bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effect of Rapamycin-Loaded Small Extracellular Vesicles Derived from Mesenchymal Stem Cells on Experimental Autoimmune Uveitis
Authors: Li Huan , Zhang Zhihui , Li Yongtao , Su Lin , Duan Yanan , Zhang Hui , An Jinying , Ni Tianwen , Li Xiaorong , Zhang Xiaomin
Published: March 2022

Autoimmune uveitis is a major cause of vision loss and glucocorticoids are major traditional medications, which may induce serious complications. Rapamycin has been demonstrated to exhibit immunosuppressive effects and is promising to be used in treating uveitis by intravitreal injection. However, repeated and frequent intravitreal injections increase the risk of severe ocular complications, while the efficacy of subconjunctival injection of rapamycin is low since it is difficult for rapamycin to penetrate eyeball. Recently, small extracellular vesicles (sEVs) have attracted considerable research interest as natural drug delivery systems that can efficiently cross tissues and biological membranes. SEVs derived from mesenchymal stem cells (MSC-sEVs) also can exert immunosuppressive effect and ameliorate experimental autoimmune uveitis (EAU). The aim of this study was to construct a Rapamycin-loaded MSC-sEVs delivery system (Rapa-sEVs) and investigate its therapeutic effect on EAU by subconjunctival injection. Rapa-sEVs were prepared by sonication and characterized by nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Clinical and histological scores were obtained to assess the treatment efficacy. Additionally, T cell infiltration was evaluated by flow cytometry. The results indicated that Rapa-sEVs could reach the retinal foci after subconjunctival injection. Compared to sEVs and rapamycin alone, Rapa-sEVs can produce a more marked therapeutic effect and reduce ocular inflammatory cell infiltration. Overall, MSC-sEVs have significant potential for the delivery of rapamycin to treat EAU. Subconjunctival injection of Rapa-sEVs may be contender for efficacious steroid-sparing immunomodulatory therapy.
Diagnostic Performance of Rapid Antigen Testing for SARS-CoV-2: The COVid-19 AntiGen (COVAG) study
Authors: Wertenauer Christoph , Brenner Michael Geovana , Dressel Alexander , Pfeifer Caroline , Hauser Ulrike , Wieland Eberhard , Mayer Christian , Mutschmann Caren , Roskos Martin , Wertenauer Hans-Jörg , Moissl Angela P. , Lorkowski Stefan , März Winfried
Published: March 2022

Background

Rapid diagnostic testing for SARS-Cov-2 antigens is used to combat the ongoing pandemic. In this study we aimed to compare two RDTs, the SD Biosensor Q SARS-CoV-2 Rapid Antigen Test (Roche) and the Panbio COVID-19 Ag Rapid Test (Abbott), against rRT-PCR.

Methods

We included 2,215 all-comers at a diagnostic center between February 1 and March 31, 2021. rRT-PCR-positive samples were examined for SARS-CoV-2 variants.

Findings

Three hundred and thirty eight participants (15%) were rRT-PCR-positive for SARS-CoV-2. The sensitivities of Roche-RDT and Abbott-RDT were 60.4 and 56.8% (P < 0.0001) and specificities 99.7% and 99.8% (P = 0.076). Sensitivity inversely correlated with rRT-PCR-Ct values. The RDTs had higher sensitivities in individuals referred by treating physicians (79.5%, 78.7%) than in those referred by health departments (49.5%, 44.3%) or tested for other reasons (50%, 45.8%), in persons without any comorbidities (74.4%, 71%) compared to those with comorbidities (38.2%, 34.4%), in individuals with COVID-19 symptoms (75.2%, 74.3%) compared to those without (31.9%, 23.3%), and in the absence of SARS-CoV-2 variants (87.7%, 84%) compared to Alpha variant carriers (77.1%, 72.3%). If 10,000 symptomatic individuals are tested of which 500 are truly positive, the RDTs would generate 38 false-positive and 124 false-negative results. If 10,000 asymptomatic individuals are tested, including 50 true positives, 18 false-positives and 34 false-negatives would be generated.

Interpretation

The sensitivities of the two RDTs for asymptomatic SARS-CoV-2 carriers are unsatisfactory. Their widespread use may not be effective in the ongoing SARS-CoV-2 pandemic. The virus genotype influences the sensitivity of the two RDTs. RDTs should be evaluated for different SARS-CoV-2 variants.
Examination of Macular Retina and Choroidal Thickness in High Myopic Amblyopia Using Spectral-Domain Optical Coherence Tomography
Authors: Wan Juan , Zhang Zhengwei , Tian Yu
Published: March 2022

Purpose

The aim of this study was to investigate changes in the retinal and choroidal thickness between high myopic amblyopia (HMA), low myopia (LM), moderate myopia (MM), high myopia (HM), and normal group (NG) using a spectral-domain optical coherence tomography (SD-OCT).

Materials and Methods

A total of 75 Chinese children (128 eyes; mean age 10.5 years) were recruited. Retinal thickness (RT) and choroidal thickness (CT) were measured at different locations including subfoveal (SF), and at 0.5 mm/1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to the fovea in superior, nasal, inferior, and temporal sectors using enhanced depth imaging (EDI) system of SD-OCT. Axial length (AL), best-corrected visual acuity (BCVA), and refraction errors were also collected.

