bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of uterine artery embolization before surgical laparoscopic myomenucleation compared to single surgical laparoscopic myomenucleation for the treatment of large fibroids and uterus myomatosus
Authors: Hertling Stefan , Schleußner Ekkehard , Graul lsabel
Published: April 2023

Aim

To determine the efficacy of preoperative uterine artery embolization (uterine artery embolization; UAE) prior to elective laparoscopic fibroid removal compared to single laparoscopic fibroid removal in women with large uterine fibroids and women with uterus myomatosus.

Material and methods

A total of 202 women with symptomatic uterine fibroids who were scheduled for elective fibroid enucleation were included in this retrospective, monocentric, non-randomized study. Two procedures were compared: women who received percutaneous UAE 24 h prior to elective laparoscopic fibroid eviction for large uterine fibroids (>6 cm) and uterus myomatosus. And women who received laparoscopic fibroid enucleation alone for large uterine fibroids and uterus myomatosus. Outcome parameters for effectiveness were the hospital stay, the operating time and the intraoperative blood loss.

Results

Women who underwent preoperative percutaneous embolization of the uterine arteries, both for large fibroids and uterus myomatosus, had significantly less blood loss, shorter hospital stays, and shorter operating times.

Conclusions

Especially women with large uterine fibroids and women with uterus myomatosus after having children can benefit from the combination therapy of preoperative percutaneous uterine embolization with subsequent laparoscopic myoma enucleation.
Characterization and virulence of Streptococcus agalactiae deficient in SaeRS of the two-component system
Authors: Li Shiyu , Li Wei , Liang Qiancai , Cao Jizhen , Li Han , Li Zhicheng , Li Anxing
Published: April 2023

There are a variety of regulatory systems in bacteria, among which the two-component system (TCS) can sense external environmental changes and make a series of physiological and biochemical reactions, which is crucial for the life activities of bacteria. As a member of TCS, SaeRS is considered to be an important virulence factor in Staphylococcus aureus, but its function in tilapia (Oreochromis niloticus)-derived Streptococcus agalactiae remains unknown. To explore the role of SaeRS in regulating virulence in the two-component system (TCS) of S. agalactiae from tilapia, ΔSaeRS mutant strain and CΔSaeRS complementary strain were constructed by homologous recombination. The results showed that the abilities of growth and biofilm formation of ΔSaeRS strain were significantly decreased when cultured in a brain heart infusion (BHI) medium (P < 0.01). Also, the survival rate of the ΔSaeRS strain in blood was decreased when compared with the wild strain S. agalactiae THN0901. Under the higher infection dose, the accumulative mortality of tilapia caused by the ΔSaeRS strain was significantly decreased (23.3%), of which THN0901 and CΔSaeRS strains were 73.3%. The results of competition experiments in tilapia showed that the invasion and colonization abilities of the ΔSaeRS strain were also dramatically lower than those of the wild strain (P < 0.01). Compared with the THN0901, the mRNA expression levels of virulence factors (fbsB, sip, cylE, bca, etc.) in the ΔSaeRS strain were significantly down-regulated (P < 0.01). SaeRS is one of the virulence factors of S. agalactiae. It plays a role in promoting host colonization and achieving immune evasion during the infection of tilapia, which provides a basis for exploring the pathogenic mechanism of S. agalactiae infected with tilapia.
Nano-functionalization and evaluation of antimicrobial activity of Tinospora cordifolia against the TolB protein of Pseudomonas aeruginosa – An antibacterial and computational study
Authors: Nath Himporna , Khataniar Ankita , Bania Kusum K. , Mukerjee Nobendu , Al-Hussain Sami A. , Zaki Magdi E. A. , Rajkhowa Sanchaita
Published: April 2023

Introduction

Antibacterial drug resistance, brought on by the overuse of antibiotics, is one of the biggest threats to human health. It is crucial to consider cutting-edge strategies, such as herbal remedies, to control multidrug-resistant (MDR) bacteria.

Methods

This study evaluated the phytochemical, antioxidant and antibacterial properties of the various Tinospora cordifolia extracts. Functionalization of the isolated active compound was done using gold (Au) and silver (Ag) nanoparticles (NPs). Further, to understand the interaction of the isolated class, Cordifolisides, with its target, various in-silico methods were used.

Results and Discussion

The plant was reported from the Charaideo district of Assam, whose methanolic stem extract showed the maximum activity towards the nosocomial pathogen Pseudomonas aeruginosa. Consequently, the active compound was isolated and characterized as belonging to the class Cordifoliside using NMR. The AuNPs and AgNPs functionalized isolates showed enhanced antimicrobial activity against P. aeruginosa compared to the unfunctionalized isolate. The most reactive compound, Cordifoliside C was determined using Density Functional Theory (DFT) analysis, whose interactions with the TolB protein were studied using molecular docking methods, which revealed good binding interactions of Cordifoliside C with the TolB protein.

