Barcoding, linear and nonlinear analysis of full-day leg movements in infants with typical development and infants at risk of developmental disabilities: Cross-sectional study.

Traditional methods do not capture the multidimensional domains and dynamic nature of infant behavioral patterns. We aim to compare full-day, in-home leg movement data between infants with typical development (TD) and infants at risk of developmental disabilities (AR) using barcoding and nonlinear analysis. Eleven infants with TD (2-10 months) and nine infants AR (adjusted age: 2-14 months) wore a sensor on each ankle for 7 days. We calculated the standard deviation for linear variability and sample entropy (SampEn) of leg acceleration and angular velocity for nonlinear variability. Movements were also categorized into 16 barcoding states, and we calculated the SampEn and proportions of the barcoding. All variables were compared between the two groups using independent-samples t-test or Mann-Whitney U test. The AR group had larger linear variability compared to the TD group. SampEn was lower in the AR group compared to TD group for both acceleration and angular velocity. Two barcoding states' proportions were significantly different between the two groups. The results showed that nonlinear analysis and barcoding could be used to identify the difference of dynamic multidimensional movement patterns between infants AR and infants with TD. This information may help early diagnosis of developmental disabilities in the future.

[Argentine consensus on late-onset Pompe's disease]. / Consenso argentino sobre enfermedad de Pompe de inicio tardío.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Changes in Echocardiographic Parameters in Iron Deficiency Patients with Heart Failure and Chronic Kidney Disease Treated with Intravenous Iron.

BACKGROUND: Treatment of iron deficiency helps to improve cardiac and renal function in patients with chronic heart failure. However, the mechanism by which this occurs is currently unclear. METHODS: We undertook a double-blind, randomised, placebo-controlled study of intravenous iron sucrose treatment (200mg/mL weekly for five weeks) in patients with chronic heart failure, chronic kidney disease and iron-deficiency anaemia receiving optimal treatment for chronic heart failure (N=60). Markers of disease severity, iron status, anaemia and inflammation were measured during a six-month follow-up period, and evaluation of echocardiographic parameters was performed at baseline and six months after treatment. RESULTS: At six months after treatment initiation, intravenous iron was associated with reduced severity of the symptoms of chronic heart failure and improved renal function (both p<0.001 versus control). Also, ferritin and transferrin saturation levels were increased, as were haemoglobin levels, whereas inflammatory markers were reduced (all p<0.001 versus control). Left ventricular systolic and diastolic diameters were increased and improved left ventricular function correlated with iron status in patients receiving intravenous iron but not patients in the control group. CONCLUSIONS: Intravenous iron treatment was associated with improved myocardial functional parameters and cardiac dimensions in patients with anaemia and chronic kidney disease.

Not Only Protein: Dietary Supplements to Optimize the Skeletal Muscle Growth Response to Resistance Training: The Current State of Knowledge.

Regarding skeletal muscle hypertrophy, resistance training and nutrition, the most often discussed and proposed supplements include proteins. Although, the correct amount, quality, and daily distribution of proteins is of paramount importance for skeletal muscle hypertrophy, there are many other nutritional supplements that can help and support the physiological response of skeletal muscle to resistance training in terms of muscle hypertrophy. A healthy muscle environment and a correct whole muscle metabolism response to the stress of training is a prerequisite for the increase in muscle protein synthesis and, therefore, muscle hypertrophy. In this review, we discuss the role of different nutritional supplements such as carbohydrates, vitamins, minerals, creatine, omega-3, polyphenols, and probiotics as a support and complementary factors to the main supplement i.e., protein. The different mechanisms are discussed in the light of recent evidence.

Corticomuscular and intermuscular coherence as a function of age and walking balance difficulty.

We determined beta-band intermuscular (IMC) and corticomuscular coherence (CMC) as a function of age and walking balance difficulty. Younger (n=14, 23y) and older individuals (n=19, 71y) walked 13 m overground, on a 6-cm-wide ribbon overground, and on a 6-cm-wide (5-cm-high) beam. Walking distance as a proxy for walking balance and speed were computed. CMC was estimated between electroencephalographic signal at Cz electrode and surface electromyographic signals of seven leg muscles, while IMC was calculated in four pairs of leg muscles, during stance and swing gait phases. With increasing difficulty, walking balance decreased in old individuals and speed decreased gradually independent of age. Beam walking increased IMC, while age increased IMC in proximal muscle pairs, and decreased IMC in distal muscle pairs. Age and difficulty increased CMC independent of gait phases. Concluding, CMC and IMC increased with walking balance difficulty and age, except for distal muscle pairs, which had lower IMC with age. These findings suggest an age-related increase in corticospinal involvement in the neural control of walking balance. DATA AVAILABILITY: The datasets used in this study are available from the corresponding author upon reasonable request.