Results

No significant differences were found in subfoveal retinal thickness (SFRT). Moreover, a significantly thinner subfoveal choroidal thickness (SFCT) was found in HMA compared to NG, LM, and MM, but not compared to HM. RT at 0.5 mm to fovea, HMA was significantly thinner compared to LM and MM in the three sectors (superior, inferior, and temporal). Nevertheless, no significant differences were found compared to NG and HM. CT at 0.5 mm to fovea, HMA was the significantly thinnest in all four sectors compared to NG, LM, and MM. RT at 1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to fovea, HMA was thinner compared to NG, LM, and MM. CT at 1.0 mm/1.5 mm/2.0 mm/2.5 mm/3.0 mm to fovea, HMA was thinner compared to NG, LM, and MM. At the superior and inferior sectors, HMA showed to be statistically thinner compared with HM. Moreover, SFCT in the HMA, HM, and NG were negatively correlated with AL.

Conclusions

Thinner retina and choroidal tissue appear to be related to HMA, and thus can be used as useful parameters for discovering the underlying mechanisms of the disease.
Case Report: Lyme Borreliosis and Pregnancy - Our Experience
Authors: Trevisan Giusto , Ruscio Maurizio , di Meo Nicola , Nan Katiuscia , Cinco Marina , Trevisini Sara , Forgione Patrizia , Bonin Serena
Published: March 2022

Lyme Borreliosis (LB) is an infection transmitted by Ixodes sp. ticks. Its early manifestation includes erythema migrans rash. Since the discovery of LB in 1975, the question arose as to whether this infection could be vertically transmitted from mother to fetus during pregnancy, as transplacental transmission has already been known for other spirochetoses, such as syphilis, relapsing fever and leptospirosis. The first confirmed case with positive Lyme serology was described in 1985 in a 28-year- old mother who had acquired Lyme in the first trimester and then developed an erythema migrans rash. Subsequently, transmission of Borrelia burgdorferi sl. in humans from mother to fetus has been documented through identification of Borrelia spirochetes in fetal tissues/and or placenta by various methods including culture, PCR and indirect immunofluorescence. Adverse birth outcomes, which are limited in case of prompt LB treatment, included spontaneous miscarriage, preterm birth and hyperbilirubinemia, but also cardiac involvement and cutaneous angiomas have been documented although rarely. No significant associations were found between adverse outcomes at birth and the trimester of infection. Patients treated for gestational LB had a lower frequency of miscarriages and premature births, as also the frequency of congenital malformations was similar to that observed in the normal population. The recommended treatment for LB in pregnancy is Amoxicillin, 1 g 3 times a day for 14–21 days. In the present study, we report our case series, which includes 11 pregnant women, 6 of which developed erythema migrans during pregnancy (between week 8 and 34), 3 had myoarticular or neurological symptoms and 2 had positive serology, but did not develop any clinical symptoms. Our data stress on the importance of early antibiotic treatment also in seropositive gestating women without symptoms in order to avoid any possible complication to fetus and newborns.
Virtual Simulation in Undergraduate Medical Education: A Scoping Review of Recent Practice
Authors: Wu Qingming , Wang Yubin , Lu Lili , Chen Yong , Long Hui , Wang Jun
Published: March 2022

Virtual simulation (VS) as an emerging interactive pedagogical strategy has been paid more and more attentions in the undergraduate medical education. Because of the fast development of modern computer simulation technologies, more and more advanced and emerging VS-based instructional practices are constantly increasing to promote medical education in diverse forms. In order to describe an overview of the current trends in VS-based medical teaching and learning, this scoping review presented a worldwide analysis of 92 recently published articles of VS in the undergraduate medical teaching and learning. The results indicated that 98% of included articles were from Europe, North America, and Asia, suggesting a possible inequity in digital medical education. Half (52%) studies reported the immersive virtual reality (VR) application. Evidence for educational effectiveness of VS in medical students’ knowledge or skills was sufficient as per Kirkpatrick’s model of outcome evaluation. Recently, VS has been widely integrated in surgical procedural training, emergency and pediatric emergency medicine training, teaching of basic medical sciences, medical radiation and imaging, puncture or catheterization training, interprofessional medical education, and other case-based learning experiences. Some challenges, such as accessibility of VS instructional resources, lack of infrastructure, “decoupling” users from reality, as well as how to increase students’ motivation and engagement, should be addressed.
A Bibliometric Analysis of Publications on Endoscopic Ultrasound
Authors: Chen Xiaoli , He Huiqin , Chen Xin , Chen Xueqin , Wen Zhenzhen , Xu Mengque , Fang Yanfei , He Xingkang
Published: March 2022

Background

Over the past 40 years, endoscopic ultrasound (EUS) has become a safe and effective tool for both diagnostic and therapeutic applications. A growing number of articles have been published annually. We aimed to explore global scientific outputs and hotspots of EUS published by different countries, organizations, and authors.

Methods

The global literature regarding EUS during the 1900–2020 period was identified from the Web of Science (WOS) Core database. “Bibliometrix” and software VOSviewer were applied to perform bibliometric analysis.