Conclusion

This study offers enormous potential for drug design and might be used as a pipeline to address the urgent problem of multidrug-resistance in bacteria.
Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation
Authors: Zhang Ping-Ping , He Xue-Ping , Tang Wen , Chen Han-Wei , Han Yuan-Yuan
Published: April 2023

Introduction

Vaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing.

Methods

Vaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities.

Results

The microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study.

Conclusion

These findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.
Microbial cell wall sorption and Fe–Mn binding in rhizosphere contribute to the obstruction of cadmium from soil to rice
Authors: Li Jie , Guo Yi-Kai , Zhao Qing-Xia , He Ji-Zheng , Zhang Qian , Cao Hong-Ying , Liang Chao-Qiong
Published: April 2023

Screening high-tolerant microorganisms to cadmium (Cd) and revealing their bio-obstruction mechanism could be significant for Cd regulation from farmland to the food chain. We examined the tolerance and bio-removal efficiency of Cd ions of two bacterial strains, Pseudomonas putida 23483 and Bacillus sp. GY16, and measured the accumulation of Cd ions in rice tissues and its different chemical forms in soil. The results showed that the two strains had high tolerance to Cd, but the removal efficiency was decreased successively with increasing Cd concentrations (0.05 to 5 mg kg−1). Cell-sorption accounted for the major proportion of Cd removal compared with excreta binding in both strains, which was conformed to the pseudo-second-order kinetics. At the subcellular level, Cd was mostly taken up by the cell mantle and cell wall, and only a small amount entered into the cytomembrane and cytoplasmic with time progressed (0 to 24 h) in each concentration. The cell mantle and cell wall sorption decreased with increasing Cd concentration, especially in the cytomembrane and cytoplasmic. The scanning electron microscope (SEM) and energy dispersive X-ray (EDS) analysis verified that Cd ions were attached to the cell surface, and the functional groups of C-H, C-N, C=O, N-H, and O-H in the cell surface may participate in cell-sorption process tested by the FTIR analysis. Furthermore, inoculation of the two strains significantly decreased Cd accumulation in rice straw and grain but increased in the root, increased Cd enrichment ratio in root from soil, decreased Cd translocation ratio from root to straw and grain, and increased the Cd concentrations of Fe–Mn binding form and residual form in rhizosphere soil. This study highlights that the two strains mainly removed Cd ions in solution through biosorption and passivated soil Cd as Fe–Mn combined form ascribe to its characteristics of manganese-oxidizing, eventually achieving bio-obstruction of Cd from soil to rice grain.
SNP rs3803264 polymorphisms in THSD1 and abnormally expressed mRNA are associated with hemorrhagic stroke
Authors: Chen Changying , Gu Xincheng , Liu Fangyuan , Sun Congyong , Mu Jialin , Jin Defu , Sui Xuemei , Geng Deqin , Li Qingqing , Jiang Yuzhang , Shen Chong
Published: April 2023

Background

Thrombospondin Type 1 Domain Containing Protein 1 (THSD1) has been suggested to be a new regulator of endothelial barrier function in the angiogenesis process, preserving vascular integrity. We sought to characterize the association of THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.

Methods

A case–control study was conducted with 843 HS cases and 1,400 healthy controls. A cohort study enrolled 4,080 participants free of stroke at baseline in 2009 and followed up to 2022. A synonymous variant, the main tag SNP rs3803264 of the THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.

Results

In the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 0.030]. In the cohort study, a similar association strength of rs3803264 dominant model and the risk of HS was observed with the incidence rate ratio (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity <0.001). For the subjects without hypertension, we observed THSD1 mRNA expression had a negative correlation with systolic blood pressure (SBP; ρ = −0.334, p = 0.022).

Conclusion

SNP rs3803264 polymorphisms in THSD1 are associated with the decreased risk of HS and interacted with dyslipidemia, and a non-linear association was observed between THSD1 mRNA expression and the risk of HS.
Association between occlusal support and cognitive impairment in older Chinese adults: a community-based study
Authors: Da Dongxin , Ge Suyu , Zhang Hao , Zeng Xiaoli , Jiang Yiwei , Yu Jin , Wang Huning , Wu Wanqing , Xiao Zhenxu , Liang Xiaoniu , Zhao Qianhua , Ding Ding , Zhang Ying
Published: April 2023

Introduction

The loss of occlusal support due to tooth loss is associated with systemic diseases. However, there was little about the association between occlusal support and cognitive impairment. The cross-sectional study aimed to investigate their association.

