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Accurate pairing of amino acids and tRNAs is a prerequisite for faithful translation of genetic information during protein biosynthesis. Here we present the effects of proteome-wide mistranslation of isoleucine (Ile) by canonical valine (Val) or non-proteinogenic norvaline (Nva) in a genetically engineered Escherichia coli strain with an editing-defective isoleucyl-tRNA synthetase (IleRS). Editing-defective IleRS efficiently mischarges both Val and Nva to tRNAIle and impairs the translational accuracy of Ile decoding. When mistranslation was induced by the addition of Val or Nva to the growth medium, an Ile-to-Val or Ile-to-Nva substitution of up to 20 % was measured by high-resolution mass spectrometry. This mistranslation level impaired bacterial growth, promoted the SOS response and filamentation during stationary phase, caused global proteome dysregulation and upregulation of the cellular apparatus for maintaining proteostasis, including the major chaperones (GroES/EL, DnaK/DnaJ/GrpE and HtpG), the disaggregase ClpB and the proteases (Lon, HslV/HslU, ClpA, ClpS). The most important consequence of mistranslation appears to be non-specific protein aggregation, which is effectively counteracted by the disaggregase ClpB. Our data show that E. coli can sustain high isoleucine mistranslation levels and remain viable despite excessive protein aggregation and severely impaired translational fidelity. However, we show that inaccurate translation lowers bacterial resilience to heat stress and decreases bacterial survival at elevated temperatures.
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Escherichia coli , Resiliencia Psicológica , Escherichia coli/genética , Escherichia coli/metabolismo , Isoleucina , Proteoma/metabolismo , Agregado de Proteínas , Isoleucina-ARNt Ligasa/química , Isoleucina-ARNt Ligasa/genética , Isoleucina-ARNt Ligasa/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismoRESUMEN
Background: Many autistic children experience motor skill deficits which can impact other areas of functioning, and research on therapeutic interventions for motor skills in autism is in a preliminary stage. Music-based therapies have been used extensively to address motor skills in non-autistic populations. Though a handful of studies exist on the effects of music-based therapies for movement in autistic children, none have investigated the possibility of administering sessions via telehealth. This mixed-methods pilot study investigated whether nine Neurologic Music Therapy (NMT)® sessions via telehealth would improve motor and attention skills in autistic children. Methods: Five autistic children between five and 10 years of age participated in the study, with support from their caregivers. Motor skills were assessed using the Bruininks-Oseretsky Test of Motor Proficiency second edition, short form (BOT-2 SF), and a selective attention and sustained attention task were taken from the Test of Everyday Attention for Children, Second Edition (TEA-Ch2). Caregivers and the two neurologic music therapists involved in the study provided qualitative input about the perceived effectiveness of telehealth NMT for the children involved. Their responses were analyzed using qualitative content analysis. Caregivers also filled out a Sensory Profile 2 assessment prior to the onset of sessions so that each child's sensory profile could be compared to their motor and attention results. Results: Statistically significant improvements in motor skills were observed between pre-test assessment and a two-week follow-up assessment. Results from attention test scores were not significant. Caregivers and neurologic music therapists generally perceived sessions positively and noted the importance of having caregivers actively involved. When compared with individual progress on the BOT-2 SF assessment, sensory profile results revealed that children with fewer sensory sensitivities tended to improve the most on motor skills. The improvements in motor skills and positive caregiver and therapist views of telehealth indicate that NMT motor interventions administered via telehealth are a promising avenue of therapeutic support for movement skill development in autistic children.
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Developmental coordination disorder (DCD) remains largely underdiagnosed and masked by other co-occurring conditions. The aim of this study was to (1) provide the first review of research regarding auditory-motor timing and synchronization abilities in children with DCD and (2) examine whether reduced motor performance may be associated with difficulties in auditory perceptual timing. The scoping review was carried out across five major databases (MEDLINE, Embase, PsycINFO, CINAHL, and Scopus) in accordance with the PRISMA-ScR guidelines. Studies were screened by two independent reviewers against the inclusion criteria, without publication date restrictions. From an initial return of 1673 records, 16 articles were included in the final review and synthesized based on the timing modality studied (i.e., auditory-perceptual, motor, or auditory-motor). Results suggest that children with DCD have difficulties with rhythmic movements both with and without external auditory cues and further indicate that variability in and slowness of motor response are key characteristics of DCD, regardless of the experimental task. Importantly, our review highlights a significant gap in the literature regarding auditory perceptual abilities in DCD. In addition to testing auditory perception, future studies should compare the performance of children with DCD on paced and unpaced tasks to determine whether auditory stimuli contribute to a more or less stable performance. This knowledge may inform future therapeutic interventions.