Results

The annual growth rate of publications from 1980 to 2020 was around 16% and the number of EUS-related articles had experienced a sudden increase in the last decade. Bhutani MS was the most productive author over the past years, with 94 publications. Hawes RH had the highest number of citations, with 6,034 citations. The United States and institutions from United States dominated the EUS research. Among the journals, GASTROINTESTINAL ENDOSCOPY published the highest number of articles, followed by ENDOSCOPY. The majority of top 10 frequently cited references were cited more than 200 times. Carcinoma, diagnosis, fine-needle-aspiration, cytology, and pancreatitis were the important keywords in co-occurrence analysis of keywords. Recent studies focused more on tissue acquisition, size of the needle, lumen-apposing metal stent, and fine-needle- biopsy.

Conclusion

Research on EUS has significantly increased in the last decade globally and it will continue to increase. Active collaboration among different authors and countries was observed in the EUS field. Tissue acquisition, size of the needle, apposing metal stent, and fine-needle-biopsy might be the latest research frontiers and should receive more attention.
The N1038S Substitution and 1153EQTRPKKSV1162 Deletion of the S2 Subunit of QX-Type Avian Infectious Bronchitis Virus Can Synergistically Enhance Viral Proliferation
Authors: Li Shuyun , Fan Shunyi , Li Nianning , Shen Yuxi , Xiang Xuelian , Chen Wen , Xia Jing , Han Xinfeng , Cui Min , Huang Yong
Published: March 2022

The S2 subunit of infectious bronchitis virus (IBV) plays a critical role in the process of IBV infection. A comparison between the S2 subunit sequence of chicken embryo kidney cell (CEK) adapted virulent QX-like IBV strain SczyC30 (hereafter referred to as zy30) and its CEK-attenuated strain, SczyC100, revealed an N1038S substitution in S2 subunit and a 1154EQTRPKKSV1162 residue deletion in the C-terminus of the S2 subunit. In order to explore whether these two mutations are related to changes in the biological characteristics of IBV, we firstly constructed an infectious clone of zy30 using a bacterial artificial chromosome (BAC), which combines the transcription of infectious IBV genomic RNA in non-susceptible BHK-21 cells with the amplification of rescued virus rzy30 in CEK cells. Then, three recombinant viruses, including an rzy30S2-N1038S strain that contained the N1038S substitution, an rzy30S2-CT9△ strain that contained the 1154EQTRPKKSV1162 deletion, and an rzy30S2-N1038S-CT9△ strain that contained both mutations, were constructed using rescued virus rzy30 as the backbone. The results showed that each mutation did not significantly affect the replication titer in CEK cells but reduced pathogenicity in chickens, while in combination, the N1038S substitution and 1154EQTRPKKSV1162 deletion improved the proliferation efficiency in CEK cells and reduced pathogenicity, compared to rzy30 strain. The contribution made by the 1154EQTRPKKSV1162 deletion in reducing pathogenicity was higher than that of N1038S substitution. Our results revealed that the N1038S substitution and 1154EQTRPKKSV1162 deletion in S2 subunit were deeply involved in the replication efficiency of IBV and contributed to reduction of viral pathogenicity.
Application of per-Residue Energy Decomposition to Design Peptide Inhibitors of PSD95 GK Domain
Authors: Tian Miao , Li Hongwei , Yan Xiao , Gu Jing , Zheng Pengfei , Luo Sulan , Zhangsun Dongting , Chen Qiong , Ouyang Qin
Published: March 2022

Specific interaction between the postsynaptic density protein 95 (PSD95) and synapse-associated protein 90/postsynaptic density 95–associated protein (SAPAP) is crucial for excitatory synaptic development and plasticity. Designing inhibitors that target the guanylate kinase (GK) domain of PSD95, which is responsible for the interaction, is a promising manipulation tool for the investigation of the function of PSD95 GK and the etiology of its related psychiatric disorders. Herein, we designed new peptide inhibitors of PSD95 GK/SAPAP with higher binding affinity by using molecular dynamics simulations. First, the interactions between PSD95 GK and their reported phosphorylated and unphosphorylated peptides were explored by molecular dynamics simulations. Besides the hydrogen bonding interactions mediated by the phospho-serine (p-Ser) or corresponding phosphomimic residue Asp/Glu, the hydrophobic interactions from the other amino acids also contribute to the PSD95 GK/SAPAP interaction. As an unphosphorylated synthetic peptide with moderate binding affinity and relatively lower molecular weight, the QSF inhibitory peptide was selected for further modification. Based on per-residue energy decomposition results of the PSD95 GK/QSF complex, ten peptides were designed to enhance the binding interactions, especially the hydrophobic interactions. The top-ranked five peptides with lower binding energy were eventually synthesized. The binding affinities of the synthesized peptides were determined using fluorescence polarization (FP) assay. As expected, all peptides have higher binding affinity than the QSF peptide (Ki = 5.64 ± 0.51 μM). Among them, F10W was the most potent inhibitor (Ki = 0.75 ± 0.25 μM), suggesting that enhancement of the hydrophobic interactions is an important strategy for the design of new inhibitory peptides targeting PSD95 GK.
Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis
Authors: Arif Sheikh Mohammed , Floto R. Andres , Blundell Tom L.
Published: March 2022