Methods

Cognitive function was assessed and diagnosed in 1,225 community-dwelling adults aged 60 years or older in Jing’an District, Shanghai. Participants were diagnosed with mild cognitive impairment (MCI) by Peterson’s criteria, or dementia, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We determined the number of functional occlusal supporting areas according to Eichner classifications. We used multivariate logistic regression models to analyze the relationship between occlusal support and cognitive impairment and mediation effect models to analyze the mediation effect of age.

Results

Six hundred sixty participants were diagnosed with cognitive impairment, averaging 79.92 years old. After adjusting age, sex, education level, cigarette smoking, alcohol drinking, cardiovascular disease, and diabetes, individuals with poor occlusal support had an OR of 3.674 (95%CI 1.141–11.829) for cognitive impairment compared to those with good occlusal support. Age mediated 66.53% of the association between the number of functional occlusal supporting areas and cognitive impairment.

Discussion

In this study, cognitive impairment was significantly associated with the number of missing teeth, functional occlusal areas, and Eichner classifications with older community residents. Occlusal support should be a significant concern for people with cognitive impairment.
Chronic consumption of a hypercaloric diet increases neuroinflammation and brain senescence, promoting cognitive decline in middle-aged female Wistar rats
Authors: Salas-Venegas Verónica , Santín-Márquez Roberto , Ramírez-Carreto Ricardo Jair , Rodríguez-Cortés Yesica María , Cano-Martínez Agustina , Luna-López Armando , Chavarría Anahí , Konigsberg Mina , López-Díazguerrero Norma Edith
Published: April 2023

Being overweight and obesity are world health problems, with a higher prevalence in women, defined as abnormal or excessive fat accumulation that increases the risk of chronic diseases. Excess energy leads to adipose expansion, generating hypertrophic adipocytes that produce various pro-inflammatory molecules. These molecules cause chronic low-intensity inflammation, affecting the organism’s functioning and the central nervous system (CNS), inducing neuroinflammation. The neuroinflammatory response during obesity occurs in different structures of the CNS involved in memory and learning, such as the cortex and the hippocampus. Here we analyzed how obesity-related peripheral inflammation can affect CNS physiology, generating neuroinflammation and promoting cellular senescence establishment. Since some studies have shown an increase in senescent cells during aging, obesity, and neurodegenerative diseases, we proposed that cellular senescence participation may contribute to the cognitive decline in an obesity model of middle-aged female Wistar rats. The inflammatory state of 6 and 13 months-old female Wistar rats fed with a hypercaloric diet was measured in serum and CNS (cortex and hippocampus). Memory was evaluated using the novel object recognition (NOR) test; the presence of senescent markers was also determined. Our data suggest that the systemic inflammation generated by obesity induces a neuroinflammatory state in regions involved in learning and memory, with an increase in senescent markers, thus proposing senescence as a potential participant in the negative consequences of obesity in cognition.
A new understanding of the cognitive reappraisal technique: an extension based on the schema theory
Authors: Wang Ya-Xin , Yin Bin
Published: April 2023

Cognitive reappraisal is a widely utilized emotion regulation strategy that involves altering the personal meaning of an emotional event to enhance attention to emotional responses. Despite its common use, individual differences in cognitive reappraisal techniques and the spontaneous recovery, renewal, and reinstatement of negative responses across varying contexts may limit its effectiveness. Furthermore, detached reappraisal could cause distress for clients. According to Gross’s theory, cognitive reappraisal is an effortless process that can occur spontaneously. When guided language triggers cognitive reappraisal as an emotion regulation strategy in laboratory or counseling settings, clients experience improved emotional states, but this induced strategy may not necessarily guide them in regulating emotions in similar future situations. Therefore, effectively applying cognitive reappraisal techniques in clinical practice to help clients alleviate emotional distress in daily life remains a significant concern. Exploring the mechanism of cognitive reappraisal reveals that reconstructing stimulus meaning is akin to extinction learning, which entails fostering cognitive contingency that the original stimulus provoking negative emotions will no longer result in negative outcomes in the current context. However, extinction learning is a new learning process rather than an elimination process. The activation of new learning relies on the presentation of critical cues, with contextual cues often playing a vital role, such as a safe laboratory or consulting room environment. We propose a new understanding of cognitive reappraisal based on the schema theory and the dual-system theory, emphasizing the significance of environmental interaction and feedback in constructing new experiences and updating schemata. This approach ultimately enriches the schema during training and integrates the new schema into long-term memory. Bottom-up behavioral experiences as schema enrichment training provide the foundation for top-down regulation to function. This method can assist clients in activating more suitable schemata probabilistically when encountering stimuli in real life, forming stable emotions, and achieving transfer and application across diverse contexts.
Assessment of a single trial impact on the amplitude of the averaged event related potentials
Authors: Fedorov Georgy O. , Levichkina Ekaterina , Limanskaya Alexandra V. , Pigareva Marina L. , Pigarev Ivan N.
Published: April 2023

