bluuebunny/crossref_metadata_2025 huggingface dataset:
The ratio of serum neuron-specific enolase level to admission glasgow coma scale score is associated with diffuse axonal injury in patients with moderate to severe traumatic brain injury
Authors: Chen Weiliang , Wang Guanjun , Yao Chunyu , Zhu Zujian , Chen Rui , Su Wen , Jiang Rongcai
Published: September 2022

Background

Moderate to severe traumatic brain injury (TBI) is frequently accompanied by diffuse axonal injury (DAI). Considering the low sensitivity of computed tomography (CT) examination for microbleeds and axonal damage, identification of DAI is difficult using conventional diagnostic methods in the acute phase. Neuron-specific enolase (NSE) has been demonstrated to be increased in serum following various types of TBI and is already clinically/commercially available. We conjecture that serum NSE level to admission GCS score ratio (NGR) may be a useful indicator for the early diagnosis of DAI.

Methods

This study included 115 patients with moderate-to-severe TBI who underwent NSE measurements within 6 h after injury and brain magnetic resonance imaging (MRI) within 30 days. The positive and negative DAI groups were divided according to MRI findings.

Results

Among the 115 patients, 49 (42.6%) were classified into the DAI group and 66 (57.4%) patients into the non-DAI group by clinical MRI. The NGR of patients without DAI was found to be significantly lower than those of patients with DAI (p < 0.0001). NGR presented the largest Pearson r value (r = 0.755, 95% CI 0.664–0.824, p < 0.0001) and high diagnostic accuracy for DAI [area under the curve (AUC) = 0.9493; sensitivity, 90.91%; and specificity, 85.71%]. Patients with TBI presenting with higher NGR were more likely to suffer an unfavorable neurological outcome [6-month extended Glasgow Outcome Scale (GOSE) 1–4].

Conclusions

The NGR on admission could serve as an independent predictor of DAI with moderate-to-severe TBI.
Efficacy of a multiple-component and multifactorial personalized fall prevention program in a mixed population of community-dwelling older adults with stroke, Parkinson's Disease, or frailty compared to usual care: The PRE.C.I.S.A. randomized controlled trial
Authors: La Porta Fabio , Lullini Giada , Caselli Serena , Valzania Franco , Mussi Chiara , Tedeschi Claudio , Pioli Giulio , Bondavalli Massimo , Bertolotti Marco , Banchelli Federico , D'Amico Roberto , Vicini Roberto , Puglisi Silvia , Clerici Pierina Viviana , Chiari Lorenzo ,   The PRECISA Group
Published: September 2022

Background

Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge.

Aim

To evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care.

Design

Randomized Controlled Trial (NCT03592420, clinicalTrials.gov).

Setting

Outpatients in two Italian centers.

Population

403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke.

Methods

After the randomization, the described interventions were administered to the intervention group (n = 203). The control group (n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3).

Results

690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest (p = 0.004) and the Fullerton Advanced Balance Scale (p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations.

Conclusions

The intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences.
Vagus nerve stimulation in children with drug-resistant epilepsy of monogenic etiology
Authors: Xie Han , Ma Jiayi , Ji Taoyun , Liu Qingzhu , Cai Lixin , Wu Ye
Published: September 2022

Vagus nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy (DRE). The present study evaluated the efficacy of VNS in pediatric patients with DRE of monogenic etiology. A total of 20 patients who received VNS treatment at our center were followed up every 3 months through outpatient visits or a remote programming platform. The median follow-up time was 1.4 years (range: 1.0–2.9). The rate of response to VNS at 12 months of follow-up was 55.0% (11/20) and the seizure-free rate was 10.0% (2/20). We found that 75.0% (3/4) of patients with an SCN1A variant had a >50% reduction in seizure frequency. Patients with pathogenic mutations in the SLC35A2, CIC, DNM1, MBD5, TUBGCP6, EEF1A2, and CHD2 genes or duplication of X q28 (MECP2 gene) had a >50% reduction in seizure frequency. Compared with the preoperative electroencephalography (EEG), at 6, 12, 18, and 24 months after stimulator implantation, the percentage of the patients whose background frequency increased >1.5 Hz was respectively, 15.0% (3/20), 50.0% (10/20), 58.3% (7/12) and 62.5% (5/8); the percentage of the patients whose interictal EEG showed a >50% decrease in spike number was respectively 10% (2/20), 40.0% (8/20), 41.6% (5/12) and 50.0% (4/8). In the 9 patients with no response to VNS treatment, there was no difference in terms of spike number and background frequency between preoperative and postoperative EEG. Five of the 20 children (25.0%) reached new developmental milestones or acquired new skills after VNS compared to the preoperative evaluation. The efficacy of VNS in pediatric patients with DRE of monogenic etiology is consistent with that in the overall population of pediatric DRE patients. Patients with Dravet syndrome (DS), tuberous sclerosis complex (TSC), or Rett syndrome/MECP2 duplication syndrome may have a satisfactory response to VNS, but it is unclear whether patients with rare variants of epilepsy-related genes can benefit from the treatment.
Night blood pressure variability, brain atrophy, and cognitive decline
Authors: Yu Ji Hee , Kim Regina E. Y. , Park So Young , Lee Da Young , Cho Hyun Joo , Kim Nam Hoon , Yoo Hye Jin , Seo Ji A , Kim Seong Hwan , Kim Sin Gon , Choi Kyung Mook , Baik Sei Hyun , Shin Chol , Kim Nan Hee
Published: September 2022