A pilot study assessing reliability and age-related differences in corticomuscular and intramuscular coherence in ankle dorsiflexors during walking.

Corticomuscular (CMC) and intramuscular (intraMC) coherence represent measures of corticospinal interaction. Both CMC and intraMC can be assessed during human locomotion tasks, for example, while walking. Corticospinal control of gait can deteriorate during the aging process and CMC and intraMC may represent an important monitoring means. However, it is unclear whether such assessments represent a reliable tool when performed during walking in an ecologically valid scenario and whether age-related differences may occur. Wireless surface electroencephalography and electromyography were employed in a pilot study with young and old adults during overground walking in two separate sessions. CMC and intraMC analyses were performed in the gathered beta and lower gamma frequencies (i.e., 13-40 Hz). Significant log-transformed coherence area was tested for intersessions test-retest reliability by determining intraclass correlation coefficient (ICC), yielding to low reliability in CMC in both younger and older adults. intraMC exclusively showed low reliability in the older adults, whereas intraMC in the younger adults revealed similar values as previously reported: test-retest reliability [ICC (95% CI): 0.44 (-0.23, 0.87); SEM: 0.46; MDC: 1.28; MDC%: 103; Hedge's g (95% CI): 0.54 (-0.13, 1.57)]. Significant differences between the age groups were observed in intraMC by either comparing the two groups with the first test [Hedge's g (95% CI): 1.55 (0.85, 2.15); p-value: .006] or with the retest data [Hedge's g (95% CI): 2.24 (0.73, 3.70); p-value: .005]. Notwithstanding the small sample size investigated, intraMC seems a moderately reliable assessment in younger adults. The further development and use of this measure in practical settings to infer corticospinal interaction in human locomotion in clinical practice is warranted and should help to refine the analysis. This necessitates involving larger sample sizes as well as including a wider number of lower limb muscles. Moreover, further research seems warranted by the observed differences in modulation mechanisms of corticospinal control of gait as ascertained by intraMC between the age groups.

Corticospinal Control of Human Locomotion as a New Determinant of Age-Related Sarcopenia: An Exploratory Study.

Sarcopenia is a muscle disease listed within the ICD-10 classification. Several operational definitions have been created for sarcopenia screening; however, an international consensus is lacking. The Centers for Disease Control and Prevention have recently recognized that sarcopenia detection requires improved diagnosis and screening measures. Mounting evidence hints towards changes in the corticospinal communication system where corticomuscular coherence (CMC) reflects an effective mechanism of corticospinal interaction. CMC can be assessed during locomotion by means of simultaneously measuring Electroencephalography (EEG) and Electromyography (EMG). The aim of this study was to perform sarcopenia screening in community-dwelling older adults and explore the possibility of using CMC assessed during gait to discriminate between sarcopenic and non-sarcopenic older adults. Receiver Operating Characteristic (ROC) curves showed high sensitivity, precision and accuracy of CMC assessed from EEG Cz sensor and EMG sensors located over Musculus Vastus Medialis [Cz-VM; AUC (95.0%CI): 0.98 (0.92-1.04), sensitivity: 1.00, 1-specificity: 0.89, p < 0.001] and with Musculus Biceps Femoris [Cz-BF; AUC (95.0%CI): 0.86 (0.68-1.03), sensitivity: 1.00, 1-specificity: 0.70, p < 0.001]. These muscles showed significant differences with large magnitude of effect between sarcopenic and non-sarcopenic older adults [Hedge's g (95.0%CI): 2.2 (1.3-3.1), p = 0.005 and Hedge's g (95.0%CI): 1.5 (0.7-2.2), p = 0.010; respectively]. The novelty of this exploratory investigation is the hint toward a novel possible determinant of age-related sarcopenia, derived from corticospinal control of locomotion and shown by the observed large differences in CMC when sarcopenic and non-sarcopenic older adults are compared. This, in turn, might represent in future a potential treatment target to counteract sarcopenia as well as a parameter to monitor the progression of the disease and/or the potential recovery following other treatment interventions.

