All protocols were reviewed and approved by the Institutional Animal Care and Use Committee of MPI Research for compliance with regulations prior to study initiation. The brachial nerve block procedure was performed in an MPI Research surgical suite using aseptic technique. General anesthesia was induced and maintained with isoflurane to effect delivered in oxygen through a facemask. Each dose was administered by nerve block once on Day Inhibitors,research,lifescience,medical 1. A 22g 3.5inch needle was used to perform a brachial plexus nerve block in the left thoracic limb [15]. After placement the needle was slowly withdrawn while each treatment was injected. The animals were closely monitored

during anesthetic recovery for physiological disturbances including cardiovascular/respiratory depression, hypothermia, and excessive BVD-523 in vitro bleeding from the injection site. Using a standard, Inhibitors,research,lifescience,medical by weight, block randomization procedure, 20 males and 20 females were assigned to five groups in each study. Each group consisted of 4 males and 4 females. Groups 1, 2, and 3 received Inhibitors,research,lifescience,medical EXPAREL 9, 18, and 25mg/kg (or

30mg/kg), respectively. Group 4 received bupivacaine solution 9mg/kg, Group 5 received saline. In rabbits, EXPAREL was administered at a dose volume of 0.6, 1.2, and 1.2mL/kg, respectively. In dogs, EXPAREL was administered at a dose volume of 0.6, 1.2, and 1.0mL/kg, respectively. (The dogs intended for the 30mg/kg group were erroneously administered only 1.0mL/kg (25mg/mL) resulting in a dose level of 25mg/kg.) Bupivacaine

solution and saline control was administered at a dose volume of 1.2mL/kg in each species. Following dose administration, animals were Inhibitors,research,lifescience,medical observed without further treatment. Four animals (2 males and 2 females) in each group were sacrificed on Day 3, and the remainder (designated as recovery animals, 2 males and 2 females) were observed for an additional two weeks until Day 15 sacrifice. Endpoints included physical examinations, clinical Inhibitors,research,lifescience,medical signs, clinical pathology, hematology, organ weight, first and histopathology of a standard list of tissues (including injection sites) on Day 3 and Day 15, as well as pharmacokinetics (PK) on Day 1 through 96 hours postdosing. 2.2.2. Pharmacokinetic Data Analysis Plasma bupivacaine concentrations were measured using a validated LC/MS/MS assay in rabbit and dog K3EDTA plasma in the concentrations ranging from 10.0 to 10,000ng/mL. The lower quantitation limit was 10ng/mL. The PK parameters were evaluated by a noncompartmental model using WinNonlin, version 5.0 (Pharsight Corp., Mountain View, California). The PK parameters were maximum plasma concentration (Cmax ), time at which the Cmax occurred (tmax ), and area under the plasma concentration-time data from time 0 to selected time point (t) (AUC0-t ).

51 Similarly, ERT in postmenopausal women appears to be associated with a higher risk of venous thrombosis during the first year of use.52 However, whether ERT INCB018424 molecular weight imposes a risk for ischemic stroke in postmenopausal women is unclear. We now understand that the dose of estrogen administered and the route of estrogen delivery are key components in determining clotting potential. At higher Inhibitors,research,lifescience,medical doses, oral estrogen, which enters the body via the enterohepatic

system, can stimulate the production of thrombogenic factors53,54 predominantly through its actions on the liver. Alternatively, lower doses of estrogen, delivered orally or transdermally, may not significantly

affect hemostasis.53,55-57 Importantly, transdermal delivery of estrogen bypasses enterohepatic circulation and may thus prevent estrogen-mediated stimulation of thrombogenic factors in the liver. Inhibitors,research,lifescience,medical Collectively, these findings highlight the importance of low, physiological doses in estrogen replacement of postmenopausal women. ERT and stroke: overview of clinical studies Studies have only begun to explore the actions of hormone replacement on stroke in the clinical setting. Data from several human studies clearly indicate that Inhibitors,research,lifescience,medical estrogen exerts protection against stroke58-61; however, many studies report cither protective trends or no significant, Inhibitors,research,lifescience,medical effect, of estrogen58,59,62-72 and few

