diagnostic Yield of Small Bowel Videocapsule Endoscopy in Patients with Iron Deficiency Anemia. A Systematic Review and meta-analysis
Authors: Rossi Roberta Elisa , Zullo Angelo , Ferretti Silvia , Migliorisi Giulia , Gatta Luigi , De Francesco Vincenzo , Del Forno Alessandro , Marcozzi Giacomo , Masoni Benedetta , Franchellucci Gianluca , Hassan Cesare , Repici Alessandro
Published: January 2024

Background and Aim:

Gastrointestinal (GI) bleeding or malabsorption represents the most frequent aetiologies of iron deficiency anemia (IDA). The cause of IDA remains undetermined in ~10% to 20% of patients undergoing upper and lower GI endoscopies. In this scenario, a small bowel examination with videocapsule endoscopy (VCE) is recommended. We performed a systematic review with meta-analysis to evaluate the diagnostic yield of VCE in patients with IDA without overt bleeding, assessing the prevalence of either any lesion or lesions at high potential of bleeding.

Materials and Methods:

A computerized literature search was performed using relevant keywords to identify all the pertinent articles published until March 2023.

Results:

Twelve studies with a total of 1703 IDA patients (Males: 47%; age range: 19-92 y) were included in this systematic review. The diagnostic yield of VCE for overall lesions in the small bowel was 61% (95% CI=44-77; 95 CI=97.2-98.1; I
2=97.7%). When analyzing only small bowel lesions likely responsible of IDA, the diagnostic yield was 40% (95% CI=27-53; 95% CI=95.3-97; I
2=96.3%).

Conclusion:

VCE plays a relevant role in the diagnostic work-up of patients with IDA without overt bleeding with a satisfactory diagnostic yield.
The role of chest computed tomography in the evaluation and management of chronic obstructive pulmonary disease
Authors: Burkes Robert M. , Zafar Muhammad A. , Panos Ralph J.
Published: January 2024

Purpose of review

The purpose of this review is to compile recent data on the clinical associations of computed tomography (CT) scan findings in the literature and potential avenues for implementation into clinical practice.

Recent findings

Airways dysanapsis, emphysema, chronic bronchitis, and pulmonary vascular metrics have all recently been associated with poor chronic obstructive pulmonary disease (COPD) outcomes when controlled for clinically relevant covariables, including risk of mortality in the case of emphysema and chronic bronchitis. Other authors suggest that CT scan may provide insight into both lung parenchymal damage and other clinically important comorbidities in COPD.

CT scan findings in COPD relate to clinical outcomes. There is a continued need to develop processes to best implement the results of these studies into clinical practice.
Predictors for Super-Responders in Cardiac Resynchronization Therapy
Authors: Vătășescu Radu Gabriel , Târtea Georgică Costinel , Iorgulescu Corneliu , Cojocaru Cosmin , Deaconu Alexandru , Badiul Alexandru , Goanță Emilia-Violeta , Bogdan Ștefan , Cozma Dragoș
Published: January 2024

Background:

Prediction of cardiac resynchronization therapy (CRT) response, particularly a super-response, is of great importance.

Study Question:

The aim of our study was to assess the predictors for super-responders in CRT.

Study Design:

We conducted a retrospective, observational study, which finally included 622 patients with heart failure treated with CRT between January 2008 and May 2020 who had a minimal follow-up of 6 months after CRT.

Measures and Outcomes:

A total of 192 super-responders, defined by a left ventricular ejection fraction (LVEF) of at least 45%, and/or minimum 15% increase in LVEF and an improvement of the New York Heart Association functional class by at least 2 degrees at the last follow-up, and the rest of 430 patients who did not fulfill the super-responder criteria.

Results:

The highest rate of super-responders (41.91%, n = 171) was at patients with left ventricle-only pacing with optimal fusion (OPT) compared with patients with biventricular (BiV) pacing (9.81%, n = 21, P < 0.000). In the OPT group, univariable analysis showed that nonischemic cardiomyopathy, a smaller degree of mitral regurgitation, and better left ventricle function at enrollment were predictors for super-response compared with the BiV group where a narrower QRS after implantation, nonischemic cardiomyopathy, and a better baseline LVEF were predictors for super-responders. In the multivariable analysis, both narrower QRS after implantation and nonischemic cardiomyopathy were independent predictors for super-response in the BiV group compared with OPT where nonischemic cardiomyopathy remained the only independent predictor for super-response.

