Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Late Palaeozoic South American pectinids revised: biostratigraphical and palaeogeographical implications

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intravenous versus inhalation anaesthesia for one-lung ventilation

BackgroundThis is an update of a Cochrane Review first published in The Cochrane Library, Issue 2, 2008.The technique called one-lung ventilation can confine bleeding or infection to one lung, prevent rupture of a lung cyst or, more commonly, facilitate surgical exposure of the unventilated lung. During one-lung ventilation, anaesthesia is maintained either by delivering an inhalation anaesthetic to the ventilated lung or by infusing an intravenous anaesthetic. It is possible that the method chosen to maintain anaesthesia may affect patient outcomes. Inhalation anaesthetics may impair hypoxic pulmonary vasoconstriction (HPV) and increase intrapulmonary shunt and hypoxaemia.ObjectivesThe objective of this review was to evaluate the effectiveness and safety of intravenous versus inhalation anaesthesia for one-lung ventilation.Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library (2012, Issue 11); MEDLINE (1966 to November 2012); EMBASE (1980 to November 2012); Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS, 1982 to November 2012) and ISI web of Science (1945 to November 2012), reference lists of identified trials and bibliographies of published reviews. We also contacted researchers in the field. No language restrictions were applied. The date of the most recent search was 19 November 2012. The original search was performed in June 2006.Selection criteriaWe included randomized controlled trials and quasi-randomized controlled trials of intravenous (e. g. propofol) versus inhalation (e. g. isoflurane, sevoflurane, desflurane) anaesthesia for one-lung ventilation in both surgical and intensive care participants. We excluded studies of participants who had only one lung (i.e. pneumonectomy or congenital absence of one lung).Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsWe included in this updated review 20 studies that enrolled 850 participants, all of which assessed surgical participants no studies investigated one-lung ventilation performed outside the operating theatre. No evidence indicated that the drug used to maintain anaesthesia during one-lung ventilation affected participant outcomes. The methodological quality of the included studies was difficult to assess as it was reported poorly, so the predominant classification of bias was 'unclear'.Authors' conclusionsVery little evidence from randomized controlled trials suggests differences in participant outcomes with anaesthesia maintained by intravenous versus inhalational anaesthesia during one-lung ventilation. If researchers believe that the type of drug used to maintain anaesthesia during one-lung ventilation is important, they should design randomized controlled trials with appropriate participant outcomes, rather than report temporary fluctuations in physiological variables.

Anticoagulant treatment for subsegmental pulmonary embolism

BackgroundAcute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the cardiovascular diseases, after coronary artery disease and stroke.The advent of multi-detector computed tomographic pulmonary angiography (CTPA) has allowed better assessment of PE regarding visualisation of the peripheral pulmonary arteries, increasing its rate of diagnosis. More cases of peripheral PEs, such as isolated subsegmental PE (SSPE) and incidental PE, have thereby been identified. These two conditions are usually found in patients with few or none of the classic PE symptoms such as haemoptysis or pleuritic pain, acute dyspnoea or circulatory collapse. However, in patients with reduced cardio-pulmonary (C/P) reserve the classic PE symptoms can be found with isolated SSPEs. Incidental SSPE is found casually in asymptomatic patients, usually by diagnostic imaging performed for other reasons (for example routine CT for cancer staging in oncologic patients).Traditionally, all PEs are anticoagulated in a similar manner independent of the location, number and size of the thrombi. It has been suggested that many patients with SSPE may be treated without benefit, increasing adverse events by possible unnecessary use of anticoagulants.Patients with isolated SSPE or incidental PE may have a more benign clinical presentation compared with those with proximal PEs. However, the clinical significance in patients and their prognosis have to be studied to evaluate whether anticoagulation therapy is required.ObjectivesTo assess the effectiveness and safety of anticoagulation therapy versus no intervention in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE.Search methodsThe Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). MEDLINE, EMBASE, LILACS and clinical trials databases were also searched (October 2013).Selection criteriaRandomised controlled trials of anticoagulation therapy versus no intervention in patients with SSPE or incidental SSPE.Data collection and analysisTwo review authors inspected all citations to ensure reliable selection. We planned for two review authors to independently extract data and to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions.Main resultsNo studies were identified that met the inclusion criteria.Authors' conclusionsThere is no randomised controlled trial evidence for the effectiveness and safety of anticoagulation therapy versus no intervention in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE, and therefore we can not draw any conclusions. Well-conducted research is required before informed practice decisions can be made.