report deleterious effects of estrogen.62,66,73,74 Preliminary results from the latest clinical study, the Women’s Estrogen for Stroke Trial (WEST), indicate that estrogen docs not protect against the rate of either nonfatal stroke or death in postmenopausal women with a history of stroke.75 In parallel with studies that fail to detect estrogen-mediated protection of the heart in women with cardiovascular disease,16 or of the brain in women with AD,43 the results of WEST suggest that estrogen does not effectively protect against, or Inhibitors,research,lifescience,medical reverse a disease process that has already been initiated. To date, clinical studies have mainly probed whether ERT significantly affects the incidence and mortality of stroke. The outcomes of many of these studies are varied and often appear to be contradictory. Thus, we cannot yet draw clear conclusions much from the existing data due to several confounding issues. The lack of uniformity among the data in clinical reports may result, from several inconsistencies.44 First, stroke is a mixed group of diseases with varying etiologies. If ERT decreases or increases the risk of specific stroke subtypes, effects of estrogen may be distorted and/or masked when strokes arc grouped together and classified differently among the studies.

The oral risperidone group had persistent symptoms or side effects. Patients had high scores in the positive and negative syndrome scale (PANSS), even though they were considered stable. However, these patients

could not be considered refractory to antipsychotics. Subjects were switched to RLAI from their previous therapeutic Inhibitors,research,lifescience,medical medications as follows. Subjects were given an initial dose of RLAI 25 mg in addition to their previous therapeutic medications, and received gluteal injections at 2-week intervals, alternating the left and right sides. After 4 weeks, by which point the blood concentration had started to rise, the dosages of the subjects’ previous therapeutic medications were reduced so that the subjects received total dosages equivalent to the dosages of their previous therapeutic medications. After 6 weeks, the RLAI dosage was increased as necessary to optimize the dose, and all subjects were receiving RLAI monotherapy. It was therefore possible to investigate the intrinsic effect of cognitive Inhibitors,research,lifescience,medical function of RLAI. Following RLAI Inhibitors,research,lifescience,medical optimal dose adjustment, wherever possible the dosages of any concomitant medications, including anti-Parkinson’s medications, were reduced. When switching subjects to RLAI, the antipsychotic equivalents calculation

table of Inagaki and Inada was used as a guideline for calculating antipsychotic equivalents [Inagaki and Inada, 2010], and the subjects’

daily dosages was calculated in terms of risperidone equivalents. Only patients who had provided voluntarily informed consent in writing to participate in this study upon receiving a full explanation of the purpose and method of the study were enrolled, while patient Inhibitors,research,lifescience,medical confidentiality was afforded all due consideration, as were ethical considerations. Clinical and cognitive assessments The following clinical and cognitive assessments were performed both at baseline and Inhibitors,research,lifescience,medical at 24 weeks by the psychiatrist providing the actual therapy. There were no reliability tests for those who applied the PANSS and cognitive tests. However, assessor training was provided to ensure a certain degree of reliability. PANSS was used to investigate efficacy [Kay et al. 1987]. Cognitive function was assessed using the Wisconsin Card Sorting Test: Keio Version (KWCST) [Kashima, 2002], and St why Marianna University School of Medicine’s Computerized Memory Test (Selleck CDK inhibitor STM-COMET) [Suzuki et al. 2011] as the executive function test and verbal memory function and attention function tests, respectively. The KWCST is the WCST [Heaton et al. 1993], which is the most widely used test of frontal lobe function, with several revisions made by Kashima [2002], the most significant of which are the reduction in the number of response cards from Milner’s 128 to 48, and the reorganization of the method used to give instructions in two stages.

Diverse reasons for this high use of unmodified ECT have been put forth, such as lack of equipment, personnel and anesthesiologists, contraindication for anesthesia, convenience, emergency, and economic purposes (Chanpattana et al. 2005b). Whether these arguments are acceptable in this modern era and in light of knowledge about benefits and harms of ECT is another question. In spite of attempts to ban it (Mudur 2002), the debate defending unmodified ECT practice (Andrade et al. 2010), and

