The care in death situations: some reflections

A percepção das vivências de morte e morrer tem sofrido transformações ao longo da história, passando de uma experiência tranqüila e até mesmo desejada a uma possibilidade impregnada de angústias e que deve ser evitada a todo custo. Neste contexto, os profissionais de saúde têm uma responsabilidade grande em discutir e refletir sobre a questão de modo que possam oferecer um cuidado autêntico e compromissado com o ser humano, em sua plenitude. Este trabalho se propõe a discutir, a partir da perspectiva da fenomenologia de Heidegger, a questão da morte como parte inerente à existência humana, atentando para a necessidade de que se compreendam as relações de cuidado e as formas de relacionamento humano de modo que se possibilite o preparo dos profissionais de saúde para compartilhar com os pacientes de um momento existencial que pode e deve ser vivido com dignidade.The perceptions about death and die have changed trough history, at first it was a pacific and wished experience but became a full of angst possibility, a situation that have to be avoid desperately. At this context, the health professionals have a great responsibility in promoting discussions and reflections about this question, trying to offer an authentic care, engaged whit the human being in his plenitude. This article has the purpose of discussing, based on Heidegger phenomenology, the death theme as a part of human existence, considering the necessity to understand the care practices and the ways of human relationships looking for enabling health workers to share with patients this existential moment that must to be lived with dignity

Belgian rare diseases plan in clinical pathology : identification of key biochemical diagnostic tests and establishment of reference laboratories and financing conditions

BackgroundOne objective of the Belgian Rare Diseases plan is to improve patients' management using phenotypic tests and, more specifically, the access to those tests by identifying the biochemical analyses used for rare diseases, developing new financing conditions and establishing reference laboratories.MethodsA feasibility study was performed from May 2015 until August 2016 in order to select the financeable biochemical analyses, and, among them, those that should be performed by reference laboratories. This selection was based on an inventory of analyses used for rare diseases and a survey addressed to the Belgian laboratories of clinical pathology (investigating the annual analytical costs, volumes, turnaround times and the tests unavailable in Belgium and outsourced abroad). A proposal of financeable analyses, financing modalities, reference laboratories' scope and budget estimation was developed and submitted to the Belgian healthcare authorities. After its approval in December 2016, the implementation phase took place from January 2017 until December 2019.ResultsIn 2019, new reimbursement conditions have been published for 46 analyses and eighteen reference laboratories have been recognized. Collaborations have also been developed with 5 foreign laboratories in order to organize the outsourcing and financing of 9 analyses unavailable in Belgium.ConclusionsIn the context of clinical pathology and rare diseases, this initiative enabled to identify unreimbursed analyses and to meet the most crucial financial needs. It also contributed to improve patients' management by establishing Belgian reference laboratories and foreign referral laboratories for highly-specific analyses and a permanent surveillance, quality and financing framework for those tests

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators’ practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (≥ 2 g/kg/day) and BCAA supplementation (100–250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/ improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes.A.G.C. is supported by FIS P118/00111, FI21/0073 ‘Instituto de Salud Carlos III (ISCIII)’ and ‘Fondo Europeo de desarrollo regional (FEDER)’

A pesquisa em enfermagem: notas de ordem histórica e metodológica

O artigo se propõe a algumas considerações sobre a pesquisa em enfermagem no que se refere ao referencial teórico e caminhos metodológicos. Com esse intuito, seus autores resgatam o momento em que a enfermagem passa por um redirecionamento do método clássico de investigação para novas propostas metodológicas, contemplando outros objetos de estudo, possibilitando, assim, novos horizontes epistemológicos para a geração do conhecimento. Discutem questões relacionadas à coerência interna da pesquisa qualitativa, à observância de seus pressupostos filosóficos, ressaltando a importância da produção de conhecimentos que respondam às indagações do assistir e do cuidar em enfermagem.The article aims at making some considerations on nursing research in relation to this theoretical framework and methodological pathways. For that purpose the authors recapture the moment when nursing goes through a redirecting of the classical investigation method to new epistemological horizons for knowledge generation. The authors also discuss issues related to the internal coherence of qualitative research and the observance of philosophical premises emphasising the importance of the production of knowledge in response to queries on the assisting and caring in nursing

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided. This article is protected by copyright. All rights reserved

Probing Transient Valence Orbital Changes with Picosecond Valence-to-Core X-ray Emission Spectroscopy

We probe the dynamics of valence electrons in photoexcited [Fe(terpy)₂]²⁺ in solution to gain deeper insight into the Fe–ligand bond changes. We use hard X-ray emission spectroscopy (XES), which combines element specificity and high penetration with sensitivity to orbital structure, making it a powerful technique for molecular studies in a wide variety of environments. A picosecond-time-resolved measurement of the complete 1s X-ray emission spectrum captures the transient photoinduced changes and includes the weak valence-to-core (vtc) emission lines that correspond to transitions from occupied valence orbitals to the nascent core-hole. Vtc-XES offers particular insight into the molecular orbitals directly involved in the light-driven dynamics; a change in the metal–ligand orbital overlap results in an intensity reduction and a blue energy shift in agreement with our theoretical calculations and more subtle features at the highest energies reflect changes in the frontier orbital populations

CrypTFlow2: Practical 2-Party Secure Inference

We present CrypTFlow2, a cryptographic framework for secure inference over realistic Deep Neural Networks (DNNs) using secure 2-party computation. CrypTFlow2 protocols are both correct -- i.e., their outputs are bitwise equivalent to the cleartext execution -- and efficient -- they outperform the state-of-the-art protocols in both latency and scale. At the core of CrypTFlow2, we have new 2PC protocols for secure comparison and division, designed carefully to balance round and communication complexity for secure inference tasks. Using CrypTFlow2, we present the first secure inference over ImageNet-scale DNNs like ResNet50 and DenseNet121. These DNNs are at least an order of magnitude larger than those considered in the prior work of 2-party DNN inference. Even on the benchmarks considered by prior work, CrypTFlow2 requires an order of magnitude less communication and 20x-30x less time than the state-of-the-art