bluuebunny/crossref_metadata_2025 huggingface dataset:
Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?
Authors: Insuela Daniella Bianchi Reis , Ferrero Maximiliano Ruben , Coutinho Diego de Sá , Martins Marco Aurélio , Carvalho Vinicius Frias
Published: December 2020

Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE2and the cyclopentenone prostaglandin15-Deoxy-Delta-12,14-PGJ2(15d-PGJ2) while from LOXs are the LXA4and LXB4. In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblastsin vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotypein vitroandin vivo. Although PGE2and LXA4showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2caused side effects, while LXA4presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.
Effects of In Vivo Gluten Challenge on PBMC Gene Expression Profiles in Diet Treated Celiac Disease
Authors: Yohannes Dawit A. , de Kauwe Andrea , Kaukinen Katri , Kurppa Kalle , Mäki Markku , Anderson Robert P. , Linnarsson Sten , Greco Dario , Saavalainen Päivi
Published: December 2020

The pathological mechanisms that lead to the onset and reactivation of celiac disease (CD) remain largely unknown. While gluten free diet (GFD) improves the intestinal damage and associated clinical symptoms in majority of cases, it falls short of providing full recovery. Additionally, late or misdiagnosis is also common as CD presents with a wide range of symptoms. Clear understanding of CD pathogenesis is thus critical to address both diagnostic and treatment concerns. We aimed to study the molecular impact of short gluten exposure in GFD treated CD patients, as well as identify biological pathways that remain altered constitutively in CD regardless of treatment. Using RNAseq profiling of PBMC samples collected from treated CD patients and gluten challenged patient and healthy controls, we explored the peripheral transcriptome in CD patients following a short gluten exposure. Short gluten exposure of just three days was enough to alter the genome-wide PBMC transcriptome of patients. Pathway analysis revealed gluten-induced upregulation of mainly immune response related pathways, both innate and adaptive, in CD patients. We evaluated the perturbation of biological pathways in sample-specific manner. Compared to gluten exposed healthy controls, pathways related to tight junction, olfactory transduction, metabolism of unsaturated fatty acids (such as arachidonic acid), metabolism of amino acids (such as cysteine and glutamate), and microbial infection were constitutively altered in CD patients regardless of treatment, while GFD treatment appears to mostly normalize immune response pathways to “healthy” state. Upstream regulator prediction analysis using differentially expressed genes identified constitutively activated regulators relatively proximal to previously reported CD associated loci, particularly SMARCA4 on 19p13.2 and CSF2 on 5q31. We also found constitutively upregulated genes in CD that are in CD associated genetic loci such as MEF2BNB-MEF2B (BORCS8-MEF2B) on 19p13.11 and CSTB on 21q22.3. RNAseq revealed strong effects of short oral gluten challenge on whole PBMC fraction and constitutively altered pathways in CD PBMC suggesting important factors other than gluten in CD pathogenesis.
Seasonal Food Web Dynamics in the Antarctic Benthos of Tethys Bay (Ross Sea): Implications for Biodiversity Persistence Under Different Seasonal Sea-Ice Coverage
Authors: Caputi Simona Sporta , Careddu Giulio , Calizza Edoardo , Fiorentino Federico , Maccapan Deborah , Rossi Loreto , Costantini Maria Letizia
Published: December 2020

Determining food web architecture and its seasonal cycles is a precondition for making predictions about Antarctic marine biodiversity under varying climate change scenarios. However, few scientific data concerning Antarctic food web structure, the species playing key roles in web stability and the community responses to changes in sea-ice dynamics are available. Based on C and N stable isotope analysis, we describe Antarctic benthic food webs and the diet of species occurring in shallow waters (Tethys Bay, Ross Sea) before and after seasonal sea-ice break-up. We hypothesized that the increased availability of primary producers (sympagic algae) following sea-ice break-up affects the diet of species and thus food web architecture. Basal resources had distinct isotopic signatures that did not change after sea-ice break-up, enabling a robust description of consumer diets based on Bayesian mixing models. Sympagic algae had the highest δ13C (∼−14‰) and red macroalgae the lowest (∼−37‰). Consumer isotopic niches and signatures changed after sea-ice break-up, reflecting the values of sympagic algae. Differences in food web topology were also observed. The number of taxa and the number of links per taxon were higher before the thaw than after it. After sea-ice break-up, sympagic inputs allowed consumers to specialize on abundant resources at lower trophic levels. Foraging optimization by consumers led to a simpler food web, with lower potential competition and shorter food chains. However, basal resources and Antarctic species such as the bivalve Adamussium colbecki and the sea-urchin Sterechinus neumayeri were central and highly connected both before and after the sea-ice break-up, thus playing key roles in interconnecting species and compartments in the web. Any disturbance affecting these species is expected to have cascading effects on the entire food web. The seasonal break-up of sea ice in Antarctica ensures the availability of resources that are limiting for coastal communities for the rest of the year. Identification of species playing a key role in regulating food web structure in relation to seasonal sea-ice dynamics, which are expected to change with global warming, is central to understanding how these communities will respond to climate change.
The Relevance of Complementary and Integrative Medicine in the COVID-19 Pandemic: A Qualitative Review of the Literature
Authors: Seifert Georg , Jeitler Michael , Stange Rainer , Michalsen Andreas , Cramer Holger , Brinkhaus Benno , Esch Tobias , Kerckhoff Annette , Paul Anna , Teut Michael , Ghadjar Pirus , Langhorst Jost , Häupl Thomas , Murthy Vijay , Kessler Christian S.
Published: December 2020

