bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidural Analgesia Versus Lumbar Plexus Blockade After Hip Reconstruction Surgery in Children With Cerebral Palsy and Intrathecal Baclofen Pumps: A Comparison of Safety and Efficacy
Authors: Samineni Aneesh V. , Eklund Susan E. , Miller Patricia E. , Buxton Kristin , Snyder Brian D. , Matheney Travis H. , Watkins Colyn J. , Stone Scellig S.D. , Alrayashi Walid , Brusseau Roland , Shore Benjamin J.
Published: January 2022

Background:

Epidural analgesia is commonly used for pain control after reconstructive hip surgery, but its use is controversial in the presence of an intrathecal baclofen pump (ITB). The purpose of this retrospective study was to investigate the rate of serious anesthetic and postoperative complications as well as the efficacy of epidural analgesia compared with lumbar plexus blocks (LPBs) for pain management after neuromuscular hip reconstruction in children with cerebral palsy (CP) and ITB.

Methods:

Pediatric patients with CP and ITB undergoing hip reconstructive surgery from 2010 to 2019 were retrospectively identified. Patients receiving epidural analgesia were compared with those receiving LPB. Morphine milligram equivalents per kilogram were used as a surrogate measure for pain-related outcomes, as pain scores were reported with wide ranges (eg, 0 to 5/10), making it unfeasible to compare them across the cohort. Postoperative complications were graded using the modified Clavien-Dindo classification.

Results:

Forty-four patients (26/44, 59% male) underwent surgery at an average age of 10.3 years (SD=3.4 y, range: 4 to 17 y). The majority utilized LPB (28/44, 64%) while the remaining utilized epidural (16/44, 36%). There were no differences in rates of serious complications, including no cases of ITB malfunction, damage, or infection. During the immediate postoperative course, patients who received LPB had higher morphine milligram equivalents per kilogram requirements than patients who received epidural analgesia.

Conclusions:

In patients with CP undergoing hip reconstruction surgery with an ITB in situ, epidural anesthesia was associated with improved analgesia compared with LPB analgesia, with a similar risk for adverse outcomes. Epidural catheters placed using image-guided insertion techniques can avoid damage to the ITB catheter while providing effective postoperative pain control without increasing rates of complications in this complex patient population.

Level of Evidence:

Level III.
Acupuncture – a national heritage of China to the world: international clinical research advances from the past decade
Authors: Liu Baoyan , Chen Bo , Guo Yi , Tian Lixin
Published: January 2022

Acupuncture originated in China and is an important component of traditional Chinese medicine. The elucidation of its anesthetic mechanisms, the medical needs of Western societies, as well as the proven therapeutic effects of this technique have made it the most widely used medical practice in the world. The concept of evidence-based medicine has been introduced in acupuncture research for technical improvement and the production of high-quality clinical evidence. Upon reviewing the acupuncture clinical research over the past 10 years, we found the gradually increasing range of diseases that it benefits, from pain management to neoplasms and genitourinary, digestive, and mental disorders. Acupuncture is included in a number of international guidelines for clinical practice. However, high-quality clinical evidence to support the efficacy and effectiveness of acupuncture is lacking as a result of multiple exceptional clinical trials conducted by Western researchers that have yielded antagonistic results. Future clinical research should focus on exploring objective evaluation methods for studying the therapeutic effects of acupuncture.
Assessment of Occupational Exposure in Medical Practice in the Region of Hohhot, China, for the Period 2004–2020
Authors: Xu Xiao , Fan Shengnan , Tang Xiaohao , Li Mengxue , Liu Xiang , Zhang Ziyang , Zhang Shuai , Sun Zhichao , Deng Jun
Published: January 2022

Individual monitoring is of great significance in efforts to protect the health of radiation workers and improve the level of radiation protection and management. This paper presents a retrospective analysis of occupational exposure to ionizing radiation from medical practice in the region of Hohhot, China, from 2004 to 2020. Results show that the average annual effective dose of occupationally exposed workers in medical practice significantly declined from 1.44 mSv in 2005 to 0.29 mSv in 2020 (Z = −5.23, P < 0.05). The number of medical radiation workers increased by 181%, the composition of radiation workers whose average annual effective dose exceeded 1 mSv decreased, and the number of radiation workers whose average annual effective dose was less than or equal to the minimum detection level (MDL) increased yearly over the 17-y study period. It was found that the dose of 1.106 mSv received by workers in interventional radiology is significantly higher than the doses of 0.52 mSv in dental radiology, 0.47 mSv in radiotherapy, and 0.33 mSv in all other medical uses (Z = 3.71, 9.13, 5.93, respectively; P < 0.05). The distribution ratios of workers in nuclear medicine and interventional radiology whose annual individual effective dose exceeded 5 mSv were 0.040 and 0.043, respectively, which are significantly higher than those in other occupational categories (χ
2 = 307.11, P < 0.05). It was also shown that the average annual effective dose of 0.67 mSv in interventional radiology is significantly higher than that of 0.17 mSv in radiotherapy (Z = 3.39, P < 0.05) in 2020. According to these observations, the exposure of radiation workers in medical practice in Hohhot meets the requirements of the China standard. This study shows that the status of radiation workers in medical practice has obviously improved during the period 2004–2020. However, it is still necessary to focus on the protection of groups with high occupational exposure risk, and the continuous improvement of protection measures, monitoring means, and radiation workers’ training, especially for the workers in the fields of interventional radiology and nuclear medicine.
Patient Pathways in Cardiology: Should Pharmaceutical and Medical Device Companies Care?
Authors: Kwok Chun Shing , Muntean Elena-Andra , Foster Will , Mallen Christian D.
Published: January 2022