voices claiming this practice to be unjustified and unethical (Grunhaus 2010) is ongoing today. Unmodified ECT is still practiced in some parts of Russia, Turkey, and Spain (Zeren et al. 2003; Inhibitors,research,lifescience,medical Nelson 2005; Bertolin-Guillen et al. 2006), and international guidelines (American Psychiatric Association 2001; Royal College of Psychiatrists 2005; Enns et al. 2010) appear to have failed (Strachan 2001) in influencing important Sepantronium Bromide cost aspects of today’s ECT practice. The practice in many countries Inhibitors,research,lifescience,medical of Asia (Chanpattana and Kramer 2004; Chanpattana et al. 2005a, b, 2010), Latin America (Levav and Gonzalez 1996), and Africa (Odejide et al. 1987; Mugisha and Ovuga 1991; Selis et al. 2008; James et al. 2010) bear a resemblance Inhibitors,research,lifescience,medical to the beginning of ECTs medical history in Europe (Cerletti and Bini 1938). The Asian practice of today resembles practice

that was used in Finland in 1944 and 1964 (Huuhka et al. 2000), where the majority of ECT-treated patients were diagnosed with schizophrenia (75–78%) and treated unmodified. Likewise, in 1944 in Finland, ECT was (Huuhka et al. 2000) more often given to men than women (36% women). In 1997 in Finland, a major shift occurred toward majority of patients (78%) having affective disorders (unipolar/bipolar depression) and treated modified

(Huuhka et al. Inhibitors,research,lifescience,medical 2000). This shift in Western Inhibitors,research,lifescience,medical world practice and the increasing use of ECT among women is also found both in USA and Australia, in the 1980s to 1990s (Galletly et al. 1991; Rosenbach et al. 1997). Similar changes seem to be occurring in some areas of Asia (Alhamad 1999; Naqvi and Khan 2005; Ahikari et al. 2008; Chanpattana et al. 2010). One reason for the lingering ECT use among patients with schizophrenia might be availability of antipsychotic medication, such as in Thailand, where the essential drug list from the Ministry of Health does not include antipsychotics (Chanpattana and Kramer 2004). Also, shortage of anesthesiologist and negative images is another explanation that Florfenicol is given for having hindered Japanese psychiatrists from reforming ECT practice for a long time (Motohashi et al. 2004). Another explanation of practice differences, diagnostic and gender disparities between Asia and Europe, Australia and New Zealand, and USA might be the historical use of ECT, being much longer in Europe where it originated in 1938 (Cerletti and Bini 1938) and its early spreading to the United States (Cerletti and Bini 1938; Hemphill and Walter 1941; Shorter 2009).

Acknowledgments Financial supporting of this project by the Vice Chancellery of Research of the Isfahan University of Medical Sciences is acknowledged. The paper is extracted from the dissertation of Sindokht Soltanzadeh, the Pharm D student of Isfahan University of Medical Sciences. This contribution is presented at International Conference on Nanotechnology: Fundamentals and Applications (July 2011, Ottawa, Canada ICNFA 2011, http://international-aset.com/).
Poor Inhibitors,research,lifescience,medical solubility in water is a well-recognized obstacle for efficient oral or parenteral drug administration [1, 2].

Liposomes are among the most widely used type of pharmaceutical nanocarriers for small and Navitoclax mouse poorly water-soluble

drug molecules [3]. These drugs preferentially partition into the hydrophobic Inhibitors,research,lifescience,medical compartment that is formed by the hydrocarbon tails of the liposomal lipids. Liposomes have been used in their first generation (conventional liposomes) predominantly as long-circulating transport vehicles [4, 5], followed by a second generation that improved the circulation time further by decorating the surface with PEG-chains (stealth liposomes [6]). Third-generation liposomes are now being engineered to contain targeting Inhibitors,research,lifescience,medical ligands [7] and to carry out stimuli-sensitive triggering of the drug release [8]. An important property of liposome-based drug delivery is the release kinetics of the drug from the host, which has been investigated for a number of Inhibitors,research,lifescience,medical model systems [9–12]. Experimental investigations of the transfer of temoporfin between two different types of liposomes (i.e., from donor liposomes to acceptor liposomes) have recently been carried out using a mini ion exchange column technique Inhibitors,research,lifescience,medical [13]. The column separates donor from acceptor liposomes and thus allows to monitor the time dependence of the drug transfer. It is observed that, typically, the transfer

follows an apparent first-order behavior, characterized by a single exponential function. This is remarkable given the complexity of the system, with the drug molecules being able to migrate from the donor to the acceptor liposomes via different physical mechanisms. In fact, there are two mechanisms that, in general, act PDK4 simultaneously. The first mechanism is the transfer of drugs upon collisions between two liposomes. In this case, the drug molecules directly migrate from one liposome to another with minimal exposure to the aqueous phase. The second mechanism refers to the transfer of drugs via diffusion through the aqueous phase. We note that the collision mechanism has been invoked, for example, to explain the transfer of lipids [14] and cholesterol [15] between vesicles, and the transfer of fatty acids between vesicles and fatty acid binding proteins [16].

