Feeling controlled or being in control? Apps for self-management among older people with neurological disability.

PURPOSE: The aim of this paper was to describe how people living with a neurological disability such as multiple sclerosis, Parkinson's disease and stroke reason regarding using apps to facilitate self-management in everyday life. MATERIAL AND METHODS: A qualitative research approach with a focus group methodology was used. The sample comprised 16 participants, 11 men and 5 women, with an average age of 64 years (ranging from 51-80 years). Six participants were diagnosed with multiple sclerosis, six with Parkinson's disease and four with stroke. Data were analyzed using thematic analysis, which is a method for identifying, analyzing and reporting patterns. RESULTS: The results formed two themes. The first theme "using apps to have control of my health" comprises two subthemes; "monitor and take responsibility for a healthy lifestyle" and "compensate to facilitate everyday life". The second theme "using the app as a tool and means for communication" also comprised two subthemes; "dare to trust the app" and "feeling safe when sharing information with health care professionals". CONCLUSIONS: The use of apps put increased responsibility on the person and had the possibility to make them more involved in their own care. The use of an app can facilitate a healthy lifestyle and help to monitor disease-specific symptoms. In order to be able to use apps for communication with the health care sector legislation and safety issues need to be considered.Implications for rehabilitationApps can be used for self-management if they are safe and can be trusted.People with neurological disabilities want to be involved in their healthcare and needs to be addressed by health care professionals.The use of apps grasp over a wide variety of areas this is something that may be considered in health care and something that can be addressed by interdisciplinary approaches.Ordinary health-oriented apps and disease-specific apps were used differently and for different purposes.

The Use of Apps for Health in Persons with Multiple Sclerosis, Parkinson's Disease and Stroke - Barriers and Facilitators.

INTRODUCTION: The importance of mobile health has increased during recent years but few studies have described the use of apps among persons with neurological disabilities. AIM: The aim of this paper was to describe how persons ageing with a neurological disability experience barriers and facilitators in relation to using apps in everyday life. METHOD: A qualitative approach was used. 16 persons with neurological disorders participated in two group discussions. Data were analyzed by content analysis. RESULTS: The analysis formed four categories; Impairments make apps harder to use, Use of apps is increased by learnability and sharing, Valuating the information in an app, and Apps act supportive and motivating. CONCLUSION: The participants used apps in the same way as persons without disabilities. Impairments and trustworthiness were perceived as barriers, which need to be acknowledged when developing apps for this population. Use of apps was facilitated by the possibility to share data and to connect with others. Apps may have the potential to improve self-management for persons ageing with disabilities but further research is needed.

Myopathology in congenital myopathies.

Congenital myopathies are clinically and genetically a heterogeneous group of early onset neuromuscular disorders, characterized by hypotonia and muscle weakness. Clinical severity and age of onset are variable. Many patients are severely affected at birth while others have a milder, moderately progressive or nonprogressive phenotype. Respiratory weakness is a major clinical aspect that requires regular monitoring. Causative mutations in several genes have been identified that are inherited in a dominant, recessive or X-linked manner, or arise de novo. Muscle biopsies show characteristic pathological features such as nemaline rods/bodies, cores, central nuclei or caps. Small type 1 fibres expressing slow myosin are a common feature and may sometimes be the only abnormality. Small cores (minicores) devoid of mitochondria and areas showing variable myofibrillar disruption occur in several neuromuscular disorders including several forms of congenital myopathy. Muscle biopsies can also show more than one structural defect. There is considerable clinical, pathological and genetic overlap with mutations in one gene resulting in more than one pathological feature, and the same pathological feature being associated with defects in more than one gene. Increasing application of whole exome sequencing is broadening the clinical and pathological spectra in congenital myopathies, but pathology still has a role in clarifying the pathogenicity of gene variants as well as directing molecular analysis.

Increased Bone Mineral Content During Rapid Weight Gain Therapy in Anorexia Nervosa.