Widely used in neuroscience the averaging of event related potentials is based on the assumption that small responses to the investigated events are present in every trial but can be hidden under the random noise. This situation often takes place, especially in experiments performed at hierarchically lower levels of sensory systems. However, in the studies of higher order complex neuronal networks evoked responses might appear only under particular conditions and be absent otherwise. We encountered this problem studying a propagation of interoceptive information to the cortical areas in the sleep-wake cycle. Cortical responses to various visceral events were present during some periods of sleep, then disappeared for a while and restored again after a period of absence. Further investigation of the viscero-cortical communication required a method that would allow labeling the trials contributing to the averaged event related responses–“efficient trials,” and separating them from the trials without any response. Here we describe a heuristic approach to solving this problem in the context of viscero-cortical interactions occurring during sleep. However, we think that the proposed technique can be applicable to any situation where neuronal processing of the same events is expected to be variable due to internal or external factors modulating neuronal activity. The method was first implemented as a script for Spike 2 program version 6.16 (CED). However, at present a functionally equivalent version of this algorithm is also available as Matlab code athttps://github.com/george-fedorov/erp-correlations.
Cerebello-cortical functional connectivity may regulate reactive balance control in older adults with mild cognitive impairment
Authors: Kannan Lakshmi , Bhatt Tanvi , Ajilore Olusola
Published: April 2023

Background

Older adults with mild cognitive impairment (OAwMCI) experience a two-fold increased risk of falling compared to their cognitively intact counterparts. This increased risk could be attributed to impairments in balance control mechanisms (both volitional and reactive), however, the exact neural substrates contributing to the balance impairments remain unclear. While changes in functional connectivity (FC) networks in volitional balance control tasks have been well highlighted, the relationship between these changes and reactive balance control has not been examined. Therefore, this study aims to explore the relationship between FC networks of the brain obtained during resting state fMRI (no visualization or active task performed) and behavioral measures on a reactive balance task in OAwMCI.

Methods

Eleven OAwMCI (< 25/30 on MoCA, > 55 years) underwent fMRI and were exposed to slip-like perturbations on the Activestep treadmill. Postural stability, i.e., dynamic center of mass motion state (i.e., its position and velocity) was computed to determine reactive balance control performance. The relationship between reactive stability and FC networks was explored using the CONN software.

Results

OAwMCI with greater FC in default mode network-cerebellum (r2 = 0.43, p < 0.05), and sensorimotor-cerebellum (r2 = 0.41, p < 0.05) network exhibited lower reactive stability. Further, people with lower FC in middle frontal gyrus-cerebellum (r2 = 0.37, p < 0.05), frontoparietal-cerebellum (r2 = 0.79, p < 0.05) and cerebellar network-brainstem (r2 = 0.49, p < 0.05) exhibited lower reactive stability.

Conclusion

Older adults with mild cognitive impairment demonstrate significant associations between reactive balance control and cortico-subcortical regions involved in cognitive-motor control. Results indicate that the cerebellum and its communications with higher cortical centers could be potential substrates contributing to impaired reactive responses in OAwMCI.
Twenty-four-hour ambulatory blood pressure variability and association with ischemic stroke subtypes in the subacute stage
Authors: Wang Lijuan , Xia Xiaoshuang , Liu Xin , Wu Guilin , Wang Yanna , Yang Dongliang , Liu Peilin , Chen Zhuangzhuang , Wang Lin , Li Xin
Published: April 2023

Background and purpose

Blood pressure (BP) variability (BPV) increases the risk of cerebral disease in both hemorrhagic and ischemic strokes. However, whether BPV is associated with different types of ischemic stroke remains unclear. In this study, we explored the relationship between BPV and ischemic stroke subtypes.

Methods

We enrolled consecutive patients aged 47–95 years with ischemic stroke in the subacute stage. We categorized them into four groups based on their artery atherosclerosis severity, brain magnetic resonance imaging markers, and disease history: large-artery atherosclerosis, branch atheromatous disease, small-vessel disease, and cardioembolic stroke. Twenty-four-hour ambulatory blood pressure monitoring was performed, and the mean systolic blood pressure/diastolic blood pressure, standard deviation, and coefficient of variation were calculated. A multiple logistic regression model and random forest were used to test the relationship between BP and BPV in the different types of ischemic stroke.

