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Medicina Oral, Patologia Oral Y Cirugia... Nov 2018This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
Preemptive analgesia-related gene and protein expression in third molar surgeries under non steroidal anti-inflammatory drug protocols: A PROSPERO-registered systematic review of clinical studies.
BACKGROUND
This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
MATERIAL AND METHODS
A PROSPERO-registered systematic review (CRD42017060455) was conducted following the PRISMA statement to summarize current knowledge on gene expression in third molar surgeries. A search was performed in PubMed's Medline and Scopus databases, without date or language restrictions, using the logical expression {[(Third molar) OR (preemptive) OR (cyclooxygenase inhibitors) OR (acute inflammation) AND (gene expression)]}.
RESULTS
All studies included in the analysis evaluated gene expression in a third molar extraction model, using the preemptive analgesia methodology in seven investigations. The sample analyzed was obtained from gingival tissue biopsy (n=4), blood (n=1), transudate (n=1) and gingival tissue biopsy/transudate (n=1). There were differences with respect to evaluated genes, drug protocol, sample studied, and method for evaluating gene expression.
CONCLUSIONS
Third molar surgeries were found to be associated with different COX-related gene expression patterns. Although inflammatory events following the surgical procedure are associated with COX isoforms, data from preemptive analgesia studies are scarce, especially from studies correlating gene expression and clinical parameters. In the future, from a clinical perspective, identifying the molecular targets of a drug based on individual gene expression may be helpful to delineate specific third molar, surgery-related, preemptive analgesia protocols.
Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Gene Expression; Humans; Molar, Third; Prostaglandin-Endoperoxide Synthases; Protein Biosynthesis
PubMed: 30341263
DOI: 10.4317/medoral.22576 -
Archives of Oral Biology Nov 2018The aim of the present systematic review was to offer a timeline of the events taking place during orthodontic tooth movement(OTM).
OBJECTIVES
The aim of the present systematic review was to offer a timeline of the events taking place during orthodontic tooth movement(OTM).
MATERIALS AND METHODS
Electronic databases PubMed, Web of Science and EMBASE were searched up to November 2017. All studies describing the expression of signaling proteins in the periodontal ligament(PDL) of teeth subjected to OTM or describing the expression of signaling proteins in human cells of the periodontal structures subjected to static mechanical loading were considered eligible for inclusion for respectively the in-vivo or the in-vitro part. Risk of bias assessment was conducted according to the validated SYRCLE's RoB tool for animal studies and guideline for assessing quality of in-vitro studies for in-vitro studies.
RESULTS
We retrieved 7583 articles in the initial electronic search, from which 79 and 51 were finally analyzed. From the 139 protein investigated, only the inflammatory proteins interleukin(IL)-1β, cyclooxygenase(COX)-2 and prostaglandin(PG)-E2, osteoblast markers osteocalcin and runt-related transcription factor(RUNX)2, receptor activator of nuclear factor kappa-B ligand(RANKL) and osteoprotegerin(OPG) and extracellular signal-regulated kinases(ERK)1/2 are investigated in 10 or more studies.
CONCLUSION
The investigated proteins were presented in a theoretical model of OTM. We can conclude that the cell activation and differentiation and recruitment of osteoclasts is mediated by osteocytes, osteoblasts and PDL cells, but that the osteogenic differentiation is only seen in stem cell present in the PDL. In addition, the recently discovered Ephrin/Ephs seem to play an role parallel with the thoroughly investigated RANKL/OPG system in mediating bone resorption during OTM.
Topics: Animals; Biomarkers; Humans; Intracellular Signaling Peptides and Proteins; Signal Transduction; Tooth Movement Techniques
PubMed: 30130671
DOI: 10.1016/j.archoralbio.2018.08.003 -
Inflammation Research : Official... Jan 2019Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia...
BACKGROUND
Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated.
OBJECTIVES
We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB.
METHODS
We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB.
RESULTS
We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB 8-isoPGF, and phospholipases A activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs.
CONCLUSION
Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.
Topics: Animals; Biomarkers; Humans; Lyme Disease; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Severity of Illness Index
PubMed: 30121835
DOI: 10.1007/s00011-018-1180-5 -
Medicine Jul 2018PGE1 has been studied for prevention of CI-AKI in several RCTs and significant heterogeneous results exist. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
PGE1 has been studied for prevention of CI-AKI in several RCTs and significant heterogeneous results exist.
METHODS
We searched PubMed, EMBase, and Cochrane Central Register of Controlled Trials up to December 26, 2017 for RCTs comparing PGE1 with placebo or other active medications for the prevention of CI-AKI in patients. Odds ratio and 95% confidence interval (CI) were used for pooling dichotomous data, while mean difference and 95% confidence interval for pooling continuous data.
RESULTS
Seven RCTs involving 1760 patients were included in this meta-analysis. All these 7 trials reported the incidence of CI-AKI and compared with placebo or other treatment options, PGE1 was associated with a reduced risk of CI-AKI (OR: 0.38, 95% CI: 0.28-0.53; P < .001) and only a trend for lower post procedure serum creatinine (Scr) levels compared with control groups at 48 hours (MD: -0.03 mg/dL, 95% CI: -0.08 to 0.02 mg/dL; P = .25; 6 trials combined). But the postprocedure Scr levels were significantly reduced in PGE1 groups compared with control groups at 72 hours (MD: -0.07 mg/dL, 95% CI: -0.11 to -0.04 mg/dL; P < .001; 4 trials combined). We also meta-analyzed the postprocedure cystatin C (CysC) at 24 and 48 hours with 2 trials. There were lower postprocedure CysC levels in PGE1 groups than those in control groups (MD: -0.18 mg/L, 95% CI: -0.33 to -0.03 mg/L; P = .02 at 24 hours and MD: -0.14 mg/L, 95% CI: -0.23 to -0.06 mg/L; P = .001 at 48 hours).
CONCLUSIONS
PGE1 provides effective nephroprotection against CI-AKI and may act as a part of effective prophylactic pharmacological regimens.
Topics: Acute Kidney Injury; Alprostadil; Contrast Media; Creatinine; Female; Humans; Incidence; Male; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30024512
DOI: 10.1097/MD.0000000000011416 -
The Cochrane Database of Systematic... Apr 2018Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best.
OBJECTIVES
To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished trial reports (30 June 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled comparisons or cluster trials of effectiveness or side-effects of uterotonic drugs for preventing PPH.Quasi-randomised trials and cross-over trials are not eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available drugs. We stratified our primary outcomes according to mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of drug administration, to detect subgroup effects.The absolute risks in the oxytocin are based on meta-analyses of proportions from the studies included in this review and the risks in the intervention groups were based on the assumed risk in the oxytocin group and the relative effects of the interventions.
MAIN RESULTS
This network meta-analysis included 140 randomised trials with data from 88,947 women. There are two large ongoing studies. The trials were mostly carried out in hospital settings and recruited women who were predominantly more than 37 weeks of gestation having a vaginal birth. The majority of trials were assessed to have uncertain risk of bias due to poor reporting of study design. This primarily impacted on our confidence in comparisons involving carbetocin trials more than other uterotonics.The three most effective drugs for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination. These three options were more effective at preventing PPH ≥ 500 mL compared with oxytocin, the drug currently recommended by the WHO (ergometrine plus oxytocin risk ratio (RR) 0.69 (95% confidence interval (CI) 0.57 to 0.83), moderate-quality evidence; carbetocin RR 0.72 (95% CI 0.52 to 1.00), very low-quality evidence; misoprostol plus oxytocin RR 0.73 (95% CI 0.60 to 0.90), moderate-quality evidence). Based on these results, about 10.5% women given oxytocin would experience a PPH of ≥ 500 mL compared with 7.2% given ergometrine plus oxytocin combination, 7.6% given carbetocin, and 7.7% given misoprostol plus oxytocin. Oxytocin was ranked fourth with close to 0% cumulative probability of being ranked in the top three for PPH ≥ 500 mL.The outcomes and rankings for the outcome of PPH ≥ 1000 mL were similar to those of PPH ≥ 500 mL. with the evidence for ergometrine plus oxytocin combination being more effective than oxytocin (RR 0.77 (95% CI 0.61 to 0.95), high-quality evidence) being more certain than that for carbetocin (RR 0.70 (95% CI 0.38 to 1.28), low-quality evidence), or misoprostol plus oxytocin combination (RR 0.90 (95% CI 0.72 to 1.14), moderate-quality evidence)There were no meaningful differences between all drugs for maternal deaths or severe morbidity as these outcomes were so rare in the included randomised trials.Two combination regimens had the poorest rankings for side-effects. Specifically, the ergometrine plus oxytocin combination had the higher risk for vomiting (RR 3.10 (95% CI 2.11 to 4.56), high-quality evidence; 1.9% versus 0.6%) and hypertension [RR 1.77 (95% CI 0.55 to 5.66), low-quality evidence; 1.2% versus 0.7%), while the misoprostol plus oxytocin combination had the higher risk for fever (RR 3.18 (95% CI 2.22 to 4.55), moderate-quality evidence; 11.4% versus 3.6%) when compared with oxytocin. Carbetocin had similar risk for side-effects compared with oxytocin although the quality evidence was very low for vomiting and for fever, and was low for hypertension.