A usability study of a multicomponent video game-based training for older adults.

BACKGROUND: Aging is often accompanied by a decline in sensory, motor and cognitive functions. These age- and lifestyle-related impairments may lead to reduced daily life functioning including gait disturbances, falling and injuries. Most daily life activities, e.g. walking, are tasks which require the concurrent interplay of physical and cognitive functions. Promising options for combined physical-cognitive training are video game-based physical exercises, so-called exergames. This study aimed to [i] determine the usability of a newly developed multicomponent exergame and [ii] explore its effects on physical functions, cognition and cortical activity. METHODS: Twenty-one healthy and independently living older adults were included (10 female, 71.4 ± 5.8 years, range: 65-91) and performed 21 training sessions (each 40 min) over seven weeks. The multicomponent exergame included strength and balance training with Tai Chi-inspired and dance exercises. Participants rated the usability of the exergame (System Usability Scale) and reported on their emotional experience (Game Experience Questionnaire). Attendance and attrition rates were calculated to determine training compliance. Before and after the intervention, physical and cognitive functions as well as resting state electroencephalography (EEG) were assessed. RESULTS: Results showed a high training attendance rate (87.1%, 18/21 training sessions on average) and a low attrition rate (9.5%, 2 drop-outs). System usability was rated high with a mean score of 75/100. Affective game experience was rated favorable. Gait speed under dual-task condition, lower extremity muscle strength and reaction times in a cognitive task (divided attention) showed significant improvements (p < .05). No significant pre-post differences were found for resting state EEG. CONCLUSIONS: The newly developed exergame seems usable for healthy older adults. Nevertheless, some aspects of the exergame prototype can and should be improved. The training showed to positively influence physical and cognitive functions in a small convenience sample. Future trials are warranted which evaluate the feasibility and usability of the exergame training in a more "real-life" in-home setting and assess the behavioral and neuroplastic changes in a larger population after a longer training period with comparison to a control group.

Playing Exergames Facilitates Central Drive to the Ankle Dorsiflexors During Gait in Older Adults; a Quasi-Experimental Investigation.

PURPOSE: Gait training might be of particular importance to reduce fall risk in older adults. In the present study we explore the hypothesis that video game-based training will increase tibialis anterior (TA) muscle EMG-EMG coherence and relates to functional measures of lower limb control. METHODS: We focus on video game-based training performed in standing position, where the subjects have to lift their toes to place their feet on different target zones in order to successfully play the game. This type of training is hypothesized leading to progressive changes in the central motor drive to TA motor neurons and, consequently, improved control of ankle dorsiflexion during gait. RESULTS: Twenty older adults, 79 ± 8 years old, 13 females/7 males, participated. Results showed a significant difference against 0 in the experimental ΔPOST condition in dual-task walking and beta Frequency Of Interest (p = 0.002). Walking under dual task condition showed significant change over time in minimal Toe Clearance for both the left [χ2(2) = 7.46, p = 0.024, n = 20] and right [χ2(2) = 8.87, p = 0.012, n = 20] leg. No change in lower extremity function was detectable. CONCLUSION: Overall we conclude that the initiation of an exergame-based training in upright standing position improves neural drive to the lower extremities in older adults, effects on minimal Toe Clearance and seems an acceptable form of physical exercise for this group.

A Pilot Study of an In-Home Multicomponent Exergame Training for Older Adults: Feasibility, Usability and Pre-Post Evaluation.

Aging is associated with sensory, motor and cognitive impairments that may lead to reduced daily life functioning including gait disturbances, falls, injuries and mobility restrictions. A strong need exists for implementing effective evidence-based interventions for healthy aging. Therefore, the aim of this study was to (i) evaluate the feasibility and usability of an in-home multicomponent exergame training and (ii) explore its effects on physical functions, cognition and cortical activity. Twenty-one healthy and independently living older adults were included (11 female, 74.4 ± 7.0 years, range: 65-92 years) and performed 24 trainings sessions (each 40 min) over eight weeks. The first part was conducted in a living lab (home-like laboratory environment), the second part at participants' home. The multicomponent exergame included Tai Chi-inspired exercises, dance movements and step-based cognitive games to train strength, balance and cognition. Attendance and attrition rates were calculated and safety during training was evaluated to determine feasibility. Participants rated the usability of the exergame (System Usability Scale) and reported on their game experience (Game Experience Questionnaire). Physical and cognitive functions and cortical activity (resting state electroencephalopathy) were assessed pre and post intervention. Results showed a high training attendance rate for the living lab and the home-based setting (91.7 and 91.0%, respectively) with a rather high attrition rate (28.6%, six drop-outs). Half of the drop-out reasons were related to personal or health issues. System usability was rated acceptable with a mean score of 70.6/100. Affective game experience was rated favorable. Significant improvements were found for minimal toe clearance, short-term attentional span, and information processing speed (p < 0.05). No significant pre-post differences were found for cortical activity. To summarize, the exergame is generally feasible and usable for healthy older adults applied in an in-home setting and provides an overall positive emotional game experience. Nevertheless, flawless technical functionality should be a mandatory consideration. Additionally, the training might have potential positive influence on specific functions in older adults. However, the efficacy has to be evaluated in a future randomized controlled trial assessing the behavioral and neuroplastic changes in a larger population after a longer training period.

Assessing Brain-Muscle Connectivity in Human Locomotion through Mobile Brain/Body Imaging: Opportunities, Pitfalls, and Future Directions.

Assessment of the cortical role during bipedalism has been a methodological challenge. While surface electroencephalography (EEG) is capable of non-invasively measuring cortical activity during human locomotion, it is associated with movement artifacts obscuring cerebral sources of activity. Recently, statistical methods based on blind source separation revealed potential for resolving this issue, by segregating non-cerebral/artifactual from cerebral sources of activity. This step marked a new opportunity for the investigation of the brains' role while moving and was tagged mobile brain/body imaging (MoBI). This methodology involves simultaneous mobile recording of brain activity with several other body behavioral variables (e.g., muscle activity and kinematics), through wireless recording wearable devices/sensors. Notably, several MoBI studies using EEG-EMG approaches recently showed that the brain is functionally connected to the muscles and active throughout the whole gait cycle and, thus, rejecting the long-lasting idea of a solely spinal-driven bipedalism. However, MoBI and brain/muscle connectivity assessments during human locomotion are still in their fledgling state of investigation. Mobile brain/body imaging approaches hint toward promising opportunities; however, there are some remaining pitfalls that need to be resolved before considering their routine clinical use. This article discusses several of these pitfalls and proposes research to address them. Examples relate to the validity, reliability, and reproducibility of this method in ecologically valid scenarios and in different populations. Furthermore, whether brain/muscle connectivity within the MoBI framework represents a potential biomarker in neuromuscular syndromes where gait disturbances are evident (e.g., age-related sarcopenia) remains to be determined.

Physical Activity, Nutrition, Cognition, Neurophysiology, and Short-Time Synaptic Plasticity in Healthy Older Adults: A Cross-Sectional Study.

The aging brain undergoes remodeling processes because of biological and environmental factors. To counteract brain aging, neuronal plasticity should be preserved. The aim of this study was to test if the capacity of generating short-time synaptic plasticity in older adults may be related to either physical activity, nutritional status, cognition, or neurophysiological activity. Thirty-six participants (mean age 73.3 ± 5.9 years) received transcranial magnetic stimulation in combination with peripheral nerve stimulation to experimentally induce short-time synaptic plasticity by paired associative stimulation (PAS). Adaptations in neuronal excitability were assessed by motor-evoked potential (MEP) in the right m. tibialis anterior before and after PAS. The Physical Activity Questionnaire 50+ and the StepWatchTM captured physical activity levels. Nutritional status was assessed by the Mini Nutritional Assessment. Cognition was assessed by reaction time for a divided attention test and with the Montreal Cognitive Assessment. Neurophysiological activity was assessed by electroencephalography during the divided attention test. MEPs of the highest stimulation intensity resulted significantly different comparing before, 5 min, or 30 min after PAS (p < 0.05). Data-driven automatic hierarchical classification of the individual recruitment curve slopes over the three-time points indicated four different response types, however, response groups did not significantly differ based on physical activity, nutritional status, cognition, or neurophysiological activity. In a second-level analysis, participants having an increased slope showed a significant higher energy expenditure (z = -2.165, p = 0.030, r = 0.36) and revealed a significant higher power activity in the alpha frequency band (z = -2.008, p = 0.046, r = 0.37) at the prefrontal-located EEG electrodes, compared to the participants having a decreased slope. This study hints toward older adults differing in their neuronal excitability which is strongly associated to their short-time synaptic plasticity levels. Furthermore, a physically active lifestyle and higher EEG power in the alpha frequency band seem to be connected to the capacity of generating long-term potentiation-like synaptic plasticity in older adults. Future studies should consider more sensitive assessments and bigger sample sizes to get a broad scope of the older adults' population.

