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O Seminário Desnaturalização dos desastres e mobilização comunitária: novo regime de produção de saber foi resultado de um conjunto de reflexões e ações que vêm sendo realizadas compartilhadamente entre academia, organizações e movimentos comunitários que identificam a necessidade de aprofundar, com a sociedade, a discussão em torno de um entendimento mais geral do que é desastre. Do seminário participaram especialistas e pesquisadores, que trabalham nessa direção e que demonstram que a vulnerabilidade socioambiental se ancora desde a dita descoberta das Américas em processos de assimetria e desqualificação de saberes. Os saberes dominantes não são comuns à população. A combinação entre poder e saber facilita o não-reconhecimento das necessidades dos cidadãos e portanto, a não resolução dessas necessidades de existência e vida. Durante o seminário, foram realizadas apresentações de experiências com objetivo de ampliar o debate e oferecer um espaço de troca. A geração de novos valores e cultura política é um desafio complexo do processo de tornar-se protagonista de sua história. O seminário fundamentalmente foi um encontro de redes, motivado pela compreensão de que a mobilização comunitária e um novo regime de saber devem emergir dessa ação em redes, desses encontros de encontros, dessa rede de redes.

Friedreich ataxia is the most frequent hereditary ataxia among Caucasians. Almost invariably, the disease is caused by homozygous GAA triplet repeat expansions in the first intron of the frataxin gene, FXN, whereas point mutations or deletions in conjunction with an expanded GAA tract account for the remaining cases. The expanded intronic alleles interfere with FXN transcription, decreasing the production of normally functioning frataxin protein to 5-20% of normal. Deficient frataxin levels result in excessive mitochondrial iron accumulation, reduced iron-sulfur clusters vital for mitochondrial energy production, and increased intracellular oxidative damage. To date, no cure has emerged and treatments remain largely supportive, despite extensive ongoing research and several rationale strategies have been attempted.

Metabolic ataxias are rare. They usually start in the childhood and often have autosomal recessive inheritance. They may also present in adulthood. The diagnosis is important since some patients may be successfully managed with diet and treatments.

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, intracerebral haemorrhages, and focal neurological deficits. Familial form shows an autosomal dominant pattern of inheritance with incomplete penetrance and variable clinical expression. Three genes have been identified causing familial CCM: KRIT1/CCM1, MGC4607/ CCM2, and PDCD10/CCM3. Aim of this study is to report additional PDCD10/CCM3 families poorly described so far which account for 10-15% of hereditary cerebral cavernous malformations. Our group investigated 87 consecutive Italian affected individuals (i.e. positive Magnetic Resonance Imaging) with multiple/familial CCM through direct sequencing and Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis. We identified mutations in over 97.7% of cases, and PDCD10/ CCM3 accounts for 13.1%. PDCD10/CCM3 molecular screening revealed four already known mutations and four novel ones. The mutated patients show an earlier onset of clinical manifestations as compared to CCM1/CCM2 mutated patients. The study of further families carrying mutations in PDCD10/CCM3 may help define a possible correlation between genotype and phenotype; an accurate clinical follow up of the subjects would help define more precisely whether mutations in PDCD10/ CCM3 lead to a characteristic phenotype.

The prevalence and clinical consequences of diaphragmatic dysfunction (DD) during acute exacerbations of COPD (AECOPD) remain unknown. The aim of this study was (i) to evaluate the prevalence of DD as assessed by ultrasonography (US) and (ii) to report the impact of DD on non-invasive mechanical ventilation (NIV) failure, length of hospital stay and mortality in severe AECOPD admitted to respiratory intensive care unit (RICU).Forty-one consecutive AECOPD patients with respiratory acidosis admitted over a 12-month period to the RICU of the University Hospital of Modena were studied. Diaphragmatic ultrasound (DU) was performed on admission before starting NIV. A change in diaphragmatic thickness (ΔTdi) less than 20% during spontaneous breathing was considered to confirm the presence of dysfunction (DD+). NIV failure and other clinical outcomes (duration of mechanical ventilation MV, tracheostomy, length of hospital stay and mortality) were recorded.A total of 10 out of 41 patients (24.3%) presented DD+, which was significantly associated with steroid use (P = 0.002, R-squared = 0.19). DD+ correlated with NIV failure (P0.001, R-squared = 0.27), longer intensive care unit (ICU) stay (P = 0.02, R-squared = 0.13), prolonged MV (P = 0.023, R-squared = 0.15) and need for tracheostomy (P = 0.006, R-squared = 0.20). Moreover, the Kaplan-Meyer survival estimates showed that NIV failure (log-rank test P value = 0.001, HR = 8.09 (95% CI: 2.7-24.2)) and mortality in RICU (log-rank test P value = 0.039, HR = 4.08 (95% CI: 1.0-16.4)) were significantly associated with DD+.In hospitalized AECOPD patients submitted to NIV, severe DD was seen in almost one-quarter of patients. DD may cause NIV failure, and impacts on the use of clinical resources and on the patient's short-term mortality.

Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (ΔTdi) with a new parameter (ΔTmax index).41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in some patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or total lung capacity (TLC), and their ratio (ΔTmax) were recorded. Changes (Δ) in Tdi indices during tidal volume (ΔTdiVt) and maximal inspiration (ΔTdiTLC) were also assessed.ΔTdiTLC (p0.001) and ΔTmax (p = 0.007), but not ΔTdiVt, differed between patients and controls. Significant correlation (p 0.05) was found between ΔTdiTLC, ΔTmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Δtmax than with ΔtdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25).Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. ΔTmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests.

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.

Friedreich ataxia (FRDA) is caused by a GAA expansion in the first intron of the FXN gene, which encodes frataxin. Four percent of patients harbor a point mutation on one allele and a GAA expansion on the other. We studied an Italian patient presenting with symptoms suggestive of FRDA, and carrying a single expanded 850 GAA allele. As a second diagnostic step, frataxin was measured in peripheral blood mononuclear cells, and proved to be in the pathological range (2.95 pg/μg total protein, 12.7 % of control levels). Subsequent sequencing revealed a novel deletion in exon 5a (c.572delC) which predicted a frameshift at codon 191 and a premature truncation of the protein at codon 194 (p.T191IfsX194). FXN/mRNA expression was reduced to 69.2 % of control levels. Clinical phenotype was atypical with absent dysarthria, and rapid disease progression. L-Buthionine-sulphoximine treatment of the proband's lymphoblasts showed a severe phenotype as compared to classic FRDA.

Summary Background Spinocerebellar ataxias (SCAs) are autosomal, dominantly inherited, fully penetrant neurodegenerative diseases. Our aim was to study the preclinical stage of the most common SCAs: SCA1, SCA2, SCA3, and SCA6. Methods Between Sept 13, 2008, and Dec 1, 2011, offspring or siblings of patients with SCA1, SCA2, SCA3, or SCA6 were enrolled into a prospective, longitudinal observational study at 14 European centres. To be eligible for inclusion in our study, individuals had to have no ataxia and be aged 18–50 years if directly related to individuals with SCA1, SCA2, or SCA3, or 35–70 years if directly related to individuals with SCA6. We did anonymous genetic testing to identify mutation carriers. We assessed participants with clinical scales, questionnaires, and performance-based coordination tests. In eight of the 14 centres, participants underwent MRI. We analysed relations between outcome variables and time from onset (defined as the difference between present age and estimated age at ataxia onset). This study is registered with ClinicalTrials.gov, number NCT01037777. Findings 276 participants met inclusion criteria and agreed to participate, of whom 12 (4%) were excluded from final analysis because DNA samples were missing or genotyping failed. Estimated time from onset was −9 years (IQR −13 to −6) in 50 carriers of the SCA1 mutation, −12 years (–15 to −9) in 31 SCA2 mutation carriers, −8 years (–11 to −6) in 26 SCA3 mutation carriers, and −18 years (–22 to −16) in 16 SCA6 mutation carriers. Compared with non-carriers of each mutation, SCA1 mutation carriers had higher median scores on the scale for the assessment and rating of ataxia (SARA; 0·5 [IQR 0–1·0] vs 0 [0–0]; p=0·0052), as did SCA2 mutation carriers (0·5 [0–2·0] vs 0 [0–0·5]; p=0·0037). SCA2 mutation carriers had lower SCA functional index scores than did non-carriers (–0·43 [–0·91 to −0·07] vs 0·09 [–0·30 to 0·56]; p=0·0007). SCA2 mutation carriers had worse composite cerebellar functional scores than did their non-carrier counterparts (0·915 [0·861–0·959] vs 0·849 [0·764–0·886]; p=0·0039). All other differences between carriers and non-carriers were non-significant. In SCA1 and SCA2 mutation carriers, SARA scores were increased in participants who were closer to the estimated age at onset (SCA1: r =0·36, p=0·0112; SCA2: r =0·50, p=0·0038). 83 individuals (30%) underwent MRI. Voxel-based morphometry showed grey-matter loss in the brainstem and cerebellum in SCA1 and SCA2 mutation carriers, and normalised brainstem volume was lower in SCA2 mutation carriers (median 0·015, range 0·012–0·016) than in non-carriers (0·019, 0·017–0·021; p=0·0107). Interpretation Preclinical SCA1 and SCA2 mutation carriers seem to have mild coordination deficits and abnormalities in the brain that are more common in carriers who are closer to the estimated onset of ataxia. Individuals in this early disease stage could be targeted in future preventive trials. Funding ERA-Net E-Rare and Polish Ministry of Science and Higher Education.

