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Investigating fundamental processes in biology requires the ability to ground broad questions in species-specific natural history. This is particularly true in the study of behavior because an organism's experience of the environment will influence the expression of behavior and the opportunity for selection. Here, we provide a review of the natural history and behavior of burying beetles of the genus Nicrophorus to provide the groundwork for comparative work that showcases their remarkable behavioral and ecological diversity. Burying beetles have long fascinated scientists because of their well-developed parenting behavior, exhibiting extended post-hatching care of offspring that varies extensively within and across taxa. Despite the burgeoning success of burying beetles as a model system for the study of behavioral evolution, there has not been a review of their behavior, ecology, and evolution in over 25 years. To address this gap, we leverage a developing community of researchers who have contributed to a detailed knowledge of burying beetles to highlight the utility of Nicrophorus for investigating the causes and consequences of social and behavioral evolution.
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OBJECTIVE: Previous research has demonstrated different cannabis-related outcomes depending on the goal of cannabis use (i.e., recreational, medical, hybrid of both), underscoring the need to identify variables associated with specific goals of use, particularly in understudied populations. METHOD: This report utilized data from a national survey of menopausal individuals using non-probability sampling. Respondents reporting current regular (≥1x/month) cannabis use (medical n=35, recreational n=61, and hybrid n=102) were included in multivariate logistic regression analyses examining demographic, clinical (e.g., menopause-related symptomatology), and cannabis-related variables associated with goal of cannabis use. RESULTS: Overall, increased number of medical conditions was associated with medical and hybrid use relative to recreational use (ps≤.047), and greater menopause-related symptomatology was associated with medical relative to hybrid use (p=.001). Lower education level was associated with hybrid relative to recreational use (p=.010). Lastly, increased number of modes of use was associated with hybrid use relative to medical and recreational use (ps≤.001). CONCLUSIONS: Results suggest medical and hybrid consumers with more medical conditions and more severe clinical symptoms that are not sufficiently alleviated by conventional treatments may be more open to cannabinoid-based therapies. Additionally, as lower education level is often associated with recreational cannabis use, results suggest hybrid consumers may begin as recreational consumers who then expand their use for medical purposes. Further, more varied modes of use for hybrid consumers may reflect different product selection based on goal of use. Future research should investigate the etiology of hybrid cannabis use and predictors of long-term outcomes associated with goals of use.
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Maintaining functional adipose innervation is critical for metabolic health. We found that subcutaneous white adipose tissue (scWAT) undergoes peripheral neuropathy (PN) with obesity, diabetes, and aging (reduced small-fiber innervation and nerve/synaptic/growth-cone/vesicle markers, altered nerve activity). Unlike with nerve injuries, peripheral nerves do not regenerate with PN, and therefore new therapies are needed for treatment of this condition affecting 20-30 million Americans. Here, we validated a gene therapy approach using an adipocyte-tropic adeno-associated virus (AAV; serotype Rec2) to deliver neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) directly to scWAT to improve tissue-specific PN as a proof-of-concept approach. AAVRec2-BDNF intra-adipose delivery improved tissue innervation in obese/diabetic mice with PN, but after longer periods of dietary obesity there was reduced efficacy, revealing a key time window for therapies. AAVRec2-NGF also increased scWAT innervation in obese mice and was more effective than BDNF, likely because Rec2 targeted adipocytes, the tissue's endogenous NGF source. AAVRec2-NGF also worked well even after 25 weeks of dietary obesity, unlike BDNF, which likely needs a vector that targets its physiological cellular source (stromal vascular fraction cells). Given the differing effects of AAVs carrying NGF versus BDNF, a combined therapy may be ideal for PN.
