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Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

Abstract:

Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

Procedia PDF Downloads 329

Authors: Kimberly Winnie Achieng Otieno

Abstract:

Nairobi Hospital plays a pivotal role in healthcare provision in East and Central Africa, yet it faces challenges in providing accessible dialysis care and managing health information efficiently. This paper explores strategic interventions to enhance dialysis care, access and streamline health information management, fostering an integrated and patient-centered healthcare system. Challenges at Nairobi Hospital: The Nairobi Hospital currently grapples with insufficient dialysis machines, resulting in extended turn around time in between dialysis sessions for patients. This issue stems from both staffing bottle necks and infrastructural limitations given our growing demand for renal care services. Paper-based records and fragmented information systems hinder the hospital’s ability to manage health data effectively. A lack of hospital systems integration with other facilities jeopardizes patient care access by posing challenges. These inefficiencies hinder collaborative efforts within the healthcare network. An investment in the expanding Nairobi Hospital dialysis facilities to communities is crucial with the high number of new cases of patients with chronic kidney disease. Setting up satellite clinics that are closer to people who live in areas far from the main hospital will ensure better access. This includes acquiring physical space within the greater Nairobi region, and the incorporation of mobile dialysis units to reach underserved areas. By decentralizing services, Nairobi Hospital can extend its reach and cater to a larger patient population. Community Outreach and Education: Implementing educational programs on kidney health within local communities is vital for early detection and prevention. Collaborating with local leaders and organizations can establish a proactive approach to renal health hence reducing the demand for acute dialysis interventions. it can amplify this effort by expanding Nairobi Hospital’s corporate social responsibility outreach program. Increasing the hospital’s footprint would also require an equal ramp up of staff recruitment. Support for continuous training programs will ensure that healthcare providers stay abreast of evolving practices, contributing to improved patient outcomes and service quality. Streamlining Health Information Management: Fully embracing a shift to 100% Electronic Health Records (EHRs) is a transformative step toward efficient health information management. Customizing these systems to Nairobi Hospital’s specific needs allows for seamless data recording, retrieval, and sharing among healthcare professionals. Doing so will help the hospital guarantee a continuum of care for patients transferring from other facilities. A 100% transition to digital record will also pose its own security threats. Ensuring robust security measures protects patient data and builds trust. Adherence to healthcare data privacy regulations is non-negotiable, and a comprehensive strategy for encryption, access controls, and regular audits should be implemented. Integrating systems to enable interoperability with other healthcare providers facilitates a cohesive healthcare network. Shared information promotes a holistic understanding of patients’ medical history, minimizing redundancies and enhancing overall care quality. Implementation Strategies: To manage the transition to community-based care and EHRs effectively, a phased implementation approach is recommended. Prioritizing dialysis care improvements, at a local level, in the initial stages allows the hospital to address immediate patient needs, followed by the integration of health information management changes. Engaging hospital staff, patients, and local communities is paramount. Collaboration with government agencies, non-governmental organizations (NGOs), and international partners enhances support and resources for successful implementation. Conclusion: By strategically enhancing dialysis care access and streamlining health information management, Nairobi Hospital can strengthen its position as a leading healthcare institution in both East and Central Africa. This comprehensive approach aligns with the hospital’s commitment to providing high-quality, accessible, and patient-centered care in the evolving landscape of healthcare delivery.

Keywords: Africa, urology, diaylsis, healthcare

Procedia PDF Downloads 17