Background:During the COVID-19 pandemic people are facing risks of adverse health effects due to the restrictions implemented such as quarantine measures, reduced social contact, and self-isolation. In this qualitative review, we collected data on potential preventive and therapeutic health benefits of Complementary and Integrative Medicine (CIM) that might be useful during the COVID-19 pandemic. We have reviewed the scientific literature to summarize CIM practices that could be beneficial for improving physical and mental health and well-being of the population under the current pandemic circumstances. It must be noted that this review is not SARS-CoV-2 specific and we explicitly do not intend to make any SARS-CoV-2 specific health claims in this article.

Methods and Findings:A qualitative, non-systematic literature review was conducted in Medline to identify literature describing preventive and therapeutic CIM approaches for strengthening mental and physical health. For a variety of CIM approaches clinical evidence was identified, indicating beneficial effects. CIM approaches include specific dietary measures and selected micronutrients, physical activity, techniques from Mind-Body Medicine, single botanicals or botanical compounds, and spending time in nature among others. The effects of CIM measures on conditions like obesity and hypertension are of special relevance here, as these conditions are considered as risk factors for a severe course of COVID-19. Moreover, a possibly direct effect of CIM approaches on immune functions and clinical parameters in respiratory tract infections, such as influenza, were identified. The findings of this review could be helpful for clinicians, patients, and the general population during the current pandemic when discussing and/or considering CIM options.

Conclusions:CIM offers a variety of preventive and therapeutic options for strengthening physical and mental resilience, which could also be useful in the current COVID-19 pandemic. The evidence of CIM approaches with a potential benefit in the COVID-19 pandemic in different areas is worth to be analyzed. While this qualitative review has several obvious limitations, it might serve as useful starting point for further research on this topic.
Enzymatic Browning in Wheat Kernels Produces Symptom of Black Point Caused by Bipolaris sorokiniana
Authors: Li Qiaoyun , Xu Kaige , Wang Siyu , Li Mengyu , Jiang Yumei , Liang Xiaolong , Niu Jishan , Wang Chenyang
Published: December 2020

To understand the blackening mechanism in black point diseased kernels, ultraviolet–visible light (UV–Vis) and Fourier-transform infrared (FT-IR) absorbance spectra of extracts made from the blackening parts of black point-affected (BP) kernels and the analogous part of black point-free (BPF) kernels were measured using susceptible wheat genotypes “PZSCL6” inoculated with Bipolaris sorokiniana (the dominant pathogen causing this disease). In addition, metabolite differences between BP and BPF kernels were identified by a method that combines gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high resolution mass spectrometry (LC-MS). Successively, symptoms of black point were produced in vitro. The results showed (i) the spectroscopic properties of the extracts from BP and BPF kernels were very similar, with an absorption peak at 235 nm and a small shoulder at 280–300 nm in both UV–Vis spectra and shared vibrations at 3400–3300, 2925 and 2852, 1512 and 1463, 1709, 1220, 600–860 cm–1 in FT-IR spectra that are consistent with similar bonding characteristics. In contrast, spectroscopic properties of extracts from wheat kernels were different from those of synthetic melanin and extracellular and intracellular melanin produced by B. sorokiniana. (ii) Levels of 156 metabolites in BP kernels were different from those in BPF kernels. Among those 156 metabolites, levels of phenolic acids (ferulic acid and p-coumaric acid), 11 phenolamides compounds, and four benzoxazinone derivatives were significantly higher in BP kernels than in BPF kernels. (iii) Symptom of black point could be produced in vitro in wheat kernels with supplement of phenol substrate (catechol) and H2O2. This result proved that blackening substance causing symptom of black point was produced by enzymatic browning in wheat kernels instead of by B. sorokiniana.
Evaluating ELISA, Immunofluorescence, and Lateral Flow Assay for SARS-CoV-2 Serologic Assays
Authors: Michel Moïse , Bouam Amar , Edouard Sophie , Fenollar Florence , Di Pinto Fabrizio , Mège Jean-Louis , Drancourt Michel , Vitte Joana
Published: December 2020

Background

The SARS-CoV-2 outbreak has emerged at the end of 2019. Aside from the detection of viral genome with specific RT-PCR, there is a growing need for reliable determination of the serological status. We aimed at evaluating five SARS-CoV-2 serology assays.