As seen in Figure 4, the grand averaged P100 waveforms (mean latency 118 ± 4 msec) for the remaining three conditions (SIM, TVd, TT) displayed a bilateral distribution at parietal sites and maximal amplitude at electrode site PZ. Results showed a main effect of condition observed at electrode

sites P4 (F2,28 = 7.95, P = 0.002), PZ (F2,28 = 5.97, P = 0.007), and P3 (F2,28 = 10.73, P < 0.001). Tukey's post hoc tests showed that for each electrode site, the amplitude of the P100 was larger in the SIM compared to the TVd task (P < 0.05) and the TT task (P < 0.05, Fig. 5B). A main effect of condition was found for the P100 latency Inhibitors,research,lifescience,medical at electrode P4 using separate one-way repeated measures ANOVA (F2,28 = 3.64, P = 0.04). However, Tukey's post hoc analysis revealed no statistically significant differences between conditions. Furthermore, no main effect

of condition was found for electrodes PZ (F2,28 = 1.02, P = 0.37) Inhibitors,research,lifescience,medical or P3 (F2,28 = 0.36, P = 0.7). Figure 4 Grand averaged P100 waveforms. Grand average P100 waveforms are shown for parietal electrode Inhibitors,research,lifescience,medical sites (P3, PZ, P4) for SIM, TVd, and TT conditions. The P100 ERP component is labeled on the trace for electrode site P3. Gray, red, and black traces show SIM, … Behavioral data Figure 6 shows the behavioral means and standard error bars for each task-relevant crossmodal condition: SIM (mean = 92, SE = 3.3), VTd (mean = 83, SE = 2.9), TVd (mean = 98, SE = 3.4). A one-way repeated measures ANOVA was performed on the error differences represented as a percent score across all conditions and showed that there was a main effect of condition (F2,16 = 8.45, P = 0.003). Inhibitors,research,lifescience,medical Post hoc Tukey’s test showed that performance in the VTd condition was significantly different than the TVd task. Participants tended to produce lesser force than the ideal target in the VTd condition. There were no other

differences between conditions. Figure 6 Group means for behavioral data. The gray bar graph represents group data for the visual + buy AMD3100 tactile simultaneous condition (SIM), the red bar graph represents group data for the condition where tactile stimuli were Inhibitors,research,lifescience,medical presented 100 msec … Discussion In this study, we used EEG and crossmodal stimuli (visual + vibrotactile) to examine the roles of visual information and attentional relevance in modulating early cortical responses generated in SI. To test the influence of bottom-up sensory-sensory interactions Ketanserin and top-down attentional processes on early modality-specific cortical responses, we devised a novel experimental protocol that manipulated the temporal onsets of task-relevant crossmodal (visual + tactile) interactions. In one condition, visual stimuli preceded the onset of tactile stimuli by 100 msec (i.e., VTd), in order to observe the influence of the visual modality on the P50 component generated in SI. In another condition, tactile stimuli preceded the onset of visual stimuli by 100 msec (i.e.

The variables used as explanatory variables in the logistic model were derived from data sought from callers by call workers, for instance, ‘how is his consciousness?’ Under an emergency situation, the number of such questions is inevitably limited. Patient’s age, consciousness level, breathing status, walking ability, position, and complexion were selected as data that a call worker should seek in the interview

protocol. There may be factors for assessing the life threat risk other than the variables used in the current algorithm. If other indicative factors are found in the future, they should be part of the interview protocol and should be included as explanatory variables in the model. The coefficients Inhibitors,research,lifescience,medical of the logistic model were estimated by logistic regression analyses whose dependent variable is 1 if the patient’s

