Myelination deficits in the auditory brainstem of a mouse model of Fragile X Syndrome, a possible mechanism for auditory phenotypes

1AbstractAuditory symptoms are one of the most frequent sensory issues described in people with Fragile X Syndrome (FXS), the most common genetic form of intellectual disability. However, the mechanisms that lead to these symptoms are under explored. In this study, we examined whether alterations in myelination in auditory brainstem circuitry contribute to auditory impairments in FXS mice. Specifically, we studied myelinated fibers that terminate in the Calyx of Held, which encode temporally precise sound arrival time, and are some of the most heavily myelinated axons in the brain. We measured anatomical myelination characteristics using coherent anti-stokes Raman spectroscopy (CARS) and electron microscopy (EM) in a FXS mouse model in the medial nucleus of the trapezoid body (MNTB) where the Calyx of Held synapses. We measured number of mature oligodendrocytes (OL) and oligodendrocyte precursor cells (OPCs) to determine if changes in myelination were due to changes in the number of myelinating or immature glial cells. The two microscopy techniques (EM and CARS) showed a decrease in fiber diameter in FXS mice. Additionally, EM results indicated reductions in myelin thickness and axon diameter, and an increase in g-ratio, a measure of structural and functional myelination. Lastly, we showed an increase in both OL and OPCs in MNTB sections of FXS mice suggesting that the myelination phenotype is not due to an overall decrease in number of myelinating OLs. This is the first study to show that a potential myelination mechanism can explain alterations seen in FXS at the level of the auditory brainstem.

Primary Progressive Aphasia: Toward a Pathophysiological Synthesis

Purpose of Review The term primary progressive aphasia (PPA) refers to a diverse group of dementias that present with prominent and early problems with speech and language. They present considerable challenges to clinicians and researchers. Recent Findings Here, we review critical issues around diagnosis of the three major PPA variants (semantic variant PPA, nonfluent/agrammatic variant PPA, logopenic variant PPA), as well as considering ‘fragmentary’ syndromes. We next consider issues around assessing disease stage, before discussing physiological phenotyping of proteinopathies across the PPA spectrum. We also review evidence for core central auditory impairments in PPA, outline critical challenges associated with treatment, discuss pathophysiological features of each major PPA variant, and conclude with thoughts on key challenges that remain to be addressed. Summary New findings elucidating the pathophysiology of PPA represent a major step forward in our understanding of these diseases, with implications for diagnosis, care, management, and therapies.

Merle allele variations in the Mudi dog breed and their effects on phenotypes

A retrotransposon insertion in the SILV gene is associated with a peculiar phenotype of dog, known as a merle. It is characterised by various areas of their coat colour becoming diluted due to a malfunction in the eumelanin-producing pigment cells. Recent studies have shown that the exact size of the short interspersed element (SINE) insertion is in correlation with specific phenotypic attributes, but was not able to absolutely confine dogs to a certain colour pattern. Our study focused on the merle variations occurring in the Mudi breed. Altogether, 123 dog samples from 11 countries were tested and genotyped. The exact length of the merle alleles were determined by automated fluorescent capillary fragment analysis. The most frequent merle genotype in this Mudi sample collection was the ‘classic’ merle (m/M: 61.8%), whereas other variants, such as atypical (m/Ma and m/Ma+: 5.7%), harlequin (m/Mh: 13.8%), double merle (M/M: 0.8%) and mosaic profiles (17.9%) were also observed. The practical significance of testing this mutation is that, phenotypically, not only merle dogs are carriers of this insertion, but also the so-called hidden merle individuals (where the merle phenotype is fully covered by the pheomelanin-dominated colouration) are potentially capable of producing unintentionally homozygous ‘double merle’ progeny with ophthalmologic, viability and auditory impairments.

