bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Upper Airway Characteristics on Disease Severity and CPAP Therapy in Chinese Patients With OSA: An Observational Retrospective Study
Authors: Zhang Cheng , Chen Mingxin , Shen Yane , Gong Yuhong , Ma Jing , Wang Guangfa
Published: March 2022

Objective

The characteristics of the upper airway (UA) are important for the evaluation and treatment of obstructive sleep apnea (OSA). This study aimed to investigate the association of UA characteristics with OSA severity, titration pressure, and initiation of and 3-month compliance with continuous positive airway pressure (CPAP).

Methods

This retrospective study included consecutive patients examined using a semi-quantitative UA evaluation system (combination with physical examination and awake endoscopy) during 2008–2018 at the Department of Respiratory and Critical Care Medicine, Peking University First Hospital. First, the differences in UA characteristics were compared between patients with simple snorers and mild OSA and those with moderate-to-severe OSA. Then, the effect of UA characteristics on the initiation to CPAP therapy and 3-month adherence to CPAP was conducted.

Results

Overall, 1,002 patients were included, including 276 simple snorers and patients in the mild OSA group [apnea-hypopnea index (AHI) <15] and 726 patients in the moderate-to-severe OSA group (AHI ≥15). Tongue base hypertrophy, tonsillar hypertrophy, mandibular recession, neck circumstance, and body mass index (BMI) were independent risk factors for moderate-to-severe OSA. Among those patients, 119 patients underwent CPAP titration in the sleep lab. The CPAP pressures in patients with thick and long uvulas, tonsillar hypertrophy, lateral pharyngeal wall stenosis, and tongue hypertrophy were higher than those of the control group (P < 0.05, respectively). The logistic regression analysis showed that nasal turbinate hypertrophy, mandibular retrusion, and positive Müller maneuver in the retropalate and retroglottal regions were independent predictors for the initiation of home CPAP treatment.

Conclusion

Multisite narrowing and function collapse of the UA are important factors affecting OSA severity, CPAP titration pressure, and the initiation of home CPAP therapy. Clinical evaluation with awake endoscopy is a safe and effective way for the assessment of patients with OSA in internal medicine.
Comparison of the Pathway to the Inner Ear Between Postauricular and Intramuscular Injection of Dexamethasone in Guinea Pigs
Authors: Chen Aiping , Liu Wenwen , Xu Lei , Hou Zhiqiang , Fan Zhaomin , Wang Haibo , Wang Mingming
Published: March 2022

Background

Postauricular injection as a local therapy has been confirmed to be effective for inner ear diseases. However, the mechanism for the drugs entering the inner ears remains unknown. This study aims to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection, and explore the pathway of the drugs entering the inner ears.

Methods

An in vivo optical imaging system was used to conduct a time course observation to compare the distribution of dexamethasone by intramuscular injection with that by postauricular injection in male guinea pigs. The drug availability in the tympanic mucosa, tympanum, endolymphatic sac, and cochlea was observed by a confocal laser scanning microscope.

Results

The local fluorescent intensity by postauricular injection was significantly higher in the inner ears, and lower in partial peripheral organs, than that by the intramuscular injection. The drug metabolism by postauricular injection exhibited an obviously sustained release effect in the inner ears. Drugs by postauricular injection might enter the endolymphatic sac through the posterior auricular artery and occipital artery, as well as the connections of the mastoid emissary vein, sigmoid sinus and endolymphatic sac.

Conclusion

More drugs concentrated in the inner ear for longer therapeutic time and less systemic delivery implied more effective and less risk of side effects through postauricular injection than intramuscular injection safer for the treatment of inner ear diseases.
A Novel TBK1 Variant (Lys694del) Presenting With Corticobasal Syndrome in a Family With FTD-ALS Spectrum Diseases: Case Report
Authors: Seibert Kaitlin , Smith Heather , Lapins Allison , Pytel Peter , Mastrianni James A.
Published: March 2022

Several variants of the TANK-Binding Kinase 1 (TBK1) gene have been associated with frontotemporal dementia - amyotrophic lateral sclerosis (FTD-ALS) spectrum diseases. Corticobasal syndrome (CBS) is characterized by asymmetric limb rigidity, dystonia or myoclonus, in association with speech or limb apraxia, cortical sensory deficit, and/or alien limb. It can result from a variety of underlying pathologies and although typically sporadic, it has been occasionally associated with MAPT and GRN variants. We describe here the proband of a family with multiple occurrences of FTD-ALS spectrum disease who developed an isolated right-sided primary asymmetric akinetic-rigid syndrome and subsequent speech and cognitive dysfunction associated with contralateral anterior temporal lobe atrophy on MRI and corresponding hypometabolism by FDG-PET. Genetic testing revealed a novel Lys694del variant of the TBK1 gene and Type A TDP-43 pathology in a predominantly frontotemporal distribution contralateral to the affected side. To our knowledge this is the first report of CBS as the initial expression of a TBK1 variant. This case emphasizes the importance of considering TBK1 genetic screening in patients with CBS, as this may be an underrepresented population on the spectrum of genetic FTD-ALS.
Current Cigarette Smoking Is Associated With a High Seizure Frequency and Anxiety Symptoms in People With Epilepsy
Authors: Zhong Rui , Li Zhuan , Zhang Xinyue , Chen Qingling , Lin Weihong
Published: March 2022

Purpose

This study aims to answer the following questions: how many people with epilepsy (PWE) have cigarette smoking habits? Which demographic or clinical characteristics are associated with cigarette smoking? Is cigarette smoking related to depressive and anxiety symptoms in PWE?