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Attention-deficit/hyperactivity disorder (ADHD) and developmental coordination disorder (DCD) co-occur in approximately 50% of cases. This study aimed to characterize the behavioral, cognitive, and neurobiological profiles of co-occurring ADHD and DCD diagnoses by mapping, synthesizing, and providing a critical appraisal of the existing literature. A systematic search was conducted across four databases (MEDLINE, PsycINFO, Embase, and Scopus) to identify studies comparing a coexisting ADHD+DCD diagnosis to ADHD and DCD alone. From 2353 screened articles, 15 behavioral and 10 neuroimaging studies were included. Collectively, these studies suggest that the comorbid ADHD+DCD presentation constitutes a more severe phenotype characterized by neurocognitive differences associated with both conditions. Despite sharing some common neural features, our findings support the separate etiology hypothesis indicating that neural network alterations in individuals with ADHD+DCD represent a unique neural pattern rather than a sum of ADHD and DCD characteristics. Considering the heterogeneity inherent to both ADHD and DCD, future studies should involve rigorous and comprehensive assessment procedures to delineate how different subtypes of each diagnosis relate to distinct performance characteristics.
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INTRODUCTION: Papillary thyroid carcinomas (PTC) are the most common thyroid malignancies that are often diagnosed as microcarcinomas when the tumor is less than one centimetre in diameter. Currently, there are no valid stratification strategies that would reliably assess the risk of lateral neck metastases and optimize surgical treatment. MATERIALS AND METHODS: Aiming to find potential tissue biomarkers of metastatic potential, we conducted a cross-sectional proteomic pilot study on formalin-fixed paraffin-embedded tissues of metastatic (N = 10) and non-metastatic (N = 10) papillary thyroid microcarcinoma patients. Samples were analysed individually using liquid chromatography/mass spectrometry, and the differentially expressed proteins (DEP) were functionally annotated. RESULTS: We identified five overexpressed DEPs in the metastatic group (EPB41L2, CSE1L, GLIPR2, FGA and FGG) with a known association to tumour biology. Using bioinformatic-based tools, we found markedly different profiles of significantly enriched biological processes between the two groups. CONCLUSIONS: The identified DEPs might have a role as potential tissue biomarkers for PTC metastases. However, further prospective research is needed to confirm our findings.
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Carcinoma , Neoplasias de la Tiroides , Humanos , Proteómica , Estudios Transversales , Proyectos Piloto , Metástasis Linfática , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Cáncer Papilar Tiroideo/patología , BiomarcadoresRESUMEN
The use of telehealth within music therapy practice has increased through necessity in recent years. To contribute to the evolving evidence base, this current study on Telehealth Music Therapy (TMT) was undertaken to investigate the telehealth provision experiences of music therapists internationally. Participants completed an anonymous online cross-sectional survey covering demographics, clinical practice, telehealth provision, and telehealth perceptions. Descriptive and inferential statistics, in combination with thematic analysis, were used to analyze the data. A total of 572 music therapists from 29 countries experienced in providing TMT took part in this study. The results showed that the overall number of clinical hours (TMT and in-person hours combined) declined due to the pandemic. Participants also reported reduced perceived success rates in utilizing both live and pre-recorded music in TMT sessions when compared to in-person sessions. Although many music therapists rose to the challenges posed by the pandemic by incorporating TMT delivery modes, there was no clear agreement on whether TMT has more benefits than drawbacks; however, reported benefits included increased client access and caregiver involvement. Furthermore, a correlation analysis revealed moderate-to-strong positive associations between respondents who perceived TMT to have more benefits than drawbacks, proficiency at administering assessments over telehealth, and perceived likelihood of using telehealth in the future. Regarding the influence of primary theoretical orientation and work setting, respondents who selected music psychotherapy as a primary theoretical orientation had more experience providing TMT prior to the pandemic while those primarily working in private practice were most inclined to continue TMT services post-pandemic. Benefits and drawbacks are discussed and future recommendations for TMT are provided.