Results

A total of 286 patients, including 150 men (73.0 ± 12.3 years) and 136 women (77.8 ± 9.6 years) were included in the study. Of these, 86 (30.1%) patients had large-artery atherosclerosis, 76 (26.6%) had branch atheromatous disease, 82 (28.7%) had small-vessel disease, and 42 (14.7%) had cardioembolic stroke. There were statistically significant differences in BPV between subtypes of ischemic stroke in 24-h ambulatory blood pressure monitoring. The random forest model showed that BP and BPV were important features associated with ischemic stroke. Multinomial logistic regression analysis demonstrated that systolic blood pressure levels; systolic blood pressure variability at 24 h, daytime and nighttime; and nighttime diastolic blood pressure were independent risk factors for large-artery atherosclerosis after adjustment for confounders. When compared to branch atheromatous disease and small-vessel disease, nighttime diastolic blood pressure and standard deviation of diastolic blood pressure were significantly associated with patients in the cardioembolic stroke group. However, a similar statistical difference was not seen in patients with large-artery atherosclerosis.

Conclusion

The results of this study indicate a discrepancy in blood pressure variability among different ischemic stroke subtypes during the subacute stage. Higher systolic blood pressure and systolic blood pressure variability during the 24 h, daytime, and nighttime, and nighttime diastolic blood pressure were independent predictors for large-artery atherosclerosis stroke. Increased nighttime diastolic BPV was an independent risk factor for cardioembolic stroke.
Increase in conduction velocity in myelinated nerves due to stretch – An experimental verification
Authors: Sharmin Sabrina , Karal Mohammad Abu Sayem , Mahbub Zaid Bin , Rabbani Khondkar Siddique-e
Published: April 2023

Background

Based on published experimental evidence, a recent publication revealed an anomalous phenomenon in nerve conduction: for myelinated nerves the nerve conduction velocity (NCV) increases with stretch, which should have been the opposite according to existing concepts and theories since the diameter decreases on stretching. To resolve the anomaly, a new conduction mechanism for myelinated nerves was proposed based on physiological changes in the nodal region, introducing a new electrical resistance at the node. The earlier experimental measurements of NCV were performed on the ulnar nerve at different angles of flexion, focusing at the elbow region, but left some uncertainty for not reporting the lengths of nerve segments involved so that the magnitudes of stretch could not be estimated.

Aims

The aim of the present study was to relate NCV of myelinated nerves with different magnitudes of stretch through careful measurements.

Method

Essentially, we duplicated the earlier published NCV measurements on ulnar nerves at different angles of flexion but recording appropriate distances between nerve stimulation points on the skin carefully and assuming that the lengths of the underlying nerve segment undergoes the same percentages of changes as that on the skin outside.

Results

We found that the percentage of nerve stretch across the elbow is directly proportional to the angle of flexion and that the percentage increase in NCV is directly proportional to the percentage increase in nerve stretch. Page’s L Trend test also supported the above trends of changes through obtained p values.

Discussion

Our experimental findings on myelinated nerves agree with those of some recent publications which measured changes in CV of single fibres, both myelinated and unmyelinated, on stretch. Analyzing all the observed results, we may infer that the new conduction mechanism based on the nodal resistance and proposed by the recent publication mentioned above is the most plausible one to explain the increase in CV with nerve stretch. Furthermore, interpreting the experimental results in the light of the new mechanism, we may suggest that the ulnar nerve at the forearm is always under a mild stretch, with slightly increased NCV of the myelinated nerves.
Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia
Authors: Jia Rufei , Yuan Xiuxia , Zhang Xiaoyun , Song Peilun , Han Shaoqiang , Wang Shuying , Li Yajun , Zhang Siwei , Zhao Xinyi , Zhang Yu , Cheng Jingliang , Song Xueqin
Published: April 2023

Objective

The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ).

Methods

Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons.

Results

Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)].

Conclusion

Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.
Gamma sensory entrainment for cognitive improvement in neurodegenerative diseases: opportunities and challenges ahead
Authors: Sahu Prangya Parimita , Tseng Philip
Published: April 2023

Neural oscillations have been categorized into various frequency bands that are mechanistically associated with different cognitive functions. Specifically, the gamma band frequency is widely implicated to be involved in a wide range of cognitive processes. As such, decreased gamma oscillation has been associated with cognitive declines in neurological diseases, such as memory dysfunction in Alzheimer’s disease (AD). Recently, studies have attempted to artificially induce gamma oscillations by using 40 Hz sensory entrainment stimulation. These studies reported attenuation of amyloid load, hyper-phosphorylation of tau protein, and improvement in overall cognition in both AD patients and mouse models. In this review, we discuss the advancements in the use of sensory stimulation in animal models of AD and as a therapeutic strategy in AD patients. We also discuss future opportunities, as well as challenges, for using such strategies in other neurodegenerative and neuropsychiatric diseases.
Functional and structural readouts for early detection of retinal involvement in multiple sclerosis
Authors: Al-Nosairy Khaldoon O. , Duscha Alexander , Buhr Henrike , Lipp Antonia , Desel Christiane , Hegelmaier Tobias , Thieme Hagen , Haghikia Aiden , Hoffmann Michael B.
Published: April 2023

Introduction

The retina, a window into the brain, allows for the investigation of many disease-associated inflammatory and neurodegenerative changes affecting the central nervous system (CNS). Multiple sclerosis (MS), an autoimmune disease targeting the CNS, typically impacts on the visual system including the retina. Hence, we aimed to establish innovative functional retinal measures of MS-related damage, e.g., spatially resolved non-invasive retinal electrophysiology, backed by established morphological retinal imaging markers, i.e., optical coherence tomography (OCT).

Methods

20 healthy controls (HC) and 37 people with MS [17 without history of optic neuritis (NON) and 20 with (HON) history of optic neuritis] were included. In this work, we differentially assessed photoreceptor/bipolar cells (distal retina) and retinal ganglion cell (RGC, proximal retina) function besides structural assessment (OCT). We compared two multifocal electroretinography-based approaches, i.e., the multifocal pattern electroretinogram (mfPERG) and the multifocal electroretinogram to record photopic negative response (mfERGPhNR). Structural assessment utilized peripapillary retinal nerve fiber layer thickness (pRNFL) and macular scans to calculate outer nuclear thickness (ONL) and macular ganglion cell inner plexiform layer thickness (GCIPL). One eye was randomly selected per subject.

Results

In NON, photoreceptor/bipolar cell layer had dysfunctional responses evidenced by reduced mfERGPhNR-N1 peak time of the summed response, but preserved structural integrity. Further, both NON and HON demonstrated abnormal RGC responses as evidenced by the photopic negative response of mfERGPhNR (mfPhNR) and mfPERG indices (P < 0.05). Structurally, only HON had thinned retina at the level of RGCs in the macula (GCIPL, P < 0.01) and the peripapillary area (pRNFL, P < 0.01). All three modalities showed good performance to differentiate MS-related damage from HC, 71–81% area under curve.

Conclusion

In conclusion, while structural damage was evident mainly for HON, functional measures were the only retinal read-outs of MS-related retinal damage that were independent of optic neuritis, observed for NON. These results indicate retinal MS-related inflammatory processes in the retina prior to optic neuritis. They highlight the importance of retinal electrophysiology in MS diagnostics and its potential as a sensitive biomarker for follow-up in innovative interventions.
Transcriptional networks of transient cell states during human prefrontal cortex development
Authors: Singh Aditi , Tiwari Vijay K.
Published: April 2023

The human brain is divided into various anatomical regions that control and coordinate unique functions. The prefrontal cortex (PFC) is a large brain region that comprises a range of neuronal and non-neuronal cell types, sharing extensive interconnections with subcortical areas, and plays a critical role in cognition and memory. A timely appearance of distinct cell types through embryonic development is crucial for an anatomically perfect and functional brain. Direct tracing of cell fate development in the human brain is not possible, but single-cell transcriptome sequencing (scRNA-seq) datasets provide the opportunity to dissect cellular heterogeneity and its molecular regulators. Here, using scRNA-seq data of human PFC from fetal stages, we elucidate distinct transient cell states during PFC development and their underlying gene regulatory circuitry. We further identified that distinct intermediate cell states consist of specific gene regulatory modules essential to reach terminal fate using discrete developmental paths. Moreover, using in silico gene knock-out and over-expression analysis, we validated crucial gene regulatory components during the lineage specification of oligodendrocyte progenitor cells. Our study illustrates unique intermediate states and specific gene interaction networks that warrant further investigation for their functional contribution to typical brain development and discusses how this knowledge can be harvested for therapeutic intervention in challenging neurodevelopmental disorders.
The regeneration-responsive element careg monitors activation of Müller glia after MNU-induced damage of photoreceptors in the zebrafish retina
Authors: Bise Thomas , Pfefferli Catherine , Bonvin Marylène , Taylor Lea , Lischer Heidi E. L. , Bruggmann Rémy , Jaźwińska Anna
Published: April 2023