Methods

An in-house immunofluorescence assay (IFA), two ELISA kits (EUROIMMUN® ELISA SARS-CoV-2 IgG and NovaLisa® SARS-CoV-2 IgG and IgM) and two lateral flow assays (T-Tek® SARS-CoV-2 IgG/IgM Antibody Test Kit and Sure Bio-tech® SARS-CoV-2 IgM/IgG Antibody Rapid Test) were compared on 40 serums from RT-PCR-confirmed SARS-CoV-2 infected patients and 10 SARS-CoV-2 RT-PCR negative subjects as controls.

Results

Control subjects tested negative for SARS-CoV-2 antibodies with all five systems. Estimated sensitivities varied from 35.5 to 71.0% for IgG detection and from 19.4 to 64.5% for IgM detection. For IgG, in-house IFA, EuroImmun, T-Tek and NovaLisa displayed 50–72.5% agreement with other systems except IFA vs EuroImmun and T-Tek vs NovaLisa. Intermethod agreement for IgM determination was between 30 and 72.5%.

Discussion

The overall intermethod agreement was moderate. This inconsistency could be explained by the diversity of assay methods, antigens used and immunoglobulin isotype tested. Estimated sensitivities were low, highlighting the limited value of antibody detection in CoVID-19.

Conclusion

Comparison of five systems for SARS-CoV-2 IgG and IgM antibodies showed limited sensitivity and overall concordance. The place and indications of serological status assessment with currently available tools in the CoVID-19 pandemic need further evaluations.
Assessment of Safety and Probiotic Traits of Enterococcus durans OSY-EGY, Isolated From Egyptian Artisanal Cheese, Using Comparative Genomics and Phenotypic Analyses
Authors: Hussein Walaa E. , Abdelhamid Ahmed G. , Rocha-Mendoza Diana , García-Cano Israel , Yousef Ahmed E.
Published: December 2020

AnEnterococcus duransstrain, designated OSY-EGY, was previously isolated from artisanal cheese. In this work, comparative genomic and phenotypic analyses were utilized to assess the safety characteristics and probiotic traits of the bacterium. The comparative genomic analysis revealed that the strain is distantly related to potentially pathogenicEnterococcusspp. The genome was devoid of genes encoding acquired antibiotic resistance or marker virulence factors associated withEnterococcusspp. Phenotypically, the bacterium is susceptible to vancomycin, ampicillin, tetracycline, chloramphenicol, and aminoglycosides and does not have any hemolytic or gelatinase activity, or cytotoxic effect on Caco-2 cells. Altogether, these findings confirm the lack of hazardous traits inE. duransOSY-EGY. MiningE. duransOSY-EGY genome, for probiotic-related sequences, revealed genes associated with acid and bile salts tolerance, adhesion, competitiveness, antioxidant activitiy, antimicrobial activity, essential amino acids production, and vitamins biosynthesis. Phenotypically,E. duransOSY-EGY was tolerant to acidic pH (3.0), and presence of 0.3% bile salts. The bacterium showed adhesion capability to Caco-2 cells, cholesterol-lowering effect, DPPH scavenging activity, and antimicrobial activity against several Gram-positive pathogenic bacteria. Based on the current work, we propose thatE. duransOSY-EGY is a potentially safe strain with desirable probiotic and antimicrobial traits. Thus, the investigated strain could be a promising candidate for several industrial applications.
Mitochondrial Dynamics and Bioenergetic Alteration During Inflammatory Activation of Astrocytes
Authors: Rahman Md Habibur , Suk Kyoungho
Published: December 2020

Mitochondria are essential cellular organelles that act as metabolic centers and signaling platforms and have been identified as an important subcellular target in a broad range of neuropathologies. Studies on the role of mitochondria in neurological disorders have primarily focused on neurons. However, dysfunctional mitochondria in glial cells, particularly astrocytes, have recently gained research attention due to their close involvement in neuroinflammation and metabolic and neurodegenerative disorders. Furthermore, alterations in mitochondrial energy metabolism in astrocytes have been reported to modulate cellular morphology and activity and induce the release of diverse proinflammatory mediators. Moreover, emerging evidence suggests that dysregulation of mitochondrial dynamics characterized by aberrant fission and fusion events in glial cells is closely associated with the inflammatory activation of glia. In this mini-review, we cover the recent advances in the molecular aspects of astrocytic mitochondrial dynamics and their metabolic changes under the pathological conditions of the central nervous system (CNS).
Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain
Authors: Tran Emily L. , Crawford LaTasha K.
Published: December 2020

