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Biomedical subjects

Michael Sjöström

Publications and source records attributed to Michael Sjöström.

At least 19 recordsLinked to original sources

Hand span influences optimal grip span in male and female teenagers.

PURPOSE: To determine if there is an optimal grip span for determining the maximum handgrip strength in male and female teenagers, and if the optimal grip span was related to hand span. If they are related then the second aim was to derive a mathematic equation relating hand span and optimal grip span. METHODS: One hundred healthy teenage boys (15.1 +/- 1.1 y) and 106 girls (15.4 +/- 1.3 y) were evaluated (age range, 13-18 y). Each hand was randomly tested on 10 occasions using 5 different grip spans, allowing a 1-minute rest between attempts. The hand span was measured from the tip of the thumb to the tip of the small finger with the hand opened as wide as possible. RESULTS: The results showed that an optimal grip span to determine the maximum handgrip strength was identified for both genders, and the optimal grip span and hand span correlated in both genders. CONCLUSIONS: The results suggest that there is an optimal grip span to which the dynamometer should be adjusted when measuring handgrip strength in teenagers. The optimal grip span was influenced by hand span in both genders. For males the optimal grip span can be derived from the equation y = x/7.2 + 3.1 cm, and for females from the equation y = x/4 + 1.1 cm. where y is the optimal grip span and x is the hand-span. These equations may improve the reliability and accuracy of the results and may guide clinicians and researchers in selecting the optimal grip span on the hand dynamometer when measuring handgrip strength in teenagers.

Adolescent↗

Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS data--a potential tool for multi-parametric diagnosis.

A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e.g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample (approximately 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.

Animals↗

Sex-specific, male-line transgenerational responses in humans.

Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Overkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Overkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene-environment interactions in development and health.

Adult↗

The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity.

INTRODUCTION: The International Physical Activity Questionnaire (IPAQ) was developed to measure health-related physical activity (PA) in populations. The short version of the IPAQ has been tested extensively and is now used in many international studies. The present study aimed to explore the validity characteristics of the long-version IPAQ. SUBJECTS AND METHODS: Forty-six voluntary healthy male and female subjects (age, mean +/- standard deviation: 40.7 +/- 10.3 years) participated in the study. PA indicators derived from the long, self-administered IPAQ were compared with data from an activity monitor and a PA log book for concurrent validity, and with aerobic fitness, body mass index (BMI) and percentage body fat for construct validity. RESULTS: Strong positive relationships were observed between the activity monitor data and the IPAQ data for total PA (rho = 0.55, P < 0.001) and vigorous PA (rho = 0.71, P < 0.001), but a weaker relationship for moderate PA (rho = 0.21, P = 0.051). Calculated MET-h day(-1) from the PA log book was significantly correlated with MET-h day(-1) from the IPAQ (rho = 0.67, P < 0.001). A weak correlation was observed between IPAQ data for total PA and both aerobic fitness (rho = 0.21, P = 0.051) and BMI (rho = 0.25, P = 0.009). No significant correlation was observed between percentage body fat and IPAQ variables. Bland-Altman analysis suggested that the inability of activity monitors to detect certain types of activities might introduce a source of error in criterion validation studies. CONCLUSIONS: The long, self-administered IPAQ questionnaire has acceptable validity when assessing levels and patterns of PA in healthy adults.

Adipose Tissue↗

Multivariate methods in the development of a new tablet formulation: excipient mixtures and principal properties.

A tablet formulation for direct compression has previously been studied using multivariate design. An optimization study of one of the most important tablet properties, disintegration time, revealed that excipients with Principal Properties (PP's) that were predicted as suitable by the model were not represented within the studied material. The feasibility of using mixtures of excipients in the multivariate approach to tablet formulation to solve this problem has been investigated in the present study. By mixing different excipients of the same excipient class, it should be possible to obtain mixtures with the predicted PP's, which in turn should give a formulation with the desired properties. In order to investigate the utility of this approach, separate mixture designs were applied to both binders and fillers (diluents). As reported here, the Partial Least Squares Projections to Latent Structures (PLS) model developed in the previously published screening study has been validated in the sense that the interesting region of the PP space identified in it has been shown to contain excipients, pure or mixed, that give the formulation suitable properties. Formulations with suitable properties were found with the mixture experiments. The local models also offer several alternatives for the composition of the formulation that yield the desired disintegration time.

