Acne dysbiosis happens when there is a microbial imbalance of the over-growth of
s (
) in the acne microbiome. In our previous study, we demonstrated that
(
, a probiotic skin bacterium) can exploit ...glycerol fermentation to produce short-chain fatty acids (SCFAs) which have antimicrobial activities to suppress the growth of
. Unlike glycerol, sucrose is chosen here as a selective fermentation initiator (SFI) that can specifically intensify the fermentation activity of
, but not
. A co-culture of
and fermenting
in the presence of sucrose significantly led to a reduction in the growth of
. The reduction was abolished when
was co-cultured with non-fermenting
. Results from nuclear magnetic resonance (NMR) analysis revealed four SCFAs (acetic acid, butyric acid, lactic acid, and succinic acid) were detectable in the media of
sucrose fermentation. To validate the interference of
sucrose fermentation with
, mouse ears were injected with both
and
plus sucrose or phosphate buffered saline (PBS). The level of macrophage-inflammatory protein-2 (MIP-2) and the number of
in ears injected with two bacteria plus sucrose were considerably lower than those in ears injected with two bacteria plus PBS. Our results demonstrate a precision microbiome approach by using sucrose as a SFI for
, holding future potential as a novel modality to equilibrate dysbiotic acne.
Speckle tracking is the latest available technology in echocardiography. However, the technology is still mainly used as a research tool. The potential applications of speckle tracking are many, ...including cardiac synchronization, regional wall motion analysis, and in the areas of cardiac mechanic studies. This review presents the background theory of speckle tracking echocardiography (STE) and how this technology can be extended to velocity vector analysis, strain, and torsion measurements. The interpretations of these measurements are covered. We also present some potential applications in the critical care setting.
Speckle tracking is almost always available in high-end ultrasound machines. The technology has been applied to velocity vector analysis, strain and strain rate measurements, and twist and torsion analysis. Torsion analysis and velocity vector analyses are impossible without using speckle tracking. Speckle tracking-derived strain is superior to tissue Doppler strain because it is angle-independent. A number of studies demonstrated that STE is useful in left and right heart assessments and can be used in assessing preload and afterload.
Speckle tracking can be used to measure instantaneous myocardial contractility, strain, and left ventricular torsion. It is still a research tool at present, but shows the promise of being a clinical tool in the future.
Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3'-triiodothyronine (T3) is achieved by the ...sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxia-inducible factor-dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1alpha interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1alpha and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3.
This project addresses the issue of detecting intruders from hiding behind privacy-protecting anonymity networks. The freely available Tor and the SOCKS proxy services have been popular tools that ...provide circuit-based anonymous connections to network users. However, recent security breaches reveal that SSH and HTTPS have been used to launch attacks by malicious users by taking advantage of these services to hide their identities. This paper investigates strategies to detect SSH and HTTPS connections via the circuit-based anonymity networks, to help servers and websites defend against anonymous intruders. We evaluate our approaches with SSH and HTTPS connections and show that they achieve high performance for both applications. Our detection algorithms are based on the extra latency delays introduced by the presence of the anonymity networks. Since the latency disparity is sensitive to the location of the anonymity network, our algorithms must be evaluated in the most challenging scenarios. The detection rates for all four combinations of SSH/HTTPS applications via Tor/SOCKS networks were very high, with a low false-positive rate. To demonstrate the robustness of our approach in the Tor case, we tested our method in multiple Tor circuit node selection strategies. The approach can be applied to other applications meeting the same criteria.
Transthoracic 3D cardiac analysis is enticing in its potential simplicity and wealth of data available. It has been suggested to be accurate vs magnetic resonance imaging in relatively stable ...patients, but feasibility and agreement with conventional echocardiographic assessment of stroke volume (SV) have not been thoroughly assessed in critically ill patients, who are traditionally harder to image. The objectives of this study were to compare 3D transthoracic volumetric analysis vs Doppler assessment of SV (which is suggested to be accurate in the critically ill) and Simpson's biplane assessment in a cohort typical of the intensive care unit (ICU), where accurate assessment is important: mechanically ventilated patients with a significant ventilation/perfusion (V/Q) mismatch. We hypothesised that it would be feasible but might lack agreement.
Patients were imaged within 24 hours of admission. Inclusion criteria were adult patients, V/Q mismatch present (defined as a ratio of arterial oxygen partial pressure to fractional inspired oxygen < 300), and mechanically ventilated with Doppler SV assessment possible. Biventricular echocardiographic volumetric analysis was performed using Siemens SC2000 along with standard Simpson's biplane and Doppler SV assessment. 3D images were unacceptable if two segments or more were unable to be seen in two volumetric planes. 3D left ventricular (3DLV) and 3D right ventricular (3DRV) analyses were performed with the Tomtec Imaging and Siemens Acuson platforms, respectively.