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful. Studies that interrogate uninjured neurons in search of cell-specific mechanisms have shown that nerve injury alters intact, uninjured neurons resulting in an activity that drives stimulus-evoked pain. This review of neuropathic pain mechanisms summarizes cell-type-specific pathology of uninjured sensory neurons and the sensory ganglia that house their cell bodies. Uninjured neurons have demonstrated a wide range of molecular and neurophysiologic changes, many of which are distinct from those detected in injured neurons. These intriguing findings include expression of pain-associated molecules, neurophysiological changes that underlie increased excitability, and evidence that intercellular signaling within sensory ganglia alters uninjured neurons. In addition to well-supported findings, this review also discusses potential mechanisms that remain poorly understood in the context of nerve injury. This review highlights key questions that will advance our understanding of the plasticity of sensory neuron subpopulations and clarify the role of uninjured neurons in developing anti-pain therapies.
Usefulness of 3D T1-SPACE in Combination With 3D-TOF MRA for Follow-Up Evaluation of Intracranial Aneurysms Treated With Pipeline Embolization Devices
Authors: Shao Qiuji , Wu Qiaowei , Li Qiang , Li Tianxiao , Li Li , Chang Kaitao , Wang Meiyun
Published: December 2020

Object: Follow-up evaluation of intracranial aneurysms treated by flow-diverting stents using MRI is challenging due to the presence of imaging artifacts. This study evaluated 3D T1-SPACE in combination with 3D-TOF sequence for follow-up evaluation of intracranial aneurysms treated with Pipeline embolization devices.

Methods: Forty patients with 53 intracranial aneurysms who were treated with Pipeline Embolization Devices from October 2018 to July 2019 were enrolled in this study. All patients were evaluated for aneurysm occlusion and stent patency 4 to 7 months post-treatment using 3D T1-SPACE sequence, 3D-TOF MRA, and DSA examinations.

Results: With regards to aneurysm occlusion, the intermodality (DSA and 3D-TOF MRA) agreement was good (κ = 0.755). The specificity of 3D-TOF MRA was 94.4% (34/36), the sensitivity was 76.5% (13/17), the total coincidence rate was 88.7% (47/53). With regards to the patency of the stented arteries after PED treatment, 3D T1-SPACE sequence was more accurate compared to 3D-TOF MRA (Z = −6.283, P < 0.001), with a no-artifact rate of 95.7% (44/46).

Conclusions: 3D T1-SPACE sequence provides better image quality and higher accuracy for evaluating stented parent arteries compared to TOF-MRA. 3D-TOF MRA may be valuable in the evaluation of aneurysm occlusion. The combination of these two modalities may be used for long-term follow-up of intracranial aneurysms treated with Pipeline Embolization Devices.
Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese
Authors: Li Xing , Zhu Jiajia , Peng Yu , Guan Hongbing , Chen Jinyu , Wang Zhanhang , Zheng Dong , Cheng Nan , Wang Honghao
Published: December 2020

Background: Single nucleotide polymorphisms (SNPs) that occur within genes encoding inflammatory cytokines can result in quantitative or qualitative changes in their expression or functionality, potentially leading to the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study sought to evaluate the relationship between SNPs in inflammatory cytokines genes and the incidence of anti-NMDAR encephalitis in the Southern Han Chinese.

Methods: In total, we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls who had no first-degree relative with autoimmune diseases. Genotyping determination of all 309 patients was conducted for the IL-1β rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872, and IL-17 rs2275913 gene SNPs.

Results: We observed statistically significant differences in the frequencies of G allele in IL-1β rs16944 between anti-NMDAR encephalitis and controls (p = 0.017). Also, IL-1β, IL-4, IL-6, IL-10, and IL-17 SNPs were not associated with the disease (p > 0.05).

Conclusions: We found that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile, and we found that the decreased frequency of G allele in IL-1β rs16944 showed a protective role for anti-NMDAR encephalitis in the Southern Han Chinese.
Transcranial Direct Current Stimulation and Mirror Therapy for Neuropathic Pain After Brachial Plexus Avulsion: A Randomized, Double-Blind, Controlled Pilot Study
Authors: Ferreira Clarice Martins , de Carvalho Carolina Dias , Gomes Ruth , Bonifácio de Assis Erickson Duarte , Andrade Suellen Marinho
Published: December 2020

Introduction: Although transcranial direct current stimulation (tDCS) and mirror therapy (MT) have benefits in combating chronic pain, there is still no evidence of the effects of the simultaneous application of these techniques in patients with neuropathic pain. This study aims to assess the efficacy of tDCS paired with MT in neuropathic pain after brachial plexus injury.

Methods: In a sham controlled, double-blind, parallel-group design, 16 patients were randomized to receive active or sham tDCS administered during mirror therapy. Each patient received 12 treatment sessions, 30 min each, during a period of 4 weeks over M1 contralateral to the side of the injury. Outcome variables were evaluated at baseline and post-treatment using the McGill questionnaire, Brief Pain Inventory, and Medical Outcomes Study 36–Item Short-Form Health Survey. Long-term effects of treatment were evaluated at a 3-month follow-up.

Results: An improvement in pain relief and quality of life were observed in both groups (p ≤ 0.05). However, active tDCS and mirror therapy resulted in greater improvements after the endpoint (p ≤ 0.02). No statistically significant differences in the outcome measures were identified among the groups at follow-up (p ≥ 0.12). A significant relationship was found between baseline pain intensity and outcome measures (p ≤ 0.04). Moreover, the results showed that state anxiety is closely linked to post-treatment pain relief (p ≤ 0.05).