Antidepressants for anorexia nervosa

Background Anorexia Nervosa ( AN) is an illness characterised by extreme concern about body weight and shape, severe self-imposed weight loss, and endocrine dysfunction. In spite of its high mortality, morbidity and chronicity, there are few intervention studies on the subject.Objectives The aim of this review was to evaluate the efficacy and acceptability of antidepressant drugs in the treatment of acute AN.Search strategy The strategy comprised of database searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, MEDLINE (1966 to April 28th, 2005), EMBASE (1980 to week 36, 2004), PsycINFO (1969 to August week 5, 2004), handsearching the International Journal of Eating Disorders and searching the reference lists of all papers selected. Personal letters were sent to researchers in the field requesting information on unpublished or in-progress trials.Selection criteria All randomised controlled trials of antidepressant treatment for AN patients, as de fined by the Diagnostic and Statistical Manual, fourth edition (DSM-IV) or similar international criteria, were selected.Data collection and analysis Quality ratings were made giving consideration to the strong relationship between allocation concealment and potential for bias in the results; studies meeting criteria A and B were included. Trials were excluded if non-completion rates were above 50%. The standardised mean difference and relative risk were used for continuous data and dichotomous data comparisons, respectively. Whenever possible, analyses were performed according to intention- to-treat principles. Heterogeneity was tested with the I-squared statistic. Weight change was the primary outcome. Secondary outcomes were severity of eating disorder, depression and anxiety symptoms, and global clinical state. Acceptability of treatment was evaluated by considering non-completion rates.Main results Only seven studies were included. Major methodological limitations such as small trial size and large confidence intervals decreased the power of the studies to detect differences between treatments, and meta-analysis of data was not possible for the majority of outcomes. Four placebo-controlled trials did not find evidence that antidepressants improved weight gain, eating disorder or associated psychopathology. Isolated findings, favouring amineptine and nortriptyline, emerged from the antidepressant versus antidepressant comparisons, but cannot be conceived as evidence of efficacy of a specific drug or class of antidepressant in light of the findings from the placebo comparisons. Non-completion rates were similar between the compared groups.Authors' conclusions A lack of quality information precludes us from drawing de finite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice.

Letteratura parascolastica e nazionalismo nella Prima Repubblica

In the early decades of Brazilian Republic, didactic literature played an important role in contributing to the «spirit of national integration», as José Veríssimo recommended. But, in addition to fighting the «parochialism» of different regions of the vast country, didactic literary works intended to combat the «foreign threat» represented by uncontrolled immigration and the economic and military imperialism. Brief analysis of Contos Pátrios (1894) and A Pátria Brasileira (1909), written by Olavo Bilac and Coelho Neto, and Porque Me Ufano do Meu País (1901), by earl of Afonso Celso, aims to reveal some of the resources used by the authors to elicit the feeling of brotherhood, solidarity and collective bond among Brazilian children, driving away threats that hung over the country. It also indicates that the interpretation of the national past, from which came the heroes, martyrs and leaders to be worshiped and imitated by children, radically opposed the monarchist Afonso Celso and the republicans Bilac and Coelho Neto.