A shared goal of patients, providers, and the companies that produce new therapies is to have these therapies used according to guidelines. Health services specialize in patient care and may lack the capabilities to take a product from conception through to everyday use. This results in a mutually beneficial relationship between health services and industry. The market for cardiovascular drugs is significant, which results in competition between companies. While traditional methods of observational analysis may be able to determine to what extent drugs and devices are being prescribed or implanted by health providers, there is less real-world patient level insight as to why patients are taking (or not taking) these treatments and why one agent is chosen over another. Considering patient pathways is a novel approach that can be utilized to understand real-world patient activities. This approach focuses on the patient flow across the healthcare system and barriers at each stage including identification of patients, diagnostic testing, the decisions on treatment, and prescribing can help identify ways of improving the utilization based on guidelines. It overcomes several assumptions related to patient and clinician decision-making and practical considerations such as geography and availability of health services. In this article, we introduce the concept of patient pathways and why considering them maybe of interest to companies. As significant resources are invested to bring a product to market, this approach can help define if there are missed opportunities for their products to be utilized and potential barriers to implementation.
TRANSSCLERAL INCISION FOR PEELING SUBRETINAL PROLIFERATION TISSUE IN GRADE C PROLIFERATIVE VITREORETINOPATHY
Authors: Fan Wen , Shen Han , Su Na , Yuan Songtao
Published: January 2022

Purpose:

The purpose of this study was to investigate the clinical outcomes of an optimized method to clearly remove the subretinal proliferative tissue by transscleral puncture into the subretinal space in patients with grade C proliferative vitreoretinopathy without inducing retinal injury.

Methods:

This was a prospective clinical observation study. Eight consecutive patients who had undergone optimized vitrectomy surgery for retinal detachment complicated by grade C proliferative vitreoretinopathy were investigated. Subretinal proliferation was cleared by adding one additional scleral 23-gauge trocar under the detached retina at 9 mm to 10 mm from the limbus. After the sclera is pierced, the puncture knife changed its direction without touching the retina. 23-G intraocular forceps were used to remove the proliferation strand or membrane through the puncture channel.

Results:

Retinal reattachment was achieved in each case without a retinotomy. The mean best-corrected visual acuity was improved within the first 1 month (P = 0.039) and remained stable at the following phase. There were no postoperative complications, such as reoccurrence of retinal detachment or proliferative vitreoretinopathy. No postoperative hemorrhage or hypotension was observed.

Conclusion:

The satisfying results demonstrated the feasibility of this cost-effective, easy-to-follow, transscleral vitrectomy method in treating retinal detachment with grade C proliferative vitreoretinopathy.
CAROTID CAVERNOUS SINUS FISTULA FINDINGS IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BEFORE AND AFTER PERCUTANEOUS EMBOLIZATION
Authors: del Mar Schilt-Catafal Maria , Pastor-Escartín Félix , Martínez-Piñero Ana , Neira-Ibáñez Paulina , Manfreda-Domínguez Laura , Duch-Samper Antonio M.
Published: January 2022

Background/Purpose:

Optical coherence tomography angiography has been used to evaluate the posterior segment in a wide variety of pathologies because it is a noninvasive image technique, but its role in the evaluation of the retina in a case of carotid cavernous sinus fistula has not been described yet.

Methods & Results:

We present a patient who consulted with spontaneous left superior eyelid hematoma and was diagnosed with left indirect carotid cavernous sinus fistula. In this study, optical coherence tomography angiography was used to evaluate the different macular capillary plexuses in a patient with carotid cavernous sinus fistula and a clinical situation of secondary local venous stasis before and after percutaneous embolization. Augmented vessel density was seen in superficial and deep capillary plexuses and in choriocapillaris before the percutaneous embolization, and a decrease of the parameters was seen after the treatment.

Conclusion:

All macular capillary plexuses presented with augmented vessel density levels that normalized after treatment. These findings were previously undescribed, and they suggest that optical coherence tomography angiography may be useful to initially evaluate patients with carotid cavernous sinus fistula who are planned to undergo embolization and to follow them up until normalization of the vascular structures is reported.
PACHYCHOROID DISEASE ASSOCIATED WITH GEOGRAPHIC ATROPHY AND SUBRETINAL DRUSENOID DEPOSITS
Authors: Manayath George J. , Verghese Shishir , Narendran Venkatapathy
Published: January 2022

Purpose:

To report an atypical case of pachychoroid spectrum disease associated with subretinal drusenoid deposits and geographic atrophy.

Methods:

Case report.