Conclusion: Active tDCS combined with mirror therapy has a short-term effect of pain relief, however, levels of pain and anxiety at the baseline should be considered.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT04385030.
Evaluation of Surgical Clipping and Endovascular Coiling on Oculomotor Nerve Palsy Caused by Internal Carotid Artery Aneurysm
Authors: Sun Zhenqing , Yan Xueqiang , Li Xiaolong , Wu Jie
Published: December 2020

Objectives: Internal carotid artery (ICA) aneurysm often leads to oculomotor nerve palsy (ONP) that impairs eye movement. Currently, microsurgical clipping and endovascular coiling are the two major options to treat ONP. The purpose of the current study is to compare the clinical outcomes of the two methods in patients with ONP caused by ICA aneurysm.

Patients and Methods: In the present study, we assessed the prognostic factors and recovery outcomes of a total of 90 ICA aneurysm-induced ONP patients, where 50 of them were treated with microsurgical clipping and 40 of them were treated with endovascular coiling. Within the endovascular coiling group, 20 of the patients were treated with balloon-assisted coiling and the other 20 were treated with stent-assisted coiling.

Results: Overall, we achieved a 59% (53 out of 90) full recovery rate. Both surgical clipping and endovascular coiling treatment methods achieved similar recovery outcomes in the tested patients. However, within the endovascular coiling group, balloon-assisted coiling treatment demonstrated a significantly higher full recovery rate (17 out of 20) compared to stent-assisted coiling treatment (eight out of 20).

Conclusion: In general, no significant difference was identified between the surgical and coiling treatments, and both procedures were considered as beneficial for ICA aneurysm-induced ONP.
Alteration of Cortical and Subcortical Structures in Children With Profound Sensorineural Hearing Loss
Authors: Qu Hang , Tang Hui , Pan Jiahao , Zhao Yi , Wang Wei
Published: December 2020

Profound sensorineural hearing loss (SNHL) is an auditory disability associated with auditory and cognitive dysfunction. Due to distinct pathogenesis, some associated structural and functional changes within the brain have been investigated in previous studies, but whole-brain structural alterations are incompletely understood. We extended the exploration of neuroanatomic differences in whole-brain structure in children with profound SNHL who are primarily users of Chinese sign language (CSL). We employed surface-based morphometry (SBM) and subcortical analyses. T1-weighted magnetic resonance images of 26 children with profound SNHL and 27 age- and sex-matched children with normal hearing were analyzed. Compared with the normal control (NC) group, children with profound SNHL showed diverse structural changes in surface-based and subcortical analyses, including decreased cortical thickness in the left postcentral gyrus, superior parietal lobule, paracentral lobule, precuneus, the right transverse temporal gyri, and the middle temporal gyrus; a noticeable increase in the Local Gyrification Index (LGI) in the left precuneus and superior parietal lobule; and diverse changes in gray-matter volume (GMV) in different brain regions. Surface-based vertex analyses revealed regional contractions in the right thalamus, putamen, pallidum, and the brainstem of children with profound SNHL when compared with those in the NC group. Volumetric analyses showed decreased volumes of the right thalamus and pallidum in children with profound SNHL. Our data suggest that children with profound SNHL are associated with diffuse cerebral dysfunction to cortical and subcortical nuclei, and revealed neuroplastic reorganization in the precuneus, superior parietal lobule, and temporal gyrus. Our study provides robust evidence for changes in connectivity and structure in the brain associated with hearing loss.
Cognitive Outcomes for Essential Tremor Patients Selected for Thalamic Deep Brain Stimulation Surgery Through Interdisciplinary Evaluations
Authors: Jones Jacob D. , Orozco Tatiana , Bowers Dawn , Hu Wei , Jabarkheel Zakia , Chiu Shannon , Ramirez-Zamora Adolfo , Foote Kelly , Okun Michael S. , Wagle Shukla Aparna
Published: December 2020

Objective: Deep brain stimulation (DBS) targeted to the ventral intermediate (VIM) nucleus of the thalamus is effective for motor symptoms in essential tremor (ET), but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients (pre-DBS and 1+ year after DBS).

Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function.

Results: We identified 50 ET DBS patients; 29 (58%) males; the mean age of tremor onset was 35.84 (±21.50) years with a median age of 38 years. The mean age at DBS was 68.18 (±10.07) years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment (pre vs. post) and age of tremor onset (<38 vs. >38 years); F(1,30) = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment (pre vs. post) and complications vs. no complications subgroups; F(1,45) = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant.

Conclusion: In this large cohort of ET patients with (>30% improvements), DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS.
A Nomogram Model Identifies Eosinophilic Frequencies to Powerfully Discriminate Kawasaki Disease From Febrile Infections
Authors: Liu Xiao-Ping , Huang Yi-Shuang , Xia Han-Bing , Sun Yi , Lang Xin-Ling , Li Qiang-Zi , Liu Chun-Yi , Kuo Ho-Chang , Huang Wei-Dong , Liu Xi
Published: December 2020

Background: Kawasaki disease (KD) is a form of systemic vasculitis that occurs primarily in children under the age of 5 years old. No single laboratory data can currently distinguish KD from other febrile infection diseases. The purpose of this study was to establish a laboratory data model that can differentiate between KD and other febrile diseases caused by an infection in order to prevent coronary artery complications in KD.