Chemistry, Pharmaceutical↗

Robustness testing of a tablet formulation using multivariate design.

A total of 45 experiments were carried out to evaluate the robustness of two similar tablet formulations--a product of two strengths--with respect to normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. The formulations consist of 10 ingredients. Because of the differing amounts of active pharmaceutical ingredients, the two formulations also differ in the amounts of two of the diluents and one of the binders. The excipients and active pharmaceutical ingredient were characterized in terms of multiple variables, and principal properties were calculated with principal component analysis. A Plackett and Burman design was applied to the principal properties. The relationships between the design factors and two responses, mean disintegration time and mean crushing strength, were evaluated by using regression methods. Both formulations were found to be robust under controlled conditions.

Chemistry, Pharmaceutical↗

Relations of total physical activity and intensity to fitness and fatness in children: the European Youth Heart Study.

BACKGROUND: It is unclear how the amount and intensity of physical activity (PA) are associated with cardiovascular fitness (CVF) and body fatness in children. OBJECTIVE: We aimed to examine the associations of total PA and intensity levels to CVF and fatness in children. DESIGN: A cross-sectional study of 780 children aged 9-10 y from Sweden and Estonia was conducted. PA was measured by accelerometry and was expressed as min/d of total PA, moderate PA, and vigorous PA. CVF was measured with a maximal ergometer bike test and was expressed as W/kg. Body fat was derived from the sum of 5 skinfold-thickness measurements. Multiple regression analysis was used to determine the degree to which variance in CVF and body fat was explained by PA, after control for age, sex, and study location. RESULTS: Lower body fat was significantly associated with higher levels of vigorous PA, but not with moderate or total PA. Those children who engaged in >40 min vigorous PA/d had lower body fat than did those who engaged in 10-18 min vigorous PA/d. Total PA, moderate PA, and vigorous PA were positively associated with CVF. Those children who engaged in >40 min vigorous PA/d had higher CVF than did those who accumulated <18 min vigorous PA/d. CONCLUSIONS: The results suggest that PA of vigorous intensity may have a greater effect on preventing obesity in children than does PA of lower intensity, whereas both total and at least moderate to vigorous PA may improve children's CVF.

Adipose Tissue↗

Inflammatory proteins are related to total and abdominal adiposity in a healthy adolescent population: the AVENA Study.

BACKGROUND: In adults, obesity is characterized by a state of chronic low-grade inflammation accompanied by moderately high concentrations of acute phase inflammatory proteins. Recent results regarding C-reactive protein (CRP) point to a similar status in adolescents; however, studies of associations of the serum inflammatory proteins CRP, ceruloplasmin, and complement factors C3 and C4 with body fat distribution remain scarce. OBJECTIVE: We aimed to establish the possible relations of serum inflammatory proteins with body fat estimates and body fat distribution in an apparently healthy adolescent population. DESIGN: This report included 472 adolescents (248 males and 224 females) aged 13-18.5 y who were recruited from the Spanish cross-sectional multicenter AVENA Study for whom anthropometric and immunologic data were complete. The concentrations of the serum proteins and the in vitro production of cytokines (interleukin 6 and tumor necrosis factor alpha) by isolated and stimulated white blood cells were measured. Relations with anthropometric measurements were explored by using simple and partial correlations. RESULTS: CRP, C3, and C4 were correlated with central obesity (as measured by waist circumference) and total body fat in both sexes (P < 0.01) and with ceruloplasmin in females only. After further adjustment for BMI, C3 remained independently associated with central obesity (P < 0.05). Production of the cytokines by white blood cells did not seem to be affected by an excess of body fat. CONCLUSIONS: Total body fat seems to be associated with a chronic low-grade systemic inflammation in apparently healthy adolescents. Central obesity is independently associated with C3 concentrations, which makes this marker especially interesting for further studies of obesity-related diseases.

Abdominal Fat↗

Novel mutations in the 5'-UTR of the FOLR1 gene.

