Physical training and high-protein diet improved muscle strength, parent-reported fatigue, and physical quality of life in children with Pompe disease.

Exercise has proven to be an effective adjuvant treatment to enzyme replacement therapy (ERT) in mildly affected adult Pompe patients. The aim of this study was to investigate the effects of a 12-week tailored lifestyle intervention, consisting of physical training and a high protein diet (2 grams/kg), in children with Pompe disease. This randomized controlled semi-crossover trial investigated the effects of a lifestyle intervention on the primary outcome: exercise capacity. Secondary outcomes were: muscle strength, core stability, motor function, physical activity levels, quality of life, fatigue, fear of exercise, caloric intake, energy balance, body composition, and safety. Fourteen Pompe patients with a median age of 10.6 [IQR: 7.2-14.5], of whom six classic infantile patients, participated in the lifestyle intervention. At baseline, patients had a lower exercise capacity compared to healthy peers (median 70.3% [IQR: 54.8%-98.6%] of predicted). After the intervention, absolute Peak VO2 improved significantly (1279 mL/min [1012.5-2006] vs. 1352 mL/min [1101.5-2069], p = 0.039), but not compared to the control period. Muscle strength of the hip flexors, hip abductors, elbow extensors, neck extensors, knee extensors, and core stability improved significantly compared to the control period. Children reported a significant increase on the change in health domain of quality of life, parents reported significantly better scores on the quality of life domains: physical functioning, change in health, family cohesion, and fatigue. A 12-week tailored lifestyle intervention for children with Pompe disease seemed safe and led to improvements in muscle strength, core stability, quality of life, and parent-reported fatigue. Pompe patients with a stable disease trajectory seemed to benefit the most from the intervention.

Physical Training and Healthy Diet Improved Bowel Symptoms, Quality of Life, and Fatigue in Children With Inflammatory Bowel Disease.

OBJECTIVES: Physical activity programs have been suggested as adjunctive therapy in adult inflammatory bowel disease (IBD) patients. We assessed the effects of a 12-week lifestyle intervention in children with IBD. METHODS: This study was a randomized semi-crossover controlled trial, investigating a 12-week lifestyle program (3 physical training sessions per week plus personalized healthy dietary advice) in children with IBD. Endpoints were physical fitness (maximal and submaximal exercise capacity, strength, and core stability), patient-reported outcomes (quality of life, fatigue, and fears for exercise), clinical disease activity (fecal calprotectin and disease activity scores), and nutritional status (energy balance and body composition). Change in maximal exercise capacity (peak VO 2 ) was the primary endpoint; all others were secondary endpoints. RESULTS: Fifteen patients (median age 15 [IQR: 12-16]) completed the program. At baseline, peak VO 2 was reduced (median 73.3% [58.8-100.9] of predicted). After the 12-week program, compared to the control period, peak VO 2 did not change significantly; exercise capacity measured by 6-minute walking test and core-stability did. While medical treatment remained unchanged, Pediatric Crohn's Disease Activity Index decreased significantly versus the control period (15 [3-25] vs 2.5 [0-5], P = 0.012), and fecal calprotectin also decreased significantly but not versus the control period. Quality of life (IMPACT-III) improved on 4 out of 6 domains and total score (+13 points) versus the control period. Parents-reported quality of life on the child health questionnaire and total fatigue score (PedsQoL Multidimensional Fatigue Scale) also improved significantly versus the control period. CONCLUSIONS: A 12-week lifestyle intervention improved bowel symptoms, quality of life, and fatigue in pediatric IBD patients.

Muscle fiber-type distribution, fiber-type-specific damage, and the Pompe disease phenotype.

Pompe disease is a lysosomal storage disorder caused by acid α-glucosidase deficiency and characterized by progressive muscle weakness. Enzyme replacement therapy (ERT) has ameliorated patients' perspectives, but reversal of skeletal muscle pathology remains a challenge. We studied pretreatment biopsies of 22 patients with different phenotypes to investigate to what extent fiber-type distribution and fiber-type-specific damage contribute to clinical diversity. Pompe patients have the same fiber-type distribution as healthy persons, but among nonclassic patients with the same GAA mutation (c.-32-13T>G), those with early onset of symptoms tend to have more type 2 muscle fibers than those with late-onset disease. Further, it seemed that the older, more severely affected classic infantile patients and the wheelchair-bound and ventilated nonclassic patients had a greater proportion of type 2x muscle fibers. However, as in other diseases, this may be caused by physical inactivity of those patients.

