176 research outputs found

    Effect of bisphosphonates on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces

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    Purpose: This study investigated the effects of bisphosphonates (BPs) namely Alendronate (ALN) and Zoledronate (ZA) on the osteogenic activity of osteoprogenitor cells cultured on titanium surfaces at therapeutic doses in order to assess if altered osteoblastogenesis could compromise osseointegration and contribute in etiopathogenesis of painful disorders like BPrelated Osteonecrosis of the Jaw (BRONJ) following implant placement. Materials and Methods: MC3T3-E1 Subclone 4 cells were utilised in this study. Therapeutic doses of ALN and ZA were calculated based off reported peak plasma concentrations. The viability, proliferation, adhesion, and mineralisation potential of cells was assessed using a LIVE/DEAD stain, alamarBlue® assay, immunofluorescence microscopy, and Alizarin Red S staining respectively. Results: Therapeutic doses of ZA negatively affected cell viability, whereas therapeutic doses of ALN significantly enhanced cell differentiation and the amount of bone formation compared to the control. Conclusions: The findings of this study may provide some insight into the pathogenesis of BRONJ developing following implant placement in patients treated with ZA and may have promising implications towards improved wound healing and osseointegration in patients treated with ALN

    Risk of Incident Coronary Heart Disease Events in Men Compared to Women by Menopause Type and Race

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139125/1/jah31016.pd

    Short- and Long-term Immunological and Virological Outcome in HIV-Infected Infants According to the Age at Antiretroviral Treatment Initiation

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    The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both group

    Plasma proteomic signatures of enteric permeability among hospitalized and community children in Kenya and Pakistan

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    We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2: 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2: 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

    Plasma proteomic signatures associated with enteric permeability among hospitalized and community children under two years of age in Kenya and Pakistan

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    We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2 : 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2 : 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

    Enteric permeability, systemic inflammation, and post-discharge growth among a cohort of hospitalized children in Kenya and Pakistan

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    Objectives: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. Methods: Children aged 2–23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. Results: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15–0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00–0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα (P = 0.017), CD14 (P = 0.078), and IL-6 (P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα (P = 0.004) and approached significance with CD14 (P = 0.078) and IL-6 (P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. Conclusions: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children
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