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1.
Psychosom Med ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38973740

ABSTRACT

OBJECTIVE: A positive association has previously been observed in healthy volunteers between emotional awareness (EA), the ability to identify and describe emotional experiences in oneself and others, and resting heart rate variability (HRV), which is dominated by vagus nerve activity. The current study aimed to investigate the EA-HRV association across multiple assessments in a "real-world" ambulatory context in patients with long QT syndrome (LQTS) who are at genetic risk for sudden cardiac death. METHOD: Participants (157 LQTS patients; MeanAge = 35.1, SDAge = 10.4; 115 women) completed the levels of emotional awareness scale (LEAS) on one occasion, which served as our measure of EA. In an ecological momentary assessment study involving 10 assessments per day over three days, multiple 5-minute ECG assessments (Mean = 24.6, SD = 5.1) were obtained in each patient using a Holter monitor, from which high-frequency HRV (HF-HRV) was computed on each occasion. RESULTS: There was a significant positive association between LEAS scores and HF-HRV controlling for biobehavioral covariates. We also detected a similar inverse relation between EA and mean heart rate. CONCLUSION: These findings suggest that, in patients with a well-defined genetic risk for ventricular arrhythmia and sudden death, the ability to experience emotions in a complex and differentiated way covaries with greater parasympathetic influences on the heart. These findings are consistent with the overlapping neural substrates of EA and HRV and their common contribution to adaptive emotional responding, consistent with the Neurovisceral Integration Model.

2.
Affect Sci ; 5(2): 69-81, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39050040

ABSTRACT

The biopsychosocial model of challenge and threat emphasizes how individuals appraise stress. Close relationship theories emphasize the interpersonal context, communication, and outcomes that arise from stress. We integrate these approaches by examining the individual variability surrounding appraisals of sufficient (more challenge, less threat) or insufficient (more threat, less challenge) resources to cope with demands and examining how these appraisals are associated with couples' behavior and feelings toward each other. Across three studies, 459 romantic couples (N = 918), and various potentially stressful in-lab conversations (extra-dyadic problem, dislikes about each other, dependability, and relationship conflict), we found evidence that stress appraisals indicative of more challenge and less threat were associated with more approach- and less avoidance-oriented behaviors within interactions. These approach- and avoidance-oriented behaviors were associated with greater feelings of relationship security and well-being after the conversation. However, whose (actors or partners) appraisals and behaviors were associated with security and well-being varied across the three studies. This work provides theoretical and empirical evidence for an interpersonal emphasis on intraindividual stress appraisal processes through a dyadic and close relationships lens. Our integrative theoretical framework breaks away from the idea that stress is inherently "bad" or "maladaptive" to show that appraising stress as more manageable (more challenge, less threat) is associated with more relationship behaviors that approach incentives and less that avoid threats and enhance feelings of relationship security and well-being. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00235-3.

3.
Biol Psychol ; 191: 108828, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38885893

ABSTRACT

Proactive interference (PI) is the disruptive effect of no longer relevant information on current working memory (WM) processing. PI effects in EEG data have been previously found to be altered in healthy aging, although it remains unclear the extent to which such changes reflect delayed or different brain mechanisms employed to overcome PI. Hence, we had twenty-six young (18-34 years) and sixteen old (53-68 years) healthy adults complete a Recent Probes task while EEG was recorded. Compared to young adults, old adults were slower, less accurate and less able to discriminate when they last saw a given stimulus, but PI effects on reaction time were greater in the former, likely due to a general difficulty that old adults had in the task. Temporo-spatial principal component analysis of the EEG data showed young and older adults to differ in terms of temporal and spatial characteristics of brain activity associated with resolving PI. YA showed a factor indicative of a medial frontal negativity (MFN) that showed greater amplitude in low compared to high PI trials. OA, in contrast, showed a late positive component (LPC), although similarly with larger amplitude in low compared to high PI trials. The modulation of the MFN component in YA may reflect the recruitment of cognitive control to overcome PI. The modulation of the LPC in OA may represent the detection of conflict between familiarity and context recollection during PI.