Methods

A total of 524 PWE were included in the final analysis. Demographic and clinical data were gathered and recorded. Smoking status was identified. The associations of smoking status with the clinical features of epilepsy and depressive and anxiety symptoms were evaluated by logistic regression models.

Results

The overall prevalence of cigarette smoking was 23.5% (123 PWE) in this sample. In the multivariate logistic regression model, men (adjusted OR = 10.414, 95% CI: 5.552–19.535, P < 0.001), high seizure frequency (adjusted OR = 1.474, 95% CI: 1.043–2.084, P = 0.028), and anxiety symptoms (adjusted OR = 2.473, 95% CI: 1.483–4.112, P = 0.001) were shown to have independent associations with cigarette smoking in PWE.

Conclusion

Our findings suggested that the overall prevalence of cigarette smoking was 23.5% in adults with epilepsy, which is slightly lower than that (26.6%) in general adults in China. In the present study, cigarette smoking was associated with men, high seizure frequency, and anxiety symptoms in PWE. Further prospective clinical studies with larger sample sizes are required to confirm our findings.
Epidemiology of Moyamoya Angiopathy in Eastern India
Authors: Das Shambaditya , Dubey Souvik , Das Suman , Hazra Avijit , Pandit Alak , Ghosh Ritwik , Ray Biman Kanti
Published: March 2022

Introduction

Moyamoya angiopathy (MMA) is a chronic, progressive intracranial vasculopathy with variation in prevalence and clinical manifestations across different populations. This study was aimed to estimate the frequency of MMA as an etiology of stroke and its epidemiological features in the largest cohort of MMA patients in India.

Method

A single-centered cross-sectional observational study over a period of 5 years (2016–2021) was undertaken among consecutive stroke and transient ischemic attack (TIA) patients to look for the presence of MMA angiographically. Each patient with angiographically proven MMA was further evaluated for demographic, clinical, and radiological characteristics.

Results

Among 10,250 consecutive stroke and TIA patients (ischemic = 78%, hemorrhagic = 22%), frequency of MMA was 1.56% (n = 160); 15.3% among children. Female preponderance (Male:Female = 1:1.4) was noted among 160 MMA patients, with bimodal age distribution, first peak at 3–8 years, and a shorter second peak at 41–47 years. Childhood-onset MMA was seen in 75 (46.9%) with commonest initial neurological symptom of fixed-motor-weakness (44.0%), followed by TIA (26.7%); while 85 (53.1%) had adult-onset MMA with fixed-motor-weakness (50.6%) followed by headache (24.7%) as the predominant initial neurological symptom; seizure significantly higher in children (p < 0.001) and headache in adults (p = 0.012). Transient and fixed neurological manifestations constituted 87.5 and 69.4% respectively, of symptoms throughout the disease course. Cerebral infarction (45.0%) and TIA (21.9%) were the commonest types of MMA. On brain imaging, infarction was noted in 80.6%, hemorrhage in 11.3%, significantly higher among adults (p < 0.001). Cortical infarct and Gyral pattern were commoner in children (p = 0.004), subcortical infarcts in adults (p = 0.018). Frequent Suzuki staging observed was stage 4 (31.3%), followed by stage 3 (30.0%). Involvement of posterior circulation was detected in 55.6%, brain atrophy at the time of diagnosis was seen in 65.0%.

Conclusion

MMA is an important etiological consideration in patients with stroke, especially in children. It can present with a myriad of transient neurological symptoms, frequently overlooked, leading to delayed diagnosis, and contributing to socio-economic burden. Indian MMA showed aberrations in its gender predisposition, age distribution, frequency of familial cases, disease manifestation, and type of stroke, in comparison to its Japanese and Caucasian counterparts pointing to the inter- and intra-continent differences of MMA phenotype. Future development of the Indian MMA national registry is of essence.
LGMD D2 TNPO3-Related: From Clinical Spectrum to Pathogenetic Mechanism
Authors: Costa Roberta , Rodia Maria Teresa , Pacilio Serafina , Angelini Corrado , Cenacchi Giovanna
Published: March 2022