Subject(s)
Adipocytes , Brain-Derived Neurotrophic Factor , Dependovirus , Genetic Therapy , Genetic Vectors , Obesity , Subcutaneous Fat , Animals , Dependovirus/genetics , Obesity/therapy , Obesity/metabolism , Mice , Genetic Therapy/methods , Adipocytes/metabolism , Genetic Vectors/administration & dosage , Genetic Vectors/genetics , Subcutaneous Fat/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Disease Models, Animal , Nerve Growth Factor/metabolism , Nerve Growth Factor/genetics , Nerve Growth Factors/metabolism , Nerve Growth Factors/genetics , Gene Transfer Techniques , Humans , Male , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/genetics , Transduction, GeneticABSTRACT
This paper presents the design, microfabrication, and demonstration of a novel microfluidic grinding mill for the lysis of the dinoflagellate, Alexandrium, a neurotoxin-producing genus of algae that is responsible for red tide and paralytic shellfish poisoning. The mill consists of a high-speed, hydrodynamically driven microrotor coupled to a micro grinding mill that lyses robust algal cells by mechanical abrasion with single-pass efficiencies as high as 97%. These efficiencies are comparable to, or better than, current mechanical and chemical lysing methods without adding complications associated with harsh chemical additives that can interfere with subsequent downstream bioanalysis. Release of cytoplasm from lysed algae was confirmed using polymerase chain reaction (PCR) amplification of Alexandrium DNA using dinoflagellate primers.
Subject(s)
Dinoflagellida , Polymerase Chain Reaction , DNA PrimersABSTRACT
OBJECTIVE: Essential vocal tremor (EVT) manifests as nearly rhythmic modulations of fundamental frequency (fo) and intensity and causes a shaky voice. Although research on behavioral therapy for EVT is limited, previous studies have shown that a breathy voice reduces the perception of simulated EVT and might be an effective compensatory strategy. The current study aimed to measure the acoustical and perceptual effects of a breathy voice strategy in speakers with EVT. STUDY DESIGN: A single-case experimental design (SCED) was used to investigate acoustical effects, and a pair comparison listening task was used to investigate perceptual effects. METHODS: Three participants with EVT matched five different levels of breathiness produced by a computational model. Acoustical analyses of the rate and extent of fo and intensity modulation were performed to estimate EVT severity for baseline and treatment trials. Statistical analyses were completed using Tau-U. Twenty novice listeners participated in the perceptual study to determine if treatment trials sounded less "shaky" than baseline trials. Statistical analyses were completed using one sample t tests. RESULTS: The acoustical effects were variable across different levels of breathiness for all three participants. All participants were able to adjust their levels of breathiness based on auditory models and verbal cues but did not achieve the target levels of breathiness. Listeners did not perceive the breathy trials to be less "shaky" than baseline trials for any level of breathiness. CONCLUSION: The breathy voice strategy had variable effects on the acoustical measures of EVT, supporting the use of a single-case experimental design to investigate the effectiveness of behavioral treatment for EVT. Listeners perceived breathy trials to be "shakier" than baseline trials, which was inconsistent with our hypothesis and previous studies of EVT. Future research should evaluate the use of a breathy voice in speakers with confirmed laryngeal tremor, optimize cueing for breathiness, and provide more opportunities to practice the breathy strategy.
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Background: Despite the significance of menopause as a natural biological milestone experienced by approximately half the population, few studies have evaluated factors associated with menopause-related shame and stigma. Given previous research indicating increased shame and stigma are associated with negative outcomes that directly impact health (e.g., reduced access to health care), it is critical to identify variables associated with menopause-related shame and stigma. Materials and Methods: As part of a larger, national survey, 214 perimenopausal (n = 111) and postmenopausal (n = 103) individuals completed self-report questionnaires assessing demographics and menopause-related symptoms, shame, and stigma. Regression analyses examined variables associated with shame and stigma. Results: Over a third of respondents reported feeling shame related to their menopause-related symptoms (37.4%), while the majority of respondents reported feeling stigma associated with symptoms (82.7%). In addition, most respondents endorsed talking about their symptoms with friends, family, partners, or doctors (80.8%), and felt that their peers might experience the same symptoms (93.9%). Regression analyses identified several significant predictor variables; in particular, more severe psychosocial and urogenital symptoms, higher education level, and younger age were significantly associated with greater odds of reporting shame and stigma. Conclusions: Overall, findings suggest that even though menopausal individuals report feeling their symptoms are similar to their peers, shame and stigma are significantly associated with these symptoms, which may be impacted by symptom severity and socioeconomic factors. Results suggest that younger individuals (i.e., those just entering perimenopause) with more education may be more likely to feel shame and stigma, which could inform interventional strategies and improve clinical outcomes.
