Identification and distribution of anaerobic bacteria isolated from clinical specimens in a University Hospital: 4 years’ experience

Anaerobes, which are components of microbiota, can cause life-threatening infections. Because of their fastidious nature, they are difficult to isolate and are often overlooked. The goal of this study was to identify the anaerobic bacteria isolated from clinical specimens at the Central Laboratory of Hacettepe University Hospital in 2015-2018 and to evaluate the distribution of the isolated bacterial species among the different specimen types. The anaerobic bacteria isolated from the specimens were identified by the conventional methods and MALDI-TOF MS.Overall, 15,300 anaerobic cultures were studied. Of these, 14,434 (94.3%) were blood samples and 866 (5.7%) were other clinical specimens. A total of 138 anaerobic bacteria were isolated: 62 (44.9%) were isolated from blood samples and 76 (55.1%) from other specimens. The most isolated anaerobes from blood cultures were Bacteroides spp. (41.9%), followed by Cutibacterium acnes (25.8%) and Clostridium spp. (9.7%). The most isolated anaerobes from the other specimens were Gram-negative bacilli, including Bacteroides spp. (15.8%), Fusobacterium spp. (14.5%), Prevotella spp. (14.5%), and Porphyromonas spp. (2.6%). Anaerobic Finegoldia magna represented the major species among the isolated Gram-positive bacteria (10.5%). Anaerobic growth was observed in 0.4% of all the blood cultures and in 5.8% of the positive blood cultures. The results of our study showed that the incidence of anaerobic bacteremia was stable during the 2015-2018 period.Anaerobes, which are components of microbiota, can cause life-threatening infections. Because of their fastidious nature, they are difficult to isolate and are often overlooked. The goal of this study was to identify the anaerobic bacteria isolated from clinical specimens at the Central Laboratory of Hacettepe University Hospital in 2015-2018 and to evaluate the distribution of the isolated bacterial species among the different specimen types. The anaerobic bacteria isolated from the specimens were identified by the conventional methods and MALDI-TOF MS.Overall, 15,300 anaerobic cultures were studied. Of these, 14,434 (94.3%) were blood samples and 866 (5.7%) were other clinical specimens. A total of 138 anaerobic bacteria were isolated: 62 (44.9%) were isolated from blood samples and 76 (55.1%) from other specimens. The most isolated anaerobes from blood cultures were Bacteroides spp. (41.9%), followed by Cutibacterium acnes (25.8%) and Clostridium spp. (9.7%). The most isolated anaerobes from the other specimens were Gram-negative bacilli, including Bacteroides spp. (15.8%), Fusobacterium spp. (14.5%), Prevotella spp. (14.5%), and Porphyromonas spp. (2.6%). Anaerobic Finegoldia magna represented the major species among the isolated Gram-positive bacteria (10.5%). Anaerobic growth was observed in 0.4% of all the blood cultures and in 5.8% of the positive blood cultures. The results of our study showed that the incidence of anaerobic bacteremia was stable during the 2015-2018 period

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

Multi-aspect analysis of ureteral access sheath usage in retrograde intrarenal surgery: A RIRSearch group study

Objective: To evaluate the effect of ureteral access sheath (UAS) use and calibration change on stone-free rate and complications of retrograde intrarenal surgery (RIRS). Methods: Data from 568 patients undergoing RIRS for kidney or upper ureteral stones were retrospectively included. Firstly, patients were compared after 1:1 propensity score matching, according to UAS usage during RIRS (UAS used [+] 87 and UAS non-used [?] 87 patients). Then all UAS+ patients (n=481) were subdivided according to UAS calibration: 9.5–11.5 Fr, 10–12 Fr, 11–13 Fr, and 13–15 Fr. Primary outcomes of the study were the success and complications of RIRS. Results: Stone-free rate of UAS+ patients (86.2%) was significantly higher than UAS? patients (70.1%) after propensity score matching (p=0.01). Stone-free rate increased with higher caliber UAS (9.5–11.5 Fr: 66.7%; 10–12 Fr: 87.3%; 11–13 Fr: 91.3%; 13–15 Fr: 100%; p<0.0001). Postoperative complications of UAS+ patients (11.5%) were significantly lower than UAS? patients (27.6%) (p=0.01). Complications (8.7%) with 9.5–11.5 Fr UAS was lower than thicker UAS (17.3%) but was not statistically significant (p=0.08). UAS usage was an independent factor predicting stone-free status or peri- and post-operative complications (odds ratio [OR] 3.654, 95% confidence interval [CI] 1.314–10.162; OR 4.443, 95% CI 1.350–14.552; OR 4.107, 95% CI 1.366–12.344, respectively). Conclusion: Use of UAS in RIRS may increase stone-free rates, which also increase with higher caliber UAS. UAS usage may reduce complications; however, complications seemingly increase with higher UAS calibration. © 2022 Editorial Office of Asian Journal of Urolog

mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France

Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV

Regulation of proteasome assembly and activity in health and disease

The proteasome degrades most cellular proteins in a controlled and tightly regulated manner and thereby controls many processes, including cell cycle, transcription, signalling, trafficking and protein quality control. Proteasomal degradation is vital in all cells and organisms, and dysfunction or failure of proteasomal degradation is associated with diverse human diseases, including cancer and neurodegeneration. Target selection is an important and well-established way to control protein degradation. In addition, mounting evidence indicates that cells adjust proteasome-mediated degradation to their needs by regulating proteasome abundance through the coordinated expression of proteasome subunits and assembly chaperones. Central to the regulation of proteasome assembly is TOR complex 1 (TORC1), which is the master regulator of cell growth and stress. This Review discusses how proteasome assembly and the regulation of proteasomal degradation are integrated with cellular physiology, including the interplay between the proteasome and autophagy pathways. Understanding these mechanisms has potential implications for disease therapy, as the misregulation of proteasome function contributes to human diseases such as cancer and neurodegeneration.</p

Reply to Intraocular pressure during micturition in benign prostatic hyperplasia

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Reply to "Intraocular pressure during micturition in benign prostatic hyperplasia"

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Analyses of the mechanical, electrical and electromagnetic shielding properties of thermoplastic composites doped with conductive nanofillers

The purpose of this study is to observe effect of incorporating vapor-grown carbon nanofibers with various amounts in polyvinylidene fluoride matrix in terms of mechanical strength and electromagnetic shielding effectiveness. Thermoplastic conductive nanocomposites were prepared by heat-pressed compression molding. Vapor-grown carbon nanofibers were utilized at various weight ratios (1 wt.%, 3 wt.%, 5 wt.%, and 8 wt.%) as conductive and reinforcing materials. Polyvinylidene fluoride was used as a thermoplastic polymer matrix. Scanning electron microscopic analysis was conducted in order to characterize the morphology and structural properties of the nanocomposites and results revealed well dispersion of carbon nanofibers within the matrix for all concentrations. Mechanical characteristics were investigated according to standards. Findings proved that overall increments of 16%, 37.5%, and 56% were achieved in terms of tensile strength, elasticity modulus, and impact energy, respectively, where a total reduction of 44.8% was observed in terms of elongation for 8 wt.% vapor-grown nanofiber matrix compared to that of 0 wt.%. Electromagnetic shielding effectiveness's of the nanocomposites were determined by standard protocol using coaxial transmission line measurement technique in the frequency range of 15–3000 MHz. It was observed that resistance, sheet resistance, and resistivity of nanocomposites depicted substantial reduction with the increment in nanofiber content. Nevertheless, it was observed that nanofiber content, dispersion, and network formation within the composites were highly influent on the electromagnetic shielding effectiveness performance of the structures