Enhanced hippocampal LTP but normal NMDA receptor and AMPA receptor function in a rat model of CDKL5 deficiency disorder.

BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5-/y rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.

Glutaric Acidemia Type 1: Diagnosis, Clinical features, and Outcome in a Portuguese Cohort.

INTRODUCTION: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid, and glutarylcarnitine, especially in the brain. GA1-affected children are clinically characterized by macrocephaly. Neurological abnormalities usually appear between 6 and 18 months of age, often triggered by a catabolic event. On the other hand, several biochemically affected individuals may remain asymptomatic or experience an insidious onset of mild neurological abnormalities. METHODS: Retrospective study of GA1 patients followed at a Portuguese Hereditary Metabolic Disease Center, to characterize the phenotypic and genotypic variations associated with GA1. Therefore, we analyzed the clinical, neuroradiological, biochemical, and genetic information from 14 patients. RESULTS: 14 patients (four months-27 years old) were identified in the last 26 years, 9 were male, 1 was from a consanguineous family. 11 were diagnosed by newborn screening (NBS), and 3 identified following clinical symptoms (later diagnosed, LD). There were 3 phenotypic presentations: 6 asymptomatic, 3 with a motor disability after encephalopathic crisis (EC), and 5 with insidious onset. Acute EC occurred in 1/3 of the LD patients and in 2/11 NBS-identified patients. About urinary GA concentrations: 5 were low excretors (LE), 9 were high excretors (HE). All LE showed symptoms, and 2 had EC. Concerning HE, 3 showed symptoms and 1 had EC. GCDH analysis showed: 6 compound heterozygotes and 8 homozygotes. most frequent variant was c.1204C>T (p.R402W). All of them received appropriate therapy from the time of diagnosis, with a mean age of 23.3 months in LD patients and 13.3 days in NBS-identified patients. CONCLUSION: The outcomes were different between the two groups: all the LD patients presented motor dysfunction however in the NBS-identified patients only 5 developed this symptom. Patients identified by NBS had better outcomes showing that NBS enables an early diagnosis, and treatment, and consequently improves the clinical outcomes for these patients. No correlation was observed with clinical phenotype between LE and HE, as both groups can suffer the most severe neurological manifestations. These conclusions are in agreement with previous cohorts described in the literature.

Influência dos estilos de liderança no burnout dos enfermeiros: uma scoping review / Influence of leadership styles on nurses' burnout: a scoping review / Influencia de los estilos de liderazgo en el agotamiento de las enfermeras: una scoping review

Objetivo: identificar quais os estilos de liderança utilizados por enfermeiros gestores e compreender a sua influência no burnoutdos enfermeiros no contexto de trabalho.Método: scoping review, realizada em abril de 2021, conduzida de acordo com a metodologia de Joanna Briggs Institute. Dois revisores independentes avaliaram a relevância dos artigos, a extração e síntese dos dados. Resultados: foram identificados 3.532 estudos na pesquisa bibliográfica, dos quais sete estudos apresentaram as características de elegibilidade para a inclusão na revisão. Os estilos de liderança identificados na literatura foram a liderança transformacional e liderança autêntica que revelam um impacto positivo na redução do burnout; a liderança laissez-faire que, pelo contrário, promove um ambiente facilitador do desenvolvimento da síndrome em estudo; a liderança transacional, por sua vez, não demonstrou resultados significativos na diminuição e prevenção de burnout, assim como, a liderança autocrática, carismática e situacional cujos resultados não se demonstraram quantificáveis para a sua prevenção. Conclusão: o estilo de liderança transformacional foi aquele que maior relevância demonstrou tanto na prevenção como diminuição do desenvolvimento de burnoutnos enfermeiros.

Objective: identify which leadership styles are used by nurse managers and understand their influence on nurse's burnout nurses in the work context. Method: scoping review, carried out in April 2021, conducted according to the Joanna Briggs Institute methodology. Two independent reviewers assessed the relevance of the articles, the extraction and synthesis of data. Results: 3.532 studies were identified in the literature search, of which seven studies presented the eligibility characteristics for inclusion in the review.The leadership styles identified in the literature were transformational leadership and authentic leadership that reveal a positive impact on reducing burnout; laissez-faire leadership that, on the contrary, promotes an environment that facilitates the development of the syndrome under study; transactional leadership, in turn, did not show significant results in reducing and preventing burnout, as well as autocratic, charismatic and situational leadership whose results were not quantifiable for its prevention.Conclusion: it was concluded that the transformational leadership style was the one that showed the greatest relevance both in preventing and reducing the development of burnoutin nurses.

Objetivo: identificar qué estilos de liderazgo son utilizados por las enfermeras gestoras y comprender su influencia en el agotamiento de las enfermeras en el contexto de trabajo.Método: scoping review, realizado en abril de 2021, según la metodología Joanna Briggs Institute. Dos revisores independientes evaluaron la relevancia de los artículos, la extracción y síntesis de datos. Resultados: se identificaron 3.532 estudios en la búsqueda bibliográfica, de los cuales siete estudios presentaron las características de elegibilidad para su inclusión en la revisión. Los estilos de liderazgo identificados en la literatura fueron el liderazgo transformacional y el liderazgo auténtico que revelan un impacto positivo en la reducción del burnout; liderazgo laissez-faire que, por el contrario, promueve un entorno que facilita el desarrollo del síndrome en estudio; el liderazgo transaccional, por su parte, no mostró resultados significativos enla reducción y prevención del burnout, así como el liderazgo autocrático, carismático y situacional cuyos resultados no fueron cuantificables para su prevención. Conclusión: se concluyó que el estilo de liderazgo transformacional fue el que mostró mayor relevancia tanto en la prevención como en la reducción del desarrollo del burnout en enfermeros.

Laparoscopic approach for a spontaneous posterior rectus sheath hernia.

Spontaneous posterior rectus sheath hernia is perhaps one of the rarest hernias described only in a few published cases. We present the case of a small bowel herniation through the posterior rectus sheath in a woman without previous abdominal surgical history, resulting in acute small bowel obstruction who was successfully treated by laparoscopy. This is the first case report of this kind of hernia managed with laparoscopic technique. Although the laparoscopic approach is not considered standard treatment for strangulated hernias, in selected cases, it allows the identification and repair of the defect.

Psychosocial impact of Parkinson's disease-associated dysarthria: Cross-cultural adaptation and validation of the Dysarthria Impact Profile into European Portuguese.

AIM: The present study sought to make a cross-cultural adaptation of the Dysarthria Impact Profile (DIP) for European Portuguese (EP) and validate it for use in Parkinson's disease (PD) patients. METHODS: The cross-cultural adaptation was carried out in accordance with the guidelines. The EP version of the DIP was administered to 80 people with PD, and 30 sex- and age-matched control participants. Psychometric properties, acceptability, feasibility reliability (internal consistency and intrarater agreement) and validity (construct, convergent and known-groups validity) were assessed using other assessment tools (motor disability and impairment, and voice impact). RESULTS: Overall, the EP-DIP final version has the same conceptual meaning, semantics, idiomatic and score equivalences as the original version. Statistical analyses showed adequate feasibility (missing data <5%), good acceptability (ceiling or floor effects <15%; high requests of assistance to complete the questionnaire), satisfactory internal consistency (Cronbach's α = 0.9), weak-to-moderate intrarater reliability, good construct validity, strong convergent validity (with the Voice Handicap Index; Spearman's P = -0.8) and good known-groups validity (between those with PD and control participants). CONCLUSIONS: The EP-DIP version displays the salient features of a valid patient-based assessment tool used to measure the psychosocial impact of slight-to-mild dysarthria in people with PD. Geriatr Gerontol Int 2018; 18: 767-774.

Frenchay dysarthria assessment (FDA-2) in Parkinson's disease: cross-cultural adaptation and psychometric properties of the European Portuguese version.

Hypokinetic dysarthria is a common symptom in those with Parkinson's disease (PD); there is currently no standardized or validated tool for assessing speech in this population. To translate into European Portuguese (EP) the FDA-2 and perform a cultural adaptation followed by an evaluation of its psychometric properties in PD in a sample of people with PD in different stages of disease progression. Translation, back-translation, experts' analysis, pre-test and final version test were performed. The EP version of the FDA-2 was administered to 80 people with PD (PwP) with dysarthria, feasibility and acceptability, reliability (internal consistency and inter-rater reliability) and validity (face and convergent) were measured. Overall, the EP-FDA-2 proved to be similar to the original demonstrating the same conceptual meanings, semantics, idiomatic and score equivalences. It has good feasibility (missing data <5 %), acceptability (ceiling and floor effects <15 %), a high reliability of the total score (0.94), an excellent inter-rater agreement for the total score (0.96) and moderate to large construct validity for 81 % of its items. It is well correlated with the gold standard for disease severity assessment in PD, the MDS-UPDRS. The EP-FDA-2 has shown the salient features of a valid tool that can be used by speech and language therapists in the assessment of dysarthria in PD in clinical practice as in the research field.