Limb-girdle muscular dystrophies (LGMDs) are clinically and genetically heterogeneous diseases presenting with a wide clinical spectrum. Autosomal dominant LGMDs represent about 10–15% of LGMDs and include disorders due to defects of DNAJB6, transportin-3 (TNPO3), HNRNPDL, Calpain-3 (CAPN3), and Bethlem myopathy. This review article aims to describe the clinical spectrum of LGMD D2 TNPO3-related, a rare disease due to heterozygous mutation in theTNPO3gene.TNPO3encodes for transportin-3, which belongs to the importin beta family and transports into the nucleus serine/arginine-rich (SR) proteins, such as splicing factors, and HIV-1 proteins, thus contributing to viral infection. The purpose of this review is to present and compare the clinical features and the genetic and histopathological findings described in LGMD D2, performing a comparative analytical description of all the families and sporadic cases identified. Even if the causative gene and mutations of this disease have been identified, the pathogenic mechanisms are still an open issue; therefore, we will present an overview of the hypotheses that explain the pathology of LGMD D2 TNPO3-related.
Responsiveness of the Traumatic Brain Injury Quality of Life Cognition Banks in Recent Brain Injury
Authors: Tyner Callie E. , Kisala Pamela A. , Boulton Aaron J. , Sherer Mark , Chiaravalloti Nancy D. , Sander Angelle M. , Bushnik Tamara , Tulsky David S.
Published: March 2022

Patient report of functioning is one component of the neurocognitive exam following traumatic brain injury, and standardized patient-reported outcomes measures are useful to track outcomes during rehabilitation. The Traumatic Brain Injury Quality of Life measurement system (TBI-QOL) is a TBI-specific extension of the PROMIS and Neuro-QoL measurement systems that includes 20 item banks across physical, emotional, social, and cognitive domains. Previous research has evaluated the responsiveness of the TBI-QOL measures in community-dwelling individuals and found clinically important change over a 6-month assessment interval in a sample of individuals who were on average 5 years post-injury. In the present study, we report on the responsiveness of the TBI-QOL Cognition–General Concerns and Executive Function item bank scores and the Cognitive Health Composite scores in a recently injured sample over a 1-year study period. Data from 128 participants with complicated mild, moderate, or severe TBI within the previous 6 months were evaluated. The majority of the sample was male, white, and non-Hispanic. The participants were 18–92 years of age and were first evaluated from 0 to 5 months post-injury. Eighty participants completed the 1-year follow-up assessment. Results show acceptable standard response mean values (0.47–0.51) for all measures and minimal detectable change values ranging from 8.2 to 8.8 T-score points for Cognition–General Concerns and Executive Functioning measures. Anchor rating analysis revealed that changes in scores on the Executive Function item bank and the Cognitive Health Composite were meaningfully associated with participant-reported changes in the areas of attention, multitasking, and memory. Evaluation of change score differences by a variety of clinical indicators demonstrated a small but significant difference in the three TBI-QOL change scores by TBI injury severity grouping. These results support the responsiveness of the TBI-QOL cognition measures in newly injured individuals and provides information on the minimal important differences for the TBI-QOL cognition measures, which can be used for score interpretation by clinicians and researchers seeking patient-reported outcome measures of self-reported cognitive QOL after TBI.
Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury
Authors: Wong Joshua K. , Deuschl Günther , Wolke Robin , Bergman Hagai , Muthuraman Muthuraman , Groppa Sergiu , Sheth Sameer A. , Bronte-Stewart Helen M. , Wilkins Kevin B. , Petrucci Matthew N. , Lambert Emilia , Kehnemouyi Yasmine , Starr Philip A. , Little Simon , Anso Juan , Gilron Ro’ee , Poree Lawrence , Kalamangalam Giridhar P. , Worrell Gregory A. , Miller Kai J. , Schiff Nicholas D. , Butson Christopher R. , Henderson Jaimie M. , Judy Jack W. , Ramirez-Zamora Adolfo , Foote Kelly D. , Silburn Peter A. , Li Luming , Oyama Genko , Kamo Hikaru , Sekimoto Satoko , Hattori Nobutaka , Giordano James J. , DiEuliis Diane , Shook John R. , Doughtery Darin D. , Widge Alik S. , Mayberg Helen S. , Cha Jungho , Choi Kisueng , Heisig Stephen , Obatusin Mosadolu , Opri Enrico , Kaufman Scott B. , Shirvalkar Prasad , Rozell Christopher J. , Alagapan Sankaraleengam , Raike Robert S. , Bokil Hemant , Green David , Okun Michael S.
Published: March 2022

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.
A Preliminary Study of the Efficacy of Transcranial Direct Current Stimulation in Trigeminal Neuralgia
Authors: Babakhani Babak , Tabatabaei Narges Hoseini , Elisevich Kost , Sadeghbeigi Narges , Barzegar Mojtaba , Mobarakeh Neda Mohammadi , Eyvazi Fatemeh , Khazaeipour Zahra , Taheri Arman , Nazem-Zadeh Mohammad-Reza
Published: March 2022

The purpose of this study is to assess the efficacy of transcranial direct current stimulation (tDCS) in patients with treatment-refractory trigeminal neuralgia (TN) and examine the utility of neuroimaging methods in identifying markers of such efficacy. Six patients with classical TN refractory to maximal medical treatment, underwent tDCS (three cases inhibitory/cathodic and three cases excitatory/anodic stimulation). All patients underwent pre- and posttreatment functional magnetic resonance imaging (fMRI) during block-design tasks (i.e., Pain, Pain + tDCS, tDCS) as well as single-shell diffusion MRI (dMRI) acquisition. The precise locations of tDCS electrodes were identified by neuronavigation. Five therapeutic tDCS sessions were carried out for each patient with either anodic or cathodic applications. The Numeric Rating Scale of pain (NRS) and the Headache Disability Index (HDI) were used to score the subjective efficacy of treatment. Altered activity of regional sites was identified by fMRI and associated changes in the spinothalamocortical sensory tract (STCT) were measured by the dMRI indices of fractional anisotropy (FA) and mean diffusivity (MD). Fiber counts of the bilateral trigeminal root entry zone (REZ) were performed as an added measure of fiber loss or recovery. All patients experienced a significant reduction in pain scores with a substantial decline in HDI (P value < 0.01). Following a course of anodic tDCS, the ipsilateral caudate, globus pallidus, somatosensory cortex, and the contralateral globus pallidus showed a significantly attenuated activation whereas cathodic tDCS treatment resulted in attenuation of the thalamus and globus pallidus bilaterally, and the somatosensory cortex and anterior cingulate gyrus contralaterally. dMRI analysis identified a substantial increase (>50%) in the number of contralateral sensory fibers in the STCT with either anodic or cathodic tDCS treatment in four of the six patients. A significant reduction in FA (>40%) was observed in the ipsilateral REZ in the posttreatment phase in five of the six patients. Preliminary evidence suggests that navigated tDCS presents a promising method for alleviating the pain of TN. Different patterns of activation manifested by anodic and cathodic stimulation require further elaboration to understand their implication. Activation and attenuation of responses at various sites may provide further avenues for condition treatment.
Abnormal Cerebrovascular Reactivity and Functional Connectivity Caused by White Matter Hyperintensity Contribute to Cognitive Decline
Authors: Yang Dan , Qin Ruomeng , Chu Lan , Xu Hengheng , Ni Ling , Ma Junyi , Shao Pengfei , Huang Lili , Zhang Bing , Zhang Meijuan , Xu Yun
Published: March 2022

Aims

This study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline.

Methods

A total of 233 WMH subjects were recruited and categorized into WMH-I (n = 106), WMH-II (n = 72), and WMH-III (n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored.

Results

Subjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = −0.1248, 95% CI: −0.4689, −0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = −0.1436, 95% CI: −0.4584, −0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG.

Conclusion

The CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals.
Optimizing a Behavioral Sleep Intervention for Gynecologic Cancer Survivors: Study Design and Protocol
Authors: Fox Rina S. , Gaumond Julia S. , Zee Phyllis C. , Kaiser Karen , Tanner Edward J. , Ancoli-Israel Sonia , Siddique Juned , Penedo Frank J. , Wu Lisa M. , Reid Kathryn J. , Parthasarathy Sairam , Badger Terry A. , Rini Christine , Ong Jason C.
Published: March 2022

Sleep difficulties, particularly symptoms of insomnia and circadian disruption, are among the primary complaints of gynecologic cancer survivors before, during, and after treatment. Moreover, difficulty sleeping has been linked to poorer health-related quality of life and elevated symptom burden in this population. Although leading behavioral sleep interventions have demonstrated efficacy among cancer survivors, up to 50% of survivors are non-adherent to these treatments, likely because these interventions require labor-intensive behavior and lifestyle changes. Therefore, there is a need for more effective and acceptable approaches to diminish sleep disturbance among cancer survivors. This manuscript describes the methodology of a two-part study guided by the Multiphase Optimization Strategy (MOST) framework to identify a streamlined behavioral sleep intervention for gynecologic cancer survivors. Three candidate intervention components previously shown to decrease sleep disturbance will be evaluated, including sleep restriction, stimulus control, and systematic bright light exposure. Participants will be adult women with a history of non-metastatic gynecologic cancer who have completed primary treatment and who report current poor sleep quality. Fifteen participants will be recruited for Part 1 of the study, which will utilize qualitative methods to identify barriers to and facilitators of intervention adherence. Results will inform changes to the delivery of the candidate intervention components to promote adherence in Part 2, where 80 participants will be recruited and randomized to one of eight conditions reflecting every possible combination of the three candidate intervention components in a full factorial design. Participants will complete assessments at baseline, post-intervention, and 3-months post-intervention. Part 2 results will identify the combination of candidate intervention components that yields the most efficacious yet efficient 6-week intervention for diminishing sleep disturbance. This is the first known study to apply the MOST framework to optimize a behavioral sleep intervention and will yield a resource-efficient treatment to diminish sleep disturbance, improve health-related quality of life, and decrease symptom burden among gynecologic cancer survivors. ClinicalTrials.gov Identifier: NCT05044975.
Targeted Interventions to Increase Blood Pressure and Decrease Anaesthetic Concentrations Reduce Intraoperative Burst Suppression: A Randomised, Interventional Clinical Trial
Authors: Georgii Marie-Therese , Kreuzer Matthias , Fleischmann Antonia , Schuessler Jule , Schneider Gerhard , Pilge Stefanie
Published: March 2022

Background

It has been suggested that intraoperative electroencephalographic (EEG) burst suppression (BSupp) may be associated with post-operative neurocognitive disorders in the elderly, and EEG-guided anaesthesia may help to reduce BSupp. Despite of this suggestion, a standard treatment does not exist, as we have yet to fully understand the phenomenon and its underlying pathomechanism. This study was designed to address two underlying phenomena—cerebral hypoperfusion and individual anaesthetic overdose.

