Staphylococcus epidermidis is the leading coagulase negative staphylococci (CoNS) species associated with healthcare associated infections. In order to de-escalate antimicrobial therapy, isolates of ...S. epidermidis lacking the blaZ gene should be eligible for targeted antimicrobial therapy. However, testing the susceptibility of coagulase negative staphylococci (CoNS) to penicillin G is no longer recommended by EUCAST, given the low performances for penicillinase detection in CoNS. The objective of this work was to determine a phenotypic method with high performance for detecting penicillinase production in S. epidermidis.
Four techniques for the detection of penicillinase production (disk diffusion, zone edge test, nitrocefin test, Minimal Inhibitory Concentration (MIC) by automated system Vitek2®) were evaluated on 182 S. epidermidis isolates, using identification of blaZ gene by PCR as the reference method. The performance of the methods for penicillinase detection was compared by the sensitivity, the specificity, the negative predictive value and the positive predictive value, and with Cohen's kappa statistical test. Among the 182 S. epidermidis included in this study, 55 carried the blaZ gene. The nitrocefin test, characterized by a poor sensitivity (91%), was therefore excluded from S. epidermidis penicillinase detection. The algorithm proposed here for the penicillinase detection in S. epidermidis involved two common antimicrobial susceptibility techniques: disk diffusion method and MIC by Vitek2® system. Disk diffusion method, interpreted with a 26 mm breakpoint for penicillin G, was associated with a high sensitivity (98%) and specificity (100%). This method was completed with zone edge test for S. epidermidis with penicillin G diameter from 26 to 35 mm (sensitivity of 98%). The Vitek2® system is associated with a low sensitivity (93%) and a high specificity (99%) This low sensitivity is associated with false negative results, in isolates with 0.12 mg/L Penicillin G MIC values and blaZ positive. Thus for penicillin G MIC of 0.06 mg/L or 0.12 mg/L, a second step with disc diffusion method is suggested.
According to our results, the strategy proposed here allows the interpretation of penicillin G susceptibility in S. epidermidis isolates, with an efficient detection of penicillin G resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The manufacture of cement is the single largest industrial source of CO
2(g)
emissions into the atmosphere. We report here an electrochemical flow reactor (electrolyser) that continuously converts ...limestone (CaCO
3(s)
) into Ca(OH)
2(s)
at a high rate of product formation (486 mg h
−1
at 100 mA cm
−2
). The Ca(OH)
2(s)
product (slaked lime) is a chemical precursor to cement clinker, the main component of Portland cement, and other cement varieties. This three-compartment electrolyser operates with ∼100% current efficiency at a cell voltage of 2.9 V and generates pure O
2(g)
, H
2(g)
, and CO
2(g)
streams that can be utilized downstream without purification. To demonstrate this feature, we feed the CO
2(g)
released from limestone directly to a second electrolyser that valorizes CO
2(g)
into higher value carbon-containing products (
e.g.
, CO). A preliminary life-cycle analysis indicates that the proposed electrochemical process can decrease the amount of CO
2
emitted per tonne of cement by 75% and achieve cost-parity with incumbent cement manufacturing processes.
We report here an electrochemical flow reactor that converts limestone (CaCO
3(s)
) into Ca(OH)
2(s)
at a high production rate and co-produces pure CO
2(g)
.
Abstract
Environmental merits are a common motivation for many urban agriculture (UA) projects. One powerful way of quantifying environmental impacts is with life cycle assessment (LCA): a method ...that estimates the environmental impacts of producing, using, and disposing of a good. LCAs of UA have proliferated in recent years, evaluating a diverse range of UA systems and generating mixed conclusions about their environmental performance. To clarify the varied literature, we performed a systematic review of LCAs of UA to answer the following questions: What is the scope of available LCAs of UA (geographic, crop choice, system type)? What is the environmental performance and resource intensity of diverse forms of UA? How have these LCAs been done, and does the quality and consistency allow the evidence to support decision making? We searched for original, peer-reviewed LCAs of agricultural production at UA systems, and selected and evaluated 47 papers fitting our analysis criteria, covering 88 different farms and 259 production systems. Focusing on yield, water consumption, greenhouse gas emissions, and cumulative energy demand, using functional units based on mass of crops grown and land occupied, we found a wide range of results. We summarized baseline ranges, identified trends across UA profiles, and highlighted the most impactful parts of different systems. There were examples of all types of systems—across physical set up, crop type, and socio-economic orientation—achieving low and high impacts and yields, and performing better or worse than conventional agriculture. However, issues with the quality and consistency of the LCAs, the use of conventional agriculture data in UA settings, and the high variability in their results prevented us from drawing definitive conclusions about the environmental impacts and resource use of UA. We provided guidelines for improving LCAs of UA, and make a strong case that more research on this topic is necessary to improve our understanding of the environmental impacts and benefits of UA.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac ...complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection.
Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction.
Male sex was more common in the COVID-19 group (
=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (
=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (
=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (
=0.69,
=1.00,
=0.46,
=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations.
This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.
Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucinous cells and basal cells. They ...often have prominent surrounding intra-alveolar mucin, which can lead to diagnostic confusion with mucinous adenocarcinoma. Recognition of the ciliated component is the key to diagnosis of CMPT. The literature contains few reported cases to date, all occurring in East-Asian patients. Although follow-up data are limited, CMPT seems to be an indolent tumor with very good prognosis, leading some to question whether it is a reactive or hamartomatous lesion. However, a very recent molecular study has identified BRAF (40%) and EGFR (30%) alterations in CMPT, supporting a truly neoplastic process. Here for the first time, we report 4 cases of morphologically typical CMPT in western patients, occurring in 1 man (60 y) and 3 women (71 to 83 y). Interestingly, 1 case occurred in background of pronounced small airway disease with necrotizing bronchiolitis and multiple carcinoid tumorlets. We further analyzed 1 tumor using a 50 gene next-generation sequencing oncology panel that identified 2 pathogenic mutations (BRAF V600E and AKT1 E17K). Our study is the first to describe that CMPT can occur in western (non-Asian) patients. Our data confirm BRAF V600E mutation as a probable driver in a subset of these tumors, along with AKT1 mutation, which further supports that CMPT are indolent pulmonary neoplasms.
Distinguishing independent primary tumors from intrapulmonary metastases in non-small-cell carcinoma remains a clinical dilemma with significant clinical implications. Using next-generation DNA ...sequencing, we developed a chromosomal rearrangement-based approach to differentiate multiple primary tumors from metastasis.
Tumor specimens from patients with known independent primary tumors and metastatic lesions were used for lineage test development, which was then applied to multifocal tumors. Laser capture microdissection was performed separately for each tumor. Genomic DNA was isolated using direct in situ whole-genome amplification methodology, and next-generation sequencing was performed using an Illumina mate-pair library protocol. Sequence reads were mapped to the human genome, and primers spanning the fusion junctions were used for validation polymerase chain reaction.
A total of 41 tumor samples were sequenced (33 adenocarcinomas ADs and eight squamous cell carcinomas SQCCs), with a range of three to 276 breakpoints per tumor identified. Lung tumors predicted to be independent primary tumors based on different histologic subtype did not share any genomic rearrangements. In patients with lung primary tumors and paired distant metastases, shared rearrangements were identified in all tumor pairs, emphasizing the patient specificity of identified breakpoints. Multifocal AD and SQCC samples were reviewed independently by two pulmonary pathologists. Concordance between histology and genomic data occurred in the majority of samples. Discrepant tumor samples were resolved by genome sequencing.
A diagnostic lineage test based on genomic rearrangements from mate-pair sequencing demonstrates promise for distinguishing independent primary from metastatic disease in lung cancer.
Carrier mobility in doped conjugated polymers is limited by Coulomb interactions with dopant counterions. This complicates studying the effect of the dopant's oxidation potential on carrier ...generation because different dopants have different Coulomb interactions with polarons on the polymer backbone. Here, dodecaborane (DDB)‐based dopants are used, which electrostatically shield counterions from carriers and have tunable redox potentials at constant size and shape. DDB dopants produce mobile carriers due to spatial separation of the counterion, and those with greater energetic offsets produce more carriers. Neutron reflectometry indicates that dopant infiltration into conjugated polymer films is redox‐potential‐driven. Remarkably, X‐ray scattering shows that despite their large 2‐nm size, DDBs intercalate into the crystalline polymer lamellae like small molecules, indicating that this is the preferred location for dopants of any size. These findings elucidate why doping conjugated polymers usually produces integer, rather than partial charge transfer: dopant counterions effectively intercalate into the lamellae, far from the polarons on the polymer backbone. Finally, it is shown that the IR spectrum provides a simple way to determine polaron mobility. Overall, higher oxidation potentials lead to higher doping efficiencies, with values reaching 100% for driving forces sufficient to dope poorly crystalline regions of the film.
The effect of dopant redox potential on the chemical doping of conjugated polymers is studied using dodecaborane dopants whose potential can be tuned at constant size and shape. The 2‐nm dodecaborane clusters preferentially intercalate into the polymer crystalline lamellae, and the doping efficiency increases with redox potential. The isolation of the counteranion from the hole leads to improved carrier mobility.