Methods: This study consisted of a total of 800 children (249 KD and 551 age- and gender-matched non-KD febrile infection illness) as a case-control study. Laboratory findings were analyzed using univariable, multivariable logistic regression, and nomogram models.

Results: We selected 562 children at random as the model group and 238 as the validation group. The predictive nomogram included high eosinophil percentage (100 points), high C-reactive protein (93 points), high alanine transaminase (84 points), low albumin (79 points), and high white blood cell (64 points), which generated an area under the curve of 0.873 for the model group and 0.905 for the validation group. Eosinophilia showed the highest OR: 5.015 (95% CI:−3.068–8.197) during multiple logistic regression. The sensitivity and specificity in the validation group were 84.1 and 86%, respectively. The calibration curves of the validation group for the probability of KD showed near an agreement to the actual probability.

Conclusion: Eosinophilia is a major factor in this nomogram model and had high precision for predicting KD. This report is the first among the existing literature to demonstrate the important role of eosinophil in KD by nomogram.
Case Report: A de novo CTNNB1 Nonsense Mutation Associated With Neurodevelopmental Disorder, Retinal Detachment, Polydactyly
Authors: KE Zhongling , CHEN Yanhui
Published: December 2020

CTNNB1 gene mutation was firstly reported related to intellectual disability in 2012, to explore the clinical phenotype and genotype characteristics of CTNNB1 mutation, we collected and analyzed the clinical data of a child with a neurodevelopmental disorder caused by a mutation of CTNNB1. The child had dysmorphic features, microcephaly, hypotonia, polydactyly, retinal detachment, and neurodevelopmental disorder, with a de novo mutation of CTNNB1 c.1603C > T, p.R535X. The patient was diagnosed as Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) and was given rehabilitation training. After 4 months of rehabilitation training, she improved in gross motor function. We found that CTNNB1 mutation can cause neurodevelopmental disorder, which could be accompanied by retinal detachment and polydactyly. The retinal detachment had only been reported in two Asian patients, and we firstly reported the phenotype of polydactyly in the CTNNB1 mutation. This report not only helps to expand the clinical phenotype spectrum of the CTNNB1 gene mutation but also prompts a new insight into genetic diagnosis in patients with a neurodevelopmental disorder, retinal detachment, and polydactyly.
Relationship Between Mutans Streptococci and Lactobacilli in the Oral Cavity and Intestine of Obese and Eutrophic Children With Early Childhood Caries—Preliminary Findings of a Cross-Sectional Study
Authors: Indiani Claudia Maria dos Santos Pereira , Rizzardi Karina Ferreira , Crescente Camila Lopes , Steiner-Oliveira Carolina , Nobre-dos-Santos Marinês , Parisotto Thaís Manzano
Published: December 2020

This brief communication assessed whether there was any relationship between the counts of lactobacilli (LB) and mutans streptococci (MS) in the oral cavity and intestine of obese and eutrophic children with early childhood caries (ECC). Seventy-eight preschoolers were assigned into the following groups: 1. obese children with ECC (OECC), 2. eutrophic children with ECC (EECC), 3. obese caries-free children (OCF), and 4. eutrophic caries-free children (ECF). The diagnosis of obesity and ECC was based on the World Health Organization criteria. Dental plaque and fecal samples were collected to assess the counts of MS and LB using selective media. Data were evaluated by Poisson regression analysis, Wilcoxon test, and Sign test. Microbial indicators of ECC in obese children were MS counts in the intestine [rate ratio (RR): 4.38] and presence of LB in the oral cavity (RR: 2.12). The indicators in eutrophic children were MS levels and the presence of LB, both in the oral cavity (RR: 6.35/1.50) and intestine (RR: 2.35/2.38) (p < 0.05). The comparison between MS levels in the mouth and in the intestine revealed significant differences only in the ECF group (p = 0.04). Regarding LB presence in the mouth vs. in the intestine, except for the OCF group (p = 0.03), no other statistical differences were found. Our preliminary findings highlighted that the levels of MS and the presence of LB in the oral cavity, as well as in the lower gastrointestinal tract were associated with ECC. Moreover, obesity was found to influence this relationship.
Social and Behavioral Difficulties in 10-Year-Old Children With Congenital Heart Disease: Prevalence and Risk Factors
Authors: Werninger Isabelle , Ehrler Melanie , Wehrle Flavia M. , Landolt Markus A. , Polentarutti Susanne , Valsangiacomo Buechel Emanuela R. , Latal Beatrice
Published: December 2020