Patients with anorexia nervosa (AN) are at high risk of reduced bone mass. Osteocalcin (OC), a bone formation marker, has been proposed to act as a link between bone and energy metabolism. We investigated how the 3 forms of OC respond during a 12-week intensive nutrition therapy in AN patients, in whom large changes in energy metabolism are expected.Twenty-two female AN patients, mean 20.9 years of age, with a starting mean body mass index (BMI) 15.5 kg/m2 (minimum-maximum) (13.4-17.3 kg/m2) completed the study. Biochemical markers, body composition, bone mass by DXA, and pQCT were assessed. Subjects gained in median 9.9 kg (5.5-17.0 kg), and BMI increased from median 15.4 kg/m2 (13.4-17.3 kg/m2) to 19.0 kg/m2 (16.2-20.6 kg/m2), p<0.0001. Fat mass increased from median 11.4% (4.4-24.8%) to 26.7% (16.9-39.8%). Total OC, carboxylated OC (cOC), undercarboxylated OC (ucOC), and bone-specific alkaline phosphatase (BALP) increased during the study period. No change was observed for the resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX). Total body bone mineral content (BMC) increased, but no changes were found for whole body or lumbar spine bone mineral density. Tibial trabecular density measured by pQCT decreased. Total OC, cOC, and ucOC were not associated with BMI, insulin or body composition parameters. This prospective study demonstrates that all 3 forms of OC (total OC, cOC, ucOC) increase during rapid weight gain. BALP increased while the resorption marker CTX was unchanged, which corroborate with the increased total body BMC.

NMR-based metabolic profiling in healthy individuals overfed different types of fat: links to changes in liver fat accumulation and lean tissue mass.

BACKGROUND: Overeating different dietary fatty acids influence the amount of liver fat stored during weight gain, however, the mechanisms responsible are unclear. We aimed to identify non-lipid metabolites that may differentiate between saturated (SFA) and polyunsaturated fatty acid (PUFA) overfeeding using a non-targeted metabolomic approach. We also investigated the possible relationships between plasma metabolites and body fat accumulation. METHODS: In a randomized study (LIPOGAIN study), n=39 healthy individuals were overfed with muffins containing SFA or PUFA. Plasma samples were precipitated with cold acetonitrile and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Pattern recognition techniques were used to overview the data, identify variables contributing to group classification and to correlate metabolites with fat accumulation. RESULTS: We previously reported that SFA causes a greater accumulation of liver fat, visceral fat and total body fat, whereas lean tissue levels increases less compared with PUFA, despite comparable weight gain. In this study, lactate and acetate were identified as important contributors to group classification between SFA and PUFA (P<0.05). Furthermore, the fat depots (total body fat, visceral adipose tissue and liver fat) and lean tissue correlated (P(corr)>0.5) all with two or more metabolites (for example, branched amino acids, alanine, acetate and lactate). The metabolite composition differed in a manner that may indicate higher insulin sensitivity after a diet with PUFA compared with SFA, but this needs to be confirmed in future studies. CONCLUSION: A non-lipid metabolic profiling approach only identified a few metabolites that differentiated between SFA and PUFA overfeeding. Whether these metabolite changes are involved in depot-specific fat storage and increased lean tissue mass during overeating needs further investigation.

A Large Deletion Affecting TPM3, Causing Severe Nemaline Myopathy.

BACKGROUND AND OBJECTIVES: Nemaline myopathy may be caused by pathogenic variants in the TPM3 gene and is then called NEM1. All previously identified disease-causing variants are point mutations including missense, nonsense and splice-site variants. The aim of the study was to identify the disease-causing gene in this patient and verify the NM diagnosis. METHODS: Mutation analysis methods include our self-designed nemaline myopathy array, The Nemaline Myopathy Comparative Genomic Hybridisation Array (NM-CGH array), whole-genome array-CGH, dHPLC, Sanger sequencing and whole-exome sequencing. The diagnostic muscle biopsy was investigated further by routine histopathological methods. RESULTS: We present here the first large (17-21 kb) aberration in the α-tropomyosinslow gene (TPM3), identified using the NM-CGH array. This homozygous deletion removes the exons 1a and 2b as well as the promoter of the TPM3 isoform encoding Tpm3.12st. The severe phenotype included paucity of movement, proximal and axial weakness and feeding difficulties requiring nasogastric tube feeding. The infant died at the age of 17.5 months. Muscle biopsy showed variation in fibre size and rods in a population of hypotrophic muscle fibres expressing slow myosin, often with internal nuclei, and abnormal immunolabelling revealing many hybrid fibres. CONCLUSIONS: This is the only copy number variation we have identified in any NM gene other than nebulin (NEB), suggesting that large deletions or duplications in these genes are very rare, yet possible, causes of NM.

Targeted array comparative genomic hybridization--a new diagnostic tool for the detection of large copy number variations in nemaline myopathy-causing genes.

Nemaline myopathy (NM) constitutes a heterogeneous group of congenital myopathies. Mutations in the nebulin gene (NEB) are the main cause of recessively inherited NM. NEB is one of the most largest genes in human. To date, 68 NEB mutations, mainly small deletions or point mutations have been published. The only large mutation characterized is the 2.5 kb deletion of exon 55 in the Ashkenazi Jewish population. To investigate any copy number variations in this enormous gene, we designed a novel custom comparative genomic hybridization microarray, NM-CGH, targeted towards the seven known genes causative for NM. During the validation of the NM-CGH array we identified two novel deletions in two different families. The first is the largest deletion characterized in NEB to date, (∼53 kb) encompassing 24 exons. The second deletion (1 kb) covers two exons. In both families, the copy number change was the second mutation to be characterized and shown to have been inherited from one of the healthy carrier parents. In addition to these novel mutations, copy number variation was identified in four samples in three families in the triplicate region of NEB. We conclude that this method appears promising for the detection of copy number variations in NEB.

Mobility and mobility-related participation outcomes of powered wheelchair and scooter interventions after 4-months and 1-year use.

PURPOSE: The aim was to investigate outcomes of powered wheelchair and scooter interventions after 4-months and 1-year use regarding need for assistance when moving around, frequency of mobility-related participation, easiness/difficulty in mobility during participation, and number of participation aspects performed in everyday life. METHOD: The study was a prospective cohort study, using an instrument focusing on mobility-related participation outcomes of mobility device interventions (NOMO 1.0), at baseline, after 4-months and 1-year use. RESULTS: The results show that the outcomes in terms of participation frequency and easiness in mobility occur in a short time perspective, and that the effects remained stable at 1-year follow-up. The frequency of going for a walk increased most prominently (26%). Even though the majority of the participation aspects were not performed, more often they became easier to perform: 56-91% found that shopping, walking and visiting family/friends were easier. Moreover, independence outdoors and indoors increased. CONCLUSIONS: This small study provides knowledge about the outcomes of powered wheelchairs and scooters in terms of mobility and mobility-related participation in real-life situations. The study supports results from former studies, but even so, larger studies are required in order to provide evidence for the effectiveness of powered wheelchairs and scooters. [Box: see text].

LDL-associated apolipoprotein J and lysozyme are associated with atherogenic properties of LDL found in type 2 diabetes and the metabolic syndrome.

OBJECTIVES: Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyse the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL. DESIGN: Low-density lipoprotein from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro. RESULTS: ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with size-exclusion chromatography, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL. CONCLUSIONS: Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase lysozyme in LDL from those with type 2 diabetes.

Safety and efficacy of mid-term pregnancy termination using aglepristone in dogs.

OBJECTIVES: To investigate effects and side effects of aglepristone in terminating pregnancy in bitches. METHODS: Twenty-two bitches were treated in mid-pregnancy with subcutaneous injections of aglepristone at a total dose of 20 mg/kg. Short-term follow-up (one to two weeks after treatment) included clinical examination and abdominal ultrasonography in 18 of the dogs. Long-term telephone follow-up was recorded for all 22 dogs. RESULTS: Pregnancy was terminated in 21 bitches (95 per cent). Signs of abortion occurred one to eight days after treatment. Vaginal discharge was evident in 17 (77 per cent) dogs. Obvious signs of parturition were seen in nine (41 per cent) dogs. Eight dogs (36 per cent) developed anorexia, and in two (9 per cent) of the dogs a local reaction at the injection site was evident. Two dogs developed pyometra two and four years after treatment, respectively. CLINICAL SIGNIFICANCE: Aglepristone, when administered in mid-gestation, is effective in terminating pregnancy. Side effects are few and transient.

Correlation of in vitro dissolution rate and apparent solubility in buffered media using a miniaturized rotating disk equipment: Part I. Comparison with a traditional USP rotating disk apparatus.

A correlation of the logarithmic values of the in vitro dissolution rate, G, and the apparent solubility, S, was evaluated in phosphate and ammonium acetate buffer at an initial pH of 7. The dissolution rates were determined with a newly designed and build miniaturized rotating disk equipment, as well as with a traditional rotating disk apparatus. The two apparatuses gave the same correlation pattern of logG and logS. Thirteen diverse drug substances from all of the classes in the Biopharmaceutics Classification System (BCS) were used for the correlation in the phosphate buffer system, with the results from the miniaturized apparatus only. A coefficient of determination, R2, of 0.982 was found if bases formulated as hydrochloride salts were excluded in the correlation. The miniaturized equipment is used for rapid screening of the dissolution rate, approximately 10 min for one run, and consumes small amounts of substance (about 5 mg) and dissolution media. All quantifications were performed by using reversed phase high-performance liquid chromatography (RPHPLC) with a diode array detector (DAD), integrated with the miniaturized rotating disk equipment.

Correlation of in vitro dissolution rate and apparent solubility in buffered media using a miniaturized rotating disk equipment: Part II. Comparing different buffer media.

A correlation of the logarithmic values of the in vitro dissolution rate, G, and apparent solubility, S, was made for seven different drug substances from all of the classes in the Biopharmaceutics Classification System (BCS), in four different phosphate buffers. The effect of inorganic salts added as sodium chloride, sodium nitrate, sodium phosphate and sodium sulfate in the buffer media was investigated for the correlation. Triethanolammonium acetate buffer was also included in the study of the correlation of logG vs. logS. The pH was 7.0 ± 0.1 in all of the buffers to mimic a pH condition in intestinal fluids. The dissolution rate was determined with a newly constructed miniaturized rotating disk equipment, which enables fast determinations and consumes only minute quantities of substance (about 5 mg). The solubility was determined by conventional shake-flask methodology, using 1.5 mL solution volumes. All quantifications were performed with reversed phase high-performance liquid chromatography (RP-HPLC) and diode array detection (DAD). The different inorganic anions seemed to affect the solubility more than the dissolution rate. The phosphate and nitrate ions decreased the solubility for amines compared to the chloride ion. The best correlations of logG and logS were however obtained with a triethanolammonium acetate buffer. The good correlation (R2 = 0.991) may be sufficient in initial screening of drug solubility, based on dissolution rates in aqueous buffer media.

Increased lipolysis by secretory phospholipase A(2) group V of lipoproteins in diabetic dyslipidaemia.

BACKGROUND: Lipolysis of lipoproteins by secretory phospholipase A(2) group V (sPLA(2)-V) promotes inflammation, lipoprotein aggregation and foam cell formation--all considered as atherogenic mechanisms. OBJECTIVE: In this study, we compared the susceptibility to sPLA(2)-V lipolysis of VLDL and LDL from individuals with type 2 diabetes and the metabolic syndrome (T2D-MetS) and from healthy controls. Design. VLDL and LDL were isolated from 38 T2D-MetS subjects and 38 controls, treated pair-wise. Extent of sPLA(2)-V lipolysis was measured as release of nonesterified free fatty acids (NEFA). In a subset of the subjects, lipoprotein composition was determined as a relationship between lipid and apolipoprotein components. RESULTS: Mean paired increase in sPLA(2)-V lipolysis after 1 h for T2D-MetS versus control was 2.0 micromol NEFA l(-1) for VLDL (P = 0.004) and 0.75 micromol NEFA l(-1) for LDL (P = 0.001). There were also substantial differences in lipoprotein composition between the groups. T2D-MetS VLDL had higher triglyceride and cholesterol contents than control VLDL. T2D-MetS LDL was smaller and contained more triglycerides and less cholesterol than control LDL. Both VLDL and LDL from T2D-MetS subjects also contained more apolipoprotein CIII per particle. CONCLUSION: VLDL and LDL from T2D-MetS individuals were more susceptible to sPLA(2)-V lipolysis than those from control individuals. This may result in elevated levels of NEFA and lysophosphatidylcholine, both in circulation and in LDL, possibly contributing to the elevated inflammatory state and increased risk of cardiovascular diseases seen in these individuals.

How can we prevent cardiovascular disease in diabetes.

Evidence based goals for the treatment and prevention of atherosclerosis in diabetes are given in international and national guidelines. The importance of optimal control of lipids and blood pressure has been shown in several studies. With available drugs and behavioural modifications the treatment goals can be reached in most cases. However, only a few patients with diabetes are treated optimally today. A major possibility to reduce cardiovascular disease in diabetes is to treat patients according to guidelines. New treatment targets may include specific treatment of the dyslipidaemia, manifested in high levels of small dense LDL and low HDL, active anti-inflammatory treatments, specific reduction of inflammatory activity in adipose tissue, reduced volume of adipose tissue, antioxidants and reduction of advanced glycosylation endproducts production. Possible strategies for these treatments are available, and should be evaluated in clinical trials.