Cystic fibrosis (CF) is progressive genetic disease that predisposes lungs and other organs to multiple long-lasting microbial infections. Pseudomonas aeruginosa is the most prevalent and deadly pathogen among these microbes. Lung function of CF patients worsens following chronic infections with P. aeruginosa and is associated with increased mortality and morbidity. Emergence of multidrug-resistant, extensively drug-resistant and pandrug-resistant strains of P. aeruginosa due to intrinsic and adaptive antibiotic resistance mechanisms has failed the current anti-pseudomonal antibiotics. Hence new antibacterials are urgently needed to treat P. aeruginosa infections. Structure-guided fragment-based drug discovery (FBDD) is a powerful approach in the field of drug development that has succeeded in delivering six FDA approved drugs over the past 20 years targeting a variety of biological molecules. However, FBDD has not been widely used in the development of anti-pseudomonal molecules. In this review, we first give a brief overview of our structure-guided FBDD pipeline and then give a detailed account of FBDD campaigns to combat P. aeruginosa infections by developing small molecules having either bactericidal or anti-virulence properties. We conclude with a brief overview of the FBDD efforts in our lab at the University of Cambridge towards targeting P. aeruginosa infections.
Internetwork Connectivity Predicts Cognitive Decline in Parkinson’s and Is Altered by Genetic Variants
Authors: Wei Xiangyu , Shen Qian , Litvan Irene , Huang Mingxiong , Lee Roland R. , Harrington Deborah L.
Published: March 2022

In Parkinson’s disease (PD) functional changes in the brain occur years before significant cognitive symptoms manifest yet core large-scale networks that maintain cognition and predict future cognitive decline are poorly understood. The present study investigated internetwork functional connectivity of visual (VN), anterior and posterior default mode (aDMN, pDMN), left/right frontoparietal (LFPN, RFPN), and salience (SN) networks in 63 cognitively normal PD (PDCN) and 43 healthy controls who underwent resting-state functional MRI. The functional relevance of internetwork coupling topologies was tested by their correlations with baseline cognitive performance in each group and with 2-year cognitive changes in a PDCN subsample. To disentangle heterogeneity in neurocognitive functioning, we also studied whether α-synuclein (SNCA) and microtubule-associated protein tau (MAPT) variants alter internetwork connectivity and/or accelerate cognitive decline. We found that internetwork connectivity was largely preserved in PDCN, except for reduced pDMN-RFPN/LFPN couplings, which correlated with poorer baseline global cognition. Preserved internetwork couplings also correlated with domain-specific cognition but differently for the two groups. In PDCN, stronger positive internetwork coupling topologies correlated with better cognition at baseline, suggesting a compensatory mechanism arising from less effective deployment of networks that supported cognition in healthy controls. However, stronger positive internetwork coupling topologies typically predicted greater longitudinal decline in most cognitive domains, suggesting that they were surrogate markers of neuronal vulnerability. In this regard, stronger aDMN-SN, LFPN-SN, and/or LFPN-VN connectivity predicted longitudinal decline in attention, working memory, executive functioning, and visual cognition, which is a risk factor for dementia. Coupling strengths of some internetwork topologies were altered by genetic variants. PDCN carriers of the SNCA risk allele showed amplified anticorrelations between the SN and the VN/pDMN, which supported cognition in healthy controls, but strengthened pDMN-RFPN connectivity, which maintained visual memory longitudinally. PDCN carriers of the MAPT risk allele showed greater longitudinal decline in working memory and increased VN-LFPN connectivity, which in turn predicted greater decline in visuospatial processing. Collectively, the results suggest that cognition is maintained by functional reconfiguration of large-scale internetwork communications, which are partly altered by genetic risk factors and predict future domain-specific cognitive progression.
Oral Mucosa Derived α−Synuclein as a Potential Diagnostic Biomarker for Parkinson′s Disease
Authors: Zheng Yuanchu , Yu Zhenwei , Zhao Jiajia , Cai Huihui , Wang Zhan , Wang Xuemei , Feng Tao
Published: March 2022

Background

Pathological α-synuclein (α-Syn) is not only exclusive to the central nervous system (CNS) in Parkinson’s disease (PD), but also extended to biofluids and peripheral tissues including oral cavity. Both oral mucosa and nervous system are derived from ectodermal tissue, and potentially share common disease-specific characteristics. Oral mucosal exfoliative cytology is a non-invasive technique, which is an easily acceptable for patients and ordinary people. The purpose of this study was to determine the abnormal accumulation of α-Syn in oral mucosa of PD patients and to learn the diagnostic utility of oral mucosa α-Syn for PD.

Methods

The oral mucosa samples were obtained from 57 patients with PD and 51 age-matched controls by cytological brush. Immunofluorescence analysis was used to investigate the presence and subcellular localization of α-Syn, phosphorylated α-Syn at Ser129 (pS129) and oligomeric α-Syn in the oral mucosa cells of PD patients and controls. Images taken as Z-stacks were analyzed for 3D reconstruction to visualize the α-Syn intracellular localization. Then, the concentrations of α-Syn, pS129, and oligomeric α-Syn in oral mucosa samples were measured using electrochemiluminescence assays.

