Bacterial multi-solute transporters

Bacterial membrane proteins of the SbmA/BacA family are multi-solute transporters that mediate the uptake of structurally diverse hydrophilic molecules, including aminoglycoside antibiotics and antimicrobial peptides. Some family members are full-length ATP-binding cassette (ABC) transporters, whereas other members are truncated homologues that lack the nucleotide-binding domains and thus mediate ATP-independent transport. A recent cryo-EM structure of the ABC transporter Rv1819c from Mycobacterium tuberculosis has shed light on the structural basis for multi-solute transport and has provided insight into the mechanism of transport. Here, we discuss how the protein architecture makes SbmA/BacA family transporters prone to inadvertent import of antibiotics and speculate on the question which physiological processes may benefit from multi-solute transport

Long-Term Halo Follow-Up Confirms Less Invasive Treatment of Low-Grade Cartilaginous Tumors with Radiofrequency Ablation to Be Safe and Effective

Background: Radiofrequency ablation (RFA) is a minimally invasive alternative in the treatment of bone tumors. Long-term follow-up has not been described in current literature. Detailed analysis of mid- and long-term follow-up after RFA treatment for a cohort of patients with low-grade cartilaginous tumors (atypical cartilaginous tumors and enchondroma) was performed. The results, complications, and development of halo dimensions over time are presented. Methods: Data of all patients with an RFA procedure for an ACT between 2007-2018 were included. Ablation area is visible on baseline MRI, 3 months post-procedure, and is called halo. Volume was measured on MR images and compared to different follow-up moments to determine the effect of time on halo volume. Follow-up was carried out 3 months and 1, 2, 5, and 7 years after the procedure. Occurrence of complications and recurrences were assessed. Results: Of the 137 patients included, 82 were analyzed. Mean follow-up time was 43.6 months. Ablation was complete in 73 cases (89.0%). One late complication occurred, while no recurrences were seen. Halo dimensions of height, width, and depth decreased with a similar rate, 21.5% on average in the first year. Subsequently, this decrease in halo size continues gradually during follow-up, indicating bone revitalization. Conclusion: RFA is a safe and effective treatment in low-grade cartilaginous tumors with an initial success rate of 89.0%. Extended follow-up shows no local recurrences and gradual substitution of the halo with normal bone

Improving UAV-SfM time-series accuracy by co-alignment and contributions of ground control or RTK positioning

Unmanned Aerial Vehicle Structure from Motion (UAV-SfM) photogrammetry is increasingly applied to topographic change detection, which requires multitemporal Digital Surface Models (DSMs) with high relative accuracy. Of these tools, Ground Control Points (GCPs) and an image processing method called co-alignment have so far shown promising results for change detection studies. However, there is still insufficient research on the extent of improving 3D model accuracy by combining these tools. In our study we assess absolute and relative accuracy of 120 DSMs generated through 24 workflows of UAV-SfM photogrammetry. Surveys were acquired with two different UAVs with Real Time Kinematic (RTK) or generic Global Navigation Satellite System (GNSS) positioning, and processed with varying combinations of survey co-alignment and GCPs. We show that co-alignment reduces relative errors to below 2 cm regardless of positioning quality. A single RTK survey in a co-aligned project is sufficient to obtain high absolute xy accuracy, but GCPs for at least one survey are still required to reduce absolute z error. We demonstrate that co-aligning RTK surveys with generic GNSS surveys results in RTK class accuracy for all surveys, even when mixed sensor grades are used. Our findings enable high-accuracy change detection with lower accuracy archived images when combined with RTK surveys. For future UAV-SfM change detection studies, we recommend to apply co-alignment for all studies, and where possible to include GCPs and RTK image coordinates in one survey to optimize absolute accuracy. Collecting and digitizing GCPs in multiple surveys has shown little additional benefit when co-alignment is applied and therefore may be omitted to save time, especially in challenging field conditions

Virtual Reality Relaxation for Reducing Perceived Stress of Intensive Care Nurses During the COVID-19 Pandemic

During the COVID-19 pandemic ICU nurses endure high levels of stress. VR relaxation (VRelax, containing 360° immersive environments) provides an easy-to-use and effective means to induce positive affect and reduce perceived stress. We investigated feasibility and immediate effect on perceived stress of VRelax use by ICU nurses during work shifts. ICU nurses working with COVID-19 patients in an academic hospital could use VRelax as a 10-min break during their shift. Primary outcome was the difference between perceived stress immediately before and after VRelax use measured by a single-question VAS-stress scale. Statistically significant difference of the mean VAS-stress before and after use was determined using the paired t student test. A socio-demographic questionnaire, a questionnaire on perceived stress and stress resilience and VRelax user experiences were sent by email. Eighty-six (26%) nurses used VRelax at least once; 77% (N=66) of these filled out the VAS-stress scale before and after use of VRelax. Mean perceived stress lowered with 39.9% after use of VRelax (mean difference=14.0, SD=13.3, p<0.005). Mean score on the perceived stress scale-10 was 11.4 (SD=6.50), mean score on the Connor-Davidson Resilience Scale-10 was 29.0 (SD=5.51). Sixty-two percentage of the ICU nurses thought VRelax was helpful to reduce stress. Main barrier for use was a high workload. It is feasible for nurses to use VRelax in an ICU context. VRelax is an effective intervention to reduce immediate perceived stress and is of added value in stressful situations as during the COVID-19 pandemic, inducing a positive affective state and lowering perceived stress

