bluuebunny/crossref_metadata_2025 huggingface dataset:
Robot Assisted MRI-Guided LITT of the Anterior, Lateral, and Medial Temporal Lobe for Temporal Lobe Epilepsy
Authors: Gupta Kunal , Dickey Adam S. , Hu Ranliang , Faught Edward , Willie Jon T.
Published: November 2020

Robotic systems have fundamentally altered the landscape of functional neurosurgery. These allow automated stereotaxy with high accuracy and reliability, and are rapidly becoming a mainstay in stereotactic surgeries such as deep brain stimulation (DBS), stereoelectroencephalography (SEEG), and stereotactic laser ablation/MRI guided laser interstitial thermal therapy (MRgLITT). Robotic systems have been effectively applied to create a minimally invasive approach for diagnostics and therapeutics in the treatment of epilepsy, utilizing robots for expeditious and accurate stereotaxy for SEEG and MRgLITT. MRgLITT has been shown to approach open surgical techniques in efficacy of seizure control while minimizing collateral injury. We describe the use of robot assisted MRgLITT for a minimally invasive laser anterior temporal lobotomy, describing the approach and potential pitfalls. Goals of MRgLITT are complete ablation of the epileptogenic zone and avoiding injury to uninvolved structures. In the middle fossa these include structures such as cranial nerves in the skull base and cavernous sinus and the thalamus. These can be mitigated with careful trajectory planning and control of laser ablation intensity.
RNA Sequencing of Human Peripheral Blood Cells Indicates Upregulation of Immune-Related Genes in Huntington's Disease
Authors: Andrade-Navarro Miguel A. , Mühlenberg Katja , Spruth Eike J. , Mah Nancy , González-López Adrián , Andreani Tommaso , Russ Jenny , Huska Matthew R. , Muro Enrique M. , Fontaine Jean-Fred , Amstislavskiy Vyacheslav , Soldatov Alexei , Nietfeld Wilfried , Wanker Erich E. , Priller Josef
Published: November 2020

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a trinucleotide repeat expansion in the Huntingtin gene. As disease-modifying therapies for HD are being developed, peripheral blood cells may be used to indicate disease progression and to monitor treatment response. In order to investigate whether gene expression changes can be found in the blood of individuals with HD that distinguish them from healthy controls, we performed transcriptome analysis by next-generation sequencing (RNA-seq). We detected a gene expression signature consistent with dysregulation of immune-related functions and inflammatory response in peripheral blood from HD cases vs. controls, including induction of the interferon response genes, IFITM3, IFI6 and IRF7. Our results suggest that it is possible to detect gene expression changes in blood samples from individuals with HD, which may reflect the immune pathology associated with the disease.
Neurological Complications and Noninvasive Multimodal Neuromonitoring in Critically Ill Mechanically Ventilated COVID-19 Patients
Authors: Battaglini Denise , Santori Gregorio , Chandraptham Karthikka , Iannuzzi Francesca , Bastianello Matilde , Tarantino Fabio , Ball Lorenzo , Giacobbe Daniele Roberto , Vena Antonio , Bassetti Matteo , Inglese Matilde , Uccelli Antonio , Rocco Patricia Rieken Macedo , Patroniti Nicolò , Brunetti Iole , Pelosi Paolo , Robba Chiara
Published: November 2020

Purpose: The incidence and the clinical presentation of neurological manifestations of coronavirus disease-2019 (COVID-19) remain unclear. No data regarding the use of neuromonitoring tools in this group of patients are available.

Methods: This is a retrospective study of prospectively collected data. The primary aim was to assess the incidence and the type of neurological complications in critically ill COVID-19 patients and their effect on survival as well as on hospital and intensive care unit (ICU) length of stay. The secondary aim was to describe cerebral hemodynamic changes detected by noninvasive neuromonitoring modalities such as transcranial Doppler, optic nerve sheath diameter (ONSD), and automated pupillometry.

Results: Ninety-four patients with COVID-19 admitted to an ICU from February 28 to June 30, 2020, were included in this study. Fifty-three patients underwent noninvasive neuromonitoring. Neurological complications were detected in 50% of patients, with delirium as the most common manifestation. Patients with neurological complications, compared to those without, had longer hospital (36.8 ± 25.1 vs. 19.4 ± 16.9 days, p < 0.001) and ICU (31.5 ± 22.6 vs. 11.5±10.1 days, p < 0.001) stay. The duration of mechanical ventilation was independently associated with the risk of developing neurological complications (odds ratio 1.100, 95% CI 1.046–1.175, p = 0.001). Patients with increased intracranial pressure measured by ONSD (19% of the overall population) had longer ICU stay.