Results

Immunofluorescence images revealed the increased α-Syn, pS129, and oligomeric α-Syn levels in oral mucosa cells of PD patients than age-matched controls. The intracellular distributions of α-Syn species were determine by Z-stack images with 3D reconstruction, and α-Syn was detected in both the nucleus and cytoplasm. However, pS129 was mainly located in the cytoplasm, and oligomeric α-Syn was highly expressed in the nucleus and perinuclear cytoplasm. The concentrations of three α-Syn species were significantly increased in the oral mucosa cell samples of PD patients than controls (α-Syn, p = 0.001; pS129, p = 0.002; oligomeric α-Syn, p = 0.013). In PD patients, the oral mucosa α-Syn and oligomeric α-Syn levels were significantly correlated with Hoehn-Yahr scales (α-Syn, r = 0.495, p = 0.001; oligomeric α-Syn, r = 0.324, p = 0.03). The area under curve (AUC) of ROC analysis using an integrative model including α-Syn, pS129, and oligomeric α-Syn for PD diagnosis was 0.749, with 66.7% sensitivity and 72.5% specificity.

Conclusion

This study for the first time demonstrated increased expressions of α-Syn, pS129, and oligomeric α-Syn in oral mucosa cells from PD patients, which serve as useful and non-invasive PD diagnostic biomarkers.
Cerebellar Circuits for Classical Fear Conditioning
Authors: Hwang Kyoung-Doo , Kim Sang Jeong , Lee Yong-Seok
Published: March 2022

Accumulating evidence indicates that the cerebellum is critically involved in modulating non-motor behaviors, including cognition and emotional processing. Both imaging and lesion studies strongly suggest that the cerebellum is a component of the fear memory network. Given the well-established role of the cerebellum in adaptive prediction of movement and cognition, the cerebellum is likely to be engaged in the prediction of learned threats. The cerebellum is activated by fear learning, and fear learning induces changes at multiple synaptic sites in the cerebellum. Furthermore, recent technological advances have enabled the investigation of causal relationships between intra- and extra-cerebellar circuits and fear-related behaviors such as freezing. Here, we review the literature on the mechanisms underlying the modulation of cerebellar circuits in a mammalian brain by fear conditioning at the cellular and synaptic levels to elucidate the contributions of distinct cerebellar structures to fear learning and memory. This knowledge may facilitate a deeper understanding and development of more effective treatment strategies for fear-related affective disorders including post-traumatic stress or anxiety related disorders.
Regulation of Social Recognition Memory in the Hippocampal Circuits
Authors: Wang Xinnian , Zhan Yang
Published: March 2022

Social recognition memory reflects the ability of the social animals to recognize and remember familiar individuals of the same species. The unique ability for mammals to recognize conspecifics is essential and beneficial when animals conduct daily social activities. This brief review summarizes a brain network underlying social recognition memory and explores the possible relationships between social isolation and social recognition memory. Finally, we introduce some possible related molecular mechanisms underlying social recognition memory. These findings help us explore potential targeting brain areas or circuits of social communication disorder.
COVID-19 Outcomes in Myasthenia Gravis Patients: Analysis From Electronic Health Records in the United States
Authors: Kim Youngran , Li Xiaojin , Huang Yan , Kim Minseon , Shaibani Aziz , Sheikh Kazim , Zhang Guo-Qiang , Nguyen Thy Phuong
Published: March 2022

Background

Myasthenia gravis (MG) is an autoimmune, neuromuscular condition and patients with MG are vulnerable due to immunosuppressant use and disease manifestations of dyspnea and dysphagia during the coronavirus disease 2019 (COVID-19) pandemic.

Methods

We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Primary outcomes, such as hospitalization, ventilator use, intensive care unit (ICU) admission, and death in COVID-19 patients with MG, were compared with those of COVID-19 patients without MG: the subgroups of non-MG included those with rheumatoid arthritis (RA), systemic lupus (SLE), and multiple sclerosis (MS). We further analyzed factors affecting mortality, such as age, race/ethnicity, comorbidities, and MG treatments.

Results

Among 421,086 individuals with COVID-19, there were 377 patients with MG, 7,362 patients with RA, 1,323 patients with SLE, 1,518 patients with MS, and 410,506 patients without MG. Patients with MG were older and had more comorbidities compared with non-MG patients and had the highest rates of hospitalization (38.5%), ICU admission (12.7%), ventilator use (3.7%), and mortality (10.6%) compared with all other groups. After adjusting for risk factors, patients with MG had increased risks for hospitalization and ICU compared with patients with non-MG and with RA but had risks similar to patients with SLE and with MS. The adjusted risk for ventilator use was similar across all groups, but the risk for mortality in patients with MG was lower compared with the SLE and MS groups. Among patients with MG, age over 75 years and dysphagia were predictors for increased COVID-19 mortality, but the recent MG treatment was not associated with COVID-19 mortality.

