GALM Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 362 amino acids (1-342 a.a.) and having a molecular mass of 39.9 kDa. The GALM is fused to a 20 amino acid His-Tag at N-terminus and purified by proprietary chromatographic techniques.
MGSSHHHHHH SSGLVPRGSH MASVTRAVFG ELPSGGGTVE KFQLQSDLLR VDIISWGCTI TALEVKDRQG RASDVVLGFA ELEGYLQKQP YFGAVIGRVA NRIAKGTFKV DGKEYHLAIN KEPNSLHGGV RGFDKVLWTP RVLSNGVQFS RISPDGEEGY PGELKVWVTY TLDGGELIVN YRAQASQATP VNLTNHSYFN LAGQASPNIN DHEVTIEADT YLPVDETLIP TGEVAPVQGT AFDLRKPVEL GKHLQDFHLN GFDHNFCLKG SKEKHFCARV HHAASGRVLE VYTTQPGVQF YTGNFLDGTL KGKNGAVYPK HSGFCLETQN WPDAVNQPRF PPVLLRPGEE YDHTTWFKFS VA.
The GALM method is built upon a conceptual behavioral change model developed after extensive literature review. This model operates on the principle that behavioral change represents a process where different determinants vary in significance throughout the behavior modification journey. The theoretical framework acknowledges three key determinant categories affecting physical activity in older adults:
Availability factors: The lack of suitable, low-threshold sports activities designed for diverse older adult populations
Personal characteristics: Including socioeconomic status and self-efficacy levels
Dropout mechanisms: Particularly the absence of adequate social support
The model posits that determinants such as direct approach methods, self-efficacy development, social support structures, and enjoyment in movement fluctuate in importance as participants progress through different stages of behavioral change. This theoretical foundation guided the development of the three-component intervention structure (house-to-house approach, structured exercise program, and continuation groups) that characterizes the GALM methodology .
GALM research employs a specific validated questionnaire developed to identify and select appropriate participants from the target population. The selection process follows a structured protocol:
A house-to-house approach targets 800-1,000 senior citizens (or multiples thereof)
Participants are screened using a specially developed questionnaire that has been validated for reliability
Selection focuses on sedentary (inactive or insufficiently active) individuals aged 55-65
The screening identifies individuals with specific characteristics common to the target population
Research samples typically exhibit high prevalence of chronic conditions (approximately 30% have one or more chronic illnesses) and distinct social positioning (over 70% are no longer in active employment). This rigorous selection methodology ensures study samples accurately represent the target population, enhancing the validity of research findings and their generalizability to similar demographic groups .
The primary assessment instrument employed in GALM research is the Groningen Fitness Test for the Elderly (GFO), developed by Human Movement Sciences at the University of Groningen. This comprehensive assessment tool:
Additionally, researchers collect data on potentially mediating variables of physical activity behavior change through validated instruments measuring self-efficacy, social support, perceived fitness, and enjoyment. These measurements allow for multivariate analysis of behavioral change mechanisms and identification of key psychological factors influencing program adherence .
GALM research employs sophisticated methodological approaches to measure and analyze mediating variables:
Longitudinal data collection: Researchers obtain data on mediating variables (self-efficacy, social support, perceived fitness, and enjoyment) at multiple timepoints throughout the 18-month intervention period
Prospective analysis: Statistical techniques identify significant differences in these variables between measurement points
Discriminant analysis: This technique examines relationships between mediating variables and program adherence
Canonical correlation: Applied to determine the strength of relationships between variable clusters and behavioral outcomes
Research findings have demonstrated significant differences in several mediating variables over time, though some changes contradicted initial hypotheses. Discriminant analysis has proven particularly valuable, yielding canonical correlations of 0.50 after 6 months and 0.66 after 18 months between adherers and non-adherers. These analyses enabled correct classification of 73.8% of subjects after 6 months and 80.0% after 18 months, providing substantive evidence for the predictive value of these mediating variables .
Researchers implementing GALM studies face several methodological challenges:
Selection bias: The house-to-house recruitment approach reaches only approximately 18% of the target population, potentially introducing selection bias
Heterogeneity of participants: The target population exhibits high prevalence of chronic conditions (30%) and varied social circumstances, creating potential confounding variables
Measurement constraints: While fitness outcomes can be objectively measured through standardized tests, many mediating variables rely on self-report measures
Intervention fidelity: Ensuring consistent implementation across multiple sites and instructors requires robust protocols and training
Attribution of effects: Distinguishing intervention effects from external influences in an 18-month program presents analytical challenges
Researchers have developed several methodological adaptations to address these challenges, including specialized approaches for participants unable to engage in standard protocols due to health limitations (SCALA program), customized approaches for those preferring individual rather than group activities (Personal Exercise Plan), and culturally adapted approaches for ethnic minority seniors .
Adherence analysis represents a critical component of GALM research methodology. Studies indicate that approximately 70% of initial participants remain active after the 18-month intervention period. Researchers employ several methodological strategies to account for adherence patterns:
Discriminant analysis: Identifies mediating variables that distinguish adherers from non-adherers
Temporal comparison: Examines how canonical correlations between variables and adherence strengthen over time (0.50 at 6 months to 0.66 at 18 months)
Predictive modeling: Uses early measurement data to classify participants (with 73.8-80.0% accuracy) regarding likely long-term adherence
Social cognitive theory application: Tests the generalizability of social cognitive theory-driven variables to the Dutch population
These analytical approaches have substantially expanded understanding of factors influencing physical activity behavior maintenance in older adults, contributing to refinement of both the theoretical model and intervention strategies. Research findings suggest that while manipulation of mediating variables was partially successful, certain variables demonstrated stronger discriminative power between adherers and non-adherers than initially hypothesized .
The GALM research protocol integrates three distinct intervention components implemented over an 18-month period:
This comprehensive approach reflects application of the theoretical behavior change model, addressing availability barriers through accessible programming, personal characteristic limitations through adaptable activities, and dropout mechanisms through social integration and enjoyment-focused design.
Maintaining intervention fidelity across multiple implementation sites represents a significant methodological challenge. GALM research addresses this through several structural mechanisms:
Standardized materials and protocols:
GALM manual providing detailed implementation guidelines
Standard material file containing all necessary letters and protocols
Training videos for house-to-house visitors and fitness test leaders
Structured training programs:
Specialized GALM course for supervisors of GALM groups
Regionalized training delivery across four Netherlands regions
Collaboration with KNGU (Royal Dutch Gymnastics Union) for supervisor recruitment and training
Ongoing support mechanisms:
Centralized coordination:
This comprehensive approach to fidelity maintenance ensures methodological consistency while allowing appropriate adaptation to local contexts, enhancing both internal and external validity of research findings.
Longitudinal research has yielded several key findings regarding GALM's effectiveness in changing physical activity behavior among sedentary older adults:
Participation rates: The house-to-house approach successfully engages approximately 18% of targeted sedentary seniors in GALM projects
Retention rates: Approximately 70% of initial participants remain active after the 18-month intervention period
Mediating variables: Significant changes in self-efficacy, social support, perceived fitness, and enjoyment were observed throughout the intervention period
Discriminative power: Mediating variables reliably discriminated between long-term adherers and non-adherers with increasing accuracy over time (73.8% at 6 months, 80.0% at 18 months)
GALM research has made significant contributions to expanding the generalizability of social cognitive theory to new populations and contexts:
Cross-cultural application: Research findings demonstrate that social cognitive theory-driven variables can be effectively applied to Dutch populations, extending previously established relationships beyond their original cultural contexts
Age-specific validation: Results confirm the applicability of social cognitive constructs to older adult populations (55-65 years), validating their relevance across the lifespan
Variable relationship refinement: Research findings identify which social cognitive variables most powerfully discriminate between adherers and non-adherers in this population
Temporal dimension: Longitudinal results demonstrate how relationships between variables and behavioral outcomes evolve over extended time periods (18 months)
These findings substantially advance understanding of how social cognitive theory operates in diverse contexts, providing evidence-based support for its cross-cultural and cross-age application while refining understanding of its most powerful predictive components.