Results:

A 67-year-old woman presented for a routine examination. Her best-corrected visual acuity was 20/20 in both eyes. Based on fundus examination and multimodal imaging findings, the presence of subretinal drusenoid deposits and geographic atrophy was seen in the right eye, which was associated with pachychoroid. The left eye revealed two active polypoidal lesions suggestive of polypoidal choroidal vasculopathy with subretinal drusenoid deposits, geographic atrophy, and a thick choroid with dilated outer choroidal vessels. She underwent an intravitreal injection of ranibizumab followed by focal laser to the polypoidal lesion in the left eye. At 3-month posttreatment, her best-corrected visual acuity was maintained at 20/20 in the left eye, with a good anatomical outcome.

Conclusion:

This case highlights a previously unreported unique association of a pachychoroid disease spectrum with geographic atrophy and with subretinal drusenoid deposits.
FULL-THICKNESS MACULAR HOLE FORMATION FOLLOWING PANRETINAL PHOTOCOAGULATION FOR PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Alsberge Joseph B. , McDonald H. Richard
Published: January 2022

Purpose:

To report two patients who developed full-thickness macular holes following panretinal photocoagulation for proliferative diabetic retinopathy.

Methods:

Case series.

Results:

Case 1 was a 58-year-old woman with Type 1 diabetes mellitus and proliferative diabetic retinopathy and Case 2, a 72-year-old man with Type 2 diabetes mellitus and proliferative diabetic retinopathy. Before panretinal photocoagulation, each patient had an epiretinal membrane and an irregular foveal contour noted on optical coherence tomography. At 2 months follow-up, each patient showed foveal floor thinning and Case 2 also had a lamellar macular hole. At 6 months follow-up, each patient had a full-thickness macular hole. Each were successfully repaired with vitrectomy, membrane peeling, and gas tamponade.

Conclusion:

The relationship between hole formation and previous panretinal photocoagulation in the patients reported here is unclear and possibly coincidental.
Outcomes of Surgical Interventions in Primary Congenital Glaucoma Patients
Authors: Suvannachart Pukkapol , Surukrattanaskul Supawan , Chansangpetch Sunee , Manassakorn Anita , Tantisevi Visanee , Rojanapongpun Prin
Published: January 2022

Purpose:

The aim was to report long-term surgical success of primary congenital glaucoma (PCG) patients in Thailand.

Materials and Methods:

PCG patients who underwent one of the following primary operations: trabeculotomy, goniotomy, trabeculectomy, combined trabeculotrabeculectomy (CTT) and diode transscleral cyclophotocoagulation (TSCPC) between January 1992 and January 2018 were reviewed. Surgical success was defined as intraocular pressure (IOP) between 5 and 21 mm Hg with or without antiglaucoma medications. Failure was defined as IOP ≤5 or ≥21 mm Hg for 2 consecutive visits, or when an additional glaucoma surgery was required to control IOP. Survival curves were analyzed using multilevel mixed-effect Weibull model.

Results:

A total of 81 eyes from 55 PCG patients were included. Surgical procedures involved 20 goniotomies, 15 trabeculotomies, 16 trabeculectomies, 15 CTT, and 15 TSCPC. Median follow-up time was 24 months (interquartile range: 9 to 60 mo). Overall success rates were 68.8% at 1 year, 63.8% at 3 years, and 53.7% at 5 years. All types of surgery except TSCPC had comparable cumulative 1 year success rates ranging from 78.5% to 83.3%. Cumulative success rates of trabeculotomy (80.05%) and CTT (79.4%) were maintained at 3 and 5 years and were the highest among all procedures at 5 years. TSCPC had a significantly lower success rate compared with other types of surgery (hazard ratio: 7.4 to 13.1, all P=0.01). All patients receiving primary TSCPC showed no success at 48 months.

Conclusion:

Primary trabeculotomy and primary CTT demonstrated the highest long-term success rates in PCG patients.
Clinical Features and Corrected Factors with Neurosyphilis in HIV/Syphilis Co-Infected Patients Based on Stage of Syphilis
Authors: Wang Yuan-Yuan , Shi Mei , Guan Zhi-Fang , Zhang Lei , Gu Xin , Lu Hai-Kong , Qi Teng-Fei , Ni Li-Yan , Wu Juan , Zhao Wei , Peng Rui-Rui , Zhu Lin , Zhou Ping-Yu
Published: January 2022

Objective:

Neurosyphilis is challenging to diagnose, especially in patients with human immunodeficiency virus (HIV)/syphilis co-infection. The aim of this study was to profile the clinical features of neurosyphilis and evaluate the correlation between neurosyphilis and clinical or laboratory factors among patients with HIV/syphilis co-infection.

Methods:

We retrospectively analyzed the data of 479 HIV/syphilis co-infected patients examined between August 2009 and September 2018. A multivariate logistic regression model was used to identify factors correlated with neurosyphilis.

