ABSTRACT
A taxonomic study of deep-sea polychaetes collected at a depth of 2,805 m off the northern coast of California revealed a scaleworm of the family Sigalionidae with an attached parasitic copepod. The copepod represents an undescribed genus of the family Herpyllobiidae, comprising mesoparasitic copepods chiefly recorded from polychaetes of the family Polynoidae. Blakerius gen. nov. diverges from the other herpyllobiid genera by its possession of 1) a chalice-shaped ectosoma with several protuberances along the posterior margin and a long cylindrical shaft with a hyaline coating and integumental sculpturing, a short stalk with a small, anteriorly placed sclerotized ring, 2) a relatively large, discoid-shaped endosoma with digitiform process, and 3) attached male copepodids with 3-segmented antennules, containing limbless sac-like males. The new genus is compared with other herpyllobiids. This discovery increases the number of known herpyllobiid genera to six and is the first record of a herpyllobiid parasitizing a sigalionid polychaete.urn: lsid: zoobank.org:pub:5E31FEED-D3EB-460E-AEA4-02A9D3A778D6.
Subject(s)
Copepoda , Polychaeta , Species Specificity , Animals , Copepoda/classification , Copepoda/anatomy & histology , Polychaeta/parasitology , Male , California , FemaleABSTRACT
BACKGROUND: The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale to assess cerebellar ataxia but faces some criticisms about the relevancy of all its items. OBJECTIVES: To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts. METHODS: We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios. RESULTS: Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations. CONCLUSION: SARA and its item's progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.
Subject(s)
Disease Progression , Severity of Illness Index , Spinocerebellar Ataxias , Humans , Spinocerebellar Ataxias/physiopathology , Middle Aged , Male , Female , Adult , Cohort Studies , Longitudinal Studies , AgedABSTRACT
BACKGROUND: Progressive loss of standing balance is a feature of Friedreich's ataxia (FRDA). OBJECTIVES: This study aimed to identify standing balance conditions and digital postural sway measures that best discriminate between FRDA and healthy controls (HC). We assessed test-retest reliability and correlations between sway measures and clinical scores. METHODS: Twenty-eight subjects with FRDA and 20 HC completed six standing conditions: feet apart, feet together, and feet tandem, both with eyes opened (EO) and eyes closed. Sway was measured using a wearable sensor on the lumbar spine for 30 seconds. Test completion rate, test-retest reliability with intraclass correlation coefficients, and areas under the receiver operating characteristic curves (AUCs) for each measure were compared to identify distinguishable FRDA sway characteristics from HC. Pearson correlations were used to evaluate the relationships between discriminative measures and clinical scores. RESULTS: Three of the six standing conditions had completion rates over 70%. Of these three conditions, natural stance and feet together with EO showed the greatest completion rates. All six of the sway measures' mean values were significantly different between FRDA and HC. Four of these six measures discriminated between groups with >0.9 AUC in all three conditions. The Friedreich Ataxia Rating Scale Upright Stability and Total scores correlated with sway measures with P-values <0.05 and r-values (0.63-0.86) and (0.65-0.81), respectively. CONCLUSION: Digital postural sway measures using wearable sensors are discriminative and reliable for assessing standing balance in individuals with FRDA. Natural stance and feet together stance with EO conditions suggest use in clinical trials for FRDA. © 2024 International Parkinson and Movement Disorder Society.
