bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome sequencing of Listeria monocytogenes isolated from the first listeriosis foodborne outbreak in South Korea
Authors: Lee Seung Hun , Lee Sangmi , Park Sang Hun , Koo Ok Kyung
Published: June 2023

Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans with severe symptoms. In South Korea, listeriosis had only been reported sporadically among hospitalized patients until the first foodborne outbreak occurred in 2018. In this study, a L. monocytogenes strain responsible for this outbreak (FSCNU0110) was characterized via whole genome sequencing and compared with publicly available L. monocytogenes genomes of the same clonal complex (CC). Strain FSCNU0110 belonged to multilocus sequence typing (MLST)-based sequence type 224 and CC224, and core genome MLST-based sublineage 6,178. The strain harbored tetracycline resistance gene tetM, four other antibiotic resistance genes, and 64 virulence genes, including Listeria pathogenicity island 1 (LIPI-1) and LIPI-3. Interestingly, llsX in LIPI-3 exhibited a characteristic SNP (deletion of A in position 4, resulting in a premature stop codon) that was missing among all CC224 strains isolated overseas but was conserved among those from South Korea. In addition, the tetM gene was also detected only in a subset of CC224 strains from South Korea. These findings will provide an essential basis for assessing the characteristics of CC224 strains in South Korea that have shown a potential to cause listeriosis outbreaks.
Effects of the pyrE deletion mutant from Bacillus thuringiensis on gut microbiota and immune response of Spodoptera exigua
Authors: Zhao Dan , Wu Han , Li Yazi , Wang Qian , Ji Yujie , Guo Xiaochang , Guo Wei
Published: June 2023

The gut microbiota is essential for the growth and development of insects, and the intestinal immune system plays a critical role in regulating the homeostasis of intestinal microorganisms and their interactions with pathogenic bacteria. Infection with Bacillus thuringiensis (Bt) can disrupt the gut microbiota of insects, but the regulatory factors governing the interaction between Bt and gut bacteria are not well understood. Uracil secreted by exogenous pathogenic bacteria can activate DUOX-mediated reactive oxygen species (ROS) production, which helps maintain intestinal microbial homeostasis and immune balance. To elucidate the regulatory genes involved in the interaction between Bt and gut microbiota, we investigate the effects of uracil derived from Bt on gut microbiota, and host immunity using a uracil deficient Bt strain (Bt GS57△pyrE) obtained by homologous recombination. We analyze the biological characteristics of the uracil deficient strain and found that the deletion of uracil in Bt GS57 strain changed the diversity of gut bacteria in Spodoptera exigua, as investigated using Illumina HiSeq sequencing. Furthermore, qRT-PCR analysis showed that compared with Bt GS57 (control), the expression of the SeDuox gene and the level of ROS were significantly decreased after feeding with Bt GS57△pyrE. Adding uracil to Bt GS57△pyrE restored the expression level of DUOX and ROS to a higher level. Additionally, we observed that PGRP-SA, attacin, defensin and ceropin genes were significant different in the midgut of S. exigua infected by Bt GS57 and Bt GS57△pyrE, with a trend of increasing first and then decreasing. These results suggest that uracil regulates and activates the DUOX-ROS system, affects the expression of antimicrobial peptide genes, and disturb intestinal microbial homeostasis. We preliminarily speculate that uracil is a key factor in the interaction between Bt and gut microbiota, and these findings provide a theoretical basis for clarifying the interaction between Bt, host, and intestinal microorganisms, as well as for gaining new insights into the insecticidal mechanism of B. thuringiensis in insects.
A broad-host-range lytic phage vB_VhaS-R18L as a candidate against vibriosis
Authors: Cai Lanlan , Tian Yuan , Li Ziqiang , Yang Yunlan , Ai Chunxiang , Zhang Rui
Published: June 2023

Vibriosis is one of the most common bacterial diseases that cause high rates of mortality and considerable economic losses in aquaculture. Phage therapy has been considered as a promising alternative method to antibiotics in the biocontrol of infectious diseases. Genome sequencing and characterization of the phage candidates are prerequisites before field applications to ensure environmental safety. In this study, a lytic phage, named vB_VhaS-R18L (R18L), was isolated from the coastal seawater of Dongshan Island, China. The phage was characterized in terms of morphology, genetic content, infection kinetics, lytic profile, and virion stability. Transmission electronic microscopy indicated that R18L is siphovirus-like, comprising an icosahedral head (diameter 88.6 ± 2.2 nm) and a long noncontractile tail (225 × 11 nm). Genome analysis indicated R18L to be a double-stranded DNA virus with a genome size of 80,965 bp and a G + C content of 44.96%. No genes that encode known toxins or genes implicated in lysogeny control were found in R18L. A one-step growth experiment showed that R18L had a latent period of approximately 40 min and a burst size of 54 phage particles per infected cell. R18L showed lytic activity against a wide range of at least five Vibrio species (V. alginolyticus, V. cholerae, V. harveyi, V. parahemolyticus, and V. proteolyticus). R18L was relatively stable at pH 6–11 and at temperatures ranging from 4°C to 50°C. The broad lytic activity across Vibrio species and the stability in the environment make R18L a potential candidate for phage therapy in controlling vibriosis in aquaculture systems.
Global review of the H5N8 avian influenza virus subtype
Authors: Rafique Saba , Rashid Farooq , Mushtaq Sajda , Ali Akbar , Li Meng , Luo Sisi , Xie Liji , Xie Zhixun
Published: June 2023

