Phage Therapy of Mycobacterium Infections : Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease

Background Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification. Methods Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid. Results No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these. Conclusions Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.We describe 20 consecutive cases of bacteriophage treatment of Mycobacterium infections. We observed no adverse reactions, favorable outcomes in at least 50% of patients, no evidence of phage resistance, and neutralizing immune reactions that do not correlate with treatment success.Peer reviewe

Thrive: Undergraduate Research Journal [Fall 2021, Volume 1, Number 1]

UNDERGRADUATE RESEARCH JOURNAL OF UNIVERSITY OF SOUTH FLORIDA\u27S STUDENT ORGANIZATION URJ VOLUME 1 | FALL 2021https://digitalcommons.usf.edu/thrive/1000/thumbnail.jp

Advancements in NORM metrology – Results and impact of the European joint research project MetroNORM

Proceedings of the 7th International Conference on Radionuclide Metrology - Low Level Radioactivity Measurement Techniques (ICRM-LLRMT), 26 -30 September 2016, Seattle, USAInternational audienceThe results of the three years European Metrology Research Programme's (EMRP) joint research project 'Metrology for processing materials with high natural radioactivity' (MetroNORM) are presented. In this project, metrologically sound novel instruments and procedures for laboratory and in-situ NORM activity measurements have been developed. Additionally, standard reference materials and sources for traceable calibration and improved decay data of natural radionuclides have been established

Advancements in NORM metrology - Results and impact of the European joint research project MetroNORM

The results of the three years European Metrology Research Programme’s (EMRP) joint research project ‘Metrology for processing materials with high natural radioactivity’ (MetroNORM) are presented. In this project, metrologically sound novel instruments and procedures for laboratory and in-situ NORM activity measurements have been developed. Additionally, standard reference materials and sources for traceable calibration and improved decay data of natural radionuclides have been established.JRC.G.2-Standards for Nuclear Safety, Security and Safeguard

PPAR alpha: an emerging therapeutic target in diabetic microvascular damage

The global pandemic of diabetes mellitus portends an alarming rise in the prevalence of microvascular complications, despite advanced therapies for hyperglycemia, hypertension and dyslipidemia. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is expressed in organs affected by diabetic microvascular disease (retina, kidney and nerves), and its expression is regulated specifically in these tissues. Experimental evidence suggests that PPAR alpha activation attenuates or inhibits several mediators of vascular damage, including lipotoxicity, inflammation, reactive oxygen species generation, endothelial dysfunction, angiogenesis and thrombosis, and thus might influence intracellular signaling pathways that lead to microvascular complications. PPAR alpha has emerged as a novel target to prevent microvascular disease, via both its lipid-related and lipid-unrelated actions. Despite strong experimental evidence of the potential benefits of PPAR alpha agonists in the prevention of vascular damage, the evidence from clinical studies in patients with diabetes mellitus remains limited. Promising findings from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study on microvascular outcomes are countered by elevations in participants' homocysteine and creatinine levels that might potentially attenuate the benefits of PPAR alpha activation. This Review focuses on the role of PPAR alpha activation in diabetic microvascular disease and highlights the available experimental and clinical evidence from studies of PPAR alpha agonists

Gaia Focused Product Release: Spatial distribution of two diffuse interstellar bands

Diffuse interstellar bands (DIBs) are absorption features seen in optical and infrared spectra of stars and extragalactic objects that are probably caused by large and complex molecules in the galactic interstellar medium (ISM). Here we investigate the Galactic distribution and properties of two DIBs identified in almost six million stellar spectra collected by the Gaia Radial Velocity Spectrometer. These measurements constitute a part of the Gaia Focused Product Release to be made public between the Gaia DR3 and DR4 data releases. In order to isolate the DIB signal from the stellar features in each individual spectrum, we identified a set of 160 000 spectra at high Galactic latitudes (|b| ≥ 65) covering a range of stellar parameters which we consider to be the DIB-free reference sample. Matching each target spectrum to its closest reference spectra in stellar parameter space allowed us to remove the stellar spectrum empirically, without reference to stellar models, leaving a set of six million ISM spectra. Using the star&amp;apos;s parallax and sky coordinates, we then allocated each ISM spectrum to a voxel (VOlume piXEL) on a contiguous three-dimensional grid with an angular size of 1.8 (level 5 HEALPix) and 29 unequally sized distance bins. Identifying the two DIBs at 862.1 nm (λ862.1) and 864.8 nm (λ864.8) in the stacked spectra, we modelled their shapes and report the depth, central wavelength, width, and equivalent width (EW) for each, along with confidence bounds on these measurements. We then explored the properties and distributions of these quantities and compared them with similar measurements from other surveys. Our main results are as follows: (1) the strength and spatial distribution of the DIB λ862.1 are very consistent with what was found in Gaia DR3, but for this work we attained a higher signal-to-noise ratio in the stacked spectra to larger distances, which allowed us to trace DIBs in the outer spiral arm and beyond the Scutum-Centaurus spiral arm; (2) we produced an all-sky map below ±65 of Galactic latitude to ∼4000 pc of both DIB features and their correlations; (3) we detected the signals of DIB λ862.1 inside the Local Bubble (≲200 pc); and (4) there is a reasonable correlation with the dust reddening found from stellar absorption and EWs of both DIBs with a correlation coefficient of 0.90 for λ862.1 and 0.77 for λ864.8.Funder: for funding information see Appendix D in https://doi.org/10.1051/0004-6361/202347103;Full text license: CC BY</p

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes