bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential key variants in mandibular premolar hypodontia through whole-exome sequencing
Authors: Lee Shinyeop , Ahn Hyunsoo , Kim Hyeonhye , Lee Kwanghwan , Kim Sanguk , Lee Jae Hoon
Published: September 2023

Determining genotype–phenotype correlations in patients with hypodontia is important for understanding disease pathogenesis, although only a few studies have elucidated it. We aimed to identify genetic variants linked to non-syndromic bilateral mandibular second premolar hypodontia in a Korean population for the first time by specifying the phenotype of hypodontia. Twenty unrelated individuals with non-syndromic bilateral mandibular second premolar hypodontia were enrolled for whole-exome sequencing. Using a tooth agenesis gene set panel consisting of 112 genes based on literature, potential candidate variants were screened through variant filtering and prioritization. We identified 13 candidate variants in 12 genes, including a stop-gain variant (c.4750C>T) in LAMA3. Through the functional enrichment analysis of the prioritized genes, several terms related to tooth development were enriched in a protein–protein interaction network of candidate genes for mandibular premolar hypodontia. The hypodontia group also had approximately 2-fold as many mutated variants in all four genes related to these key terms, which are CDH1, ITGB4, LAMA3, LAMB3, as those in the 100 healthy control group individuals. The relationship between enriched terms and pathways and mandibular premolar hypodontia was also investigated. In addition, we identified some known oligodontia variants in patients with hypodontia, strengthening the possibility of synergistic effects in other genes. This genetic investigation may be a worthwhile preliminary attempt to reveal the pathogenesis of tooth agenesis and sets a background for future studies.
Combination of trio-based whole exome sequencing and optical genome mapping reveals a cryptic balanced translocation that causes unbalanced chromosomal rearrangements in a family with multiple anomalies
Authors: Xie Min , Xue Jiangyang , Zhang Yuxin , Zhou Ying , Yu Qi , Li Haibo , Li Qiong
Published: September 2023

Background: Balanced translocation (BT) carriers can produce imbalanced gametes and experience recurrent spontaneous abortions (RSAs) and even give birth to a child with complex chromosomal disorders. Here, we report a cryptic BT, t(5; 6) (p15.31; p25.1), in the proband’s grandmother, which caused unbalanced chromosomal rearrangements and various anomalies in the two subsequent generations. We also provide a thorough overview of the application of optical genome mapping (OGM) to identify chromosomal structural variants (SVs).

Methods: Trio-based whole exome sequencing (Trio-WES) was conducted to explore the genetic basis of the phenotype of the proband and her mother. High-resolution karyotype analysis and OGM detection were performed on the proband’s grandparents to trace the origin of the unbalanced rearrangements between chromosomes 5 and 6. A PubMed search was conducted with the following keywords: “OGM” and “SVs.” Then, relevant studies were collected and systematically reviewed.

Results: The proband and her mother presented with various anomalies, whereas the grandmother was healthy but had a history of four abnormal pregnancies. Trio-WES revealed a heterozygous duplication on the terminal region of chromosome 5p and a heterozygous deletion on the proximal end of chromosome 6p in the proband and her mother. High-resolution karyotype analysis revealed no aberrant karyotypes in either grandparent, whereas OGM detection revealed a cryptic BT, t(5; 6)(p15.31; p25.1), in the proband’s grandmother. An overwhelming majority of research publications have verified the clinical utility of OGM in detecting SVs.

Conclusion: The results of this study revealed that the unbalanced chromosomal rearrangements and many anomalies observed in multiple members of the family were attributable to the cryptic BT carried by the proband’s grandmother. This study supports that OGM has a unique advantage for detecting cryptic BTs, and can be used as a first-tier genetic test for the etiological diagnosis of infertility, RSAs, and other complex genetic disorders.
Adipose transcriptome in the scalp of androgenetic alopecia
Authors: Cruz Criselda Jean G. , Hong Yi-Kai , Aala Wilson Jr. F. , Tsai Ren-Yeu , Chung Pei-Lun , Tsai Yau-Sheng , Hsu Chao-Kai , Yang Chao-Chun
Published: September 2023

Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.
Effect of trans-nasal humidified rapid insufflation ventilatory exchange on reflux and microaspiration in patients undergoing laparoscopic cholecystectomy during induction of general anesthesia: a randomized controlled trial
Authors: Ding Yinyin , Huang Tianfeng , Ge Yali , Gao Ju , Zhang Yang
Published: September 2023

Background

Reflux aspiration is a rare but serious complication during induction of anesthesia. The primary aim of this study is to compare the incidence of reflux and microaspiration in patients undergoing laparoscopic cholecystectomy during induction of general anesthesia using either a facemask or trans-nasal humidified rapid insufflation ventilatory exchange.