Orthomyxoviruses are negative-sense, RNA viruses with segmented genomes that are highly unstable due to reassortment. The highly pathogenic avian influenza (HPAI) subtype H5N8 emerged in wild birds in China. Since its emergence, it has posed a significant threat to poultry and human health. Poultry meat is considered an inexpensive source of protein, but due to outbreaks of HPAI H5N8 from migratory birds in commercial flocks, the poultry meat industry has been facing severe financial crises. This review focuses on occasional epidemics that have damaged food security and poultry production across Europe, Eurasia, the Middle East, Africa, and America. HPAI H5N8 viral sequences have been retrieved from GISAID and analyzed. Virulent HPAI H5N8 belongs to clade 2.3.4.4b, Gs/GD lineage, and has been a threat to the poultry industry and the public in several countries since its first introduction. Continent-wide outbreaks have revealed that this virus is spreading globally. Thus, continuous sero- and viro-surveillance both in commercial and wild birds, and strict biosecurity reduces the risk of the HPAI virus appearing. Furthermore, homologous vaccination practices in commercial poultry need to be introduced to overcome the introduction of emergent strains. This review clearly indicates that HPAI H5N8 is a continuous threat to poultry and people and that further regional epidemiological studies are needed.
Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
Authors: Kawai Yoshikazu , Errington Jeff
Published: June 2023

Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled “L-form” state that requires the loss of cell wall integrity. L-forms may have an important role in antibiotic resistance and recurrent infection. Recent work has revealed that inhibition of de novo PG precursor synthesis efficiently induces the L-form conversion in a wide range of bacteria, but the molecular mechanisms remain poorly understood. Growth of walled bacteria requires the orderly expansion of the PG layer, which involves the concerted action not just of synthases but also degradative enzymes called autolysins. Most rod-shaped bacteria have two complementary systems for PG insertion, the Rod and aPBP systems. Bacillus subtilis has two major autolysins, called LytE and CwlO, which are thought to have partially redundant functions. We have dissected the functions of autolysins, relative to the Rod and aPBP systems, during the switch to L-form state. Our results suggest that when de novo PG precursor synthesis is inhibited, residual PG synthesis occurs specifically via the aPBP pathway, and that this is required for continued autolytic activity by LytE/CwlO, resulting in cell bulging and efficient L-form emergence. The failure of L-form generation in cells lacking aPBPs was rescued by enhancing the Rod system and in this case, emergence specifically required LytE but was not associated with cell bulging. Our results suggest that two distinct pathways of L-form emergence exist depending on whether PG synthesis is being supported by the aPBP or RodA PG synthases. This work provides new insights into mechanisms of L-form generation, and specialisation in the roles of essential autolysins in relation to the recently recognised dual PG synthetic systems of bacteria.
Uncovering neuroinflammation-related modules and potential repurposing drugs for Alzheimer's disease through multi-omics data integrative analysis
Authors: Li Shensuo , Lu Changhao , Zhao Zhenzhen , Lu Dong , Zheng Guangyong
Published: June 2023

Background

Neuroinflammation is one of the key factors leading to neuron death and synapse dysfunction in Alzheimer's disease (AD). Amyloid-β (Aβ) is thought to have an association with microglia activation and trigger neuroinflammation in AD. However, inflammation response in brain disorders is heterogenous, and thus, it is necessary to unveil the specific gene module of neuroinflammation caused by Aβ in AD, which might provide novel biomarkers for AD diagnosis and help understand the mechanism of the disease.

Methods

Transcriptomic datasets of brain region tissues from AD patients and the corresponding normal tissues were first used to identify gene modules through the weighted gene co-expression network analysis (WGCNA) method. Then, key modules highly associated with Aβ accumulation and neuroinflammatory response were pinpointed by combining module expression score and functional information. Meanwhile, the relationship of the Aβ-associated module to the neuron and microglia was explored based on snRNA-seq data. Afterward, transcription factor (TF) enrichment and the SCENIC analysis were performed on the Aβ-associated module to discover the related upstream regulators, and then a PPI network proximity method was employed to repurpose the potential approved drugs for AD.

Results

A total of 16 co-expression modules were primarily obtained by the WGCNA method. Among them, the green module was significantly correlated with Aβ accumulation, and its function was mainly involved in neuroinflammation response and neuron death. Thus, the module was termed the amyloid-β induced neuroinflammation module (AIM). Moreover, the module was negatively correlated with neuron percentage and showed a close association with inflammatory microglia. Finally, based on the module, several important TFs were recognized as potential diagnostic biomarkers for AD, and then 20 possible drugs including ibrutinib and ponatinib were picked out for the disease.

Conclusion

In this study, a specific gene module, termed AIM, was identified as a key sub-network of Aβ accumulation and neuroinflammation in AD. Moreover, the module was verified as having an association with neuron degeneration and inflammatory microglia transformation. Moreover, some promising TFs and potential repurposing drugs were presented for AD based on the module. The findings of the study shed new light on the mechanistic investigation of AD and might make benefits the treatment of the disease.
Gait performance and prefrontal cortex activation during single and dual task walking in older adults with different cognitive levels
Authors: Weng Wei-Han , Yang Yea-Ru , Yeh Nai-Chen , Ku Pei-Hsin , Wang Po-Shan , Liao Ying-Yi , Wang Ray-Yau
Published: June 2023

Background

Growing evidence shows the cognitive function influences the motor performance. The prefrontal cortex (PFC) as a part of the executive locomotor pathway is also important for cognitive function. This study investigated the differences in motor function and brain activity among older adults with different cognitive levels, and examined the significance of cognition on motor functions.