Results:

The overall prevalence of neurosyphilis was 21.7%. The prevalence of neurosyphilis differed among patients with primary (11.1%), secondary (20.1%), and latent syphilis (29.1%). The prevalences of neurosyphilis in patients with serological non-response and serofast patients were 26.1% and 6.3%, respectively, while 12.5% of patients with serological relapse had neurosyphilis. Patients with secondary and latent syphilis had serum rapid plasma reagin (RPR) titers (per unit) of 1.44-fold [95% confidence interval (CI): 1.08–1.93, P 
= 0.014] and 2.73-fold (95% CI: 1.49–5.00, P 
= 0.001), respectively, which increased the risk of confirmed neurosyphilis. Among patients with latent syphilis, a serum RPR titer of ≥1:32 and peripheral blood CD4 cell count of ≤350/mL were significantly associated with neurosyphilis, with adjusted odds ratios of 9.45 (95% CI: 1.86–48.03, P 
= 0.007) and 3.75 (95% CI: 1.11–12.66, P 
= 0.033), respectively.

Conclusion:

A serum RPR titer of ≥1:32 and a peripheral blood CD4 cell count of ≤350/mL have predictive value in screening for neurosyphilis among HIV-positive patients with latent syphilis.
2021 ELSO Adult and Pediatric Anticoagulation Guidelines
Authors: McMichael Ali B.V. , Ryerson Lindsay M. , Ratano Damian , Fan Eddy , Faraoni David , Annich Gail M.
Published: January 2022

Disclaimer:

These guidelines for adult and pediatric anticoagulation for extracorporeal membrane oxygenation are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise. These guidelines do not take the place of physicians’ and other health professionals’ judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.
A Simple Technique for Reliable Donor Organ Temperature Management With the SherpaPak System
Authors: Kawabori Masashi , Posawatz David A. , Chen Frederick Y. , Couper Gregory S.
Published: January 2022

Here, we present our technique for thermoregulation of cardiac preservation solution with the SherpaPak device before heart transplantation. If it is above the ideal range (5–10°C) to avoid organ injury and ensure proper function, the cardiac preservation solution bag should be placed in ice water to bring down temperature until the ideal range is achieved. SherpaPak has limitation in immediately correcting initial temperatures outside of the normal range, so we believe this simple step should be included into standard SherpaPak procedure to ensure its effectiveness and to preserve the best organ function.
Changes in the characteristics of trauma patients after the early COVID-19 outbreak
Authors: Park Jiye , Jung Kyoungwon , Kwon Junsik , Moon Jonghwan , Huh Yo , Heo Yun Jung , Kang Byung Hee
Published: January 2022

Gyeonggi-do (Gyeonggi province) has the second highest number of coronavirus disease (COVID-19) cases in the Republic of Korea after Seoul, with approximately 25% of the COVID-19 patients as of January 2021. Our center is a level I trauma center located in south Gyeonggi-do, and we aimed to evaluate whether the characteristics of trauma patients changed after the COVID-19 pandemic.

We retrospectively reviewed the trauma patients registered with the Korea Trauma Database of the Center from February 2019 to January 2021. The patients were dichotomized into pre-coronavirus disease (pre-COVID) and coronavirus disease (COVID) groups, and their trauma volumes, injury characteristics, intentionality, and outcomes were compared.

A total of 2628 and 2636 patients were included in the pre-COVID and COVID groups, respectively. During the COVID-19 period, motorcycle accidents, bicycle accidents, and penetrating injury cases increased, and pedestrian traffic accidents, slips, and injury by machines decreased. The average daily number of patients in the COVID group was lower in March (5.6 ± 2.6/day vs 7.2 ± 2.4/day, P = .014) and higher in September (9.9 ± 3.2/day vs 7.7 ± 2.0/day, P = .003) compared to the pre-COVID group. The COVID group also had a higher ratio of direct admissions (67.5% vs 57.2%, P < .001), proportion of suicidal patients (4.1% vs 2.7%, P = .005), and injury severity scores (14 [9–22] vs 12 [4–22], P < .001) than the pre-COVID group. The overall mortality (4.7% vs 4.9%, P = .670) and intensive care unit length of stay (2 [0–3] days vs 2 [0–4] days, P = .153) was not different between the 2 groups.

Although the total number of patients did not change, the COVID-19 pandemic affected the number of monthly admissions and the injury mechanisms changed. More severely injured patients were admitted directly to the trauma center.
Reducing Opioid-Induced Constipation Post-Cardiac Surgery
Authors: Rodrigues Miranda A. , Lofton Tochie , Tume Sebastian C. , Lemming Katherine I.
Published: January 2022

Background:

Pain management with opioids and underutilization of prophylaxis for constipation can prolong a patient's hospital length of stay and impede pain management efforts.

Problem:

In pediatric postoperative cardiac patients, opioid therapy is a common approach to pain management but often places them at greater risk for constipation due to anatomy and age.

Methods:

A retrospective review of 50 patients' medical records for baseline data was conducted, and a survey evaluated providers' current knowledge and practice.

Interventions:

The intervention was an electronic order set that provided decision support. Additionally, prophylactic measures were supported by a validated assessment tool that created a common language to report constipation risk.

Results:

Although not statistically significant, postintervention data demonstrated a 21.5% decrease in postoperative constipation and a 57% increase in ordered bowel regimens.