A 12-week lifestyle intervention: effects on fatigue, fear, and nutritional status in children with a Fontan circulation.

Introduction: Children and adolescents with a Fontan circulation are less physically active compared to healthy peers. In the current study, effects of a 12-week lifestyle intervention on fatigue, fears regarding exercise, caloric intake, rest energy expenditure (REE), and body composition were measured in children with a Fontan circulation. Methods: This study was a semi-cross-over randomized controlled trial. The lifestyle intervention consisted of a 12-week high-weight resistance training (three supervised training sessions a week) supported by high-protein diet (>2 g/kg) and tailored recommended caloric intake. Fatigue (measured by the validated PedsQol Multidimensional Fatigue Scale), fears regarding exercise (measured on a fear thermometer), REE (measured using indirect calorimetry), caloric intake and body composition using air displacement plethysmography, and four-skinfold method were measured before and after the intervention and control period. Results: Twenty-seven pediatric Fontan patients, median age 12.9 years (IQR: 10.5-16.2), of the included 28 patients successfully completed the program. Before training, both child- and parent-reported levels of fatigue were significantly worse on all domains (general, sleep/rest, and cognitive fatigue) compared to healthy peers. After training, parent-reported fatigue significantly improved on the general and cognitive fatigue domains [effect size +16 points (7-25), p < 0.001, and +10 points (2-17), p = 0.015, compared to the control period]. Before training, fear regarding exercise scored on the fear thermometer was low for both children and parents (median score 1 and 2, respectively, on a scale of 0-8). After training, child-reported fear decreased further compared to the control period [effect size -1.4 points (-2.3 to -0.6), p = 0.001]. At baseline, children had increased REE +12% compared to reference values, which did not change after exercise. Children ate an average of 637 calories below recommended intake based on REE, caloric deficit became smaller after the intervention, and protein intake increased compared to the control period [-388 calories (-674 to -102), p = 0.008, and +15 g (0.4-30), p = 0.044]. Body fat percentage did not change significantly. Conclusion: A 12-week lifestyle intervention improved parent-reported fatigue symptoms in the children, further decreased child-reported fears, and increased caloric and protein intake.

Effects of enzyme replacement therapy on cardiac function in classic infantile Pompe disease.

OBJECTIVE: Patients with classic infantile Pompe disease are born with a hypertrophic cardiomyopathy, which resolves after treatment with Enzyme replacement therapy (ERT). We aimed to assess potential deterioration of cardiac function over time using myocardial deformation analysis. METHODS: Twenty-seven patients treated with ERT were included. Cardiac function was assessed at regular time intervals (before and after start with ERT) using conventional echocardiography and myocardial deformation analysis. Separate linear mixed effect models were used to asses temporal changes within the first year and the long-term follow-up period. Echocardiograms of 103 healthy children served as controls. RESULTS: A total of 192 echocardiograms were analyzed. Median follow-up was 9.9 years (IQR: 7.5-16.3). Mean LVMI before start of ERT was increased 292.3 g/m2 (95% CI: 202.8-381.8, mean Z-score + 7.6) and normalized after 1 year of ERT 87.3 g/m2 (CI: 67.5-107.1, mean Z-score + 0.8, p < 0.001). Mean shortening fraction was within normal limits before start of ERT, up to 22 years of follow-up. Cardiac function measured by RV/LV longitudinal, and circumferential strain was diminished before start of ERT, but normalized (<-16%) within 1 year after start of ERT, and all remained within normal limits during follow-up. Only LV circumferential strain gradually worsened in Pompe patients (+0.24%/year) during follow-up compared to controls. LV longitudinal strain was diminished in Pompe patients, but did not change significantly over time compared to controls. CONCLUSION: Cardiac function, measured using myocardial deformation analysis, normalizes after start of ERT, and seems to remain stable over a median follow-up period of 9.9 years.