4.
Article in English | MEDLINE | ID: mdl-38822696

ABSTRACT

INTRODUCTION: Perceived responsiveness, or the extent to which one feels understood, validated and cared for by close others, plays a crucial role in people's well-being. Can this interpersonal process also protect people at risk? We assessed whether fluctuations in suicidal ideation were associated with fluctuations in the degree of perceived responsiveness that psychiatric patients (admitted in the context of suicide or indicating suicidal ideation) experienced in daily interactions immediately after discharge. METHODS: Fifty-seven patients reported on suicidal ideation (5 times a day) and perceived responsiveness (daily) for four consecutive weeks. The effects of established risk factors-thwarted belongingness, perceived burdensomeness, and hopelessness-were assessed as well. RESULTS: The more patients felt that close others had been responsive to them, the less suicidal ideation they reported. At low levels of thwarted belongingness, perceived burdensomeness, or hopelessness, perceived responsiveness seemed to play a protective role, negatively co-occurring with suicidal ideation. When thwarted belongingness, perceived burdensomeness, and hopelessness were high, perceived responsiveness did not have an effect. CONCLUSION: Perceived responsiveness could be a protective factor for suicidal ideation for people at risk only when they are experiencing low levels of negative perceptions. When experiencing highly negative perceptions, however, perceived responsiveness seems to matter less.

5.
Health Psychol ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38635187

ABSTRACT

OBJECTIVE: We examined the links of supportive and conflictual peer interactions to mood and self-care via ecological momentary assessment. METHOD: Adolescents with Type 1 diabetes (n = 167, 49% female) recruited between 2018 and 2021 were prompted 8 times a day for 8 days to complete brief surveys that measured perceived social interactions, affect, and self-care. RESULTS: Cross-sectional analyses revealed between- and within-person (WP) links of peer support to positive mood and conflict to negative mood. Between-person peer support was linked to healthy self-care, but WP support was not. Lagged analyses showed conflictual interactions were associated with self-care decline. There was some evidence that females did not benefit as much from support and were more bothered by conflict than others. CONCLUSIONS: Results underscore differences in between- and WP links of social interactions to health. Individual differences in support were more influential than conflict, but conflictual interactions had more momentary effects than supportive interactions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

6.
JCI Insight ; 9(9)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38512434

ABSTRACT

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, striatal contributions to motor deficits using f-ATXN1146Q/2Q;Rgs9-Cre mice revealed that mice lacking ATXN1146Q/2Q in striatal medium-spiny neurons showed a trending improvement in rotarod performance at 30 weeks of age. Surprisingly, a prominent role for muscle contributions to disease was revealed in f-ATXN1146Q/2Q;ACTA1-Cre mice based on their recovery from kyphosis and absence of muscle pathology. Collectively, data from the targeted conditional deletion of the expanded allele demonstrated CNS and peripheral contributions to disease and highlighted the need to consider muscle in addition to the brain for optimal SCA1 therapeutics.


Subject(s)
Ataxin-1 , Disease Models, Animal , Muscle, Skeletal , Spinocerebellar Ataxias , Animals , Ataxin-1/genetics , Ataxin-1/metabolism , Mice , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/metabolism , Humans , Male , Mice, Transgenic , Gene Knock-In Techniques , Female , Phenotype , Neurons/metabolism , Neurons/pathology
7.
Immunity ; 57(4): 890-903.e6, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38518779

ABSTRACT

The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the VH1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells, performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs. In contrast to what has been seen in chronically infected donors, the bNAbs used a variety of VH genes and targeted at least three distinct E2 antigenic sites, including sites previously thought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolved convergently, acquiring breadth-enhancing somatic mutations. These findings demonstrate that HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenic sites that should be the target of vaccine-induced bNAbs.