Outpatient versus inpatient treatment for acute pulmonary embolism

Background: Pulmonary embolism (PE) is a common life-threatening cardiovascular condition, with an incidence of 23 to 69 new cases per 100,000 people per year. Outpatient treatment instead of traditional inpatient treatment in selected non-high-risk patients with acute PE might provide several advantages, such as reduction of hospitalizations, substantial cost saving and an improvement in health-related quality of life. Objectives: To compare the efficacy and safety of outpatient versus inpatient treatment for acute PE for the outcomes of all-cause and PE-related mortality; bleeding; and adverse events such as hemodynamic instability, recurrence of PE and patients'satisfaction.Search methodsThe Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched October 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 9). The TSC also searched clinical trials databases. The review authors searched LILACS (last searched November 2014). Selection criteria: Randomized controlled trials of outpatient versus inpatient treatment in people diagnosed with acute PE. Data collection and analysis: Two review authors selected relevant trials, assessed methodological quality, and extracted and analyzed data. Main results: We included one study, involving 339 participants. We ranked the quality of the evidence as very low due to not blinding the outcome assessors, the small number of events with imprecision in the confidential interval (CI), the small sample size and it was not possible to verify publication bias. For all outcomes, the CIs were wide and included clinically significant treatment effects in both directions: short-term mortality (30 days) (RR 0.33, 95% CI 0.01 to 7.98, P = 0.49), long-term mortality (90 days) (RR 0.98, 95% CI 0.06 to 15.58, P = 0.99), major bleeding at 14 days (RR 4.91, 95% CI 0.24 to 101.57, P = 0.30) and 90 days (RR 6.88, 95% CI 0.36 to 134.14, P = 0.20), recurrent PE within 90 days (RR 2.95, 95% CI 0.12 to 71.85, P = 0.51) and participant satisfaction (RR 0.97, 95% CI 0.92 to 1.03, P = 0.30). PE-related mortality, minor bleeding, and adverse course such as hemodynamic instability and compliance were not assessed by the single included study. Authors' conclusions: Current very low quality evidence from one published randomized controlled trial did not provide sufficient evidence to assess the efficacy and safety of outpatient versus inpatient treatment for acute PE in overall mortality, bleeding and recurrence of PE adequately. Further well-conducted research is required before informed practice decisions can be made.

Surgical interventions for treating pectus excavatum

Background: Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual's life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives: To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods: With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual's condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction. Date of the most recent searches: 14 January 2014. Selection criteria: We considered randomized or quasi-randomized controlled trials that compared traditional surgery with minimally invasive surgery for treating pectus excavatum. Data collection and analysis: Two review authors independently assessed the eligibility of the trials identified and agreed trial eligibility after a consensus meeting. The authors also assessed the risk of bias of the eligible trials. Main results: Initially we located 4111 trials from the electronic searches and two further trials from other resources. All trials were added into reference management software and the duplicates were excluded, leaving 2517 studies. The titles and abstracts of these 2517 studies were independently analyzed by two authors and finally eight trials were selected for full text analysis, after which they were all excluded, as they did not fulfil the inclusion criteria. Authors' conclusions: There is no evidence from randomized controlled trials to conclude what is the best surgical option to treat people with pectus excavatum.

Surgical interventions for treating pectus excavatum

Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual’s life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual’s condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction.

Active cutaneous warming systems to prevent intraoperative hypothermia: a systematic review

This study analyzed the evidence available in the literature concerning the effectiveness of different active cutaneous warming systems to prevent intraoperative hypothermia. This is a systematic review with primary studies found in the following databases: CINAHL, EMBASE, Cochrane Register of Controlled Trials and Medline. The sample comprised 23 randomized controlled trials. There is evidence in the literature indicating that the circulating water garment system is the most effective in maintaining patient body temperature. These results can support nurses in the decision-making process concerning the implementation of effective measures to maintain normothermia, though the decision of health services concerning which system to choose should also take into account its cost-benefit status given the cost related to the acquisition of such systems.

Propter adhorantium auctoritatem voluntate. Legittimazione, patronage e propaganda nelle Gesta Regum Anglorum di Guglielmo di Malmesbury