We have previously reported two novel mutations in the 5'-untranslated region (UTR) of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations, 92 patient samples with elevated levels of homocysteine were screened by single-strand conformation polymorphism (SSCP) between nt -425 and -782, and -712 and -1110. Between nt -425 and -782 we did not find any mutations. Between nt -712 and -1110 there were three novel mutations. One subject had two mutations very close to each other, c.-856C>T and c.-921T>C. Two subjects had a c.-1043G>A mutation. To get an idea of the prevalence of FOLR1 mutations in an unselected population, we also screened 692 healthy school children for mutations. In this cohort, between nt -188 and +272 we discovered one novel mutation, a single nucleotide substitution, c.-18C>T, in addition to five children with the 25-bp deletion mutation previously described by us. Thus, so far we have discovered six novel mutations in the 5'-UTR region of the gene for folate receptor-alpha. We genotyped all 17 subjects with a FOLR1 mutation for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism, and developed new single-nucleotide polymorphism (SNP) genotyping protocols for MTHFR 1298A>C and 1793G>A utilising Pyrosequencing technology. None of the 17 subjects had the 677TT genotype, which ruled out this as a cause of elevated homocysteine levels, which was observed in some of the subjects. Further studies of mutations in the 5'-UTR of FOLR1, and in particular of their interplay with folate intake status, are warranted.

5' Untranslated Regions↗

MASQOT: a method for cDNA microarray spot quality control.

BACKGROUND: cDNA microarray technology has emerged as a major player in the parallel detection of biomolecules, but still suffers from fundamental technical problems. Identifying and removing unreliable data is crucial to prevent the risk of receiving illusive analysis results. Visual assessment of spot quality is still a common procedure, despite the time-consuming work of manually inspecting spots in the range of hundreds of thousands or more. RESULTS: A novel methodology for cDNA microarray spot quality control is outlined. Multivariate discriminant analysis was used to assess spot quality based on existing and novel descriptors. The presented methodology displays high reproducibility and was found superior in identifying unreliable data compared to other evaluated methodologies. CONCLUSION: The proposed methodology for cDNA microarray spot quality control generates non-discrete values of spot quality which can be utilized as weights in subsequent analysis procedures as well as to discard spots of undesired quality using the suggested threshold values. The MASQOT approach provides a consistent assessment of spot quality and can be considered an alternative to the labor-intensive manual quality assessment process.

Data Interpretation, Statistical↗

Outcomes of comprehensive lifestyle modification in inpatient setting.

OBJECTIVE: To examine the effectiveness of a 4-week inpatient non-pharmacological risk factor modification programme for individuals with the metabolic syndrome. The aim of the program was to reduce patients' over risks for stroke and myocardial infarction. METHODS: A prospective clinical study including 2468 patients--1096 men and 1372 women--with and average age of 50 +/- 10 years. The patients were referred to the programme from primary care units and hospitals where treatment options were exhausted. RESULTS: All risk factor levels for stroke and myocardial infarction decreased. The reduction of weight among men was 4.7 +/- 2.6 kg and 3.8 +/- 1.8 kg among women from an initial weight of 96 +/- 17 kg and 85 +/- 16 kg, respectively. The patients systolic and diastolic blood pressure decreased by 15/10 mmHg for men and 14/9 mmHg among women from initial average for the whole population of 148/90 +/- 19/11 mmHg and 146/87 +/- 19/12 mmHg, respectively. The greatest decrease in weight and blood pressure occurred in men and women with an initial body mass index of > or = 30 and with a diastolic blood pressure of > or = 90; in this group, the average reductions in weight were 5.8 +/- 2.4 kg for men and 4.4 +/- 1.7 kg for women; the reductions in systolisk/diastolisk blood pressure were 22/15 +/- 16/9 mmHg (p < 0.001) for both men and women. A reduction of medication (DDD) although not a goal was also achieved. CONCLUSION: The results prove the value of a comprehensive and highly structured inpatient approach to lifestyle modification. PRACTICE IMPLICATIONS: The results should give cause to trials with half-way strategies integrating features from the inpatient programme into the design of risk factor interventions.

Aged↗

High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses.

In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography-mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples: a complex mixture of standard compounds and Arabidopsis samples.