Conclusions: Neurological complications are common in critically ill patients with COVID-19 receiving invasive mechanical ventilation and are associated with prolonged ICU length of stay. Multimodal noninvasive neuromonitoring systems are useful tools for the early detection of variations in cerebrovascular parameters in COVID-19.
Psychopathological Comorbidities and Clinical Variables in Patients With Medication Overuse Headache
Authors: Migliore Simone , Paolucci Matteo , Quintiliani Livia , Altamura Claudia , Maffi Sabrina , D’Aurizio Giulia , Curcio Giuseppe , Vernieri Fabrizio
Published: November 2020

The psychopathological profile of patients with medication overuse headache (MOH) appears to be particularly complex. To better define it, we evaluated their performance on a targeted psychological profile assessment. We designed a case-control study comparing MOH patients and matched healthy controls (HC). Headache frequency, drug consumption, HIT-6, and MIDAS scores were recorded. All participants filled in the following questionnaires: Beck Depression Inventory-II Edition (BDI-2), trait subtest of State-Trait Anxiety Inventory (STAI-Y), Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsiveness Scale (BIS-11), Toronto Alexithymia Scale (TAS-20). The primary endpoint was to establish if MOH patients have an altered psychopathological profile. The secondary endpoint was to establish whether the worst profile correlates with the worsening of headache and disability measures. We enrolled 48 consecutive MOH patients and 48 HC. MOH patients showed greater difficulty in recognition/regulation of emotions (DERS, TAS-20), depression (BDI-2), anxiety (STAI-Y), and impulsiveness (BIS-11). We found a positive correlation among DERS, BDI-2, STAI-Y, and BIS scores and MIDAS and HIT-6 scores and among DERS and headache frequency and drug consumption. MOH patients showed a high rate of emotion regulation difficulties, depression, and anxiety, which may negatively affect their headaches. The ability to regulate/recognize emotions may play a central role in sustaining medication overuse.
Motor Point Stimulation in Spinal Paired Associative Stimulation can Facilitate Spinal Cord Excitability
Authors: Fok Kai Lon , Kaneko Naotsugu , Sasaki Atsushi , Nakagawa Kento , Nakazawa Kimitaka , Masani Kei
Published: November 2020

Paired associative stimulation at the spinal cord (spinal PAS) has been shown to increase muscle force and dexterity by strengthening the corticomuscular connection, through spike timing dependent plasticity. Typically, transcranial magnetic stimulation (TMS) and transcutaneous peripheral nerve electrical stimulation (PNS) are often used in spinal PAS. PNS targets superficial nerve branches, by which the number of applicable muscles is limited. Alternatively, a muscle can be activated by positioning the stimulation electrode on the “motor point” (MPS), which is the most sensitive location of a muscle to electrical stimulation. Although this can increase the number of applicable muscles for spinal PAS, nobody has tested whether MPS can be used for the spinal PAS to date. Here we investigated the feasibility of using MPS instead of PNS for spinal PAS. Ten healthy male individuals (26.0 ± 3.5 yrs) received spinal PAS on two separate days with different stimulation timings expected to induce (1) facilitation of corticospinal excitability (REAL) or (2) no effect (CONTROL) on the soleus. The motor evoked potentials (MEP) response curve in the soleus was measured prior to the spinal PAS, immediately after (0 min) and at 10, 20, 30 min post-intervention as a measure of corticospinal excitability. The post-intervention MEP response curve areas were larger in the REAL condition than the CONTROL conditions. Further, the post-intervention MEP response curve areas were significantly larger than pre-intervention in the REAL condition but not in the CONTROL condition. We conclude that MPS can facilitate corticospinal excitability through spinal PAS.
tVNS Increases Liking of Orally Sampled Low-Fat Foods: A Pilot Study
Authors: Öztürk Lina , Büning Pia Elisa , Frangos Eleni , de Lartigue Guillaume , Veldhuizen Maria G.
Published: November 2020

Recently a role for the vagus nerve in conditioning food preferences was established in rodents. In a prospective controlled clinical trial in humans, invasive vagus nerve stimulation shifted food choice toward lower fat content. Here we explored whether hedonic aspects of an orally sampled food stimulus can be modulated by non-invasive transcutaneous vagus nerve stimulation (tVNS) in humans. In healthy participants (n= 10, five women, 20–32 years old, no obesity) we tested liking and wanting ratings of food samples with varying fat or sugar content with or without tVNS in a sham-controlled within-participants design. To determine effects of tVNS on food intake, we also measured voluntary consumption of milkshake. Spontaneous eye blink rate was measured as a proxy for dopamine tone. Liking of low-fat, but not high-fat puddings, was higher for tVNS relative to sham stimulation. Other outcomes showed no differences. These findings support a role for the vagus nerve promoting post-ingestive reward signals. Our results suggest that tVNS may be used to increase liking of low-calorie foods, which may support healthier food choices.
Dynamic Causal Modeling for fMRI With Wilson-Cowan-Based Neuronal Equations
Authors: Sadeghi Sadjad , Mier Daniela , Gerchen Martin F. , Schmidt Stephanie N. L. , Hass Joachim
Published: November 2020