Background

Although blood pressure variability (BPV) has emerged as a novel risk factor for Alzheimer's disease, few studies have examined the effects of night BPV on brain structure and function. This study investigated the association of night BPV with brain atrophy and cognitive function changes.

Methods

The analysis included 1,398 participants with valid ambulatory blood pressure (BP) monitoring at baseline and both baseline and 4-year follow-up brain magnetic resonance images who were recruited from the Korean Genome and Epidemiology Study. Participants underwent a comprehensive neuropsychological test battery. BPV was derived from ambulatory BP monitoring and calculated as a standard deviation (SD) of 24-h and daytime and nighttime BP.

Results

During the median follow-up of 4.3 years, increased SD of night systolic or diastolic BP was an indicator of total brain volume reduction, while daytime BPV or night average BP was not associated with total brain volume changes. High SD of night systolic BP was associated with reduced gray matter (GM) volume, independent of average night BP, and use of antihypertensive drugs. It also was associated with a reduction of temporal GM volume, mostly driven by atrophy in the left entorhinal cortex and the right fusiform gyrus. In cognitive performance, high variability of night systolic BP was associated with a decrease in visual delayed recall memory and verbal fluency for the category.

Conclusion

Increased night BPV, rather than night mean BP, was associated with reduced brain volume and cognitive decline. High night BPV could be an independent predictor for rapid brain aging in a middle-aged population.
Biomarkers involved in the pathogenesis of cerebral small-vessel disease
Authors: Liu Xiaolu , Sun Pei , Yang Jing , Fan Yuhua
Published: September 2022

Cerebral small-vessel disease (CSVD) has been found to have a strong association with vascular cognitive impairment (VCI) and functional loss in elderly patients. At present, the diagnosis of CSVD mainly relies on brain neuroimaging markers, but they cannot fully reflect the overall picture of the disease. Currently, some biomarkers were found to be related to CSVD, but the underlying mechanisms remain unclear. We aimed to systematically review and summarize studies on the progress of biomarkers related to the pathogenesis of CSVD, which is mainly the relationship between these indicators and neuroimaging markers of CSVD. Concerning the pathophysiological mechanism of CSVD, the biomarkers of CSVD have been described as several categories related to sporadic and genetic factors. Monitoring of biomarkers might contribute to the early diagnosis and progression prediction of CSVD, thus providing ideas for better diagnosis and treatment of CSVD.
Vertical ground reaction force oscillation during standing on hard and compliant surfaces: The “postural rhythm”
Authors: Sozzi Stefania , Do Manh-Cuong , Schieppati Marco
Published: September 2022

When a person stands upright quietly, the position of the Centre of Mass (CoM), the vertical force acting on the ground and the geometrical configuration of body segments is accurately controlled around to the direction of gravity by multiple feedback mechanisms and by integrative brain centres that coordinate multi-joint movements. This is not always easy and the postural muscles continuously produce appropriate torques, recorded as ground reaction force by a force platform. We studied 23 young adults during a 90 s period, standing at ease on a hard (Solid) and on a compliant support (Foam) with eyes open (EO) and with eyes closed (EC), focusing on the vertical component of the ground reaction force (VGRF). Analysis of VGRF time series gave the amplitude of their rhythmic oscillations (the root mean square, RMS) and of their frequency spectrum. Sway Area and Path Length of the Centre of Pressure (CoP) were also calculated. VGRF RMS (as well as CoP sway measures) increased in the order EO Solid ≈ EC Solid < EO Foam < EC Foam. The VGRF frequency spectra featured prevailing frequencies around 4–5 Hz under all tested conditions, slightly higher on Solid than Foam support. Around that value, the VGRF frequencies varied in a larger range on hard than on compliant support. Sway Area and Path Length were inversely related to the prevailing VGRF frequency. Vision compared to no-vision decreased Sway Area and Path Length and VGRF RMS on Foam support. However, no significant effect of vision was found on VGRF mean frequency for either base of support condition. A description of the VGRF, at the interface between balance control mechanisms and sway of the CoP, can contribute information on how upright balance is maintained. Analysis of the frequency pattern of VGRF oscillations and its role in the maintenance of upright stance should complement the traditional measures of CoP excursions in the horizontal plane.
Poor sleep quality is associated with fatigue and depression in early Parkinson's disease: A longitudinal study in the PALS cohort
Authors: Koh Matthew Rui En , Chua Cong Yang , Ng Samuel Yong-Ern , Chia Nicole Shuang-Yu , Saffari Seyed Ehsan , Chen Regina Yu-Ying , Choi Xinyi , Heng Dede Liana , Neo Shermyn Xiumin , Tay Kay Yaw , Au Wing Lok , Tan Eng-King , Tan Louis Chew-Seng , Xu Zheyu
Published: September 2022

Background

Sleep disorders are common in Parkinson's disease (PD). However, the longitudinal relationship between sleep quality and the other non-motor symptoms of PD has not been well characterized, especially in early PD.

