Identification of the main glutamine and glutamate transporters in Staphylococcus aureus and their impact on c-di-AMP production

A Staphylococcus aureus strain deleted for the c‐di‐AMP cyclase gene dacA is unable to survive in rich medium unless it acquires compensatory mutations. Previously identified mutations were in opuD, encoding the main glycine‐betaine transporter, and alsT, encoding a predicted amino acid transporter. Here, we show that inactivation of OpuD restores the cell size of a dacA mutant to near wild‐type (WT) size, while inactivation of AlsT does not. AlsT was identified as an efficient glutamine transporter, indicating that preventing glutamine uptake in rich medium rescues the growth of the S. aureus dacA mutant. In addition, GltS was identified as a glutamate transporter. By performing growth curves with WT, alsT and gltS mutant strains in defined medium supplemented with ammonium, glutamine or glutamate, we revealed that ammonium and glutamine, but not glutamate promote the growth of S. aureus. This suggests that besides ammonium also glutamine can serve as a nitrogen source under these conditions. Ammonium and uptake of glutamine via AlsT and hence likely a higher intracellular glutamine concentration inhibited c‐di‐AMP production, while glutamate uptake had no effect. These findings provide, besides the previously reported link between potassium and osmolyte uptake, a connection between nitrogen metabolism and c‐di‐AMP signalling in S. aureus

Influenza vaccination and hospitalisation in Elderly Health Centres.

1. A cohort of Elderly Health Centres was examined to determine whether influenza vaccination decreased hospitalisation and mortality. 2. In the influenza season, influenza vaccination reduced all-cause mortality by half and cardiorespiratory hospitalisation by a quarter. The extent to which influenza vaccination protects older people from serious morbidity and mortality needs to be confirmed in appropriately designed studies, so that scarce health care resources can be used effectivelypublished_or_final_versio

Comparing the Job Satisfaction and Intention to Leave of Different Categories of Health Workers in Tanzania, Malawi, and South Africa.

Job satisfaction is an important determinant of health worker motivation, retention, and performance, all of which are critical to improving the functioning of health systems in low- and middle-income countries. A number of small-scale surveys have measured the job satisfaction and intention to leave of individual health worker cadres in different settings, but there are few multi-country and multi-cadre comparative studies. The objective of this study was to compare the job satisfaction and intention to leave of different categories of health workers in Tanzania, Malawi, and South Africa. We undertook a cross-sectional survey of a stratified cluster sample of 2,220 health workers, 564 from Tanzania, 939 from Malawi, and 717 from South Africa. Participants completed a self-administered questionnaire, which included demographic information, a 10-item job satisfaction scale, and one question on intention to leave. Multiple regression was used to identify significant predictors of job satisfaction and intention to leave. There were statistically significant differences in job satisfaction and intention to leave between the three countries. Approximately 52.1% of health workers in South Africa were satisfied with their jobs compared to 71% from Malawi and 82.6% from Tanzania (χ2=140.3, p<0.001). 18.8% of health workers in Tanzania and 26.5% in Malawi indicated that they were actively seeking employment elsewhere, compared to 41.4% in South Africa (χ2=83.5, p<0.001). The country differences were confirmed by multiple regression. The study also confirmed that job satisfaction is statistically related to intention to leave. We have shown differences in the levels of job satisfaction and intention to leave between different groups of health workers from Tanzania, Malawi, and South Africa. Our results caution against generalising about the effectiveness of interventions in different contexts and highlight the need for less standardised and more targeted HRH strategies than has been practised to date

Zero-Liquid Discharge Desalination of Hypersaline Shale Gas Wastewater: Challenges and Future Directions

