Delivery of multipotent adult progenitor cells via a functionalized plasma polymerized surface accelerates healing of murine diabetic wounds.

Introduction: Stem cell therapies have been investigated as potential treatment modalities for chronic wounds however there has been limited success to date. Multipotent Adult Progenitor Cells (MAPCs©) have been identified as having potential as an allogenic stem cell product due to their high population doubling number and their characteristic dampening of T-cell proliferation. This helps to prevent autoimmunity and graft/cell rejection. Methods: We have developed a dressing, consisting of medical grade silicone coated with a heptylamine plasma polymer, which supports the growth and transfer of MAPCs to skin. To determine if the dressing can deliver functional stem cells into diabetic wounds, they were loaded with MAPCs and then placed over excisional wounds in both normal and diabetic mice. Results and discussion: Accelerated healing was observed in both the normal and diabetic wounds with wound gape being significantly smaller at day 3 when compared to controls. Wound analysis showed that treatment with the MAPC dressings dampened the inflammatory response with reduced numbers of neutrophils and macrophages observed. Additionally, an increase in pro-angiogenic VEGF and CD31 positive endothelial cells was observed indicating improved new blood vessel formation. The MAPC dressings had no effect on fibrosis with collagen I and III being equally affected in both control and treated wounds. Overall, the functionalized MAPC dressings improve healing responses particularly in diabetic mice with impaired healing responses and therefore, show potential for development as an advanced therapeutic approach for the treatment of chronic diabetic wounds.

Health problems associated with irritable bowel syndrome: analysis of a primary care registry.

BACKGROUND: Associations between irritable bowel syndrome and other health problems have been described, but comprehensive reports are missing, especially in primary care. AIMS: To investigate which health problems are associated with irritable bowel syndrome, how they cluster together and when they are typically diagnosed relative to irritable bowel syndrome. METHODS: We used Intego, a general practice registry in Flanders, Belgium. Patients with an irritable bowel syndrome diagnosis (n = 13 701) were matched with controls without gastrointestinal diagnosis and controls with organic gastrointestinal disease. Long-term prevalences of 680 symptoms and diagnoses were compared between patients and controls. Results were summarised using functional enrichment analysis and visualised in a network and we calculated incidence rate ratios in the 10 years before and after the irritable bowel syndrome diagnosis for the network's key components. RESULTS: Various symptoms and infections, but not neoplasms, were enriched in irritable bowel syndrome patients compared to both control groups. We characterised the comorbidities of irritable bowel syndrome as psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms. These had a uniform incidence in the years around the irritable bowel syndrome diagnosis, and did not structurally precede or follow irritable bowel syndrome. CONCLUSIONS: Irritable bowel syndrome shares long-term associations with psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms in primary care. Clinicians are encouraged to take comorbidities into account when diagnosing and managing irritable bowel syndrome, as this may have important treatment implications.

The relationship between grip strength and muscle mass (MM), inflammatory biomarkers and physical performance in community-dwelling very old persons.

The main consequence of the loss of MM and muscle strength is limitations of physical performance and disability in older people. It is unclear whether a decline in functional capacity results from the loss of MM and/or the qualitative impairment of the muscle tissue. The aim of our research was to investigate the relationship between physical performance and grip strength, inflammatory markers and MM in a population of community-dwelling very old persons. This study is a cross-sectional analysis within the BELFRAIL-study, a cohort study of subjects aged 80 years and older (n=567). MM was assessed by bioelectrical impedance. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations were determined on fasting blood samples. Logistic regression analysis was build using a low physical performance level evaluated according to Short Physical Performance Battery (SPPB) (dependent variable) and grip strength, pro-inflammatory status and MM (independent variables) adjusted for age and for the total number of chronic diseases. Low SPPB scores were associated with grip strength scores for women (OR 0.86 (95% CI 0.77-0.96)), and for men (OR 0.89 (95% CI 0.81-0.96)). The relationships between low SPPB and MM or inflammatory profile were not significant. Our results show that low physical performance remains associated with low grip strength even after considering other risk factors for sarcopenia in the oldest old and support the hypothesis that low muscle strength is a better indicator than low MM. The role of an inflammatory component in the age-related loss of muscle strength and function could not be confirmed.

The influence of renal function on vitamin D metabolism in the very elderly.

OBJECTIVES: Hypovitaminosis D and chronic kidney disease (CKD) are highly prevalent in older adults. The factors correlating with 25-OH-vitamin D and PTH levels were analyzed in older adults with and without CKD. DESIGN: We performed a cross-sectional analysis embedded within the BELFRAIL study. SETTING: A population-based prospective cohort study of the very elderly in Belgium. PARTICIPANTS: 325 participants, all aged 80 or older. MEASURMENTS: Time of year and LAPAQ score were used as proxies for sunshine exposure. Vitamin D3 supplementation, gender, institutionalisation, age, level of education, and serum calcium and phosphorus level were examined as possible confounders in the analyses. RESULTS: There was no correlation between the presence of CKD and low 25-OH-vitamin D levels, but there was a significant (p<0.01) correlation between CKD and high PTH levels. Among the participants with a normal eGFR, the LAPACQ score, vitamin D supplementation, season, log PTH value and eGFR were correlated with log 25-OH-vitamin D levels. Among the participants with CKD, only vitamin D supplementation, log PTH levels and serum calcium levels were correlated with log 25-OH-vitamin D levels. Gender, log 25-OH-vitamin D values, serum calcium and phosphorus levels and eGFR were correlated with log PTH values in the patients with normal eGFR. Log 25-OH-vitamin D values, serum phosphorus levels, vitamin D supplementation (p=0.07), season (p=0.10) and eGFR were correlated with log PTH values in the patients with CKD. CONCLUSION: Exposure to sunshine and an active lifestyle were correlated with higher 25-OH-vitamin D levels in older adults without CKD. The PTH level in patients with CKD may be influenced by the season.

Least absolute regression network analysis of the murine osteoblast differentiation network.

MOTIVATION: We propose a reverse engineering scheme to discover genetic regulation from genome-wide transcription data that monitors the dynamic transcriptional response after a change in cellular environment. The interaction network is estimated by solving a linear model using simultaneous shrinking of the least absolute weights and the prediction error. RESULTS: The proposed scheme has been applied to the murine C2C12 cell-line stimulated to undergo osteoblast differentiation. Results show that our method discovers genetic interactions that display significant enrichment of co-citation in literature. More detailed study showed that the inferred network exhibits properties and hypotheses that are consistent with current biological knowledge.