Methods

Normal control (NC), individuals with mild cognitive impairment (MCI) or mild dementia (MD) were enrolled in this study. All participants received a comprehensive assessment including cognitive function, motor function, PFC activity during walking, and fear of fall. The assessment of cognitive function included general cognition, attention, executive function, memory, and visuo-spatial. The assessment of motor function included timed up and go (TUG) test, single walking (SW), and cognitive dual task walking (CDW).

Results

Individuals with MD had worse SW, CDW and TUG performance as compared to individuals with MCI and NC. These gait and balance performance did not differ significantly between MCI and NC. Motor functions all correlated with general cognition, attention, executive function, memory, and visuo-spatial ability. Attention ability measured by trail making test A (TMT-A) was the best predictor for TUG and gait velocity. There were no significant differences in PFC activity among three groups. Nevertheless, the PFC activated more during CDW as compared with SW in individuals with MCI (p = 0.000), which was not demonstrated in the other two groups.

Conclusion

MD demonstrated worse motor function as compared to NC and MCI. The greater PFC activity during CDW in MCI may be considered as a compensatory strategy for maintaining the gait performance. Motor function was related to the cognitive function, and the TMT A was the best predictor for the gait related performance in present study among older adults.
Neuronal ApoE4 in Alzheimer’s disease and potential therapeutic targets
Authors: Zhang Lan , Xia Yiyuan , Gui Yuran
Published: June 2023

The most prevalent genetic risk factor for Alzheimer’s disease (AD) is Apolipoprotein E (ApoE), a gene located on chromosome 19 that encodes three alleles (e2, e3, and e4) that give rise to the ApoE subtypes E2, E3, and E4, respectively. E2 and E4 have been linked to increased plasma triglyceride concentrations and are known to play a critical role in lipoprotein metabolism. The prominent pathological features of AD mainly include senile plaques formed by amyloid β (Aβ42) aggregation and neuronal fibrous tangles (NFTs), and the deposited plaques are mainly composed of Aβ hyperphosphorylation and truncated head. In the central nervous system, the ApoE protein is primarily derived from astrocytes, but ApoE is also produced when neurons are stressed or affected by certain stress, injury, and aging conditions. ApoE4 in neurons induces Aβ and tau protein pathologies, leading to neuroinflammation and neuronal damage, impairing learning and memory functions. However, how neuronal ApoE4 mediates AD pathology remains unclear. Recent studies have shown that neuronal ApoE4 may lead to greater neurotoxicity, which increases the risk of AD development. This review focuses on the pathophysiology of neuronal ApoE4 and explains how neuronal ApoE4 mediates Aβ deposition, pathological mechanisms of tau protein hyperphosphorylation, and potential therapeutic targets.
Vasculature in the mouse colon and spatial relationships with the enteric nervous system, glia, and immune cells
Authors: Wang Lixin , Yuan Pu-Qing , Taché Yvette
Published: June 2023

The distribution, morphology, and innervation of vasculature in different mouse colonic segments and layers, as well as spatial relationships of the vasculature with the enteric plexuses, glia, and macrophages are far from being complete. The vessels in the adult mouse colon were stained by the cardiovascular perfusion of wheat germ agglutinin (WGA)-Alexa Fluor 448 and by CD31 immunoreactivity. Nerve fibers, enteric glia, and macrophages were immunostained in the WGA-perfused colon. The blood vessels entered from the mesentery to the submucosa and branched into the capillary networks in the mucosa and muscularis externa. The capillary net formed anastomosed rings at the orifices of mucosa crypts, and the capillary rings surrounded the crypts individually in the proximal colon and more than two crypts in the distal colon. Microvessels in the muscularis externa with myenteric plexus were less dense than in the mucosa and formed loops. In the circular smooth muscle layer, microvessels were distributed in the proximal, but not the distal colon. Capillaries did not enter the enteric ganglia. There were no significant differences in microvascular volume per tissue volume between the proximal and distal colon either in the mucosa or muscularis externa containing the myenteric plexus. PGP9.5-, tyrosine hydroxylase-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers were distributed along the vessels in the submucosa. In the mucosa, PGP9.5-, CGRP-, and vasoactive intestinal peptide (VIP)-immunoreactive nerves terminated close to the capillary rings, while cells and processes labeled by S100B and glial fibrillary acidic protein were distributed mainly in the lamina propria and lower portion of the mucosa. Dense Iba1 immunoreactive macrophages were closely adjacent to the mucosal capillary rings. There were a few macrophages, but no glia in apposition to microvessels in the submucosa and muscularis externa. In conclusion, in the mouse colon, (1) the differences in vasculature between the proximal and distal colon were associated with the morphology, but not the microvascular amount per tissue volume in the mucosa and muscle layers; (2) the colonic mucosa contained significantly more microvessels than the muscularis externa; and (3) there were more CGRP and VIP nerve fibers found close to microvessels in the mucosa and submucosa than in the muscle layers.
Comparison of fluorescence biosensors and whole-cell patch clamp recording in detecting ACh, NE, and 5-HT
Authors: Zhang Kun , Han Yanfei , Zhang Peng , Zheng Yuqiong , Cheng Aobing
Published: June 2023