Methods

We conducted a single-center, randomized, controlled trial. Thirty patients were allocated to either a facemask or a trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) group. Pre-oxygenation for 5 min with a facemask or THRIVE, positive pressure ventilation for 2 min or THRIVE for 2 min after anesthesia induction was followed. Before endotracheal intubation, the secretion above and below the glottis was collected to measure pepsin content and analyze blood gas. The ELISA assay for supra- and subglottic human pepsin content was used to detect the presence of reflux and microaspiration. The primary outcome was the incidence of reflux and microaspiration. Secondary outcomes were apnea time, PaO2 before tracheal intubation, and the end-expiratory carbon dioxide partial pressure.

Results

Patients in the THRIVE group had a significantly longer apnea time (379.55 ± 94.12 s) compared to patients in the facemask group (172.96 ± 58.87 s; p < 0.001). There were no differences observed in PaO2 between the groups. A significant difference in gastric insufflation, reflux, and microaspiration was observed between the groups. Gastric insufflation was 6.9% in the THRIVE group vs. 28.57% kPa in the facemask group (p = 0.041); reflux was 10.34% in the THRIVE group vs. 32.14% kPa in the facemask group (p = 0.044); and microaspiration was 0% in the THRIVE group vs. 17.86% kPa in the facemask group (p = 0.023).

Conclusion

The application of THRIVE during induction of general anesthesia reduced the incidence of reflux and microaspiration while ensuring oxygenation and prolonged apnea time in laparoscopic cholecystectomy patients. THRIVE may be an optimal way to administer oxygen during the induction of general anesthesia in laparoscopic cholecystectomy patients.

Clinical trial registration

Chinese Clinical Trial Registry, No: ChiCTR2100054086, https://www.chictr.org.cn/indexEN.html.
Effects of microbial agent application on the bacterial community in ginger rhizosphere soil under different planting years
Authors: Wang Qian , Song Juan , Zhang Jinlian , Qin Xiaojuan , Kang Yihao , Huang Shilv , Zhou Shengmao , Chen Tingsu
Published: September 2023

Ginger is one of the important spice crops in the world. Due to the prevalence of ginger wilt disease and the lack of effective prevention and control methods, the planting area, total production and value have declined sharply, which have become a key factor restricting ginger industry development in China. Understanding the influence of microbial agents on the rhizosphere microbiota of ginger will facilitate developing novel technologies for the prevention and control of ginger wilt disease. In the new planting and continuous cropping ginger fields, using large-root ginger and microbial agents, two inoculation levels (inoculation and no inoculation) were designed, and high-throughput sequencing technology was used to study the bacterial community structure in the rhizosphere soil at mature stage of ginger. The results showed that newly planted ginger showed a significant yield advantage over continuous cropping ginger, with a yield increase of 39% to 56%, and the lowest ginger wilt disease index. The community structure at the phylum level of soil bacteria in each treatment was very similar to that in the control, but the abundance of some taxonomic units changed significantly. The four dominant phyla of bacteria in mature ginger rhizosphere soil were Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteria, accounting for 72.91% to 89.09% of the total. The microbial agent treatment of continuous cropping had beneficial microorganisms such as Acidobacteria and Gemmatimonadetes with abundances increased by 12.2% and 17.1%, respectively, compared to the control. The microbial inoculant treatment of newly planted ginger increased the abundance of Acidobacteria and Gemmatimonadetes by 34.4% and 10.7%, respectively, compared to the control. The composition of bacterial communities were affected by changes in soil properties. Redundancy analysis showed that the hydrolysable nitrogen, available phosphorus, available potassium, and organic matter were significantly related to the composition of soil bacterial communities. Therefore, the microbial agents can not only promote the proliferation of beneficial microorganisms in the continuous cropping soil but also further reshape the soil bacterial community structure by changing the soil physicochemical properties such as effective phosphorus. These results provided a reference for related research on the impact of ginger continuous cropping on soil environment and soil management improvement in ginger fields.
Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome
Authors: Chhimwal Jyoti , Anand Prince , Mehta Priyanka , Swarnkar Mohit Kumar , Patial Vikram , Pandey Rajesh , Padwad Yogendra
Published: September 2023

The importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent times. However, the inevitable changes in gut microbiota during progression of the disease merits closer look. The present work intends to assess the time-dependent gut dysbiosis in MAFLD, its implications in disease progression and role of plant-derived prebiotics in its attenuation. Male C57BL/6J mice were given western diet (WD) for up to 16 weeks and phloretin was administered orally. The fecal samples of mice were collected every fourth week for 16 weeks. The animals were sacrificed at the end of the study and biochemical and histological analyses were performed. Further, 16S rRNA amplicon sequencing analysis was performed to investigate longitudinal modification of gut microbiome at different time points. Findings of our study corroborate that phloretin alleviated the metabolic changes and mitigated circulating inflammatory cytokines levels. Phloretin treatment resists WD induced changes in microbial diversity of mice and decreased endotoxin content. Prolonged exposure of WD changed dynamics of gut microbiota abundance and distribution. Increased abundance of pathogenic taxa like Desulfovibrionaceae, Peptostreptococcus, Clostridium, and Terrisporobacter was noted. Phloretin treatment not only reversed this dysbiosis but also modulated taxonomic signatures of beneficial microbes like Ruminococcus, Lactobacillus, and Alloprevotella. Therefore, the potential of phloretin to restore gut eubiosis could be utilized as an intervention strategy for the prevention of MAFLD and related metabolic disorders.
Salmonella enterica relies on carbon metabolism to adapt to agricultural environments
Authors: Han Min , Schierstaedt Jasper , Duan Yongming , Nietschke Monika , Jechalke Sven , Wolf Jacqueline , Hensel Michael , Neumann-Schaal Meina , Schikora Adam
Published: September 2023

