Dodsoningram1057

Regression against a satellite-based model for wildfire smoke shows that outdoor, but not indoor gas-phase PAH concentrations are likely associated with wildfire events. These results point toward the need to include gas-phase pollutants such as PAHs in air pollution risk assessment.Background Several fixation methods have been introduced in medial patellofemoral ligament (MPFL) reconstruction. However, the optimal management of patients with recurrent patellar dislocation remains controversial. Purpose To present a case series with a minimum 2-year follow-up of 29 patients with recurrent patellar dislocation who underwent a new transosseous suture fixation technique for MPFL reconstruction. Study Design Case series; Level of evidence, 4. Methods From January 2014 through February 2016, a total of 29 patients with recurrent patellar dislocation for which the MPFL was reconstructed with transosseous suture patellar fixation were studied. All patients were available for follow-up (mean, 37.52 months; range, 26-48 months). The patellar attachment was fixed by transosseous patellar sutures. The International Knee Documentation Committee (IKDC) subjective knee score, Kujala score, Tegner score, range of motion, congruence angle, patellar tilt angle, and complications were assessed both pre- a. © The Author(s) 2020.Background Shoulder function after rotator cuff repair is associated with patient satisfaction after surgery. Several studies have demonstrated that the muscle strength ratio (external rotators/internal rotators) is an important factor to evaluate shoulder function, but little is known about the relationship between the preoperative muscle strength ratio and postoperative shoulder function. Purpose To evaluate the effect of the preoperative muscle strength ratio of the shoulder rotators on function after rotator cuff repair. Study Design Cohort study; Level of evidence, 3. Methods The study participants were patients with small- to medium-sized rotator cuff tears diagnosed by magnetic resonance imaging; 77 patients were included in the analysis. Preoperative muscle strength was assessed through use of isokinetic equipment. Patients were classified into 2 groups (normal and abnormal) according to a normal strength ratio range of 55% to 75%, with "abnormal" meaning a deviation of more than 15% from the normal range. AZD1080 concentration The American Shoulder and Elbow Surgeons (ASES) score and the Constant score were used to evaluate shoulder function preoperatively and postoperatively at 6 months, 1 year, and 2 years. Results There were 30 patients in the normal group and 47 in the abnormal group, with a preoperative muscle strength ratio of 63.5% ± 5.5% and 42.6% ± 6.1%, respectively. The ASES score was 88.6 ± 9.1 in the normal group and 77.5 ± 13.6 in the abnormal group at 2 years postoperatively, and the Constant score was 82.7 ± 8.4 in the normal group and 69.5 ± 13.4 in the abnormal group at 2 years postoperatively. A significant difference was found in postoperative shoulder function between the normal and abnormal groups. Conclusion This study demonstrated that the preoperative muscle strength ratio was associated with postoperative shoulder function. The preoperative muscle strength ratio should be considered an important predictor of shoulder function after rotator cuff repair. © The Author(s) 2020.Background Country-level epidemiological data about alcohol-related problems is useful for planning prevention and treatment services. Heavy Alcohol Consumption (HAC) and Alcohol Use Disorder (AUD) are two syndromes of alcohol-related problems that have been recognized worldwide. Study of the epidemiological determinants of HAC and AUD in different sociocultural contexts could inform hypotheses about the etiology or the consequences of alcohol-related problems. Objectives We assessed the prevalence and associations of HAC and AUD with sociodemographic variables adjusting for common mental disorders in a representative sample of the general population of Greece (N = 4894 participants). The period of data collection just preceded the emergence of the financial crisis in Greece. Results The majority of the population did not report HAC, AUD or abstinence from alcohol. HAC was reported by 12.7% (95% CI 11.8-13.6) of the population while 3.1% (95% CI 2.7-3.6) met criteria for AUD. Younger age, divorce, lower educational level, living in an urban area, physical health problems, and smoking were associated with a higher prevalence of both conditions. Presence of severe financial difficulties and never married family status were associated with a higher prevalence of HAC but not AUD. HAC was associated with nonspecific psychiatric morbidity while AUD was associated with more specific psychiatric disorders. Conclusion/Importance. Both alcohol-related problems are frequent in the general population and have common and distinct determinants. The comparison between the findings of our study and those of similar studies during or after the period of financial austerity in Greece, would offer the opportunity to assess the possible effects of changes in the economical context in the determinants of alcohol-related problems. Copyright © 2020 Stefanos Bellos et al.Proteins from the ferredoxin (Fd) and flavodoxin (Fld) families function as low potential electrical transfer hubs in cells, at times mediating electron