Children with congenital heart disease (CHD) may be at increased risk for neurodevelopmental impairments. Long-term behavioral profiles and respective risk factors are less frequently described. The aim of this study was to evaluate multidimensional behavioral outcomes and associated medical, psychological, and social risk factors in children with complex CHD. At 10-years of age, 125 children with CHD were assessed for general behavioral difficulties, attention deficit hyperactivity disorder (ADHD)-related behavior, and social interaction problems and were compared to normative data. Medical and cardiac factors, IQ, maternal mental health at 4 years of age and parental socioeconomic status were tested as predictors for all behavioral outcomes. Children with CHD showed no significant differences in general behavioral difficulties. However, increased ADHD-related symptoms (p < 0.05) and difficulties in social interaction (p < 0.05) were observed. In 23% of the children, a combination of ADHD-related symptoms and social interaction problems was reported by parents. In multivariate analyses, IQ (p < 0.01) and maternal mental health (p < 0.03) at 4 years of age were found to be predictive for all behavioral outcomes at 10 years while medical and cardiac risk factors were not. Our findings reveal significant difficulties in ADHD-related symptoms and social interaction problems with a significant comorbidity. Behavioral difficulties were not detected with a screening tool but with disorder-specific questionnaires. Furthermore, we demonstrate the importance of maternal mental health during early childhood on later behavioral outcomes of children with CHD. This underlines the importance of identifying and supporting parents with mental health issues at an early stage in order to support the family and improve the child's neurodevelopment.
Trends in Physical Fitness Among School-Aged Children and Adolescents: A Systematic Review
Authors: Masanovic Bojan , Gardasevic Jovan , Marques Adilson , Peralta Miguel , Demetriou Yolanda , Sturm David Joseph , Popovic Stevo
Published: December 2020

Introduction and Objective: This systematic review aimed to analyse the international evolution of fitness with its distributional changes in the performance on tests of physical fitness among school-aged children and adolescents.

Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the search was undertaken in four international databases (ERIC, PubMed, Scopus, and Web of Science) to identify the studies reporting temporal trends in the physical fitness among school-aged children and adolescents.

Results: A total of 485 potential articles were identified, of which 19 articles were relevant for the qualitative synthesis; 1,746,023 children and adolescents from 14 countries (China, Finland, Sweden, Belgium, New Zealand, Denmark, Spain, Norway, Mozambique, Poland, USA, Lithuania, Portugal, Canada), for the period between 1969 and 2017 were included. The subjects were tested using 45 motor tests from eight battery tests. The quality of the study in eight articles was rated as strong, while in 11 articles it was rated as moderate.

Discussion: The vast majority of studies show a constant decline in strength and endurance. Three Chinese studies show an increase in strength from 1985 to 1995 and then a decline until 2014. For endurance, similar patterns were found in the two most comprehensive Chinese studies. The decline in flexibility is also evident in European countries. For agility, speed, balance, and coordination, the trend differs among populations.
Prevalence and Cognitive Profiles of Children With Comorbid Literacy and Motor Disorders
Authors: Downing Cameron , Caravolas Markéta
Published: December 2020

There is a high prevalence of comorbidity between neurodevelopmental disorders. Contemporary research of these comorbidities has led to the development of multifactorial theories of causation, including the multiple deficit model (MDM). While several combinations of disorders have been investigated, the nature of association between literacy and motor disorders remains poorly understood. Comorbid literacy and motor disorders were the focus of the two present studies. In Study 1, we examined the prevalence of comorbid literacy and motor difficulties relative to isolated literacy and motor difficulties in a community sample (N = 605). The prevalence of comorbidity was five times greater than expected by chance alone, implying some relationship between difficulties. In Study 2, we examined the cognitive profiles of children with literacy and motor disorders amongst a subsample of children from Study 1 (N = 153). Children with literacy disorder had deficits in phonological processing, selective attention, and memory whilst children with motor disorder had deficits in visuospatial processing and memory, suggesting the disorders should be considered to have both independent and shared (memory) cognitive risk factors. Children with comorbid literacy and motor disorder demonstrated an additive combination of these deficits. Together, these findings are consistent with predictions from the MDM.
Stress, Emotional Intelligence and the Intention to Use Cannabis in Spanish Adolescents: Influence of COVID-19 Confinement
Authors: Liébana-Presa Cristina , Martínez-Fernández María Cristina , Benítez-Andrades José Alberto , Fernández-Martínez Elena , Marqués-Sánchez Pilar , García-Rodríguez Isaías
Published: December 2020