Subject(s)
Menopause , Social Stigma , Female , Humans , Menopause/psychology , Shame , Perimenopause , Surveys and QuestionnairesABSTRACT
Targeted exome-based genotype by sequencing (t-GBS), a sequencing technology that tags SNPs and haplotypes in gene-rich regions was used in previous genome-wide association studies (GWAS) for sodicity tolerance in bread wheat. Thirty-nine novel SNPs including 18 haplotypes for yield and yield-components were identified. The present study aimed at developing SNP-derived markers by precisely locating new SNPs on ~180 bp allelic sequence of t-GBS, marker validation, and SNP functional characterization based on its exonic location. We identified unknown locations of significant SNPs/haplotypes by aligning allelic sequences on to IWGSC RefSeqv1.0 on respective chromosomes. Eighteen out of the target 39 SNP locations fulfilled the criteria for producing PCR markers, among which only eight produced polymorphic signals. These eight markers associated with yield, plants m-2, heads m-2, and harvest index, including a pleiotropic marker for yield, harvest index, and grains/head were validated for its amplification efficiency and phenotypic effects in focused identification germplasm strategy (FIGS) wheat set and a doubled haploid (DH) population (Scepter/IG107116). The phenotypic variation explained by these markers are in the range of 4.1-37.6 in the FIGS population. High throughput PCR-based genotyping using new markers and association with phenotypes in FIGS wheat set and DH population validated the effect of functional SNP on closely associated genes-calcineurin B-like- and dirigent protein, basic helix-loop-helix (BHLH-), plant homeodomain (PHD-) and helix-turn-helix myeloblastosis (HTH myb) type -transcription factor. Further, genome-wide SNP annotation using SnpEff tool confirmed that these SNPs are in gene regulatory regions (upstream, 3'-UTR, and intron) modifying gene expression and protein-coding. This integrated approach of marker design for t-GBS alleles, SNP functional annotation, and high-throughput genotyping of functional SNP offers translation solutions across crops and complex traits in crop improvement programs.
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Speaking elicits a suppressed neural response when compared with listening to others' speech, a phenomenon known as speaker-induced suppression (SIS). Previous research has focused on investigating SIS at constrained levels of linguistic representation, such as the individual phoneme and word level. Here, we present scalp EEG data from a dual speech perception and production task where participants read sentences aloud then listened to playback of themselves reading those sentences. Playback was separated into immediate repetition of the previous trial and randomized repetition of a former trial to investigate if forward modeling of responses during passive listening suppresses the neural response. Concurrent EMG was recorded to control for movement artifact during speech production. In line with previous research, ERP analyses at the sentence level demonstrated suppression of early auditory components of the EEG for production compared with perception. To evaluate whether linguistic abstractions (in the form of phonological feature tuning) are suppressed during speech production alongside lower-level acoustic information, we fit linear encoding models that predicted scalp EEG based on phonological features, EMG activity, and task condition. We found that phonological features were encoded similarly between production and perception. However, this similarity was only observed when controlling for movement by using the EMG response as an additional regressor. Our results suggest that SIS operates at a sensory representational level and is dissociated from higher order cognitive and linguistic processing that takes place during speech perception and production. We also detail some important considerations when analyzing EEG during continuous speech production.
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Reading , Speech Perception , Humans , Speech Perception/physiology , Speech/physiology , Electroencephalography , LanguageABSTRACT
In-person undergraduate research experiences (UREs) promote students' integration into careers in life science research. In 2020, the COVID-19 pandemic prompted institutions hosting summer URE programs to offer them remotely, raising questions about whether undergraduates who participate in remote research can experience scientific integration and whether they might perceive doing research less favorably (i.e., not beneficial or too costly). To address these questions, we examined indicators of scientific integration and perceptions of the benefits and costs of doing research among students who participated in remote life science URE programs in Summer 2020. We found that students experienced gains in scientific self-efficacy pre- to post-URE, similar to results reported for in-person UREs. We also found that students experienced gains in scientific identity, graduate and career intentions, and perceptions of the benefits of doing research only if they started their remote UREs at lower levels on these variables. Collectively, students did not change in their perceptions of the costs of doing research despite the challenges of working remotely. Yet students who started with low cost perceptions increased in these perceptions. These findings indicate that remote UREs can support students' self-efficacy development, but may otherwise be limited in their potential to promote scientific integration.