Subject(s)
Hepacivirus , Hepatitis C , Humans , Broadly Neutralizing Antibodies , Epitopes , Antibodies, Neutralizing , Viral Envelope Proteins/genetics
8.
Emotion ; 24(5): 1338-1342, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38451726

ABSTRACT

Expressing emotions with others can be difficult as it puts individuals in a position of potential vulnerability. Research suggests that people are willing to express their emotions with communal partners; however, few studies have examined processes that might explain how this occurs. Using a cross-sectional design, we examined interpersonal accuracy and empathic effort as factors that support the likelihood of expression in communal relationships. Participants (N = 219) reported the communal motivation, accuracy, and effort they perceived from five targets varying in closeness (e.g., best friend, acquaintance, etc.); they rated their likelihood of expressing happiness, pride, gratitude, sadness, anxiety, guilt, and anger with each target. Perceived accuracy and effort were both significant mediators of the association between perceived communal motivation and reported likelihood of expressing all emotions. Perceived accuracy was a stronger predictor of the likelihood of expression than effort. These findings indicate that perceiving greater accuracy and effort each independently supports a greater likelihood of expression. A willingness to express emotions is critical to developing close relationships and the current work identifies processes that may encourage this willingness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Emotions , Empathy , Interpersonal Relations , Motivation , Humans , Male , Female , Emotions/physiology , Empathy/physiology , Young Adult , Adult , Cross-Sectional Studies , Social Perception , Adolescent
9.
Neuroimage ; 290: 120569, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38461959

ABSTRACT

Functional near infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both measure the hemodynamic response, and so both imaging modalities are expected to have a strong correspondence in regions of cortex adjacent to the scalp. To assess whether fNIRS can be used clinically in a manner similar to fMRI, 22 healthy adult participants underwent same-day fMRI and whole-head fNIRS testing while they performed separate motor (finger tapping) and visual (flashing checkerboard) tasks. Analyses were conducted within and across subjects for each imaging approach, and regions of significant task-related activity were compared on the cortical surface. The spatial correspondence between fNIRS and fMRI detection of task-related activity was good in terms of true positive rate, with fNIRS overlap of up to 68 % of the fMRI for analyses across subjects (group analysis) and an average overlap of up to 47.25 % for individual analyses within subject. At the group level, the positive predictive value of fNIRS was 51 % relative to fMRI. The positive predictive value for within subject analyses was lower (41.5 %), reflecting the presence of significant fNIRS activity in regions without significant fMRI activity. This could reflect task-correlated sources of physiologic noise and/or differences in the sensitivity of fNIRS and fMRI measures to changes in separate (vs. combined) measures of oxy and de-oxyhemoglobin. The results suggest whole-head fNIRS as a noninvasive imaging modality with promising clinical utility for the functional assessment of brain activity in superficial regions of cortex physically adjacent to the skull.


Subject(s)
Magnetic Resonance Imaging , Spectroscopy, Near-Infrared , Adult , Humans , Magnetic Resonance Imaging/methods , Spectroscopy, Near-Infrared/methods , Hemodynamics/physiology , Skull
10.
J Healthc Manag ; 69(2): 132-139, 2024.
Article in English | MEDLINE | ID: mdl-38467026

ABSTRACT

GOAL: Accurate prediction of operating room (OR) time is critical for effective utilization of resources, optimal staffing, and reduced costs. Currently, electronic health record (EHR) systems aid OR scheduling by predicting OR time for a specific surgeon and operation. On many occasions, the predicted OR time is subject to manipulation by surgeons during scheduling. We aimed to address the use of the EHR for OR scheduling and the impact of manipulations on OR time accuracy. METHODS: Between April and August 2022, a pilot study was performed in our tertiary center where surgeons in multiple surgical specialties were encouraged toward nonmanipulation for predicted OR time during scheduling. The OR time accuracy within 5 months before trial (Group 1) and within the trial period (Group 2) were compared. Accurate cases were defined as cases with total length (wheels-in to wheels-out) within ±30 min or ±20% of the scheduled duration if the scheduled time is ≥ or <150 min, respectively. The study included single and multiple Current Procedural Terminology code procedures, while procedures involving multiple surgical specialties (combo cases) were excluded. PRINCIPAL FINDINGS: The study included a total of 8,821 operations, 4,243 (Group 1) and 4,578 (Group 2), (p < .001). The percentage of manipulation dropped from 19.8% (Group 1) to 7.6% (Group 2), (p < .001), while scheduling accuracy rose from 41.7% (Group 1) to 47.9% (Group 2), (p = .0001) with a significant reduction of underscheduling percentage (38.7% vs. 31.7%, p = .0001) and without a significant difference in the percentage of overscheduled cases (15% vs. 17%, p = .22). Inaccurate OR hours were reduced by 18% during the trial period (2,383 hr vs. 1,954 hr). PRACTICAL APPLICATIONS: The utilization of EHR systems for predicting OR time and reducing manipulation by surgeons helps improve OR scheduling accuracy and utilization of OR resources.