Dynamic causal modeling (DCM) is an analysis technique that has been successfully used to infer about directed connectivity between brain regions based on imaging data such as functional magnetic resonance imaging (fMRI). Most variants of DCM for fMRI rely on a simple bilinear differential equation for neural activation, making it difficult to interpret the results in terms of local neural dynamics. In this work, we introduce a modification to DCM for fMRI by replacing the bilinear equation with a non-linear Wilson-Cowan based equation and use Bayesian Model Comparison (BMC) to show that this modification improves the model evidences. Improved model evidence of the non-linear model is shown for our empirical data (imitation of facial expressions) and validated by synthetic data as well as an empirical test dataset (attention to visual motion) used in previous foundational papers. For our empirical data, we conduct the analysis for a group of 42 healthy participants who performed an imitation task, activating regions putatively containing the human mirror neuron system (MNS). In this regard, we build 540 models as one family for comparing the standard bilinear with the modified Wilson-Cowan models on the family-level. Using this modification, we can interpret the sigmoid transfer function as an averaged f-I curve of many neurons in a single region with a sigmoidal format. In this way, we can make a direct inference from the macroscopic model to detailed microscopic models. The new DCM variant shows superior model evidence on all tested data sets.
Cortical Oscillatory Signatures Reveal the Prerequisites for Tinnitus Perception: A Comparison of Subjects With Sudden Sensorineural Hearing Loss With and Without Tinnitus
Authors: Lee Sang-Yeon , Choi Byung Yoon , Koo Ja-Won , De Ridder Dirk , Song Jae-Jin
Published: November 2020

Just as the human brain works in a Bayesian manner to minimize uncertainty regarding external stimuli, a deafferented brain due to hearing loss attempts to obtain or “fill in” the missing auditory information, resulting in auditory phantom percepts (i.e., tinnitus). Among various types of hearing loss, sudden sensorineural hearing loss (SSNHL) has been extensively reported to be associated with tinnitus. However, the reason that tinnitus develops selectively in some patients with SSNHL remains elusive, which led us to hypothesize that patients with SSNHL with tinnitus (SSNHL-T) and those without tinnitus (SSNHL-NT) may exhibit different cortical activity patterns. In the current study, we compared resting-state quantitative electroencephalography findings between 13 SSNHL-T and 13 SSNHL-NT subjects strictly matched for demographic characteristics and hearing thresholds. By performing whole-brain source localization analysis complemented by functional connectivity analysis, we aimed to determine the as-yet-unidentified cortical oscillatory signatures that may reveal potential prerequisites for the perception of tinnitus in patients with SSNHL. Compared with the SSNHL-NT group, the SSNHL-T group showed significantly higher cortical activity in Bayesian inferential network areas such as the frontopolar cortex, orbitofrontal cortex (OFC), and pregenual anterior cingulate cortex (pgACC) for the beta 3 and gamma frequency bands. This suggests that tinnitus develops in a brain with sudden auditory deafferentation only if the Bayesian inferential network updates the missing auditory information and the pgACC-based top-down gatekeeper system is actively involved. Additionally, significantly increased connectivity between the OFC and precuneus for the gamma frequency band was observed in the SSNHL-T group, further suggesting that tinnitus derived from Bayesian inference may be linked to the default mode network so that tinnitus is regarded as normal. Taken together, our preliminary results suggest a possible mechanism for the selective development of tinnitus in patients with SSNHL. Also, these areas could serve as the potential targets of neuromodulatory approaches to preventing the development or prolonged perception of tinnitus in subjects with SSNHL.
Dream Generation and Recall in Daytime NREM Sleep of Patients With Narcolepsy Type 1
Authors: Cipolli Carlo , Pizza Fabio , Bellucci Claudia , Mazzetti Michela , Tuozzi Giovanni , Vandi Stefano , Plazzi Giuseppe
Published: November 2020

The less rigid architecture of sleep in patients with narcolepsy type 1 (NT1) compared with healthy subjects may provide new insights into some unresolved issues of dream experience (DE), under the assumption that their DE frequencies are comparable. The multiple transition from wakefulness to REM sleep (sleep onset REM period: SOREMP) during the five trials of the Multiple Sleep Latency Test (MSLT) appears of particular interest. In MSLT studies, NT1 patients reported a DE after about 80% of SOREMP naps (as often as after nighttime REM sleep of themselves and healthy subjects), but only after about 30% of NREM naps compared to 60% of daytime and nighttime NREM sleep of healthy subjects. To estimate accurately the “real” DE frequency, we asked participants to report DE (“dream”) after each MSLT nap and, in case of failure, to specify if they were unable to retrieve any content (“white dream”) or DE did not occur (“no-dream”). The proportions of dreams, white dreams, and no dreams and the indicators of structural organization of DEs reported after NREM naps by 17 adult NT1 patients were compared with those reported by 25 subjects with subjective complaints of excessive daytime sleepiness (sc-EDS), who take multiple daytime NREM naps. Findings were consistent with the hypothesis of a failure in recall after awakening rather than in generation during sleep: white dreams were more frequent in NT1 patients than in sc-EDS subjects (42.86 vs 17.64%), while their frequency of dreams plus white dreams were similar (67.86 and 61.78%) and comparable with that of NREM-DEs in healthy subjects. The longer and more complex NREM-DEs of NT1 patients compared with sc-EDS subjects suggest that the difficulty in DE reporting depends on their negative attitude toward recall of contents less vivid and bizarre than those they usually retrieve after daytime SOREMP and nighttime REM sleep. As this attitude may be reversed by some recall training before MSLT, collecting wider amounts of DE reports after NREM naps would cast light on both the across-stage continuity in the functioning of cognitive processes underlying DE and the difference in content and structural organization of SOREM-DEs preceded by N1 or also N2 sleep.
Characterizing Measurement Error in Dietary Sodium in Longitudinal Intervention Studies
Authors: Pittman Adam , Stuart Elizabeth A. , Siddique Juned
Published: November 2020