Fetal baboon sex-specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction

Objective:To investigate in vitro adipocyte differentiation in baboon fetuses in response to reduced maternal nutrition.Design:Cross-sectional comparison of adipocyte differentiation in normally grown fetuses and fetuses of pregnant baboons fed 70% of the control global diet from 30 days of pregnancy to term.Subjects:The subjects comprised control (CTR) fetuses (five female and five male) of mothers fed ad libitum and fetuses of mothers fed 70% of the global diet consumed by CTR (maternal nutrient reduction (MNR), five female and five male fetuses). The expression of genes/proteins involved in adipogenesis (PPARγ, FABP4 and adiponectin) and brown adipose tissue development (UCP1, TBX15 and COXIV) were determined in in vitro-differentiated stromal-vascular cultures from subcutaneous abdominal, subcutaneous femoral and omental adipose tissue depots. Adipocyte number per area (mm 2) was determined histologically to assist in the evaluation of adipocyte size.Results:Maternal suboptimal nutrition suppressed growth of male but not female fetuses and led to adipocyte hypertrophy accompanied by increased markers of white- and, particularly, brown-type adipogenesis in male but not female fetuses.Conclusion:Adipose tissue responses to fetal nonhuman primate undernutrition are sexually dimorphic. While female fetuses adapt adequately, the male ones enhance pathways involved in white and brown adipose tissue development but are unable to compensate for a delayed development of adipose tissue associated with intrauterine growth restriction. These differences need to be considered when assessing developmental programming of adiposity in response to suboptimal maternal nutrition. © 2014 Macmillan Publishers Limited

The pharmacokinetics of antibiotics in cystic fibrosis

Introduction Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. Areas covered The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF. Expert opinion For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class-dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ss-lactam antibiotics, aminoglycosides, fluoroquinolones, and trimethoprim. We, therefore, recommend following class-specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls. Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity

Оголені душі

Рецензія на книги: Слапчук Василь. Осiнь за щокою: Роман. - К.: Факт, 2006. - 280 с. та Сорока Петро. Денники 2004 - 2005. - Тернопiль: Сорока, 2006. - 364 с

Interim thymus and activation regulated chemokine versus interim F-18-fluorodeoxyglucose positron-emission tomography in classical Hodgkin lymphoma response evaluation

Serum thymus and activation regulated chemokine (TARC) levels reflect classical Hodgkin lymphoma (cHL) disease activity and correspond with treatment response. We compared mid-treatment interim TARC (iTARC) with interim 18 F-fluorodeoxyglucose positron-emission tomography (iPET) imaging to predict modified progression-free survival (mPFS) in a group of 95 patients with cHL. High iTARC levels were found in nine and positive iPET in 17 patients. The positive predictive value (PPV) of iTARC for a 5-year mPFS event was 88% compared to 47% for iPET. The negative predictive value was comparable at 86% for iTARC and 85% for iPET. Serum iTARC levels more accurately reflect treatment response with a higher PPV compared to iPET

Eradication of Pseudomonas aeruginosa in cystic fibrosis patients with inhalation of dry powder tobramycin

BACKGROUND: Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in patients with cystic fibrosis (CF). Tobramycin nebulization is used for the eradication of Pa infection. Nowadays, tobramycin dry powder inhalation (DPI) is available as well. This study reports the results of eradicating Pa with tobramycin DPI versus nebulization. METHODS: Adult CF patients with a Pa isolation between September 2010 and September 2017 from the University Medical Centre Groningen (UMCG), the Netherlands, were included in this retrospective study. RESULTS: In total 27 Pa isolations were recorded. In 13 of these, eradication was attempted with tobramycin, 7 with DPI and 6 with nebulization. DPI eradicated Pa successfully in six isolations (85.7%). Of these, one patient received additional oral ciprofloxacin and one received intravenous ceftazidime. Nebulization eradicated three Pa isolations (50.0%), in two of these, additional oral ciprofloxacin was given. CONCLUSION: Eradication rates of DPI tobramycin are comparable with those for nebulized tobramycin reported in the literature. This study suggests that DPI tobramycin is an alternative to nebulized tobramycin for eradication of Pa. TRIAL REGISTRATION: The Medical Ethics Committee of the UMCG granted a waiver (METC2017-349), as they concluded that this study was not subject to the Medical Research Involving Human Subjects Act. The reviews of this paper are available via the supplemental material section

Chemical-looping combustion - a thermodynamic study

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