Subject(s)
Electronic Health Records , Personnel Staffing and Scheduling , Humans , Operative Time , Pilot Projects , Time Factors
11.
Neurorehabil Neural Repair ; 38(3): 167-175, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38357877

ABSTRACT

BACKGROUND: There is an increasing need for motor assessments after stroke that can be performed quickly and remotely. The Fast Outcome Categorization of the Upper Limb after Stroke-4 (FOCUS-4) assessment remotely classifies upper limb outcome into 1 of 4 categories after stroke and was developed via retrospective analysis of Action Research Arm Test (ARAT) scores. OBJECTIVE: The aim of this study was to prospectively evaluate the accuracy and reliability of FOCUS-4 assessments for categorizing upper limb outcome after stroke when administered remotely during a videocall compared to an in-person ARAT. METHODS: Data were collected from 26 participants at 3 months post-stroke (3M), 27 participants at 6 months post-stroke (6M), and 56 participants at the chronic stage of stroke (>6M). Participants performed an in-person ARAT and a remote FOCUS-4 assessment administered during a videocall, and accuracy was evaluated by comparing the upper limb outcome categories. Participants at the chronic stage of stroke also performed a second remote FOCUS-4 assessment to assess between-day reliability. RESULTS: Overall accuracy of the remote FOCUS-4 assessment was 88% at 3M and 96% at 6M. Overall accuracy of the first and second remote FOCUS-4 assessments at the chronic stage was 75% and 79%, respectively. Reliability of the FOCUS-4 assessment at the chronic stage was 82%. The remote FOCUS-4 assessment was most accurate and reliable for participants with mild or severe upper limb functional impairment. CONCLUSIONS: The remote FOCUS-4 assessment has potential to classify upper limb functional capacity or to screen possible participants for stroke trials, but external validation is required.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Reproducibility of Results , Retrospective Studies , Treatment Outcome , Upper Extremity , Recovery of Function
12.
Immunity ; 57(1): 40-51.e5, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38171362

ABSTRACT

Individuals who clear primary hepatitis C virus (HCV) infections clear subsequent reinfections more than 80% of the time, but the mechanisms are poorly defined. Here, we used HCV variants and plasma from individuals with repeated clearance to characterize longitudinal changes in envelope glycoprotein E2 sequences, function, and neutralizing antibody (NAb) resistance. Clearance of infection was associated with early selection of viruses with NAb resistance substitutions that also reduced E2 binding to CD81, the primary HCV receptor. Later, peri-clearance plasma samples regained neutralizing capacity against these variants. We identified a subset of broadly NAbs (bNAbs) for which these loss-of-fitness substitutions conferred resistance to unmutated bNAb ancestors but increased sensitivity to mature bNAbs. These data demonstrate a mechanism by which neutralizing antibodies contribute to repeated immune-mediated HCV clearance, identifying specific bNAbs that exploit fundamental vulnerabilities in E2. The induction of bNAbs with these specificities should be a goal of HCV vaccine development.