Reduction of gastroenteritis morbidity in high-risk infants.

A method of predicting infants at high risk for developing gastroenteritis was validated in a prospective study. The ability to predict a high-risk subset of the population is particularly important if risk can be reduced with preventive measures. Performance of a preventive educational task in the field by community health workers was associated with a significantly lower rate of morbidity from gastroenteritis among high-risk infants, while achieving no significant reduction among the average-risk group.

Periodontal treatment without maintenance. A retrospective study in 44 patients.

This study presents our findings on 44 patients who were treated for periodontal disease and for varying reasons elected not to participate in the maintenance aspect of periodontal care. All patients were initially given intensive instructions in personal oral hygiene, along with initial scaling and root planing. Each patient had two or more quadrants of pocket reduction therapy. Tooth mortality revealed a mean annual adjusted tooth loss rate of 0.22 (4.7%). Between examinations, breakdown in the health status of furcations was noted. Mean probing depth scores at the second examination showed no significant differences from the first examination scores. Measurements of bone levels revealed a worsening of bone scores between examinations. The results of this study show that periodontal therapy without maintenance is of little value in terms of restoring periodontal health.

Tissue distribution of indices of lysine catabolism in growing swine.

The primary pathway of lysine degradation in pigs presumably depends on the bifunctional protein α-aminoadipate δ-semialdehyde synthase (AASS), which contains lysine α-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH) activities. In liver, AASS is restricted to the mitochondrial matrix and lysine is presumptively transported through the plasma membrane by a cationic AA transporter (CAT1/2) and through the inner mitochondrial membrane by 1 or both mitochondrial ornithine transporters (ORC-1/ORC-2). Lysyl oxidase (LO) may represent an alternative pathway of lysine oxidation. The objective of this experiment was to analyze the distribution of indices of lysine catabolism in various pig tissues. We assessed LKR, SDH, and LO activities, lysine oxidation, mRNA abundance of LKR, CAT1/2, and ORC1/2, and AASS protein abundance (via SDH antibody) in liver, heart, kidney medulla and cortex, triceps, longissimus, whole intestine, enterocytes, and intestine stripped of enterocytes in 10 growing pigs, weighing ∼25 kg. The LKR activity differed across tissues (P<0.001) and was greatest in liver, intestine, and kidney samples, and LKR mRNA abundance (P<0.001) was greatest in liver; although, LKR activity and mRNA abundance were detected in all other tissues. Activity of SDH (P<0.001) and SDH mRNA abundance (P<0.001) were affected by tissue and were greatest in liver compared with all other tissues analyzed. The AASS protein abundance (P<0.001) was greatest in whole intestine and liver. Activity of LO (P<0.0001) was greatest in muscle samples. The abundance of ORC-1 (P<0.001) and ORC-2 mRNA (P<0.001) differed among tissues, and ORC-1 was greatest in liver, kidney, and intestinal preparations, and ORC-2 mRNA abundance was greatest in liver and intestine. Interestingly, LKR activity was correlated with ORC-1 (r=0.32, P<0.05) and ORC-2 (r=0.41, P<0.05) expression. The expression of CAT-1 was uniform in all tissues, whereas CAT-2 (P<0.01) was greatest in liver. In conclusion, these data indicate that extra-hepatic tissues contribute to lysine catabolism as do enzymes other than LKR.

Upgrade of the resonance ionization laser ion source at ISOLDE on-line isotope separation facility: new lasers and new ion beams.

The resonance ionization laser ion source (RILIS) produces beams for the majority of experiments at the ISOLDE on-line isotope separator. A substantial improvement in RILIS performance has been achieved through a series of upgrade steps: replacement of the copper vapor lasers by a Nd:YAG laser; replacement of the old homemade dye lasers by new commercial dye lasers; installation of a complementary Ti:Sapphire laser system. The combined dye and Ti:Sapphire laser system with harmonics is capable of generating beams at any wavelength in the range of 210-950 nm. In total, isotopes of 31 different elements have been selectively laser-ionized and separated at ISOLDE, including recently developed beams of samarium, praseodymium, polonium, and astatine.