Objectives

We aimed to demonstrate that targeted anaesthetic interventions—treating intraoperative hypotension and/or reducing the anaesthetic concentration—reduce BSupp.

Methods

We randomly assigned patients to receive EEG-based interventions during anaesthesia or EEG-blinded standard anaesthesia. If BSupp was detected, defined as burst suppression ratio (BSR) > 0, the primary intervention aimed to adjust the mean arterial blood pressure to patient baseline (MAP intervention) followed by reduction of anaesthetic concentration (MAC intervention).

Results

EEG-based intervention significantly reduced total cumulative BSR, BSR duration, and maximum BSR. MAP intervention caused a significant MAP increase at the end of a BSR > 0 episode compared to the control group. Coincidentally, the maximum BSR decreased significantly; in 55% of all MAP interventions, the BSR decreased to 0% without any further action. In the remaining events, additional MAC intervention was required.

Conclusion

Our results show that targeted interventions (MAC/MAP) reduce total cumulative amount, duration, and maximum BSR > 0 in the elderly undergoing general anaesthesia. Haemodynamic intervention already interrupted or reduced BSupp, strengthening the current reflections that hypotension-induced cerebral hypoperfusion may be seen as potential pathomechanism of intraoperative BSupp.

Clinical Trial Registration

NCT03775356 [ClinicalTrials.gov], DRKS00015839 [German Clinical Trials Register (Deutsches Register klinischer Studien, DRKS)].
Adherence to Mediterranean Diet Is Associated With Better Glycemic Control in Children With Type 1 Diabetes: A Cross-Sectional Study
Authors: Dominguez-Riscart Jesus , Buero-Fernandez Nuria , Garcia-Zarzuela Ana , Morales-Perez Celia , Garcia-Ojanguren Ana , Lechuga-Sancho Alfonso M.
Published: March 2022

Type 1 diabetes (T1D) is a chronic condition, with increased morbidity and mortality, due to a higher rate of cardiovascular disease among other factors. Cardiovascular risk increases with the worse glycemic profile. Nutrition has a deep impact on diabetes control. Adherence to the Mediterranean diet (MD) has been shown to decrease cardiovascular risk in children and adults with obesity and adults with type 2 diabetes, but its impact on T1D children has been scarcely analyzed. We hypothesized that the degree of adherence to MD could relate to the increased time in range in children with T1D.

Patients and Methods

Cross-sectional analysis involving two university hospitals. We measured the adherence to MD with the Mediterranean Diet Quality Index for children and teenagers (KIDMED) questionnaire, which is a validated tool for this purpose. A score of <5 indicates poor adherence to MD, while a good adherence is indicated by a score of >7. Demographic and clinical data were registered on the same day that the questionnaire was taken, with informed consent. Additionally, the patients' ambulatory glucose profiles (AGPs), were registered from the participants' glucose monitors (continuous or flash devices), and daily insulin needs were recorded from patients' insulin pumps (n=28). Other cardiovascular risk factors such as lipid profile, vitamin D levels, and other biochemical parameters were registered from a blood test, performed 2 weeks before recruitment, as part of the patients' annual screening.

Results

Ninety-seven patients (44 girls), with an average age of 11.4 years (± 3.01), were included. Seventy-one of them were on multiple daily injection regimens, and all had either continuous or flash glucose monitoring. Fifty-three had HbA1c levels of <7.5%, while only 21 had a time in range (TIR) of >70%. Contingency analysis showed that the odds of having HbA1c <7.5% increase in children with KIDMED score of >7 (O.R. 2.38; ICR 1.05–5.41; p = 0.036). Moreover, the KIDMED score and the HbA1c levels were negatively correlated (R: −0.245; p-value: 0.001), while the KIDMED score and TIR showed a positive correlation (R: 0.200; p-value: 0.009).

Conclusions

Our data suggest that adherence to MD may contribute to better glycemic control in children. This should be taken into account at the time of nutritional education on T1D patients and their families.
The Interaction Between Non-Coding RNAs and Calcium Binding Proteins
Authors: Ghafouri-Fard Soudeh , Majidpoor Jamal , Shoorei Hamed , Hussen Bashdar Mahmud , Hadayat Jamal Hazha , Baniahmad Aria , Taheri Mohammad , Mokhtari Majid
Published: March 2022