Conclusion:

More focus is needed toward prophylactic bowel regimens to reduce the risk in this already high-risk population.
Using Experiential Learning to Affect Perceived Knowledge of Disaster Preparedness Among Hospital-Based Personnel
Authors: Shostrand Lisa M. , Miller Genina , Bowers Cynthia
Published: January 2022

Perceived knowledge deficits in disaster preparedness are widespread among hospital-based nurses and healthcare professionals. Experiential learning programs provide enhanced disaster preparedness familiarity among hospital-based healthcare staff. A disaster preparedness education class was offered at a midwestern suburban hospital to promote increased knowledge perception. The Emergency Preparedness Information Questionnaire was administered to assess disaster preparedness familiarity. The posttest scores after the experiential learning yielded statistically significant results (t = 46.90, p < .001) for increased disaster preparedness familiarity.
PTP-PEST Regulated Membranous/Cytoplasmic Translocation of p120ctn in the Lung Cancer Resistance to Tyrosine Kinase Inhibitor
Authors: Liu Wei-Wei , Hu Jing , Zhao Yue , Wang Rui , Han Qiang , Rong Xue-Zhu , Wang Si-Yao , Wang En-Hua , Wu Mei-Xi , Wang Si , Liu Yang
Published: January 2022

Our previous studies indicate that resistance induction using first-generation tyrosine kinase inhibitors (TKIs) in lung cancer is accompanied with p120-catenin (p120ctn) cytoplasmic translocation from the membrane. However, the molecular mechanism underlying p120ctn intracytoplasmic translocation has not yet been reported. We performed immunohistochemistry to detect the correlation of p120ctn distribution with protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) and p120ctn Y335 phosphorylation levels in non–small cell lung cancer (NSCLC) patients. After resistance induction using first-generation TKIs in lung cancer cells, Western blotting and substrate trapping were used to assess PTP-PEST expression and its influence on p120ctn Y335 phosphorylation, as well as the role of p120ctn Y335 phosphorylation on the association of p120ctn with E-cadherin and p120ctn membrane/cytoplasm translocation. In 197 samples collected from NSCLC patients, cytoplasmic p120ctn and enhanced p120ctn Y335 phosphorylation were associated with decreased PTP-PEST. After resistance induction using gefitinib, decreased PTP-PEST expression was accompanied by enhanced phosphorylation of p120ctn Y335 and p120ctn translocated to the cytoplasm. In gefitinib-resistant cells, PTP-PEST overexpression restrained p120ctn Y335 phosphorylation and restored membrane p120ctn expression. PTP-PEST enhanced the interaction of p120ctn with E-cadherin and elevated p120ctn membrane expression. However, increased p120ctn-Y335F mutant had no effect on p120ctn interaction with E-cadherin and membrane/cytoplasm translocation compared with the control group. In conclusion, resistance to first-generation TKIs inhibited PTP-PEST expression, which promoted p120ctn-Y335 phosphorylation and reduced the interaction of p120ctn with E-cadherin, resulting in p120ctn cytoplasmic translocation.
Induction of Cellular Senescence in Rat Vaginal Fibroblasts and Treatment With Senolytics: An in Vitro Model for the Study of Pelvic Organ Prolapse
Authors: Florian-Rodriguez Maria E. , Hare Adam M. , Gaddam Neha G. , Shi Haolin , Keller Patrick , Word Ruth Ann
Published: January 2022

Objective

The objective of this study was to develop an in vitro model of cellular senescence using rat vaginal fibroblasts and determine the effects of treatment with senolytics.

Methods

Rat vaginal tissue biopsies were collected. Primary vaginal fibroblasts were isolated and characterized by immunofluorescence. To induce cellular senescence, fibroblasts were treated with etoposide at 3, 10, and 20 mM for 24 hours, followed by treatment with the senolytics dasatinib (1 mM) and/or quercetin (20 mM). After treatment, RNA was extracted and the expression of selected genes was quantified. Immunostaining of senescence markers was also performed.

Results

Fibroblasts were confirmed by positive immunostaining for α-smooth muscle actin and vimentin, and negative immunostaining for pan-cytokeratin. Treatment with etoposide resulted in a dose-dependent increase in expression of the senescence-associated secretory phenotype markers MMP-7, MMP-9, and IL-b1 (P < 0.05) compared with controls. Immunostaining showed increased expression of γ-H2A and p21 after treatment with etoposide. Cells treated with dasatinib and quercetin after etoposide treatment had decreased expression of p21, MMP-7, MMP-9, and IL-1b compared with cells treated only with etoposide (P < 0.05).

Conclusions

Upregulation of senescence-associated factors provided evidence that senescence can be induced in vaginal fibroblasts in vitro. Furthermore, treatment with the senolytics dasatinib and quercetin abrogated the senescence phenotype induced by etoposide in rat vaginal fibroblasts. Our findings provide a novel model for the study and development of new therapies targeting the disordered extracellular matrix associated with pelvic organ prolapse.
Comparison of Amantadine, Modafinil, and Standard of Care in the Acute Treatment of Disorders of Consciousness After Severe Traumatic Brain Injury
Authors: Hintze Trager D. , Small Clay E. , Montgomery Josephine , Reveles Kelly R. , Hafeez Shaheryar , Barthol Colleen A.
Published: January 2022

Objective

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Many patients who experience severe TBI have persistent disorders of consciousness. Amantadine and modafinil are used for some neurological disorders; however, a comparison of the 2 medications in TBI has not been reported. This study compared the effectiveness of amantadine, modafinil, and standard of care (SOC) on disorders of consciousness after TBI.

