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Introduction: Acquired communication impairments (ACIs) can significantly hinder the development and functioning of language and communication in children, impeding their social interactions and self-expression. Music therapy is emerging as a favourable practice in supporting children with ACIs; however, a deeper understanding of the clinical practices of music therapists with this population is required to advance service provision. Method: This study employed an online cross-sectional descriptive survey to investigate current approaches, clinical interventions, and outcome measures used by music therapists working with young children with ACIs to address language- and communication-oriented goals. Fifty-four music therapists across ten countries completed a 16-item online questionnaire. Descriptive statistics and conventional content analysis were used to analyse the data. Results: Respondents demonstrated a notable preference for humanistic and integrative approaches in their clinical practice. Among the diverse range of interventions employed by music therapists, song singing, vocal improvisation, and music and play emerged as the most effective techniques for supporting individuals with ACIs in achieving their communication goals. Additionally, collaborative endeavours with speech and language therapists were considered the most impactful approach to intervention. Respondents also sought alternative non-standardised evaluation methods, driven by a scarcity of suitable measures, to evaluate the effectiveness of their work. Discussion: There exists a high degree of heterogeneity in clinical practices amongst music therapists working with children with ACIs, reflecting diverse backgrounds and approaches. The absence of clear trends or dominant approaches emphasises the necessity for further research to establish evidence-based practices for this population. [ABSTRACT FROM AUTHOR]

The genome organization of woodpeckers has several distinctive features e.g., an uncommon accumulation of repetitive sequences, enlarged Z chromosomes, and atypical diploid numbers. Despite the large diversity of species, there is a paucity of detailed cytogenomic studies for this group and we thus aimed to rectify this. Genome organization patterns and hence evolutionary change in the microchromosome formation of four species (Colaptes campestris, Veniliornis spilogaster, Melanerpes candidus, and Picumnus nebulosus) was established through fluorescence in situ hybridization using bacterial artificial chromosomes originally derived from Gallus gallus and Taeniopygia guttata. Findings suggest that P. nebulosus (2n = 110), which was described for the first time, had the most basal karyotype among species of Picidae studied here, and probably arose as a result of fissions of avian ancestral macrochromosomes. We defined a new chromosomal number for V. spilogaster (2n = 88) and demonstrated microchromosomal rearrangements involving C. campestris plus a single, unique hitherto undescribed rearrangement in V. spilogaster. This comprised an inversion after a fusion involving the ancestral microchromosome 12 (homologous to chicken microchromosome 12). We also determined that the low diploid number of M. candidus is related to microchromosome fusions. Woodpeckers thus exhibit significantly rearranged karyotypes compared to the putative ancestral karyotype. [ABSTRACT FROM AUTHOR]

The Cuculiformes are a family of over 150 species that live in a range of habitats, such as forests, savannas, and deserts. Here, bacterial artificial chromosome (BAC) probes (75 from chicken and 14 from zebra finch macrochromosomes 1–10 +ZW and for microchromosomes 11–28 (except 16)) were used to investigate chromosome homologies between chicken and the squirrel cuckoo (Piaya cayana). In addition, repetitive DNA probes were applied to characterize the chromosome organization and to explore the role of these sequences in the karyotype evolution of P. cayana. We also applied BAC probes for chicken chromosome 17 and Z to the guira cuckoo (Guira guira) to test whether this species has an unusual Robertsonian translocation between a microchromosome and the Z chromosome, recently described in the smooth-billed ani (Crotophaga ani). Our results revealed extensive chromosome reorganization with inter- and intrachromosomal rearrangements in P. cayana, including a conspicuous chromosome size and heterochromatin polymorphism on chromosome pair 20. Furthermore, we confirmed that the Z-autosome Robertsonian translocation found in C. ani is also found in G. guira, not P. cayana. These findings suggest that this translocation occurred prior to the divergence between C. ani and G. guira, but after the divergence with P. cayana. [ABSTRACT FROM AUTHOR]