Subject(s)
Friedreich Ataxia , Postural Balance , Humans , Friedreich Ataxia/physiopathology , Friedreich Ataxia/diagnosis , Postural Balance/physiology , Male , Female , Adult , Middle Aged , Reproducibility of Results , Young Adult , Standing PositionABSTRACT
BACKGROUND: Maintaining balance is crucial for independence and quality of life. Loss of balance is a hallmark of spinocerebellar ataxia (SCA). OBJECTIVE: The aim of this study was to identify which standing balance conditions and digital measures of body sway were most discriminative, reliable, and valid for quantifying balance in SCA. METHODS: Fifty-three people with SCA (13 SCA1, 13 SCA2, 14 SCA3, and 13 SCA6) and Scale for Assessment and Rating of Ataxia (SARA) scores 9.28 ± 4.36 and 31 healthy controls were recruited. Subjects stood in six test conditions (natural stance, feet together and tandem, each with eyes open [EO] and eyes closed [EC]) with an inertial sensor on their lower back for 30 seconds (×2). We compared test completion rate, test-retest reliability, and areas under the receiver operating characteristic curve (AUC) for seven digital sway measures. Pearson's correlations related sway with the SARA and the Patient-Reported Outcome Measure of Ataxia (PROM ataxia). RESULTS: Most individuals with SCA (85%-100%) could stand for 30 seconds with natural stance EO or EC, and with feet together EO. The most discriminative digital sway measures (path length, range, area, and root mean square) from the two most reliable and discriminative conditions (natural stance EC and feet together EO) showed intraclass correlation coefficients from 0.70 to 0.91 and AUCs from 0.83 to 0.93. Correlations of sway with SARA were significant (maximum r = 0.65 and 0.73). Correlations with PROM ataxia were mild to moderate (maximum r = 0.56 and 0.34). CONCLUSION: Inertial sensor measures of extent of postural sway in conditions of natural stance EC and feet together stance EO were discriminative, reliable, and valid for monitoring SCA. © 2024 International Parkinson and Movement Disorder Society.
Subject(s)
Postural Balance , Spinocerebellar Ataxias , Humans , Postural Balance/physiology , Male , Female , Middle Aged , Spinocerebellar Ataxias/physiopathology , Spinocerebellar Ataxias/diagnosis , Adult , Aged , Reproducibility of Results , Severity of Illness IndexABSTRACT
BACKGROUND: Fatigue is a prevalent and debilitating symptom in neurological disorders, including spinocerebellar ataxias (SCAs). However, the risk factors of fatigue in the SCAs as well as its impact have not been well investigated. OBJECTIVES: To study the prevalence of fatigue in SCAs, the factors contributing to fatigue, and the influence of fatigue on quality of life. METHODS: Fatigue was assessed in 418 participants with SCA1, SCA2, SCA3, and SCA6 from the Clinical Research Consortium for the Study of Cerebellar Ataxia using the Fatigue Severity Scale. We conducted multi-variable linear regression models to examine the factors contributing to fatigue as well as the association between fatigue and quality of life. RESULTS: Fatigue was most prevalent in SCA3 (52.6%), followed by SCA1 (36.7%), SCA6 (35.7%), and SCA2 (35.6%). SCA cases with fatigue had more severe ataxia and worse depressive symptoms. In SCA3, those with fatigue had a longer disease duration and longer pathological CAG repeat numbers. In multi-variable models, depressive symptoms, but not ataxia severity, were associated with more severe fatigue. Fatigue, independent of ataxia and depression, contributed to worse quality of life in SCA3 and SCA6 at baseline, and fatigue continued affecting quality of life throughout the disease course in all types of SCA. CONCLUSIONS: Fatigue is a common symptom in SCAs and is closely related to depression. Fatigue significantly impacts patients' quality of life. Therefore, screening for fatigue should be considered a part of standard clinical care for SCAs.
Subject(s)
Fatigue , Quality of Life , Spinocerebellar Ataxias , Humans , Quality of Life/psychology , Spinocerebellar Ataxias/psychology , Spinocerebellar Ataxias/complications , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/epidemiology , Male , Fatigue/psychology , Fatigue/epidemiology , Female , Middle Aged , Adult , Aged , Severity of Illness Index , Prevalence , Depression/epidemiology , Depression/psychologyABSTRACT
SCA6 patients with the same size CAG repeat allele can vary significantly in age at onset (AAO) and clinical progression. The specific external factors affecting SCA6 have yet to be investigated. We assessed the effect of early life events on AAO, severity, and progression in SCA6 patients using a social determinant of health approach. We performed a survey of biological and social factors in SCA6 patients enrolled in the SCA6 Network at the University of Chicago. AAO of ataxia symptoms and patient-reported outcome measure (PROM) of ataxia were used as primary outcome measures. Least absolute shrinkage and selection operation (LASSO) regressions were used to identify which early life factors are predictive of SCA6 AAO, severity, and progression. Multiple linear regression models were then used to assess the degree to which these determinants influence SCA6 health outcomes. A total of 105 participants with genetically confirmed SCA6 completed the assessments. SCA6 participants with maternal difficulty during pregnancy, active participation in school sports, and/or longer CAG repeats were determined to have earlier AAO. We found a 13.44-year earlier AAO for those with maternal difficulty in pregnancy than those without (p = 0.008) and a 12.31-year earlier AAO for those active in school sports than those who were not (p < 0.001). Higher education attainment was associated with decreased SCA6 severity and slower progression. Early life biological and social factors can have a strong influence on the SCA6 disease course, indicating that non-genetic factors can contribute significantly to SCA6 health outcomes.
Subject(s)
Age of Onset , Disease Progression , Spinocerebellar Ataxias , Humans , Female , Male , Adult , Middle Aged , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/epidemiology , Severity of Illness Index , Social Determinants of Health , Young AdultABSTRACT
The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.
Subject(s)
Spinocerebellar Ataxias , Humans , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/psychology , Spinocerebellar Ataxias/diagnosis , Spinocerebellar Ataxias/physiopathology , Male , Female , Middle Aged , Adult , Aged , Executive Function/physiology , Neuropsychological Tests , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Cohort StudiesABSTRACT
Spinocerebellar ataxias (SCAs) are familial neurodegenerative diseases involving the cerebellum and spinocerebellar tracts. While there is variable involvement of corticospinal tracts (CST), dorsal root ganglia, and motor neurons in SCA3, SCA6 is characterized by a pure, late-onset ataxia. Abnormal intermuscular coherence in the beta-gamma frequency range (IMCßγ) implies a lack of integrity of CST or the afferent input from the acting muscles. We test the hypothesis that IMCßγ has the potential to be a biomarker of disease activity in SCA3 but not SCA6. Intermuscular coherence between biceps brachii and brachioradialis muscles was measured from surface EMG waveforms in SCA3 (N = 16) and SCA6 (N = 20) patients and in neurotypical subjects (N = 23). IMC peak frequencies were present in the ß range in SCA patients and in the γ range in neurotypical subjects. The difference between IMC amplitudes in the γ and ß ranges was significant when comparing neurotypical control subjects to SCA3 (p < 0.01) and SCA6 (p = 0.01) patients. IMCßγ amplitude was smaller in SCA3 patients compared to neurotypical subjects (p < 0.05), but not different between SCA3 and SCA6 patients or between SCA6 and neurotypical subjects. IMC metrics can differentiate SCA patients from normal controls.
Subject(s)
Machado-Joseph Disease , Spinocerebellar Ataxias , Humans , CerebellumABSTRACT
The current study aimed to identify profiles of youth presenting with a unique combination of environmental characteristics and understand the differential relationship between profile membership, anxiety, and depression symptoms. Data were drawn from 158 Latino youth between the ages of 11 and 13. Youth provided information on community violence exposure, acculturative stress, familial and peer support, and parental supervision. Main analyses included Latent Profile Analysis and Multivariate Analysis of Variance. Support for a four-profile model was found. Profiles are distinguished by mean levels of community violence exposure, acculturative stress, familial and peer support, and parental supervision. Profile membership was significantly associated with anxiety and depression, separately. Those belonging to the profile with the highest levels of environmental risk reported the highest levels of anxiety and depression. Findings contribute to a personalized understanding of risk and protective experiences in the environment for Latino youth.
Subject(s)
Anxiety , Depression , Exposure to Violence , Social Environment , Adolescent , Child , Humans , Hispanic or LatinoABSTRACT
With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.
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Cyfip1, the gene encoding cytoplasmic FMR1 interacting protein 1, has been of interest as an autism candidate gene for years. A potential role in autism spectrum disorder (ASD) is suggested by its location on human chromosome 15q11-13, an instable region that gives rise to a variety of copy number variations associated with syndromic autism. In addition, the CYFIP1 protein acts as a binding partner to Fragile X Messenger Ribonucleoprotein (FMRP) in the regulation of translation initiation. Mutation of FMR1, the gene encoding FMRP, causes Fragile X syndrome, another form of syndromic autism. Here, in mice overexpressing CYFIP1, we study response properties of cerebellar Purkinje cells to activity of the climbing fiber input that originates from the inferior olive and provides an instructive signal in sensorimotor input analysis and plasticity. We find that CYFIP1 overexpression results in enhanced localization of the synaptic organizer neurexin 1 (NRXN1) at climbing fiber synaptic input sites on Purkinje cell primary dendrites and concomitant enhanced climbing fiber synaptic transmission (CF-EPSCs) measured using whole-cell patch-clamp recordings from Purkinje cells in vitro. Moreover, using two-photon measurements of GCaMP6f-encoded climbing fiber signals in Purkinje cells of intact mice, we observe enhanced responses to air puff stimuli applied to the whisker field. These findings resemble our previous phenotypic observations in a mouse model for the human 15q11-13 duplication, which does not extend to the Cyfip1 locus. Thus, our study demonstrates that CYFIP1 overexpression shares a limited set of olivo-cerebellar phenotypes as those resulting from an increased number of copies of non-overlapping genes located on chromosome 15q11-13.
ABSTRACT
BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke. CASE PRESENTATION: A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic "hot spot" of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools. CONCLUSIONS: This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.
Subject(s)
Bell Palsy , Ischemic Stroke , Ophthalmoplegia, Chronic Progressive External , Stroke , Male , Humans , Aged , Ophthalmoplegia, Chronic Progressive External/complications , Ophthalmoplegia, Chronic Progressive External/genetics , Stroke/complications , Stroke/diagnostic imaging , PatientsABSTRACT
Objectives: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a common cause of late-onset ataxia that often presents with chronic cough. This study is the first to characterize the CANVAS cough both objectively and subjectively. Methods: A cross-sectional study of 13 patients was conducted. Medical records and available esophagram, modified barium swallow study, esophageal manometry, and video laryngostroboscopy data were reviewed. Leicester cough questionnaire (LCQ) and Eating Assessment Tool-10 were administered to evaluate quality of life (QoL) impairments and dysphagia symptoms, respectively. CANVAS history questionnaire was developed to characterize the clinical course. Results: 92% of patients endorsed chronic cough that preceded gait instability by a median of 16 years. Cough was dry (67%), disturbed sleep (75%), triggered by various factors, including talking, eating, and dry/spicy foods, did not respond to standard reflux therapy, and inconsistently responded to neuromodulators and superior laryngeal nerve injections. Despite perceived cough severity worsening or remaining constant in most patients, no correlation was found between cough duration and total LCQ scores. Patients reported significantly more negative social QoL impacts compared to physical QoL impacts. Ataxia duration and years of cough before ataxia symptoms were directly and inversely correlated with total LCQ scores, respectively. Imaging data revealed esophageal dysmotility (71%), vestibular penetration (57%), vestibular aspiration (14%), supraglottic compression (63%), vocal fold lesions/atrophy (50%), and arytenoid erythema (38%). Conclusion: Chronic cough is a hallmark presenting symptom in CANVAS with predominantly psychosocial QoL effects and unrecognized laryngeal alterations. In cases of idiopathic, refractory chronic cough, genetic testing for CANVAS should be considered, especially in association with sensory, cerebellar, and/or vestibular involvement. Level of evidence: VI.