X-inactivation patterns in carriers of X-linked myotubular myopathy.

X-linked myotubular myopathy is a rare severe muscle disorder in affected male neonates. Most female carriers are free from symptoms. Skewed X inactivation has been proposed to be responsible for the affected phenotype seen in some carriers. We have compared the X inactivation patterns in blood DNA with the clinical phenotype in carriers of X-linked myotubular myopathy. The X-inactivation analysis was performed using HpaII predigestion of DNA followed by polymerase chain reaction of the highly polymorphic CAG repeat of the androgen receptor (AR) gene. The frequency of skewed X inactivation was similar in the X-linked myotubular myopathy carriers (22%) and in 235 controls (18%). Three overtly affected carriers had skewed X inactivation with the mutated X as the predominantly active X in at least two of them. Four females with mild symptoms had random X inactivation. The unaffected X-linked myotubular myopathy carriers had either skewed X inactivation in favour of expression from the normal X or random X-inactivation. Thus, there was a tendency for females with a more severe phenotype to have a skewed pattern of X inactivation, while females with an intermediate phenotype had a random pattern of X-inactivation.

Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation.

X-linked myotubular myopathy is a severe congenital myopathy in males, caused by mutations in the myotubularin (MTM1) gene on chromosome Xq28. In heterozygous carriers of MTM1 mutations, clinical symptoms are usually absent or only mild. We report a 6-year-old girl presenting at birth with marked hypotonia and associated feeding and respiratory difficulties. A muscle biopsy performed at 5 months suggested a diagnosis of myotubular myopathy. On examination at 6 years she had marked facial weakness with bilateral ptosis and external ophthalmoplegia, severe axial and proximal weakness and a mild scoliosis. Muscle magnetic resonance imaging showed a distinctive pattern of muscle involvement. Molecular genetic investigation of the MTM1 gene identified a heterozygous mutation in exon 12. X-inactivation studies in lymphocytes showed an extremely skewed pattern (97:3). This case emphasizes that investigation of the MTM1 gene and X-inactivation studies are indicated in isolated females with histopathological and clinical findings suggestive of myotubular myopathy.

De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy.

We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis. In this patient, we demonstrate heterozygosity for a de novo CGT-CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation identified in a constitutively expressed exon of TPM3 in a nemaline myopathy patient, but is similar to recently described mutations in beta-tropomyosin (TPM2) associated with nemaline myopathy and mutations in fast alpha-tropomyosin (TPM1) which cause hypertrophic cardiomyopathy.

Environmental risk of particulate and soluble platinum group elements released from gasoline and diesel engine catalytic converters.

A comparison of platinum-group element (PGE) emission between gasoline and diesel engine catalytic converters is reported within this work. Whole raw exhaust fumes from four catalysts of three different types were examined during their useful lifetime, from fresh to 80,000 km. Two were gasoline engine catalysts (Pt-Pd-Rh and Pd-Rh), while the other two were diesel engine catalysts (Pt). Samples were collected following the 91441 EUDC driving cycle for light-duty vehicle testing, and the sample collection device used allowed differentiation between the particulate and soluble fractions, the latter being the most relevant from an environmental point of view. Analyses were performed by inductively coupled plasma-mass spectrometry (ICP-MS) (quadrupole and high resolution), and special attention was paid to the control of spectral interference, especially in the case of Pd and Rh. The results obtained show that, for fresh catalysts, the release of particulate PGE through car exhaust fumes does not follow any particular trend, with a wide range (one-two orders of magnitude) for the content of noble metals emitted. The samples collected from 30,000-80,000 km present a more homogeneous PGE release for all catalysts studied. A decrease of approximately one order of magnitude is observed with respect to the release from fresh catalysts, except in the case of the diesel engine catalyst, for which PGE emission continued to be higher than in the case of gasoline engines. The fraction of soluble PGE was found to represent less than 10% of the total amount released from fresh catalysts. For aged catalysts, the figures are significantly higher, especially for Pd and Rh. Particulate PGE can be considered as virtually biologically inert, while soluble PGE forms can represent an environmental risk due to their bioavailability, which leads them to accumulate in the environment.