Birds (Aves) are the most speciose of terrestrial vertebrates, displaying Class-specific characteristics yet incredible external phenotypic diversity. Critical to agriculture and as model organisms, birds have adapted to many habitats. The only extant examples of dinosaurs, birds emerged ~150 mya and >10% are currently threatened with extinction. This review is a comprehensive overview of avian genome ("chromosomic") organization research based mostly on chromosome painting and BAC-based studies. We discuss traditional and contemporary tools for reliably generating chromosome-level assemblies and analyzing multiple species at a higher resolution and wider phylogenetic distance than previously possible. These results permit more detailed investigations into inter- and intrachromosomal rearrangements, providing unique insights into evolution and speciation mechanisms. The 'signature' avian karyotype likely arose ~250 mya and remained largely unchanged in most groups including extinct dinosaurs. Exceptions include Psittaciformes, Falconiformes, Caprimulgiformes, Cuculiformes, Suliformes, occasional Passeriformes, Ciconiiformes, and Pelecaniformes. The reasons for this remarkable conservation may be the greater diploid chromosome number generating variation (the driver of natural selection) through a greater possible combination of gametes and/or an increase in recombination rate. A deeper understanding of avian genomic structure permits the exploration of fundamental biological questions pertaining to the role of evolutionary breakpoint regions and homologous synteny blocks. [ABSTRACT FROM AUTHOR]

Swyer syndrome is where an individual has the karyotype of a typical male yet is phenotypically a female. The lack of a (functional) SRY gene located on the Y‐chromosome is implicated in some cases of the Swyer syndrome, although many Swyer individuals with an apparently fully functional SRY gene have also been documented. The present study undertook whole genome sequence analyses of eight cattle with suspected Swyer syndrome and compared their genome to that of both a control male and female. Sequence analyses coupled with female phenotypes confirmed that all eight individuals had the 60,XY sex reversal Swyer syndrome. Seven of the eight Swyer syndrome individuals had a deletion on the Y chromosome encompassing the SRY gene (i.e., SRY−). The eighth individual had no obvious mutation in the SRY gene (SRY+) or indeed in any reported gene associated with sex reversal in mammals; a necropsy was performed on this individual. No testicles were detected during the necropsy. Histological examination of the reproductive tract revealed an immature uterine body and horns with inactive glandular tissue of normal histological appearance; both gonads were elongated, a characteristic of most reported cases of Swyer in mammals. The flanking sequence of 11 single nucleotide polymorphisms within 10 kb of the SRY gene are provided to help diagnose some cases of Swyer syndrome. These single nucleotide polymorphisms will not, however, detect all cases of Swyer syndrome since, as evidenced from the present study (and other studies), some individuals with the Swyer condition still contain the SRY gene (i.e., SRY+). [ABSTRACT FROM AUTHOR]

