Sustainable extraction of pesticides in food and environmental samples using emerging green adsorbents

There are many emerging adsorbents, with relatively high adsorption capacities, that can be used during the extraction of pesticides from complex matrices. Poly(ionic liquids) are among these emerging adsorbents. The applications of poly(ionic liquids) as adsorbents during pesticide pre-concentration are explored in this paper. Some researchers have taken advantage of the adhesive nature of polydopamine and used it to synthesise adsorbents with relatively high adsorption capacities. The use of polydopamine-based sorbents during pesticide pre-concentration is also reviewed in this paper. Deep eutectic solvents, on the other hand, can be used to synthesise adsorbents to extract pesticides in complex matrices. This is usually done either by immobilising it on a solid support or by polymerisation. Applications of deep eutectic solvent-based adsorbents during pesticide extraction are discussed in detail in this review. In addition, this review has explored the challenges associated with the use of these emerging adsorbents during the extraction of pesticides as well as the future prospects.     

Rapid Drug Tolerance and Dramatic Sterilizing Effect of Moxifloxacin Monotherapy in a Novel Hollow-Fiber Model of Intracellular Mycobacterium kansasii Disease

Mycobacterium kansasii is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed. Moxifloxacin has good MICs for M. kansasii. However, good preclinical models to identify optimal doses currently are lacking. We developed a novel hollow fiber system model of intracellular M. kansasii infection. We indexed the efficacy of the standard combination regimen, which was a kill rate of −0.08 ± 0.05 log₁₀ CFU/ml/day (r² = 0.99). We next performed moxifloxacin dose-effect and dose-scheduling studies at a half-life of 11.1 ± 6.47 h. Some systems also were treated with the efflux pump inhibitor reserpine. The highest moxifloxacin exposure, as well as lower exposures plus reserpine, sterilized the cultures by day 7. This suggests that efflux pump-mediated tolerance at low ratios of the area under the concentration-time curve from 0 to 24 h (AUC_0–24) to MICs is an early bacterial defense mechanism but is overcome by higher exposures. The highest rate of moxifloxacin monotherapy sterilization was −0.82 ± 0.15 log₁₀ CFU/ml/day (r² = 0.97). The moxifloxacin exposure associated with 80% of maximal kill (EC₈₀) was an AUC_0–24/MIC of 317 (the non-protein-bound moxifloxacin AUC_0–24/MIC was 158.5). We performed Monte Carlo simulations of 10,000 patients in order to identify the moxifloxacin dose that would achieve or exceed the EC₈₀. The simulations revealed an optimal moxifloxacin dose of 800 mg a day. The MIC susceptibility breakpoint at this dose was 0.25 mg/liter. Thus, moxifloxacin, at high enough doses, is suitable to study in patients for the potential to add rapid sterilization to the standard regimen.     

Metformin and heart failure–related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials

Heart Failure Reviews - Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure–related outcomes...     

Twin pregnancies in Cardiff and Vale of Glamorgan over four decades: natural twinning is on the increase

Objective

To assess trends in twinning over four decades using a population-based registry.

Design

Ecological study to conduct trend analysis of twin pregnancies in a geographically defined area over 40 years.

Setting

All pregnancies in the Cardiff and Vale of Glamorgan area of South Wales from 1965 to 2004, as recorded in the Cardiff Birth Survey (CBS) database.

Methods

Trends of the incidence of all twin pregnancies (≥18 weeks of gestation) were calculated in 5-year increments, beginning with 1965–1969 and ending in 2000–2004. Natural twinning rates could only be calculated for the terminal five time periods (i.e., 1980–1984, 1985–1989, 1990–1994, 1995–1999, and 2000–2004), when information regarding non-spontaneous (iatrogenic) twinning was first collected in the database. All results were adjusted for maternal age.

Results

The total twinning rate was 13.1 per 1000 pregnancies in the 1st time period (1965–1969). Subsequently, there was a gradual reduction in twinning, reaching a nadir of 10.3 per 1000 for the time period 1980–1985 (Z = 3.15, P value < 0.001). This was followed by a gradual increase in twinning, reaching a maximum of 15.7 per 1000 for both 1995–1999 and 2000–2004 (Z = −5.18, P value < 0.0001). After exclusion of the cases of iatrogenic pregnancies, the natural twinning rate showed a continuous and gradual increase from 10 per 1000 spontaneous pregnancies in 1980–1984 to 13.3 per 1000 in 2000–2004 (Z = −5.08, P value < 0.0001).

Conclusion

The data showed a gradual, continuous increase in natural twinning rates over the last two decades. Such an increase cannot be attributed to the rise in maternal age alone.     

Labor induction with vaginal misoprostol and extra-amniotic prostaglandin F2alpha gel.