EMCEI 2017 - Euro-Mediterranean Conference for Environmental IntegrationUnconventional natural gas extraction from tight shale reservoirs, or shale gas, has recently emerged as an attractive energy resource to face the rising worldwide demand. Over the past decade, advanced technologies of horizontal drilling and hydraulic fracturing (“fracking”) have allowed the economic viability of shale gas exploration from rather unattainable deposits. Apart from optimistic growth projections, shale gas production is also responsible for worrying environmental and social implications, which are related, among others, to elevated freshwater consumption and hazardous wastewater generation. Within this framework, the ability of zero-liquid discharge desalination to promote water reuse and/or water recycling is critical for shale gas industry. Hence, application of effective desalination processes is mandatory to treat the large amounts of polluting hypersaline wastewater, alleviating environmental and public health impacts and enhancing overall shale gas process sustainability. This work outlines the challenges and future directions for ZLD desalination of shale gas wastewater.This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 640979

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5&nbsp;years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0&nbsp;mg/kg/every other week (qow), elosulfase alfa 2.0&nbsp;mg/kg/week (weekly) or placebo for 24&nbsp;weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95&nbsp;% CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95&nbsp;% CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95&nbsp;% CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95&nbsp;% CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24&nbsp;weeks in both regimens. In the weekly dose group, 22.4&nbsp;% of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3&nbsp;% of all infusions in this group) over 6&nbsp;months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): ASL pipeline inventory

Purpose: To create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly available pipelines to guide novice ASL users in selecting their optimal pipeline. Methods: Developers self-assessed their pipelines using a questionnaire developed by the Task Force 1.1 of the ISMRM Open Science Initiative for Perfusion Imaging. Additionally, each publicly available pipeline was evaluated by two independent testers with basic ASL experience using a scoring system created for this purpose. Results: The developers of 21 pipelines filled the questionnaire. Most pipelines are free for noncommercial use (n = 18) and work with the standard NIfTI (Neuroimaging Informatics Technology Initiative) data format (n = 15). All pipelines can process standard 3D single postlabeling delay pseudo-continuous ASL images and primarily differ in their support of advanced sequences and features. The publicly available pipelines (n = 9) were included in the independent testing, all of them being free for noncommercial use. The pipelines, in general, provided a trade-off between ease of use and flexibility for configuring advanced processing options. Conclusion: Although most ASL pipelines can process the common ASL data types, only some (namely, ASLPrep, ASLtbx, BASIL/Quantiphyse, ExploreASL, and MRICloud) are well-documented, publicly available, support multiple ASL types, have a user-friendly interface, and can provide a useful starting point for ASL processing. The choice of an optimal pipeline should be driven by specific data to be processed and user experience, and can be guided by the information provided in this ASL inventory

Variation of cataract surgery costs in four different graded providers of China

<p>Abstract</p> <p>Background</p> <p>China has the largest population of cataract patients in the world. However, the cataract surgery rate per million remains low in China. We carried out a survey on costs of cataract surgery from four different graded providers in China and analyzed differences in cost among these clinics.</p> <p>Methods</p> <p>1,189 patients were recruited for the study in four eye clinics, located in two provinces, Guangdong province in southern China and Hubei province in central China. The average cost of each cataract surgery episode was calculated including cost of intraocular lens, cost of drugs and facility cost. We also collected information on reimbursement and disposable annual income of local residents.</p> <p>Results</p> <p>Mean total cost per cataract intervention of four different providers varied considerably, ranging from US$1,293 in Union Hospital to US$ 536 in Jingshan County Hospital. In all providers, except for Jingshan County Hospital, the cost exceeded annual disposable income of local rural residents. As to the proportion of patients with reimbursement, the figure for Union Hospital was only 36%, while for other three clinics it was more than 60%. There was a significant difference between mean reimbursement ratios, with the highest ratio in Zhongshan Ophthalmic Center being 71%.</p> <p>Conclusions</p> <p>Significant differences in costs of cataract surgery were found among the 4 different graded providers. A part of the cost was borne by patients. Proportion of patients with reimbursement and mean reimbursement ratios were higher in economically developed regions than in economically developing regions. Much more financial support should be directed into the rural New Cooperative Medical Scheme to raise the reimbursement ratio in rural China.</p