In contrast to mammals, zebrafish can regenerate their damaged photoreceptors. This capacity depends on the intrinsic plasticity of Müller glia (MG). Here, we identified that the transgenic reporter careg, a marker of regenerating fin and heart, also participates in retina restoration in zebrafish. After methylnitrosourea (MNU) treatment, the retina became deteriorated and contained damaged cell types including rods, UV-sensitive cones and the outer plexiform layer. This phenotype was associated with the induction of careg expression in a subset of MG until the reconstruction of the photoreceptor synaptic layer. Single-cell RNA sequencing (scRNAseq) analysis of regenerating retinas revealed a population of immature rods, defined by high expression of rhodopsin and the ciliogenesis gene meig1, but low expression of phototransduction genes. Furthermore, cones displayed deregulation of metabolic and visual perception genes in response to retina injury. Comparison between careg:EGFP expressing and non-expressing MG demonstrated that these two subpopulations are characterized by distinct molecular signatures, suggesting their heterogenous responsiveness to the regenerative program. Dynamics of ribosomal protein S6 phosphorylation showed that TOR signaling became progressively switched from MG to progenitors. Inhibition of TOR with rapamycin reduced the cell cycle activity, but neither affected careg:EGFP expression in MG, nor prevented restoration of the retina structure. This indicates that MG reprogramming, and progenitor cell proliferation might be regulated by distinct mechanisms. In conclusion, the careg reporter detects activated MG, and provides a common marker of regeneration-competent cells in diverse zebrafish organs, including the retina.
Non-neutralizing antibodies to SARS-Cov-2-related linear epitopes induce psychotic-like behavior in mice
Authors: Xu Jinming , Wei Hui , You Pengsheng , Sui Jiaping , Xiu Jianbo , Zhu Wanwan , Xu Qi
Published: April 2023

Objective

An increasing number of studies have reported that numerous patients with coronavirus disease 2019 (COVID-19) and vaccinated individuals have developed central nervous system (CNS) symptoms, and that most of the antibodies in their sera have no virus-neutralizing ability. We tested the hypothesis that non-neutralizing anti-S1-111 IgG induced by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could negatively affect the CNS.

Methods

After 14-day acclimation, the grouped ApoE-/- mice were immunized four times (day 0, day 7, day 14, day 28) with different spike-protein-derived peptides (coupled with KLH) or KLH via subcutaneous injection. Antibody level, state of glial cells, gene expression, prepulse inhibition, locomotor activity, and spatial working memory were assessed from day 21.

Results

An increased level of anti-S1-111 IgG was measured in their sera and brain homogenate after the immunization. Crucially, anti-S1-111 IgG increased the density of microglia, activated microglia, and astrocytes in the hippocampus, and we observed a psychomotor-like behavioral phenotype with defective sensorimotor gating and impaired spontaneity among S1-111-immunized mice. Transcriptome profiling showed that up-regulated genes in S1-111-immunized mice were mainly associated with synaptic plasticity and mental disorders.

Discussion

Our results show that the non-neutralizing antibody anti-S1-111 IgG induced by the spike protein caused a series of psychotic-like changes in model mice by activating glial cells and modulating synaptic plasticity. Preventing the production of anti-S1-111 IgG (or other non-neutralizing antibodies) may be a potential strategy to reduce CNS manifestations in COVID-19 patients and vaccinated individuals.
Prefrontal modulation of anxiety through a lens of noradrenergic signaling
Authors: Bouras Nadia N. , Mack Nancy R. , Gao Wen-Jun
Published: April 2023

Anxiety disorders are the most common class of mental illness in the U.S., affecting 40 million individuals annually. Anxiety is an adaptive response to a stressful or unpredictable life event. Though evolutionarily thought to aid in survival, excess intensity or duration of anxiogenic response can lead to a plethora of adverse symptoms and cognitive dysfunction. A wealth of data has implicated the medial prefrontal cortex (mPFC) in the regulation of anxiety. Norepinephrine (NE) is a crucial neuromodulator of arousal and vigilance believed to be responsible for many of the symptoms of anxiety disorders. NE is synthesized in the locus coeruleus (LC), which sends major noradrenergic inputs to the mPFC. Given the unique properties of LC-mPFC connections and the heterogeneous subpopulation of prefrontal neurons known to be involved in regulating anxiety-like behaviors, NE likely modulates PFC function in a cell-type and circuit-specific manner. In working memory and stress response, NE follows an inverted-U model, where an overly high or low release of NE is associated with sub-optimal neural functioning. In contrast, based on current literature review of the individual contributions of NE and the PFC in anxiety disorders, we propose a model of NE level- and adrenergic receptor-dependent, circuit-specific NE-PFC modulation of anxiety disorders. Further, the advent of new techniques to measure NE in the PFC with unprecedented spatial and temporal resolution will significantly help us understand how NE modulates PFC function in anxiety disorders.
Evaluation of the Preventive Effects of Fish Oil and Sunflower Seed Oil on the Pathophysiology of Sepsis in Endotoxemic Rats
Authors: Kuo Yen-Shou , Hu Mei-Hua , Chan Wei-Hung , Huang Tien-Yu , Chou Yu-Ching , Huang Go-Shine
Published: April 2023

Graphical Abstract

Effects of dietary supplementation of fish oil and sunflower seed oil on the levels of BUN, creatinine, GPT, hemoglobin, hematocrit, lactate, glucose, LDH, Na+, K+, Ca2+, and Mg2+). Data are expressed as mean ± SD. BUN, blood urea nitrogen; GPT, glutamate pyruvate transaminase; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; n, number of rats that survived.
Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study
Authors: Chen Geng-dong , Pang Ting-ting , Li Peng-sheng , Zhou Zi-xing , Gou Xiao-yan , Wang Hai-yan , Lin Dong-xin , Fan Da-zhi , Li Hong-li , Liu Zheng-ping
Published: April 2023

Background and Aims

The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study.

