Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare recessive disorders with prenatal onset, characterized by hypoplasia of pons and cerebellum. Mutations in a small number of genes have been reported to cause PCH, and the vast majority of PCH cases are explained by mutations in TSEN54, which encodes a subunit of the tRNA splicing endonuclease complex. Here we report three families with homozygous truncating mutations in TBC1D23 who display moderate to severe intellectual disability and microcephaly. MRI data from available affected subjects revealed PCH, small normally proportioned cerebellum, and corpus callosum anomalies. Furthermore, through in utero electroporation, we show that downregulation of TBC1D23 affects cortical neuron positioning. TBC1D23 is a member of the Tre2-Bub2-Cdc16 (TBC) domain-containing RAB-specific GTPase-activating proteins (TBC/RABGAPs). Members of this protein family negatively regulate RAB proteins and modulate the signaling between RABs and other small GTPases, some of which have a crucial role in the trafficking of intracellular vesicles and are involved in neurological disorders. Here, we demonstrate that dense core vesicles and lysosomal trafficking dynamics are affected in fibroblasts harboring TBC1D23 mutation. We propose that mutations in TBC1D23 are responsible for a form of PCH with small, normally proportioned cerebellum and should be screened in individuals with syndromic pontocereballar hypoplasia.

A Case Report of Resection of a Mediastinal Paraganglioma: Why All the Fuss?

Mediastinal paragangliomas are rare tumors that have only been reported in individual cases or limited case series. Surgical resection of these tumors can be challenging, as they are highly vascular and intimately related to the great vessels. Surgery is usually performed via median sternotomy with or without cardiopulmonary bypass. We present the case of a mediastinal paraganglioma that was resected via a left-sided posterolateral thoracotomy. Histopathology revealed a completely resected 38-mm paraganglioma with a positive station 5 lymph node, indicative of locally aggressive disease. Hereditary paragangliomas are associated with malignant transformation; therefore, genetic testing is important. These tumors do not respond well to chemoradiotherapy, and consequently lifelong surveillance for early detection of recurrence is recommended.

Experiences of nurses practising home-based palliative care in a rural South African setting.

BACKGROUND: Home-based care is necessary in rural South Africa owing to the impact of the HIV/AIDS epidemic, inaccessible health-care institutions, and overcrowding in hospitals. Palliative care has been introduced as part of home-based care and there is a call for research to inform practice, training, and support of caregivers. This exploratory paper reports on four nurses' experiences of providing home-based palliative care (HBPC) in rural KwaZulu-Natal. METHODOLOGY: The study employed the qualitative method of photo-elicitation, which was used as a launching point for individual one-to-one interviews with the participants. FINDINGS: HBPC increases access to care and provides a means of humanizing care and supporting patients in familiar community structures. It also enables nurses to practise independently and facilitates practise of traditional customs and use of traditional medicines. Challenges include patients' understanding of palliative care and nurses being placed at risk. CONCLUSION: The study uncovered several benefits to HBPC for patients and nurses, but also highlighted various challenges in its implementation. Further research is needed before any recommendations for practice, training, and support can be made.

Effects of semantic context on access to words of low imageability in deep-phonological dysphasia: a treatment case study.

BACKGROUND: Deep dysphasia is a relatively rare subcategory of aphasia, characterised by word repetition impairment and a profound auditory-verbal short-term memory (STM) limitation. Repetition of words is better than nonwords (lexicality effect) and better for high-image than low-image words (imageability effect). Another related language impairment profile is phonological dysphasia, which includes all of the characteristics of deep dysphasia except for the occurrence of semantic errors in single word repetition. The overlap in symptoms of deep and phonological dysphasia has led to the hypothesis that they share the same root cause, impaired maintenance of activated representation of words, but that they differ in severity of that impairment, with deep dysphasia being more severe. AIMS: We report a single-subject multiple baseline, multiple probe treatment study of a person who presented with a pattern of repetition that was consistent with the continuum of deep-phonological dysphasia: imageability and lexicality effects in repetition of single and multiple words and semantic errors in repetition of multiple-word utterances. The aim of this treatment study was to improve access to and repetition of low-imageability words by embedding them in modifier-noun phrases that enhanced their imageability. METHODS & PROCEDURES: The treatment involved repetition of abstract noun pairs. We created modifier-abstract noun phrases that increased the semantic and syntactic cohesiveness of the words in the pair. For example, the phrases "long distance" and "social exclusion" were developed to improve repetition of the abstract pair "distance-exclusion". The goal of this manipulation was to increase the probability of accessing lexical and semantic representations of abstract words in repetition by enriching their semantic -syntactic context. We predicted that this increase in accessibility would be maintained when the words were repeated as pairs, but without the contextual phrase. OUTCOMES & RESULTS: Treatment outcomes indicated that increasing the semantic and syntactic cohesiveness of low-imageability and low-frequency words later improved this participant's ability to repeat those words when presented in isolation. CONCLUSIONS: This treatment approach to improving access to abstract word pairs for repetition was successful for our participant with phonological dysphasia. The approach exemplifies the potential value in manipulating linguistic characteristics of stimuli in ways that improve access between phonological and lexical-semantic levels of representation. Additionally, this study demonstrates how principles of a cognitive model of word processing can be used to guide treatment of word processing impairments in aphasia.