Background: Previous measurement error work that investigates the relationship between a nutritional biomarker and self-reported intake levels has typically been at a single time point, in a single treatment group, or with respect to basic patient demographics. Few studies have examined the measurement error structure in longitudinal randomized trials, and whether the error varies across time or group. This structure is crucial to understand, however, in order to correct for measurement error in self-reported outcomes and properly interpret the longitudinal effects of dietary interventions.

Methods: Using two longitudinal randomized controlled trials with internal longitudinal validation data (urinary biomarkers and self-reported values), we examine the relationship between urinary sodium and self-reported sodium and whether this relationship changes as a function of time and/or treatment condition. We do this by building a mixed effects regression model, allowing for a flexible error variance-covariance structure, and testing all possible interactions between time, treatment condition, and self-reported intake.

Results: Using a backward selection approach, we arrived at the same final model for both validation data sets. We found no evidence that measurement error changes as a function of self-reported sodium. However, we did find evidence that urinary sodium can differ by time or treatment condition even when conditioning on self-reported values.

Conclusion: In longitudinal nutritional intervention trials it is possible that measurement error differs across time and treatment groups. It is important for researchers to consider this possibility and not just assume non-differential measurement error. Future studies should consider data collection strategies to account for the potential dynamic nature of measurement error, such as collecting internal validation data across time and treatment groups when possible.
Cancer-Associated Fibroblast Density, Prognostic Characteristics, and Recurrence in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis
Authors: Knops Alexander M. , South Andrew , Rodeck Ulrich , Martinez-Outschoorn Ubaldo , Harshyne Larry A. , Johnson Jennifer , Luginbuhl Adam J. , Curry Joseph M.
Published: November 2020

Introduction

The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.

Methods

We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.

Results

Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).

Conclusions

Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
18F-FDG PET/CT Metrics Are Correlated to the Pathological Response in Esophageal Cancer Patients Treated With Induction Chemotherapy Followed by Neoadjuvant Chemo-Radiotherapy
Authors: Simoni Nicola , Rossi Gabriella , Benetti Giulio , Zuffante Michele , Micera Renato , Pavarana Michele , Guariglia Stefania , Zivelonghi Emanuele , Mengardo Valentina , Weindelmayer Jacopo , Giacopuzzi Simone , de Manzoni Giovanni , Cavedon Carlo , Mazzarotto Renzo
Published: November 2020

Background and Objective

The aim of this study was to assess the ability of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) to provide functional information useful in predicting pathological response to an intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for both esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients.

Material and Methods

Esophageal carcinoma (EC) patients, treated in our Center between 2014 and 2018, were retrospectively reviewed. The nCRT protocol schedule consisted of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks with concurrent radiotherapy (50–50.4 Gy in 25–28 fractions). Three 18F-FDG PET/CT scans were performed: before (PET1) and after (PET2) induction chemotherapy (IC), and prior to surgery (PET3). Correlation between PET parameters [maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)], radiomic features and tumor regression grade (TGR) was investigated.

Results

Fifty-four patients (35 ADC, 19 SCC; 48 cT3/4; 52 cN+) were eligible for the analysis. Pathological response to nCRT was classified as major (TRG1-2, 41/54, 75.9%) or non-response (TRG3-4, 13/54, 24.1%). A major response was statistically correlated with SCC subtype (p = 0.02) and smaller tumor length (p = 0.03). MTV and TLG measured prior to IC (PET1) were correlated to TRG1-2 response (p = 0.02 and p = 0.02, respectively). After IC (PET2), SUVmean and TLG correlated with major response (p = 0.03 and p = 0.04, respectively). No significance was detected when relative changes of metabolic parameters between PET1 and PET2 were evaluated. At textural quantitative analysis, three independent radiomic features extracted from PET1 images ([JointEnergy and InverseDifferenceNormalized of GLCM and LowGrayLevelZoneEmphasis of GLSZM) were statistically correlated with major response (p < 0.0002).

Conclusions

18F-FDG PET/CT traditional metrics and textural features seem to predict pathologic response (TRG) in EC patients treated with induction chemotherapy followed by neoadjuvant chemo-radiotherapy. Further investigations are necessary in order to obtain a reliable predictive model to be used in the clinical practice.
Intraoperative Recurrent Laryngeal Nerve Monitoring During Pediatric Cardiac and Thoracic Surgery: A Mini Review
Authors: Lawlor Claire M. , Zendejas Benjamin , Baird Christopher , Munoz-San Julian Carlos , Jennings Russell W. , Choi Sukgi S.
Published: November 2020

Objective: Review techniques for intraoperative recurrent laryngeal nerve (RLN) monitoring during pediatric surgery for esophageal atresia, tracheoesophageal fistula, tracheobronchomalacia, and cardiac surgery.