Salmonella enterica, a foodborne and human pathogen, is a constant threat to human health. Agricultural environments, for example, soil and plants, can be ecological niches and vectors for Salmonella transmission. Salmonella persistence in such environments increases the risk for consumers. Therefore, it is necessary to investigate the mechanisms used by Salmonella to adapt to agricultural environments. We assessed the adaptation strategy of S. enterica serovar Typhimurium strain 14028s to agricultural-relevant situations by analyzing the abundance of intermediates in glycolysis and the tricarboxylic acid pathway in tested environments (diluvial sand soil suspension and leaf-based media from tomato and lettuce), as well as in bacterial cells grown in such conditions. By reanalyzing the transcriptome data of Salmonella grown in those environments and using an independent RT-qPCR approach for verification, several genes were identified as important for persistence in root or leaf tissues, including the pyruvate dehydrogenase subunit E1 encoding gene aceE. In vivo persistence assay in tomato leaves confirmed the crucial role of aceE. A mutant in another tomato leaf persistence-related gene, aceB, encoding malate synthase A, displayed opposite persistence features. By comparing the metabolites and gene expression of the wild-type strain and its aceB mutant, fumarate accumulation was discovered as a potential way to replenish the effects of the aceB mutation. Our research interprets the mechanism of S. enterica adaptation to agriculture by adapting its carbon metabolism to the carbon sources available in the environment. These insights may assist in the development of strategies aimed at diminishing Salmonella persistence in food production systems.
First application of a droplet digital PCR to detect Toxoplasma gondii in mussels
Authors: Mancusi Andrea , Proroga Yolande T. R. , Giordano Angela , Girardi Santa , D’Orilia Francescantonio , Pinto Renato , Sarnelli Paolo , Rinaldi Laura , Capuano Federico , Maurelli Maria Paola
Published: September 2023

Toxoplasmosis, caused by the protozoan Toxoplasma gondii, is one of the main food-, water- and soil-borne zoonotic disease worldwide. Over the past 20 years many papers were published on the transmission of T. gondii by marine animals, including mollusks, which can concentrate the oocysts and release them. Sporulated oocysts may remain viable and infective for 18 months in seawater. Therefore, raw or undercooked bivalve mollusks pose a risk to humans. This study aimed to apply and validate for the first time a very sensitive digital droplet polymerase chain reaction (ddPCR) protocol to detect and quantify T. gondii DNA in mussels. Four concentration levels: 8000 genomic copies (gc)/μL, 800 gc/μL, 80 gc/μL, 8 gc/μL of a T. gondii reference DNA were tested. DNA was extracted from 80 pools of mussels (Mytilus galloprovincialis). Forty pools were contaminated with T. gondii reference DNA and used as positive controls, while 40 pools were used as negative controls. DdPCR reaction was prepared using a protocol, previously developed by the authors, for detection of T. gondii in meat. Amplification was obtained up 8 gc/μL. All infected replicates resulted positive, as well as no droplets were detected in negative controls. The droplets produced in the reaction ranged from 8,828 to 14,075 (average 12,627 droplets). The sensitivity and specificity of ddPCR were 100% (95%CI = 94.3–99.9). In addition, 100 pools of mussels collected in the Gulf of Naples were used to validate the protocol. Of these 16% were positive (95% CI = 9.7–25.0) for T. gondii. Samples were also tested by real-time PCR and no positive samples were found. Data obtained from ddPCR showed good identification of negative and positive samples with higher specificity and efficiency than real-time PCR. This tool could be very useful for a rapid sensitive detection of low DNA concentrations of T. gondii in mussels, reducing the risk of toxoplasmosis in humans.
Emergence of the fourth mobile sulfonamide resistance gene sul4 in clinical Salmonella enterica
Authors: Peng Kai , Deng Jianping , Zou Nianli , Sun Xinran , Huang Weifeng , Li Ruichao , Yang Xiaorong
Published: September 2023

The fourth mobile sulfonamide resistance gene sul4 has been discovered in many metagenomic datasets. However, there is no reports of it in cultured bacteria. In this study, a sul4 positive clinical Salmonella enterica SC2020597 was obtained by conventional Salmonella isolation methods and characterized by species identification and antimicrobial susceptibility testing. Meanwhile, the genomic DNA was sequenced using both long-read and short-read methods. Following that, the complete genome was analyzed by bioinformatic methods. The sul4 gene in S. enterica SC2020597 differed from the sul4 identified in metagenomic data by one amino acid and could confer full resistance to sulfamethoxazole. Genetic location analysis showed that the sul4 in SC2020597 was carried by a complex chromosomally integrated hybrid plasmid. ISCR20-like was strongly associated with the mobilization of sul4 by core genetic context analysis. To the best of our knowledge, this is the first report of the emergence of sul4 in clinically cultured S. enterica. More important, the sul4 has the potential to spread to other bacteria with the help of mobile elements.
The influence of precipitation timing and amount on soil microbial community in a temperate desert ecosystem
Authors: Xiao Yao , Bao Fang , Xu Xiaotian , Yu Ke , Wu Bo , Gao Ying , Zhang Junzhong
Published: September 2023

Introduction

Global climate change may lead to changes in precipitation patterns. This may have a significant impact on the microbial communities present in the soil. However, the way these communities respond to seasonal variations in precipitation, particularly in the context of increased precipitation amounts, is not yet well understood.