Conclusions

COVID-19 patients with MG are more likely to be admitted to the hospital and require ICU care. Older age and patients with dysphagia had an increased risk of mortality.
Using Motor Imagery to Access Alternative Attentional Strategies When Navigating Environmental Boundaries to Prevent Freezing of Gait – A Perspective
Authors: How Daniella , Wagner Heiko , Brach Michael
Published: March 2022

Freezing of gait can cause reduced independence and quality of life for many with Parkinson’s disease. Episodes frequently occur at points of transition such as navigating a doorway. Therapeutic interventions, i.e., drugs and exercise, do not always successfully mitigate episodes. There are several different, but not exclusive causes for freezing of gait. People with freezing of gait are able to navigate dynamic situations like stairways by utilizing a different attentional strategy to over-ground walking, but may freeze when passing through a doorway. The question is, is it possible to employ a special attentional strategy to prevent freezing at this point? Motor imagery allows for learning motor skills in absolute safety and has been widely employed in a variety of populations, including other neuro-compromised groups. Motor imagery is not studied in a homologous manner in people with Parkinson’s Disease, leading to conflicting results, but may have the potential to establish a different attentional strategy which allows a subject to mitigate freezing of gait episodes. This paper will identify and discuss the questions that still need to be answered in order to consider this approach i.e., can this population access motor imagery, can motor imagery alter the attentional strategy employed when moving through doorways, what is the best motor imagery approach for people with Parkinson’s Disease and freezing of gait, and what dosage is most effective, while briefly outlining future research considerations.
The Obese Brain: Mechanisms of Systemic and Local Inflammation, and Interventions to Reverse the Cognitive Deficit
Authors: Salas-Venegas Verónica , Flores-Torres Rosa Pamela , Rodríguez-Cortés Yesica María , Rodríguez-Retana Diego , Ramírez-Carreto Ricardo Jair , Concepción-Carrillo Luis Edgar , Pérez-Flores Laura Josefina , Alarcón-Aguilar Adriana , López-Díazguerrero Norma Edith , Gómez-González Beatriz , Chavarría Anahí , Konigsberg Mina
Published: March 2022

Overweight and obesity are now considered a worldwide pandemic and a growing public health problem with severe economic and social consequences. Adipose tissue is an organ with neuroimmune-endocrine functions, which participates in homeostasis. So, adipocyte hypertrophy and hyperplasia induce a state of chronic inflammation that causes changes in the brain and induce neuroinflammation. Studies with obese animal models and obese patients have shown a relationship between diet and cognitive decline, especially working memory and learning deficiencies. Here we analyze how obesity-related peripheral inflammation can affect central nervous system physiology, generating neuroinflammation. Given that the blood-brain barrier is an interface between the periphery and the central nervous system, its altered physiology in obesity may mediate the consequences on various cognitive processes. Finally, several interventions, and the use of natural compounds and exercise to prevent the adverse effects of obesity in the brain are also discussed.
Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I
Authors: de Oliveira Galassi Taynah , Fernandes Paula Franson , Salgado Afonso Shiguemi Inoue , Cidral-Filho Francisco José , Piovezan Anna Paula , Lüdtke Daniela Dero , Mack Josiel Mileno , Weber Kenneth A. , Reed William R. , Bobinski Franciane , Martins Daniel F.
Published: March 2022

Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1β concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals’ locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.
Astrocytes and Microglia Exhibit Cell-Specific Ca2+ Signaling Dynamics in the Murine Spinal Cord
Authors: Rieder Phillip , Gobbo Davide , Stopper Gebhard , Welle Anna , Damo Elisa , Kirchhoff Frank , Scheller Anja
Published: March 2022

The spinal cord is the main pathway connecting brain and peripheral nervous system. Its functionality relies on the orchestrated activity of both neurons and glial cells. To date, most advancement in understanding the spinal cord inner mechanisms has been made either byin vivoexposure of its dorsal surface through laminectomy or by acuteex vivoslice preparation, likely affecting spinal cord physiology in virtue of the necessary extensive manipulation of the spinal cord tissue. This is especially true of cells immediately responding to alterations of the surrounding environment, such as microglia and astrocytes, reacting within seconds or minutes and for up to several days after the original insult. Ca2+signaling is considered one of the most immediate, versatile, and yet elusive cellular responses of glia. Here, we induced the cell-specific expression of the genetically encoded Ca2+indicator GCaMP3 to evaluate spontaneous intracellular Ca2+signaling in astrocytes and microglia. Ca2+signals were then characterized in acuteex vivo(both gray and white matter) as well as in chronicin vivo(white matter) preparations using MSparkles, a MATLAB-based software for automatic detection and analysis of fluorescence events. As a result, we were able to segregate distinct astroglial and microglial Ca2+signaling patterns along with method-specific Ca2+signaling alterations, which must be taken into consideration in the reliable evaluation of any result obtained in physiological as well as pathological conditions. Our study revealed a high degree of Ca2+signaling diversity in glial cells of the murine spinal cord, thus adding to the current knowledge of the astonishing glial heterogeneity and cell-specific Ca2+dynamics in non-neuronal networks.
Long Non-coding RNA and mRNA Expression Change in Spinal Dorsal Horn After Exercise in Neuropathic Pain Rats
Authors: Song Ge , Zhang Wei-Ming , Wang Yi-Zu , Guo Jia-Bao , Zheng Yi-Li , Yang Zheng , Su Xuan , Chen Yu-Meng , Xie Qing , Wang Xue-Qiang
Published: March 2022