The communication between neurons and, in some cases, between neurons and non-neuronal cells, through neurotransmission plays a crucial role in various physiological and pathological processes. Despite its importance, the neuromodulatory transmission in most tissues and organs remains poorly understood due to the limitations of current tools for direct measurement of neuromodulatory transmitters. In order to study the functional roles of neuromodulatory transmitters in animal behaviors and brain disorders, new fluorescent sensors based on bacterial periplasmic binding proteins (PBPs) and G-protein coupled receptors have been developed, but their results have not been compared to or multiplexed with traditional methods such as electrophysiological recordings. In this study, a multiplexed method was developed to measure acetylcholine (ACh), norepinephrine (NE), and serotonin (5-HT) in cultured rat hippocampal slices using simultaneous whole-cell patch clamp recordings and genetically encoded fluorescence sensor imaging. The strengths and weaknesses of each technique were compared, and the results showed that both techniques did not interfere with each other. In general, genetically encoded sensors GRABNE and GRAB5HT1.0 showed better stability compared to electrophysiological recordings in detecting NE and 5-HT, while electrophysiological recordings had faster temporal kinetics in reporting ACh. Moreover, genetically encoded sensors mainly report the presynaptic neurotransmitter release while electrophysiological recordings provide more information of the activation of downstream receptors. In sum, this study demonstrates the use of combined techniques to measure neurotransmitter dynamics and highlights the potential for future multianalyte monitoring.
Ceramide in cerebrovascular diseases
Authors: Yuan Huiqi , Zhu Bin , Li Cao , Zhao Zhigang
Published: June 2023

Ceramide, a bioactive sphingolipid, serves as an important second messenger in cell signal transduction. Under stressful conditions, it can be generated from de novo synthesis, sphingomyelin hydrolysis, and/or the salvage pathway. The brain is rich in lipids, and abnormal lipid levels are associated with a variety of brain disorders. Cerebrovascular diseases, which are mainly caused by abnormal cerebral blood flow and secondary neurological injury, are the leading causes of death and disability worldwide. There is a growing body of evidence for a close connection between elevated ceramide levels and cerebrovascular diseases, especially stroke and cerebral small vessel disease (CSVD). The increased ceramide has broad effects on different types of brain cells, including endothelial cells, microglia, and neurons. Therefore, strategies that reduce ceramide synthesis, such as modifying sphingomyelinase activity or the rate-limiting enzyme of the de novo synthesis pathway, serine palmitoyltransferase, may represent novel and promising therapeutic approaches to prevent or treat cerebrovascular injury-related diseases.
A review of studies on gut microbiota and levodopa metabolism
Authors: Zhong Zhe , Ye Min , Yan Fuling
Published: June 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease globally. Levodopa (L-dopa) has been the cornerstone for treating Parkinson’s since the 1960s. However, complications such as “wearing-off” and dyskinesia inevitably appear with disease progression. With the further development of microbiomics in recent years, It has been recognized that gut microbiota plays a crucial role in Parkinson’s disease pathogenesis. However, Little is known about the impact of gut microbiota in PD treatment, especially in levodopa metabolism. This review examines the possible mechanisms of gut microbiota, such as Helicobacter pylori, Enterobacter faecalis, and Clostridium sporogenes, affecting L-dopa absorption. Furthermore, we review the current status of gut microbiota intervention strategies, providing new insights into the treatment of PD.
Supporting stroke survivors to meet their personal rehabilitation needs in community-based arm rehabilitation: development of initial programme theories to explore what may work for whom, how and under what circumstances
Authors: Schnabel Stefanie , van Wijck Frederike , Kidd Lisa
Published: June 2023

Objective

This study explored what worked for whom, how and under what circumstances in a community-based augmented arm rehabilitation programme that was designed to enable stroke survivors to meet their personal rehabilitation needs.

Design

A mixed methods realist-informed study of data from a randomised controlled feasibility trial, comparing augmented arm rehabilitation after stroke with usual care. The analysis was designed to develop initial programme theories and refine these through triangulation of qualitative and quantitative trial data. Participants with a confirmed stroke diagnosis and stroke-related arm impairment were recruited from five health boards in Scotland. Only data from participants in the augmented group were analysed. The augmented intervention comprised evidence-based arm rehabilitation (27 additional hours over 6 weeks) including self-managed practice, and focused on individual rehabilitation needs identified through the Canadian Occupational Performance Measure (COPM). The COPM indicated to which extent rehabilitation needs were met following the intervention, the Action Research Arm Test provided data on changes in arm function, and qualitative interviews provided information about the context and potential mechanisms of action.

Findings

Seventeen stroke survivors (11 males, age range 40–84 years, NIHSS median (IQR) 6 (8)) were included. Median (IQR) COPM Performance and Satisfaction scores (min.1-max.10) improved from pre-intervention 2 (5) to post-intervention 5 (7). Findings suggested that meeting rehabilitation needs was facilitated by strengthening participants’ sense of intrinsic motivation (through grounding exercises in everyday activities linked to valued life roles, and enabling them to overcome barriers to self-managed practice), and via therapeutic relationships (through trust and expertise, shared decision-making, encouragement and emotional support). Collectively, these mechanisms enabled stroke survivors to build confidence and gain mastery experience necessary to engage in new self-managed practice routines.