Background The evolution of the techniques used in the intensive care setting over the past decades has led on one side to better survival rates in patients with acute conditions and severely impaired vital functions. On the other side, it has resulted in a growing number of patients who survive an acute event, but who then become dependent on one or more life support techniques. Such patients are called chronically critically ill patients. Materials & Methods No absolute definition of the disease is currently available, although most patients are characterized by the need for prolonged mechanical ventilation. Mortality rates are still high even after dismissal from intensive care unit (ICU) and transfer to specialized rehabilitation care settings. Results In recent years, some studies have tried to clarify the pathophysiological characteristics underlying chronic critical illness (CCI), a disease that is also characterized by severe endocrine and inflammatory impairments, partly accounting for the almost constant set of symptoms. Discussion Currently, no specific treatment is available. However, a strategic early therapeutic approach on ICU admission might try to prevent the progress of the acute disease towards chronic critical illness.

Chorea is a movement disorder which may be associated with immunologic diseases, in particular in the presence of antiphospholipid antibodies (aPL). Choreic movements have been linked to the isolated presence of plasmatic aPL, or to primary, or secondary antiphospholipid syndrome. The highest incidence of aPL-related chorea is detected in children and females. The presentation of chorea is usually subacute and the course monophasic. Choreic movements can be focal, unilateral, or generalized. High plasmatic titers of aPL in a choreic patient can suggest the diagnosis of aPL-related chorea; neuroimaging investigation does not provide much additional diagnostic information. The most relevant target of aPL is β2-glycoprotein I, probably responsible for the thrombotic manifestations of antiphospholipid syndrome. Etiology of the movement disorder is not well understood but a neurotoxic effect of aPL has been hypothesized, leading to impaired basal ganglia cell function and development of neuroinflammation. Patients affected by aPL-related chorea have an increased risk of thrombosis and should receive antiplatelet or anticoagulant treatment.

Mutations in the SPG3A gene represent a significant cause of autosomal dominant hereditary spastic paraplegia with early onset and pure phenotype. We describe an Italian family manifesting a complex phenotype, characterized by cerebellar involvement in the proband and amyotrophic lateral sclerosis-like syndrome in her father, in association with a new mutation in SPG3A. Our findings further widen the notion of clinical heterogeneity in SPG3A mutations.