OBJECTIVE: To compare the effectiveness of vaginally administered misoprostol with extra-amniotic prostaglandin F2alpha (PGF2alpha) gel for induction of labor. METHOD: A randomized controlled trial, with women allocated to receive either misoprostol 50 microg intra-vaginally or extra-amniotic PGF2alpha gel 5 mg, was conducted in Harare Maternity Hospital. A total of 152 women were admitted for induction of labor with a term singleton, pregnancy and cephalic presentation were recruited. The main outcome was duration of induction. RESULTS: There were no differences in the characteristics of women in the two groups at recruitment. In the misoprostol group there was a significantly reduced need for augmentation of labor with oxytocin (OR=0.36; 95% C.I. 0.17-0.73) and delivery by cesarean section for failure to progress (OR=0.11; 95% C.I. 0.00-0.88). The risk for duration of induction to vaginal delivery exceeding 12, 18 or 24 h was reduced by 18%, 38% and 68%, respectively, but only the risk for duration >24 h was significantly reduced (OR=0.32; 95%C.I. 0.11-0.91). The mean duration of induction was shorter in the misoprostol group, 15.2 vs. 23.6 h (P=0.02). There were no differences in fetal outcome. CONCLUSION: Misoprostol 50 microg was associated with less use of oxytocin in labor, a shorter induction to delivery interval and fewer cesarean sections for failure to progress when compared with extra-amniotic PGF2alpha gel.     

Relation of parity to pregnancy outcome in a rural community in Zimbabwe

This population-based cohort study was conducted to compare pregnancy complications and outcome among nulliparous, low (1-5) and high (> or = 6) parity women. Women who registered for antenatal care and gave birth in Guru District, Zimbabwe, between January 1995 and June 1998 were classified into groups by parity. The women were compared for baseline characteristics, utilisation of health facilities and occurrence of pregnancy complications such as hypertensive disorders of pregnancy, haemorrhage, pre-term delivery, operative delivery, low birth weight and perinatal death. In estimating risk, primiparous (parity = 1) women were used as referents. Pregnancy records for 10,569 women were analysed. Mean ages of nulliparous and high parity (> or = 6) women were 20.1 and 37.7 years respectively (p < 0.001). Prevalence of anaemia at booking (haemoglobin < or =10.5 g/dl) was reduced in nulliparous compared to multiparous women (11.7% vs 16.8%; p > or = 0.001). Nulliparous women were likely to book early (< or = 20 weeks) for antenatal care, have a higher number of visits (> or = 6) and fewer home births. Nulliparous women had higher risk for low birth weight (RR 1.70; 95% CI 1.36 - 2.13). Compared to low parity women, nulliparous and high parity women had an elevated risk of hypertensive complications RR 1.62 (95% CI 1.37-1.92) and RR 1.64 (95% CI 1.29 - 2.07) respectively. The risk of developing any pregnancy complications was highest in nulliparous women (RR 1.48; 95% 1.31- 1.67). In conclusion, nulliparous women had an increased risk of pregnancy complications. High parity women with no previous complicated pregnancy were at low risk of complications.     

Quantitative assessment of the activity of antituberculosis drugs and regimens

Introduction: Identification of optimal drug doses and drug combinations is crucial for optimized treatment of tuberculosis.

Areas covered: An unprecedented level of research activity involving multiple approaches is seeking to improve tuberculosis treatment. This report is a review of the quantitative methods currently used on clinical data sets to identify drug exposure targets and optimal drug combinations for tuberculosis treatment. A high-level summary of the methods, including the strengths and weaknesses of each method and potential methodological improvements is presented. Methods incorporating data generated from multiple sources such as in vitro and clinical studies, and their potential to provide better estimates of pharmacokinetic/pharmacodynamic (PK/PD) targets, are discussed. PK/PD relationships identified are compared between different studies and data analysis methods.

Expert opinion: The relationships between drug exposures and tuberculosis treatment outcomes are complex and require analytical methods capable of handling the multidimensional nature of the relationships. The choice of a method is guided by its complexity, interpretability of results, and type of data available.     

Amikacin Pharmacokinetics/Pharmacodynamics in a Novel Hollow-Fiber Mycobacterium abscessus Disease Model

The treatment of pulmonary Mycobacterium abscessus disease is associated with very high failure rates and easily acquired drug resistance. Amikacin is the key drug in treatment regimens, but the optimal doses are unknown. No good preclinical model exists to perform formal pharmacokinetics/pharmacodynamics experiments to determine these optimal doses. We developed a hollow-fiber system model of M. abscessus disease and studied amikacin exposure effects and dose scheduling. We mimicked amikacin human pulmonary pharmacokinetics. Both amikacin microbial kill and acquired drug resistance were linked to the peak concentration-to-MIC ratios; the peak/MIC ratio associated with 80% of maximal kill (EC₈₀) was 3.20. However, on the day of the most extensive microbial kill, the bacillary burden did not fall below the starting inoculum. We performed Monte Carlo simulations of 10,000 patients with pulmonary M. abscessus infection and examined the probability that patients treated with one of 6 doses from 750 mg to 4,000 mg would achieve or exceed the EC₈₀. We also examined these doses for the ability to achieve a cumulative area under the concentration-time curve of 82,232 mg · h/liter × days, which is associated with ototoxicity. The standard amikacin doses of 750 to 1,500 mg a day achieved the EC₈₀ in ≤21% of the patients, while a dose of 4 g/day achieved this in 70% of the patients but at the cost of high rates of ototoxicity within a month or two. The susceptibility breakpoint was an MIC of 8 to 16 mg/liter. Thus, amikacin, as currently dosed, has limited efficacy against M. abscessus. It is urgent that different antibiotics be tested using our preclinical model and new regimens developed.