Subject(s)
Antibodies, Neutralizing , Hepatitis C , Humans , Broadly Neutralizing Antibodies , Hepatitis C Antibodies/chemistry , Hepacivirus , Viral Envelope Proteins/genetics
13.
Emotion ; 24(2): 329-344, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37561518

ABSTRACT

Most emotion regulation research investigates how individuals manage their own emotions but in everyday life, emotion regulation often takes place in an interpersonal context-that is, through the intervention of others, especially close relationship partners. In this manuscript, we describe a 2-week daily diary study of 197 couples, in which we examined the nature and effectiveness of partners' attempts at interpersonal emotion regulation. Organized around the extended process model of emotion regulation (Gross, 2015), we examined the frequency and perceived effectiveness of six strategies for regulating negative emotions and two strategies for regulating positive emotions, as well as the impact of emotional regulation effectiveness on relationship satisfaction. Results indicated that situation modification was the most common approach to regulating negative emotions, whereas savoring was most common for positive emotions. Most strategies were perceived to be effective by both regulators and their targets, with the exception of suppression for negative emotion, for which evidence was mixed, and dampening for positive emotion, which was not viewed as effective. The influence of emotion regulation on relationship satisfaction depended on one's perspective: Regulators felt that their effective efforts benefitted their relationships, but even when targets experienced emotion regulation as effective, they indicated no improvements in relationship satisfaction, perhaps because the emotion-eliciting events were still salient to them. Broadly speaking, this research highlights the value of examining emotion regulation in an interpersonal context, and in the context of partners' ordinary, everyday social interaction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Emotional Regulation , Humans , Emotional Regulation/physiology , Interpersonal Relations , Emotions/physiology , Social Interaction , Personal Satisfaction
14.
Neuron ; 112(3): 362-383.e15, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38016472

ABSTRACT

Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a deep learning method to predict disease state accurately and identified specific features that enable accurate distinction of wild-type and SCA1 cells. Together, this work reveals new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration.


Subject(s)
Spinocerebellar Ataxias , Animals , Mice , Humans , Ataxin-1/genetics , Mice, Transgenic , Spinocerebellar Ataxias/metabolism , Cerebellum/metabolism , Purkinje Cells/metabolism , Disease Models, Animal
15.
bioRxiv ; 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37961407

ABSTRACT

One of the characteristic areas of brainstem degeneration across multiple spinocerebellar ataxias (SCAs) is the inferior olive (IO), a medullary nucleus that plays a key role in motor learning. In addition to its vulnerability in SCAs, the IO is also susceptible to a distinct pathology known as hypertrophic olivary degeneration (HOD). Clinically, HOD has been exclusively observed after lesions in the brainstem disrupt inhibitory afferents to the IO. Here, for the first time, we describe HOD in another context: spinocerebellar ataxia type 1 (SCA1). Using the genetically-precise SCA1 knock-in mouse model (SCA1-KI; both sexes used), we assessed SCA1-associated changes in IO neuron structure and function. Concurrent with degeneration, we found that SCA1-KI IO neurons are hypertrophic, exhibiting early dendrite lengthening and later somatic expansion. Unlike in previous descriptions of HOD, we observed no clear loss of IO inhibitory innervation; nevertheless, patch-clamp recordings from brainstem slices reveal that SCA1-KI IO neurons are hyperexcitable. Rather than synaptic disinhibition, we identify increases in intrinsic membrane excitability as the more likely mechanism underlying this novel SCA1 phenotype. Specifically, transcriptome analysis indicates that SCA1-KI IO hyperexcitability is associated with a reduced medullary expression of ion channels responsible for spike afterhyperpolarization (AHP) in IO neurons - a result that has a functional consequence, as SCA1-KI IO neuron spikes exhibit a diminished AHP. These results reveal membrane excitability as a potential link between disparate causes of IO degeneration, suggesting that HOD can result from any cause, intrinsic or extrinsic, that increases excitability of the IO neuron membrane.