•Canopy habitats require more attention in times of global biodiversity loss.•Using LiDAR and canopy fogging, we link canopy structure and arthropod communities.•We use machine learning regression to ...select variables driving arthropod communities.•Canopy structure drives arthropod communities stronger than tree species identity.•Structural complexity and variability of inter and intra-canopy gaps are key drivers.
Forest canopies host an abundant but often neglected diversity of arthropods, which requires careful attention in times of ongoing biodiversity loss. Yet, how tree species composition interacts with canopy structure in shaping arthropod communities remains largely unknown. Here, by combining mobile laser scanning and insecticidal fogging with a machine learning algorithm, we studied which canopy architectural properties affect canopy arthropod communities in monospecific and mixed stands of broadleaved European beech and the coniferous Norway spruce and non-native Douglas fir in Germany. Evaluating the abundances and ecological guild diversity of ∼ 90,000 arthropods and 27 partly novel high-resolution structural variables, we identified vegetation volume and tree species identity as weak predictors of arthropod abundance and ecological guild diversity. In contrast, structural heterogeneity, i.e. structural complexity, vertical layering and variability of canopy gaps—which were highest in coniferous stands—were strong positive drivers. Despite this, arthropod ecological guild diversity was lower in non-native Douglas fir. Mixed stands had intermediate arthropod abundance and ecological guild diversity. Our study shows that habitat heterogeneity and tree species-identity are closely interlinked in shaping associated canopy arthropod communities. Positive effects of habitat heterogeneity on arthropod ecological guild diversity were often uncoupled from resource availability, and the key role of our novel intra-canopy gap indices suggests that they should be considered as indicators in future research on forest heterogeneity-diversity relationships. Broadleaf-conifer mixtures may be suitable to mediate negative tree-species identity effects when adapting forests to global change.
Literature reports that mature microRNA (miRNA) can be methylated at adenosine, guanosine and cytosine. However, the molecular mechanisms involved in cytosine methylation of miRNAs have not yet been ...fully elucidated. Here we investigated the biological role and underlying mechanism of cytosine methylation in miRNAs in glioblastoma multiforme (GBM).
RNA immunoprecipitation with the anti-5methylcytosine (5mC) antibody followed by Array, ELISA, dot blot, incorporation of a radio-labelled methyl group in miRNA, and miRNA bisulfite sequencing were perfomred to detect the cytosine methylation in mature miRNA. Cross-Linking immunoprecipiation qPCR, transfection with methylation/unmethylated mimic miRNA, luciferase promoter reporter plasmid, Biotin-tagged 3'UTR/mRNA or miRNA experiments and in vivo assays were used to investigate the role of methylated miRNAs. Finally, the prognostic value of methylated miRNAs was analyzed in a cohorte of GBM pateints.
Our study reveals that a significant fraction of miRNAs contains 5mC. Cellular experiments show that DNMT3A/AGO4 methylated miRNAs at cytosine residues inhibit the formation of miRNA/mRNA duplex and leading to the loss of their repressive function towards gene expression. In vivo experiments show that cytosine-methylation of miRNA abolishes the tumor suppressor function of miRNA-181a-5p miRNA for example. Our study also reveals that cytosine-methylation of miRNA-181a-5p results is associated a poor prognosis in GBM patients.
Together, our results indicate that the DNMT3A/AGO4-mediated cytosine methylation of miRNA negatively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
One of the most effective ways to tune the electronic properties of conjugated polymers is to dope them with small‐molecule oxidizing agents, creating holes on the polymer and molecular anions. ...Undesirably, strong electrostatic attraction from the anions of most dopants localizes the holes created on the polymer, reducing their mobility. Here, a new strategy utilizing a substituted boron cluster as a molecular dopant for conjugated polymers is employed. By designing the cluster to have a high redox potential and steric protection of the core‐localized electron density, highly delocalized polarons with mobilities equivalent to films doped with no anions present are obtained. AC Hall effect measurements show that P3HT films doped with these boron clusters have conductivities and polaron mobilities roughly an order of magnitude higher than films doped with F4TCNQ, even though the boron‐cluster‐doped films have poor crystallinity. Moreover, the number of free carriers approximately matches the number of boron clusters, yielding a doping efficiency of ≈100%. These results suggest that shielding the polaron from the anion is a critically important aspect for producing high carrier mobility, and that the high polymer crystallinity required with dopants such as F4TCNQ is primarily to keep the counterions far from the polymer backbone.
Chemical doping of conjugated polymers produces polarons via charge transfer. The counterions produced using traditional small‐molecule dopants are proximal to the polaron and thus limit polaron mobility due to Coulomb attraction. A boron cluster‐based dopant that shields the charge on the counterion from the polaron is designed. This allows the creation of nearly 100% free polarons with high mobility.