AUTHORS' CONCLUSIONS
Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.
Topics: Drug Therapy, Combination; Ergonovine; Female; Fever; Humans; Hypertension; Misoprostol; Network Meta-Analysis; Oxytocics; Oxytocin; Postpartum Hemorrhage; Vomiting
PubMed: 29693726
DOI: 10.1002/14651858.CD011689.pub2 -
Prostaglandins, Leukotrienes, and... Feb 2018Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Omega-3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far.
METHODS
A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity.
RESULTS
Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements [elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009)]. Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events [eructation (belching; p = 0.010); nausea (p = 0.044)] and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL).
CONCLUSION
RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.
Topics: Blood Glucose; Cholesterol, LDL; Dietary Supplements; Docosahexaenoic Acids; Dysgeusia; Eczema; Eicosapentaenoic Acid; Exanthema; Humans; Patient Safety; Randomized Controlled Trials as Topic
PubMed: 29482765
DOI: 10.1016/j.plefa.2018.01.001 -
Journal of Dermatological Science Apr 2018Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis is a rare genetic disease which predominantly affects skin, bone and soft connective... (Review)
Review
BACKGROUND
Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis is a rare genetic disease which predominantly affects skin, bone and soft connective tissue. It is characterized by the triad of pachydermia, digital clubbing and periostosis of long bones. Arthralgia or arthritis is also present in most of the cases. Genetic studies have identified the impaired PGE2 metabolism as a culprit for hypertrophic osteoarthropathy in PHO cases. We conducted a systematic review to examine the effectiveness of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), a PGE2 synthesis blocker to reduce the symptoms among PHO patients.
METHODS
We searched the evidence in five databases; Cochrane Library, CINAHL, EMBASE, MEDLINE, and PubMed. We reported the evidence using narrative synthesis.
RESULTS
Out of 238 identified studies, we selected 26 for the synthesis. All were case reports which included a total of 54 patients. Among them, 39 patients were treated with at least one type of NSAIDs. Around 70% of the patients treated with NSAIDs had clinical improvement for their symptoms, mostly arthritis or arthralgia symptoms.
CONCLUSION
NSAIDs were effective in improving arthralgia or arthritis symptoms in majority of the PHO patients. Therefore, we recommend the use of NSAIDs in PHO patients to treat arthralgia or arthritis.
Topics: Cyclooxygenase Inhibitors; Dinoprostone; Humans; Osteoarthropathy, Primary Hypertrophic; Rare Diseases; Treatment Outcome
PubMed: 29305259
DOI: 10.1016/j.jdermsci.2017.12.012 -
Advances in Medical Sciences Mar 2018Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rheumatoid arthritis is characterized by the production of eicosanoids, cytokines, adhesion molecules, infiltration of T and B lymphocytes in the synovium and oxygen reduction accompanied by the cartilage degradation. Eicosanoids are responsible for the progressive destruction of cartilage and bone, however neither steroids, nor the non steroidal anti-inflammatory drugs (NSAIDs), cannot slow down cartilage and bone destruction providing only symptomatic improvement. The current rheumatoid arthritis treatment options include mainly the use of disease-modifying anti-rheumatic drugs, the corticosteroids, the NSAIDs and biological agents.
METHODS
PubMed, Cochrane, and Embase electronic database were used as the main sources for extracting several articles, reviews, original papers in English for further review and analysis on the implication of arachidonic acid metabolites with rheumatoid arthritis and different strategies of targeting arachidonic acid metabolites, different enzymes or receptors for improving the treatment of rheumatoid arthritis patients.
