Natively oxidized amino acid residues in the spinach PS I-LHC I supercomplex

Photosynthesis Research - Reactive oxygen species (ROS) production is an unavoidable byproduct of electron transport under aerobic conditions. Photosystem II (PS II), the cytochrome  b6/f...     

Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study

BackgroundAcute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.Methods and findingsPatients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27–62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.ConclusionsThis multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Etienne Macedo and colleagues report on a point-of-care testing program for acute kidney injury and disease in high-risk primary care patients.     

Development of an effective novel validated stability-indicating HPLC method for the resolution of brivaracetam stereoisomeric impurities

Reverse-phase high-performance liquid chromatography method has been developed for the determination of brivaracetam stereoisomeric impurities such as (R,S)-brivaracetam, (R,R)-brivaracetam, and (S,S)-brivaracetam with good resolution using the chiral column, Chiral PAK IG-U (100 × 3.0 mm; 1.6 μm). The method is simple, stability-indicating, and compatible with LC–MS. The separation was achieved with the mobile phase consisted of 10 mM ammonium bicarbonate along with acetonitrile in an isocratic mode. The column temperature and wavelength were monitored at 40°C and 215 nm, respectively. The method showed adequate specificity, sensitivity, linearity, accuracy, precision, and robustness inline to ICH tripartite guidelines. The limit of detection and quantification limits were 0.3 and 0.8 μg ml⁻¹, respectively, for all stereoisomeric impurities and brivaracetam. The developed method was found to be linear over the concentration range of 0.8–5.6 μg ml⁻¹ for stereoisomeric impurities with a correlation coefficient >0.999. The method was precise (%RSD < 5.0), robust, and accurate (with 85%–115% recovery). The values of retention times of stereoisomeric impurities, (R,S)-brivaracetam, (R,R)-brivaracetam, and (S,S)-brivaracetam, were 4.9, 5.4, and 6.6 min, respectively, and resolution among the impurities were 2.0, 3.3, and 4.7, respectively. In addition, forced degradation studies were performed to prove that method was stability-indicating. The enrichment of isomeric impurity, (R,R)-brivaracetam, was observed under basic stress conditions of brivaracetam and proposed a plausible mechanism to enhance that isomeric impurity. As well, a good separation among brivaracetam and its stereoisomeric impurity peaks was observed in the presence of degradation products and process-related impurities.     

Modelling population dynamics in a unicellular social organism community using a minimal model and evolutionary game theory

Most unicellular organisms live in communities and express different phenotypes. Many efforts have been made to study the population dynamics of such complex communities of cells, coexisting as well-coordinated units. Minimal models based on ordinary differential equations are powerful tools that can help us understand complex phenomena. They represent an appropriate compromise between complexity and tractability; they allow a profound and comprehensive analysis, which is still easy to understand. Evolutionary game theory is another powerful tool that can help us understand the costs and benefits of the decision a particular cell of a unicellular social organism takes when faced with the challenges of the biotic and abiotic environment. This work is a binocular view at the population dynamics of such a community through the objectives of minimal modelling and evolutionary game theory. We test the behaviour of the community of a unicellular social organism at three levels of antibiotic stress. Even in the absence of the antibiotic, spikes in the fraction of resistant cells can be observed indicating the importance of bet hedging. At moderate level of antibiotic stress, we witness cyclic dynamics reminiscent of the renowned rock–paper–scissors game. At a very high level, the resistant type of strategy is the most favourable.     

Waist Circumference Measurement by Site,Posture, Respiratory Phase,and Meal Time: Implications for Methodology

Waist circumference (WC) has been advocated as a simple, reliable, and cost‐effective measure to understand an individual's cardio‐metabolic risk. Although several protocols exist for measuring WC, the variation induced by a few factors has not been investigated. We compared several established and experimental WC measurement protocols to identify factors that may cause variations in WC measurement. In this cross‐sectional study, we examined the variations in the measurement of waist circumference (WC) measures carried out in 11 ways differing by anatomical site, posture, respiratory phase, and time since last meal, using repeated measure analysis of variance (using mixed models) after Tukey‐Kramer adjustment. We estimated the proportion of variance in percentage of body fat (%BF) and fat‐free mass (FFM) explained by each of the WC measures. We studied 123 apparently healthy Asian Indians (75 females), with mean (s.d.) age of 34 (8.7) years and BMI of 23.9 (4.8) kg/m². Overall, the mean of WCs measured using the 11 protocols were statistically different. Further, post hoc analysis showed statistically significant, yet mostly small, differences between most of the pairs. No single WC measure explained highest variance in %BF or FFM for both genders. Although, the National Institute of Health (NIH), USA, protocol was convenient and may be less prone to errors, at present it does not control for many variables tested in this study. Measures of WC measured using different protocols were statistically different. We suggest that the site of measurement, posture, phase of respiration, and time since last meal should be standardized for the development of a protocol for measurement of WC for worldwide use.