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The short-term mortality and rehospitalization rates after admission for acute heart failure (AHF) remain high, despite the high level of adherence to contemporary practice guidelines. Observational data from non-randomized studies in AHF strongly support the in-hospital administration of oral evidence-based modifying chronic heart failure (HF) medications (i.e., b-blockers, ACE inhibitors, mineralocorticoid receptor antagonists) to reduce morbidity and mortality. Interestingly, a well-designed prospective randomized multicenter study (PIONEER-HF) showed an improved clinical outcome and stress/injury biomarker profile after in-hospital administration of sacubitril/valsartan (sac/val) as compared to enalapril, in hemodynamically stable patients with AHF. However, sac/val implementation during hospitalization remains suboptimal due to the lack of an integrated individualized plan or well-defined appropriateness criteria for transition to oral therapies, an absence of specific guidelines regarding dose selection and the up-titration process, and uncertainty regarding patient eligibility. In the present expert consensus position paper, clinical practical recommendations are proposed, together with an action plan algorithm, to encourage and facilitate sac/val administration during hospitalization after an AHF episode with the aim of improving efficiencies of care and resource utilization.

Introduction Spinal muscular atrophy (SMA) most prominently affects proximal limb and bulbar muscles. Despite older case descriptions, ocular motor neuron palsies or other oculomotor abnormalities are not considered part of the phenotype. Methods We investigated oculomotor function by testing saccadic eye movements of 15 patients with SMA. Their performance was compared with that of age-matched healthy controls. Horizontal rightward and leftward saccades were recorded by means of video-oculography, whereas subjects looked at light-emitting diode targets placed at ±5°, ±10°, and ±15° eccentricities. Results No differences in saccade amplitude gains, peak velocities, peak velocity-to-amplitude ratios, or durations were observed between controls and patients. More specifically, for 5° target eccentricities, patients had a mean saccadic peak velocity of 153°/s, whereas for 10° and 15° these values were 268°/s and 298°/s, respectively. The corresponding mean peak velocities of the control group were 151°/s, 264°/s, and 291°/s. Discussion Our results indicate that patients with SMA perform fast and accurate horizontal saccades without evidence of extraocular muscle weakness. These quantitative oculomotor data corroborate clinical experience that neuro-ophthalmic symptoms in SMA are not common and, if present, should prompt suspicion for an alternative neuromuscular disorder.

Background Myotonic dystrophy type 2 (DM2) is a neuromuscular disorder characterized by myotonia and muscle weakness, with no medical treatment to prevent a decline in decline. It is unknown whether exercise training is effective in DM2. The aim of this study was to investigate the effect of exercise training on functional capacity and body composition in these patients. Methods Body composition and functional capacity were evaluated at the beginning (T1) and end (T2) of a 12 wk control period, and again after 16 wk of exercise training (T3) in 10 patients. Results No changes were recorded after the control period. Handgrip strength, 5× sit to stand, timed up and go, 6 min walk distance, lean body mass (LBM), and bone mineral density (BMD) increased while arterial pressure decreased after training. Conclusions These results suggest that supervised exercise training improves functional capacity, LBM, and BMD in ambulatory DM2 patients.

Pompe disease is a rare autosomal recessive disorder caused by the deficiency of acid α-glycosidase resulting in accumulation of glycogen in the lysosomes. The late-onset form of the disease (LOPD) causes primarily progressive muscle weakness and respiratory insufficiency. Enzyme replacement therapy (ERT) introduced in 2006, showed mild improvement or stabilization of the symptoms although long-term data are limited. Aim of the study was to describe the progression of body composition and walking ability in LOPD patients receiving ERT consistently for 9 years.Lean body mass, bone mineral density, body fat and 6 min walking distance were assessed in three male and three female LOPD patients (height 165.8 ± 11.2 cm, age 42.3 ± 11.8yrs, body mass 71.1 ± 20.8 kg, at study entry), every three years, for 9 years since ERT initiation (T0, T3, T6, T9).Total body and upper extremities' lean mass remained unchanged (The current data show that enzyme replacement therapy may preserve lean body mass, bone mineral density and walking capacity in LOPD patients.