Methods

To explore this issue, a five-year (2012–2016) field study was conducted at the northeast boundary of the Ulan Buh Desert, examining the effects of increased precipitation during different periods of the growing season on both bacterial and fungal communities. The study included five precipitation pattern treatments: a control group (C), as well as groups receiving 50 and 100% of the local mean annual precipitation amount (145 mm) during either the early growing season (E50 and E100) or the late growing season (L50 and L100). The taxonomic composition of the soil bacterial and fungal communities was analyzed using Illumina sequencing.

Results

After 5 years, the bacterial community composition had significantly changed in all treatment groups, with soil bacteria proving to be more sensitive to changes in precipitation timing than to increased precipitation amounts within the desert ecosystem. Specifically, the alpha diversity of bacterial communities in the late growing season plots (L50 and L100) decreased significantly, while no significant changes were observed in the early growing season plots (E50 and E100). In contrast, fungal community composition remained relatively stable in response to changes in precipitation patterns. Predictions of bacterial community function suggested that the potential functional taxa in the bacterial community associated with the cycling of carbon and nitrogen were significantly altered in the late growing season (L50 and L100).

Discussion

These findings emphasize the importance of precipitation timing in regulating microbial communities and ecosystem functions in arid regions experiencing increased precipitation amounts.
Trait anxiety modulates the detection sensitivity of negative affect in speech: an online pilot study
Authors: K Achyuthanand , Prasad Saurabh , Chakrabarty Mrinmoy
Published: September 2023

Acoustic perception of emotions in speech is relevant for humans to navigate the social environment optimally. While sensory perception is known to be influenced by ambient noise, and bodily internal states (e.g., emotional arousal and anxiety), their relationship to human auditory perception is relatively less understood. In a supervised, online pilot experiment sans the artificially controlled laboratory environment, we asked if the detection sensitivity of emotions conveyed by human speech-in-noise (acoustic signals) varies between individuals with relatively lower and higher levels of subclinical trait-anxiety, respectively. In a task, participants (n = 28) accurately discriminated the target emotion conveyed by the temporally unpredictable acoustic signals (signal to noise ratio = 10 dB), which were manipulated at four levels (Happy, Neutral, Fear, and Disgust). We calculated the empirical area under the curve (a measure of acoustic signal detection sensitivity) based on signal detection theory to answer our questions. A subset of individuals with High trait-anxiety relative to Low in the above sample showed significantly lower detection sensitivities to acoustic signals of negative emotions – Disgust and Fear and significantly lower detection sensitivities to acoustic signals when averaged across all emotions. The results from this pilot study with a small but statistically relevant sample size suggest that trait-anxiety levels influence the overall acoustic detection of speech-in-noise, especially those conveying threatening/negative affect. The findings are relevant for future research on acoustic perception anomalies underlying affective traits and disorders.
Septic encephalopathy in the elderly – biomarkers of potential clinical utility
Authors: Schütze Sandra , Drevets Douglas A. , Tauber Simone C. , Nau Roland
Published: September 2023

Next to acute sickness behavior, septic encephalopathy is the most frequent involvement of the brain during infection. It is characterized by a cross-talk of pro-inflammatory cells across the blood–brain barrier, by microglial activation and leukocyte migration, but not by the entry of infecting organisms into the brain tissue. Septic encephalopathy is very frequent in older persons because of their limited cognitive reserve. The predominant clinical manifestation is delirium, whereas focal neurological signs and symptoms are absent. Electroencephalography is a very sensitive method to detect functional abnormalities, but these abnormalities are not specific for septic encephalopathy and of limited prognostic value. Routine cerebral imaging by computer tomography usually fails to visualize the subtle abnormalities produced by septic involvement of the brain. Magnetic resonance imaging is by far more sensitive to detect vasogenic edema, diffuse axonal injury or small ischemic lesions. Routine laboratory parameters most suitable to monitor sepsis, but not specific for septic encephalopathy, are C-reactive protein and procalcitonin. The additional measurement of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-α increases the accuracy to predict delirium and an unfavorable outcome. The most promising laboratory parameters to quantify neuronal and axonal injury caused by septic encephalopathy are neurofilament light chains (NfL) and S100B protein. Neuron-specific enolase (NSE) plasma concentrations are strongly influenced by hemolysis. We propose to determine NSE only in non-hemolytic plasma or serum samples for the estimation of outcome in septic encephalopathy.
Sociodemographic and clinical characteristics and access to health care in patients with spinal muscular atrophy in Argentina
Authors: Vazquez Gabriel Adolfo , Nasif Salomé , Marciano Sebastián , Pagotto Vanina
Published: September 2023