Calcium binding proteins (CBP) are a group of proteins mediating the effects of calcium on cellular functions. These proteins can regulate calcium levels inside the cells and contribute in several cellular functions through transporting this ion across cell membranes or decoding related signals. Recent studies have shown that several non-coding RNAs interact with CBPs to affect their expression or activity. The interactions between these transcripts and CBPs have implications in the pathoetiology of human disorders, including both neoplastic and non-neoplastic conditions. In the current review, we describe the interactions between three classes of non-coding RNAs (long non-coding RNAs, circular RNAs, and microRNAs) and a number of CBPs, particularly CAB39, S100A1, S100A4, S100A7 and S100P. This kind of interaction has been verified in different pathological contexts such as drug-induced cardiotoxicity, osteoblasts cytotoxicity, acute lung injury, myocardial ischemia/reperfusion injury, proliferative diabetic retinopathy, glomerulonephritis, as well as a wide array of neoplastic conditions.
Risk Factors Leading to Anti-TNF Alpha Therapies in Pediatric Severe Uveitis
Authors: Osswald Delphine , Rameau Anne-Cécile , Terzic Joëlle , Sordet Christelle , Bourcier Tristan , Sauer Arnaud
Published: March 2022

Purpose

Pediatric uveitis is the leading cause of acquired child blindness, due to unremitting inflammation and long-term steroid exposition. Biotherapies with anti-tumor necrosis factor alpha (anti-TNFα) are effective in controlling inflammation for severe pediatric uveitis in recent studies. Major concern of anti-TNFα prescription is the balance between the severity of the disease and side effects of the drug. The aim of the present study is to describe a cohort of children with severe uveitis and to highlight the risk factors for a pejorative development that led to the prescription of anti-TNFα drugs.

Method

A retrospective case-control study was carried out on children with uveitis associated with systemic inflammatory disease or idiopathic uveitis, with a minimum follow-up of 5 years. Anti-TNFα-treated patients (case) were studied and compared with patients who were not requiring anti-TNFα (control). Univariate logistic regression analyses were performed to compare both groups and determine the risk factors for anti-TNFα therapy.

Results

Seventy-three cases of pediatric uveitis were included, 13 cases and 60 controls. The risk factors associated with increased odds of anti-TNFα therapy were initial systemic disorder associated with uveitis [OR = 11.22 (1.37–91.85), p = 0.0241), family history of autoimmune diseases [OR = 9.43 (2.27–39.15), p = 0.0020], uveitis diagnosis before the age of 6 [OR = 4.05 (1.16–14.13), p = 0.0284], eye surgery [OR = 26.22 (2.63–261.77), p = 0.0054], ocular complications at the first slit lamp exam [OR = 67.11 (3.78–1191.69), p = 0.0042], low visual acuity at diagnosis (≥0.3 logMAR) [OR = 11.76 (2.91–47.62), p = 0.0005] and especially low binocular acuity at diagnosis (≥0.3 logMAR) [OR = 8.75 (1.93–39.57), p = 0.0048], panuveitis [OR = 9.17 (2.23–37.60), p = 0.0021], having positive ANA [OR = 3.89 (1.07–14.11), p = 0.0391], and positive HLA B27 [OR = 9.43 (2.27–39.16), p = 0.0020].

Conclusion

Those risk factors could be used to establish a new follow-up and treatment schedule for severe uncontrolled uveitis. This could help to better predict the best time to start anti-TNF therapy.
Compound Heterozygous Variants in a Surviving Patient With Alkuraya-Kučinskas Syndrome: A New Case Report and a Review of the Literature
Authors: Yue Ling , Jin Mei , Wang Xin , Wang Jing , Chen Ling , Jia Rong , Yang Zuozhen , Yang Fan , Li Jingman , Chen Cuiying , Zheng Huacheng , Yang Huafang
Published: March 2022

Background

Alkuraya–Kučinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot, and global developmental delay. Most reported cases were cases of premature termination of pregnancies or neonatal deaths. To date, limited studies of nine surviving patients with global developmental delay and intellectual disability have been reported. In this study, we report another surviving patient.

Methods

Whole-exome sequencing was utilized for the proband, and variants were filtered, annotated, and classified. Candidate variants were validated by Sanger sequencing of the proband and his family. The literature was reviewed; the prognosis among different regions and the variant type was analyzed.

Results

A non-synonymous variant [NM_015312.3: exon29: c.4892C>G (p.Pro1631Arg)] was identified and validated in the patient's father. A frameshift duplication [NM_015312.3: exon62: c.10872dupA (p.Arg3625Lysfs*5)] that caused early translation termination was identified in his mother. The literature was reviewed, variants were classified into three regions of KIAA1109, and their survival status was summarized.