Background: Promising genetic treatments targeting the molecular defect of severe early-onset genetic conditions are expected to dramatically improve patients’ quality of life and disease epidemiology. Spinal Muscular Atrophy (SMA), is one of these conditions and approved therapeutic approaches have recently become available to patients. Objective: Analysis of genetic and clinical data from SMA patients referred to the single public-sector provider of genetic services for the disease throughout Greece followed by a retrospective assessment in the context of epidemiology and genotype-phenotype associations. Methods: Molecular genetic analysis and retrospective evaluation of findings for 361 patients tested positive for SMA- and 862 apparently healthy subjects from the general population. Spearman rank test and generalized linear models were applied to evaluate secondary modifying factors with respect to their impact on clinical severity and age of onset. Results: Causative variations- including 5 novel variants- were detected indicating a minimal incidence of about 1/12,000, and a prevalence of at least 1.5/100,000. For prognosis a minimal model pertaining disease onset before 18 months was proposed to include copy numbers of NAIP (OR = 9.9;95% CI, 4.7 to 21) and SMN2 (OR = 6.2;95% CI, 2.5–15.2) genes as well as gender (OR = 2.2;95% CI, 1.04 to 4.6). Conclusions: This long-term survey shares valuable information on the current status and practices for SMA diagnosis on a population basis and provides an important reference point for the future assessment of strategic advances towards disease prevention and health care planning.

Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field that aim to improve patients’ care. Limited work, however, has been performed on rare diseases, including DM1. We have previously shown that specific microRNAs (miRNAs) can be used as potential biomarkers for DM1 progression. In this report, we aimed to identify novel serum-based biomarkers for DM1 through high-throughput next-generation sequencing. A number of miRNAs were identified that are able to distinguish DM1 patients from healthy individuals. Two miRNAs were selected, and their association with the disease was validated in a larger panel of patients. Further investigation of miR-223-3p, miR-24-3p, and the four previously identified miRNAs, miR-1-3p, miR-133a-3p, miR-133b-3p, and miR-206-3p, showed elevated levels in a DM1 mouse model for all six miRNAs circulating in the serum compared to healthy controls. Importantly, the levels of miR-223-3p, but not the other five miRNAs, were found to be significantly downregulated in five skeletal muscles and heart tissues of DM1 mice compared to controls. This result provides significant evidence for its involvement in disease manifestation., Graphical abstract, Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. In this study, two novel miRNAs were identified to be elevated in DM1 patients compared to healthy individuals and suggested as potential biomarkers. Additionally, six miRNAs were investigated in tissues and serum of a DM1 mouse model.

Espousing experiential learning theories, internships have captured the attention of tertiary education programs in almost all business-related fields. Due to their vocational nature, hospitality and tourism programs have been amongst the first to incorporate such experiences in their curriculum, whereas relevant research has surged over the past two decades. This study aims to systematically review internship-specific literature, critique and synthesize the existing conceptual capital, identify important gaps, and highlight an agenda for future research. Sixty-nine articles are reviewed and analyzed with the use of a standardized coding scheme and content analysis. Findings, of interest to industry stakeholders, aim to enhance our understanding of the relevant literature and identify vital areas for future research that would further extend internship-related theories and practices. Finally, the impact of the unprecedented COVID-19 pandemic on internship practices is discussed, with suggestions aiming to highlight areas of both interest and concern.

Patients with myasthenia gravis treated with methotrexate are usually young and sexually active. Therefore, sexual dysfunction associated with MTX treatment should be considered and specifically searched in them as it can be an under‐recognized cause of treatment failure or poor compliance

Assessing long-term mortality and identifying predictors of death in adults with mitochondrial diseases. We retrospectively included adult patients with genetically proven mitochondrial diseases referred to our centre between January 2000 and June 2016, and collected information relative to their genetic testing, clinical assessments, and vital status. We performed single and multiple variable analyses in search of predictors of total mortality, and calculated hazard ratios (HR) and 95% confidence intervals (CI). We included 267 patients (women 59%; median age 43.3 [31.3-54.2] years), including 111 with mitochondrial DNA (mtDNA) single large-scale deletions, 65 with m.3243A>G, 24 with m.8344A>G, 32 with other mtDNA point mutations, and 36 patients with nuclear genes mutations. Over a median follow-up of 8.9 years (0.3 to 18.7), 61 patients (22.8%) died, at a median age of 50.7 (37.9-51.9) years. Primary cause of death was cardiovascular disease in 16 patients (26.2%), respiratory in 11 (18.0%), and gastrointestinal in 5 (8.1%). By multiple variable analysis, diabetes (HR 2.75; 95% CI 1.46-5.18), intraventricular cardiac conduction defects (HR 3.38; 95% CI 1.71-6.76) and focal brain involvement (HR 2.39; 95% CI 1.25-4.57) were independent predictors of death. Adult patients with mitochondrial diseases present high morbidity that can be independently predicted by the presence of diabetes, intraventricular cardiac conduction defects, and focal brain involvement.