Conclusions:

In this retrospective study, OPT CRT programing was an additional predictor of super-response to CRT besides nonischemic cardiomyopathy.
Reduced Branched-Chain Amino Acid Intake Improved High-Fat Diet-Induced Nonalcoholic Fatty Pancreas Disease in Mice
Authors: Lu Jun , Pan Ting , Gao Jie , Cai Xinghua , Zhang Huihui , Sha Wenjun , Lei Tao
Published: January 2024

Objective

To explore the effects of branched-chain amino acids (BCAAs) on nonalcoholic fatty pancreas disease (NAFPD) and its possible mechanism in high-fat diet (HFD) induced mice.

Materials and Methods

Pancreatic morphology and lipid infiltration was assessed by hematoxylin-eosin staining and immunohistochemistry, and lipid levels in the pancreas were determined using colorimetric enzymatic method. Relevant mechanism was investigated using western blotting and biochemical test.

Results

In HFD-fed mice, dietary BCAAs restriction could attenuate body weight increase, improve glucose metabolism, and reduce excessive lipid accumulation in the pancreas. Furthermore, expression of AMPKα and downstream uncoupling protein 1 were upregulated, while genes related to mammalian target of rapamycin complex 1 (mTORC1) signal pathway and lipid de novo synthesis were suppressed in HFD-BCAA restriction group compared with HFD and HFD-high BCAAs fed mice. In addition, BCAA restriction upregulated expression of BCAAs related metabolic enzymes including PPM1K and BCKDHA, and decreased the levels of BCAAs and branched chain keto acid in the pancreas. However, there was no difference in levels of lipid content in the pancreas and gene expression of AMPKα and mTORC1 between HFD and HFD-high BCAAs groups.

Conclusions

Branched-chain amino acid restriction ameliorated HFD-induced NAFPD in mice by activation of AMPKα pathway and suppression of mTORC1 pathway.
Supporting the Role Transition of Interim Nurse Managers
Authors: Parchment Joy , Galura Sandra , Warshawsky Nora
Published: January 2024

Executive nurse leaders may rely on interim nurse managers (INMs) to fill vacated nurse manager positions open for an extended time. To optimize the INM role for future leadership succession planning, ongoing professional development for this role is critical. The authors describe the use of evidence in the creation of onboarding leadership resources to support the role transition of INMs within a healthcare environment over a 100-day period.
Is it Smoke and Mirrors? Detection of Inferior Vena Cava Thrombus by Focused Cardiac Ultrasound
Authors: Soma Gauthami , DeGuardi John , Iqbal Ammarah U. , Leviter Julie , Riera Antonio
Published: January 2024

Inferior vena cava assessment is a standard component of focused cardiac ultrasound, traditionally used to qualify intravascular volume status. In this case series, we demonstrate that pediatric focused cardiac ultrasound can also diagnose inferior vena cava thrombi and masses, while distinguishing them from a potentially benign smoke-like artifact.
Evaluation of Mandibular Lingual and Foramen Location in Class I, Class II, and Class III Patients and its Significance in Sagittal Split Ramus Osteotomy
Authors: Wang Yu , Zhang Dong , Guo Xiaoshuang , Jin Xiaolei
Published: January 2024

The precise location of the mandibular lingual (ML) and foramen (MF) is clinically significant because they are crucial anatomic markers for the inferior alveolar nerve protection in sagittal split ramus osteotomy. To determine the position of the ML and MF among subjects with class I, class II, and class III skeletal patterns to obtain information that could be useful for interventions in mandibular ramus. A retrospective study of 324 mandibular ramus from 162 patients was performed to evaluate the distance from the MF to the occlusal plane (OP) and the distance of the ML to the MF, OP, and the margin of the mandible ramus. The MF was more often located below the OP in class III (55.1%), compared with class I (29.0%) and class II (45.3%) patients (P<0.05). The distance from the ML to the MF in skeletal Class III patients (10.15 ± 1.56 mm) was found to be greater than class I (9.25 ± 1.52 mm) and class II (8.34 ± 1.79 mm) patients (P<0.001). And the distance from the ML to the OP was shown to be longer in class III (9.40 ± 2.53 mm) than in class I (6.85 ± 2.55 mm) and class II (6.99 ± 2.53 mm) patients (P<0.001). Therefore, we believe that a low medial horizontal cut at the height of OP is dangerous for Class III patients. And the safe zone for the high medial horizontal cut over the ML should be determined according to the patient’s skeletal patterns.
Treatment Strategy of Intracranial Anterior Circulation Aneurysm Presenting with Cerebral Ischemia: A Single-Center Experience
Authors: Guo Wenqiang , Wang Xingdong , Tong Xiaoguang
Published: January 2024

Objective:

To investigate the clinical characteristics and treatment strategy of anterior circulation aneurysm presenting with cerebral ischemia.