Arabidopsis↗

Extraction, interpretation and validation of information for comparing samples in metabolic LC/MS data sets.

LC/MS is an analytical technique that, due to its high sensitivity, has become increasingly popular for the generation of metabolic signatures in biological samples and for the building of metabolic data bases. However, to be able to create robust and interpretable (transparent) multivariate models for the comparison of many samples, the data must fulfil certain specific criteria: (i) that each sample is characterized by the same number of variables, (ii) that each of these variables is represented across all observations, and (iii) that a variable in one sample has the same biological meaning or represents the same metabolite in all other samples. In addition, the obtained models must have the ability to make predictions of, e.g. related and independent samples characterized accordingly to the model samples. This method involves the construction of a representative data set, including automatic peak detection, alignment, setting of retention time windows, summing in the chromatographic dimension and data compression by means of alternating regression, where the relevant metabolic variation is retained for further modelling using multivariate analysis. This approach has the advantage of allowing the comparison of large numbers of samples based on their LC/MS metabolic profiles, but also of creating a means for the interpretation of the investigated biological system. This includes finding relevant systematic patterns among samples, identifying influential variables, verifying the findings in the raw data, and finally using the models for predictions. The presented strategy was here applied to a population study using urine samples from two cohorts, Shanxi (People's Republic of China) and Honolulu (USA). The results showed that the evaluation of the extracted information data using partial least square discriminant analysis (PLS-DA) provided a robust, predictive and transparent model for the metabolic differences between the two populations. The presented findings suggest that this is a general approach for data handling, analysis, and evaluation of large metabolic LC/MS data sets.

Chromatography, Liquid↗

A new metabonomic strategy for analysing the growth process of the poplar tree.

High-resolution, magic angle spinning, proton nuclear magnetic resonance (1H HR/MAS NMR) spectroscopy and multivariate data analysis using batch processing (BP) were applied to the analysis of two different genotypes of poplar tree (Populus tremula L. x tremuloides Michx.) containing an antisense construct of PttMYB76 and control (wild-type). A gene encoding a MYB transcription factor, with unknown function, PttMYB76, was selected from a cambial expressed sequence tag (EST) library of poplar tree (Populus tremula L. x tremuloides Michx.) for metabonomic characterization. The PttMYB76 gene is believed to affect different paths in the phenyl propanoid synthetic pathway. This pathway leads to the formation of S- and G-lignin, flavonoids and sinapate esters. Milled poplar samples collected at the internodes of the tree were analysed using 1H HR/MAS NMR spectroscopy. The application of multivariate BP of the NMR results revealed a growth-related gradient in the plant internode direction, as well as the discrimination between the trees with down-regulated PttMYB76 expression and wild-type populations. This paper focuses on the potential of a new analytical multivariate approach for analysing time-related plant metabonomic data. The techniques used could, with the aid of suitable model compounds, be of high relevance to the detection and understanding of the different lignification processes within the two types of poplar tree. Additionally, the findings highlight the importance of applying robust and organized multivariate data analysis approaches to facilitate the modelling and interpretation of complex biological data sets.

Journal Article↗

Socio-demographic determinants of initiation and duration of breastfeeding in northwest Russia.

AIM: This study examines socio-demographic determinants of initiation and duration of breastfeeding in a community-based cohort in northwest Russia. METHODS: All infants born to women who were registered at the antenatal clinics in Severodvinsk in 1999 comprised the cohort (n=1399) and were followed up at 1 y. Data on maternal and infant characteristics as well as the duration of breastfeeding were obtained from medical records. Proportional hazard analysis was applied to quantify the effect of the selected factors on the risk of breastfeeding discontinuation adjusted for potential confounders. RESULTS: Only 1.3% of infants were never breastfed. Breastfeeding rates were 75.0% and 47.2% at 3 and 6 mo, respectively. Maternal age and early initiation of prenatal care were positively associated with breastfeeding initiation rates. Increased risks of breastfeeding discontinuation were found in teenage mothers (OR=1.45, 95% CI: 1.06-1.99), in mothers with basic education (OR=1.68, 95% CI: 1.06-2.66) and in unmarried mothers (OR=1.19, 95% CI: 1.03-1.38). Women with no previous deliveries were more likely to breastfeed longer (OR=0.74, 95% CI: 0.62-0.90). CONCLUSIONS: Compared with previous studies in Russia, almost universal initiation and considerably higher rates of breastfeeding at specific time points were found. Social variations in initiation and duration of breastfeeding should raise concern of inequalities in breastfeeding practices in transitional Russia.