Summary Background Data: Literature was reviewed for reports of intraoperative recurrent laryngeal nerve monitoring in cervical, thoracic, and cardiac surgical procedures which place the RLNs at risk for injury.

Methods: Review paper.

Results: The RLN is at risk during pediatric surgery for esophageal atresia, tracheoesophageal fistula, tracheobronchomalacia, and cardiac surgery. Intraoperative nerve monitoring has decreased rates of RLN injury in thyroid surgery. Intraoperative RLN monitoring techniques appropriate for pediatric surgery are discussed, including endotracheal tubes with integrated surface electrodes, adhesive surface electrodes for smaller endotracheal tubes, endolaryngeal electrodes, and automatic periodic continuous intra-operative stimulation.

Conclusions: Multiple techniques exist to monitor the RLN in children undergoing cervical, cardiac, and thoracic surgery. Monitoring the RLN during procedures that place the RLNs at risk may help decrease the rate of RLN injury.
Comparable Intestinal and Hepatic First-Pass Effect of YL-IPA08 on the Bioavailability and Effective Brain Exposure, a Rapid Anti-PTSD and Anti-Depression Compound
Authors: Gao You , Yang Chunmiao , Wang Lingchao , Xiang Yanan , Zhang Wenpeng , Li Yunfeng , Zhuang Xiaomei
Published: November 2020

YL-IPA08, exerting rapid antidepressant-like and anxiolytic-like effects on behaviors by translocator protein (TSPO) mediation, is a novel compound that has been discovered and developed at our institute. Fit-for-purpose pharmacokinetic properties is urgently needed to be discovered as early as possible for a new compound. YL-IPA08 exhibited low bioavailability (∼6%) during the preliminary pharmacokinetics study in rats after oral administration. Our aim was to determine how metabolic disposition by microsomal P450 enzymes in liver and intestine limited YL-IPA08’s bioavailability and further affected brain penetration to the target. Studies of in vitro metabolic stability and permeability combined with in vivo oral bioavailability, panel CYP inhibitor co-administration via different routes, and double cannulation rats were conducted to elucidate the intestinal and hepatic first-pass effect of YL-IPA08 on bioavailability. Unbound brain-to-plasma ratio (Kp,uu) in rats was determined at steady state. Results indicated that P450-mediated elimination appeared to be important for its extensive first-pass effect with comparative contribution of gut (35%) and liver (17%), and no significant species difference was observed. The unbound concentration of YL-IPA08 in rat brain (6.5 pg/ml) was estimated based on Kp,uu (0.18) and was slightly higher than in vitro TSPO-binding activity (4.9 pg/ml). Based on the onset efficacy of YL-IPA08 toward TPSO in brain and Kp,uu, therapeutic human plasma concentration was predicted to be ∼27.2 ng/ml would easily be reached even with unfavorable bioavailability.
A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats
Authors: Huang Shuo , Tang Yanyan , Liu Tianjun , Zhang Ning , Yang Xueyan , Yang Dingwei , Hong Ge
Published: November 2020

Many studies proposed that oxidative stress and apoptosis are key mechanisms in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). Xylose-pyrogallol conjugate (XP) is an original effective antioxidant that showed decent antioxidant and anti-apoptosis effect before. Thus the therapeutic effect and mechanism of XP in preventing CI-AKI in the short and long term were investigated in this research. Renal function and histological grade were evaluated to determine the severity of renal injury. Kidney samples were then collected for the measurement of oxidative stress markers and the detection of apoptosis. Transmission electron microscopy (TEM) and western blot of mitochondrial protein were utilized for the analysis of the mitochondrial conditions. The results demonstrated that the CI-AKI rats caused a significant decrease in renal function accompanied by a remarkable increase in Malondialdehyde (MDA), bax, caspase-3, cytochrome c (Cyt C) level, TdT-mediated dUTP nick end labeling (TUNEL) positive apoptotic cells, and damaged mitochondria, while a decline in antioxidase activities and mitochondrial superoxide dismutase 2 (SOD2) expression compared with the control rats. However, when XP (50 or 100 or 200 mg/kg/day) was given orally for consecutive 7 days before CI-AKI modeling, XP (200 mg/kg) showed a better capability to restore renal dysfunction, histopathological appearance, the level of apoptosis, mitochondrial damage, oxidative stress, and fibrosis generation without interference in computed tomographic imaging. Our study indicated that antioxidant XP played a nephroprotective role probably via antiapoptotic and antioxidant mechanisms. Besides, XP may regulate the mitochondria pathway via decreasing the ratio of bax/bcl-2, inhibiting caspase-3 expression, cytochrome c release, and superoxide dismutase 2 activity. Overall, XP as a high-efficient antioxidant may have the potentials to prevent CI-AKI.
Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain
Authors: Li Yi , Yin Lu , Fan Zhongmin , Su Binxiao , Chen Yu , Ma Yan , Zhong Ya , Hou Wugang , Fang Zongping , Zhang Xijing
Published: November 2020