Conclusion

We reported another survival proband with Alkuraya–Kučinskas syndrome driven by KIAA1109. Our case expands the genotypic spectrum of Alkuraya–Kučinskas syndrome and explored the relationship between the variant region and survival.
Characteristics of Exogenous Allergen in Breast Milk and Their Impact on Oral Tolerance Induction
Authors: Kosmeri Chrysoula , Rallis Dimitrios , Kostara Maria , Giapros Vasileios , Siomou Ekaterini , Tsabouri Sophia
Published: March 2022

Food allergy is a common health problem in childhood since its prevalence was estimated to range from 6. 5 to 24.6% in European countries. Recently, a lot of research has focused on the impact of breastfeeding on oral tolerance induction. Since it was found that breast milk contains immunologically active food antigens, it would be very helpful to clarify the factors of antigen shedding that promotes oral tolerance. This narrative review aimed to summarize the latest evidence from experimental and human studies regarding allergen characteristics in human milk that may influence oral tolerance induction. A literature search in PubMed, MEDLINE, and Google Scholar was conducted. The diet of the mother was found to have a direct impact on allergen amount in the breastmilk, while antigens had different kinetics in human milk between women and depending on the antigen. The mode of antigen consumption, such as the cooking of an antigen, may also affect the allergenicity of the antigen in human milk. The dose of the antigen in human milk is in the range of nanograms per milliliter; however, it was found to have a tolerogenic effect. Furthermore, the presence of antigen-specific immunoglobulins, forming immune complexes with antigens, was found more tolerogenic compared to free allergens in experimental studies, and this is related to the immune status of the mother. While examining available data, this review highlights gaps in knowledge regarding allergen characteristics that may influence oral tolerance.
Lymphatic Valve Dysfunction in Western Diet-Fed Mice: New Insights Into Obesity-Induced Lymphedema
Authors: Castorena-Gonzalez Jorge A.
Published: March 2022

A two-way connection between obesity and lymphatic dysfunction has now been established. Clinical studies have demonstrated that obesity significantly increases the risk for developing secondary lymphedema. Using animal-models, obesity and metabolic syndrome have been linked to different aspects of lymphatic structural abnormalities and lymphatic dysfunction, including impaired contractility, impaired flow-mediated responses, impaired fluid transport, as well as increased permeability, and abnormal dendritic cell migration among others. Dysfunction of lymphatic valves is a main form of lymphatic dysfunction, known to result in severe edematous phenotypes; however, the extent of lymphatic valve deficiency in secondary lymphedema, including obesity-induced lymphedema, remains unknown. Therefore, the aims of the present study were 1) to determine whether western diet-induced obesity results in lymphatic valve dysfunction, and 2) to determine whether lymphatic valve dysfunction in western diet-induced obesity results from the diet itself, or as a consequence of the metabolic alterations induced by the diet. First, we quantitatively assessed and compared valve function in isolated popliteal and mesenteric collecting lymphatic vessels from control and western diet-induced obese C57BL/6J (WT) mice. Feeding a western diet for 14 weeks induced obesity and elevated plasma glucose and cholesterol levels when compared to controls. The function of lymphatic valves in popliteal lymphatics was not affected by diet-induced obesity; however, significant back-leak of pressure was observed in mesenteric lymphatic valves. Dysfunctional, leaky valves from obese animals also required significantly higher adverse pressure to trigger valve closure. Importantly, when subjected to treatment with a western diet, globally deficient PAI-1 mice were significantly protected against metabolic dysfunction and displayed fully functional, competent mesenteric lymphatic valves. In conclusion, our findings show for the first time that, in association with the metabolic alterations induced by the western diet, lymphatic valve dysfunction can be a critical component of obesity-induced lymphedema.
Tacrolimus Loaded Cationic Liposomes for Dry Eye Treatment
Authors: Chen Xiang , Wu Jicheng , Lin Xueqi , Wu Xingdi , Yu Xuewen , Wang Ben , Xu Wen
Published: March 2022

Eye drops are ophthalmic formulations routinely used to treat dry eye. However, the low ocular bioavailability is an obvious drawback of eye drops owing to short ocular retention time and weak permeability of the cornea. Herein, to improve the ocular bioavailability of eye drops, a cationic liposome eye drop was constructed and used to treat dry eye. Tacrolimus liposomes exhibit a diameter of around 300 nm and a surface charge of +30 mV. Cationic liposomes could interact with the anionic ocular surface, extending the ocular retention time and improving tacrolimus amount into the cornea. The cationic liposomes notably prolonged the ocular retention time of eye drops, leading to an increased tacrolimus concentration in the ocular surface. The tacrolimus liposomes were also demonstrated to reduce reactive oxygen species and dry eye–related inflammation factors. The use of drug-loaded cationic liposomes is a good formulation in the treatment of ocular disease; the improved ocular retention time and biocompatibility give tremendous scope for application in the treatment of ocular disease, with further work in the area recommended.
Traditional Chinese Medicines as Effective Reversals of Epithelial-Mesenchymal Transition Induced-Metastasis of Colorectal Cancer: Molecular Targets and Mechanisms
Authors: Ge Hongzhang , Xu Chao , Chen Haitao , Liu Ling , Zhang Lei , Wu Changhong , Lu Yi , Yao Qinghua
Published: March 2022