16.
Front Neurosci ; 17: 1278828, 2023.
Article in English | MEDLINE | ID: mdl-37954878

ABSTRACT

Objective: To determine sex differences in the neurochemical concentrations measured by in vivo proton magnetic resonance spectroscopy (1H MRS) of healthy mice on a genetic background commonly used for neurodegenerative disease models. Methods: 1H MRS data collected from wild type mice with C57BL/6 or related genetic backgrounds in seven prior studies were used in this retrospective analysis. To be included, data had to be collected at 9.4 tesla magnetic field using advanced 1H MRS protocols, with isoflurane anesthesia and similar animal handling protocols, and a similar number of datasets from male and female mice had to be available for the brain regions analyzed. Overall, 155 spectra from female mice and 166 spectra from male mice (321 in total), collected from six brain regions (brainstem, cerebellum, cortex, hippocampus, hypothalamus, and striatum) at various ages were included. Results: Concentrations of taurine, total creatine (creatine + phosphocreatine), ascorbate, glucose and glutamate were consistently higher in male vs. female mice in most brain regions. Striatum was an exception with similar total creatine in male and female mice. The sex difference pattern in the hypothalamus was notably different from other regions. Interaction between sex and age was significant for total creatine and taurine in the cerebellum and hippocampus. Conclusion: Sex differences in regional neurochemical levels are small but significant and age-dependent, with consistent male-female differences across most brain regions. The neuroendocrine region hypothalamus displays a different pattern of sex differences in neurochemical levels. Differences in energy metabolism and cellular density may underlie the differences, with higher metabolic rates in females and higher osmoregulatory and antioxidant capacity in males.

17.
mBio ; : e0146823, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37877702

ABSTRACT

Wastewater-based epidemiology is a powerful tool for monitoring the emergence and spread of viral pathogens at the population scale. Typical polymerase chain reaction (PCR)-based methods of quantitative and genomic monitoring of viruses in wastewater provide high sensitivity and specificity. However, these methods are limited to the surveillance of target viruses in a single assay and require prior knowledge of the target genome(s). Metagenomic sequencing methods may represent a target-agnostic approach to viral wastewater monitoring, allowing for the detection of a broad range of target viruses, including potentially novel and emerging pathogens. In this study, targeted and untargeted metagenomic sequencing methods were compared with tiled-PCR sequencing for the detection and genotyping of viral pathogens in wastewater samples. Deep shotgun metagenomic sequencing was unable to generate sufficient genome coverage of human pathogenic viruses for robust genomic epidemiology, with samples dominated by bacteria. Hybrid-capture enrichment of shotgun libraries for respiratory viruses led to significant increases in genome coverage for a range of targets. Tiled-PCR sequencing led to further improvements in genome coverage compared to hybrid capture for severe acute respiratory syndrome coronavirus 2, enterovirus D68, norovirus GII, and human adenovirus F41 in wastewater samples. In conclusion, untargeted shotgun sequencing was unsuitable for genomic monitoring of the low virus concentrations in wastewater samples analyzed in this study. Hybrid-capture enrichment represented a viable method for simultaneous genomic epidemiology of a range of viral pathogens, while tiled-PCR sequencing provided the optimal genome coverage for individual viruses with the minimum sequencing depth. IMPORTANCE Most public health initiatives that monitor viruses in wastewater have utilized quantitative polymerase chain reaction (PCR) and whole genome PCR sequencing, mirroring techniques used for viral epidemiology in individuals. These techniques require prior knowledge of the target viral genome and are limited to monitoring individual or small groups of viruses. Metagenomic sequencing may offer an alternative strategy for monitoring a broad spectrum of viruses in wastewater, including novel and emerging pathogens. In this study, while amplicon sequencing gave high viral genome coverage, untargeted shotgun sequencing of total nucleic acid samples was unable to detect human pathogenic viruses with enough sensitivity for use in genomic epidemiology. Enrichment of shotgun libraries for respiratory viruses using hybrid-capture technology provided genotypic information on a range of viruses simultaneously, indicating strong potential for wastewater surveillance. This type of targeted metagenomics could be used for monitoring diverse targets, such as pathogens or antimicrobial resistance genes, in environmental samples.