Neurological dysfunction, one of the severe manifestations of sepsis in patients, is closely related to increased mortality and long-term complications in intensive care units, including sepsis-associated encephalopathy (SAE) and chronic pain. The underlying mechanisms of these sepsis-induced neurological dysfunctions are elusive. However, it has been well established that microglia, the dominant resident immune cell in the central nervous system, play essential roles in the initiation and development of SAE and chronic pain. Microglia can be activated by inflammatory mediators, adjacent cells and neurotransmitters in the acute phase of sepsis and then induce neuronal dysfunction in the brain. With the spotlight focused on the relationship between microglia and sepsis, a deeper understanding of microglia in SAE and chronic pain can be achieved. More importantly, clarifying the mechanisms of sepsis-associated signaling pathways in microglia would shed new light on treatment strategies for SAE and chronic pain.
Formulation and Development of Transferrin Targeted Solid Lipid Nanoparticles for Breast Cancer Therapy
Authors: Bhagwat Geeta S. , Athawale Rajani B. , Gude Rajeev P. , Md Shadab , Alhakamy Nabil A. , Fahmy Usama A. , Kesharwani Prashant
Published: November 2020

Breast cancer is conventionally treated by surgery, chemotherapy and radiation therapy followed by post operational hormonal therapy. Tamoxifen citrate is a best option to treat breast cancer because its selective estrogen receptor modulation activity. Owing to its antiestrogenic action on breast as well as uterine cells, Tamoxifen citrate shows uterine toxicity. The dose 20 mg per day of Tamoxifen citrate required to show therapeutic effect causes side effects and toxicity to vital organs such as liver, kidney and uterus. In the present study, transferrin-conjugated solid lipid nanoparticles (SLNs) were successfully prepared to enhance the active targeting of tamoxifen citrate in breast cancer. Developed formulations were evaluated for particle size, surface charge, surface morphology and in vitro dissolution studies. Developed formulations exhibited more cytotoxicity as compared to pure Tamoxifen citrate solution in time as well as concentration dependent manner on human breast cancer MCF-7 cells. Further, cell uptake and flow cytometry studies confirmed the qualitative uptake of developed D-SLN and SMD-SLN by human breast cancer MCF-7 cells. Overall, proposed study highlights that transferrin engineered nanocarriers could enhance the therapeutic response of nanomedicines for breast cancer treatment.
Challenges in Process Dissociation Measures for Moral Cognition
Authors: Kunnari Anton , Sundvall Jukka R. I. , Laakasuo Michael
Published: November 2020

The process dissociation procedure (PDP) for moral cognition was created to separately measure two dispositions of moral judgment based on the dual-process theory of moral reasoning: deontological and utilitarian inclinations. In this paper we raise some concerns from a psychometrics perspective regarding the structure, reliability, and validity of the moral PDP as a measure of individual differences. Using two simulation studies as well as a real sample ofN= 1,010, we investigate the psychometric properties of the moral PDP. We present novel evidence showing that (1) some correlations between PDP parameters are mathematical artifacts, and as such cannot be taken as evidence in support of a theory, (2) there are severe response inconsistencies within dilemma batteries, and (3) reliability estimates for these scores seem to be far below the accepted standards. We discuss some potential theoretical and content-related reasons for these statistical issues and their implications. We conclude that in their current form, PDP measures of utilitarian and deontological tendencies are sub-optimal for assessing individual differences.
Inclusive Leadership Promotes Challenge-Oriented Organizational Citizenship Behavior Through the Mediation of Work Engagement and Moderation of Organizational Innovative Atmosphere
Authors: Chen Lu , Luo Fan , Zhu Xiaomei , Huang Xinjian , Liu Yanhong
Published: November 2020

Challenge-oriented organizational citizenship behavior or the organization-improving tasks employees perform beyond their job description is important for high organizational performance, but the organizational factors influencing it are poorly understood. In this study, we explored how inclusive leadership influences employees’ challenge-oriented organizational citizenship behavior in the Chinese context, drawing on data from 558 employees in high-tech industries. Multivariate correlation analysis showed that inclusive leadership promotes employees’ challenge-oriented organizational citizenship behavior and that this influence is partly mediated by work engagement. Further, it showed that organizational innovative atmosphere has a moderating effect on the relationship between inclusive leadership and employees’ challenge-oriented organizational citizenship behavior. In effect, this study expands the range of predictive variables for challenge-oriented organizational citizenship behavior and provides not only theoretical insight but also practical guidance for leaders who seek to motivate this behavior in their employees.
An Exploration of Factors Linked to Academic Performance in PISA 2018 Through Data Mining Techniques
Authors: Gamazo Adriana , Martínez-Abad Fernando
Published: November 2020