condition resulted in death or was recognized as life-threatening by Inhibitors,research,lifescience,medical physicians at the ED. Otherwise the dependent variable was 0. Although the current algorithm was constructed with the dependent variable of such outcome, i.e., 1 or 0 mentioned above, there may be other outcomes or indices that serve as the optimum yardstick for determining advanced life support intervention. Obtaining accurate information from the Inhibitors,research,lifescience,medical initial call to the emergency services is crucial for developing a well-organized algorithm. The information on the patient’s condition is quite accurately recorded under the new system because the information was entered into a computer-based triage form Inhibitors,research,lifescience,medical during the phone call. In the meantime, the information obtained from callers is prone to being inaccurate if the callers do not observe patients sufficiently to give the accurate information required. Such cases should be excluded from the targets of call triage. A logistic model does not yet exist that can assess the patient’s risk of death when Inhibitors,research,lifescience,medical calls are made to emergency services by the patients themselves. Such a model is unlikely to be developed no matter how much data will be collected, because only a small

percentage of such cases resulted in a critical condition. Methods other than a quantitative approach may be preferable to predict the chance of a critical condition occurring when an emergency call is made by the patient. Conclusion A patient’s life threat risk can be quantitatively expressed at the moment of the emergency call with a moderate Adenosine level of accuracy. The algorithm for estimating a patient’s life threat risk should be improved further as more data are collected. Competing Selleck Alisertib interests The copyright of the computer-based triage form used in the study belongs to Yokohama City University. Authors’ contributions KO designed the study and drafted the manuscript. NS and YM managed data collection. KO and CK analyzed the data. SM helped to draft the manuscript. All authors contributed substantially to the revision of the draft manuscript.

Poor adherence to treatment Despite the obvious need for treatment of psychosis itself and the comorbid conditions, the treatment of recent-onset psychosis patients is a most challenging task. Substance abuse and lack of insight into the illness, and consequently poor adherence to treatment, are the most often quoted reasons for this difficulty71 Unfortunately it appears that poor insight is more common and severe in recent-onset psychosis patients who have the most severe and pervasive form of illness in terms of general psychopathology, positive and negative symptoms, as well as cognitive domains.72 This in turn underscores the challenge Inhibitors,research,lifescience,medical of treating

the less insightful patients; Inhibitors,research,lifescience,medical they are the ones who need treatment most and are also the least likely to accept it. While many of the first-episode patients with poor insight are admitted and occasionally treated involuntarily73 for the long-term maintenance treatment, the patient’s active cooperation is essential. It is a particularly difficult challenge to convince patients who have remitted from their first episode of psychosis and who are not yet familiar with the cycling nature of the disease that, despite absence of

active psychotic symptoms, they can benefit from maintenance treatment.74 Long-term studies indicate that, if not maintained on antipsychotic medication, more than 50% of the patients Inhibitors,research,lifescience,medical who remitted from the first episode of psychosis will PF-04691502 nmr exacerbate during the first year following remission75 and the percentage will rise during the subsequent years. Although most practicing psychiatrists and guidelines will recommend that a remitted patient who had a single episode of psychosis should be treated for Inhibitors,research,lifescience,medical at least 1 year, there are a number of unanswered questions that reflect the limitations of the current clinical knowledge: Is there a preferred maintenance strategy or drug? Can we identify the 50% of the patients who despite lack of maintenance treatment, will not exacerbate during

Inhibitors,research,lifescience,medical first the first year? Can we identify the patients who will exacerbate despite maintenance treatment? Considering that there are no satisfactory answers for the last two questions and considering the drugs’ adverse effects, how does pharmacological treatment impact on the quality of life? Most guidelines recommend for maintenance atypical rather than typical31 antipsychotics in this population. This recommendation is supported by a recent trial comparing low-dose haloperidol with low-dose risperidone in recent-onset psychosis patients, which demonstrated in a posthoc analysis that, once remitted, more patients randomized to risperidone maintained remission for longer periods of time than with haloperidol.23 It is not clear at this time if this is a class effect or if it is limited to risperidone.

One of the caveats for the second step of MDMS-based platform and the class-specific tandem MS-based platform is that both cannot be applied to a lipid class for which a class-specific and sensitive PIS or NLS is not present (e.g., cardiolipin). Special quantification methods have been developed in MDMS-based shotgun lipidomics

for these classes. These methods include derivatizing a moiety of head group to provide a sensitive, class-specific tandem MS (e.g., derivatization Inhibitors,research,lifescience,medical of primary amine in head group of ethanolamine-containing classes with Fmoc chloride to allow a facile neutral loss of Fmoc from the tagged species), and exploiting the this website uniqueness of individual lipid classes (e.g., M + 0.5 isotopologue patterns for doubly-charged cardiolipin species) for quantification. The other caveat for the