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Distant metastasis is the major cause of cancer-related mortality in patients with CRC. Epithelial-mesenchymal transition (EMT) is a critical process triggered during tumor metastasis, which is also the main impetus and the essential access within this duration. Therefore, targeting EMT-related molecular pathways has been considered a novel strategy to explore effective therapeutic agents against metastatic CRC. Traditional Chinese medicines (TCMs) with unique properties multi-target and multi-link that exert their therapeutic efficacies holistically, which could inhibit the invasion and metastasis ability of CRC cells via inhibiting the EMT process by down-regulating transforming growth factor-β (TGF-β)/Smads, PI3K/Akt, NF-κB, Wnt/β-catenin, and Notch signaling pathways. The objective of this review is to summarize and assess the anti-metastatic effect of TCM-originated bioactive compounds and Chinese medicine formulas by mediating EMT-associated signaling pathways in CRC therapy, providing a foundation for further research on the exact mechanisms of action through which TCMs affect EMT transform in CRC.
Associations of Fentanyl, Sufentanil, and Remifentanil With Length of Stay and Mortality Among Mechanically Ventilated Patients: A Registry-Based Cohort Study
Authors: Wang Wen , He Qiao , Wang Mingqi , Kang Yan , Ji Peng , Zhu Shichao , Zhang Rui , Zou Kang , Sun Xin
Published: March 2022

Background: As the first-line treatment for mechanically ventilated patients with critical illness, fentanyl and its analogs (e.g., sufentanil and remifentanil) are commonly used in the intensive care unit (ICU). However, the pharmacokinetics, metabolism, and potency of these agents differed. Their effects on clinical outcomes have not been well-understood.

Materials and Methods: Using a well-established registry, we conducted a cohort study. Patients who consistently underwent mechanical ventilation (MV) for more than 24 h were identified. We used a time-varying exposure definition, in which we coded each type of opioids as prescribed or not prescribed on each day from initiation of MV to extubation and ICU discharge. We used Fine-Gray competing risk models to compare the effects of fentanyl, sufentanil, and remifentanil on hazards for extubation, ventilator mortality, ICU discharge, and ICU mortality. All models were adjusted using a combination of fixed-time and time-varying covariates. Missing data were imputed using multiple imputation by chained equations.

Results: A total of 8,165 patients were included. There were, respectively, 4,778, 4,008, and 2,233 patients receiving at least 1 day of fentanyl, sufentanil, and remifentanil dose. Compared to fentanyl, sufentanil was associated with shorter duration to extubation (hazard ratio 1.31, 95% CI, 1.20–1.41) and ICU discharge (hazard ratio 1.63, 95% CI, 1.38–1.92), and remifentanil was associated with shorter duration to extubation (hazard ratio 1.60, 95% CI, 1.40–1.84) and ICU discharge (hazard ratio 2.02, 95% CI, 1.43–2.84). No significant differences in time to extubation (Hazard ratio 1.14, 95% CI, 0.92–1.41) and ICU discharge (Hazard ratio 1.31, 95% CI, 0.81–2.14) were found between sufentanil and remifentanil. No differences were observed between any two of the agents regarding ventilator mortality or ICU mortality. The effects were similar in patients with versus without surgery.

Conclusion: Sufentanil and remifentanil may be superior to fentanyl in shortening the time to extubation and ICU discharge. The effects on ventilator mortality and ICU mortality appeared similar across these agents, while further research is warranted.
Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome
Authors: Monaghan Ann , Jennings Glenn , Xue Feng , Byrne Lisa , Duggan Eoin , Romero-Ortuno Roman
Published: March 2022

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres® NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25–78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HRnadir: 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR = 1.09, 95% CI: 1.01–1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOHAS) orthostatic hypotension, but neither correlated with OIAS. Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OItilt). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOHtilt (2 to HR > 120 bpm), but six did not report OItilt. In conclusion, OIAS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).
Surface-Enhanced Raman Scattering Spectroscopy Combined With Chemical Imaging Analysis for Detecting Apple Valsa Canker at an Early Stage
Authors: Fang Shiyan , Zhao Yanru , Wang Yan , Li Junmeng , Zhu Fengle , Yu Keqiang
Published: March 2022

Apple Valsa canker (AVC) with early incubation characteristics is a severe apple tree disease, resulting in significant orchards yield loss. Early detection of the infected trees is critical to prevent the disease from rapidly developing. Surface-enhanced Raman Scattering (SERS) spectroscopy with simplifies detection procedures and improves detection efficiency is a potential method for AVC detection. In this study, AVC early infected detection was proposed by combining SERS spectroscopy with the chemometrics methods and machine learning algorithms, and chemical distribution imaging was successfully applied to the analysis of disease dynamics. Results showed that the samples of healthy, early disease, and late disease sample datasets demonstrated significant clustering effects. The adaptive iterative reweighted penalized least squares (air-PLS) algorithm was used as the best baseline correction method to eliminate the interference of baseline shifts. The BP-ANN, ELM, Random Forest, and LS-SVM machine learning algorithms incorporating optimal spectral variables were utilized to establish discriminative models to detect of the AVC disease stage. The accuracy of these models was above 90%. SERS chemical imaging results showed that cellulose and lignin were significantly reduced at the phloem disease-health junction under AVC stress. These results suggested that SERS spectroscopy combined with chemical imaging analysis for early detection of the AVC disease was feasible and promising. This study provided a practical method for the rapidly diagnosing of apple orchard diseases.