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COVID-19 , Students , Humans , PandemicsABSTRACT
Increasing numbers of individuals have access to cannabinoid-based products containing various amounts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and other cannabinoids. Exposure to specific cannabinoids likely influences outcomes; however, current methods for quantifying cannabis exposure do not account for the cannabinoid concentrations of the products used. We developed CannaCount, an examiner-driven metric that quantifies estimated maximum possible cannabinoid exposure by accounting for variables related to cannabinoid concentration, duration, frequency, and quantity of use. To demonstrate feasibility and applicability, CannaCount was used to quantify estimated maximum THC and CBD exposure in 60 medical cannabis patients enrolled in a two-year, longitudinal, observational study. Medical cannabis patients reported using a variety of product types and routes of administration. Calculating estimated exposure to THC and CBD was possible for the majority of study visits, and the ability to generate estimated cannabinoid exposure improved over time, likely a function of improved product labeling, laboratory testing, and more informed consumers. CannaCount is the first metric to provide estimated maximum possible exposure to individual cannabinoids based on actual cannabinoid concentrations. This metric will ultimately facilitate cross-study comparisons and can provide researchers and clinicians with detailed information regarding exposure to specific cannabinoids, which will likely have significant clinical impact.
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Cannabidiol , Cannabinoids , Cannabis , Hallucinogens , Medical Marijuana , Humans , Dronabinol , Cannabinoid Receptor AgonistsABSTRACT
The timing of life events (phenology) can be influenced by climate. Studies from around the world tell us that climate cues and species' responses can vary greatly. If variation in climate effects on phenology is strong within a single ecosystem, climate change could lead to ecological disruption, but detailed data from diverse taxa within a single ecosystem are rare. We collated first sighting and median activity within a high-elevation environment for plants, insects, birds, mammals and an amphibian across 45 years (1975-2020). We related 10 812 phenological events to climate data to determine the relative importance of climate effects on species' phenologies. We demonstrate significant variation in climate-phenology linkage across taxa in a single ecosystem. Both current and prior climate predicted changes in phenology. Taxa responded to some cues similarly, such as snowmelt date and spring temperatures; other cues affected phenology differently. For example, prior summer precipitation had no effect on most plants, delayed first activity of some insects, but advanced activity of the amphibian, some mammals, and birds. Comparing phenological responses of taxa at a single location, we find that important cues often differ among taxa, suggesting that changes to climate may disrupt synchrony of timing among taxa.
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Ecosystem , Insecta , Animals , Climate Change , Seasons , Temperature , Birds , MammalsABSTRACT
BACKGROUND: Bronchiectasis has been observed in association with systemic sclerosis (SSc). Theorised aetiology includes aspiration related to oesophageal dysmotility, immunosuppressant medication use and the direct effect of collagen deposition on airway calibre. AIMS: To detail bronchiectasis prevalence in an SSc population who have had a high-resolution computed tomography (HRCT) of the thorax. We assessed whether oesophageal dysmotility, demographic variables, SSc duration or subclass were associated with bronchiectasis. METHODS: Participants in the Australian Scleroderma Cohort Study (ASCS) with a HRCT were included. The ASCS provided demographic and clinical data. HRCT studies were reviewed for bronchiectasis, oesophageal dilatation and interstitial lung disease (ILD). Traction bronchiectasis associated with ILD was recorded as a separate entity to bronchiectasis. Oesophageal dysmotility was defined by symptoms and/or oesophageal dilatation. RESULTS: Of the 256 participants, 16.4% (n = 42) had bronchiectasis. Logistic regression analysis revealed no significant association between bronchiectasis and oesophageal dysmotility (observed in 95.7%), any demographic variable, SSc duration or subclass. A negative association between bronchiectasis and ILD was observed (P = 0.009; odds ratio 0.322; 95% confidence intervals 0.137-0.756). CONCLUSION: Those with SSc appear to have an increased risk for bronchiectasis. Since bronchiectasis was not more frequent in participants with a longer duration of SSc, we hypothesise that its development is not related to immunosuppression alone. Oesophageal dysmotility was almost universal in our population such that its effect on bronchiectasis development could not be concluded. A negative association between bronchiectasis and ILD reflects that bronchiectasis occurring alongside ILD was recorded as a separate entity.