Ninety-two patients were included (83 in sinus, 9 in atrial fibrillation). 3DLV and 3DRV analyses were feasible in 72% and 55% of patients, respectively; however, they underestimated SV compared with Doppler by 2.6 ml (± 10.4) and 4.1 ml (± 15.4), respectively. Limits of agreement for 2D, 3DLV and 3DRV volumetric analysis techniques were large.
3DLV and 3DRV volumetric analyses appear feasible (obtainable) in the majority of mechanically ventilated ICU patients. Compared with the Doppler method, 3DLV and 3DRV volumetric analyses underestimate SV. The large limits of agreement between the methods also cast doubt on their comparability. Given the scenarios in which SV analysis is required (e.g., assessment of cardiac performance), our study cautions against the use of 3D SV clinically.
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two ...complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS. The majority of pSTAT5 peaks contain a central palindromic GAS element, TTCYXRGAA. There was significant enrichment for GATA motifs and CACCC-box motifs within the neighbourhood of pSTAT5-bound peaks, and GATA1 and/or KLF1 co-occupancy at many sites. Using 4sU-RNA-seq we determined the EPO-induced transcriptome and validated differentially expressed genes using dynamic CAGE data and qRT-PCR. We identified known direct pSTAT5 target genes such as Bcl2l1, Pim1 and Cish, and many new targets likely to be involved in driving erythroid cell differentiation including those involved in mRNA splicing (Rbm25), epigenetic regulation (Suv420h2), and EpoR turnover (Clint1/EpsinR). Some of these new EpoR-JAK2-pSTAT5 target genes could be used as biomarkers for monitoring disease activity in polycythaemia vera, and for monitoring responses to JAK inhibitors.
Patients with severe clinical manifestations of coronavirus disease 2019 (COVID-19) present particular diagnostic and management challenges to critical care physicians, including identifying and ...responding to concurrent bacterial and fungal coinfections. This study evaluates risk factors for in-hospital mortality in patients admitted to the intensive care unit with severe COVID-19 during circulation of the B.1.617.2 (Delta) variant, including the impact of immunomodulators and bacterial and/or fungal coinfection. This retrospective cohort study enrolled patients with severe COVID-19. A Cox proportional hazard ratio analysis identified risk factors for in-hospital mortality. Outcomes were also compared between patients receiving and not receiving immunomodulatory therapy alongside standard care. Ninety patients admitted to the intensive care unit were enrolled. On multivariate analysis, the greatest risk factors for in-hospital mortality were invasive mechanical ventilation (hazard ratio (HR) 1/4 15.27; 95% confidence interval (CI) 3.29-71.0; P < 0.001), elevated body mass index (HR 1/4 1.07 per unit; 95% CI 1.02-1.13; P 1/4 0.007) and older age (HR 1/4 1.53 per decade; 95% CI 1.05-2.24; P 1/4 0.028). Bacterial and/or fungal coinfection occurred at equal frequency in patients receiving and not receiving immunomodulatory therapy. However, in patients receiving immunomodulators, coinfection carried a significantly higher mortality risk (63.0%) compared with those without coinfection (15.4%; P 1/4 0.038). Mortality from severe COVID-19 is significantly higher in older patients and those with elevated body mass index and requiring mechanical ventilation. Immunomodulatory therapy necessitates vigilance towards evolving coinfection in the intensive care setting.
There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling ...of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole-blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole-blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3,677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3,677 genes, biological pathway analysis identified 86 genes significantly downregulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis, including lymphocyte depletion, reduced T-lymphocyte activation, and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of downregulation found in nonsurvivors compared with survivors. The results show that whole-blood gene expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression-based assay, to assess immunosuppression, and to guide immunotherapy in future clinical trials.
PurposeThe purpose of this paper is to explore differences in the behavioural intentions of consumers in different countries, i.e. Japan, UK and Taiwan by employing a customer-based value ...model.Design/methodology/approachA total of 305 consumers of one of Japan's brand and chain stores, Muji, were interviewed. The moderating effects of cultural and economic distances from the home country of the firm were also tested.FindingsThe results showed that cultural distance moderates the impact of symbolic, experiential and aesthetic value on purchase intention; however, economic distance was found to only influence monetary value.Originality/valueCross-cultural studies on customer value in the retailing industry are limited. The findings from this study offer several implications for those firms that adopt a globalization strategy using another perspective, while to some degree glocalization could be a better strategy.
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