Charadriidae comprise 142 valid species and the most recent checklist for the occurrence of this family in Brazil describes 11 species. There are few chromosomal studies in Charadriidae, most of them using a conventional approach. In Charadrius, only five species had their karyotypes described by classical cytogenetics, of which four have 2n = 76 (C. hiaticula, C. dubius, C. vociferou and C. collaris) and one 2n = 78 (C. alexandrinus alexandrinus). Among these species, only Charadrius collaris had the karyotype studied by chromosome painting, which allowed the identification of chromosomal homeologies with the karyotypes of Gallus gallus (GGA) and Burhinus oedicnemus (BOE). According to the literature, studies performed with BAC-FISH using probes from Gallus gallus and Taeniopygia guttata (TGU) libraries have shown interactions between macro and microchromosomes and micro inversions in chromosomes previously considered conserved. Other studies have shown the fusion of several microchromosomes, forming new macrochromosomes, leading to a decrease in the 2n of some species. The present study aims to deepen the chromosomal information in Charadrius collaris through the application of BAC-FISH with probes from the GGA and TGU libraries, in order to investigate possible rearrangements within the apparently conserved karyotype of this species, and thus better clarify the evolutionary history of the species. Charadrius collaris presented 2n = 76 and fundamental number (FN) equal to 94. Comparative mapping of BAC probes from GGA and TGU in Charadrius collaris revealed hybridization signals from 26 macrochromosome probes. Probes from microchromosomes 9 to 28 of GGA were also used and revealed 31 hybridization signals. The karyotype is well conserved, but it contains a paracentric and a pericentric inversion on the CCO1 chromosome, a paracentric and a pericentric inversion on the CCO4 and the separation of GGA4 into CCO4 and CCO8, demonstrating that the BAC-FISH approach allows for greater data resolution. More studies are needed to improve the understanding of chromosomal evolution within the order Charadriiformes and thus clarify whether these characteristics demonstrated here are specific traits for Charadrius collaris or if other species share these characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Dinosaurs have been in scientific and popular culture since early fossil discoveries, but increased interest, particularly in their genomes, is expanding. Birds are reptiles, specifically theropod dinosaurs, meaning that if we compare the genomes of related reptile relations, we can get an idea of what the extinct dinosaur genomes looked like. In all animals/plants/fungi, we think of genome organization in terms of chromosomes. Genes sit on chromosomes and each cell of each individual of each species has its own unique organization. Every gene is in exactly the same spot on each chromosome, organized like continents and islands, with the genes as the cities/towns/villages. All reptiles apart from crocodilians have both big and small chromosomes in their genomes but birds particularly so, like the Philippines or Polynesia. Birds have ~80 chromosomes (far more than most organisms) and this is very consistent in most species. Recent studies suggest that this pattern was probably established ~255 million years ago as it is also mostly present in some turtles. In other words, most dinosaurs probably had chromosomes (genome organization) like chickens or emus. In this paper, we present ideas of how this may have contributed to dinosaurs being so diverse in appearance and function. Reptiles known as dinosaurs pervade scientific and popular culture, while interest in their genomics has increased since the 1990s. Birds (part of the crown group Reptilia) are living theropod dinosaurs. Chromosome-level genome assemblies cannot be made from long-extinct biological material, but dinosaur genome organization can be inferred through comparative genomics of related extant species. Most reptiles apart from crocodilians have both macro- and microchromosomes; comparative genomics involving molecular cytogenetics and bioinformatics has established chromosomal relationships between many species. The capacity of dinosaurs to survive multiple extinction events is now well established, and birds now have more species in comparison with any other terrestrial vertebrate. This may be due, in part, to their karyotypic features, including a distinctive karyotype of around n = 40 (~10 macro and 30 microchromosomes). Similarity in genome organization in distantly related species suggests that the common avian ancestor had a similar karyotype to e.g., the chicken/emu/zebra finch. The close karyotypic similarity to the soft-shelled turtle (n = 33) suggests that this basic pattern was mostly established before the Testudine–Archosaur divergence, ~255 MYA. That is, dinosaurs most likely had similar karyotypes and their extensive phenotypic variation may have been mediated by increased random chromosome segregation and genetic recombination, which is inherently higher in karyotypes with more and smaller chromosomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Numerous tiny (micro)chromosomes are a characteristic feature associated with birds, being found in smaller numbers in other organisms and absent in many, such as mammals. Although microchromosomes constitute a large portion of the genome in birds, data on them pertaining to comparative studies between birds are still scarce. This is the case in shorebirds (Charadriiformes), a group with a great variety of species. The aim of this study was to provide insight regarding the evolution of the microchromosomes of three species of shorebirds—the red knot (Calidris canutus), the wattled jacana (Jacana jacana), and the southern lapwing (Vanellus chilensis). The experiments are referred to as cross-species fluorescence in situ hybridization (FISH) mapping using probes called bacterial artificial chromosomes (or BACs), two (one labelled in red and one labelled in green) for every microchromosome. The results thus appear as the microchrochromosome with one green and one red end, revealing different patterns of organization over evolutionary time. In the red knot, they fuse together, but in the southern lapwing, they hardly change. We also described a new chromosome number for the red knot (92 in total). In conclusion, this study contributed to the understanding of microchromosomes organization and evolution of three shorebird species. Microchromosomes, once considered unimportant elements of the genome, represent fundamental building blocks of bird karyotypes. Shorebirds (Charadriiformes) comprise a wide variety of approximately 390 species and are considered a valuable model group for biological studies. Despite this variety, cytogenetic analysis is still very scarce in this bird order. Thus, the aim of this study was to provide insight into the Charadriiformes karyotype, with emphasis on microchromosome evolution in three species of shorebirds—Calidris canutus, Jacana jacana, and Vanellus chilensis—combining classical and molecular approaches. Cross-species FISH mapping applied two BAC probes for each microchromosome, GGA10–28 (except GGA16). The experiments revealed different patterns of microchromosome organization in the species investigated. Hence, while in C. canutus, we found two microchromosomes involved in chromosome fusions, they were present as single pairs in V. chilensis. We also described a new chromosome number for C. canutus (2n = 92). Hence, this study contributed to the understanding of genome organization and evolution of three shorebird species. [ABSTRACT FROM AUTHOR]