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Bronchiectasis , Esophageal Motility Disorders , Lung Diseases, Interstitial , Scleroderma, Systemic , Humans , Cohort Studies , Prevalence , Australia/epidemiology , Scleroderma, Systemic/complications , Scleroderma, Systemic/epidemiology , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/epidemiology , Bronchiectasis/diagnostic imaging , Bronchiectasis/epidemiology , Esophageal Motility Disorders/complicationsABSTRACT
INTRODUCTION: Hyperkinetic dysarthria is characterized by atypical involuntary movements within the speech mechanism that may affect the respiratory, laryngeal, pharyngeal-oral, or velopharyngeal-nasal subsystems and may alter speech production. Although articulatory impairments are commonly considered in hyperkinetic dysarthria, speakers with hyperkinetic dysarthria may also present with changes in voice quality, pitch, and loudness. In approximately 70% of speakers with hyperkinetic dysarthria, these voice alterations are associated with tremor or dystonia. The purpose of this systematic review was to investigate the association between behavioral therapy for tremor or dystonia affecting voice in speakers with hyperkinetic dysarthria and improvement in the functional, perceptual, acoustical, aerodynamic, or endoscopic characteristics of voice. METHOD: MEDLINE (PubMed), Embase, PsycINFO, and ClinicalTrials.gov online databases were searched in August 2017, December 2018, and April 2020 for relevant studies. The searches provided 4,921 unique records, and six additional unique records were added from other sources. Twelve studies met the criteria for inclusion in the systematic review. Participants who received concurrent medical treatment were included in this review to ensure that the search was inclusive of all relevant studies and informative for typical clinical scenarios. RESULTS: The most commonly administered treatment ingredient was relaxation training, which was investigated in three of the four studies on tremor and three of the eight studies on dystonia. Of these six studies, only one used an experimental design and administered relaxation training as the only behavioral approach. This single-case experiment reported a significant reduction in participant ratings of tremor severity and interference with activities of daily living, although the speaking subscale reportedly did not improve and oral medications were administered concurrently. In two group studies that tested potential behavioral therapy targets, production of a low pitch improved acoustical measures for participants with essential tremor and improved auditory-perceptual judgments for participants with laryngeal dystonia. Behavioral therapy improved functional, acoustical, and aerodynamic outcomes in participants with laryngeal dystonia who were also receiving botulinum toxin injections in a randomized cross-over study and a non-randomized controlled study. Because one study employed easy onset and breathing exercises, while the other employed loud voice exercises, the mechanism of action for improvement in voice associated with behavioral therapy requires further investigation. CONCLUSION: This systematic review describes the current evidence for treatment of tremor and dystonia affecting voice in speakers with hyperkinetic dysarthria and highlights the need for future research on behavioral therapy for these disorders.
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Behavior Therapy , Dysarthria , Dystonia , Tremor , Humans , Activities of Daily Living , Dysarthria/diagnosis , Dysarthria/etiology , Dysarthria/therapy , Dystonia/diagnosis , Dystonia/therapy , Tremor/diagnosis , Tremor/etiology , Tremor/therapyABSTRACT
OBJECTIVE: Dysphonia is a reduction in vocal quality that impacts communication and is often an early sign of a voice disorder. There is little information regarding the effects of auditory feedback control of loudness and pitch on voice quality. In this study, we used both loudness-shift and pitch-shift paradigms to study the relationship between auditory feedback control and vocal quality as measured by smoothed cepstral peak prominence (CPPS), which reflects the harmonicity of the voice signal. STUDY DESIGN: Experimental, mixed design. METHODS: We applied 200 ms loudness-shifts (± 0, 3, or 6 dB) and pitch-shifts (± 0, 50, and 100 cents) to auditory feedback during sustained vowel production in 25 healthy adults. We then measured CPPS before and after the loudness-shift or pitch-shift to investigate the effect of changes in auditory feedback on vocal harmonicity. RESULTS & CONCLUSIONS: Results showed that, on average, CPPS significantly decreased between the first half of the measured segment and the last half of the segment in the absence of auditory feedback shifts, suggesting that voice quality may be reduced across longer vowels over time. Upward and downward shifts in loudness auditory feedback caused a relative increase in CPPS, indicating an improvement in vocal harmonicity, even in cases when vocal intensity was reduced. Pitch alterations had inconsistent and minimal effects. We propose that there may be a control mechanism for voice quality that increases harmonicity of the voice signal to improve voice audibility (ie, ability to be heard) in the presence of unpredictable variability in voice intensity.