ABSTRACT
Objective : Spinocerebellar ataxias (SCAs) are familial neurodegenerative diseases involving the cerebellum and spinocerebellar tracts. While there is variable involvement of corticospinal tracts (CST), dorsal root ganglia, and motor neurons in SCA3, SCA6 is characterized by a pure, late-onset ataxia. Abnormal intermuscular coherence in the beta-gamma frequency range (IMCbg) implies lack of integrity of CST or the afferent input from the acting muscles. We test the hypothesis that IMCbg has the potential to be a biomarker of disease activity in SCA3 but not SCA6. Methods: Intermuscular coherence between biceps and brachioradialis muscles was measured from surface EMG waveforms in SCA3 (N=16) and SCA6 (N=20) patients, and in neurotypical subjects (N=23). Results: IMC peak frequencies were present in the b range in SCA patients and in the g range in neurotypical subjects. The difference between IMC amplitudes in the g and b ranges was significant when comparing neurotypical control subjects to SCA3 (p < 0.01) and SCA6 (p = 0.01) patients. IMCbg amplitude was smaller in SCA3 patients compared to neurotypical subjects (p<0.05), but not different between SCA3 and SCA6 patients or between SCA6 and neurotypical subjects. Conclusion/significance: IMC metrics can differentiate SCA patients from normal controls.
ABSTRACT
Objective Mental health among undergraduate students is a growing concern in higher education, but relatively little is known about the mental health of autistic college students. In order to better understand the unique needs of this population, the present study examines whether demographic and psychosocial correlates of anxiety and depression differ in autistic first-year college students and their non-autistic peers. Methods Secondary data analysis was conducted utilizing population-weighted data of full-time college students in their first year attending four-year colleges and universities in 2016, 2018, and 2019. Autistic and non-autistic students who self-identified as having frequent anxiety or depression were compared in terms of demographic characteristics, physical and emotional health, and academic aspirations and achievement. Results The majority of first-year students with frequent anxiety or depression in this sample tended to be white and had parents who completed a bachelor's degree or went to graduate school, with higher rates of male students in the autistic group. While autistic college freshmen with frequent anxiety or depression self-report lower overall quality of physical health (below average or lowest 10% reported by 57.3% vs. 37.1%) and higher rates of learning disabilities (25.3% vs. 4.6%) and psychological disorders (62.3% vs. 29.3%), these students also tend to outperform their non-autistic peers on standardized academic testing. Conclusion As autistic students are investing in themselves through their education and future careers, practitioners and researchers alike should be investing in accessible physical and mental health services in order to help set autistic students up for success in college and beyond.
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The family Sigalionidae is characterized, among other features, by including scale worms with large bodies. However, among sigalionids, the subfamilies Sthenelanellinae, Pholoinae, and Pisioninae stand out by their small representatives with few segments and fragile bodies. In the Tropical Northwestern Atlantic, which includes part of the Gulf of Mexico and the Caribbean Sea, these subfamilies have been rarely studied, with few species recorded, and questionable records. This contribution aims to improve the knowledge of sthenelanellins, pholoins, and pisionins in the region through a faunistic study based on material from two Mexican scientific collections: the Reference Collection of Laboratorio de Biodiversidad y Cambio Climático (BIOMARCCA) and the Reference Collection of Benthos (ECOSUR) of El Colegio de la Frontera Sur. Pisione wolfi is confirmed from the Tropical Northwestern Atlantic, and three new species are described: Sthenelanella pechi sp. nov., S. sarae sp. nov. and Taylorpholoe anabelae sp. nov. A key to all Sthenelanella and Taylorpholoe species is also included.