A genetic mutation involving only a minimal number of repeated CGG segments of the X chromosome may cause mild symptoms of fragile X syndrome. The CGG segment is a genetic building block involved in programming protein synthesis. Researchers presented the medical histories of 3 boys with a minimal number of CGG repeats and mild symptoms of fragile X syndrome. All of the patients had limited attention spans, were shy, and had some physical features characteristic of fragile X syndrome including long ears, high forehead, double jointed fingers, and enlarged testicles. The two older patients struggled with schoolwork and scored low on intelligence tests but were not considered mentally retarded. The number of CGG repeats ranged from 130 to 210 with protein synthesis associated with this gene ranging from 50% to 90% of normal., There is a broad spectrum of clinical involvement in both boys and girls affected by fragile X syndrome. Although this disorder is best known as the most common inherited cause [...]

* Introduction.--Fragile X syndrome is the most commonly known inherited form of mental retardation. The intellectual abilities range from a normal IQ with learning disabilities to severe mental retardation. In males, there is a tendency for IQ decline in childhood. The purpose of this study was to correlate variations of the molecular cytosine guanine guanine (CGG) amplification in the fragile X mental retardation-1 (FMR-1) gene with the clinical findings, including IQ and physical features. Methods.--Full-scale IQ and cytogenetic results in 116 individuals with the FMR-1 mutation were studied. The IQ testing was performed with age-appropriate standardized tests. Physical features were summarized in a physical index score for each patient. The FMR-1 results were determined with the OX1.9 probe and the following system was used: P1 indicates premutation; P2, large premutation to small full mutation; P3, full mutation; and P4, mosaic. Results/Conclusions.--The findings showed that those females with a small insert in the P1 range had a significantly higher IQ than other heterozygotes (P2, P3, and P4 categories). P4 males had a significantly higher IQ than P2 or P3 males. In cross-sectional age comparisons, the slope of the IQ decline was greater in P2 males than in P4 or P3 males. (AJDC. 1993;147:723-726), The variation in size of the gene mutation causing fragile X syndrome can cause varying degrees of disability. Fragile X syndrome is a common cause of mental retardation. Researchers examined correlations between the variations in the size of a nucleotide sequence in the fragile X syndrome gene and patients' physical features and IQ scores.Psychological and IQ tests were administered to 62 males and 61 females with fragile X syndrome. Also, each patient was given a physical feature score based on 10 attributes commonly associated with fragile X syndrome. Then cytogenetic analysis was performed for each patient to determine the length of the nucleotide sequence. In the males studied, the physical feature scores showed no correlation with the size of the nucleotide sequence. But in the female group, those with the smallest nucleotide sequence had the fewest fragile X syndrome physical attributes. Females with the smallest sequence also had the highest IQs of all females studied. IQ was found to be highest in males with a mosaic genotype, or a combination of sequence sizes.