Conclusion

This realist-informed study enabled the development of initial programme theories to explain how and in what circumstances the augmented arm rehabilitation intervention may have enabled participants to meet their personal rehabilitation needs. Encouraging participants’ sense of intrinsic motivation and building therapeutic relationships appeared instrumental. These initial programme theories require further testing, refinement, and integration with the wider literature.
Primary motor hand area corticospinal excitability indicates overall functional recovery after spinal cord injury
Authors: Dai Chun-Qiu , Gao Ming , Lin Xiao-Dong , Xue Bai-Jie , Liang Ying , Xu Mu-Lan , Wu Xiang-Bo , Cheng Gui-Qing , Hu Xu , Zhao Chen-Guang , Yuan Hua , Sun Xiao-Long
Published: June 2023

Background

After spinal cord injury (SCI), the excitability of the primary motor cortex (M1) lower extremity area decreases or disappears. A recent study reported that the M1 hand area of the SCI patient encodes the activity information of both the upper and lower extremities. However, the characteristics of the M1 hand area corticospinal excitability (CSE) changes after SCI and its correlation with extremities motor function are still unknown.

Methods

A retrospective study was conducted on the data of 347 SCI patients and 80 healthy controls on motor evoked potentials (MEP, reflection of CSE), extremity motor function, and activities of daily living (ADL) ability. Correlation analysis and multiple linear regression analysis were conducted to analyze the relationship between the degree of MEP hemispheric conversion and extremity motor function/ADL ability.

Results

The CSE of the dominant hemisphere M1 hand area decreased in SCI patients. In 0–6 m, AIS A grade, or non-cervical injury SCI patients, the degree of M1 hand area MEP hemispheric conversion was positively correlated with total motor score, lower extremity motor score (LEMS), and ADL ability. Multiple linear regression analysis further confirmed the contribution of MEP hemispheric conversion degree in ADL changes as an independent factor.

Conclusion

The closer the degree of M1 hand area MEP hemispheric conversion is to that of healthy controls, the better the extremity motor function/ADL ability patients achieve. Based on the law of this phenomenon, targeted intervention to regulate the excitability of bilateral M1 hand areas might be a novel strategy for SCI overall functional recovery.
Case report: Neuronal intranuclear inclusion disease presenting with acute encephalopathy
Authors: Bu Julia Ting , Torres Dolores , Robinson Adam , Malone Corey , Vera Juan Carlos , Daghighi Shadi , Dunn-Pirio Anastasie , Khoromi Suzan , Nowell Justin , Léger Gabriel C. , Ciacci Joseph D. , Goodwill Vanessa S. , Estrella Melanie , Coughlin David G. , Guo Yueyang , Farid Nikdokht
Published: June 2023

Neuronal intranuclear inclusion disease (NIID), a neurodegenerative disease previously thought to be rare, is increasingly recognized despite heterogeneous clinical presentations. NIID is pathologically characterized by ubiquitin and p-62 positive intranuclear eosinophilic inclusions that affect multiple organ systems, including the brain, skin, and other tissues. Although the diagnosis of NIID is challenging due to phenotypic heterogeneity, a greater understanding of the clinical and imaging presentations can improve accurate and early diagnosis. Here, we present three cases of pathologically proven adult-onset NIID, all presenting with episodes of acute encephalopathy with protracted workups and lengthy time between symptom onset and diagnosis. Case 1 highlights challenges in the diagnosis of NIID when MRI does not reveal classic abnormalities and provides a striking example of hyperperfusion in the setting of acute encephalopathy, as well as unique pathology with neuronal central chromatolysis, which has not been previously described. Case 2 highlights the progression of MRI findings associated with multiple NIID-related encephalopathic episodes over an extended time period, as well as the utility of skin biopsy for antemortem diagnosis.
Stiffness changes in internal rotation muscles of the shoulder and its influence on hemiplegic shoulder pain
Authors: Jia Fan , Zhu Xin-Rui , Kong Ling-Yu , Fan Jie-Cheng , Zhu Zong-Jing , Lin Li-Zhen , Zhang Shu-Yun , Yuan Xiang-Zhen
Published: June 2023

Background

Hemiplegic shoulder pain (HSP) is a common complication in patients with stroke. The pathogenesis of HSP is complex, and muscle hypertonia, especially the hypertonia of internal rotation muscles of the shoulder, may be one of the important causes of shoulder pain. However, the relationship between muscle stiffness and HSP has not been well studied. The purpose of this study is to explore the correlations between the stiffness of internal rotation muscles and clinical symptoms in patients with HSP.

Methods

A total of 20 HSP patients and 20 healthy controls were recruited for this study. The stiffness of internal rotation muscles was quantified using shear wave elastography, and Young's modulus (YM) of the pectoralis major (PM), anterior deltoid (AD), teres major ™, and latissimus dorsi (LD) were measured. Muscle hypertonia and pain intensity were evaluated using the Modified Ashworth Scale (MAS) and Visual Analog Scale (VAS), respectively. The mobility of the shoulder was evaluated using the Neer score. The correlations between muscle stiffness and the clinical scales were analyzed.

Results

YM of internal rotation muscles on the paretic side was higher than that of the control group in the resting and passive stretching positions (P < 0.05). YM of internal rotation muscles on the paretic side during passive stretching was significantly higher than that at rest (P < 0.05). YM of PM, TM, and LD during passive stretching were correlated with MAS (P < 0.05). In addition, the YM of TM during passive stretching was positively correlated with VAS and negatively correlated with the Neer score (P < 0.05).

Conclusion

Increased stiffness of PM, TM, and LD was observed in patients with HSP. The stiffness of TM was associated with pain intensity of the shoulder and shoulder mobility.
Detection of brain regions responsible for chronic pain in osteoarthritis: an fMRI-based neuroimaging study using deep learning
Authors: Chatterjee Indranath , Baumgartner Lea , Cho Migyung
Published: June 2023

Introduction

Chronic pain is a multifaceted condition that has yet to be fully comprehended. It is frequently linked with a range of disorders, particularly osteoarthritis (OA), which arises from the progressive deterioration of the protective cartilage that cushions the bone endings over time.

Methods

In this paper, we examine the impact of chronic pain on the brain using advanced deep learning (DL) algorithms that leverage resting-state functional magnetic resonance imaging (fMRI) data from both OA pain patients and healthy controls. Our study encompasses fMRI data from 51 pain patients and 20 healthy subjects. To differentiate chronic pain-affected OA patients from healthy controls, we introduce a DL-based computer-aided diagnosis framework that incorporates Multi-Layer Perceptron and Convolutional Neural Networks (CNN), separately.

Results

Among the examined algorithms, we discovered that CNN outperformed the others and achieved a notable accuracy rate of nearly 85%. In addition, our investigation scrutinized the brain regions affected by chronic pain and successfully identified several regions that have not been mentioned in previous literature, including the occipital lobe, the superior frontal gyrus, the cuneus, the middle occipital gyrus, and the culmen.

Discussion

This pioneering study explores the applicability of DL algorithms in pinpointing the differentiating brain regions in OA patients who experience chronic pain. The outcomes of our research could make a significant contribution to medical research on OA pain patients and facilitate fMRI-based pain recognition, ultimately leading to enhanced clinical intervention for chronic pain patients.
Research methods and efficacy of acupuncture in the treatment of Parkinson's disease: a scoping review of systematic reviews and meta-analyses
Authors: Yu Bin , Ma Shi-qi , Huang Hai-peng , Zhong Zhen , Yu Shuo , Huang Ke , Zhang Li-ying , Li Meng-yuan , Yao Lin
Published: June 2023

Introduction

Research on acupuncture for Parkinson's Disease is growing rapidly. A scoping review examines emerging evidence and is important to guide policy and practice. The purpose of this scoping review was to examine the breadth and methodological quality of systematic reviews and meta-analyses, and to map the quality of evidence of these studies to evaluate the efficacy of acupuncture for treatment of PD.

Methods

Seven literature databases were searched. Two researchers independently screened the literature and extracted relevant information (such as general characteristics, inclusion criteria, study results, and report quality).The inclusion criteria include publicly published systematic reviews/meta-analyses/systematic reviews of acupuncture treatment for Parkinson's disease. The research subjects are any patients who meet the diagnostic criteria for Parkinson's disease, and intervention measures include acupuncture treatment including electro acupuncture, scalp acupuncture, or combination with other treatment methods. The outcome indicators are all types of results related to PD and the effective measurement tools used.

Results

A total of 23 systematic reviews and/or meta-analyses of studies were included. Most of the articles were published between 2019 and 2023 (47.8%). A total of 14 articles (60.9%) were evaluated and classified, and 89 (36.8.1%) of the 242 included articles were of medium and high quality.

Discussion

This study comprehensively evaluates the quality and research methods of incorporating SRs/MAs, and concludes that acupuncture treatment for Parkinson's disease may be significant. Considering the shortcomings in research design and methodology, it is not possible to draw conclusions on the evidence of acupuncture treatment for PD at this stage, but it does not mean that acupuncture treatment is ineffective. We hope to focus on improving research design and methods in the study of acupuncture treatment for Parkinson's disease, an increase the credibility of research results.
Aging in multiple sclerosis: from childhood to old age, etiopathogenesis, and unmet needs: a narrative review
Authors: Capasso Nicola , Virgilio Eleonora , Covelli Antonio , Giovannini Beatrice , Foschi Matteo , Montini Federico , Nasello Martina , Nilo Annacarmen , Prestipino Elio , Schirò Giuseppe , Sperandei Silvia , Clerico Marinella , Lanzillo Roberta
Published: June 2023

Multiple sclerosis (MS) primarily affects adult females. However, in the last decades, rising incidence and prevalence have been observed for demographic extremes, such as pediatric-onset MS (POMS; occurring before 18 years of age) and late-onset MS (corresponding to an onset above 50 years). These categories show peculiar clinical-pathogenetic characteristics, aging processes and disease courses, therapeutic options, and unmet needs. Nonetheless, several open questions are still pending. POMS patients display an important contribution of multiple genetic and environmental factors such as EBV, while in LOMS, hormonal changes and pollution may represent disease triggers. In both categories, immunosenescence emerges as a pathogenic driver of the disease, particularly for LOMS. In both populations, patient and caregiver engagement are essential from the diagnosis communication to early treatment of disease-modifying therapy (DMTs), which in the elderly population appears more complex and less proven in terms of efficacy and safety. Digital technologies (e.g., exergames and e-training) have recently emerged with promising results, particularly in treating and following motor and cognitive deficits. However, this offer seems more feasible for POMS, being LOMS less familiar with digital technology. In this narrative review, we discuss how the aging process influences the pathogenesis, disease course, and therapeutic options of both POMS and LOMS. Finally, we evaluate the impact of new digital communication tools, which greatly interest the current and future management of POMS and LOMS patients.
Spinal neuromodulation mitigates myocardial ischemia-induced sympathoexcitation by suppressing the intermediolateral nucleus hyperactivity and spinal neural synchrony
Authors: Salavatian Siamak , Kuwabara Yuki , Wong Benjamin , Fritz Jonathan R. , Howard-Quijano Kimberly , Foreman Robert D. , Armour J. Andrew , Ardell Jeffrey L. , Mahajan Aman
Published: June 2023

Introduction

Myocardial ischemia disrupts the cardio-spinal neural network that controls the cardiac sympathetic preganglionic neurons, leading to sympathoexcitation and ventricular tachyarrhythmias (VTs). Spinal cord stimulation (SCS) is capable of suppressing the sympathoexcitation caused by myocardial ischemia. However, how SCS modulates the spinal neural network is not fully known.

Methods

In this pre-clinical study, we investigated the impact of SCS on the spinal neural network in mitigating myocardial ischemia-induced sympathoexcitation and arrhythmogenicity. Ten Yorkshire pigs with left circumflex coronary artery (LCX) occlusion-induced chronic myocardial infarction (MI) were anesthetized and underwent laminectomy and a sternotomy at 4−5 weeks post-MI. The activation recovery interval (ARI) and dispersion of repolarization (DOR) were analyzed to evaluate the extent of sympathoexcitation and arrhythmogenicity during the left anterior descending coronary artery (LAD) ischemia. Extracellular in vivo and in situ spinal dorsal horn (DH) and intermediolateral column (IML) neural recordings were performed using a multichannel microelectrode array inserted at the T2-T3 segment of the spinal cord. SCS was performed for 30 min at 1 kHz, 0.03 ms, 90% motor threshold. LAD ischemia was induced pre- and 1 min post-SCS to investigate how SCS modulates spinal neural network processing of myocardial ischemia. DH and IML neural interactions, including neuronal synchrony as well as cardiac sympathoexcitation and arrhythmogenicity markers were evaluated during myocardial ischemia pre- vs. post-SCS.

Results

ARI shortening in the ischemic region and global DOR augmentation due to LAD ischemia was mitigated by SCS. Neural firing response of ischemia-sensitive neurons during LAD ischemia and reperfusion was blunted by SCS. Further, SCS showed a similar effect in suppressing the firing response of IML and DH neurons during LAD ischemia. SCS exhibited a similar suppressive impact on the mechanical, nociceptive and multimodal ischemia sensitive neurons. The LAD ischemia and reperfusion-induced augmentation in neuronal synchrony between DH-DH and DH-IML pairs of neurons were mitigated by the SCS.

Discussion

These results suggest that SCS is decreasing the sympathoexcitation and arrhythmogenicity by suppressing the interactions between the spinal DH and IML neurons and activity of IML preganglionic sympathetic neurons.
The modulation effects of repeated transcutaneous auricular vagus nerve stimulation on the functional connectivity of key brainstem regions along the vagus nerve pathway in migraine patients
Authors: Huang Yiting , Zhang Yue , Hodges Sierra , Li Hui , Yan Zhaoxian , Liu Xian , Hou Xiaoyan , Chen Weicui , Chai-Zhang Thalia , Kong Jian , Liu Bo
Published: June 2023

Background

Previous studies have shown a significant response to acute transcutaneous vagus nerve stimulation (taVNS) in regions of the vagus nerve pathway, including the nucleus tractus solitarius (NTS), raphe nucleus (RN) and locus coeruleus (LC) in both healthy human participants and migraine patients. This study aims to investigate the modulation effect of repeated taVNS on these brainstem regions by applying seed-based resting-state functional connectivity (rsFC) analysis.

Methods

70 patients with migraine were recruited and randomized to receive real or sham taVNS treatments for 4 weeks. fMRI data were collected from each participant before and after 4 weeks of treatment. The rsFC analyses were performed using NTS, RN and LC as the seeds.

Results

59 patients (real group: n = 33; sham group: n = 29) completed two fMRI scan sessions. Compared to sham taVNS, real taVNS was associated with a significant reduction in the number of migraine attack days (p = 0.024) and headache pain intensity (p = 0.008). The rsFC analysis showed repeated taVNS modulated the functional connectivity between the brain stem regions of the vagus nerve pathway and brain regions associated with the limbic system (bilateral hippocampus), pain processing and modulation (bilateral postcentral gyrus, thalamus, and mPFC), and basal ganglia (putamen/caudate). In addition, the rsFC change between the RN and putamen was significantly associated with the reduction in the number of migraine days.

Conclusion

Our findings suggest that taVNS can significantly modulate the vagus nerve central pathway, which may contribute to the potential treatment effects of taVNS for migraine.

