Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention

An antibiotic stewardship program in a surgical ICU of a resource-limited country: Financial impact with improved clinical outcomes

Background: Antibiotic resistance (ABX-R) is alarming in lower/middle-income countries (LMICs). Nonadherence to antibiotic guidelines and inappropriate prescribing are significant contributing factors to ABX-R. This study determined the clinical and economic impacts of antibiotic stewardship program (ASP) in surgical intensive care units (SICU) of LMIC.Method: We conducted this pre and post-test analysis in adult SICU of Aga Khan University Hospital, Pakistan, and compared pre-ASP (September-December 2017) and post-ASP data (April-July 2018). January-March 2018 as an implementation/training phase, for designing standard operating procedures and training the team. We enrolled all the patients admitted to adult SICU and prescribed any antibiotic. ASP-team daily reviewed antibiotics prescription for its appropriateness. Through prospective-audit and feedback-mechanism changes were made and recorded. Outcome measures included antibiotic defined daily dose (DDDs)/1000 patient-days, prescription appropriateness, antibiotic duration, readmission, mortality, and cost-effectiveness.Result: 123 and 125 patients were enrolled in pre-ASP and post-ASP periods. DDDs/1000 patient-days of all the antibiotics reduced in the post-ASP period, ceftriaxone, cefazolin, metronidazole, piperacillin/tazobactam, and vancomycin showed statistically significant (p \u3c 0.01) reduction. The duration of all antibiotics use reduced significantly (p \u3c 0.01). Length of SICU stays, mortality, and readmission reduced in the post-ASP period. ID-pharmacist interventions and source-control-documentation were observed in 62% and 50% cases respectively. Guidelines adherence improved significantly (p \u3c 0.01). Net cost saving is 6360US$yearly, mainly through reduced antibiotics consumption, around US$ 18,000 (PKR 2.8 million) yearly.Conclusion: ASP implementation with supplemental efforts can improve the appropriateness of antibiotic prescriptions and the optimum duration of use. The approach is cost-effective mainly due to the reduced cost of antibiotics with rational use. Better source-control-documentation may further minimize the ABX-R in SICU

DNA dispose, but subjects decide. Learning and the extended synthesis

Adaptation by means of natural selection depends on the ability of populations to maintain variation in heritable traits. According to the Modern Synthesis this variation is sustained by mutations and genetic drift. Epigenetics, evodevo, niche construction and cultural factors have more recently been shown to contribute to heritable variation, however, leading an increasing number of biologists to call for an extended view of speciation and evolution. An additional common feature across the animal kingdom is learning, defined as the ability to change behavior according to novel experiences or skills. Learning constitutes an additional source for phenotypic variation, and change in behavior may induce long lasting shifts in fitness, and hence favor evolutionary novelties. Based on published studies, I demonstrate how learning about food, mate choice and habitats has contributed substantially to speciation in the canonical story of Darwin’s finches on the Galapagos Islands. Learning cannot be reduced to genetics, because it demands decisions, which requires a subject. Evolutionary novelties may hence emerge both from shifts in allelic frequencies and from shifts in learned, subject driven behavior. The existence of two principally different sources of variation also prevents the Modern Synthesis from self-referring explanations.publishedVersio