Adolescent↗

Design of experiments: an efficient strategy to identify factors influencing extraction and derivatization of Arabidopsis thaliana samples in metabolomic studies with gas chromatography/mass spectrometry.

The usual aim in metabolomic studies is to quantify the entire metabolome of each of a series of biological samples. To do this for complex biological matrices, e.g., plant tissues, efficient and reproducible extraction protocols must be developed. However, derivatization protocols must also be developed if GC/MS (one of the mostly widely used analytical methods for metabolomics) is involved. The aim of this study was to investigate how different chemical and physical factors (extraction solvent, derivatization reagents, and temperature) affect the extraction and derivatization of the metabolome from leaves of the plant Arabidopsis thaliana. Using design of experiment procedures, variation was systematically introduced, and the effects of this variation were analyzed using regression models. The results show that this approach allows a reliable protocol for metabolomic analysis of Arabidopsis to be determined with a relatively limited number of experiments. Following two different investigations an extraction and derivatization protocol was chosen. Further, the reproducibility of the analysis of 66 endogenous compounds was investigated, and it was shown that both hydrophilic and lipophilic compounds were detected with high reproducibility.

Arabidopsis↗

Recognition of fold and sugar linkage for glycosyltransferases by multivariate sequence analysis.

Glycosyltransferases (GTs) are among the largest groups of enzymes found and are usually classified on the basis of sequence comparisons into many families of varying similarity (CAZy systematics). Only two different Rossman-like folds have been detected (GT-A and GT-B) within the small number of established crystal structures. A third uncharacterized fold has been indicated with transmembrane organization (GT-C). We here use a method based on multivariate data analyses (MVDAs) of property patterns in amino acid sequences and can with high accuracy recognize the correct fold in a large data set of GTs. Likewise, a retaining or inverting enzymatic mechanism for attachment of the donor sugar could be properly revealed in the GT-A and GT-B fold group sequences by such analyses. Sequence alignments could be correlated to important variables in MVDA, and the separating amino acid positions could be mapped over the active sites. These seem to be localized to similar positions in space for the alpha/beta/alpha binding motifs in the GT-B fold group structures. Analogous, active-site sequence positions were found for the GT-A fold group. Multivariate property patterns could also easily group most GTs annotated in the genomes of Escherichia coli and Synechocystis to proper fold or organization group, according to benchmarking comparisons at the MetaServer. We conclude that the sequence property patterns revealed by the multivariate analyses seem more conserved than amino acid types for these GT groups, and these patterns are also conserved in the structures. Such patterns may also potentially define substrate preferences.

Amino Acid Motifs↗

A strategy for identifying differences in large series of metabolomic samples analyzed by GC/MS.

In metabolomics, the purpose is to identify and quantify all the metabolites in a biological system. Combined gas chromatography and mass spectrometry (GC/MS) is one of the most commonly used techniques in metabolomics together with 1H NMR, and it has been shown that more than 300 compounds can be distinguished with GC/MS after deconvolution of overlapping peaks. To avoid having to deconvolute all analyzed samples prior to multivariate analysis of the data, we have developed a strategy for rapid comparison of nonprocessed MS data files. The method includes baseline correction, alignment, time window determinations, alternating regression, PLS-DA, and identification of retention time windows in the chromatograms that explain the differences between the samples. Use of alternating regression also gives interpretable loadings, which retain the information provided by m/z values that vary between the samples in each retention time window. The method has been applied to plant extracts derived from leaves of different developmental stages and plants subjected to small changes in day length. The data show that the new method can detect differences between the samples and that it gives results comparable to those obtained when deconvolution is applied prior to the multivariate analysis. We suggest that this method can be used for rapid comparison of large sets of GC/MS data, thereby applying time-consuming deconvolution only to parts of the chromatograms that contribute to explain the differences between the samples.

Algorithms↗