Methods

All adult TBI patients admitted between January 1, 2017, and September 31, 2020 who received amantadine, modafinil, or SOC treatments were screened. Data collection included: demographics, change in Glasgow Coma Scale (GCS), location of hemorrhage, medication duration, intensive care unit and hospital length of stay, adverse drug reactions, and concomitant sedative medications. Patients in the amantadine and modafinil groups were matched 1:2 with patients who received SOC therapies. The primary outcome was change in GCS ≥ 3 from baseline to discharge.

Results

A total of 142 patients met inclusion criteria. Medications were initiated a median of 8 days from admission. Patients in the SOC group experienced a greater improvement in GCS and shorter hospital length of stay compared with amantadine. A change in GCS ≥ 3 from medication initiation to hospital discharge occurred in 46.5% of amantadine patients and 53.8% of modafinil patients.

Conclusions

In this study, TBI patients did not benefit from amantadine or modafinil compared with SOC therapies, and no differences were found between medication groups. Further studies are warranted to determine whether the addition of amantadine or modafinil in the weeks after TBI provides benefit.
Vitamin E in the treatment of tardive dyskinesia: a meta-analysis
Authors: Xu Hongyan , Qin Haoqiang , Chen Shaohua , Guan Mingjian
Published: January 2022

Long-term use of antipsychotic drugs is associated with tardive dyskinesia. At present, there is no satisfactory treatment for tardive dyskinesia. Some randomized trials suggested that vitamin E can improve tardive dyskinesia. This study was undertaken to evaluate the effects of vitamin E treatment for tardive dyskinesia. We searched internet databases for randomized controlled trials. A total of 21 studies including 854 patients with tardive dyskinesia were included in this meta-analysis. Eighteen studies reported the Abnormal Involuntary Movements Scale (AIMS) as the primary outcome. After vitamin E treatment, a decrease of 2.36 (95% CI = −3.27 to −1.45; P < 0.00001) in the AIMS was observed in the treatment group, compared with the control group. Vitamin E may offer a new avenue treatment for tardive dyskinesia.
APOE ε4 effects on hippocampal atrophy in the healthy elderly reflect future cognitive decline
Authors: Zhang Linda , Calero Miguel , Medina Miguel , Strange Bryan A.
Published: January 2022

The APOE ε4 allele is the primary genetic risk factor for late onset Alzheimer’s disease (AD). A cardinal problem in determining APOE ε4’s effect on cognition and brain structure in older individuals is dissociating prodromal changes – linked to increased AD risk – from potential phenotypic differences. To address this, we used cognitive and neuroimaging data from a large cohort of cognitively normal 69-86 year-olds with up to 8 yearly follow-ups to investigate cross-sectional and longitudinal differences between APOE ε3/ε3 homozygotes and ε3/ε4 heterozygotes. Although we found a significant age-by-genotype interaction in right hippocampal volume, once our analyses were conditionalised by future diagnosis to account for prodromal mild cognitive impairment (MCI) and AD, this effect was no longer observed. Likewise, longitudinally, rate of hippocampal atrophy was determined not by genotype, but by future diagnosis. Thus, we provide direct evidence in support of the prodromal hypothesis of APOE ε4 on brain structure.
Subsequent hip fractures in patients identified by a Fracture Liaison Service (FLS) in England and Wales – linkage of the national FLS and Hip Fracture databases
Authors: Javaid MK , Mohsin Z , Johansen A , Gregson CL , Pinedo-Villanueva R
Published: January 2022

Fracture Liaison Services (FLSs) are recommended healthcare models to deliver secondary fracture prevention and reduce the risk of subsequent fractures. Several studies have demonstrated the cost and clinical effectiveness of FLSs, but there is little real-world data on the impact of FLSs on subsequent hip fracture rates.

A cohort of 50,214 patients from the national FLS database with an index fracture of the hip, spine, or other in 2017 was linked to the National Hip Fracture Database from 2017 to 2020 to identify those patients who went on to have a subsequent hip fracture.

One in twenty (5.1%) of the 9,888 people in whom the index fracture was at the hip went on to suffer a second hip fracture within 3-4 years, despite receiving the support of an FLS. The risk of hip fracture was similar (4.7%) if the index fracture was at the spine, but lower at other sites (2.8%, p<0.001) and the interval shortest after an index hip fracture (1.1 years (0.4,2.0) p<0.001). The proportion of patients with a subsequent hip fracture was not lower by types of anti-osteoporotic medication.

This work highlights the need for alternative anti-osteoporotic management strategies to rapidly decrease the risk of subsequent hip fractures for people seen by an FLS setting with levels of risk that are even higher for patients in areas which are still not served by an FLS.
COVID-19 vaccine booster induces a strong CD8+ T cell response against Omicron variant epitopes in HLA-A*02:01+ individuals
Authors: Nguyen Andrea T. , Szeto Christopher , Chatzileontiadou Demetra S.M. , Tong Zhen Wei Marcus , Dewar-Oldis Michael J. , Cooper Lucy , Murdolo Lawton D. , Chew Keng Yih , Lineburg Katie E. , Riboldi-Tunicliffe Alan , Williamson Rachel , Gardiner Bradley J. , Jayasinghe Dhilshan , Lobos Christian A. , Ahn You Min , Grant Emma J. , Smith Corey , McMahon James , Good-Jacobson Kim L. , Barnard Peter J. , Short Kirsty R. , Gras Stephanie
Published: January 2022

The >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster.

One-Sentence Summary

CD8+ T cells response against Omicron variant epitopes is stronger after the vaccine booster.
A truncated form of the p27 CDK inhibitor translated from pre-mRNA causes G2-phase arrest
Authors: Kaida Daisuke , Satoh Takayuki , Ishida Ken , Yoshimoto Rei , Komori Kanae
Published: January 2022

Pre-mRNA splicing is an indispensable mechanism for eukaryotic gene expression. Splicing inhibition causes cell cycle arrest at G1 and G2/M phases, which is thought to be one of the reasons for the potent antitumor activity of splicing inhibitors. However, the molecular mechanisms underlying the cell cycle arrest have many unknown aspects. In particular, the mechanism of G2/M-phase arrest caused by splicing inhibition is completely unknown. Here, we found that lower and higher concentrations of pladienolide B caused M-phase and G2-phase arrest, respectively. We analyzed protein levels of cell cycle regulators and found that a truncated form of the p27 CDK inhibitor, named p27*, accumulates in G2-arrested cells. Overexpression of p27* caused partial G2-phase arrest. Conversely, knockdown of p27* accelerated exit from G2/M phase after washout of splicing inhibitor. These results suggest that p27* contributes to G2/M-phase arrest caused by splicing inhibition. We also found that p27* bound to and inhibited M-phase cyclins, although it is well known that p27 regulates G1/S transition. Intriguingly, p27*, but not full-length p27, was resistant to proteasomal degradation and remained in G2/M phase. These results suggest that p27*, which is a very stable truncated protein in G2/M phase, contributes to G2-phase arrest caused by splicing inhibition.
Optineurin mediates delivery of membrane from transferrin receptor-positive endosomes to autophagosomes
Authors: Bansal Megha , Sirohi Kapil , Moharir Shivranjani C , Swarup Ghanshyam
Published: January 2022

Autophagy is a conserved quality control mechanism that removes damaged proteins, organelles and invading bacteria through lysosome-mediated degradation. During autophagy several organelles including endoplasmic reticulum, mitochondria, plasma membrane and endosomes contribute membrane for autophagosome formation. However, the mechanisms and proteins involved in membrane delivery to autophagosomes are not clear. Optineurin (OPTN), a cytoplasmic adaptor protein, is involved in promoting maturation of phagophores into autophagosomes; it is also involved in regulating endocytic trafficking and recycling of transferrin receptor (TFRC). Here, we have examined the role of optineurin in the delivery of membrane from TFRC-positive endosomes to autophagosomes. Only a small fraction of autophagosomes was positive for TFRC, indicating that TFRC-positive endosomes could contribute membrane to a subset of autophagosomes. The percentage of TFRC-positive autophagosomes was reduced in Optineurin knockout mouse embryonic fibroblasts (Optn−/− MEFs) in comparison with normal MEFs. Upon over-expression of optineurin, the percentage of TFRC-positive autophagosomes was increased in Optn−/− MEFs. Unlike wild-type optineurin, a disease-associated mutant, E478G, defective in ubiquitin binding, was not able to enhance formation of TFRC-positive autophagosomes in Optn−/− MEFs. TFRC degradation mediated by autophagy was decreased in optineurin deficient cells. Our results suggest that optineurin mediates delivery of TFRC and perhaps associated membrane from TFRC-positive endosomes to autophagosomes, and this may contribute to autophagosome formation.
Correlations in sleeping patterns and circadian preference between spouses
Authors: Richmond Rebecca C , Howe Laurence J , Heilbron Karl , Jones Samuel , Liu Junxi ,   23andMe Research Team, Wang Xin , Weedon Michael N , Rutter Martin K , Lawlor Deborah A , Smith George Davey , Vetter Céline
Published: January 2022