THE PREVALENCE OF DIFFERENT TEACHING METHODS IN INCLUSIVE EDUCATION

Teaching methods represent the basic, regulatory elements of the teaching process. The aim of this study was to investigate the prevalence of different methods in inclusive Serbian schools. The sample consisted of 16 elementary schools attended by pupils with sensory impairments (visual and auditory impairments: N=69). 382 school classes of sixth and seventh grade were systematically observed to register the frequency of method used. Results have shown that the most frequently used method was the monologue (39,7%) followed by the dialogic method (39,2%) while other methods were used far less often (written/graphic presentation (12,3%), working with text (5,8%) and demonstration (2,8%)). The quality of teaching can be significantly lowered if one method is predominantly used in class. Implications for more effective teaching in inclusive schools are discussed, with special regard to pupils with sensory impairments.

A Little Help from My Friends: Social Support in Palliative Rehabilitation

Background Social support has been shown to buffer some difficulties of living with advanced cancer. The Palliative Rehabilitation Program (prp) was an interdisciplinary outpatient program offering post-treatment palliative rehabilitation to patients with advanced cancer. Social support was directly integrated into the program. The aim of the present study was to examine the types and sources of social support that patients found most beneficial.Methods Twelve patients participated in 30-minute semi-structured interviews. Thematic content analysis was used to explore the social support experiences of those patients in the prp. Patients were eligible to participate in the interview if they had completed the 8-week prp, spoke English, and did not have cognitive or auditory impairments affecting their ability to participate.Results The main sources of support reported by participants were team members and spouse, family, or close friends; peers attending the program; and spiritual beliefs. Social support varied based on sex and age, such that, compared with women, men reported relying less on social support, and the supportive needs of younger (≤50 years of age) and older participants differed. Team members were endorsed as frequently as family as social support.Discussion Emotional support was endorsed with the greatest frequency. The members of the interdisciplinary care team were also providers of emotional and informational support for patients, bolstering the support received from caregivers. Widowed or divorced women might rely on health care providers more readily than do married men, who chose their wives as support. Future rehabilitation programs might consider the importance of an interdisciplinary team, the formal integration of caregivers, and the incorporation of spirituality to meet the unique supportive needs of patients with advanced cancer.

THE FREQUENCY OF USAGE OF DIFFERENT WORK FORMS IN AN INCLUSIVE TEACHING ENVIRONMENT

The aim of this study was to investigate how frequently the different forms of work (frontal, individual and group) are used in the Serbian inclusive education. The sample consisted of 16 elementary schools in Serbia which pupils with sensory impairments attend (visual and auditory impairments: N=69). Systematic observation has been used on 382 classes. Results have shown that in the majority of classes the frontal form was predominantly used (67.7%). Significantly less present was the individual form (22.6%), while the variations of group work were the least frequently used. Considering the goals of inclusive education with the fact that the social engagement of pupils with sensory impairments in class can be beneficial, the frontal form alone is not enough for an effective teaching process. Despite its practicality, it is necessary to use the frontal form in balance with other work forms in all the phases of the class.

The share of the teaching methods in the inclusive education on the appropriate sample at the territory of the City of Belgrade

The aim of this study was to investigate the frequency of their usage in an inclusive teaching environment. The sample consisted of 16 elementary schools on the territory of the Republic of Serbia, which pupils with sensory impairments attend [visual and auditory impairments: N=69]. Systematic observation has been used as a method on 382 classes of sixth and seventh grade to collect data on the usage of social forms of work. Results have shown that in the two-thirds of observed classes the frontal work form was predominantly used [67.7%], following the individual work form [22.6%] present in a much lower degree, while the group work form [1.7%] and working in pairs [1.3%] were the least frequently used. Teacher-centered class is still a constant in schools, and the dominant usage of the frontal work form as well, by that very fact. This form has its advantages among which the efficiency in using the available class time stands out. However, this form by itself does not consider the social nature of learning which full understanding is mandatory for effective teaching. Therefore, it is necessary to use it in balance with individual and group forms in all phases of class.