18.
Neuron ; 111(22): 3517-3530, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37863037

ABSTRACT

One of the more transformative findings in human genetics was the discovery that the expansion of unstable nucleotide repeats underlies a group of inherited neurological diseases. A subset of these unstable repeat neurodegenerative diseases is due to the expansion of a CAG trinucleotide repeat encoding a stretch of glutamines, i.e., the polyglutamine (polyQ) repeat neurodegenerative diseases. Among the CAG/polyQ repeat diseases are Huntington's disease (HD) and spinocerebellar ataxia type 1 (SCA1), in which the expansions are within widely expressed proteins. Although both HD and SCA1 are autosomal dominantly inherited, and both typically cause mid- to late-life-onset movement disorders with cognitive decline, they each are characterized by distinct clinical characteristics and predominant sites of neuropathology. Importantly, the respective affected proteins, Huntingtin (HTT, HD) and Ataxin 1 (ATXN1, SCA1), have unique functions and biological properties. Here, we review HD and SCA1 with a focus on how their disease-specific and shared features may provide informative insights.


Subject(s)
Huntington Disease , Nervous System Diseases , Spinocerebellar Ataxias , Humans , Huntington Disease/genetics , Spinocerebellar Ataxias/genetics , Ataxin-1/genetics , Proteins/genetics , Trinucleotide Repeats , Nervous System Diseases/genetics , Genetic Association Studies , Trinucleotide Repeat Expansion/genetics
19.
J Pediatr Psychol ; 48(11): 940-951, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37740947

ABSTRACT

OBJECTIVE: The goal of the study was to examine the relations of general and diabetes-specific friend support and conflict to psychological and diabetes health among youth with type 1 diabetes. We examined gender as a moderator of these relations, and friend responsiveness and information-sharing as potential mediators. METHODS: Youth with type 1 diabetes (n = 167; M age 15.83 [SD = 0.78]; 50% female) were interviewed once in the Fall and once in the following Spring of the school year. Using multiple regression analysis, general friend support, general friend conflict, diabetes-specific support, and diabetes-specific conflict were investigated as simultaneous predictors of psychological and diabetes outcomes cross-sectionally and longitudinally over four months. RESULTS: Cross-sectionally friend conflict, including both general and diabetes-specific, was more predictive of outcomes than friend support. In cross-sectional and longitudinal analyses, gender was a significant moderator, such that several relations of general friend conflict to outcomes were significant for females but not nonfemales. Friend support revealed mixed relations to outcomes across cross-sectional and longitudinal analyses. Although we found links of friend relationship variables to mediators (perceived responsiveness; information sharing), we found little evidence of mediation. CONCLUSIONS: These findings show stronger evidence that conflictual friend relationships than supportive friend relationships are linked to health. Findings suggest that problematic friend relationships may have a stronger impact on the health of females than nonfemales. These results underscore the need to better understand the conditions under which friend support is helpful versus harmful and the reasons underlying these links.


Subject(s)
Diabetes Mellitus, Type 1 , Friends , Humans , Female , Adolescent , Male , Friends/psychology , Diabetes Mellitus, Type 1/psychology , Cross-Sectional Studies , Schools , Interpersonal Relations
20.
Sensors (Basel) ; 23(18)2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37765987

ABSTRACT

There have been sustained efforts toward using naturalistic methods in developmental science to measure infant behaviors in the real world from an egocentric perspective because statistical regularities in the environment can shape and be shaped by the developing infant. However, there is no user-friendly and unobtrusive technology to densely and reliably sample life in the wild. To address this gap, we present the design, implementation and validation of the EgoActive platform, which addresses limitations of existing wearable technologies for developmental research. EgoActive records the active infants' egocentric perspective of the world via a miniature wireless head-mounted camera concurrently with their physiological responses to this input via a lightweight, wireless ECG/acceleration sensor. We also provide software tools to facilitate data analyses. Our validation studies showed that the cameras and body sensors performed well. Families also reported that the platform was comfortable, easy to use and operate, and did not interfere with daily activities. The synchronized multimodal data from the EgoActive platform can help tease apart complex processes that are important for child development to further our understanding of areas ranging from executive function to emotion processing and social learning.


Subject(s)
Wearable Electronic Devices , Infant , Child , Humans , Software , Technology , Autonomic Nervous System
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