Photosynthetic electron flow affects H2O2 signaling by inactivation of catalase in Chlamydomonas reinhardtii

A specific signaling role for H2O2 in Chlamydomonas reinhardtii was demonstrated by the definition of a promoter that specifically responded to this ROS. Expression of a nuclear-encoded reporter gene driven by this promoter was shown to depend not only on the level of exogenously added H2O2 but also on light. In the dark, the induction of the reporter gene by H2O2 was much lower than in the light. This lower induction was correlated with an accelerated disappearance of H2O2 from the culture medium in the dark. Due to a light-induced reduction in catalase activity, H2O2 levels in the light remained higher. Photosynthetic electron transport mediated the light-controlled down-regulation of the catalase activity since it was prevented by 3-(3′4′-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II. In the presence of light and DCMU, expression of the reporter gene was low while the addition of aminotriazole, a catalase inhibitor, led to a higher induction of the reporter gene by H2O2 in the dark. The role of photosynthetic electron transport and thioredoxin in this regulation was investigated by using mutants deficient in photosynthetic electron flow and by studying the correlation between NADP-malate dehydrogenase and catalase activities. It is proposed that, contrary to expectations, a controlled down-regulation of catalase activity occurs upon a shift of cells from dark to light. This down-regulation apparently is necessary to maintain a certain level of H2O2 required to activate H2O2-dependent signaling pathways

Role of Ox-PAPCs in the Differentiation of Mesenchymal Stem Cells (MSCs) and Runx2 and PPARγ2 Expression in MSCs-Like of Osteoporotic Patients

BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into osteoblasts and adipocytes and conditions causing bone loss may induce a switch from the osteoblast to adipocyte lineage. In addition, the expression of Runx2 and the PPARγ2 transcription factor genes is essential for cellular commitment to an osteogenic and adipogenic differentiation, respectively. Modified lipoproteins derived from the oxidation of arachidonate-containing phospholipids (ox-PAPCs: POVPC, PGPC and PEIPC) are considered important factors in atherogenesis. METHODOLOGY: We investigated the effect of ox-PAPCs on osteogenesis and adipogenesis in human mesenchymal stem cells (hMSCs). In particular, we analyzed the transcription factor Runx2 and the PPARγ2 gene expression during osteogenic and adipogenic differentiation in absence and in presence of ox-PAPCs. We also analyzed gene expression level in a panel of osteoblastic and adipogenic differentiation markers. In addition, as circulating blood cells can be used as a "sentinel" that responds to changes in the macro- or micro-environment, we analyzed the Runx2 and the PPARγ2 gene expression in MSCs-like and ox-PAPC levels in serum of osteoporotic patients (OPs). Finally, we examined the effects of sera obtained from OPs in hMSCs comparing the results with age-matched normal donors (NDs). PRINCIPAL FINDINGS: Quantitative RT-PCR demonstrated that ox-PAPCs enhanced PPARγ2 and adipogenic gene expression and reduced Runx2 and osteoblast differentiation marker gene expression in differentiating hMSCs. In OPs, ox-PAPC levels and PPARγ2 expression were higher than in NDs, whereas Runx2 was lower than in ND circulant MSCs-like. CONCLUSIONS: Ox-PAPCs affect the osteogenic differentiation by promoting adipogenic differentiation and this effect may appear involved in bone loss in OPs

Simulating long-term carbon nitrogen and phosphorus biogeochemical cycling in agricultural environments

Understanding how agricultural practices alter biogeochemical cycles is vital for maintaining land productivity, food security, and other ecosystem services such as carbon sequestration. However, these are complex, highly coupled long-term processes that are difficult to observe or explore through empirical science alone. Models are required that capture the main anthropogenic disturbances, whilst operating across regions and long timescales, simulating both natural and agricultural environments, and shifts among these. Many biogeochemical models neglect agriculture or interactions between carbon and nutrient cycles, which is surprising given the scale of intervention in nitrogen and phosphorus cycles introduced by agriculture. This gap is addressed here, using a plant-soil model that simulates integrated soil carbon, nitrogen and phosphorus (CNP) cycling across natural, semi-natural and agricultural environments. The model is rigorously tested both spatially and temporally using data from long-term agricultural experiments across temperate environments. The model proved capable of reproducing the magnitude of and trends in soil nutrient stocks, and yield responses to nutrient addition. The model has potential to simulate anthropogenic effects on biogeochemical cycles across northern Europe, for long timescales (centuries) without site-specific calibration, using easily accessible input data. The results demonstrate that weatherable P from parent material has a considerable effect on modern pools of soil C and N, despite significant perturbation of nutrient cycling from agricultural practices, highlighting the need to integrate both geological and agricultural processes to understand effects of land-use change on food security, C storage and nutrient sustainability. The results suggest that an important process or source of P is currently missing in our understanding of agricultural biogeochemical cycles. The model could not explain how yields were sustained in plots with low P fertiliser addition. We suggest that plant access to organic P is a key uncertainty warranting further research, particularly given sustainability concerns surrounding rock sources of P fertiliser

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

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Prioritizing solutions to incorporate Prosthetics and Orthotics services into Iranian health benefits package: Using an analytic hierarchy process

Introduction: Health benefits package (HBP) is regarded as one of the main dimensions of health financing strategy. Even with increasing demands for prosthetics and orthotics (P&O) services to approximately 0.5% of the world’s population, only 15% of vulnerable groups have the chance to make use of such benefits. Inadequate coverage of P&O services in the HBP is accordingly one of the leading reasons for this situation in many countries, including Iran. Aims: The main objective of this study was to find and prioritize solutions in order to facilitate and promote P&O services in the Iranian HBP. Study design: A mixed-methods (qualitative-quantitative) research design was employed in this study. Methods: This study was conducted in two phases. First, semi-structured interviews were undertaken to retrieve potential solutions. Then an analytic hierarchy process (AHP) reflecting on seven criteria of acceptability, effectiveness, time, cost, feasibility, burden of disease, and fairness was performed to prioritize them. Results: In total, 26 individuals participated in semi-structured interviews and several policy solutions were proposed. Following the AHP, preventive interventions, infant-specific interventions, inpatient interventions, interventions until 6 years of age, and emergency interventions gained the highest priority to incorporate in the Iranian HBP. Conclusion: A number of policy solutions were explored and prioritized for P&O services in the Iranian HBP. Our findings provide a framework for decision- and policy-makers in Iran and other countries aiming to curb the financial burdens of P&O users, especially in vulnerable group

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities