The International Classification of Functioning Disability and Health, version for children and youth as a roadmap for projecting and programming rehabilitation in a neuropaediatric hospital unit.

Objective To test the impact of introducing a format based on the International Classification of Functioning Disability and Health, version for children and youth (ICF-CY) as a road-map for in-hospital paediatric neuro-rehabilitation on target definition, intra-team communication and workload as perceived by involved professionals. Design Single-centre pilot testing with impact assessment. Patients Team members of a tertiary care paediatric neurorehabilitation unit included 15 consecutive patients with severe neurological conditions. Methods An ICF-CY based format for rehabilitation projection and programming was constructed and tested for 12 months. The format comprises 3 sections: project, programme, and follow-up. Impact on the rehabilitation team was assessed with a questionnaire. Results All cases were described according to their specific needs with appropriate ICF-CY codes, and the interventions were linked to needs and targets. ICF-CY was judged an efficient tool in providing a road-map for rehabilitation in this setting, although concern was voiced about timing and workload. Conclusion ICF-CY may work as a road-map for in-hospital paediatric neuro-rehabilitation. Its implementation results in perceived improvements in the process. Training requirements and accurate evaluation of timing, workload and organizational context are critical issues that should be addressed before results from the present experience are generalized

Carrier-Induced Magnetic Circular Dichloism in the Magnetoresistive Pyrochlore Tl2Mn2O7

Infrared magnetic circular dichloism (MCD), or equivalently magneto-optical Kerr effect, has been measured on the Tl2Mn2O7 pyrochlore, which is well known for exhibiting a large magnetoresistance around the Curie temperature T_C ~ 120 K. A circularly polarized, infrared synchrotron radiation is used as the light source. A pronounced MCD signal is observed exactly at the plasma edge of the reflectivity near and below T_c. However, contrary to the conventional behavior of MCD for ferromagnets, the observed MCD of Tl2Mn2O7 grows with the applied magnetic field, and not scaled with the internal magnetization. It is shown that these results can be basically understood in terms of a classical magnetoplasma resonance. The absence of a magnetization-scaled MCD indicates a weak spin-orbit coupling of the carriers in Tl2Mn2O7. We discuss the present results in terms of the microscopic electronic structures of Tl2Mn2O7.Comment: 5 pages, 5 figures, submitted to J. Phys. Soc. Jp

Gal4 turnover and transcription activation

Growing evidence supports the notion that proteasome-mediated destruction of transcriptional activators can be intimately coupled to their function. Recently, Nalley et al. challenged this view by reporting that the prototypical yeast activator Gal4 does not dynamically associate with chromatin, but rather 'locks in' to stable promoter complexes that are resistant to competition. Here we present evidence that the assay used to reach this conclusion is unsuitable, and that promoter-bound, active Gal4 is indeed susceptible to competition in vivo. Our data challenge the key evidence that Nalley et al. used to reach their conclusion, and indicate that Gal4 functions in vivo within the context of dynamic promoter complexes

Rehabilitative treatment of patients with covid-19 infection: The p.a.r.m.a. evidence based clinical practice protocol

Background: The impact of the SARS-CoV-2 on the National Health System (NHS) required a reorganization of the various levels of care, which also involved the rehabilitation reality. Aim of the work: A clinical practice review of the literature was conducted to provide operational-rehabilitation guidelines adapt-ed to the local reality and to the recent corporate reorganization in the context of the COVID-19 emergency. Methods: A practice review of the available scientific evidence was regularly conducted from the start of the COVID-19 pandemic to periodically update the clinical practice guidelines. Articles that met the following inclusion criteria were included: studies conducted on human adult subjects with COVID-19 infection, un-dergoing rehabilitation in any hospitalization setting. Results: The results of this clinical practice update were periodically discussed with colleagues and collaborators in a multi-professional team, in order to guarantee a good clinical practice protocol, named P.A.R.M.A. Conclusions: The P.A.R.M.A. protocol is the result of a periodic review literature update, which has allowed us to take charge of patients affected by COVID-19 ac-cording to the most up-to-date clinical evidences, guaranteeing a shared and uniform treatment within a local reality in an era of health emergency. (www.actabiomedica.it)

Characterization of ARF-BP1/HUWE1 Interactions with CTCF, MYC, ARF and p53 in MYC-Driven B Cell Neoplasms

Transcriptional activation of MYC is a hallmark of many B cell lineage neoplasms. MYC provides a constitutive proliferative signal but can also initiate ARF-dependent activation of p53 and apoptosis. The E3 ubiquitin ligase, ARF-BP1, encoded by HUWE1, modulates the activity of both the MYC and the ARF-p53 signaling pathways, prompting us to determine if it is involved in the pathogenesis of MYC-driven B cell lymphomas. ARF-BP1 was expressed at high levels in cell lines from lymphomas with either wild type or mutated p53 but not in ARF-deficient cells. Downregulation of ARF-BP1 resulted in elevated steady state levels of p53, growth arrest and apoptosis. Co-immunoprecipitation studies identified a multiprotein complex comprised of ARF-BP1, ARF, p53, MYC and the multifunctional DNA-binding factor, CTCF, which is involved in the transcriptional regulation of MYC, p53 and ARF. ARF-BP1 bound and ubiquitylated CTCF leading to its proteasomal degradation. ARF-BP1 and CTCF thus appear to be key cofactors linking the MYC proliferative and p53-ARF apoptotic pathways. In addition, ARF-BP1 could be a therapeutic target for MYC-driven B lineage neoplasms, even if p53 is inactive, with inhibition reducing the transcriptional activity of MYC for its target genes and stabilizing the apoptosis-promoting activities of p53

Nef-mediated Clathrin-coated Pit Formation

The sequence of events leading to clathrin-coated pit (CCP) nucleation on the cell surface and to the incorporation of receptors into these endocytic structures is still imperfectly understood. In particular, the question remains as to whether receptor tails initiate the assembly of the coat proteins or whether receptors migrate into preformed CCP. This question was approached through a dissection of the mechanisms implemented by Nef, an early protein of human and simian immunodeficiency virus (HIV and SIV, respectively), to accelerate the endocytosis of cluster of differentiation antigen type 4 (CD4), the major receptor for these viruses. Results collected showed that: (a) Nef promotes CD4 internalization via an increased association of CD4 with CCP; (b) the Nef-mediated increase of CD4 association with CCP is related to a doubling of the plasma membrane area occupied by clathrin-coated structures; (c) this increased CCP number at the plasma membrane has functional consequences preferentially on CD4 uptake and does not significantly affect transferrin receptor internalization or fluid-phase endocytosis; (d) the presence of a CD4 cytoplasmic tail including a critical dileucine motif is required to induce CCP formation via Nef; and (e) when directly anchored to the cytoplasmic side of the plasma membrane, Nef itself can promote CCP formation. Taken together, these observations lead us to propose that CD4 can promote CCP generation via the connector molecule Nef. In this model, Nef interacts on one side with CD4 through a dileucine-based motif present on CD4 cytoplasmic tail and on the other side with components of clathrin-coated surface domain (i.e., adaptins). These Nef-generated complexes would then initiate the nucleation of CCP

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT–PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT–PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model