The fragile X syndrome, a common X-linked form of mental retardation and autism, affects females as well as males. previous work has shown that approximately 35% of heterozygotes (women who carry the fragile X gene) demonstrate cognitive impairment. Thirty-two girls, 18 years or younger, who demonstrate the fragile X chromosome were evaluated and compared with 19 sisters who do not demonstrate the fragile X chromosome. Evaluations included a physical examination, behavioral assessment, and intelligence testing. Significant differences (in intellectual, behavioral, and physical features) were seen between the two groups. Twenty-five percent of fragile X-positive girls had an IQ in the mentally retarded range (IQ < 70) and 28% had an IQ in the borderline range (70 to 84). Prominent ears, shyness, and poor eye contact were significant findings in fragile X-positive girls compare with fragile X-negative girls. Thirty-one percent of the fragile X-positive girls had significant attentional difficulties and most of these girls were successfully treated with stimulant medication. The majority of fragile X-positive girls in this study demonstrated significant behavioral and developmental problems which required identification and appropriate treatment. Pediatricians and health care providers should be aware of the frequency and manner with which fragile X affects females in order to initiate cytogenetic studies and treatment when indicated. Pediatrics 1992;89:395-400; fragile X syndrome girls, mental retardation, learning disabilities, attention deficit hyper-activity disorder, shyness, treatment.

The article discusses the significance of music therapy in the realm of psychology, emphasizing its role in promoting well-being, enhancing mental health, and aiding in the recovery of individuals with acquired brain injuries and dementia. Topics include the integration of music therapy into various clinical practices, the impact of music therapy on mental health care, the role of music therapy in acquired brain injury rehabilitation, and its effectiveness in dementia care.

The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro‐evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post‐meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge. [ABSTRACT FROM AUTHOR]

Squamate reptile chromosome 2 (SR2) is thought to be an important remnant of an ancestral amniote super-sex chromosome, but a recent study showed that the Siamese cobra W sex chromosome is also a part of this larger ancestral chromosome. To confirm the existence of an ancestral amniote super-sex chromosome and understand the mechanisms of amniote sex chromosome evolution, chromosome maps of two snake species [Russell's viper: Daboia russelii (DRU) and the common tiger snake: Notechis scutatus (NSC)] were constructed using bacterial artificial chromosomes (BACs) derived from chicken and zebra finch libraries containing amniote sex chromosomal linkages. Sixteen BACs were mapped on the W sex chromosome of DRU and/or NSC, suggesting that these BACs contained a common genomic region shared with the W sex chromosome of these snakes. Two of the sixteen BACs were co-localized to DRU2 and NSC2, corresponding to SR2. Prediction of genomic content from all BACs mapped on snake W sex chromosomes revealed a large proportion of long interspersed nuclear element (LINE) and short interspersed nuclear element (SINE) retrotransposons. These results led us to predict that amplification of LINE and SINE may have occurred on snake W chromosomes during evolution. Genome compartmentalization, such as transposon amplification, might be the key factor influencing chromosome structure and differentiation. Multiple sequence alignments of all BACs mapped on snake W sex chromosomes did not reveal common sequences. Our findings indicate that the SR2 and snake W sex chromosomes may have been part of a larger ancestral amniote super-sex chromosome, and support the view of sex chromosome evolution as a colorful myriad of situations and trajectories in which many diverse processes are in action. [ABSTRACT FROM AUTHOR]

Myiopsitta monachus is a small Neotropical parrot (Psittaciformes: Arini Tribe) from subtropical and temperate regions of South America. It has a diploid chromosome number 2 n = 48, different from other members of the Arini Tribe that have usually 70 chromosomes. The species has the lowest 2 n within the Arini Tribe. In this study, we combined comparative chromosome painting with probes generated from chromosomes of Gallus gallus and Leucopternis albicollis , and FISH with bacterial artificial chromosomes (BACs) selected from the genome library of G. gallus with the aim to shed light on the dynamics of genome reorganization in M. monachus in the phylogenetic context. The homology maps showed a great number of fissions in macrochromosomes, and many fusions between microchromosomes and fragments of macrochromosomes. Our phylogenetic analysis by Maximum Parsimony agree with molecular data, placing M. monachus in a basal position within the Arini Tribe, together with Amazona aestiva (short tailed species). In M. monachus many chromosome rearrangements were found to represent autopomorphic characters, indicating that after this species split as an independent branch, an intensive karyotype reorganization took place. In addition, our results show that M. monachus probes generated by flow cytometry provide novel cytogenetic tools for the detection of avian chromosome rearrangements, since this species presents breakpoints that have not been described in other species. [ABSTRACT FROM AUTHOR]