Objective

To explore the value of baseline sleep quality in predicting the progression of other non-motor symptoms in early PD.

Methods

109 early PD patients were recruited to the study. Patients were stratified into good and poor sleepers using the Pittsburgh Sleep Quality Index (PSQI). Assessments performed at baseline and 1 year follow-up included the Epworth Sleepiness Scale, Fatigue Severity Scale, Non-Motor Symptom Scale, Geriatric Depression Scale, Hospital Anxiety and Depression Scale, Apathy Scale, Montreal Cognitive Assessment and detailed neuropsychological assessments. Multivariable linear regression was performed at baseline to investigate differences in clinical scores between poor and good sleepers, while multivariable regression models were used to investigate associations between sleep quality and progression of test scores at 1 year follow-up.

Results

59 poor sleepers and 50 good sleepers were identified. At baseline, poor sleepers had greater HADS anxiety scores (p = 0.013) [2.99 (95% CI 2.26, 3.73)] than good sleepers [1.59 (95% CI 0.75, 2.42)]. After 1 year, poor sleepers had greater fatigue (FSS scores +3.60 as compared to −2.93 in good sleepers, p = 0.007) and depression (GDS scores +0.42 as compared to −0.70, p = 0.006).

Conclusion

This study shows a longitudinal association between sleep quality, fatigue, and depression in early PD patients, independent of medication effect and disease severity, this may support the hypothesis that a common serotonergic pathway is implicated in these non-motor symptoms.
How standardized are “standard protocols”? Variations in protocol and performance evaluation for slow cortical potential neurofeedback: A systematic review
Authors: Hasslinger John , Meregalli Micaela , Bölte Sven
Published: September 2022

Neurofeedback (NF) aims to alter neural activity by enhancing self-regulation skills. Over the past decade NF has received considerable attention as a potential intervention option for many somatic and mental conditions and ADHD in particular. However, placebo-controlled trials have demonstrated insufficient superiority of NF compared to treatment as usual and sham conditions. It has been argued that the reason for limited NF effects may be attributable to participants' challenges to self-regulate the targeted neural activity. Still, there is support of NF efficacy when only considering so-called “standard protocols,” such as Slow Cortical Potential NF training (SCP-NF). This PROSPERO registered systematic review following PRISMA criteria searched literature databases for studies applying SCP-NF protocols. Our review focus concerned the operationalization of self-regulatory success, and protocol-details that could influence the evaluation of self-regulation. Such details included; electrode placement, number of trials, length per trial, proportions of training modalities, handling of artifacts and skill-transfer into daily-life. We identified a total of 63 eligible reports published in the year 2000 or later. SCP-NF protocol-details varied considerably on most variables, except for electrode placement. However, due to the increased availability of commercial systems, there was a trend to more uniform protocol-details. Although, token-systems are popular in SCP-NF for ADHD, only half reported a performance-based component. Also, transfer exercises have become a staple part of SCP-NF. Furthermore, multiple operationalizations of regulatory success were identified, limiting comparability between studies, and perhaps usefulness of so-called transfer-exercises, which purpose is to facilitate the transfer of the self-regulatory skills into every-day life. While studies utilizing SCP as Brain-Computer-Interface mainly focused on the acquisition of successful self-regulation, clinically oriented studies often neglected this. Congruently, rates of successful regulators in clinical studies were mostly low (<50%). The relation between SCP self-regulation and behavior, and how symptoms in different disorders are affected, is complex and not fully understood. Future studies need to report self-regulation based on standardized measures, in order to facilitate both comparability and understanding of the effects on symptoms. When applied as treatment, future SCP-NF studies also need to put greater emphasis on the acquisition of self-regulation (before evaluating symptom outcomes).