Clinical Trial Registration: http://www.chictr.org.cn/hvshowproject.aspx?id=11101, identifier ChiCTR-INR-17010559.
Tryptophan catabolites, inflammation, and insulin resistance as determinants of chronic fatigue syndrome and affective symptoms in long COVID
Authors: Al-Hakeim Hussein Kadhem , Khairi Abed Anwar , Rouf Moustafa Shatha , Almulla Abbas F. , Maes Michael
Published: June 2023

Critical COVID-19 disease is accompanied by depletion of plasma tryptophan (TRY) and increases in indoleamine-dioxygenase (IDO)-stimulated production of neuroactive tryptophan catabolites (TRYCATs), including kynurenine (KYN). The TRYCAT pathway has not been studied extensively in association with the physiosomatic and affective symptoms of Long COVID. In the present study, we measured serum TRY, TRYCATs, insulin resistance (using the Homeostatic Model Assessment Index 2-insulin resistance, HOMA2-IR), C-reactive protein (CRP), physiosomatic, depression, and anxiety symptoms in 90 Long COVID patients, 3–10 months after remission of acute infection. We were able to construct an endophenotypic class of severe Long COVID (22% of the patients) with very low TRY and oxygen saturation (SpO2, during acute infection), increased kynurenine, KYN/TRY ratio, CRP, and very high ratings on all symptom domains. One factor could be extracted from physiosomatic symptoms (including chronic fatigue-fibromyalgia), depression, and anxiety symptoms, indicating that all domains are manifestations of the common physio-affective phenome. Three Long COVID biomarkers (CRP, KYN/TRY, and IR) explained around 40% of the variance in the physio-affective phenome. The latter and the KYN/TRY ratio were significantly predicted by peak body temperature (PBT) and lowered SpO2 during acute infection. One validated latent vector could be extracted from the three symptom domains and a composite based on CRP, KYN/TRY, and IR (Long COVID), and PBT and SpO2 (acute COVID-19). In conclusion, the physio-affective phenome of Long COVID is a manifestation of inflammatory responses during acute and Long COVID, and lowered plasma tryptophan and increased kynurenine may contribute to these effects.
A proof-of-concept study on endoscopic ultrasound-guided biopsy of detrusor muscle in porcine bladders
Authors: Teoh Jeremy Yuen-Chun , Cho Chak-Lam , Chan Ronald Cheong-Kin , Liu Kang , Zhao Hongda , Giannarini Gianluca , Enikeev Dmitry , Ng Chi-Fai , Teoh Anthony Yuen-Bun
Published: June 2023

Introduction

Conventionally, we rely on transurethral resection of bladder tumour (TURBT) for local staging of muscle-invasive bladder cancer (MIBC). However, the procedure is limited by its staging inaccuracy which may delay the definitive treatment of MIBC.

Methods

We conducted a proof-of concept study on endoscopic ultrasound (EUS)-guided biopsy of detrusor muscle in porcine bladders. Five porcine bladders were used in this experiment. Upon EUS, four layers of tissue including the mucosa (hypoechoic), submucosa (hyperechoic), detrusor muscle (hypoechoic) and serosa (hyperechoic) could be identified.

Results

A total of 37 EUS-guided biopsies were taken from 15 sites (three sites per bladder), and the mean number of biopsies taken from each site was 2.47±0.64. Among the 37 biopsies, 30 of them (81.1%) obtained detrusor muscle in the biopsy specimen. For the per biopsy site analysis, detrusor muscle was obtained in 73.3% if only one biopsy was taken, and 100% if two or more biopsies were taken from the same biopsy site. Overall, detrusor muscle was successfully obtained from all 15 biopsy sites (100%). No bladder perforation was observed throughout all biopsy processes.

Conclusion

EUS-guided biopsy of the detrusor muscle could be performed during the initial cystoscopy session, thus expediting the histological diagnosis and subsequent treatment of MIBC.
Combination of C-reactive protein/albumin ratio and time to castration resistance enhances prediction of prognosis for patients with metastatic castration-resistant prostate cancer
Authors: Mitsui Yozo , Yamabe Fumito , Hori Shunsuke , Uetani Masato , Aoki Hiroshi , Sakurabayashi Kei , Okawa Mizuho , Kobayashi Hideyuki , Nagao Koichi , Nakajima Koichi
Published: June 2023

Objective

This study aimed to identify the prediction accuracy of the combination of C-reactive protein (CRP) albumin ratio (CAR) and time to castration resistance (TTCR) for overall survival (OS) following development of metastatic castration-resistant prostate cancer (mCRPC).

Methods

Clinical data from 98 mCRPC patients treated at our institution from 2009 to 2021 were retrospectively evaluated. Optimal cutoff values for CAR and TTCR to predict lethality were generated by use of a receiver operating curve and Youden’s index. The Kaplan–Meier method and Cox proportional hazard regression models for OS were used to analyze the prognostic capabilities of CAR and TTCR. Multiple multivariate Cox models were then constructed based on univariate analysis and their accuracy was validated using the concordance index.

Results

The optimal cutoff values for CAR at the time of mCRPC diagnosis and TTCR were 0.48 and 12 months, respectively. Kaplan–Meier curves indicated that patients with CAR >0.48 or TTCR <12 months had a significantly worse OS (both p < 0.005). Univariate analysis also identified age, hemoglobin, CRP, and performance status as candidate prognostic factors. Furthermore, a multivariate analysis model incorporating those factors and excluding CRP showed CAR and TTCR to be independent prognostic factors. This model had better prognostic accuracy as compared with that containing CRP instead of CAR. The results showed effective stratification of mCRPC patients in terms of OS based on CAR and TTCR (p < 0.0001).

Conclusion

Although further investigation is required, CAR and TTCR used in combination may more accurately predict mCRPC patient prognosis.