RESULTS
We first focused on the role of individual prostaglandins and leukotrienes, in the inflammatory process of arthritis, concluding with an outline of the current clinical situation of rheumatoid arthritis and novel treatment strategies targeting the arachidonic acid pathway.
CONCLUSIONS
Extended research is necessary for the development of these novel compounds targeting the eicosanoid pathway, by increasing the levels of anti-inflammatory eicosanoids (PGD,15dPGJ), by inhibiting the production of pro-inflammatory eicosanoids (PGE, LTB, PGI) involved in rheumatoid arthritis or also by developing dual compounds displaying both the COX-2 inhibitor/TP antagonist activity within a single compound.
Topics: Arthritis, Rheumatoid; Eicosanoids; Humans; Metabolic Networks and Pathways; Metabolome
PubMed: 28818745
DOI: 10.1016/j.advms.2017.06.004 -
BMC Medical Genetics Aug 2017Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the... (Review)
Review
BACKGROUND
Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9.
METHODS
To provide an expanded view of the genes and variants associated with PAH, we performed a systematic literature review. Facilitated by a web tool, we classified, curated, and annotated most of the genes and PubMed abstracts related to PAH, in which many of the mutations and variants were not annotated in public databases such as ClinVar from NCBI. The gene list generated was compared with other available tests.
RESULTS
Our results reveal that there is genetic evidence for at least 30 genes, of which 21 genes shown specific mutations. Most of the genes are not covered by current available genetic panels. Many of these variants were not annotated in the ClinVar database and a mapping of these mutations suggest that next generation sequencing is needed to cover all mutations found in PAH or related diseases. A pathway analysis of these genes indicated that, in addition to the BMP and TGFβ pathways, there was connections with the nitric oxide, prostaglandin, and calcium homeostasis signalling, which may be important components in PAH.
CONCLUSION
Our systematic review proposes an expanded gene panel for more accurate characterization of the genetic incidence and risk in PAH. Their usage would increase the knowledge of PAH in terms of genetic counseling, early diagnosis, and potential prognosis of the disease.
Topics: Bone Morphogenetic Proteins; Databases, Genetic; Humans; Hypertension, Pulmonary; Mutation; Risk; Signal Transduction; Transforming Growth Factor beta
PubMed: 28768485
DOI: 10.1186/s12881-017-0440-5 -
Shock (Augusta, Ga.) Jan 2017The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The acute respiratory distress syndrome (ARDS) is a life-threating disorder that contributes significantly to critical illness. No specific pharmacological interventions directed at lung injury itself have proven effective in improving outcome of patients with ARDS. Platelet activation was identified as a key component in ARDS pathophysiology and may provide an opportunity for preventive and therapeutic strategies. We hypothesize that use of acetyl salicylic acid (ASA) may prevent and/or attenuate lung injury.
METHODS
We conducted a systematic review of preclinical studies and meta-analysis of clinical studies investigating the efficacy of ASA in the setting of lung injury. Medline, embase, and cochrane databases were searched.
RESULTS
The literature search yielded 1,314 unique articles. Fifteen preclinical studies and eight clinical studies fulfilled the in- and exclusion criteria. In the animal studies, the overall effect of ASA was positive, e.g., ASA improved survival and attenuated inflammation and pulmonary edema. Mechanisms of actions involved, among others, are interference with the neutrophil-platelets interaction, reduction of leukotrienes, neutrophil extracellular traps, and prostaglandins. High-dose ASA may be the drug of choice. A meta-analysis of three clinical studies showed an association between ASA use and a reduced incidence of ARDS (OR 0.59, 95% CI 0.36-0.98), albeit with substantial between-study heterogeneity. All studies had their own shortcomings in methodological quality.
CONCLUSION
This systematic review of preclinical studies and meta-analysis of clinical studies suggests a beneficial role for ASA in ARDS prevention and treatment. However, the currently available data is insufficient to justify an indication for ASA in ARDS. The body of literature does support further studies in humans. We suggest clinical trials in which the mechanisms of action of ASA in lung injury models are being evaluated to guide optimal timing and dose, before prospective randomized trials.
Topics: Animals; Aspirin; Humans; Platelet Activation; Respiratory Distress Syndrome
PubMed: 27984533
DOI: 10.1097/SHK.0000000000000745