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021260087, Identifier: CRD42021260087.
A tale of two connectivities: intra- and inter-subject functional connectivity jointly enable better prediction of social abilities
Authors: Xie Hua , Redcay Elizabeth
Published: September 2022

Naturalistic functional magnetic resonance imaging (fMRI) paradigms, such as movie viewing, are attracting increased attention, given their ability to mimic the real-world cognitive demands on attention and multimodal sensory integration. Moreover, naturalistic paradigms allow for characterizing brain network responses associated with dynamic social cognition in a model-free manner using inter-subject functional connectivity (ISFC). While intra-subject functional connectivity (FC) characterizes the individual’s brain functional architecture, ISFC characterizes the neural coupling driven by time-locked extrinsic dynamic stimuli across individuals. Here, we hypothesized that ISFC and FC provide distinct and complementary information about individual differences in social cognition. To test this hypothesis, we examined a public movie-viewing fMRI dataset with 32 healthy adults and 90 typically developing children. Building three partial least squares regression (PLS) models to predict social abilities using FC and/or ISFC, we compared predictive performance to determine whether combining two connectivity measures could improve the prediction accuracy of individuals’ social-cognitive abilities measured by a Theory of Mind (ToM) assessment. Our results indicated that the joint model (ISFC + FC) yielded the highest predictive accuracy and significantly predicted individuals’ social cognitive abilities (rho = 0.34, p < 0.001). We also confirmed that the improved accuracy was not due to the increased feature dimensionality. In conclusion, we demonstrated that intra-/inter-subject connectivity encodes unique information about social abilities, and a joint investigation could help us gain a more complete understanding of the complex processes supporting social cognition.
Modulation of the autonomic nervous system by one session of spinal low-level laser therapy in patients with chronic colonic motility dysfunction
Authors: Ali M. Khawar , Saha Shrayasee , Milkova Natalija , Liu Lijun , Sharma Kartik , Huizinga Jan D. , Chen Ji-Hong
Published: September 2022

Patients with a defecation disorder may not evoke a normal defecation reflex, or the reflex may be excessive, as a dysfunction of the spinal autonomic nervous system. Treatment with various forms of lumbar and sacral neuromodulation have shown symptom improvement, but potential changes in autonomic functioning are rarely studied. Here we evaluate the effects on autonomic function of a single session of low-level laser therapy (LLLT) on the lumbar and sacral spine in 41 patients with chronic gastrointestinal motor dysfunction. The LLLT protocol used red LED light at a wavelength of 660 nm for 10 min and infrared LED light at a wavelength of 840 nm for 10 min, followed by infrared laser light at a wavelength of 825 nm for 10 min. Effects on the autonomic nervous system were assessed by measuring heart rate variability (HRV) changes. Respiratory Sinus Arrhythmia (RSA) and Root Mean Square of Successive Differences (RMSSD) were used to quantify parasympathetic reactivity; the Baevsky’s Stress Index (SI) reflected sympathetic activity while the ratios SI/RSA and SI/RMSSD were used to show shifts in autonomic dominance. The results indicate that lumbar and sacral neuromodulation using light arrays reduced, whereas stimulation by the laser probes significantly increased parasympathetic activity. The light arrays increased whereas the laser probes significantly decreased sympathetic activity (SI). The entire protocol shifted the autonomic balance toward parasympathetic activity. The comparison of actual vs. sham neuromodulation proved that the change in HRV parameters was due to actual light stimulation and not due to the arrays and probe touching the skin. In conclusion, a single session of LLLT markedly affects autonomic nervous system activity reflected in changes in HRV which is only possible by generating activity in the spinal autonomic nerves. These results warrant a study into the effects of LLLT on restoring autonomic dysfunction in chronic refractory colonic motility disorders.
Pcdh11x controls target specification of mossy fiber sprouting
Authors: Luo Wenshu , Cruz-Ochoa Natalia Andrea , Seng Charlotte , Egger Matteo , Lukacsovich David , Lukacsovich Tamás , Földy Csaba
Published: September 2022

Circuit formation is a defining characteristic of the developing brain. However, multiple lines of evidence suggest that circuit formation can also take place in adults, the mechanisms of which remain poorly understood. Here, we investigated the epilepsy-associated mossy fiber (MF) sprouting in the adult hippocampus and asked which cell surface molecules define its target specificity. Using single-cell RNAseq data, we found lack and expression of Pcdh11x in non-sprouting and sprouting neurons respectively. Subsequently, we used CRISPR/Cas9 genome editing to disrupt the Pcdh11x gene and characterized its consequences on sprouting. Although MF sprouting still developed, its target specificity was altered. New synapses were frequently formed on granule cell somata in addition to dendrites. Our findings shed light onto a key molecular determinant of target specificity in MF sprouting and contribute to understanding the molecular mechanism of adult brain rewiring.
Quantitative behavioral evaluation of a non-human primate stroke model using a new monitoring system
Authors: Hirohata Toshikazu , Kitano Takaya , Saeki Chizu , Baba Kousuke , Yoshida Fumiaki , Kurihara Takashi , Harada Katsuhiro , Saito Shigeyoshi , Mochizuki Hideki , Shimodozono Megumi
Published: September 2022

Background

Recently, the common marmoset (Callithrix jacchus) has attracted significant interest as a non-human primate stroke model. Functional impairment in non-human primate stroke models should be evaluated quantitatively and successively after stroke, but conventional observational assessments of behavior cannot fully fit this purpose. In this paper, we report a behavioral analysis using MarmoDetector, a three-dimensional motion analysis, in an ischemic stroke model using photosensitive dye, along with an observational behavioral assessment and imaging examination.

Methods

Ischemic stroke was induced in the left hemisphere of three marmosets. Cerebral infarction was induced by intravenous injection of rose bengal and irradiation with green light. The following day, the success of the procedure was confirmed by magnetic resonance imaging (MRI). The distance traveled, speed, activity time, and jumps/climbs were observed for 28 days after stroke using MarmoDetector. We also assessed the marmosets’ specific movements and postural abnormalities using conventional neurological scores.

Results

Magnetic resonance imaging diffusion-weighted and T2-weighted images showed hyperintense signals, indicating cerebral infarction in all three marmosets. MarmoDetector data showed that the both indices immediately after stroke onset and gradually improved over weeks. Neurological scores were the worst immediately after stroke and did not recover to pre-infarction levels during the observation period (28 days). A significant correlation was observed between MarmoDetector data and conventional neurological scores.

Conclusion

In this study, we showed that MarmoDetector can quantitatively evaluate behavioral changes in the acute to subacute phases stroke models. This technique can be practical for research on the pathophysiology of ischemic stroke and for the development of new therapeutic methods.
Binary acoustic metasurfaces for dynamic focusing of transcranial ultrasound
Authors: Hu Zhongtao , Yang Yaoheng , Xu Lu , Hao Yao , Chen Hong
Published: September 2022

Transcranial focused ultrasound (tFUS) is a promising technique for non-invasive and spatially targeted neuromodulation and treatment of brain diseases. Acoustic lenses were designed to correct the skull-induced beam aberration, but these designs could only generate static focused ultrasound beams inside the brain. Here, we designed and 3D printed binary acoustic metasurfaces (BAMs) for skull aberration correction and dynamic ultrasound beam focusing. BAMs were designed by binarizing the phase distribution at the surface of the metasurfaces. The phase distribution was calculated based on time reversal to correct the skull-induced phase aberration. The binarization enabled the ultrasound beam to be dynamically steered along wave propagation direction by adjusting the operation frequency of the incident ultrasound wave. The designed BAMs were manufactured by 3D printing with two coding bits, a polylactic acid unit for bit “1” and a water unit for bit “0.” BAMs for single- and multi-point focusing through the human skull were designed, 3D printed, and validated numerically and experimentally. The proposed BAMs with subwavelength scale in thickness are simple to design, easy to fabric, and capable of correcting skull aberration and achieving dynamic beam steering.
High-definition transcranial direct current stimulation of the left middle temporal complex does not affect visual motion perception learning
Authors: Wu Di , Wang Yifan , Liu Na , Wang Panhui , Sun Kewei , Xiao Wei
Published: September 2022

Visual perceptual learning (VPL) refers to the improvement in visual perceptual abilities through training and has potential implications for clinical populations. However, improvements in perceptual learning often require hundreds or thousands of trials over weeks to months to attain, limiting its practical application. Transcranial direct current stimulation (tDCS) could potentially facilitate perceptual learning, but the results are inconsistent thus far. Thus, this research investigated the effect of tDCS over the left human middle temporal complex (hMT+) on learning to discriminate visual motion direction. Twenty-seven participants were randomly assigned to the anodal, cathodal and sham tDCS groups. Before and after training, the thresholds of motion direction discrimination were assessed in one trained condition and three untrained conditions. Participants were trained over 5 consecutive days while receiving 4 × 1 ring high-definition tDCS (HD-tDCS) over the left hMT+. The results showed that the threshold of motion direction discrimination significantly decreased after training. However, no obvious differences in the indicators of perceptual learning, such as the magnitude of improvement, transfer indexes, and learning curves, were noted among the three groups. The current study did not provide evidence of a beneficial effect of tDCS on VPL. Further research should explore the impact of the learning task characteristics, number of training sessions and the sequence of stimulation.
Advances in non-invasive tracking of wave-type electric fish in natural and laboratory settings
Authors: Raab Till , Madhav Manu S. , Jayakumar Ravikrishnan P. , Henninger Jörg , Cowan Noah J. , Benda Jan
Published: September 2022

Recent technological advances greatly improved the possibility to study freely behaving animals in natural conditions. However, many systems still rely on animal-mounted devices, which can already bias behavioral observations. Alternatively, animal behaviors can be detected and tracked in recordings of stationary sensors, e.g., video cameras. While these approaches circumvent the influence of animal-mounted devices, identification of individuals is much more challenging. We take advantage of the individual-specific electric fields electric fish generate by discharging their electric organ (EOD) to record and track their movement and communication behaviors without interfering with the animals themselves. EODs of complete groups of fish can be recorded with electrode arrays submerged in the water and then be tracked for individual fish. Here, we present an improved algorithm for tracking electric signals of wave-type electric fish. Our algorithm benefits from combining and refining previous approaches of tracking individual specific EOD frequencies and spatial electric field properties. In this process, the similarity of signal pairs in extended data windows determines their tracking order, making the algorithm more robust against detection losses and intersections. We quantify the performance of the algorithm and show its application for a data set recorded with an array of 64 electrodes distributed over a 12 m2 section of a stream in the Llanos, Colombia, where we managed, for the first time, to track Apteronotus leptorhynchus over many days. These technological advances make electric fish a unique model system for a detailed analysis of social and communication behaviors, with strong implications for our research on sensory coding.
TRPV1 in chronic pruritus and pain: Soft modulation as a therapeutic strategy
Authors: Fernández-Carvajal Asia , Fernández-Ballester Gregorio , Ferrer-Montiel Antonio
Published: September 2022