Subject(s)
Voice Quality , Voice , Adult , Humans , Feedback , Pitch Perception , PhonationABSTRACT
PURPOSE: The purpose of this study was to investigate how classically trained singers use their auditory feedback to control fundamental frequency (fo) during production of vocal vibrato. Two main questions were addressed: (1) Do singers produce reflexive foresponses to sudden perturbation of the fo of their auditory feedback during production of vibrato indicative of feedback control? (2) Do singers produce adaptive foresponses to repeated perturbation of the fo of their auditory feedback during production of vibrato indicative of feedback and feedforward control? In addition, one methodological question was addressed to determine if adaptive fo responses were more precisely assessed with or without an auditory cue for fo during the repeated fo perturbation paradigm. METHOD: Ten classically trained singers produced sustained vowels with vibrato while the fo and harmonics of their auditory feedback were suddenly perturbed by 100 cents to assess reflexive control or repeatedly perturbed by 100 cents to assess adaptive control. Half of the participants completed the repeated perturbation experiment with an auditory cue for fo, and the other half completed the experiment without an auditory cue for fo. Acoustical analyses measured changes in mean fo in response to the auditory feedback perturbations. RESULTS: On average, participants produced compensatory responses to both sudden and repeated perturbation of the fo of their auditory feedback. The magnitude of the responses to repeated perturbations was larger than the responses to sudden perturbations. Responses were also larger in the cued, repeated fo perturbation experiment than in the uncued, repeated fo perturbation experiment. CONCLUSIONS: These findings indicate that classically-trained singers use both feedforward and feedback mechanisms to control their average fo during production of vibrato. When compared to prior studies of singers producing a steady voice, the reflexive fo responses were larger in the current study, which may indicate that the feedback control system is engaged more during production of vibrato.
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Singing , Voice , Humans , Speech Acoustics , Acoustics , Feedback, SensoryABSTRACT
Background: Previous studies have demonstrated abnormal white matter (WM) microstructure in recreational cannabis consumers; however, the long-term impact of medical cannabis (MC) use on WM coherence is unknown. Accordingly, this study assessed the longitudinal impact of MC treatment on WM coherence. Given results from preclinical studies, we hypothesized that MC treatment would be associated with increased fractional anisotropy (FA) and reduced mean diffusivity (MD). Methods: As part of a larger, longitudinal investigation, patients interested in treating at least one medical condition with commercially available MC products of their choosing were assessed before initiating MC use (baseline n=37; female=25, male=12) and following three (n=31) and six (n=22) months of treatment. WM coherence was assessed via diffusion tensor imaging for bilateral regions of interest including the genu of the corpus callosum, anterior limb of the internal capsule, external capsule, and anterior corona radiata, as well as an occipital control region not expected to change over time. Results: In MC patients, FA values significantly increased bilaterally in several callosal regions relative to baseline following both 3 and 6 months of treatment; MD values significantly decreased in all callosal regions but only following 6 months of treatment. No significant changes in WM coherence were observed in the control region or in a pilot sample of treatment-as-usual patients (baseline n=14), suggesting that increased WM coherence observed in MC patients may be attributed to MC treatment as opposed to confounding factors. Interestingly, significant reductions in MD values correlated with higher cannabidiol (CBD) exposure but not Δ-9-tetrahydrocannabinol exposure. Conclusions: Overall, MC treatment was associated with increased WM coherence, which contrasts with prior research examining recreational cannabis consumers, likely related to inherent differences between recreational consumers and MC patients (e.g., product choice, age of onset). In addition, increased CBD exposure was associated with reduced MD following 6 months of treatment, extending evidence from preclinical research indicating that CBD may be neuroprotective against demyelination. However, additional research is needed to elucidate the clinical efficacy of MC treatment and the risks and benefits of long-term MC use.
