Multimorbidity and Evidence Generation

Most people with a chronic disease actually have more than one, a condition known as multimorbidity. Despite this, the evidence base to prevent adverse disease outcomes has taken a disease-specific approach. Drawing on a conference, Improving Guidelines for Multimorbid Patients, the goal of this paper is to identify challenges to the generation of evidence to support the care of people with multimorbidity and to make recommendations for improvement. We identified three broad categories of challenges: 1) challenges to defining and measuring multimorbidity; 2) challenges related to the effects of multimorbidity on study design, implementation and analysis; and 3) challenges inherent in studying heterogeneity of treatment effects in patients with differing comorbid conditions. We propose a set of recommendations for consideration by investigators and others (reviewers, editors, funding agencies, policymaking organizations) involved in the creation of evidence for this common type of person that address each of these challenges. The recommendations reflect a general approach that emphasizes broader inclusion (recruitment and retention) of patients with multimorbidity, coupled with more rigorous efforts to measure comorbidity and comorbidity burden and the influence of multimorbidity on outcomes and the effects of therapy. More rigorous examination of heterogeneity of treatment effects requires careful attention to prioritizing the most important comorbid-related questions, and also requires studies that provide greater statistical power than conventional trials have provided. Relatively modest changes in the orientation of current research along these lines can be helpful in pointing to and partially addressing selected knowledge gaps. However, producing a robust evidence base to support patient-centered decision making in complex individuals with multimorbidity, exposed to many different combinations of potentially interacting factors that can modify the risks and benefits of therapies, is likely to require a clinical research enterprise fundamentally restructured to be more fully integrated with routine clinical practice.     

Photocatalysis of nanocomposite titania–natural silica as antibacterial against Staphylococcus aureus and Pseudomonas aeruginosa

The entries of pathogenic bacteria into the human body remain a severe problem to health that can be prevented using antibacterial agents. Meanwhile, the photocatalytic technique using semiconductor nanocomposite TiO₂–SiO₂ has great potential as an antibacterial method. In order to utilize natural resources, SiO₂ supporting materials are obtained from the extraction of beach sand due to the high silica content. Therefore, this study aims to synthesize a nanocomposite of TiO₂ with SiO₂ extracted from beach sand as an antibacterial agent against Staphylococcus aureus and Pseudomonas aeruginosa. The antibacterial activity test used the dilution and optical density method. Based on XRD analysis, the crystals of TiO₂ in the synthesized composites showed a more dominant anatase structure. Furthermore, Ti–O–Si bonds were identified from the IR spectrum, which showed the interaction between TiO₂ and SiO₂. In addition, SEM-EDX results showed agglomerated spherical particles with a TiO₂–SiO₂ nanocomposite particle size of 40–107 nm. The best antibacterial activity was demonstrated by the 1 : 0.5 TiO₂–SiO₂ nanocomposite, with inactivation percentages of S. aureus and P. aeruginosa of 98.69% and 97.44%, respectively.

TiO₂ material is composited with silica obtained from natural sand with indirect sonochemistry method. The addition of SiO₂ increase the photocatalyst activity of TiO₂ as an antibacterial against S. aureus and P. aeruginosa.     

PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction

BACKGROUND: Progressive renal disease is characterized by the induction of plasminogen activator inhibitor-1 (PAI-1), suggesting that impaired activity of the renal plasmin cascade may play a role in renal fibrosis. METHODS: To test this hypothesis, the severity of renal fibrosis caused by unilateral ureteral obstruction (UUO) was compared in PAI-1 wild-type (+/+) and PAI-1 deficient (-/-) mice. The extent of interstitial inflammation and fibrosis, renal plasminogen activator and plasmin activity, and renal expression of profibrotic genes was evaluated after 3, 7, and 14 days of UUO. RESULTS: Renal PAI-1 mRNA levels increased 8- to 16-fold in the +/+ mice after UUO surgery, and PAI-1 protein was detected in kidney homogenates. Interstitial fibrosis was significantly attenuated in -/- mice compared with +/+ mice at day 7 and day 14, based on the interstitial area stained with picrosirius red and total kidney collagen content. However, neither the mean renal plasminogen activator nor plasmin activities were increased in -/- mice compared with +/+ mice. The number of interstitial macrophages were significantly lower in the -/- mice three and seven days after UUO; interstitial myofibroblasts were significantly fewer at three days. At the same time points, this altered interstitial cellularity was associated with a significant reduction in renal mRNA levels for transforming growth factor-beta and procollagens alpha 1(I) and alpha 1(III). CONCLUSIONS: These studies establish an important fibrogenic role for PAI-1 in the renal fibrogenic response. The results demonstrate that one important fibrosis-promoting function of PAI-1 is its role in the recruitment of fibrosis-inducing cells, including myofibroblasts and macrophages.