Chronic pain and pruritus are highly disabling pathologies that still lack appropriate therapeutic intervention. At cellular level the transduction and transmission of pain and pruritogenic signals are closely intertwined, negatively modulating each other. The molecular and cellular pathways involved are multifactorial and complex, including peripheral and central components. Peripherally, pain and itch are produced by subpopulations of specialized nociceptors that recognize and transduce algesic and pruritogenic signals. Although still under intense investigation, cumulative evidence is pointing to the thermosensory channel TRPV1 as a hub for a large number of pro-algesic and itchy agents. TRPV1 appears metabolically coupled to most neural receptors that recognize algesic and pruritic molecules. Thus, targeting TRPV1 function appears as a valuable and reasonable therapeutic strategy. In support of this tenet, capsaicin, a desensitizing TRPV1 agonist, has been shown to exhibit clinically relevant analgesic, anti-inflammatory, and anti-pruritic activities. However, potent TRPV1 antagonists have been questioned due to an hyperthermic secondary effect that prevented their clinical development. Thus, softer strategies directed to modulate peripheral TRPV1 function appear warranted to alleviate chronic pain and itch. In this regard, soft, deactivatable TRPV1 antagonists for topical or local application appear as an innovative approach for improving the distressing painful and itchy symptoms of patients suffering chronic pain or pruritus. Here, we review the data on these compounds and propose that this strategy could be used to target other peripheral therapeutic targets.
Förster resonance energy transfer-based kinase mutation phenotyping reveals an aberrant facilitation of Ca2+/calmodulin-dependent CaMKIIα activity in de novo mutations related to intellectual disability
Authors: Fujii Hajime , Kidokoro Hiroyuki , Kondo Yayoi , Kawaguchi Masahiro , Horigane Shin-ichiro , Natsume Jun , Takemoto-Kimura Sayaka , Bito Haruhiko
Published: September 2022

CaMKIIα plays a fundamental role in learning and memory and is a key determinant of synaptic plasticity. Its kinase activity is regulated by the binding of Ca2+/CaM and by autophosphorylation that operates in an activity-dependent manner. Though many mutations in CAMK2A were linked to a variety of neurological disorders, the multiplicity of its functional substrates renders the systematic molecular phenotyping challenging. In this study, we report a new case of CAMK2A P212L, a recurrent mutation, in a patient with an intellectual disability. To quantify the effect of this mutation, we developed a FRET-based kinase phenotyping strategy and measured aberrance in Ca2+/CaM-dependent activation dynamics in vitro and in synaptically connected neurons. CaMKIIα P212L revealed a significantly facilitated Ca2+/CaM-dependent activation in vitro. Consistently, this mutant showed faster activation and more delayed inactivation in neurons. More prolonged kinase activation was also accompanied by a leftward shift in the CaMKIIα input frequency tuning curve. In keeping with this, molecular phenotyping of other reported CAMK2A de novo mutations linked to intellectual disability revealed aberrant facilitation of Ca2+/CaM-dependent activation of CaMKIIα in most cases. Finally, the pharmacological reversal of CAMK2A P212L phenotype in neurons was demonstrated using an FDA-approved NMDA receptor antagonist memantine, providing a basis for targeted therapeutics in CAMK2A-linked intellectual disability. Taken together, FRET-based kinase mutation phenotyping sheds light on the biological impact of CAMK2A mutations and provides a selective, sensitive, quantitative, and scalable strategy for gaining novel insights into the molecular etiology of intellectual disability.
Fish oil supplementation of rats fed a high fat diet during pregnancy improves offspring insulin sensitivity
Authors: Satokar Vidit V. , Vickers Mark H. , Reynolds Clare M. , Ponnampalam Anna P. , Firth Elwyn C. , Garg Manohar L. , Barrett Carolyn J. , Cutfield Wayne S. , Albert Benjamin B.
Published: September 2022

Introduction

In rats, a maternal high-fat diet (HFD) leads to adverse metabolic changes in the adult offspring, similar to the children of mothers with obesity during pregnancy. Supplementation with a high dose of fish oil (FO) to pregnant rats fed a HFD has been shown to prevent the development of insulin resistance in adult offspring. However, the effects of supplementation at a translationally relevant dose remain unknown.