The structure and organization of a species genome at a karyotypic level, and in interphase nuclei, have broad functional significance. Although regular sized chromosomes are studied extensively in this regard, microchromosomes, which are present in many terrestrial vertebrates, remain poorly explored. Birds have more cytologically indistinguishable microchromosomes (~ 30 pairs) than other vertebrates; however, the degree to which genome organization patterns at a karyotypic and interphase level differ between species is unknown. In species where microchromosomes have fused to other chromosomes, they retain genomic features such as gene density and GC content; however, the extent to which they retain a central nuclear position has not been investigated. In studying 22 avian species from 10 orders, we established that, other than in species where microchromosomal fusion is obvious (Falconiformes and Psittaciformes), there was no evidence of microchromosomal rearrangement, suggesting an evolutionarily stable avian genome (karyotypic) organization. Moreover, in species where microchromosomal fusion has occurred, they retain a central nuclear location, suggesting that the nuclear position of microchromosomes is a function of their genomic features rather than their physical size. [ABSTRACT FROM AUTHOR]

Zolpidem has been used with mixed effects in patients presenting with Prolonged Disorders of Consciousness (PDOC). This single case report describes an interdisciplinary team (IDT) protocol combined with Zolpidem 10 mg in a single case of a patient in PDOC. 'Emily', a 44-year-old lady was admitted to a rehabilitation unit in Ireland one year post onset of subarachnoid haemorrhage. Standardized assessments diagnosed her as being in a minimally conscious state (MCS). An IDT protocol was devised to stimulate and record responses to sensory and pharmacological stimuli. The protocol was applied pre and post administration of Zolpidem 10 mg. Across standardized measures of awareness, improved results post-Zolpidem were recorded. Spontaneous, appropriate verbalization was the most significant change observed 30 min after administration of Zolpidem 10 mg. This ceased after approximately 2 h with Emily reverting to a non-verbal state. The combined effect of Zolpidem and the IDT protocol applied over an eight-week period resulted in durable functional and communicative gains for Emily, inferring neuro-plasticity. This report highlights the impact of a combined approach of intensive IDT intervention in conjunction with Zolpidem. The use of Zolpidem with this patient population warrants further investigation. [ABSTRACT FROM AUTHOR]

Collaborative governance has given rise to decision-making methodologies promoting democracy, inclusivity and transparency. This is exemplified by deliberative priority-setting (DPS) that blends cost-effectiveness analysis with stakeholder deliberation. Little is known however, about the facilitation challenges when ‘technical’ and ‘social’ elements are combined in a methodology. This paper investigates the facilitation challenges of implementing a DPS project within the English National Health Service (NHS). Our study examines the relationship between facilitation and the effectiveness of DPS processes, highlighting the importance of knowledge management as facilitators seek to translate technical information, to enhance the deliberative experience and promote legitimate decisions. [ABSTRACT FROM AUTHOR]

Genomic organisation of extinct lineages can be inferred from extant chromosome-level genome assemblies. Here, we apply bioinformatic and molecular cytogenetic approaches to determine the genomic structure of the diapsid common ancestor. We then infer the events that likely occurred along this lineage from theropod dinosaurs through to modern birds. Our results suggest that most elements of a typical 'avian-like' karyotype (40 chromosome pairs, including 30 microchromosomes) were in place before the divergence of turtles from birds ~255 mya. This genome organisation therefore predates the emergence of early dinosaurs and pterosaurs and the evolution of flight. Remaining largely unchanged interchromosomally through the dinosaur-theropod route that led to modern birds, intrachromosomal changes nonetheless reveal evolutionary breakpoint regions enriched for genes with ontology terms related to chromatin organisation and transcription. This genomic structure therefore appears highly stable yet contributes to a large degree of phenotypic diversity, as well as underpinning adaptive responses to major environmental disruptions via intrachromosomal repatterning. [ABSTRACT FROM AUTHOR]