Methods

We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia.

Results

After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1.

Conclusion

Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.
Dietary patterns derived using principal component analysis and associations with sociodemographic characteristics and overweight and obesity: A cross-sectional analysis of Iranian adults
Authors: Ebrahimi Sara , Leech Rebecca M. , McNaughton Sarah A. , Abdollahi Morteza , Houshiarrad Anahita , Livingstone Katherine M.
Published: April 2023

Introduction

This study examined the cross-sectional association between household dietary patterns and sociodemographic characteristics and BMI in a nationally representative sample of Iranian adults.

Methods

Data on 6,833 households (n = 17,824 adults) from the National Comprehensive Study on Household Food Consumption Pattern and Nutritional Status 2001–2003 were used. Principal component analysis (PCA) was used to extract dietary patterns from three household 24-h dietary recalls. Linear regression analyses were used to examine associations between dietary patterns and sociodemographic characteristics and BMI.

Results

Three dietary patterns were identified: the first was characterized by high citrus fruit intake, the second by high hydrogenated fats intake and the third by high non-leafy vegetables intake. The first and third patterns were associated with household heads with higher education and living in urban areas, while the second was associated with household heads with lower education and living in rural areas. All dietary patterns were positively associated with BMI. The strongest association was found with the first dietary pattern (β: 0.49, 95% CI: 0.43, 0.55).

Discussion

While all three dietary patterns were positively associated with BMI, the sociodemographic characteristics of Iranian adults who consumed them differed. These findings inform the design of population-level dietary interventions to address rising obesity rates in Iran.
Development of a novel definitive scoring system for an enteral feed-only model of necrotizing enterocolitis in piglets
Authors: Ragan Mecklin V. , Wala Samantha J. , Sajankila Nitin , Duff Audrey F. , Wang Yijie , Volpe Samuel G. , Al-Hadidi Ameer , Dumbauld Zachary , Purayil Nanditha , Wickham Joseph , Conces Miriam R. , Mihi Belgacem , Goodman Steven D. , Bailey Michael T. , Besner Gail E.
Published: April 2023

Introduction

Necrotizing enterocolitis (NEC) is a complex inflammatory disorder of the human intestine that most often occurs in premature newborns. Animal models of NEC typically use mice or rats; however, pigs have emerged as a viable alternative given their similar size, intestinal development, and physiology compared to humans. While most piglet NEC models initially administer total parenteral nutrition prior to enteral feeds, here we describe an enteral-feed only piglet model of NEC that recapitulates the microbiome abnormalities present in neonates that develop NEC and introduce a novel multifactorial definitive NEC (D-NEC) scoring system to assess disease severity.

Methods

Premature piglets were delivered via Caesarean section. Piglets in the colostrum-fed group received bovine colostrum feeds only throughout the experiment. Piglets in the formula-fed group received colostrum for the first 24 h of life, followed by Neocate Junior to induce intestinal injury. The presence of at least 3 of the following 4 criteria were required to diagnose D-NEC: (1) gross injury score ≥4 of 6; (2) histologic injury score ≥3 of 5; (3) a newly developed clinical sickness score ≥5 of 8 within the last 12 h of life; and (4) bacterial translocation to ≥2 internal organs. Quantitative reverse transcription polymerase chain reaction was performed to confirm intestinal inflammation in the small intestine and colon. 16S rRNA sequencing was performed to evaluate the intestinal microbiome.

Results

Compared to the colostrum-fed group, the formula-fed group had lower survival, higher clinical sickness scores, and more severe gross and histologic intestinal injury. There was significantly increased bacterial translocation, D-NEC, and expression of IL-1α and IL-10 in the colon of formula-fed compared to colostrum-fed piglets. Intestinal microbiome analysis of piglets with D-NEC demonstrated lower microbial diversity and increased Gammaproteobacteria and Enterobacteriaceae.

Conclusions

We have developed a clinical sickness score and a new multifactorial D-NEC scoring system to accurately evaluate an enteral feed-only piglet model of NEC. Piglets with D-NEC had microbiome changes consistent with those seen in preterm infants with NEC. This model can be used to test future novel therapies to treat and prevent this devastating disease.