International large-scale assessments, such as PISA, provide structured and static data. However, due to its extensive databases, several researchers place it as a reference in Big Data in Education. With the goal of exploring which factors at country, school and student level have a higher relevance in predicting student performance, this paper proposes an Educational Data Mining approach to detect and analyze factors linked to academic performance. To this end, we conducted a secondary data analysis and built decision trees (C4.5 algorithm) to obtain a predictive model of school performance. Specifically, we selected as predictor variables a set of socioeconomic, process and outcome variables from PISA 2018 and other sources (World Bank, 2020). Since the unit of analysis were schools from all the countries included in PISA 2018 (n= 21,903), student and teacher predictor variables were imputed to the school database. Based on the available student performance scores in Reading, Math, and Science, we applied k-means clustering to obtain a categorized (three categories) target variable of global school performance. Results show the existence of two main branches in the decision tree, split according to the schools’ mean socioeconomic status (SES). While performance in high-SES schools is influenced by educational factors such as metacognitive strategies or achievement motivation, performance in low-SES schools is affected in greater measure by country-level socioeconomic indicators such as GDP, and individual educational indicators are relegated to a secondary level. Since these evidences are in line and delve into previous research, this work concludes by analyzing its potential contribution to support the decision making processes regarding educational policies.
Criminal Responsibility Scale: Development and Validation of a Psychometric Tool Structured in Clinical Vignettes for Criminal Responsibility Assessments in Brazil
Authors: Meyer Leonardo Fernandez , Leal Cláudia Cristina Studart , Omena Alexandre de Almeida Souza , Mecler Katia , Valença Alexandre Martins
Published: November 2020

Criminal responsibility assessment is undertaken by psychologists or psychiatrists to assess offenders' legal capacities, which vary among countries or regional legislations. There are two psychometric tools (i.e., checklists) validated for criminal responsibility assessment: the Roger Criminal Responsibility Scale, and the rating scale of criminal responsibility for mentally disordered offenders. Despite the existence of psychometric tools structured in clinical vignettes for evaluating legal capacities, none serve the purpose of assessing criminal responsibility. This study aims to validate a novel psychometric tool structured in vignettes for the assessment of criminal responsibility called the “Criminal Responsibility Scale.” We applied the tool to 88 defendants referred for criminal responsibility assessment in a forensic medical institute in the city of Rio de Janeiro, Brazil, from December 2017 to December 2018. The validity of the Criminal Responsibility Scale and subscales were evaluated using confirmatory factor analysis. The two-factor solution proved satisfactory and met the needs for practical application of the tool (Kaiser–Meyer–Oklin = 0.82;p< 0.001). Moreover, the inter-rater reliability was evaluated by comparing the tool's final score with that of the expert's conclusion in each case and was found to be satisfactory (k= 0.667–1.0), with a resulting cutoff point of 30.50 (±2) and a Youden index of 0.509. Hence, the Criminal Responsibility Scale is an effective psychometric tool for assessments of criminal responsibility that may encourage future research in assessments of legal capacity with clinical vignette-based psychometric instruments.
Insomnia in Chinese College Students With Internet Addiction: Prevalence and Associated Clinical Correlates
Authors: Shen Yanmei , Jin Xingyue , Zhang Yaru , Huang Chunxiang , Lu Jianping , Luo Xuerong , Zhang Xiang Yang
Published: November 2020

Background: Internet addiction (IA) has gained more and more attention for its negative impact on the subjects' study and daily life. However, in a large sample, there is little research on the association between IA and insomnia in Chinese college students. This study aimed to investigate the prevalence of insomnia and its related risk factors among Chinese college students with IA.

Methods: A cross-sectional design was used to investigate 627 Chinese college students with IA. Each student completed a survey on demographic data, Internet addiction (Revised Chinese Internet Addiction Scale), depression (Self-Rating Depression Scale), insomnia (Athens Insomnia Scale), anxiety (Self-Rating Anxiety Scale), and suicidal behavior. Binary logistic regression analysis was employed to adjust for confounding factors.

Results: The prevalence of insomnia among students with IA was 54.86%. Compared with IA students without insomnia, IA students with insomnia were more likely to be younger, smoking, drinking, have anxiety, depression, suicidal ideations, suicide plans, and suicide attempts (all p < 0.05). Moreover, drinking [OR, 1.664; 95% confidence interval (CI), 1.139–2.431; p = 0.008], anxiety (OR, 2.321; 95% CI, 1.116–4.826; p = 0.024), and suicidal ideation (OR, 1.942; 95% CI:1.295–2.911; p = 0.001) were independently associated with insomnia in IA students.

Conclusions: Insomnia is very common in Chinese IA students. Drinking, anxiety, and suicidal ideation are independently correlated with insomnia. This study provides valuable evidence for school counselors and clinical professionals to assess Internet addiction, insomnia, and suicide risk.
Code-Sharing in Cost-of-Illness Calculations: An Application to Antibiotic-Resistant Bloodstream Infections
Authors: Naylor Nichola R. , Yamashita Kazuto , Iwami Michiyo , Kunisawa Susumu , Mizuno Seiko , Castro-Sánchez Enrique , Imanaka Yuichi , Ahmad Raheelah , Holmes Alison
Published: November 2020

Background: More data-driven evidence is needed on the cost of antibiotic resistance. Both Japan and England have large surveillance and administrative datasets. Code sharing of costing models enables reduced duplication of effort in research.