The FAME registry gathers the majority of patients with SMA in Argentina. From it, the clinical, sociodemographic and access to treatment characteristics were analyzed in 322 patients (range 8 months-61 years) included from 2008 to 2021. Important data were obtained for the planning of medical care of these patients such as: similar distribution of patient care in public and private hospitals, time gap between onset of symptoms and diagnoses, low level of completion of SMN2 copy count, estimate of 16 new diagnoses per year between 2014 and 2018, and 68% of patient in specific pharmacological treatment.
Cervical muscle morphometry and composition demonstrate prognostic value in degenerative cervical myelopathy outcomes
Authors: Naghdi Neda , Elliott James M. , Weber Michael H. , Fehlings Michael G. , Fortin Maryse
Published: September 2023

Objectives

This study aimed to examine whether preoperative cervical muscle size, composition, and asymmetry from magnetic resonance imaging (MRI) can predict post-operative outcomes in patients with degenerative cervical myelopathy (DCM).

Methods

A total of 171 patients with DCM were included. Relative total cross-sectional area (RCSA), functional CSA (fat-free area, FCSA), ratio of FCSA/CSA (fatty infiltration) and asymmetry of the multifidus (MF) and semispinalis cervicis (SCer) together (MF + SCer), and cervical muscle as a group (MF, SCer, semispinalis capitis, and splenius capitis) were obtained from T2-weighted axial MR images at the mid-disk, at the level of maximum cord compression and the level below. Univariate and multivariate linear regression analyses were used to assess the relationship between baseline cervical muscle measurements of interest with the modified Japanese Orthopedic Association (mJOA), Nurick Classification, Neck Disability Index (NDI), and SF-36 health survey at 6-month and 12-month post-surgery.

Results

Lower RCSA of MF + SCer, less CSA MF + SCer asymmetry and greater FCSA/CSA for the cervical muscle group (e.g., less fatty infiltration), and younger age were significant predictors of higher mJOA scores (e.g., less disability) at 6-month and 12-month post-surgery (all p < 0.05). Greater CSA asymmetry in MF + SCer and lower FCSA/CSA (e.g., more fatty infiltration) for the cervical muscle group were significant predictors of higher Nurick scores (e.g., more disability) at 6-month and 12-month post-surgery (all p < 0.05). Lower FCSA MF + Scer asymmetry, lower FCSA/CSA asymmetry of the muscle group, and greater RCSA MF + SCer were significant predictors of higher NDI scores at 6-month and 12-month post-surgery. Finally, greater FCSA/CSA asymmetry of the MF + SCer, greater FCSA asymmetry of the muscle group, greater RCSA of the muscle group, and greater CSA asymmetry of MF + SCer were significant predictors of lower post-operative SF-36 scores at 6- and 12-month post-surgery.

Conclusion

Our result suggested that cervical paraspinal muscle morphology, specifically greater asymmetry, and fatty infiltration may be important predictors of functional recovery and post-surgical outcomes in patients with DCM.
Case report: MRI changes of the inner ear in an MD patient with suspected immune dysfunction
Authors: Chen Yurun , Zhao Pengfei , Ma Xin , Diao Tongxiang , Yu Lisheng
Published: September 2023

Objectives

The primary objective of this study was to present the progressive changes from labyrinthitis to endolymphatic hydrops (EH) demonstrated in the inner ear MRI of a patient with MD and suspected immune dysfunction.

Patient

This 31-year-old male was diagnosed with MD and suspected autoimmune diseases.

Interventions

Immunosuppressants and biological agents.

Main outcomes measures

Inner ear MRI images.

Results

Changes in the patient’s progress revealed that inner ear immune and inflammatory changes might induce EH, which may eventually turn into MD.

Conclusion

This case is the first documented case of MRI revealing progressive changes from inflammatory response to endolymphatic hydrops in the inner ear. It shows the correlation between MD and inflammation visually. It is of great significance to reveal the pathogenesis of MD to further assist in the guidance of treatment decision making.
Quantitative sleep electroencephalogram and cognitive performance in Parkinson’s disease with and without rapid eye movement sleep behavior disorder
Authors: Memon Adeel A. , Catiul Corina , Irwin Zachary , Pilkington Jennifer , Memon Raima A. , Joop Allen , Wood Kimberly H. , Cutter Gary , Miocinovic Svjetlana , Amara Amy W.
Published: September 2023

Introduction

Parkinson’s disease (PD) patients with REM sleep behavior disorder (RBD) are at greater risk for cognitive decline and RBD has been associated with alterations in sleep-related EEG oscillations. This study evaluates differences in sleep quantitative EEG (qEEG) and cognition in PD participants with (PD-RBD) and without RBD (PD-no-RBD).

Methods

In this cross-sectional study, polysomnography (PSG)-derived qEEG and a comprehensive level II neuropsychological assessment were compared between PD-RBD (n = 21) and PD-no-RBD (n = 31). Following artifact rejection, qEEG analysis was performed in the frontal and central leads. Measures included Scalp-slow wave (SW) density, spindle density, morphological properties of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in NREM and REM. The neurocognitive battery had at least two tests per domain, covering five cognitive domains as recommended by the Movement Disorders Society Task Force for PD-MCI diagnosis. Differences in qEEG features and cognitive performance were compared between the two groups. Stepwise linear regression was performed to evaluate predictors of cognitive performance. Multiple comparisons were corrected using the Benjamini-Hochberg method.

Results

Spindle density and SW-spindle co-occurrence percent were lower in participants with PD-RBD compared to PD-no-RBD. The PD-RBD group also demonstrated higher theta spectral power during REM. Sleep spindles and years of education, but not RBD, were predictors of cognitive performance.

Conclusion

PD participants with RBD have alterations in sleep-related qEEG compared to PD participants without RBD. Although PD-RBD participants had worse cognitive performance compared to PD-no-RBD, regression models suggest that lower sleep spindle density, rather than presence of RBD, predicts worse comprehensive cognitive score. Future studies should include longitudinal evaluation to determine whether sleep-related qEEG alterations are associated with more rapid cognitive decline in PD-RBD.
Pay attention: you can fall! The Mini-BESTest scale and the turning duration of the TUG test provide valid balance measures in neurological patients: a prospective study with falls as the balance criterion
Authors: Caronni Antonio , Picardi Michela , Scarano Stefano , Malloggi Chiara , Tropea Peppino , Gilardone Giulia , Aristidou Evdoxia , Pintavalle Giuseppe , Redaelli Valentina , Antoniotti Paola , Corbo Massimo
Published: September 2023

Background

Balance, i.e., the ability not to fall, is often poor in neurological patients and this impairment increases their risk of falling. The Mini-Balance Evaluation System Test (Mini-BESTest), a rating scale, the Timed Up and Go (TUG) test, and gait measures are commonly used to quantify balance. This study assesses the criterion validity of these measures as balance measures.

Methods

The probability of being a faller within nine months was used as the balance criterion. The Mini-BESTest, TUG (instrumented with inertial sensors), and walking test were administered before and after inpatient rehabilitation. Multiple and LASSO logistic regressions were used for the analysis. The diagnostic accuracy of the model was assessed with the area under the curve (AUC) of the receiver operating characteristic curve. Mobility measure validity was compared with the Akaike Information Criterion (AIC).

Results

Two hundred and fourteen neurological patients (stroke, peripheral neuropathy, or parkinsonism) were recruited. In total, 82 patients fell at least once in the nine-month follow-up. The Mini-BESTest (AUC = 0.69; 95%CI: 0.62–0.76), the duration of the TUG turning phase (AUC = 0.69; 0.62–0.76), and other TUG measures were significant faller predictors in regression models. However, only the turning duration (AIC = 274.0) and Mini-BESTest (AIC = 276.1) substantially improved the prediction of a baseline model, which only included fall risk factors from the medical history (AIC = 281.7). The LASSO procedure selected gender, disease chronicity, urinary incontinence, the Mini-BESTest, and turning duration as optimal faller predictors.

Conclusion

The TUG turning duration and the Mini-BESTest predict the chance of being a faller. Their criterion validity as balance measures in neurological patients is substantial.
What is the current status of primary care in the diagnosis and treatment of patients with vertigo and dizziness in Switzerland? A national survey
Authors: Zwergal Andreas , Mantokoudis Georgios , Heg Dierik , Kerkeni Hassen , Diener Suzie , Kalla Roger , Korda Athanasia , Candreia Claudia , Welge-Lüssen Antje , Tarnutzer Alexander A.
Published: September 2023

Background

Vertigo and dizziness are among the most frequent presenting symptoms in the primary care physicians' (PCPs) office. With patients facing difficulties in describing their complaints and clinical findings often being subtle and transient, the diagnostic workup of the dizzy patient remains challenging. We aimed to gain more insights into the current state of practice in order to identify the limitations and needs of the PCPs and define strategies to continuously improve their knowledge in the care of the dizzy patient.

Materials and methods

Board-certified PCPs working in Switzerland were invited to participate in an online survey. A descriptive statistical analysis was performed, and prospectively defined hypotheses were assessed using regression analyses.

Results

A vast majority of participating PCPs (n = 152) were familiar with the key questions when taking the dizzy patient's history and with performing provocation/repositioning maneuvers when posterior-canal benign paroxysmal positional vertigo (BPPV) was suspected (91%). In contrast, strong agreement that performing the alternating cover test (21%), looking for a spontaneous nystagmus with fixation removed (42%), and performing the head-impulse test (47%) were important was considerably lower, and only 19% of PCPs were familiar with lateral-canal BPPV treatment. No specific diagnosis could be reached in substantial fractions of patients with acute (35% [25; 50%], median [inter-quartile range]) and episodic/chronic (50% [40; 65.8%]) dizziness/vertigo. Referral to specialists was higher in patients with episodic/chronic dizziness than in acutely dizzy patients (50% [20.3; 75] vs. 30% [20; 50]), with younger PCPs (aged 30–40 years) demonstrating significantly increased odds of referral to specialists (odds ratio = 2.20 [1.01–4.81], p = 0.048).