Selective activation of dopamine D1 receptors (D1Rs) has been pursued for 40 years as a therapeutic strategy for neurologic and psychiatric diseases due to the fundamental role of D1Rs in motor function, reward processing, and cognition. All known D1R-selective agonists are catechols, which are rapidly metabolized and desensitize the D1R after prolonged exposure, reducing agonist response. As such, drug-like selective D1R agonists have remained elusive. Here we report a novel series of selective, potent non-catechol D1R agonists with promising in vivo pharmacokinetic properties. These ligands stimulate adenylyl cyclase signaling and are efficacious in a rodent model of Parkinson's disease after oral administration. They exhibit distinct binding to the D1R orthosteric site and a novel functional profile including minimal receptor desensitization, reduced recruitment of β-arrestin, and sustained in vivo efficacy. These results reveal a novel class of D1 agonists with favorable drug-like properties, and define the molecular basis for catechol-specific recruitment of β-arrestin to D1Rs. [ABSTRACT FROM AUTHOR]

We are delighted here in Ireland to share with you an innovative, integrated approach to providing and improving access to Creative Arts Therapy for children and adults with acquired neurological conditions. Using the National Rehabilitation Hospital's (NRH) Quality Improvement (QI) framework we have established the Creative Arts Therapy (CAT) Service providing access to and integration of music and art therapy to specialist rehabilitation. Creative arts therapies are evidence-based professions using prescribed art and music-based methods to accomplish individualised clinical goals within a therapeutic relationship. Here at NRH we endeavour to integrate CAT within the existing interdisciplinary team (IDT) approach to support patients in achieving rehabilitation goals. CAT clinical interventions are designed to effect positive changes in the psychological, communication, physical, cognitive, or social functioning of individuals in a rehabilitation setting. Feedback from patients, their families and members of the IDT coupled with analysis of clinical data clearly identified the need and demand for an integrated, specialist CAT service. Project Aim: The aim is for all NRH patients to have access to CAT as part of their comprehensive IDT programme of rehabilitation to support their individual rehabilitation needs and goals. Project Implementation: Following a series of presentations, guidance documentation for the IDT and patients, and consultation with patients, families and other professionals a person-centred approach, where patients were empowered to engage in creating CAT interventions that met their needs, was established. Opportunities to improve patient experience of CAT were identified, for example small groups, joint IDT sessions to promote access and communication, and assessments to enhance IDT intervention. Staffing resources to support the initiative were put in place. Outcomes: CAT therapists monitored and evaluated the service using a series of qualitative and quantitative measures, which were completed by patients, families and members of the IDT. Results show that 100% of patients 'strongly agreed' that receiving CAT intervention enhanced their rehabilitation and their patient experience at the NRH. 100% of professional IDT members 'strongly agreed' that CAT contributed to the success of IDT rehabilitation outcomes. Data also indicated an extensive increase in access for patients to creative arts therapies. 66% of all NRH admissions were referred to the service during the project. A permanent CAT service has now been established at the NRH as a result of the project, which is the only hospital based creative arts therapy service in Ireland. The project has also resulted in the permanent employment of an art therapist and an additional music therapist to allow for continued access for patients. Our model has been adopted and adapted by other post-acute and home and community-based healthcare settings in Ireland. The service also received very positive feedback from CARF (Commission on Accreditation of Rehabilitation Facilities) with surveyors stating that 'The creative use of the CAT service in all programmes to enhance the functional skills of persons served is innovative and demonstrates the person-centred philosophy of care. It is a true interdisciplinary treatment modality'.". [ABSTRACT FROM AUTHOR]