GALM research has stimulated several methodological innovations with broader applications to physical activity intervention research:
Target population identification: Development and validation of specialized questionnaires for identifying sedentary older adults with high specificity
Adaptive intervention design: Creation of parallel interventions for subpopulations unable to participate in standard protocols:
SCALA program for individuals with health limitations
Personal Exercise Plan (PEP) for those preferring individualized activities
Culturally adapted approaches for ethnic minority seniors
Integrated assessment framework: Implementation of comprehensive evaluation combining objective fitness measures (Groningen Fitness Test for the Elderly) with psychological mediating variables
Discrimination-based analysis: Application of canonical correlation and discriminant analysis techniques to identify variables with greatest predictive power for long-term adherence
These methodological innovations represent significant contributions to the broader field of physical activity intervention research, providing validated approaches for addressing common challenges in participant selection, measurement, and analysis.
GALM research findings offer several evidence-based principles for designing future physical activity interventions for older adults:
Multi-component approach: The integration of personalized recruitment, structured programming, and continuation support provides a comprehensive framework addressing multiple determinants of behavior change
Mediating variable prioritization: Research has identified which variables most strongly predict long-term adherence, allowing future interventions to prioritize these factors
Temporal considerations: The strengthening relationships between variables and outcomes over time suggests interventions should be designed with sufficient duration to allow these relationships to develop
Subpopulation adaptation: The development of parallel interventions for different subgroups demonstrates the importance of tailored approaches rather than one-size-fits-all designs
These evidence-based principles can guide intervention designers in creating more effective programs, potentially increasing both initial engagement and long-term adherence rates among sedentary older adults.
Despite substantial evidence supporting GALM effectiveness, several important research gaps remain:
Mechanism clarification: While mediating variables have been identified, the precise mechanisms through which they influence behavior change require further investigation
Non-participant analysis: Research has not fully explored why 82% of the target population does not engage with the intervention when approached
Cost-effectiveness evaluation: Comprehensive analysis of program costs relative to health outcomes achieved would strengthen implementation arguments
Cross-cultural adaptation: Further research is needed on how the GALM approach might require modification for implementation in cultural contexts beyond the Netherlands
Long-term impact assessment: Studies extending beyond the 18-month program duration would provide valuable data on sustained behavior change and health outcomes
Addressing these research gaps would substantially strengthen the evidence base for GALM and similar approaches, potentially enhancing their effectiveness and implementation reach.
Evaluating GALM's broader public health impact requires methodological approaches that extend beyond individual participant outcomes:
Population-level analysis: Examining community-wide changes in physical activity rates in regions where GALM has been implemented
Healthcare utilization assessment: Analyzing changes in healthcare service usage patterns among the target population following GALM implementation
Economic impact evaluation: Calculating healthcare cost savings and productivity impacts related to improved physical function
Social network effects: Investigating whether GALM participation influences physical activity behavior among participants' social contacts
Policy influence assessment: Examining how GALM implementation has influenced regional and national policies regarding physical activity promotion for older adults
Galactose mutarotase belongs to the family of aldose epimerases. The enzyme’s active site contains two key amino acids: Glu 304, which acts as a Bronsted-Lowry base to abstract a proton, and His 170, which acts as a Bronsted-Lowry acid to donate a proton to the galactose . The molecular structure of human galactose mutarotase has been elucidated through x-ray crystallographic analysis, revealing an intricate array of 29 β-strands, 25 classical reverse turns, and 2 small α-helices .
In the Leloir pathway, galactose mutarotase catalyzes the conversion of α-D-galactose to β-D-galactose. This conversion is essential for the subsequent phosphorylation of β-D-galactose to galactose 1-phosphate by galactokinase . The pathway continues with the transfer of a UMP group from UDP-glucose to galactose 1-phosphate, generating glucose 1-phosphate and UDP-galactose. Finally, UDP-galactose is converted to UDP-glucose by UDP-galactose 4-epimerase .
Research on galactose mutarotase has provided valuable insights into the mechanisms of galactose metabolism and the structural basis of enzyme function. Understanding the enzyme’s structure and function has implications for developing treatments for metabolic disorders and for biotechnological applications .