second step of Inhibitors,research,lifescience,medical MDMS-based shotgun lipidomics is that the species determined in the second step of quantification using endogenous standards quantified in the first step may have a propagated and therefore larger experimental error than the species determined in the first step using exogenously added standard(s). To minimize the Inhibitors,research,lifescience,medical error in the second step, it is critical to reduce any potential experimental error in the first step. For example, it is important to use exclusively the species that have large S/N and can be quantified accurately from the Inhibitors,research,lifescience,medical first step as endogenous standards for the second step to reduce propagation of errors. Additionally, the propagated experimental error in the second step affects the accuracy of quantification of total amount only moderately because the species quantified in the second step account for a relatively small portion of the total in comparison to those abundant species quantified in the first step. To validate the quantitative accuracy of the two-step procedure of MDMS-based shotgun lipidomics, we have recently performed a series of experiments by spiking exogenous lipid species before or after extraction to Inhibitors,research,lifescience,medical determine the linear dynamic ranges and the matrix effects [10]. In the first set of experiments, a mouse

myocardial lipid extract was prepared without addition of any internal standards, and then diluted to a concentration of <100 pmol of total lipids/μL. To the diluted extract solution, Dichloromethane dehalogenase different amounts of di14:1 phosphatidylcholine (PC) (commonly used as an internal standard for PC class in the platform) were spiked to reach final concentrations from 0.16 to 16 pmol/μL, spanning a 100-fold range. Considering that the content of numerous endogenous PC species in the myocardial lipid extract spans over 100-fold, this set of experiments tests an overall dynamic range of 10,000 for quantification. The content of di14:1 PC was then separately determined by a full MS scan and two class-specific tandem MS scans (NLS 183.2 and NLS 189.2) with ratiometric comparisons with the base peak at m/z 812.6 (i.e.

Conclusions and key points for parents A diagnosis of Pompe disease can be overwhelming and raise many questions. Genetic counselors are health care professionals specially trained to educate families on the disease’s inheritance patterns and risks, as well as to support them through testing and family-planning decisions. Couples should be aware that the results of prenatal testing cannot Inhibitors,research,lifescience,medical predict the age of onset, clinical course, or degree of disability. Parents must be reassured that not all infants identified

as having low GAA activity through newborn screening will have Pompe disease. If the infant will develop Pompe disease, treatment is available which may ameliorate the clinical symptoms of the disorder.
Pompe disease is a rare lysosomal disorder Inhibitors,research,lifescience,medical of muscle glycogen metabolism due to alfa-glucosidase (GAA) deficiency. The prevalence of this disease is estimated to be 1:40.000. Since 2006, Enzyme Replacement Therapy (ERT) became available in Fedratinib purchase Europe and US. So far, there are no officially

approved international guidelines about ERT inclusion criteria of patients but they must have a defined diagnosis of Pompe disease confirmed by a biochemical and molecular genetic examinations (1). So far, ERT has been generally prescribed to patients with motor symptoms (muscle weakness) and/or respiratory involvement. Exclusion criteria encompassed a severe Inhibitors,research,lifescience,medical associated illness which would be expected to greatly shorten life expectancy. Alglucosidase (Myozyme) is administered Inhibitors,research,lifescience,medical biweekly i.v. as 20 mg/kg. Although the high costs of the drug, in several European countries the patients are fully supported by their Ministries of Health. In fact, in Belgium, National guidelines consider every patient with clinical symptoms of muscle and/or respiratory involvement as a candidate for ERT that, on

the other hand, should not be Inhibitors,research,lifescience,medical started in patients showing neither a clinical impact of the disease or with a limited life expectancy. In the Netherlands, the inclusion criteria are the confirmation of diagnosis via enzyme assay and mutation analysis, and patients should have demonstrable muscle weakness and/or pulmonary function < 80%. In UK, specific about guidelines, prepared by a multidisciplinary group (2007), included patients with muscle weakness and/or respiratory compromise leading to an impaired quality of life as candidate for treatment. In France, Pompe disease experts recommend to treat symptomatic patients (muscle weakness and/or respiratory involvement – FVC < 80%). In Germany and in Poland there is a generic recommendation to treat symptomatic patients. In addition, in Brazil there is a recommendation to treat symptomatic patients; mild cases have to be progressively followed by respiratory and /or muscular functional tests and/or by muscle MRI before starting ERT.