Conclusion

The assessment of dizzy patients takes longer than that of average patients in most primary care practices. Many dizzy patients remain undiagnosed even after a thorough examination, highlighting the challenges faced by PCPs and potentially leading to frequent referrals to specialists. To address this, it is crucial to promote state-of-the-art neuro-otological examination and treatment techniques that are currently neglected by most PCPs, such as “HINTS” and lateral-canal BPPV treatment. This can help reduce referral rates allowing more targeted treatment and referrals.
The different contributions of the eight prefrontal cortex subregions to reactive responses after unpredictable slip perturbations and vibrotactile cueing
Authors: Lee Beom-Chan , Choi Jongkwan , Ahn Jooeun , Martin Bernard J.
Published: September 2023

Introduction

Recent advancements in functional near-infrared spectroscopy technology have offered a portable, wireless, wearable solution to measure the activity of the prefrontal cortex (PFC) in the human neuroscience field. This study is the first to validate the different contributions made by the PFC's eight subregions in healthy young adults to the reactive recovery responses following treadmill-induced unpredictable slip perturbations and vibrotactile cueing (i.e., precues).

Methods

Our fall-inducing technology platform equipped with a split-belt treadmill provided unpredictable slip perturbations to healthy young adults while walking at their self-selected walking speed. A portable, wireless, wearable, and multi-channel (48 channels) functional near-infrared spectroscopy system evaluated the activity of PFC's eight subregions [i.e., right and left dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontopolar prefrontal cortex (FPFC), and orbitofrontal cortex (OFC)] as quantified by oxyhemoglobin and deoxyhemoglobin concentrations. A motion capture system and two force plates beneath the split-belt treadmill were used to quantify participants' kinematic and kinetic behavior. All participants completed 6 trials: 2 consecutive trials without vibrotactile cueing and with a slip perturbation (control trials); 3 trials with vibrotactile cueing [2 trials with the slip perturbation (cueing trial) and 1 trial without the slip perturbation (catch trial)], and 1 trial without vibrotactile cueing and with a slip perturbation (post-control trial). The PFC subregions' activity and kinematic behavior were assessed during the three periods (i.e., standing, walking, and recovery periods).

Results

Compared to the walkers' standing and walking periods, recovery periods showed significantly higher and lower levels of oxyhemoglobin and deoxyhemoglobin concentrations, respectively, in the right and left DLPFC, VLPFC, and FPFC, regardless of the presence of vibrotactile cueing. However, there was no significant difference in the right and left OFC between the three periods. Kinematic analyses confirmed that vibrotactile cueing significantly improved reactive recovery responses without requiring more involvement by the PFC subregions, which suggests that the sum of attentional resources is similar in cued and non-cued motor responses.

Discussion

The results could inform the design of wearable technologies that alert their users to the risks of falling and assist with the development of new gait perturbation paradigms that prompt reactive responses.
Authentication using c-VEP evoked in a mild-burdened cognitive task
Authors: Huang Zhihua , Liao Zequan , Ou Guojie , Chen Lijun , Zhang Ying
Published: September 2023

In recent years, more and more researchers are devoting themselves to the studies about authentication based on biomarkers. Among a wide variety of biomarkers, code-modulated visual evoked potential (c-VEP) has attracted increasing attention due to its significant role in the field of brain-computer interface. In this study, we designed a mild-burdened cognitive task (MBCT), which can check whether participants focus their attention on the visual stimuli that evoke c-VEP. Furthermore, we investigated the authentication based on the c-VEP evoked in the cognitive task by introducing a deep learning method. Seventeen participants were recruited to take part in the MBCT experiments including two sessions, which were carried out on two different days. The c-VEP signals from the first session were extracted to train the authentication deep models. The c-VEP data of the second session were used to verify the models. It achieved a desirable performance, with the average accuracy and F1 score, respectively, of 0.92 and 0.89. These results show that c-VEP carries individual discriminative characteristics and it is feasible to develop a practical authentication system based on c-VEP.
Testing for pharmacogenomic predictors of ppRNFL thinning in individuals exposed to vigabatrin
Authors: Boothman Isabelle , Clayton Lisa M. , McCormack Mark , Driscoll Alexandra McKibben , Stevelink Remi , Moloney Patrick , Krause Roland , Kunz Wolfram S. , Diehl Sarah , O’Brien Terence J. , Sills Graeme J. , de Haan Gerrit-Jan , Zara Federico , Koeleman Bobby P. , Depondt Chantal , Marson Anthony G. , Stefansson Hreinn , Stefansson Kari , Craig John , Johnson Michael R. , Striano Pasquale , Lerche Holger , Furney Simon J. , Delanty Norman ,   Consortium EpiPGX, Sisodiya Sanjay M. , Cavalleri Gianpiero L.
Published: September 2023

Background

The anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug.

