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The article provides a detailed examination of clinical management and support for patients with Amyotrophic Lateral Sclerosis (ALS) and other neuromuscular diseases, emphasizing the need for new evaluation tools and innovative technologies. It explores various aspects such as upper airway disorders, speech and swallow changes, remote monitoring, and the impact of dietary factors on disease progression. The study also discusses the legal and governance framework for PRECISION ALS, ensuring compliance with data protection regulations and ethical standards to facilitate international collaboration and data sharing for ALS research. The text offers a comprehensive overview of research projects related to ALS and Frontotemporal Degeneration (FTD), covering topics like caregiver experiences, the impact of COVID-19 on Motor Neurone Disease (MND) care, and the challenges faced by healthcare professionals in providing care for ALS patients. [Extracted from the article]

Abstract: Gamma production cross sections for neutron inelastic scattering, and reactions on 208Pb were measured at the Geel Electron Linear Accelerator (GELINA) from the respective thresholds up to at most 20 MeV. An unprecedented neutron energy resolution of 1.1 keV at 1 MeV (35 keV at 10 MeV) and a total uncertainty of about 5% was achieved for the integral gamma production cross section of the most intense transition in 208Pb. The gamma production cross section was measured for 29 transitions of the inelastic channel, 5 transitions of the channel and one transition of the channel. Based on the evaluated level scheme of 208Pb, the total neutron inelastic scattering cross section and the level cross sections were deduced. Four large volume HPGe (high purity germanium) detectors were used for the detection of the γ-rays. The 88.11% enriched 208Pb sample was placed at a flight path length of 198.551 m. The cross sections were measured relative to the standard cross section by continuously monitoring the neutron flux with a fission chamber containing 235U. The results are compared with the existing experimental data from the literature and with model estimates obtained with the recent TALYS 1.00 code. A good agreement of the present data is found with both the existing experimental data and with the calculations. The present work greatly expands the number of measured gamma production cross sections and the level cross sections derived for this nucleus. [Copyright &y& Elsevier]

Objectives: To expand the phenotype and genotype of VPS16 -related dystonia (DYT -VPS16 )., Methods: We report 2 patients with previously unreported VPS16 truncating variants and highlight some distinctive phenomenological characteristics of DYT- VPS16., Results: The 2 patients, who were unrelated, presented with early-onset orofacial dystonia with prominent tongue involvement. Case 1, a 37-year-old woman, developed disabling orofacial dystonia, with tongue protrusion (lingual dystonia), orofacial gesticulations, and hyperkinetic dysarthria, responsible for an odd "foreign language" quality. Case 2, a 36-year-old woman, exhibited orofacial dystonia with prominent lingual involvement and orofacial gesticulations. In both patients, orofacial dystonia led to predominant speech impairment with no or discrete swallowing difficulties., Discussion: Substantial tongue dystonia may be a distinctive feature of DYT- VPS16 . Our cases widen the phenotypic spectrum of DYT- VPS16 and may provide physicians with a new clinical clue for this disease., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Integrated care pathways can help to avoid unnecessary admissions to hospital and improve the overall quality of care for frail older patients. Although these integrated care pathways should be coordinated by GPs their level of commitment may vary., Aim: To profile GPs who had participated or had declined to participate in the Personnes Agées En Risque de Perte d'Autonomie (PAERPA) integrated care project (ICP) in the Valenciennois-Quercitain area of France between 2014 and 2019., Design and Setting: A combined qualitative and quantitative analysis of GPs who were participating in or had declined to participate in the PAERPA ICP., Method: Both GPs participating in the ICP and GPs who chose not to participate in the ICP were interviewed, and then consultation and prescription profiles for these two groups were compared., Results: Some GPs were interested in the PAERPA ICP, whereas others were opposed. The 48 qualitative interviews revealed four issues that influenced participation in the PAERPA ICP: 1) awareness of issues in care of older adults and the value of collaborative work; 2) time saving; 3) task delegation; and 4) advantages of coordination. The level of interest in the ICP for frail older adults was indirectly reflected by the data on consulting and prescribing. In GPs who participated in the PAERPA ICP there was a greater proportion of older (aged ≥70 years) patients ( P <0.05), a larger number of consultations per year ( P <0.05), and a larger number of home visits ( P <0.01), relative to GPs who declined to participate., Conclusion: The level of interest in the PAERPA ICP for frail older adults varied widely among GPs. These findings suggest that commitment to an integrated care pathway could be increased by customising the recruitment strategy as a function of the GP's profile., (© The Authors.)

