Anthrax, but Not Bacillus anthracis?

The article focuses on the other possible agents of anthrax aside from bacillus anthracis and other soil dwelling bacterium of the genus bacillus. It is stated that bacillus anthracis is a close relative of bacillus cereus and bacillus thuringiensis because of the presence of two large virulence plasmids, pXO1 and pXO2. The authors believe that bacillus cereus isolates can harbor either one or both of the B. anthracis plasmids, and they may or may not harbor anthrax toxin genes

DNA sequence conservation between the Bacillus anthracis pXO2 plasmid and genomic sequence from closely related bacteria

BACKGROUND: Complete sequencing and annotation of the 96.2 kb Bacillus anthracis plasmid, pXO2, predicted 85 open reading frames (ORFs). Bacillus cereus and Bacillus thuringiensis isolates that ranged in genomic similarity to B. anthracis, as determined by amplified fragment length polymorphism (AFLP) analysis, were examined by PCR for the presence of sequences similar to 47 pXO2 ORFs. RESULTS: The two most distantly related isolates examined, B. thuringiensis 33679 and B. thuringiensis AWO6, produced the greatest number of ORF sequences similar to pXO2; 10 detected in 33679 and 16 in AWO6. No more than two of the pXO2 ORFs were detected in any one of the remaining isolates. Dot-blot DNA hybridizations between pXO2 ORF fragments and total genomic DNA from AWO6 were consistent with the PCR assay results for this isolate and also revealed nine additional ORFs shared between these two bacteria. Sequences similar to the B. anthracis cap genes or their regulator, acpA, were not detected among any of the examined isolates. CONCLUSIONS: The presence of pXO2 sequences in the other Bacillus isolates did not correlate with genomic relatedness established by AFLP analysis. The presence of pXO2 ORF sequences in other Bacillus species suggests the possibility that certain pXO2 plasmid gene functions may also be present in other closely related bacteria

Direct hospital cost of outcome pathways in implant-based reconstruction with acellular dermal matrices

BACKGROUND: Current cost data on tissue expansion followed by exchange for permanent implant (TE/I) reconstruction lack a necessary assessment of the experience of a heterogenous breast cancer patient population and their multiple outcome pathways. We extend our previous analysis to that of direct hospital cost as bundling of payments is likely to follow the changing centralization of cancer care at the hospital level. METHODS: We performed a retrospective analysis (2003–2009) of TE/I reconstructions with or without an acellular dermal matrix (ADM), namely Alloderm RTM. Postreconstructive events were analyzed and organized into outcome pathways as previously described. Aggregated and normalized inpatient and outpatient hospital direct costs and physician reimbursement were generated for each outcome pathway with or without ADM. RESULTS: Three hundred sixty-seven patients were analyzed. The average 2-year hospital direct cost per TE/I breast reconstruction patient was $11,862 in the +ADM and$12,319 in the −ADM groups (P > 0.05). Initial reconstructions were costlier in the +ADM ($6,868) than in the −ADM ($5,615) group, but the average cost of subsequent postreconstructive events within 2 years was significantly lower in +ADM ($5,176) than −ADM ($6,704) patients (P < 0.05). When a complication occurred, but reconstruction was still completed within 2 years, greater costs were incurred in the −ADM than in the +ADM group for most scenarios, leading to a net equalization of cost between study groups. CONCLUSION: Although direct hospital cost is an important factor for resource and fund allocation, it should not remain the sole factor when deciding to use ADM in TE/I reconstruction

Hydroxytyrosol and oleuropein-enriched extracts obtained from olive oil wastes and by-products as active antioxidant ingredients for poly (Vinyl alcohol)-based films

Oxidative stability of food is one of the most important parameters affecting integrity and consequently nutritional properties of dietary constituents. Antioxidants are widely used to avoid deterioration during transformation, packaging, and storage of food. In this paper, novel poly (vinyl alcohol) (PVA)-based films were prepared by solvent casting method adding an hydroxytyrosol-enriched extract (HTyrE) or an oleuropein-enriched extract (OleE) in different percentages (5, 10 and 20% w/w) and a combination of both at 5% w/w. Both extracts were obtained from olive oil wastes and by-products using a sustainable process based on membrane technologies. Qualitative and quantitative analysis of each sample carried out by high performance liquid chromatography (HPLC) and nuclear resonance magnetic spectroscopy (NMR) proved that the main components were hydroxytyrosol (HTyr) and oleuropein (Ole), respectively, two well-known antioxidant bioactive compounds found in Olea europaea L. All novel formulations were characterized investigating their morphological, optical and antioxidant properties. The promising performances suggest a potential use in active food packaging to preserve oxidative-sensitive food products. Moreover, this research represents a valuable example of reuse and valorization of agro-industrial wastes and by-products according to the circular economy model

