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Background We performed a qualitative study to investigate the experiences of participants in a multicentre randomized controlled trial on a home-based palliative approach (HPA) for adults with severe multiple sclerosis (MS) and their caregivers. Our aim was to explore the strengths and challenges of the intervention, and circumstances that may have influenced its efficacy. Methods Participants to the qualitative study were the patients, their caregivers, patient referring physicians, and the teams who delivered the HPA intervention. We performed semi-structured one-on-one interviews with 12 patients and 15 informal caregivers chosen using a maximum variation strategy, two focus group meetings with patient referring physicians (4 participants each), and one with the HPA teams (9 participants). Results From data analysis (framework method) 38 sub-categories emerged, which were grouped into 10 categories and 3 themes: 'expectations,' 'met and unmet needs', and 'barriers’. Intervention benefits were improved control of symptoms and reduced sense of isolation of the patient-caregiver dyads. Limitations were: factors related to experimental design (difficulty of dyads in identifying examiner and team roles, additional burden for caregivers); team issues (insufficient team building /supervision, competing priorities); limitations of the intervention itself (insufficient length, lack of rehabilitation input); and external factors (resource limitations, under-responsive services/professionals). The referring physician focus groups provided little experiential data. Conclusions The HPA reduced patient symptoms and sense of isolation in patients and caregivers. The indirect role of the HPA teams, and insufficient length of the intervention were key limitations. The experimental design imposed additional burdens on the dyads. Key barriers were the paucity of available services, the demanding administrative procedures, and lack of networking facilities. These findings suggest that two major requirements are necessary for home palliative care to be effective in this patient population: HPA teams well-connected with MS rehabilitation services, and care delivered over the long-term, with variable intensity. Trial registration Current Controlled Trials ISRCTN73082124 (Registered 19/06/2014).

Background: Evidence on the efficacy of palliative care in persons with severe multiple sclerosis (MS) is scarce. Objective: To assess the efficacy of a home-based palliative approach (HPA) for adults with severe MS and their carers. Methods: Adults with severe MS-carer dyads were assigned (2:1 ratio) to either HPA or usual care (UC). At each center, a multi-professional team delivered the 6-month intervention. A blind examiner assessed dyads at baseline, 3 months, and 6 months. Primary outcome measures were Palliative care Outcome Scale-Symptoms-MS (POS-S-MS) and Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW, not assessed in severely cognitively compromised patients). Results: Of 78 dyads randomized, 76 (50 HPA, 26 UC) were analyzed. Symptom burden (POS-S-MS) significantly reduced in HPA group compared to UC ( p = 0.047). Effect size was 0.20 at 3 months and 0.32 at 6 months, and statistical significance was borderline in per-protocol analysis ( p = 0.062). Changes in SEIQoL-DW index did not differ in the two groups, as changes in secondary patient and carer outcomes. Conclusion: HPA slightly reduced symptoms burden. We found no evidence of HPA efficacy on patient quality of life and on secondary outcomes.

