Summary
Background There have been conflicting data regarding the prevalence and clinicopathological characteristics of BRAF and NRAS mutations in primary cutaneous melanoma.
Objectives To solve ...this controversy, this study used a meta‐analysis to evaluate the frequencies of BRAF and NRAS mutations, and the relationship between these mutations and clinicopathological parameters of cutaneous melanoma.
Methods Data from studies published between 1989 and 2010 were combined. The BRAF and NRAS mutations were reported in 36 and 31 studies involving 2521 and 1972 patients, respectively. The effect sizes of outcome parameters were calculated by odds ratios (OR).
Results BRAF and NRAS mutations were reported in 41% and 18% of cutaneous melanomas, respectively. The mutations were associated with histological subtype and tumour site, but not with age and sex. The BRAF mutation was frequently detected in patients with superficial spreading melanoma (OR = 2·021; P < 0·001) and in melanomas arising in nonchronic sun‐damaged skin (OR = 2·043; P = 0·001). In contrast, the NRAS mutation was frequently evident in patients with nodular melanoma (OR = 1·894; P < 0·001) and in melanomas arising in chronic sun‐damaged skin (OR = 1·887; P = 0·018).
Conclusions This pooled analysis shows that the incidences of BRAF and NRAS mutations in cutaneous melanomas differ according to histological type and tumour location based on the degree of sun exposure.
MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18–22 nucleotides) have received little ...attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.
Summary
Smoking is a major environmental factor associated with periodontal diseases. However, we still have a very limited understanding of the relationship between smoking and subgingival ...microflora in the global population. Here, we investigated the composition of subgingival bacterial communities from the pooled plaque samples of smokers and non‐smokers, 134 samples in each group, in Korean patients with moderate chronic periodontitis using 16S rRNA gene‐based pyrosequencing. A total of 17,927 reads were analyzed and classified into 12 phyla, 126 genera, and 394 species. Differences in bacterial communities between smokers and non‐smokers were examined at all phylogenetic levels. The genera Fusobacterium, Fretibacterium, Streptococcus, Veillonella, Corynebacterium, TM7, and Filifactor were abundant in smokers. On the other hand, Prevotella, Campylobacter, Aggregatibacter, Veillonellaceae GQ422718, Haemophilus, and Prevotellaceae were less abundant in smokers. Among species‐level taxa occupying > 1% of whole subgingival microbiome of smokers, higher abundance (≥ 2.0‐fold compared to non‐smokers) of seven species or operational taxonomic units (OTUs) was found: Fusobacterium nucleatum, Neisseria sicca, Neisseria oralis, Corynebacterium matruchotii, Veillonella dispar, Filifactor alocis, and Fretibacterium AY349371. On the other hand, lower abundance of 11 species or OTUs was found in smokers: Neisseria elongata, six Prevotella species or OTUs, Fusobacterium canifelinum, Aggregatibacter AM420165, Selenomonas OTU, and Veillonellaceae GU470897. Species richness and evenness were similar between the groups whereas diversity was greater in smokers than non‐smokers. Collectively, the results of the present study indicate that differences exist in the subgingival bacterial community between smoker and non‐smoker patients with chronic moderate periodontitis in Korea, suggesting that cigarette smoking considerably affects subgingival bacterial ecology.
The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. In this review, we summarize recent insights ...into the mechanism of ATM activation, focusing on the role of the Mre11/Rad50/Nbs1 (MRN) complex in this process. We also compare observations of the ATM activation process in different biological systems and highlight potential candidates for cellular factors that may participate in regulating ATM activity in human cells.
The contagiousness and deadliness of COVID-19 have necessitated drastic social management to halt transmission. The immediate effects of a nationwide lockdown were investigated by comparing matched ...samples of New Zealanders assessed before (Nprelockdown = 1,003) and during the first 18 days of lockdown (Nlockdown = 1,003). Two categories of outcomes were examined: (a) institutional trust and attitudes toward the nation and government and (b) health and well-being. Applying propensity score matching to approximate the conditions of a randomized controlled experiment, the study found that people in the pandemic/lockdown group reported higher trust in science, politicians, and police, higher levels of patriotism, and higher rates of mental distress compared to people in the prelockdown prepandemic group. Results were confirmed in within-subjects analyses. The study highlights social connectedness, resilience, and vulnerability in the face of adversity and has applied implications for how countries face this global challenge.
Public Significance Statement
This study describes the immediate effects of the COVID-19 pandemic and nationwide lockdown on levels of institutional trust and attitudes toward the nation and government and health and well-being in New Zealand, with implications for other nations. Our results suggest that a strong national response to COVID-19 may bolster national attachment and increase trust in the bodies determining and enforcing lockdown guidelines. Against a backdrop of general resilience, small increases in psychological distress serve as a warning about potential psychological consequences of lockdown and isolation.
Aims
Detection/Quantification of RNA viruses is mostly done by reverse‐transcriptase (RT)‐(q)PCR, but it does not distinguish between infectious and noninfectious viruses. Our aim was to test, how ...different pretreatments before RT‐qPCR could eliminate positivity originated from external nucleic acids or genomes of damaged particles.