Aim

To determine whether supplementation with a human-relevant dose of FO to pregnant rats can prevent the long-term adverse metabolic and cardiovascular effects of a maternal HFD on adult offspring.

Methods

Female rats (N = 100, 90 days of age) were assigned to HFD (45% kcal from fat) or control diet (CD) for 14 days prior to mating and throughout pregnancy and lactation. Following mating, dams received a gel containing 0.05 ml of FO (human equivalent 2–3 ml) or a control gel on each day of pregnancy. This produced 4 groups, CD with control gel, CD with FO gel, HFD with control gel and HFD with FO gel. Plasma and tissue samples were collected at day 20 of pregnancy and postnatal day 2, 21, and 100. Adult offspring were assessed for insulin sensitivity, blood pressure, DXA scan, and 2D echocardiography.

Results

There was an interaction between maternal diet and FO supplementation on insulin sensitivity (p = 0.005) and cardiac function (p < 0.01). A maternal HFD resulted in impaired insulin sensitivity in the adult offspring (p = 0.005 males, p = 0.001 females). FO supplementation in the context of a maternal HFD prevented the reduction in insulin sensitivity in offspring (p = 0.05 males, p = 0.0001 females). However, in dams consuming CD, FO supplementation led to impaired insulin sensitivity (p = 0.02 males, p = 0.001 females), greater body weight and reduced cardiac ejection fraction.

Conclusion

The effects of a human-relevant dose of maternal FO on offspring outcomes were dependent on the maternal diet, so that FO was beneficial to the offspring if the mother consumed a HFD, but deleterious if the mother consumed a control diet. This study suggests that supplementation with FO should be targeted to women expected to have abnormalities of metabolism such as those with overweight and obesity.
Prognostic significance of postoperative loss of skeletal muscle mass in patients underwent coronary artery bypass grafting
Authors: Shen Zi-Le , Liu Zhang , Zhang Peng , Chen Wei-Zhe , Dong Wen-Xi , Chen Wen-Hao , Lin Feng , Zang Wang-Fu , Yan Xia-Lin , Yu Zhen
Published: September 2022

Background

Increasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS).

Methods

Patients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed.

Results

The study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749–0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss.

Conclusion

Postoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.
Effect of emulsification methods on the physicochemical properties of emulsion stabilized by calcium carbonate and sodium alginate
Authors: Yang Xiaotong , Sui Haomin , Liang Hongshan , Li Bin , Yan Xiangxing , Li Jing
Published: September 2022

Our lab’s studies have found that heavy calcium carbonate (CaCO3) with sodium alginate (SA) can synergistically stabilize Pickering emulsion. However, there were significant differences in the flow characteristics of the emulsions obtained by different preparation methods during storage. Herein, in this current work, Pickering emulsions were prepared by two-step emulsifying method (SA was added into the primary emulsion stabilized by CaCO3 for secondary shearing, M1) and one-step emulsifying method (oil phase was added to homogeneous dispersed CaCO3-SA solution for one-step shearing, M2), respectively. The particle size, microstructure, rheology and microrheological properties of these two kinds of emulsions and the interaction of CaCO3 with SA were analyzed. The results showed that the droplet size of M1 emulsion was 21.78–49.62 μm, and that of M2 emulsion was 6.50–11.87 μm. M1 emulsion had stronger viscoelasticity, and could transform into a gel state during storage. However, M2 emulsion remained in flow condition all the time which was related to the interaction between SA and CaCO3 in the aqueous phase.
Does the Mediterranean diet reduce the odds of diabetic nephropathy in women? A case–control study
Authors: Noori Sahar , Mirzababaei Atieh , Abaj Faezeh , Ghaffarian-Ensaf Rasool , Mirzaei Khadijeh
Published: September 2022

Background

In recent decades, the prevalence of chronic diseases such as diabetes is increasing. One of the major complications of diabetes is diabetic nephropathy (DN), so it is important to find a way that can delay or control the onset of DN. Therefore, in this study, we investigated the relationship between the Mediterranean diet (MED) and the odds of DN.

Methods

This case–control study was performed among 210 women (30–65 years) who were referred to the Kowsar Diabetes Clinic in Semnan, Iran. Biochemical variables and anthropometric measurements were assessed. The food frequency questionnaire (FFQ) was used to calculate dietary intakes. Data from dietary intakes based on the FFQ were used to evaluate the MED score. Logistic regression was used to examine the associations.

Results

Our results showed that in the crude model with higher adherence to the MED (OR: 0.272; 95% CI: 0.154, 0.481; P = 0.001), the odds of DN has reduced by 73%, and in model 1, after controlling for potential confounders, with higher adherence to the MED (OR: 0.239; 95% CI: 0.128, 0.447; P = 0.001), the odds of DN has reduced by 76% compared to low adherence. Also, in model 1, significant associations were observed between high consumption of grains (OR: 0.360; 95% CI: 0.191, 0.676; P = 0.001), legumes (OR: 0.156; 95% CI: 0.083, 0.292; P = 0.001), vegetables (OR: 0.273; 95% CI: 0.149, 0.501; P = 0.001), fruits (OR: 0.179; 95% CI: 0.093, 0.347; P = 0.001), fish (OR: 0.459; 95% CI: 0.254, 0.827; P = 0.01), and reduced odds of DN (P < 0.05).