To the Editor: Mycobacterium marseillense was recently described as a new species belonging to the Mycobacterium avium complex (MAC) (1). We describe a case of pulmonary disease caused by M. marseillense in an immunocompetent patient. All strains isolated from the patient were preliminarily identified as M. intracellulare; however, a retrospective molecular analysis corrected the identification to M. marseillense. In December 2005, a 65-year-old man was admitted to the University Hospital, Modena, Italy, with a 2-week history of fever, cough, and hemoptysis. Physical examination detected diffuse rales, and chest radiographs showed a diffuse nodular opacity and bronchial thickening, confirmed by high-resolution computed tomography (CT) of the chest (Figure, panel A). The patient had experienced several previous episodes of hemoptysis and persistent productive cough since 1998, and tubular bronchiectasis had been detected on previous high-resolution CT images. The patient had a history of thalassemia minor, was HIV negative, and was formerly a mild smoker (10 cigarettes/day for 4 years during his youth). He had no chronic disorders and no history of immunosuppressive-drug or alcohol use. Figure High-resolution computed tomographic chest images of a man with prolonged pulmonary disease caused by Mycobacterium marseillense, Italy. A) October 6, 2005. Bilateral bronchiectasis, mainly in the middle lobe and lingula, associated with multiple nodules ... Bacterial and fungal cultures and a smear for acid-fast bacilli performed on a bronchoalveolar lavage (BAL) sample were all negative. A nontuberculous mycobacterium strain was isolated by culture and preliminarily identified as M. intracellulare by using the GenoType Mycobacterium CM/AS Kit (Hain Lifesciences, Nehren, Germany). At that time, a drug susceptibility test for isoniazid, rifampin, streptomycin, and ethambutol was improperly performed (i.e., was not applicable for MAC) by using the agar proportion method; sensitivity information for macrolides was unavailable. The strain was resistant to ethambutol and susceptible to the other drugs. The physician prescribed rifampin, isoniazid, and amikacin. After remission of fever and hemoptysis and improvement of chronic cough, the patient was discharged from the hospital. In March 2006, he was readmitted to the hospital for worsening of his condition and onset of side effects associated with rifampin and isoniazid use. The treatment was discontinued and replaced by levofloxacin, terizidone, and azithromycin, which resulted in remission of symptoms. This therapy was continued after hospital discharge. In 2007, the patient was twice admitted for follow-up and microbiological testing to determine bacteriologic status. All 3 separate sputum samples were negative for mycobacteria, other bacteria, and fungi. However, BAL sample culture results were positive for the same mycobacterium despite continued therapy with levofloxacin, terizidone, and azithromycin. During 2008, as an investigation of the possibility of persistent excretion of organisms, additional samples were collected 5 times. The sputum cultures were intermittently positive, while the BAL sample cultures were persistently positive. In May 2009, after the patient had been persistently stable and had negative culture results for 14 months, the antimicrobial drug therapy was stopped. In December 2010, the patient’s only symptom was persistent productive cough; however, the sputum culture was again positive, and high-resolution CT revealed a worsening condition of his lungs (Figure, panel B). A new antimycobacterial drug regimen of ethambutol, rifampin, and azithromycin was started, in accordance with the international guidelines of the American Thoracic Society and the Infectious Diseases Society of America (2). After the patient had received 6 months of therapy, the sputum culture result was again negative. The acid-fast bacilli smear and culture results remained negative until November 2012. The latest treatment resulted in recovery from symptoms and a more stable condition. However, cough and sputum production, although attenuated, persisted despite treatment and negative microbiological test results. High-resolution CT images (Figure, panel C) indicated overall progression of pulmonary involvement from the time of first admission. In February 2011, on the basis of the known cross-reactivity of the M. intracellulare probe with most MAC species when the GenoType Mycobacterium CM/AS assay is used (3), we determined the sequences of a portion of the rpoB gene and internal transcribed spacer–1 region in 2 strains isolated from sputum in March 2006 and June 2010. All sequences overlapped with M. marseillense type strain sequences in GenBank, showing an identity of 100% in internal transcribed spacer–1 with {"type":"entrez-nucleotide","attrs":{"text":"EU266631","term_id":"167515227","term_text":"EU266631"}}EU266631 and 99.8% (1 mismatch) in rpoB with {"type":"entrez-nucleotide","attrs":{"text":"EF584434","term_id":"157851003","term_text":"EF584434"}}EF584434. We therefore show the association of M. marseillense infection with pulmonary disease in an immunocompetent patient, helping define the clinical features and natural history of pulmonary disease caused by M. marseillense. We cannot assert whether the clinical course is associated with the intrinsic characteristics of M. marseillense infection or with the therapeutic regimen, possibly influenced by numerous adverse effects that may have compromised its effectiveness. More careful management in accordance with the American Thoracic Society and the Infectious Diseases Society of America guidelines for management of nontuberculous mycobacterial diseases could have achieved a more effective course of treatment. More case reports of pulmonary disease caused by M. marseillense are needed to support our observations and to provide more insight into its clinical picture.

We investigated how cerebellar degeneration influences the plasticity of the tprimary motor cortex (M1) by using PAS (paired associative plasticity) technique. PAS involves repeated pairs of electrical stimuli to the median nerve and transcranial magnetic stimuli of the motor cortex. If the interval between peripheral and cortical stimulation is around 21–25 ms, corticospinal excitability is increased via a long-term potentiation (LTP)-like effect within M1. Our aims were: (i) to explore the presence of a time-specific influence of cerebellar degeneration on human associative plasticity; (ii) to evaluate the role of the somatosensory pathway on the cerebellar modulation of sensory-motor plasticity. We studied 10 patients with pure cerebellar atrophy and 10 age-matched healthy subjects. Motor evoked potentials amplitudes, short-afferent inhibition, motor thresholds, I/O curves, somatosensory-evoked-potentials (SEPs) were measured before, just after and 30 min after PAS at interstimulus intervals of 21.5 and 25 ms. In cerebellar patients, LTP-like effect induced by PAS was abolished at 25 ms, but not at 21.5 ms. SEPs showed that the P25 wave amplitude was markedly reduced in patients with a more severe clinical and radiological impairment of the cerebellum. Patients with cerebellar atrophy have an altered capability to process time-specific sensory volleys, influencing the M1 plasticity.