Late onset Pompe disease (LOPD) is a slowly progressive metabolic myopathy with variable clinical severity. The advent of enzyme replacement therapy (ERT) has modified the natural course of the disease, though the treatment effect on adult patients is modest compared to infants with the classic form. This study aims to describe the long-term clinical outcome of the Greek LOPD cohort, as assessed by 6 min walk test, muscle strength using MRC grading scale and spirometry. ERT efficacy was estimated using statistical methodology that is novel in the context of Pompe disease, which at the same time is well-suited to longitudinal studies with small samples and missing data (local non-linear regression analysis). Improvement over baseline was significant at 1 year for motor performance and muscle strength (p0.05), and at 2 years for FVC-U and FVC-S (p0.05). A subgroup analysis showed that the onset of the disease before adulthood (18 years), a male gender, and a latency of more than 2 years between the onset of symptoms and ERT administration are unfavorable prognostic factors. Conclusively, this study presents longitudinal data from the Greek LOPD cohort supporting previous observations, that therapeutic delay is related to worse prognosis and treatment effects may decline after several years of ERT.

Cardiac arrhythmias refer to any abnormality or disturbance in the normal activation sequence of the myocardium and may be indicative of structural heart disease and the cause of significant cardiovascular complications and sudden cardiac death. The following review summarizes the current state-of-the-art knowledge on the role of echocardiography in the management of cardiac arrhythmias and focuses on atrial fibrillation and ventricular arrhythmias where echocardiography presents a particular diagnostic and prognostic interest. Moreover, a brief reference is made to the effect of cardiac arrhythmias and conduction abnormalities on echocardiographic examination. Keywords: Atrial fibrillation, Ventricular arrhythmias, Echocardiography

We report the clinical, morphological and molecular features of two patients with autosomal recessive SLC25A4 (ANT1) gene mutations. Furthermore, all previously published cases are reviewed to identify valuable features for future diagnosis. Patients present a common phenotype with exercise intolerance, hyperlactatemia, and hypertrophic cardiomyopathy. Muscle biopsies show wide sub-sarcolemmal mitochondrial aggregates, and increased activities of all respiratory chain complexes. The phenotype of recessive SLC25A4 (ANT1) mutations although rare, is homogenous and easily recognizable and could help orientate the molecular analysis in adults with exercise intolerance associated with hyperlactatemia.

Introduction Patients with anoctamin-5 (ANO5) mutations may present not only with limb-girdle muscular dystrophy type 2L or adult-onset Miyoshi-type myopathy but also with asymptomatic hyperCKemia, exercise intolerance, or rhabdomyolysis. Materials and methods Data from 38 patients in France with ANO5 mutations with and without muscle weakness on first examination were compared. Results Twenty patients presented without muscle weakness. Median age at symptom onset or discovery of hyperCKemia was 23 years. Creatine kinase levels ranged from 200 to 40,000 U/L. Electromyography showed a myopathic pattern in 5 patients, and muscle imaging showed involvement of posterior calf muscles in 10 patients. Mild cardiac involvement was observed in 2 patients. Sixteen patients remain free of weakness after a median follow-up period of 5 years. Discussion Asymptomatic, sometimes mild hyperCKemia or exercise intolerance is a presentation of ANO5-related myopathy and may remain isolated or precede muscle weakness by many years. Muscle Nerve 56: 1096-1100, 2017.

Polymyositis with mitochondrial pathology (PM-Mito) is a rare form of idiopathic inflammatory myopathy with no definite diagnostic criteria and similarities to both PM and sporadic inclusion body myositis (s-IBM). The aim of this study is to address the dilemma of whether PM-Mito is a subtype of inflammatory myopathy or represents a disease falling into the spectrum of s-IBM. Herein, we report four female patients diagnosed with PM-Mito, highlighting their rather atypical clinical and histopathological characteristics that seem to indicate a diagnosis away from s-IBM. Muscle weakness was rather proximal and symmetrical and lacked the selective pattern observed in s-IBM. Patients had large-scale deletions in mtDNA, reflecting the mitochondrial component in the pathology of the disease. Conclusively, our study adds to the limited data in the literature on whether PM-Mito is a distinct form of myositis or represents a prodromal stage of s-IBM. Although the latter seems to be supported by a substantial body of evidence, there are, however, important differences, such as the different patterns of muscle weakness, and the good response to treatment observed in some patients. Larger-scale studies are certainly needed to clarify pathogenesis and clinical characteristics of PM-Mito patients, especially in therapeutic and prognostic terms.