Spouses may affect each other’s sleeping behaviour. In 47,420 spouse-pairs from the UK Biobank, we found a weak positive phenotypic correlation between spouses for self-reported sleep duration (r=0.11; 95% CI=0.10, 0.12) and a weak inverse correlation for chronotype (diurnal preference) (r=-0.11; -0.12, -0.10), which replicated in up to 127,035 23andMe spouse-pairs. Using accelerometer data on 3,454 UK Biobank spouse-pairs, the correlation for derived sleep duration was similar to self-report (r=0.12; 0.09, 0.15). Timing of diurnal activity was positively correlated (r=0.24; 0.21, 0.27) in contrast to the inverse correlation for chronotype. In Mendelian randomization analysis, positive effects of sleep duration (mean difference=0.13; 0.04, 0.23 SD per SD) and diurnal activity (0.49; 0.03, 0.94) were observed, as were inverse effects of chronotype (−0.15; -0.26, -0.04) and snoring (−0.15; -0.27, -0.04). Findings support the notion that an individual’s sleep may impact that of their partner, with implications for sleep health.
Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: a retrospective cohort study
Authors: Hay James A. , Kissler Stephen M. , Fauver Joseph R. , Mack Christina , Tai Caroline G. , Samant Radhika M. , Connolly Sarah , Anderson Deverick J. , Khullar Gaurav , MacKay Matthew , Patel Miral , Kelly Shannan , Manhertz April , Eiter Isaac , Salgado Daisy , Baker Tim , Howard Ben , Dudley Joel T. , Mason Christopher E. , Nair Manoj , Huang Yaoxing , DiFiori John , Ho David D. , Grubaugh Nathan D. , Grad Yonatan H.
Published: January 2022

Background

The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

Methods

We characterized 2,875 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of variant, symptom status, age, infection history, vaccination and antibody titer to founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

Results

Among individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.2-53.6%) remained potentially infectious (Ct<30) five days post detection, with small differences across variants and vaccination history. Only seven viral rebounds (0.7%; N=999) were observed, with rebound defined as 3+ days with Ct<30 following an initial clearance of 3+ days with Ct≥30. High antibody titers against the founder SARS-CoV-2 strain predicted lower peak viral loads and shorter durations of infection. Among Omicron BA.1 infections, boosted individuals had lower pre-booster antibody titers and longer clearance times than non-boosted individuals.

Conclusions

SARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines.

Funding

Supported in part by CDC contract 200-2016-91779, Emergent Ventures at the Mercatus Center, the Huffman Family Donor Advised Fund, the MorrisSinger Fund, the National Basketball Association, and the National Basketball Players Association.
Involvement of prelimbic cortex neurons and related circuits in the acquisition of cooperative learning by pairs of rats
Authors: Conde-Moro A.R. , Rocha-Almeida F. , Gebara E. , Delgado-García J.M. , Sandi C. , Gruart A.
Published: January 2022

Social behaviors such as cooperation are crucial for mammals. A deeper knowledge of the neuronal mechanisms underlying cooperation can be beneficial for people suffering from pathologies with impaired social behavior. Our aim was to study the brain activity when two animals synchronize their behavior to obtain a mutual reinforcement. In a previous work, we showed that the activity of the prelimbic cortex (PrL) was enhanced during cooperation in rats, especially in the ones leading most cooperative trials (leader rats). In this study, we investigated the specific cell type/s in the PrL contributing to cooperative behaviors. To this end, we collected rats’ brains at key moments of the learning process to analyze the levels of c-FOS expression in the main cellular groups of the PrL (glutamatergic cells containing D1 and D2 receptors and interneurons). Leader rats showed increased c-FOS activity in cells expressing D1 receptors during cooperation. In addition, we analyzed the levels of anxiety, dominance, and locomotor behavior, finding that leader rats are in general less anxious and less dominant than followers. We also recorded local field potentials (LFPs) from the PrL, the nucleus accumbens septi (NAc), and the basolateral amygdala (BLA). Spectral analysis showed that delta activity in PrL and NAc increased when rats cooperated, while BLA activity in delta and theta bands decreased considerably during cooperation. The PrL and NAc also increased their connectivity in the high theta band during cooperation. Thus, the present work identifies the specific PrL cell types engaged in this behavior, as well as its connectivity with subcortical brain regions (BLA, NAc) during cooperation.

Significance Statement

Brain mechanisms underlying cooperative behaviors remain unknown. The present study identified specific neuronal types from the PrL cortex engaged in the acquisition of a cooperative task, as well as their connectivity with subcortical projection sites, such as the NAc and the BLA during cooperation. Rats leading the cooperation trials (designated leaders) presented an increased activation of D1-containing neurons in the PrL during cooperation. The PrL and NAc electrical activity increased when rats were cooperating, while the BLA activity increased before cooperation. The PrL and NAc showed increased functional connectivity at the moment of cooperation on the platform, whereas during the individual phase the highest connectivity was found before the animals climbed individually onto the platform.
AAV11 permits efficient retrograde targeting of projection neurons
Authors: Han Zengpeng , Luo Nengsong , Kou Jiaxin , Li Lei , Ma Wenyu , Peng Siqi , Xu Zihong , Zhang Wen , Qiu Yuxiang , Wu Yang , Wang Jie , Ye Chaohui , Lin Kunzhang , Xu Fuqiang
Published: January 2022

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.

Highlights

Naturally occurring AAV serotype capsid exhibits robust retrograde functionality

Improved distribution properties and retrograde transport efficiency

Can express Cre recombinase or calcium-sensitive functional probe for neural circuits monitoring

Can specifically target astrocytes