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Musicoterapia , Música , Telemedicina , Humanos , Estudios Transversales , Técnicos Medios en Salud , PandemiasRESUMEN
The present study examined spatial accuracy of mallet endpoints in a marimba performance context. Trained percussionists performed two- (i.e., Experiment 1) and four-mallet (i.e., Experiment 2) excerpts in three tempo conditions including slow, intermediate, and fast. Motion capture was utilized to gather data of upper-limb and mallet movements, as well as to compute velocities of the upper-limb joints. Mallet spatial accuracy was assessed by comparing mallet endpoints to a visual target positioned on the marimba. It was hypothesized that mallet spatial accuracy would be reduced as tempo condition increased, with effects on joint kinematics potentially revealing sensorimotor mechanisms underlying optimal sound production in marimba. Across both experiments, mallet accuracy was reduced as tempo condition increased. Interestingly, velocity variability in the elbows, wrists, and hands increased as mallet accuracy decreased. Such a pattern of effects suggested that sound production in marimba is suboptimal at fast relative to slow tempi. In addition, the velocity variability effects highlight the impact of motor planning mechanisms on sound production. Overall, the results shed new light on sensorimotor control in percussion which can be leveraged to enhance the training of percussionists.
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Música , Humanos , Fenómenos Biomecánicos , Movimiento , Mano , CodoRESUMEN
This cross-sectional survey investigated the transition of Neurologic Music Therapy (NMT) services from in-person (pre-COVID-19) to telehealth (since COVID-19) to (1) determine whether the use of an NMT paradigm contributes to the successful transition of therapy services to telehealth, (2) identify which NMT domains and techniques are transferable from in-person to telehealth, (3) identify whether there are differences in the transition of NMT services across different employment settings, and (4) evaluate the potential benefits and challenges of telehealth NMT. An online survey comprised of 49 closed and open-ended questions was distributed by the Academy of Neurologic Music Therapy to 2,778 NMT affiliates worldwide. The survey sought information on demographics, telehealth perceptions, technology, assessment, clinical practice, safety, and caregiver involvement. Quantitative and qualitative analyses were applied. Eighty-one participants answered the survey and the 69 who completed the survey in its entirety were included in the analysis. Results indicated that the frequency of NMT technique usage had no impact on the overall number of clinical hours retained over telehealth. Correlation analysis revealed an association between more frequent NMT usage and perceived likelihood of using telehealth in the future (i.e., once COVID-19 is no longer a major threat), as well as with fewer group sessions lost over telehealth. All NMT domains transferred to telehealth, although within the sensorimotor domain, fewer therapists implemented rhythmic auditory stimulation for telehealth sessions compared to in-person. Overall, NMTs had fewer hours for telehealth compared to in-person regardless of employment setting. Technological challenges were notable drawbacks, while major benefits included the ability to continue providing NMT when in-person sessions were not possible, increased accessibility for remote clients, and positive outcomes related to increased caregiver involvement. Based on the results, our recommendations for implementing telehealth in Neurologic Music Therapy include integrating telehealth into routine care, mitigating safety concerns, identifying those who could benefit most from remote delivery, involving caregivers, and developing/sharing resources for telehealth NMT.
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CONTEXT: Eighty-seven patients newly diagnosed with lung, breast, or gastrointestinal cancer and undergoing chemotherapy in the infusion suite of a large urban hospital in New York City. OBJECTIVE: Patients were enrolled in this study of music therapy's impact on resilience in coping with the impact of symptoms inclusive of symptom clustering. METHODS: Patients were randomly assigned to three arms: clinical instrumental improvisation or clinical vocal improvisation 43 subjects to instrumental improvisation or vocal improvisation and 44 subjects to control. All subjects received a Medical Music Psychotherapy Assessment including psychosocial information and music preferences, pre-/post-Resilience Scale, Hospital Anxiety and Depression Scale, Visual Analogue Scale/Faces Scale, and a pain-Color Analysis Scale. Interventions included 20-minute music therapy (MT) and two additional sessions. RESULTS: Significant increases in Resilience Scale in MT groups after treatment with instrumental and vocal MT interventions equally potent-reflect average changes of 3.4 and 4.83 (P = 0.625), respectively. Although Hospital Anxiety and Depression Scale scores showed little impact of MT on perceived anxiety/depression, a strong correlation is seen between vocal intervention and lower depression scores through Visual Analogue Scale-rendered postsessions. This yielded a significant decrease in pain levels immediately after MT, with the final session showing the most significant change in pain level. Resilience in enduring procedures is a necessary component of combating potential negative illness perception. CONCLUSION: Our study shows MT's facility to propel resilience in patients newly diagnosed with cancer, particularly when promoting and pairing adaptation toward coping through the expression of perceived negative effects of emotional and physiological symptoms.