Subject(s)
Cannabis , Medical Marijuana , White Matter , Humans , Female , Male , Medical Marijuana/pharmacology , Cannabis/adverse effects , White Matter/diagnostic imaging , Diffusion Tensor ImagingABSTRACT
BACKGROUND: Evidence suggests cannabidiol (CBD) has anxiolytic properties, indicating potential for novel treatment strategies. However, few clinical trials of CBD-based products have been conducted, and none thus far have examined the impact of these products on cognition. METHODS: For the open-label stage of clinical trial NCT02548559, autoregressive linear modeling assessed efficacy and tolerability of four-weeks of 1 mL t.i.d. treatment with a full-spectrum, high-CBD sublingual solution (9.97 mg/mL CBD, 0.23 mg/mL Δ-9-tetrahydrocannabinol) in 14 outpatients with moderate-to-severe anxiety, defined as ≥16 on the Beck Anxiety Inventory (BAI) or ≥11 on the Overall Anxiety Severity and Impairment Scale (OASIS). RESULTS: Findings suggest significant improvement on primary outcomes measuring anxiety and secondary outcomes assessing mood, sleep, quality of life, and cognition (specifically executive function) following treatment. Anxiety is significantly reduced at week 4 relative to baseline (BAI: 95% CI = [-21.03, -11.40], p < 0.001, OASIS: 95% CI = [-9.79, -6.07], p < 0.001). Clinically significant treatment response (≥15% symptom reduction) is achieved and maintained as early as week 1 in most patients (BAI = 78.6%, OASIS = 92.7%); cumulative frequency of treatment responders reached 100% by week 3. The study drug is well-tolerated, with high adherence/patient retention and no reported intoxication or serious adverse events. Minor side effects, including sleepiness/fatigue, increased energy, and dry mouth are infrequently endorsed. CONCLUSIONS: Results provide preliminary evidence supporting efficacy and tolerability of a full-spectrum, high-CBD product for anxiety. Patients quickly achieve and maintain symptom reduction with few side effects. A definitive assessment of the impact of this novel treatment on clinical symptoms and cognition will be ascertained in the ongoing double-blind, placebo-controlled stage.
Cannabidiol (CBD) is a compound found within the Cannabis sativa plant. Previous studies suggest CBD may reduce anxiety. In this clinical trial, 14 patients with anxiety were treated for four-weeks with a cannabis-derived study product with high levels of CBD, administered under their tongue 3 times each day. All patients knew that they were being given CBD. Following four weeks of treatment, patients reported reduced anxiety as well as improvements in mood, sleep, quality of life, and measures reflecting their self-control and ability to think flexibly. Patients did not experience any serious negative effects during the trial. The impact of this product is now being evaluated in more patients with anxiety.
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Auditory feedback control of fundamental frequency (fo) is modulated in a task-dependent manner. When voice pitch auditory feedback perturbations are applied in sentence versus sustained-vowel production, larger and faster vocal fo responses are measured in sentence production. This task-dependency reflects the scaling of auditory targets for pitch for the precision required in each speech task. When the range for the pitch auditory target is scaled down for precision (as in the sentence-production task), a greater degree of mismatch is detected from the feedback perturbation and a larger vocal response is measured. The purpose of this study was to determine whether auditory feedback control of vocal intensity is also modulated in a task-dependent manner similar to the control of vocal pitch. Twenty-five English speakers produced repetitions of a sentence and a sustained vowel while hearing their voice auditory feedback briefly perturbed in loudness (+/- 3 or 6 dB SPL, 200 ms duration). The resulting vocal intensity responses were measured, and response magnitudes were robustly larger in the sentence (mean: 1.96 dB) than vowel production (mean: 0.89 dB). Additionally, response magnitudes increased as a function of perturbation magnitude only in sentence production for downward perturbations but decreased in magnitude by perturbation magnitude for upward perturbations. Peak response latencies were robustly shorter in sentence (mean: 184.94 ms) than in vowel production (mean: 214.92 ms). Overall, these results support the hypothesis that auditory feedback control of pitch and loudness are modulated by task and that both pitch and loudness auditory targets are scaled for the precision required for the speaking task.