Methods:

We performed a retrospective review of patients with intracranial anterior circulation aneurysms presenting with cerebral ischemia examined in the Fifth Ward of the Neurosurgery Department of Tianjin Huanhu Hospital between September 2016 and September 2023. Data were reviewed for age, sex, presentation, type and size, location, treatment modalities, postoperative complications, clinical and imaging outcomes, and follow-up outcomes.

Results:

Among the 13 patients, there were 8 males and 5 females (1.6:1). Their presentations included ischemic stroke (69.23%, 9/13) and transient ischemic attack (TIA) (30.77%, 4/13). The aneurysms were dissecting (46.15%, 6/13), saccular (30.77%, 4/13), and saccular combined with thrombosis (23.08%, 3/13) in shape. There were 6 giant aneurysms, 4 large aneurysms, and 3 microaneurysms. Three (23.08%, 3/13) aneurysms were located at the internal carotid artery (ICA) and 10 (76.92%, 10/13) were located in the middle cerebral artery (MCA). A preoperative magnetic resonance perfusion (MRP) examination was performed in all patients, and 9 (69.23%, 9/13) patients showed hypoperfusion. Treatment modalities included stent-assisted embolization, direct clipping, clipping combined with bypass, resection combined with bypass, isolated combined with bypass, proximal occlusion combined with bypass, and the internal carotid artery constriction combined with bypass. Twelve (92.31%, 12/13) patients had no postoperative complications, and temporary complications occurred in 1 (7.69%, 1/13) patient. Aneurysms disappeared in 11 cases and shrank in 2 cases postoperatively. All patients were followed up for 1 to 72 months. We found no new cerebral infarction, no subarachnoid hemorrhage, and no recurrence or enlargement of aneurysms during the follow-up.

Conclusions:

Intracranial anterior circulation aneurysm presenting with cerebral ischemia is rare. Saccular aneurysms with wide neck or thrombosis and dissected aneurysms of the anterior circulation may result in cerebral ischemic attack caused by distal vascular embolism. Individualized treatment should be performed, and cerebral revascularization is an effective treatment for patients with intracranial anterior circulation aneurysms presenting with cerebral ischemia.
Orbital Fat Herniation Through Inferior Orbital Fissure and Persistent Diplopia Caused by Facial Trauma
Authors: Kitai Ryo , Fujisawa Kou , Ueno Shiho
Published: January 2024

Orbital fat herniation is often accompanied by orbital floor fractures. Furthermore, herniation through the inferior orbital fissure (IOF) is rare, and its pathophysiology remains largely unknown. Here, the authors report a case of a patient with IOF herniation and diplopia caused by orbital trauma. The patient was a 58-year-old male who had undergone reduction of a left zygomatic fracture 15 years previously; however, reduction of the lateral orbital wall displacement was not performed at that time. The patient presented with refractory diplopia following a sports-related orbital injury. Although no new facial fractures occurred, an asymmetric IOF herniation was observed in the left orbital fissure, which caused persistent diplopia. Surgical repair of the orbital fat herniation was performed 46 days after injury. Two months after the surgery, the herniation of the orbital fat and diplopia completely disappeared. Surgery for an IOF herniation should be considered when ocular symptoms persist after orbital trauma.
mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions
Authors: Bakos Tamás , Mészáros Tamás , Kozma Gergely Tibor , Berényi Petra , Facskó Réka , Farkas Henriette , Dézsi László , Heirman Carlo , de Koker Stefaan , Schiffelers Raymond , Glatter Kathryn Anne , Radovits Tamás , Szénási Gábor , Szebeni János
Published: January 2024

Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production of inflammatory cytokines, which may be key underlying processes of inflammatory AEs. In serum, Comirnaty and the control PEGylated liposome (Doxebo) caused different rises of C split products, C5a, sC5b-9, Bb and C4d, indicating stimulation of the classical pathway of C activation mainly by the liposomes, while a stronger stimulation of the alternative pathway was equal with the vaccine and the liposomes. Spikevax had similar C activation as Comirnaty, but viral or synthetic mRNAs had no such effect. In autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, Comirnaty caused increases in the levels of sC5b-9 and proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8, whereas heatinactivation of serum prevented the rises of IL-1α, IL-1β, and TNF-α. Clinical C inhibitors, Soliris and Berinert, suppressed vaccine-induced C activation in serum but did not affect cytokine production when applied individually. These findings suggest that the PEGylated lipid coating of mRNA-LNP nanoparticles can trigger C activation mainly via the alternative pathway, which may be causally related to the induction of some, but not all inflammatory cytokines. While innate immune stimulation is essential for the vaccine’s efficacy, concurrent production of C- and PBMC-derived inflammatory mediators may contribute to some of the AEs. Pharmacological attenuation of harmful cytokine production using C inhibitors likely requires blocking the C cascade at multiple points.