To examine the concurrent validity of the MATADOC with the criterion standard Coma Recovery Scale (CRS-R) for diagnostic outcomes of awareness To explore the function of comparable MATADOC items and CRS-R function scales across similar domains (e.g. auditory, visual). Prospective multisite cohort study collected concurrent MATADOC and CRS-R data using repeated measures with patients with disorders of consciousness (DOC). Raters were blinded. Three specialist inpatient rehabilitation units for DOC (US, UK, Ireland). 74 adults with prolonged DOC stemming from acquired brain injury recruited using convenience sampling. The MATADOC protocol elicits behavioral responsiveness using live music in five tasks during four clinical contacts of 15-30 minutes duration (60-120 mins total). Observed behavioral responses are rated across motor, communication, arousal, visual and auditory domains using a 14-item measure. Pre and post observation period records spontaneous behaviors. The CRS-R protocol delivers tasks in the motor, visual, auditory and communication domains in clinical contacts of 15-30 minutes duration (60 – 120 minutes in total for 4 contacts). Observed responses are rated in six function scales. Two measures of awareness: MATADOC and CRS-R. Fair (Cohen's kappa or "k"=0.238, p=.006) ranging to moderate (k=0.419, p<.001) significant agreement found between CRS-R and MATADOC diagnostic outcomes for each contact, with significant correlations between scores (mean Pearson = 0.721, p<.001). Agreement increased over repeated contacts. Moderate agreement found for overall diagnostic outcomes ranging across VS, MCS and EMCS (k=0.397, p<.001). Moderate significant agreement found between measures for motor scores (k=.556, p<.001) and visual outcomes (mean k= 0.326). No agreement was found for item outcomes assessing auditory responsiveness. The MATADOC complements the CRS-R in treatment planning for DOC. MATADOC measures of auditory responsiveness suggest musical stimuli may elicit more complex behaviors than non-music protocols. The MATADOC rates complexity of auditory localization as MCS in line with recent recommendations which may explain diagnostic outcome differences with CRS-R outcomes. None. [ABSTRACT FROM AUTHOR]

Background: Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods: A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results: Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events (SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [, ]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions: Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke therefore a definitive study using this trial design is not supported. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation. Trial Registration: ISRCTN.com [ABSTRACT FROM AUTHOR]

Background: The availability of multiple avian genome sequence assemblies greatly improves our ability to define overall genome organization and reconstruct evolutionary changes. In birds, this has previously been impeded by a near intractable karyotype and relied almost exclusively on comparative molecular cytogenetics of only the largest chromosomes. Here, novel whole genome sequence information from 21 avian genome sequences (most newly assembled) made available on an interactive browser (Evolution Highway) was analyzed. Results: Focusing on the six best-assembled genomes allowed us to assemble a putative karyotype of the dinosaur ancestor for each chromosome. Reconstructing evolutionary events that led to each species' genome organization, we determined that the fastest rate of change occurred in the zebra finch and budgerigar, consistent with rapid speciation events in the Passeriformes and Psittaciformes. Intra- and interchromosomal changes were explained most parsimoniously by a series of inversions and translocations respectively, with breakpoint reuse being commonplace. Analyzing chicken and zebra finch, we found little evidence to support the hypothesis of an association of evolutionary breakpoint regions with recombination hotspots but some evidence to support the hypothesis that microchromosomes largely represent conserved blocks of synteny in the majority of the 21 species analyzed. All but one species showed the expected number of microchromosomal rearrangements predicted by the haploid chromosome count. Ostrich, however, appeared to retain an overall karyotype structure of 2n = 80 despite undergoing a large number (26) of hitherto un-described interchromosomal changes. Conclusions: Results suggest that mechanisms exist to preserve a static overall avian karyotype/genomic structure, including the microchromosomes, with widespread interchromosomal change occurring rarely (e.g. in ostrich and budgerigar lineages). Of the species analyzed, the chicken lineage appeared to have undergone the fewest changes compared to the dinosaur ancestor. [ABSTRACT FROM AUTHOR]