Investigating the Usability and Acute Effects of a Bedside Video Console to Prefrontal Cortical Activity Alterations: A Preclinical Study in Healthy Elderly.

Elderly people at risk of developing cognitive decline; e.g., following surgery, may benefit from structured, challenging, and repetitive cognitive video training. This study assessed usability and acute effects of a newly developed bedside console (COPHYCON). Fifteen healthy elderly individuals performed a one-time 80-min intervention, including cognitive video games aimed at improving awareness and selective attention. Perceived usefulness and perceived ease of use (Technology Acceptance Model) were assessed together with measures of the achieved game level, reaction times, (in-) correct responses during ALERT and SELECT game play. Further, prefrontal cortical involvement of the regional cerebral hemoglobin saturation (rS02%) assessed with functional near infrared spectroscopy (fNIRS) (n = 5) and EEG power (n = 10) was analyzed. All participants completed the study without any adverse events. Perceived usefulness and perceived ease of use (TAM scores range 1-7) of the system varied between 3.9 and 6.3. The game levels reached for awareness varied between 9 and 11 (initial score 8-10), for reaction speed between 439 and 469 ms, and for correct responses between 74.1 and 78.8%. The highest level for the selective attention games was 2 (initial score 1), where reaction speed varied between 439 and 469 ms, correct responses between 96.2 and 98.5%, respectively. The decrease of rS02% in the right prefrontal cortex during gameplay was significantly (p < 0.001) lower, compared to the left prefrontal cortex. Four participants yielded significant lower rS02% measures after exergaming with the ALERT games (p < 0.000), but not with the SELECT games. EEG recordings of theta power significantly decreased in the averaged ~0.25-0.75 time interval for the left prefrontal cortex sensor across the cognitive game levels between the ALERT 1 and SELECT 1, as well as between SELECT 1 and 2 games. Participants rated the usability of the COPHYCON training positively. Further results indicate that video gaming may be an effective measure to affect prefrontal cortical functioning in elderly. The results warrant a clinical explorative study investigating the feasibility of the COPHYCON in a clinical setting.

Adaptations of Prefrontal Brain Activity, Executive Functions, and Gait in Healthy Elderly Following Exergame and Balance Training: A Randomized-Controlled Study.

During aging, the prefrontal cortex (PFC) undergoes age-dependent neuronal changes influencing cognitive and motor functions. Motor-learning interventions are hypothesized to ameliorate motor and cognitive deficits in older adults. Especially, video game-based physical exercise might have the potential to train motor in combination with cognitive abilities in older adults. The aim of this study was to compare conventional balance training with video game-based physical exercise, a so-called exergame, on the relative power (RP) of electroencephalographic (EEG) frequencies over the PFC, executive function (EF), and gait performance. Twenty-seven participants (mean age 79.2 ± 7.3 years) were randomly assigned to one of two groups. All participants completed 24 trainings including three times a 30 min session/week. The EEG measurements showed that theta RP significantly decreased in favor of the exergame group [L(14) = 6.23, p = 0.007]. Comparing pre- vs. post-test, EFs improved both within the exergame (working memory: z = -2.28, p = 0.021; divided attention auditory: z = -2.51, p = 0.009; divided attention visual: z = -2.06, p = 0.040; go/no-go: z = -2.55, p = 0.008; set-shifting: z = -2.90, p = 0.002) and within the balance group (set-shifting: z = -2.04, p = 0.042). Moreover, spatio-temporal gait parameters primarily improved within the exergame group under dual-task conditions (speed normal walking: z = -2.90, p = 0.002; speed fast walking: z = -2.97, p = 0.001; cadence normal walking: z = -2.97, p = 0.001; stride length fast walking: z = -2.69, p = 0.005) and within the balance group under single-task conditions (speed normal walking: z = -2.54, p = 0.009; speed fast walking: z = -1.98, p = 0.049; cadence normal walking: z = -2.79, p = 0.003). These results indicate that exergame training as well as balance training positively influence prefrontal cortex activity and/or function in varying proportion.

Switching patients with non-dialysis chronic kidney disease from oral iron to intravenous ferric carboxymaltose: effects on erythropoiesis-stimulating agent requirements, costs, hemoglobin and iron status.