The aim of the study was to investigate the relationships between vastus lateralis muscle fiber length and fiber type composition in individuals with minimal exposure to systematic resistance/power training. In sixty female physical education students (age: 21.03 ± 2.1 years, body weight: 59.8 ± 9.7 kg, body height: 166.2 ± 6.5 cm), with no experience in systematic training, lean body mass, VL muscle architecture and fiber composition type, countermovement jumping (CMJ) performance, and isometric leg press rate of force development were evaluated. Data were analyzed for all participants, as well as two equally numbered groups assigned according to their maximum countermovement jumping power (High-Power or Low-Power group). Significant but low correlations were found between type II muscle fiber percentage and fascicle length (N = 60, p &lt, 0.05). Significant correlations were found between type IIa and IIx muscle fiber percentage cross-sectional area (%CSA) and fascicle length (N = 60, r = 0.321, and r = 0.378, respectively, p &lt, 0.05). These correlations were higher for the High-Power group (r = 0.499, and r = 0.522, 0.05), and lower, and nonsignificant, for the Low-Power group. The best predictor of strength/power performance was the lean body mass of the lower extremities (r = 0.389–0.645, p &lt, 0.05). These results suggest that in females with minimal exposure to systematic training, fascicle length may be weakly linked with type II fiber areas, only in females with high-power profiles.

Blepharoptosis (ptosis) is classified, based on etiology, into mechanical, cerebral, neurogenic, neuromuscular, myogenic, and due to miscellaneous causes. Primary myopathic diseases are rare causes of blepharoptosis and many patients with myogenic ptosis undergo a series of extensive investigations before a myopathy is being considered. In this study, we report four patients with different myopathic disorders who had blepharoptosis as a presenting symptom of their disease. Moreover, we highlight frequent diagnostic errors and difficulties in patients with myopathies who present blepharoptosis. Lack of clear cut aggravation of symptoms by fatigue and response to cholinesterase inhibitors treatment, the association of proximal, distal or extraocular muscle weakness, and positive family history or evidence of a multi systemic disorder should prompt evaluation of an underlying myopathy.

A 50-year-old man with facioscapulohumeral muscular dystrophy 1 (FSHD1), scapuloperoneal weakness, and bilateral scapular winging presents a downward movement of his umbilicus while attempting to get up from the recumbent position (video 1). Beevor sign, an upward umbilicus deviation when the supine patient is flexing the neck or tries to sit up without the use of the hands, indicates lower abdominal muscle weakness. It is highly sensitive and specific, but not diagnostic, for FSHD1, because it is described in other myopathies.1,2 Beevor sign may be present in this “inverted” form, indicating predominant weakness of upper rectus abdominis muscle.

Congenital myopathies (CMs) constitute a group of heterogenous rare inherited muscle diseases with different incidences. They are traditionally grouped based on characteristic histopathological findings revealed on muscle biopsy. In recent decades, the ever-increasing application of modern genetic technologies has not just improved our understanding of their pathophysiology, but also expanded their phenotypic spectrum and contributed to a more genetically based approach for their classification. Later onset forms of CMs are increasingly recognised. They are often considered milder with slower progression, variable clinical presentations and different modes of inheritance. We reviewed the key features and genetic basis of late onset CMs with a special emphasis on those forms that may first manifest in adulthood.

The development of chronic, low-grade systemic inflammation in the elderly (inflammaging) has been associated with increased incidence of chronic diseases, geriatric syndromes, and functional impairments. The aim of this study was to examine differences in habitual physical activity (PA), dietary intake patterns, and musculoskeletal performance among community-dwelling elderly men with low and elevated systemic inflammation. Nonsarcopenic older men free of chronic diseases were grouped as ‘low’ (LSI: n = 17; 68.2 ± 2.6 years; hs-CRP: 1 mg/L) systemic inflammation according to their serum levels of high-sensitivity CRP (hs-CRP). All participants were assessed for body composition via Dual Emission X-ray Absorptiometry (DEXA), physical performance using the Short Physical Performance Battery (SPPB) and handgrip strength, daily PA using accelerometry, and daily macro- and micronutrient intake. ESI was characterized by a 2-fold greater hs-CRP value than LSI (p < 0.01). The two groups were comparable in terms of body composition, but LSI displayed higher physical performance (p < 0.05), daily PA (step count/day and time at moderate-to-vigorous PA (MVPA) were greater by 30% and 42%, respectively, p < 0.05), and daily intake of the antioxidant vitamins A (6590.7 vs. 4701.8 IU/day, p < 0.05), C (120.0 vs. 77.3 mg/day, p < 0.05), and E (10.0 vs. 7.5 mg/day, p < 0.05) compared to ESI. Moreover, daily intake of vitamin A was inversely correlated with levels of hs-CRP (r = −0.39, p = 0.035). These results provide evidence that elderly men characterized by low levels of systemic inflammation are more physically active, spend more time in MVPA, and receive higher amounts of antioxidant vitamins compared to those with increased systemic inflammation.

Introduction: Myotonic dystrophy type 2 (DM2) is an autosomal dominant inherited disorder with (CCTG)n repeat expansion in intron 1 of the CNBP gene. Methods: We studied the first 16 Greek DM2 patients who had undergone thorough evaluation. Results: The age at diagnosis ranged from 38 to 69 years. The initial symptoms were proximal weakness, myalgias, and myotonia. Clinical myotonia was elicited in 10 patients, whereas electromyographic myotonic discharges were observed in almost all patients. Subcapsular cataract was frequently present, but cardiac arrhythmias were rare. Conclusions: In this study of Greek DM2 patients, proximal weakness was the most common initial symptom. Myalgias were also reported in a few patients, yet myotonia was not a major complaint. Although DM2 is considered relatively benign, there are patients who may be affected severely. Thus, a high index of suspicion must be maintained to make a timely diagnosis, especially in those of reproductive age. Muscle Nerve 51:686–691, 2015

Background The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease. Methods We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared. Results Twelve patients (7 males) were identified. Median age at symptom onset was 24 years [IQR = 15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24 h [IQR = 21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5 years [IQR = 35.75; 66.50]. Median treatment duration was 55 months [IQR = 39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90 min and two increased their assisted walking distance, by 80 and 20 m. Conclusion Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities.

Vascular involvement in Late Onset Pompe Disease, glycogen storage disease type II characterized by limb-girdle muscle and diaphragmatic weakness, is well documented. Abnormalities of posterior cerebral circulation have mostly been reported, whereas there are also cases of associated extracerebral arteriopathy. We report the case of a 42-year-old man diagnosed with LOPD a year after renal infarct due to renal artery fibromuscular dysplasia. We propose that the association of LOPD and arteriopathy should always be considered in clinical practice. Keywords: Muscle disease, Glycogenoses, Metabolic disease (inherited), All clinical neurology

Pompe disease is an autosomal recessive disorder caused by the deficiency of acid α-glucosidase resulting in lysosomal accumulation of glycogen and abnormal autophagic function. The late-onset form of the disease is characterized by progressive skeletal and respiratory muscle dysfunction. Enzyme replacement therapy (ERT, Genzyme Corporation, Cambridge, MA, USA) was recently introduced and resulted in significant prolongation of the life expectancy of the patients with the infantile form while the results were less significant for the late-onset form. It has been postulated that the weak influence of ERT in late-onset patients might be due to a non-effective delivery of the recombinant enzyme to the skeletal muscles perhaps due to the relatively low blood flow to the resting skeletal muscles during infusion. Exercise training acutely increases the blood flow to the exercising muscles. Thus, it was hypothesized that exercise training during enzyme infusion might increase the effectiveness of the ERT therapy. Five late-onset Pompe disease patients receiving ERT and following regular exercise training for approximately 10 months, followed a 6-month period of exercise training during infusion of the recombinant enzyme. Before and after this period, body composition, isometric strength and 6 minute walking distance were determined. Analysis of the results revealed that none of these parameters changed significantly after the 6-month intervention period (e.g. 6 minute walking distance before: 532 ± 31 m, vs. after: 527 ± 29 m, P = 0.246). These results suggest that exercise training during infusion may not add significant functional changes in late-onset Pompe patients receiving ERT and undergoing regular exercise training.