Conclusion

We observed that with higher adherence to the MED, the odds of DN had reduced through mechanisms. However, additional studies are needed to confirm these findings.
The change in nutritional status is related to cardiovascular events in patients with pacemaker implantation: A 4-year follow-up study
Authors: Wang Kaijing , Lian Liyou , Chen Chengpu , Wang Meiling , Chen Chen , Hu Xiang
Published: September 2022

Background

The aim of our study was to evaluate changes in nutritional status as measured by the prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) scores, and their abilities to predict clinical prognosis in patients with pacemaker implantation (PMI).

Methods

A total of 595 patients who underwent permanent PMI from January 2011 to December 2020 were included. PNI and GNRI scores were separately calculated at the beginning day of PMI operation and at the end of 12-month follow-up, and their net changes (Δ) were calculated by PNI or GNRI scores at follow-up minus the corresponding scores on admission. The cohort patients were divided into low risk of malnutritional status (ΔPNI or ΔGNRI scores ≥ 0) and high risk of malnutritional status (ΔPNI or ΔGNRI scores < 0) groups. Primary outcome measure was a composite major adverse cardiovascular event (MCE), defined as heart failure hospitalization (HFH), myocardial infarction (MI), stroke, or death from any cause, presented as hazard ratios (HR) with 95% confidence intervals (CI) calculated by MCE in the crude or multivariate-adjusted Cox Proportional Hazards models. Receiver operating characteristic (ROC) curve analysis was used to compare the differential ability to predict incident MCEs betweenΔPNI andΔGNRI scores.

Results

In total, 16% of patients developed the MCE during the follow-up. The cumulative event rates determined by Kaplan–Meier analysis were significantly higher in the high risk of malnutritional patients compared to the low risk of malnutritional patients (P < 0.05). Adjusted multivariate analysis showed that decreased PNI scores (HR: 2.228, 95% CI: 1.482–3.350) and decreased GNRI scores (HR: 2.178, 95% CI: 1.439–3.295) were independently associated with favorable outcomes. ROC curve analysis revealed an area under curve (AUC) of 0.586 forΔPNI scores and AUC of 0.592 for ΔGNRI scores, but their predictive abilities were not statistically different.

Conclusion

Either positive change of PNI or GNRI scores were associated with reduced risk of MCEs in patients with PMI, and they have similar ability to predict clinical cardiometabolic risk. Additional enhancing nutritional status during follow-up may help to prevent unfavorable prognosis in clinical practices.
Semaphorin 3F induces colorectal cancer cell chemosensitivity by promoting P27 nuclear export
Authors: Tao Miaomiao , Ma Hongbo , Fu Xiaoyuan , Wang Cancan , Li Yanyan , Hu Xiaoqiao , Lv Renming , Zhou Gendou , Wang Jun , Liu Ruyan , Zhou Meiyu , Xu Guofa , Wang Zexin , Qin Xiurong , Long Yi , Huang Qunzhen , Chen Min , Zhou Qi
Published: September 2022

Colorectal adenocarcinoma (CRC) is the third most common malignancy worldwide. Metastatic CRC has a poor prognosis because of chemotherapy resistance. Our previous study demonstrated that semaphorin 3F (SEMA3F) signaling may contribute to reversing chemotherapy resistance in CRC cells by reducing E-cadherin and integrin αvβ3 expression levels. Another study showed that upregulation of p27 significantly increase the expression of E-cadherin and integrin. This study aimed to evaluate the effect of SEMA3F on P27 and whether it can reverse resistance in CRC cells. We compared the chemosensitivity of human colorectal cancer cell lines with different SEMA3F expression levels to 5-Fu through cell experiment and animal experiment. Then the interaction between SEMA3F and p27 and its possible mechanism were explored by Western Blot, immunofluorescence and immunocoprecipitation. We also compared the disease-free survival of 118 CRC patients with high or low expression of SEMA3F.The results showed that overexpresstion of SEMA3F enhanced the chemotherapy sensitivity and apoptosis of CRC cells in vitro and in vivo. Among 118 postoperative CRC specimens, the disease-free survival of patients with positive SEMA3F expression was significantly longer than that with negative SEMA3F expression after adjuvant treatment. Upregulation of SEMA3F in multicellular spheroid culture (MSC) could increase p27 phosphorylation at serine 10 (Ser10), subsequently promote the cytosolic translocation of P27. Overall, our results reveal a novel molecular mechanism: SEMA3F mediates the degradation of p27 and regulates its subcellular localization to enhance chemosensitivity to 5-Fu in CRC cells, rather than inhibits p27 expression.