L’oggetto di ricerca della presente tesi di dottorato è costituito dall’analisi dell’opera Gesta Regum Anglorum, del monaco benedettino Guglielmo di Malmesbury, all’interno della quale sono stati esplorati e verificati i temi di legittimazione, di patronage e di propaganda. L’opera, infatti, rimane senza un manifesto committente, ad eccezione di una primissima versione. Il titolo della tesi rivela fin da subito questo aspetto, giacché estrae un passaggio del prologo al I libro: «propter adhorantium auctoritatem voluntate», traducibile con «per le autorevoli esortazioni che ricevetti». Dopo un’analisi delle lettere dedicatorie premesse all’opera, si è ipotizzata la volontà dell’autore di dedicare le Gesta Regum Anglorum, nella loro versione definitiva, a Roberto conte di Gloucester, approfondendo in tal senso l’aspetto legittimatorio dell’opera e la possibilità che essa potesse servire come strumento per ottenere un patronage dal conte nei confronti dell’abbazia di Malmesbury. La seconda parte della tesi è incentrata sulla comparazione tra le due principali redazioni dell’opera – quella conclusa intorno al 1126/27 e quella rivista tra 1135 e 1140 – per analizzarne le modifiche, ipotizzandone la funzione come volta mitigare aspetti relativi ai principali antenati di Roberto di Gloucester (Guglielmo I e Guglielmo II). La terza parte della tesi si è concentrata sull’aspetto propagandistico dell’opera in favore del monastero di appartenenza di Guglielmo (Malmesbury) e soprattutto in favore del clero regolare, nella dicotomia che caratterizzò questo e il clero secolare durante gli anni in cui l’autore viveva. Nell’ultima parte della tesi, è stato ripreso l’aspetto legittimatorio delle Gesta Regum, tentando di fornire un’analisi delle tre raffigurazioni dei sovrani normanni d’Inghilterra, che punteggiano i tre libri finali dell’opera.

Core networks for visual-concrete and abstract thought content: a brain electric microstate analysis

Commonality of activation of spontaneously forming and stimulus-induced mental representations is an often made but rarely tested assumption in neuroscience. In a conjunction analysis of two earlier studies, brain electric activity during visual-concrete and abstract thoughts was studied. The conditions were: in study 1, spontaneous stimulus-independent thinking (post-hoc, visual imagery or abstract thought were identified); in study 2, reading of single nouns ranking high or low on a visual imagery scale. In both studies, subjects' tasks were similar: when prompted, they had to recall the last thought (study 1) or the last word (study 2). In both studies, subjects had no instruction to classify or to visually imagine their thoughts, and accordingly were not aware of the studies' aim. Brain electric data were analyzed into functional topographic brain images (using LORETA) of the last microstate before the prompt (study 1) and of the word-type discriminating event-related microstate after word onset (study 2). Conjunction analysis across the two studies yielded commonality of activation of core networks for abstract thought content in left anterior superior regions, and for visual-concrete thought content in right temporal-posterior inferior regions. The results suggest that two different core networks are automatedly activated when abstract or visual-concrete information, respectively, enters working memory, without a subject task or instruction about the two classes of information, and regardless of internal or external origin, and of input modality. These core machineries of working memory thus are invariant to source or modality of input when treating the two types of information.

Protein disulfide isomerase blocks CEBPA translation and is up-regulated during the unfolded protein response in AML

Deregulation of the myeloid key transcription factor CEBPA is a common event in acute myeloid leukemia (AML). We previously reported that the chaperone calreticulin is activated in subgroups of AML patients and that calreticulin binds to the stem loop region of the CEBPA mRNA, thereby blocking CEBPA translation. In this study, we screened for additional CEBPA mRNA binding proteins and we identified protein disulfide isomerase (PDI), an endoplasmic reticulum (ER) resident protein, to bind to the CEBPA mRNA stem loop region. We found that forced PDI expression in myeloid leukemic cells in fact blocked CEBPA translation, but not transcription, whereas abolishing PDI function restored CEBPA protein. In addition, PDI protein displayed direct physical interaction with calreticulin. Induction of ER stress in leukemic HL60 and U937 cells activated PDI expression, thereby decreasing CEBPA protein levels. Finally, leukemic cells from 25.4% of all AML patients displayed activation of the unfolded protein response as a marker for ER stress, and these patients also expressed significantly higher PDI levels. Our results indicate a novel role of PDI as a member of the ER stress-associated complex mediating blocked CEBPA translation and thereby suppressing myeloid differentiation in AML patients with activated unfolded protein response (UPR).