Methods and Results
Heat‐inactivated (80°C for 10 min) rotavirus Wa strain and faecal samples containing rotavirus or norovirus were treated with PMA/PMAxx, benzonase or crude extract RNase prior to RT‐qPCR. PMA/PMAxx pretreatments were not consistently efficient for RV, although they seemed to work to some extent for heat‐inactivated norovirus. Benzonase and RNase provided consistently 2·2–2·8 log10 reductions in the titre of faecal rotavirus.
Conclusions
All pretreatments need to be further validated for each virus separately, taking into account sample matrix and inactivation conditions. Although none of the pretreatments could completely render inactivated viruses undetectable, RNase worked most consistently for both rota‐ and norovirus.
Significance and Impact of the Study
This study sheds light on capacity of the most common pre‐RT‐qPCR treatments to eliminate damaged, noninfectious rotaviruses and noroviruses after thermal treatment. To our knowledge, this is the first time, when benzonase has been used in this context.
The topotactic phase transition in SrCoO
(x = 2.5-3.0) makes it possible to reversibly transit between the two distinct phases, i.e. the brownmillerite SrCoO
that is a room-temperature ...antiferromagnetic insulator (AFM-I) and the perovskite SrCoO
that is a ferromagnetic metal (FM-M), owing to their multiple valence states. For the intermediate x values, the two distinct phases are expected to strongly compete with each other. With oxidation of SrCoO
, however, it has been conjectured that the magnetic transition is decoupled to the electronic phase transition, i.e., the AFM-to-FM transition occurs before the insulator-to-metal transition (IMT), which is still controversial. Here, we bridge the gap between the two-phase transitions by density-functional theory calculations combined with optical spectroscopy. We confirm that the IMT actually occurs concomitantly with the FM transition near the oxygen content x = 2.75. Strong charge-spin coupling drives the concurrent IMT and AFM-to-FM transition, which fosters the near room-T magnetic transition characteristic. Ultimately, our study demonstrates that SrCoO
is an intriguingly rare candidate for inducing coupled magnetic and electronic transition via fast and reversible redox reactions.
Summary
Background
Rifaximin might decrease the risk of portal hypertension‐related complications by controlling small intestinal bacterial overgrowth.
Aim
To evaluate whether rifaximin was ...associated with the risk of death and cirrhotic complications.
Methods
We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non‐HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding.
Results
In the non‐HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio aHR, 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile‐associated diarrhoea was not different between the groups (aHR, 0.028; P = .338).
Conclusions
In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
Linked Content
This article is linked to Juang, Kang et al, Wang et al, and Borentain et al papers. To view these papers visit https://doi.org/10.1111/apt.14325, https://doi.org/10.1111/apt.14343, https://doi.org/10.1111/apt.14353 and https://doi.org/10.1111/apt.14516.
Aims
Urinary tract infections are caused primarily by uropathogenic Escherichia coli (UPEC), and indwelling catheters are usually colonized by UPEC biofilms tolerant to common antibiotics. Hence, ...UPEC biofilms pose a substantial challenge, and there is an urgent need for effective control strategies.
Methods and Results
In this study, 79 essential oils were screened for antibiofilm ability against UPEC. Components of active oils were identified, and their antibiofilm activities were also investigated using 96‐well plates with crystal violet assay, scanning electron microscopy, and confocal laser scanning microscopy. Oregano oil and thyme red oil and their major common constituents, carvacrol and thymol, significantly inhibited UPEC biofilm formation at subinhibitory concentrations (<0·01%). These findings were supported by observations that carvacrol and thymol reduced fimbriae production and the swarming motility of UPEC. Furthermore, carvacrol and thymol markedly decreased the hemagglutinating ability of UPEC, and UPEC was more easily killed by human whole blood in the presence of carvacrol and thymol.
Conclusions
Carvacrol‐rich oregano oil and thymol‐rich thyme red oil have high antibiofilm and antivirulence activities against UPEC.
Significance and Impact of Study
In the wake of rising antimicrobial resistance, we envisage that carvacrol and thymol could be used to prevent biofilm formation by UPEC and to reduce its virulence.
Abstract
The circulation pathways and subsurface cooling and freshening of warm deep water on the central Amundsen Sea shelf are deduced from hydrographic transects and four subsurface moorings. The ...Amundsen Sea continental shelf is intersected by the Dotson trough (DT), leading from the outer shelf to the deep basins on the inner shelf. During the measurement period, warm deep water was observed to flow southward on the eastern side of DT in approximate geostrophic balance. A northward outflow from the shelf was also observed along the bottom in the western side of DT. Estimates of the flow rate suggest that up to one-third of the inflowing warm deep water leaves the shelf area below the thermocline in this deep outflow. The deep current was 1.2°C colder and 0.3 psu fresher than the inflow, but still warm, salty, and dense compared to the overlying water mass. The temperature and salinity properties suggest that the cooling and freshening process is induced by subsurface melting of glacial ice, possibly from basal melting of Dotson and Getz ice shelves. New heat budgets are presented, with a southward oceanic heat transport of 3.3 TW on the eastern side of the DT, a northward oceanic heat transport of 0.5–1.6 TW on the western side, and an ocean-to-glacier heat flux of 0.9–2.53 TW, equivalent to melting glacial ice at the rate of 83–237 km3 yr−1. Recent satellite-based estimates of basal melt rates for the glaciers suggest comparable values for the Getz and Dotson ice shelves.
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