Subject(s)
Annelida , Polychaeta , Animals , West Indies , Caribbean Region , Gulf of MexicoABSTRACT
Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders, but there is no metric that predicts disease severity over time. We hypothesized that by developing a new metric, the Severity Factor (S-Factor) using immutable disease parameters, it would be possible to capture disease severity independent of clinical rating scales. Extracting data from the CRC-SCA and READISCA natural history studies, we calculated the S-Factor for 438 participants with symptomatic SCA1, SCA2, SCA3, or SCA6, as follows: ((length of CAG repeat expansion - maximum normal repeat length) /maximum normal repeat length) × (current age - age at disease onset) × 10). Within each SCA type, the S-Factor at the first Scale for the Assessment and Rating of Ataxia (SARA) visit (baseline) was correlated against scores on SARA and other motor and cognitive assessments. In 281 participants with longitudinal data, the slope of the S-Factor over time was correlated against slopes of scores on SARA and other motor rating scales. At baseline, the S-Factor showed moderate-to-strong correlations with SARA and other motor rating scales at the group level, but not with cognitive performance. Longitudinally the S-Factor slope showed no consistent association with the slope of performance on motor scales. Approximately 30% of SARA slopes reflected a trend of non-progression in motor symptoms. The S-Factor is an observer-independent metric of disease burden in SCAs. It may be useful at the group level to compare cohorts at baseline in clinical studies. Derivation and examination of the S-factor highlighted challenges in the use of clinical rating scales in this population.
Subject(s)
Spinocerebellar Ataxias , Humans , Spinocerebellar Ataxias/diagnosis , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/epidemiology , Patient Acuity , Disease ProgressionABSTRACT
Research highlights distinct temperamental, cultural, and behavioral characteristics that may contribute to the differential experience and impact of acculturative stress in Latinx youth. The current study aims to explain the risk of developing anxiety and depression by clarifying how acculturative stress interacts with individual temperamental (behavioral inhibition), cultural (values), and behavioral (active coping) characteristics in a sample of 161 Latinx youth. Main analyses included a separate hierarchical linear regression for each potential moderating variable with anxiety and depression as the outcome variable. Results indicated a significant and positive relationship between acculturative stress, anxiety, and depression. Furthermore, active coping moderated the relationship between acculturative stress and depression, such that higher levels of active coping resulted in a stronger relationship between acculturative stress and depression than at lower levels. Findings from the current study make advancements towards an understanding of individual characteristics that interact with the experience of acculturative stress, anxiety, and depression.
Subject(s)
Depression , Stress, Psychological , Humans , Adolescent , Adaptation, Psychological , Anxiety , Acculturation , Hispanic or LatinoABSTRACT
MicroRNAs, a class of small RNA regulators, function throughout neurodevelopment, from neural stem cell neurogenesis to neuronal maturation, synaptic formation, and plasticity. α1ACT, a transcription factor (TF), plays a critical role in neonatal cerebellar development by regulating an ensemble of genes.â¯Of these, ChIP-seq analysis matched near 50% genes directly regulated by α1ACT. Yet, more than half the regulated transcripts lacked direct interaction with α1ACT. To investigate whether α1ACT acts through a microRNA network, we studied α1ACT-associated simultaneous miRNA:mRNA transcriptome profiles, usingâ¯miRNA-seq paired with RNA-seq. Thirty-one differentially expressed miRNAs (DEMs) associated withâ¯α1ACT-regulated differentially expressed genes (DEGs) were profiled in α1ACT-overexpressing PC12 cells and were further validated in neonatal transgenic mouse cerebellum overexpressing α1ACT in a context-dependent manner. Here, we also demonstrated that α1ACT facilitates neurogenesis and development of dendritic synapses and is partially a result of the downregulation of the miR-99 cluster, miR-143, miR-23, miR-146, miR-363, and miR-484. On the other hand, the miR-181, miR-125, and miR-708 clusters were upregulated by α1ACT, which inhibit MAPK signaling and cell death pathways by targeting Ask1, Odc1, Atf4, and Nuf2 for decreased expression. MiR-181a-5p was verified as the most abundant DEM in neonatal cerebellum, which was further induced by α1ACT. Overall, under α1ACT modulation, up-/downregulated miRNA clusters with their paired target genes may form a regulatory network controlling the balance between the neuronal proliferation, differentiation, and cell death in the cerebellum to promote neonatal development. Our findings concerning the α1ACT-related miRNA/mRNA expression profiles in neonatal cerebellum may inform future investigations for cerebellar development.