National audience; L’étiologie de l’obésité tient à des facteurs génétiques et environnementaux, notamment nutritionnels. Nous avons montré que des différences de fonds génétiques chez la souris sont associées à une sensibilité forte (129S6), modérée (C57BL6/J) ou à une résistance (BALB/c) à l’obésité induite par un régime riche en graisse (RRG). L’objectif de ce travail est de tester le rôle de changements d’expression des microARN, déterminé par séquençage systématique de petits ARN dans le tissu adipeux blanc, sur l’adaptation physiopathologique au RRG. Les souris ont été nourries pendant une ou quinze semaines avec un régime contrôle (5 % de graisses) ou un RRG (40 % de graisse). Le séquençage des petits ARN a été effectué sur une plateforme Illumina HiSeq2000. Des algorithmes bioinformatiques ont été appliqués pour aligner les séquences sur le génome référence de souris et déterminer la quantité relative de chaque petit ARN. Résultats : Le RRG s’accompagne de modifications significatives (P < 0,05) d’expression de microARN connus (32) et de petits ARN (49) localisés dans des gènes/ESTs ou correspondant à des SnoRNA. La souche sensible C57BL6/J présente des variations d’expression de 11 et 13 microARN respectivement après 1 et 15 semaines de RRG, qui sont largement partagées avec l’autre souche sensible (129S6) (mir34b, c; mir96; mir135a1, a2, b; mir141, mir200b, c; mir449a). En revanche, chez la souche résistante BALB/c, l’expression de 4 microARN différents est modifiée après 1 semaine de RRG et aucune variation n’est retrouvée après 15 semaines. Ces résultats démontrent que l’expression de microARN et de SnoRNA connus, ainsi que de nouveaux petits ARN non encore répertoriés, est sensible à des changements de régime alimentaire. Les différences de régulation transcriptionnelle de ces ARN chez les souches susceptibles (C57BL6/J, 129S6) ou résistante (BALB/c) à l’obésité induite par le RRG suggère un rôle de ces microARNs dans la pathogénèse de l’obésité.

Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman’s test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4-dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease.

Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers. This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient’s caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. HPA and UC dyads are assessed at home by a blind examiner at baseline, and three and six months later; they also receive monthly telephone interviews. Dyads assigned to UC receive the examiner’s visits and telephone interviews, but not the team visits. Primary outcome measures are changes in symptoms (Palliative care Outcome Scale-Symptoms-MS, POS-S-MS), and quality of life (the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), not assessed in patients with severe cognitive compromise) at three and six months. Other outcomes are changes in patient functional status and mood; changes in carer quality of life, mood and caregiving burden; costs; incorporation with standard care; unplanned hospital admissions; referrals to hospice; and deaths. The experience of participants will be evaluated qualitatively by individual semi-structured interviews (HPA patients and carers) and focus group meetings (HPA patients’ caring physicians). The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention. The trial was registered with Current Controlled Trials (identifier: ISRCTN73082124 ) on 19 June 2014.

NEWFOR (NEW technologies for a better mountain FORest timber mobilization) is a research project funded by the alpine space programme. It brings together 14 institutes of the 6 countries of the alpine space with the aim of improving forest timber evaluation and mobilisation. The project considers the whole wood supply chain, from forests to wood yards, with a particular emphasis on new remote sensing technologies and geographical information systems. The report presents the major findings of the project and outlines some key issues for a better mobilisation of alpine timber ressoures.

NEWFOR (NEW technologies for a better mountain FORest timber mobilization) is a research project funded by the alpine space programme. It brings together 14 institutes of the 6 countries of the alpine space with the aim of improving forest timber evaluation and mobilisation. The project considers the whole wood supply chain, from forests to wood yards, with a particular emphasis on new remote sensing technologies and geographical information systems. The report presents the major findings of the project and outlines some key issues for a better mobilisation of alpine timber ressoures.

Un difetto della 21-idrossilazione (21OHD) nella corteccia surrenalica è la causa di oltre il 90% dei casi di iperplasia surrenalica congenita (ISC). Dal punto di vista biochimico il deficit determina una bassa concentrazione plasmatica di cortisolo e talvolta di aldosterone ed elevati livelli di 17OH-progesterone (17OHP), Δ4-androstendione (Δ4-A) e 21-desossicortisolo (21-DF), uno steroide collaterale presente in quantità insignificanti nella normale steroidogenesi. I pazienti con 21OHD sono tradizionalmente suddivisi in forme classiche (CL), tra cui una severa, con perdita di sali (PS; 75%) e una moderata, con virilizzazione semplice (VS; 25%), entrambe caratterizzate da virilizzazione prenatale/neonatale nei neonati di sesso femminile, e in forme non classiche (NC), a loro volta suddivisibili in forme sintomatiche con manifestazioni cliniche rilevabili ad età variabili nell’arco della vita, e forme asintomatiche.

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio-CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if