Exercise can help inhibition of neuropathic pain (NP), but the related mechanism remains being explored. In this research, we performed the effect of swimming exercise on the chronic constriction injury (CCI) rats. Compared with CCI group, the mechanical withdrawal threshold of rats in the CCI-Swim group significantly increased on the 21st and 28th day after CCI surgery. Second-generation RNA-sequencing technology was employed to investigate the transcriptomes of spinal dorsal horns in the Sham, CCI, and CCI-Swim groups. On the 28th day post-operation, 306 intersecting long non-coding RNAs (lncRNAs) and 173 intersecting mRNAs were observed between the CCI vs Sham group and CCI-Swim vs CCI groups. Then, the biological functions of lncRNAs and mRNAs in the spinal dorsal horn of CCI rats were then analyzed. Taking the results together, this study could provide a novel perspective for the treatment for NP.
Dietary Magnesium Intake Affects the Vitamin D Effects on HOMA-β and Risk of Pancreatic β-Cell Dysfunction: A Cross-Sectional Study
Authors: Gong Rongpeng , Liu Yuanyuan , Luo Gang , Yang Lixin
Published: March 2022

Background

Some studies have shown that, the circulating vitamin D (Vit D) concentration in the body exerts a crucial role in regulating the pancreatic β-cell function. Meanwhile, the role of magnesium is important in the synthesis of Vit D, since it is an essential element for activating Vit D. Nevertheless, there remains insufficient studies concerning whether dietary Magnesium intake influences the association between Vit D and risk of pancreatic β-cell dysfunction. Hence, this cross-sectional study aimed to assess the effect of Magnesium intake alterations on the association between serum Vit D levels and the risk of pancreatic β-cell dysfunction.

Methods

This large-scale cross-sectional study involves four cycles of National Health and Nutrition Examination Survey (NHANES) (2007–2014), with totally 4,878 participants. Groups were divided depending on the median daily intake of Magnesium, namely, the low intake group (Magnesium intake <267 Magnesium/d) and the high intake group (Magnesium intake ≥ 267 Magnesium/d). By constructing multiple multivariate linear and logistics regression models, the associations between serum Vit D levels and HOMA-β, as well as between serum Vit D levels and the risk of pancreatic β-cell dysfunction were explored at different Magnesium intakes.

Results

In this cross-sectional study, the serum Vit D level is independently correlated with the HOMA-β index [β: 0.65 (0.40–0.90)] and the risk of pancreatic β-cell dysfunction [OR: 0.95 (0.92–0.98)]. Moreover, such correlations are affected by different dietary Magnesium intakes (P for interaction < 0.001).

Conclusion

According to the results of this study, the dietary Magnesium intake influences the associations of serum Vit D levels with HOMA-β index and pancreatic β-cell dysfunction. Besides, the finding requires validation through more RCT or cohort studies.
Asymptomatic Primary Tumor Resection in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Shu Yefei , Xu Ling , Yang Wei , Xu Xiaofeng , Zheng Song
Published: March 2022

Background

In patients with metastatic colorectal cancer (mCRC) with an asymptomatic primary tumor, there is no consensus on the indication for resection of the primary tumor.

Methods

The PubMed, Embase and the Cochrane Library databases were searched from inception to November 30,2021. A meta-analysis was performed using RevMan (version 5.3.3; The Cochrane Collaboration) on the outcome of mCRC patients with or without resection of the primary tumor in 8 selected studies.

Results

This meta-analysis included 2805 colorectal cancer patients with an asymptomatic primary tumor from 8 selected studies. Primary tumor resection (PTR) patients had longer overall survival (OS: MD =6.76 [3.39, 10.12], I2 = 77%, P < 0.0001), compared with non-primary tumor resection (NPTR) patients. In the subgroup, the randomized controlled trials (RCT) PTR group didn’t have longer overall survival (OS: MD =3.79 [-3.49, 11.08], I2 = 69%, P= 0.31); the Non-RCT PTR group had longer overall survival (OS: MD =8.42 [3.14, 13.70], I2 = 89%, P= 0.002). In the meanwhile, compared with NPTR group, the 2-year overall survival rate, the 3-year overall survival rate, 5-year overall survival rate in the PTR group is higher (OR=2.35 [1.74, 3.18], I2 = 0%, P < 0.00001; OR=3.61 [2.35, 5.54], I2 = 0%, P < 0.00001; OR=3.02 [1.72, 5.33], I2 = 48%, P= 0.0001, respectively).

Conclusions

Our results from studies demonstrate that the resection of primary tumor is a prognostic factor for survival in mCRC patients. However, 2 RCTs showed the resection of primary tumor was not related with a significant survival benefit in subgroup. Therefore, a larger RCT in the era of modern chemotherapy and liver resection techniques would be helpful.
Exploring the Feasibility of Utilizing Limited Gene Panel Circulating Tumor DNA Clearance as a Biomarker in Patients With Locally Advanced Non-Small Cell Lung Cancer
Authors: Knapp Brendan , Mezquita Laura , Devarakonda Siddhartha , Aldea Mihaela , Waqar Saiama N. , Pepin Kym , Ward Jeffrey P. , Botticella Angela , Howarth Karen , Knape Charlene , Morris Clive , Govindan Ramaswamy , Besse Benjamin , Morgensztern Daniel
Published: March 2022

Introduction

Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC.