Objective: To estimate the burden of antibiotic-resistant Staphylococcus aureus bloodstream infections (BSIs) in Japan, utilizing code that was written to estimate the hospital burden of antibiotic-resistant Escherichia coli BSIs in England. Additionally, the process in which the code-sharing and application was performed is detailed, to aid future such use of code-sharing in health economics.

Methods: National administrative data sources were linked with voluntary surveillance data within the Japan case study. R software code, which created multistate models to estimate the excess length of stay associated with different exposures of interest, was adapted from previous use and run on this dataset. Unit costs were applied to estimate healthcare system burden in 2017 international dollars (I$).

Results: Clear supporting documentation alongside open-access code, licensing, and formal communication channels, helped the re-application of costing code from the English setting within the Japanese setting. From the Japanese healthcare system perspective, it was estimated that there was an excess cost of I$6,392 per S. aureus BSI, whilst oxacillin resistance was associated with an additional I$8,155.

Conclusions:S. aureus resistance profiles other than methicillin may substantially impact hospital costs. The sharing of costing models within the field of antibiotic resistance is a feasible way to increase burden evidence efficiently, allowing for decision makers (with appropriate data available) to gain rapid cost-of-illness estimates.
Novel Solutions or Rebranded Approaches: Evaluating the Use of Nature-Based Solutions (NBS) in Europe
Authors: O'Sullivan Fearghus , Mell Ian , Clement Sarah
Published: November 2020

The Nature-Based Solutions (NBS) concept is the most recent entry to discussions around how “nature” can be mobilized to render urban areas more resilient to the threat of climate change. The concept has been championed by the European Commission (EC) as a tool that can transform contemporary environmental, social and economic challenges into opportunities for innovation, bolstering Europe's position as a leader in climate change mitigation and adaptation. With its current research and innovation programme—Horizon 2020—the EC looks to position itself as the global NBS frontrunner, providing funding to cities to act as NBS demonstrator projects across the continent. These are expected to provide best-practice examples that can be replicated globally. This paper focuses on three Horizon 2020-funded NBS demonstrator projects: Connecting Nature, URBAN GreenUP and Grow Green, each of which brings together a suite of urban partners from both within and outside the European Union (EU). It examines the internal “politics” i.e., the aims and internal governance and implementation issues associated with these projects, and analyses how partners perceive the NBS concept. To engage with these aims, interviews were conducted with a diverse set of NBS “practitioners” working within the three projects. Analysis showed that the projects aim to influence climate-change resilient and sustainable urbanism through the process of retrofitting cities with small-scale green and blue interventions, as well as help the EU secure stronger diplomatic relations with neighboring non-EU countries and key international trade partners. It also illustrated that for many project partners, NBS is perceived to be a novel concept, because it re-frames pre-existing terms such as Green and Blue Infrastructure (GBI) and Ecosystem Services (ES) in a way that makes principles of urban greening more understandable to lay audiences and more politically palatable for urban governments. However, partners also warn that this framing of NBS has led to a narrow and idealized representation of nature; one that simultaneously undervalues biodiversity and oversells the capacity of natural processes to provide “solutions” to urban climate vulnerability and broader patterns of unsustainable urbanism.
Case Report: Ultrasound Sciatic and Saphenous Nerve Blocks for Tibial Malunion Surgical Correction in a Pediatric African Leopard (Panthera pardus)
Authors: Ravasio Giuliano , Brioschi Federica Alessandra , Rabbogliatti Vanessa , Gioeni Daniela , Di Cesare Federica , Corletto Federico , Oltolina Maurizio , Carnevale Liliana
Published: November 2020

Little information is available regarding ultrasound-guided locoregional anesthesia in non-domestic species. Locoregional techniques have been shown to reduce intraoperative anesthetic requirements and provide postoperative pain relief. Decreasing dosage of general anesthetics allows more stable cardiopulmonary function during anesthesia and reduces the probability of side effects. An 11-week-old African leopard (Panthera pardus) was referred for treatment of a malunion angular limb deformity secondary to a tibial and fibular fracture. The animal was scheduled to undergo angular correction of the tibia via closing wedge osteotomy and fixation with a locking plate system. Following preanesthetic medication and induction of general anesthesia, a saphenous nerve block (ropivacaine 0.5%; 0.15 ml/kg) was performed under ultrasound guidance and a sciatic nerve block (ropivacaine 0.5%; 0.15 ml/kg) was performed using ultrasound and a peripheral nerve stimulator. Intraoperative anesthetic plane was considered light, yet no abrupt cardiocirculatory changes were seen, nor was rescue analgesia required. This case report suggests that sciatic and saphenous blockade could therefore be recommended as part of a multimodal plan of analgesia for orthopedic surgeries in pediatric exotic felids.