Methods

Optical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals (n = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the following OCT measurements: (1) average ppRNFL, (2) inferior quadrant, (3) nasal quadrant, (4) superior quadrant, (5) temporal quadrant, (6) inferior nasal sector, (7) nasal inferior sector, (8) superior nasal sector, and (9) nasal superior sector. Using the summary statistics from the GWAS analyses we conducted gene-based testing using VEGAS2. We conducted nine different PRS analyses using the OCT measurements. To determine if VGB-exposed individuals were predisposed to having a thinner RNFL, we calculated their polygenic burden for retinal thickness. PRS alleles for retinal thickness were calculated using published summary statistics from a large-scale GWAS of inner retinal morphology using the OCT images of UK Biobank participants.

Results

The GWAS analyses did not identify a significant association after correction for multiple testing. Similarly, the gene-based and PRS analyses did not reveal a significant association that survived multiple testing.

Conclusion

We set out to identify common genetic predictors for VGB induced ppRNFL thinning. Results suggest that large-effect common genetic predictors are unlikely to exist for ppRNFL thinning (as a marker of VAVFL). Sample size was a limitation of this study. However, further recruitment is a challenge as VGB is rarely used today because of this adverse reaction. Rare variants may be predictors of this adverse drug reaction and were not studied here.
Genetic deletion of α7 nAChRs reduces hippocampal granule and pyramidal cell number in both sexes but impairs pattern separation in males only
Authors: Letsinger Ayland C. , Nacer Samir A. , Stevanovic Korey D. , Larson Gary J. , DeFilipp Jemma S. , Cushman Jesse D. , Yakel Jerrel L.
Published: September 2023

Introduction

Neurogenesis within the dentate gyrus is thought to play an important role in cognitive processes such as reversal learning and pattern separation. The α7 nicotinic acetylcholine receptor (α7 nAChR) is expressed early in newly formed granule cells of the dentate gyrus, though its role in neurogenesis and related cognitive function is not fully understood.

Methods

To better characterize relevant function of α7 nAChRs, we performed unbiased stereology to quantify hippocampal granule cells, pyramidal cells, and total volume and used a touchscreen operant spatial discrimination/reversal task to test pattern separation in a global α7 nAChR knockout mouse line.

Results

The knockout resulted in an ≈22% reduction in granule cells and a ≈ 20% reduction in pyramidal cells in both sexes, with no change in total hippocampal volume. However, the knockout impaired performance in the touchscreen task for males only. The sex-dependent difference in behavioral, but not stereological, results suggest a divergence in the structure–function relationship in males versus females. Detailed analyses revealed males were more biased by the initial reversal contingency relative to females indicating a potential source of the sex-specific interaction with the loss of α7 nAChRs.

Discussion

These findings argue that the α7 nAChR plays a critical role in hippocampal development, not just granule cell neurogenesis, and plays a sex-dependent role in cognitive function.
Examining the current health of Gulf War veterans with the veterans affairs frailty index
Authors: Chao Linda L.
Published: September 2023

Introduction

Gulf War Illness (GWI) is a chronic, multisymptom (e.g., fatigue, muscle/joint pain, memory and concentration difficulties) condition estimated to affect 25–32% of Gulf War (GW) veterans. Longitudinal studies suggest that few veterans with GWI have recovered over time and that deployed GW veterans may be at increased risks for age-related conditions.

Methods

We performed a retrospective cohort study to examine the current health status of 703 GW veterans who participated in research studies at the San Francisco VA Health Care System (SFVAHCS) between 2002 and 2018. We used the Veterans Affairs Frailty Index (VA-FI) as a proxy measure of current health and compared the VA-FIs of GW veterans to a group of randomly selected age- and sex-matched, non-GW veterans. We also examined GW veterans’ VA-FIs as a function of different GWI case definitions and in relationship to deployment-related experiences and exposures.

Results

Compared to matched, non-GW veterans, GW veterans had lower VA-FIs (0.10 ± 0.10 vs. 0.12 ± 0.11, p < 0.01). However, the subset of GW veterans who met criteria for severe Chronic Multisymptom Illness (CMI) at the time of the SFVAHCS studies had the highest VA-FI (0.13 ± 0.10, p < 0.001). GW veterans who had Kansas GWI exclusionary conditions had higher VA-FI (0.12 ± 0.12, p < 0.05) than veterans who were Kansas GWI cases (0.08 ± 0.08) and controls (i.e., veterans with little or no symptoms, 0.04 ± 0.06) at the time of the SFVAHCS research studies. The VA-FI was positively correlated with several GW deployment-related exposures, including the frequency of wearing flea collars.

Discussion

Although GW veterans, as a group, were less frail than non-GW veterans, the subset of GW veterans who met criteria for severe CDC CMI and/or who had Kansas GWI exclusionary conditions at the time of the SFVAHCS research studies were frailest at index date. This suggests that many ongoing studies of GWI that use the Kansas GWI criteria may not be capturing the group of GW veterans who are most at risk for adverse chronic health outcomes.