Background:We tried to determine the prevalence of carotid sinus hypersensitivity (CSH) in patients with hip fractures with and without a clear history of an accidental fall. Methods:We studied 51 patients hospitalized for a hip fracture and 51 matched controls from our outpatients department. All patients were subjected to a carotid sinus massage in the supine and upright position. Patients were categorized in accidental (Group A) and unexplained (Group B) fallers. Results:Six of 33 (18.2%) patients in Group A and 12 of 18 (66.7%) patients in Group B (P < 0.001) had a positive response to the carotid sinus massage. Nine controls (17.6%) also demonstrated CSH. Patients in Group B were older (A: 75.5 ± 8.5 years vs B: 80.1 ± 5.9 years, P =0.029) and were more likely to have a history of unexplained falls or syncope in the past (A: 0% vs B: 66.7%, P < 0.0001) than individuals in group A. Vasodepressor/mixed forms accounted for the majority of CSH responses in Group B (75%). When compared with the control group, CSH was still more common in Group B (B: 66.7% vs control: 17.6%, P < 0.0001) but not in Group A (A: 18.2% vs control: 17.6%, P =1.000). Conclusions:The prevalence of CSH is increased in elderly patients with hip fractures, only in those who present with an unexplained fall and report a history of syncope or unexplained falls in the past. The vasodepressor/mixed forms account for the majority of CSH responses in the group of unexplained fallers.

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase10% and VTI increase20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF.

Transaction processing over mobile networks faces new challenges due to limitations in bandwidth and avail- able power, as well as due to intermittent connectivity that causes loss of data and transaction aborts. Besides, the possi- bility of security breach increases substantially due to the frequent motion of clients across cells, which gives rise to novel forms of covert channels. In this paper, we first investigate to what degree this breach may occur and we also assess the suitability of existing protocols for avoiding the appearance of covert channels in mobile database access. Based on the discovery of certain vulnerabilities in these protocols, we propose an optional multi-granularity locking protocol that en- sures secure access to shared data in mobile environments without compromising their consistency or the atomicity of transactions.

Levosimendan improves central hemodynamics and symptoms in acutely decompensated chronic heart failure (CHF) patients. However, its effects on quality of life, emotional stress and functional capacity of patients with advanced CHF have not been properly investigated.Sixty-three advanced CHF patients (NYHA III-IV, LVEF30%) were randomized (2:1) to receive either a 24-h levosimendan infusion of 0.1 mug/kg/min or placebo. Questionnaires addressing quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall, Duke's Activity Status Index (DASI)] and emotional stress [Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)], as well as plasma BNP and 6-min walking distance (6MWT as a marker of exercise capacity) were assessed before treatment and at hospital discharge. A significant improvement in NYHA class (2.1 +/- 0.7 from 3.3 +/- 0.7, p0.01), 6 MWT (305 +/- 152 from 215 +/- 142 m, p0.01) and plasma BNP (598 +/- 398 from 1,078 +/- 756 pg/ml, p0.01) was observed post-treatment only in levosimendan-treated group. KCCQ functional (45 +/- 19 from 35 +/- 17%, p0.05) and overall (34 +/- 13 from 28 +/- 11%, p0.05), DASI (26 +/- 13 from 22 +/- 12, p0.05), Zung SDS (38 +/- 12 from 42 +/- 13, p0.01) and BDI (11 +/- 6 from 14 +/- 8, p0.05) scores also improved in levosimendan-treated patients, while remained unchanged in the placebo group. The hospital length stay was shorter in levosimendan group compared to placebo (3.2 +/- 1.7 versus 5.8 +/- 2.1 days, p0.01). Levosimendan-induced BNP reduction was significantly correlated with concomitant increase in 6MWT (r = 0.643, p0.001) as well as with the decrease of BDI (r = 0.30, p0.05) and Zung SDS (r = 0.25, p = 0.05).Levosimendan seems to have a beneficial effect on quality of life, physical activity and emotional stress in advanced CHF patients, reducing concurrently hospitalization length.

Introduction: Mutations in the CAV3 gene are usually inherited in an autosomal dominant manner and lead to distinct disorders including limb-girdle muscular dystrophy 1C, rippling muscle disease, and isolated creatine kinase elevation. Patients and Methods: The features of the first patients with caveolin-3 deficiency from Greece are presented. Patients’ phenotypes ranged from asymptomatic creatine kinase elevation to severe weakness of lower extremities. Clinical evaluation disclosed muscle hypertrophy in 2 patients, whereas percussion-induced muscle mounding was a consistent finding in all of them. Muscle histopathology was variable and unrelated with disease severity. The diagnosis was based on the immunohistochemical study of caveolin-3 expression and molecular analysis of the caveolin-3 gene. Conclusions: Clinical manifestations and histochemical findings in caveolinopathy patients may be mild or nonspecific or overlapping with features of other muscular dystrophies. Immunohistochemical study of caveolin-3 expression on muscle biopsy should be routinely performed when investigating isolated hyperCKemia or undetermined myopathy especially in the presence of percussion-induced muscle mounding.