transfer between overlapping sets of oxidoreductases. To better understand protein electron carrier (PEC) use across the domains of life, we evaluated the distribution of genes encoding [4Fe-4S] Fd, [2Fe-2S] Fd, and Fld electron carriers in over 7,000 organisms. Our analysis targeted genes encoding small PEC genes encoding proteins having ≤200 residues. We find that the average number of small PEC genes per Archaea (~13), Bacteria (~8), and Eukarya (~3) genome varies, with some organisms containing as many as 54 total PEC genes. Organisms fall into three groups, including those lacking genes encoding low potential PECs (3%), specialists with a single PEC gene type (20%), and generalists that utilize multiple PEC types (77%). Mapping PEC gene usage onto an evolutionary tree highlights the prevalence of [4Fe-4S] Fds in ancient organisms that are deeply rooted, the expansion of [2Fe-2S] Fds with the advent of photosynthesis and a concomitant decrease in [4Fe-4S] Fds, and the expansion of Flds in organisms that inhabit low-iron host environments. Surprisingly, [4Fe-4S] Fds present a similar abundance in aerobes as [2Fe-2S] Fds. This bioinformatic study highlights understudied PECs whose structure, stability, and partner specificity should be further characterized.As the pharmaceutical industry in Korea is reaching the golden era of drug discovery due to increased investments in research and development and government funds, the need for a more efficient tool for the quantitative analysis has emerged. Therefore, the demand for pharmacometrics (PMx) consultancy services increased. Higher quality service suitable for regulatory submission and out-licensing deals were desired. In this analysis, we compiled and summarized 3 years of experiences of Q-fitter, the first PMx consultancy service company providing PMx analysis to the pharmaceutical industry in Korea. The projects were organized by companies, company types, indications, therapeutic areas, drug development stages, purposes, and scope of services. Within each category, we subcategorized the sections and assessed proportions and a year-over-year trend. As a result, we observed an increase in the number of projects in an average of ~170% per year, with the most frequent types of companies collaborated being the domestic pharmaceutical companies. Among the projects, ~72% involved modeling and simulation using population pharmacokinetic (PK) models, and the other included non-compartmental analysis (NCA), drug-drug interaction (DDI) prediction, and interpretation of the modeling results. The most sought-after purpose in PMx analysis was first-in-human (FIH) dose prediction followed by PK analysis, next clinical trial prediction, and scenario-based simulation. Oncology has been the top therapeutic area of interest every year consisting of ~38% of total projects, followed by Neurology (~13%). From this review, we were able to characterize the PMx service needs and spot the trend of current PMx practices in Korea. Copyright © 2019 Translational and Clinical Pharmacology.The accuracy and predictability of mixture models in NONMEM® may change depending on the relative size of inter-individual differences and the size of the differences in the parameters between subpopulations. This study explored the accuracy of mixture models when dealing with missing a categorical covariate under various situations that may occur in reality. We generated simulation data under various scenarios where genotypes representing extensive metabolizers (EM) and poor metabolizers (PM) of drug-metabolizing enzymes affect the clearance of a drug by different degrees, and the inter-individual variations in clearance are different for each scenario. From each simulated datum, a specific proportion of the covariate (genotype information) was randomly removed. Based on these simulation data, the proportion of each individual subpopulation and the clearance were estimated using a mixture model. Overall, the clearance estimate was more accurate when the difference in clearance between subpopulations was large, and the inter-individual variations were small. In some scenarios that showed higher ETA or epsilon shrinkage, the clearance estimates were significantly biased. The mixture model made better predictions for individuals in the EM subpopulation than for individuals in the PM subpopulation. However, the estimated values were not significantly affected by the tested ratio, if the sample size was secured to some extent. The current simulation study suggests that when the coefficient of variation of inter-individual variations of clearance exceeds 40%, the mixture model should be used carefully, and it should be taken into account that shrinkage can bias the results. Copyright © 2019 Translational and Clinical Pharmacology.Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (Cmax) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for Cmax and area under the concentration-time curve from time 0 to the last quantifiable time point (AUClast) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for Cmax and AUClast were 1.0440 (0.9202-1.1844) and 1.0412 (0.9775-1.1090) for fimasartan, and 1.0430 (1.0156-1.0711) and 1.0339 (1.0055-1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for Cmax and AUClast of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence. Copyright © 2019 Translational and Clinical Pharmacology.