BACKGROUND: Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD. METHODS: This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11-12 g/dL and iron deficiency (ferritin <100 µg/L or transferrin saturation <20%), who were regularly treated with oral iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study. RESULTS: Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 µg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study. CONCLUSION: Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02232906.

Angiotensin-converting enzyme inhibition and angiogenesis in myocardium of obese Zucker rats.

BACKGROUND: Obesity, hypertension, and non-insulin-dependent diabetes mellitus (NIDDM) are associated with microvascular rarefaction in the myocardium and this contributes to increase cardiovascular morbidity and mortality. At present, controversial data exist in medical literature regarding the specific role of angiotensin-converting enzyme (ACE) inhibitors concerning angiogenesis in different tissues. The present study was designed to determine the possible beneficial effects of an ACE inhibitor perindopril on myocardial angiogenesis in an animal model of obesity, hypertension, and NIDDM, such as the obese Zucker rat (OZR) and control lean Zucker rats (LZR). METHODS AND RESULTS: Ten-week-old male OZR (fa/fa) and LZR (Fa/fa) were used in this study: OZR group (G1, n = 10), OZR with perindopril group (G2, n = 10); LZR group (G3, n = 10). For 6 months, G2 received a daily dose of 3 mg/kg of perindopril, by gavage, and G1 and G3 received an equal volume of vehicle throughout the experiment. After 6 months of treatment, all rats were killed, hearts were harvested for pathology studies, including immunohistochemistry, using monoclonal antibodies against rat endothelial cell (RECA-1) and endothelial nitric oxide synthase. At the end of the study, OZR treated with perindopril presented: 1) lower blood pressure (BP) (127 +/- 3.2 v 152.4 +/- 3 mm Hg, P <.01) and 2) lower heart weight/100 g body weight (0.22 +/- 0.02 v 0.36 +/- 0.04 g, P <.01) than OZR untreated. Moreover, OZR that received perindopril showed higher: 1) myocyte density (2044 +/- 67 v 847 +/- 91 myocytes/mm(2), P <.01) and 2) capillary density (1348 +/- 118 v 436 +/- 78 capillaries/mm(2), P <.01); higher amount of: 1) vascular endothelial growth factor (VEGF) in the myocardium (P <.01) and higher percentage of capillaries with positive immunostaining for eNOS (P <.01), compared with untreated OZR. There was a correlation between both the amount of VEGF in myocardium and the number of capillaries (r = 0.88; P <.01) and VEGF and eNOS expression in myocardial capillaries (r = 0.93; P <.01) in OZR treated with perindopril. Finally, OZR that received P showed an improvement in insulin/glucose ratio (P <.01) when compared with untreated OZR. CONCLUSIONS: These results suggest that ACE inhibition by perindopril improves myocardial angiogenesis in this animal model of human metabolic syndrome. The pathway that involves bradykinin, eNOS, and VEGF could be involved in this effect; however, because no additional antihypertensive treatment group was included in our study, the BP-lowering effect cannot be excluded.

[High doses of aspirin reduce natriuresis in hypertensive patients treated with enalapril]. / Dosis elevadas de aspirina disminuyen la natriuresis en hipertensos tratados con enalapril.

Angiotensin converting enzyme inhibitors have been shown to be useful in the treatment of essential hypertension while anti-platelet agents improve the overall cardiovascular risk profile in this population. Our aim was to assess the interaction of two different aspirin (ASA) doses--81 and 325 mg/day--with the antihypertensive effect of enalapril as well as their impact upon the urinary sodium excretion (Na(u)). A total of 22 patients between 35 and 65 years of age were included in a prospective double blind trial with a partial cross-over design. We excluded patients with secondary hypertension and recent use of anti-inflammatory drugs. Patients were placed on enalapril and a low sodium diet--<6 g of NaCl/day--and, sequentially, on two different doses of aspirin separated by a 10 day wash out period. Blood pressure (BP) was measured at weekly visits. Systolic, diastolic and mean BP levels decreased significantly in enalapril-treated patients (p<0.01) and no difference was detected between the two AAS dosages although a non-statistically significant difference towards better BP control was observed when 81 mg of ASA was used. Na(u) was higher at baseline when compared with the two periods under ASA (p<0.01) and Na(u) was higher with 81 mg than with 325 mg. These results suggest that in essential hypertensive individuals treated with enalapril and two ASA doses, low doses of ASA are associated with better blood pressure control and higher natriuresis.

Consenso argentino sobre enfermedad de Pompe de inicio tardío / Argentine consensus on late-onset Pompe's disease

La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency.

OBJECTIVES: Our objective was to evaluate in a double-blind, randomized, placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels together with clinical and functional parameters, in a group of anemic patients with chronic heart failure (CHF) and chronic renal failure (CRF) receiving intravenous iron therapy, without recombinant human erythropoietin (rhEPO), versus placebo. BACKGROUND: Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem. This situation is linked with a variable inflammatory status. Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status, respectively. In this double-blind, randomized, placebo-controlled study, modifications in NT-proBNP and CRP level and clinical and functional parameters, in anemic patients with CHF and CRF receiving intravenous iron therapy, without rhEPO, versus placebo were evaluated. METHODS: Forty patients with hemoglobin (Hb) <12.5 g/dl, transferrin saturation <20%, ferritin <100 ng/ml, creatinine clearance (CrCl) <90 ml/min, and left ventricular ejection fraction (LVEF) < or =35% were randomized into 2 groups (n = 20 for each). For 5 weeks, group A received isotonic saline solution and group B received iron sucrose complex, 200 mg weekly. Minnesota Living with Heart Failure Questionnaire (MLHFQ) and 6-min walk (6MW) test were performed. NT-pro brain natriuretic peptide and CRP were evaluated throughout the study. No patients received erythroprotein any time. RESULTS: After 6 months follow-up, group B showed better hematology values and CrCl (p < 0.01) and lower NT-proBNP (117.5 +/- 87.4 pg/ml vs. 450.9 +/- 248.8 pg/ml, p < 0.01) and CRP (2.3 +/- 0.8 mg/l vs. 6.5 +/- 3.7 mg/l, p < 0.01). There was a correlation initially (p < 0.01) between Hb and NT-proBNP (group A: r = -0.94 and group B: r = -0.81) and after 6 months only in group A: r = -0.80. Similar correlations were observed with Hb and CRP. Left ventricular ejection fraction percentage (35.7 +/- 4.7 vs. 28.8 +/- 2.4), MLHFQ score, and 6MW test were all improved in group B (p < 0.01). Additionally, group B had fewer hospitalizations: 0 of 20 versus group A, 5 of 20 (p < 0.01; relative risk = 2.33). CONCLUSIONS: Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF. This situation was associated with an improvement in LVEF, NYHA functional class, exercise capacity, renal function, and better quality of life.

Dosis elevadas de aspirina disminuyen la natriuresis en hipertensos tratados con enalapril / High doses of aspirin reduce natriuresis in hypertensive patients treated with enalapril

Los inhibidores de la enzima convertidora de la angiotensina (IECA) han demostrado ser eficases en el tratamiento de la hipertensión arterial. Sin embargo, una importante proporción de hipertensos recibe además antiagregación plaquetaria con ácido acetil salicílico (AAS), y la consecuente inhibición de la síntesis de prostaglandinas con AAS atenuaría el efecto vasodilatador y la mayor excreción urinaria de sodio (Na(u)) atribuidas al IECA. Nuestro objetivo fue evaluar la interacción de dos dosis de AAS (81 y 325 mg/día) sobre el efecto hipotensor del enalapril y el impacto sobre la excreción de (Na(u)) en pacientes hipertensos. Se incluyeron 22 pacientes de ambos os sexos, entre 35 y 65 años. Todos reciberon enalapril, dieta hiposódica y, secuencialmente separadas por período de (wash out), las dos dois de AAS durante los setenta días del estudio. Se evaluó: presdión arterial sistólica (PAS), diastólica (PAD), media (PAM) y (Na(u)) en un período basal (PB), con 325 y 81 mg de AAS (P1 y P2 respectivamente). Comparando el PB con P1 y P2, se observó una reduccíon significativa de la PAS, PAD, PAM (p<0.01). Al comparar la PAS, PAD, PAM entre P1 y P2, no hubo diferencias significativas. La (Na(u)) en el PB fue mayor (p<0.01)con respecto al P1 y P2, y también P2 con respecto a P1. Estos resultados sugieren que en una población de pacientes hipertensos esenciales tratados con elapril y diferentes dosis de AAS, el tratamiento con dosis bajas de AAS está asociado a mejor control de la PA y mayor eliminación de sodio urinario.