Software development for computer-supported cooperative work (CSCW) is a notoriously difficult task, involving often concurrent processes which are bound up with rigid timing constraints. To cope effectively with this difficulty, we propose in this paper the use of abstract finite-state models. The utility of these models is illustrated by encoding a CSCW system that we have built into finite-state automata, specifying in them a number of desired properties with temporal logic, and verifying these properties with model checking. By incorporating timing constraints into this process, we also gain insight into the usability of our system in real cooperative scenarios.

There is a paucity of data on muscle biopsies in females of mixed ages in terms of age-related changes. Cross sections of autopsy material including the quadriceps femoris and biceps brachii muscles were obtained from 23 healthy women, aged 24–82 years, who had suffered sudden death. We calculated the percentage of the number, and the mean diameter, of type I and type II muscle fibers within the fascicles as well as in their peripheral parts. The number of type II fibers were shown to reduce significantly with age (p < 0.005), especially in the fascicle periphery, but the percentage of type 1 fibers did not alter significantly. It was noted that type II fibers diminished in size with age, indicating a relationship between fiber size and age. This result became more apparent in the fascicle periphery (p < 0.05). In women, type II muscle fibers were seen to reduce in size and number with advancing age. We postulate that regular physical activity can increase the size of type II muscle fibers, thus helping to both prevent and treat age-related muscle loss.

Background Pompe disease is an inherited metabolic disorder characterized by α-glycosidase deficiency, which leads to lysosomal glycogen accumulation in many different tissues. The infantile form is the most severe with a rapidly fatal outcome, while the late onset form has a greater phenotypic variability, characterized by skeletal muscle dysfunction and early respiratory involvement. Bone mineral density (BMD) has been recently reported to be reduced in many patients with both forms of the disease. Enzyme replacement therapy (ERT) is now available with an undefined, impact on BMD in patients with late onset disease. Objectives The present study aimed to investigate BMD in patients with late onset form of Pompe disease before and after ERT initiation. Patients and Methods Dual x-ray absorptiometry (DEXA) was examined in four newly diagnosed patients with late onset Pompe disease and in four adults under ERT before and after ERT initiation with a treatment duration of 18 to 36 months. Results The initial DEXA showed normal total body BMD z-score in all the patients, while L2-L4 and femoral neck BMD was reduced in three and two patients, respectively. After ERT administration, two patients had an improvement in L2-L4 lumbar spine and one patient in femoral neck BMD z-score with values within normal range. Conclusions The results suggested that regional BMD may moderately reduce in some patients with the late onset form of Pompe disease, although profound osteopenia was not observed. The improvement of measurements in L2-L4 and femoral neck BMD z-score in some patients with low pre-treatment values after ERT administration needs to be confirmed in larger scale studies.

This study concerns the investigation of felodipine's influence on some parameters of vasomotion physiology. Felodipine is a new generation 1,4 dihydropyridine (1,4 DHP) Ca2+-entrance blocker with marked vascular selectivity. It was found that felodipine 1-10 μM presents a Ca2+ entrance-blocking activity when the bovine aortic smooth muscle is normal or stimulated by K+ 65.4 mM or the α-adrenoceptor agonist phenylephrine 1 μM. The same action is observed after nifedipine, a first-generation 1,4 DHP derivative with less angioselectivity in clinical practice. It was also found that felodipine 1-10 μM antagonizes the contraction of the bovine aortic ring that is induced by phenylephrine 10 μM or KCl 65.4 mM. On the contrary, felodipine 1-10 μM increases the contraction of the rat aortic ring that is induced by the same substances. It is known that some 1,4 DHP derivatives that are Ca2+ activators can also behave as Ca2+ blockers and that their final action is dependent upon membrane potential. Now it is also proved that the kind of animal species may also influence the action of the 1,4 DHP derivatives. It was finally found that felodipine increases the catecholamine stores of the sympathetic nerve terminal at the mouse heart (H) and liver (L). Obtained values were as following: control 15.00 ± 7.7 (H) and 17.72 ± 3.5 (L). Felodipine 54.50 ± 4.9 (H) and 41.54±10.4 (L). Since catecholamine stores depend on secretion (Ca2+-dependent) and reabsorption (mostly Na+-dependent) rates, the increase after felodipine may be attributed to a decreased secretion due to a Ca2+ entry inhibition. As felodipine is known to block L-channels, the active and remarkable functional role of the existing sympathetic presynaptic L-channels is confirmed.

The major method of treating disease in the developed world is through the prescription of drugs. It is estimated that, on a global basis, 3 billion prescriptions are issued annually. The fundamental process of prescribing and issuing medication is common in most parts of the world. Typically a patient will visit a General Practitioner (GP) who will diagnose any health problems and issue a prescription accordingly. It is then the duty of a pharmacist to dispense the medication based on this prescription and advise the patient on how it should be taken. In practice this process is much more complex as GP’s must not only diagnose and prescribe, but must also consider the patient’s profile in terms of possible allergies to certain medications and how the new prescription will interact with other treatments that may already have been prescribed. In addition to this, the prescribe-to-intake process for medication usually incorporates more entities than just the GP, patient and pharmacist. In many cases health insurers, government agencies and even pharmaceutical wholesalers will form part of the chain. One of the major expenses in the management of medication is payroll-time spent on the administrative duties needed to service the requirements of various health plan providers. Although not all attributed to medication related administration, it is estimated that between $0.25 and $0.40 of every healthcare dollar in the US is spent on excessive administration costs (Lee et al., 2000). As well as the inefficiencies introduced in the prescription/medication issue process, patient oriented issues are also prevalent. Medical compliance or adherence indicates the

To the Editor: We read with great interest the brief report by Wright et al, 1 which emphasizes that high levels of transaminases may be observed early in presymptomatic children with an underlying myopathy and can wrongly raise the suspicion of an underlying liver disease. According to the results of study by Wright et al, the majority of participants turned out to carry a pathogenic mutation in the dystrophin gene. On the basis of these observations, they proposed that measurement of serum creatine kinase should be obtained when clear gastrointestinal symptoms and signs are absent, and they stressed the need to combine the laboratory findings with a neurological examination. This notion may prove to be even more useful in the work-up of asymptomatic or oligosymptomatic adults with a muscle disease who are found during a routine examination to have increased aspartate aminotransferase

Fish oils have shown beneficial effects on various parameters in patients with coronary artery disease (CAD). The purpose of this study was to investigate whether the same effects can be demonstrated with a low dose of fish oil concentrate (FOC).Thirty-nine patients were studied and divided into two groups. Twenty were given 10 g fish oil (group A) and 19 were given 10 g placebo Italian olive oil (group B).Weekly anginal attacks (AA), weekly glyceryl trinitrate consumption (GTN), exercise tolerance time (ETT), serum triglycerides (ST), platelet aggregation ratio (PAR), and β- thromboglobulin were measured at eight and twelve weeks after start of treatment.1. The number of anginal attacks recorded by both groups decreased by 41% in group A reaching statistical significance (P < 0.05). No change was observed in group B.2. GTN consumption decreased in group A (P < 0.05) with no significant change in group B (P: ns).3. ETT increased significantly in group A eight and twelve weeks after start of treatment (20.6% P < 0.01, 22.6% P < 0.01). A smaller but insignificant increase was observed in group B (P: ns).4. ST decreased significantly in group A by 22% eight weeks after start of treatment (P < 0.01) and to a lesser degree (11%) twelve weeks after start of treatment (P: ns). In group B, ST slightly increased (P: ns). (continued on next page)5. No statistically significant change was observed in either group in regard to PAR and β-thromboglobulin (P: ns).These observations suggest that dietary supplementation with a low dose of FOC may have beneficial effects on the clinical status of patients with CAD. It also seems that this low dose has no impact on platelet function.

Pompe disease is a rare autosomal recessive disorder characterized by the deficiency of acid α-glycosidase resulting in lysosomal accumulation of glycogen. The late-onset disease form is characterized by progressive skeletal and respiratory muscle dysfunction. In addition to the recently introduced enzyme replacement therapy (ERT), treatments such as protein-enriched diet and exercise training have been proposed, although little is known about their effectiveness on the physical condition of such patients. Aim of the present study was to investigate the effect of exercise training on muscular strength and body composition in five patients with late-onset Pompe disease receiving ERT. All subjects followed a 20 week lasting program of supervised aerobic and progressive resistance exercise training. Before and after the training period, body composition was determined with dual X-ray absorptiometry and isometric muscular strength was measured with a specialized load transducer. Functional capacity was assessed using the 6-min shuttle walk test. A significant increase in muscular strength (15-50% at various body parts, p