ABSTRACT
OBJECTIVE: Expanding access to legal cannabis has dovetailed with increased interest in medical cannabis (MC) use; however, there is a paucity of research examining MC use to alleviate menopause-related symptoms. This survey study assessed patterns of MC use in perimenopausal and postmenopausal individuals. METHODS: Participants (perimenopausal, n = 131; postmenopausal, n = 127) completed assessments of menopause-related symptomatology and cannabis use, including modes of use, type of use, and menopause-related symptoms addressed by MC use. RESULTS: Most participants reported current cannabis use (86.1%) and endorsed using MC for menopause-related symptoms (78.7%). The most common modes of use were smoking (84.3%) and edibles (78.3%), and the top menopause-related symptoms for MC use were sleep disturbance (67.4%) and mood/anxiety (46.1%). Relative to postmenopausal participants, perimenopausal participants reported significantly worse menopause-related symptomatology on the vasomotor and psychosocial subscales of the Menopause-Specific Quality of Life Questionnaire ( P s ≤ 0.04), including greater burden of anxiety ( P = 0.01) and hot flash ( P = 0.04) symptoms. In addition, perimenopausal participants reported higher incidence of depression ( P = 0.03) and anxiety diagnoses ( P < 0.01), as well as increased use of MC to treat menopause-related mood/anxiety symptoms relative to postmenopausal participants ( P = 0.01). CONCLUSIONS: Results suggest that many individuals are currently using MC as an adjunctive treatment for menopause-related symptoms, particularly sleep disturbance and mood/anxiety. Future research should examine the impact of different MC use characteristics (e.g., cannabinoid profiles) on the efficacy of MC use for menopause-related symptoms. Increased severity and prevalence of mood and anxiety symptoms in perimenopausal participants suggest promising targets for clinical trials of cannabinoid-based therapies.
Subject(s)
Cannabinoids , Medical Marijuana , Cannabinoids/therapeutic use , Female , Hot Flashes/drug therapy , Hot Flashes/epidemiology , Humans , Medical Marijuana/therapeutic use , Perimenopause/psychology , Postmenopause/psychology , Quality of Life , Surveys and QuestionnairesABSTRACT
PURPOSE: Although relatively precise control over the extent and rate of fundamental frequency (fo) modulation may be needed for optimal production of vibrato, the role of auditory feedback in controlling vibrato is not well understood. Previous studies altered the gain and timing of auditory feedback in singers producing vibrato and showed inconsistent effects on the extent and rate of fo modulation, which may have been related to small sample sizes or limited analyses. Therefore, the purpose of this study was to further investigate whether the gain or timing of auditory feedback impacts control of vibrato in a larger sample of speakers and with advanced statistical analyses. METHOD: Ten classically-trained singers produced sustained vowels with vibrato while their auditory feedback was masked with pink noise or multi-talker babble to reduce the gain of their auditory feedback and while their auditory feedback was delayed by about 200 or 300 milliseconds to alter the timing of their auditory feedback. Acoustical analyses measured changes in the extent and rate of fo modulation in the masked and delayed trials relative to control trials. Bayesian modeling was used to analyze the effects of noise-masked, babble-masked, and delayed auditory feedback on the extent and rate of fo modulation. RESULTS: There was compelling evidence that noise masking increased the extent of fo modulation, and babble masking increased the variability in the rate of fo modulation (ie, jitter of fo modulation). Masked auditory feedback did not affect the average rate of fo modulation. Delayed auditory feedback did not affect the extent, rate, or jitter of fo modulation. CONCLUSIONS: The current study demonstrated that reducing the gain of the auditory feedback with noise masking increased the extent of fo modulation but did not affect the average rate of fo modulation in classically-trained singers producing vibrato. Reducing the gain of the auditory feedback with babble masking and altering the timing of auditory feedback with imposed delays did not affect the average extent or rate of fo modulation. However, babble masking increased the jitter of fo modulation rate, which suggests that modulated auditory feedback may affect the periodicity of fo modulation from one modulation cycle to the next. These findings clarify the role of auditory feedback in controlling vibrato and may inform the current reflex-resonance models of vibrato.