Methods

Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst®-Lung to detect mutations in 36 cancer-related genes. ctDNA clearance was defined as absence of pre-CRT variants at post-CRT1. Patients without detectable pre-CRT variants or no post-CRT1 samples were excluded.

Results

Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01).

Conclusions

Although it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer.
Moringa Oleifera Lam. in Cardiometabolic Disorders: A Systematic Review of Recent Studies and Possible Mechanism of Actions
Authors: Louisa Melva , Patintingan Cyntia Gracesella Hutami , Wardhani Bantari W. K.
Published: March 2022

Cardiometabolic disorders (CMD) have become a global emergency and increasing burden on health and economic problems. Due to the increasing need for new drugs for cardiometabolic diseases, many alternative medicines from plants have been considered and studied. Moringa oleifera Lam. (MO), one of the native plants from several Asian countries, has been used empirically by people for various kinds of illnesses. In the present systematic review, we aimed to investigate the recent studies of MO in CMD and its possible mechanism of action. We systematically searched from three databases and summarized the data. This review includes a total of 108 papers in nonclinical studies and clinical trials of MO in cardiometabolic-related disorders. Moringa oleifera, extracts or isolated compound, exerts its effect on CMD through its antioxidative, anti-inflammatory actions resulting in the modulation in glucose and lipid metabolism and the preservation of target organ damage. Several studies supported the beneficial effect of MO in regulating the gut microbiome, which generates the diversity of gut microbiota and reduces the number of harmful bacteria in the caecum. Molecular actions that have been studied include the suppression of NF-kB translocation, upregulation of the Nrf2/Keap1 pathway, stimulation of total antioxidant capacity by reducing PKCζ activation, and inhibiting the Nox4 protein expression and several other proposed mechanisms. The present review found substantial evidence supporting the potential benefits of Moringa oleifera in cardiovascular or metabolic disorders.
Kampo Medicine Promotes Early Recovery From Coronavirus Disease 2019-Related Olfactory Dysfunction: A Retrospective Observational Study
Authors: Ono Rie , Arita Ryutaro , Takayama Shin , Kikuchi Akiko , Ohsawa Minoru , Saito Natsumi , Suzuki Satoko , Ishii Tadashi
Published: March 2022

Background: Olfactory dysfunction is a common symptom in patients with coronavirus disease 2019, and it significantly deteriorates patients’ quality of life. Effective treatments remain unknown.

Purpose: To assess the effect of Japanese traditional (Kampo) medicine on coronavirus disease 2019-related olfactory dysfunction.

Study Design: Retrospective observational study.

Methods: In total, 87 patients aged ≥18 years with coronavirus disease 2019 and severe dysosmia or anosmia (Numeric Rating Scale, ≥7) at isolation facilities in Miyagi Prefecture, Japan, were enrolled from October 2020 to March 2021. Patients were divided into the Kampo group (N = 52) and the control group (N = 35) based on the treatment received. Changes in Numeric Rating Scale scores were evaluated at the first visit and 2 weeks after.

Results: The median reduction in the olfactory dysfunction score at both 1 and 2 weeks after the first visit was significantly greater in the Kampo group (6 and 8, respectively; p = 0.03) than in the control group (3 and 7, respectively; p = 0.04). We defined improvement in olfactory dysfunction as a median reduction in the olfactory dysfunction score of ≥5. Multiple logistic regression analysis demonstrated that only Kampo treatment was significantly associated with improvement in olfactory dysfunction.

Conclusion: This study suggests that Kampo medication promotes early recovery from coronavirus disease 2019-related olfactory dysfunction.
A Clinical Practice Guideline for the Emergency Management of Anaphylaxis (2020)
Authors: Li Xiaotong , Ma Qingbian , Yin Jia , Zheng Ya’an , Chen Rongchang , Chen Yuguo , Li Tianzuo , Wang Yuqin , Yang Kehu , Zhang Hongjun , Tang Yida , Chen Yaolong , Dong Hailong , Gu Qinglong , Guo Daihong , Hu Xuehui , Xie Lixin , Li Baohua , Li Yuzhen , Lin Tongyu , Liu Fang , Liu Zhiqiang , Lyu Lanting , Mei Quanxi , Shao Jie , Xin Huawen , Yang Fan , Yang Hui , Yang Wanhua , Yao Xu , Yu Chunshui , Zhan Siyan , Zhang Guoqiang , Wang Minggui , Zhu Zhu , Zhou Baoguo , Gu Jianqing , Xian Mo , Lyu Yuan , Li Zhengqian , Zheng Hangci , Cui Chang , Deng Shuhua , Huang Chao , Li Lisha , Liu Pengfei , Men Peng , Shao Chunli , Wang Sai , Ma Xiang , Wang Qiang , Zhai Suodi
Published: March 2022

Background:For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns.

Objective:This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis.

Method:The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Results:This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects.

Conclusion:For the emergency management of anaphylaxis we conclude that:

• NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis

• Prompt and proper administration of epinephrine is critical.