Introduction: Integrated care is a particularly promising approach in geriatrics - a field in which the medical, psychological and social issues are often complex. The uptake of integrated care by healthcare professionals (HCPs) is essential but varies markedly. The objective of the present study of healthcare professionals was to identify barriers to and facilitators of commitment to integrated care for seniors., Methods: We performed a two-step, qualitative study, comprising (i) six qualitative, semi-directive series of interviews with HCPs (hospital practitioners, family physicians, nurses and pharmacists) who agreed or disagreed to take part in the French national "Health Pathway of Seniors for Preserved Autonomy" (PAERPA) pilot program; and (ii) an analysis of the pooled results, in order to identify common concerns among the healthcare professionals., Results: We identified four key "barrier" and "facilitator" topics shared by HCPs who had committed to the pilot program and those who had not: (i) awareness of and/or interest in geriatric medicine and team working, (ii) the presence of a care coordinator; (iii) the provision of information about the program and about the patient, and communication between HCPs, and (iv) personal benefits for the HCPs and the patients., Key Conclusions: The four key topics identified in this large qualitative study of several healthcare professions should be considered during the design and dissemination of integrated care pathways for older patients., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Free living amoebae (FLA) including Acanthamoeba castellanii, are protozoa that feed on different microorganisms including viruses. These microorganisms show remarkable similarities with macrophages in cellular structures, physiology or ability to phagocyte preys, and some authors have therefore wondered whether Acanthamoeba and macrophages are evolutionary related. It has been considered that this amoeba may be an in vitro model to investigate relationships between pathogens and macrophagic cells. So, we intended in this study to compare the interactions between a human adenovirus strain and A. castellanii or THP-1 macrophagic cells. The results of molecular and microscopy techniques following co-cultures experiments have shown that the presence of the adenovirus decreased the viability of macrophages, while it has no effect on amoebic viability. On another hand, the viral replication occurred only in macrophages. These results showed that this amoebal model is not relevant to explore the relationships between adenoviruses and macrophages in in vitro experiments.

Coxsackieviruses B (CV-B) (Picornaviridae) are a common infectious cause of acute myocarditis in children and young adults, a disease, which is a precursor to 10-20% of chronic myocarditis and dilated cardiomyopathy (DCM) cases. The mechanisms involved in the disease progression from acute to chronic myocarditis phase and toward the DCM clinical stage are not fully understood but are influenced by both viral and host factors. Subgenomic replicons of CV-B can be used to assess viral replication mechanisms in human cardiac cells and evaluate the effects of potential antiviral drugs on viral replication activities. Our objectives were to generate a reporter replicon from a cardiotropic prototype CV-B3/28 strain and to characterize its replication properties into human cardiac primary cells. To obtain this replicon, a cDNA plasmid containing the full CV-B3/28 genome flanked by a hammerhead ribozyme sequence and an MluI restriction site was generated and used as a platform for the insertion of sequences encoding emerald green fluorescent protein (EmGFP) in place of those encoding VP3. In vitro transcribed RNA from this plasmid was transfected into HeLa cells and human primary cardiac cells and was able to produce EmGFP and VP1-containing polypeptides. Moreover, non-structural protein biological activity was assessed by the specific cleavage of eIF4G1 by viral 2A(pro). Viral RNA replication was indirectly demonstrated by inhibition assays, fluoxetine was added to cell culture and prevented the EmGFP synthesis. Our results indicated that the EmGFP CV-B3 replicon was able to replicate and translate as well as the CV-B3/28 prototype strain. Our EmGFP CV-B3 replicon will be a valuable tool to readily investigate CV-B3 replication activities in human target cell models., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Enteroviruses (EVs) are small naked single-stranded positive RNA viruses (Picornaviridae) of approximately 7,400 nucleotides divided in four species (HEV A-D) and including 120 serotypes. EVs are common human pathogens, transmitted through fecal-oral and respiratory routes. Although the majority of EV infections remains asymptomatic (90 %), these viruses are considered as one of the most common causes of acute viral illnesses in immunocompetent pediatric and adult subjects. High levels of genetic diversity allow these viruses to infect various target cells resulting in a wide spectrum of human acute pathologies including meningitis, respiratory syndromes, cutaneous syndromes, myocarditis and mother-to-child infections. During the early phases of the acute viral infection, EV can modulate the non-specific antiviral strategies developed by the infected target cell (modulation of class I MHC viral antigen presentation ; inhibition of type I interferon expression genes) and to disturb dendritic cell functions resulting in a viral immune escape. This immunological escape allows the generation of genetically modified viruses resulting from RNA genomic deletions, mutations or recombination mechanisms. Persistent replication activities of these genetically modified viruses can induce modulation of specific functions and endocellular pathways of infected cells and the development of chronic inflammatory or autoimmune mechanisms (auto-reactive T and -B cells and auto-antibodies). The persistence of these genetically modified viruses can result in direct or indirect tissue injuries that can explain a subset of chronic myocarditis and dilated cardiomyopathy (DCM), type 1 diabetes mellitus and post-polio syndrome (PPS) cases. Actually no specific and curative therapies are available against EV-induced chronic human pathologies. A better understanding of the molecular mechanisms implicated in viral persistence will stimulate the research into new therapeutic strategies to prevent and treat chronic infections caused by EVs.

Background: An autopsy case of a two-month-old male infant who suddenly and unexpectedly died during his sleep, eight days after the onset of benign varicella., Objectives: To describe post-mortem combined histological and tissue molecular biological techniques for the diagnosis of cytomegalovirus and varicella zoster virus co-infection as a cause of death., Study Design: Real-time quantitative PCR and RT-PCR assays for Herpesviruses, respiratory viruses, Adenovirus, Enterovirus and Parvovirus B19 were performed on multi-organ frozen samples and paraffin-embedded tissues in combination with histology., Results: Cytomegalovirus and varicella zoster virus were detected by molecular biology with highest viral loads detected in the lungs (4.6×10(7) and 1.9×10(5) genome copies per million of cells, respectively). Pulmonary extensive necrotizing inflammation and immunohistochemistry correlated to virological data. Virological molecular biology was negative on paraffin-embedded tissues., Conclusions: This case shows that thorough quantitative virological investigations on frozen tissues must be performed in combination with histology and immunohistochemistry for the determination of the cause of a sudden unexplained infant death., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r(2) = 0.57, P = 0.002 and r(2) = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.