The disease brought about by the SARS-CoV-2, COVID-19 coronavirus has had an unprecedented global impact. Confinement to control the outbreak may have mental health consequences for the most vulnerable in the population, including adolescents. This study aims to describe and analyze the relationships between the stress variables, Emotional Intelligence and the intention to use cannabis in healthy adolescents, before and after the end of the COVID-19 pandemic containment stage. A comparative correlational study was carried out with validated self-completed questionnaires through an online platform. The sample is made up of adolescents (n = 300) aged 13–17 from two different schools in Ponferrada (León, Spain). The analysis of correlation and differences between the groups indicate that confinement has had effects on the mental health of the adolescents, specifically on the emotional manifestations of stress. Furthermore, significant gender differences were found for stress values and Emotional Intelligence. However, no differences have been found for cannabis use intention.
The Relationship Between Serum Cytokine Levels and the Degree of Psychosis and Cognitive Impairment in Patients With Methamphetamine-Associated Psychosis in Chinese Patients
Authors: Yang Xue , Zhao Hui , Liu Xuebing , Xie Qin , Zhou Xiaoliang , Deng Qijian , Wang Gang
Published: December 2020

Background: Cytokine levels can be changed in methamphetamine (METH) use disorders (MUDs) and primary psychosis. The present study assessed serum levels of some kinds of interleukins (ILs) in METH-associated psychosis (MAP) and their relationships with psychotic symptoms and cognitive dysfunction.

Methods: Serum IL-2R, IL-6, IL-8, and IL-10 levels were examined by chemiluminescence assays in MAP patients (n = 119) and healthy controls (n = 108). The Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MOCA) were administered.

Results: Serum levels of IL-6 and IL-8 were significantly increased in MAP patients (all p < 0.05). There was a negative relationship between IL-2R levels and PANSS positive (P) subscale scores (r = −0.193, p = 0.035). IL-6, IL-8 and IL-10 levels were all negatively correlated with the naming, delayed recall and orientation subscores on the MOCA (r = −0.209, p = 0.022; r = −0.245, p = 0.007; r = −0.505, p < 0.001, respectively).

Conclusions: Our results indicate that immune disturbances are related to MAP and that IL-2R, IL-6, IL-8, and IL-10 are associated with the severity of psychotic symptoms and cognitive function impairment.
Factors Related to Non-participation in the Basque Country Colorectal Cancer Screening Programme
Authors: Solís-Ibinagagoitia M. , Unanue-Arza S. , Díaz-Seoane M. , Martínez-Indart L. , Lebeña-Maluf A. , Idigoras I. , Bilbao I. , Portillo I.
Published: December 2020

Background: Despite the high participation rates in the Basque Country, colorectal cancer screening programme (Spain), there is still a part of the population that has never participated. Since it is essential to ensure equal access to health services, it is necessary to identify the determinants of health and socio-economic factors related to non-participation in the screening programme.

Methods: Cross sectional descriptive study including all invited population in a complete round between 2015 and the first trimester of 2017. Health risk factors available in medical records and their control have been analyzed using univariate and multivariate analyses.

Results: 515,388 people were invited at the programme with a 71.9% of fecal immunochemical test participation rate. Factors that increase the risk of non-participation are: being men (OR = 1.10, 95% CI 1.09–1.12); younger than 60 (OR = 1.18, 95% CI 1.17–1.20); smoker (OR = 1.20, 95% CI 1.18–1.22); hypertensive (OR = 1.14, 95% CI 1.12–1.15) and diabetic (OR = 1.40, 95% CI 1.36–1.43); having severe comorbidity (OR = 2.09, 95% CI 2.00–2.19) and very high deprivation (OR = 1.15, 95% CI 1.12–1.17), as well as making <6 appointments to Primary Care in 3 years (OR = 2.39, 95% CI 2.33–2.45). Still, the area under the curve (AUC) indicates that there are more factors related to non-participation.

Conclusions: The participation in the Basque Country colorectal cancer-screening Programme is related to some risk factors controlled by Primary Care among others. Therefore, the involvement of these professionals could improve, not only the adherence to the CRC screening, but also other health styles and preventive interventions.
Comparison of Deaths Rates for COVID-19 across Europe During the First Wave of the COVID-19 Pandemic
Authors: Villani Leonardo , McKee Martin , Cascini Fidelia , Ricciardi Walter , Boccia Stefania
Published: December 2020

Background: Europe overall suffered greatly in the early stages of the COVID-19 pandemic but the impact of different countries varied. Italy was in the forefront, but there too there were differences, with the Lombardy region the epicentre of the pandemic.

Methods: We report Crude Mortality Rates (CMRs) from deaths reported as due to COVID-19 and, in five countries where age-specific data are available, Standardized Mortality Rates (SMRs) in the European Union and United Kingdom.

Results: As of 30th August 2020, Belgium was the country with the highest cumulative CMR (86.3/100,000), but the Lombardy region reached almost double this figure (167.6/100,000), far ahead of the corresponding figure for the rest of Italy at 37.0/100,000. SMRs could be calculated for five countries (Italy, Portugal, Sweden, Germany, and Netherlands). Among them, Sweden had the highest SMR (61.6/100,000). The corresponding figures for Italy, Netherlands, Portugal and Germany were 50.2, 41.4, 15.9, and 10.1 per 100,000, respectively.

Conclusion: It is clear that countries within Europe have performed very differently in their responses to the COVID-19 pandemic, but the many limitations in the available data must be addressed before a definitive assessment of the reasons for these differences can be made.