Involvement of β-adrenoceptors in the cardiovascular responses induced by selective adenosine A2A and A2B receptor agonists

A2A and A2B adenosine receptors produce regionally selective regulation of vascular tone and elicit differing effects on mean arterial pressure (MAP), whilst inducing tachycardia. The tachycardia induced by the stimulation of A2A or A2B receptors has been suggested to be mediated by a reflex increase in sympathetic activity. Here, we have investigated the role of β1- and β2-adrenoceptors in mediating the different cardiovascular responses to selective A2A and A2B receptor stimulation. Hemodynamic variables were measured in conscious male Sprague-Dawley rats (350–450 g) via pulsed Doppler flowmetry. The effect of intravenous infusion (3 min per dose) of the A2A-selective agonist CGS 21680 (0.1, 0.3, 1.0 µg.kg−1.min−1) or the A2B-selective agonist BAY 60–6583 (4.0, 13.3, 40.0 µg.kg−1.min−1) in the absence or following pre-treatment with the non-selective β-antagonist propranolol (1.0 mg.kg−1), the selective β1-antagonist CGP 20712A (200 µg.kg−1), or the selective β2-antagonist ICI 118,551 (2.0 mg.kg−1) was investigated (maintenance doses also administered). CGP 20712A and propranolol significantly reduced the tachycardic response to CGS 21680, with no change in the effect on MAP. ICI 118,551 increased BAY 60–6583-mediated renal and mesenteric flows, but did not affect the heart rate response. CGP 20712A attenuated the BAY 60–6583-induced tachycardia. These data imply a direct stimulation of the sympathetic activity via cardiac β1-adrenoceptors as a mechanism for the A2A- and A2B-induced tachycardia. However, the regionally selective effects of A2B agonists on vascular conductance were independent of sympathetic activity and may be exploitable for the treatment of acute kidney injury and mesenteric ischemia

Regionally selective cardiovascular responses to adenosine A2A and A2B receptor activation

Adenosine is a local mediator that regulates changes in the cardiovascular system via activation of four G protein-coupled receptors (A1, A2A, A2B, A3). Here, we have investigated the effect of A2A and A2B-selective agonists on vasodilatation in three distinct vascular beds of the rat cardiovascular system. NanoBRET ligand binding studies were used to confirm receptor selectivity. The regional hemodynamic effects of adenosine A2A and A2B selective agonists were investigated in conscious rats. Male Sprague-Dawley rats (350–450 g) were chronically implanted with pulsed Doppler flow probes on the renal artery, mesenteric artery, and the descending abdominal aorta. Cardiovascular responses were measured following intravenous infusion (3 min for each dose) of the A2A-selective agonist CGS 21680 (0.1, 0.3, 1 µg kg−1 min−1) or the A2B-selective agonist BAY 60-6583 (4,13.3, 40 µg kg−1 min−1) following predosing with the A2A-selective antagonist SCH 58261 (0.1 or 1 mg kg−1 min−1), the A2B/A2A antagonist PSB 1115 (10 mg kg−1 min−1) or vehicle. The A2A-selective agonist CGS 21680 produced a striking increase in heart rate (HR) and hindquarters vascular conductance (VC) that was accompanied by a significant decrease in mean arterial pressure (MAP) in conscious rats. In marked contrast, the A2B-selective agonist BAY 60-6583 significantly increased HR and VC in the renal and mesenteric vascular beds, but not in the hindquarters. Taken together, these data indicate that A2A and A2B receptors are regionally selective in their regulation of vascular tone. These results suggest that the development of A2B receptor agonists to induce vasodilatation in the kidney may provide a good therapeutic approach for the treatment of acute kidney injury

COVID-19-Induced Myocarditis: Pathophysiological Roles of ACE2 and Toll-like Receptors

The clinical manifestations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection responsible for coronavirus disease 2019 (COVID-19) commonly include dyspnoea and fatigue, and they primarily involve the lungs. However, extra-pulmonary organ dysfunctions, particularly affecting the cardiovascular system, have also been observed following COVID-19 infection. In this context, several cardiac complications have been reported, including hypertension, thromboembolism, arrythmia and heart failure, with myocardial injury and myocarditis being the most frequent. These secondary myocardial inflammatory responses appear to be associated with a poorer disease course and increased mortality in patients with severe COVID-19. In addition, numerous episodes of myocarditis have been reported as a complication of COVID-19 mRNA vaccinations, especially in young adult males. Changes in the cell surface expression of angiotensin-converting enzyme 2 (ACE2) and direct injury to cardiomyocytes resulting from exaggerated immune responses to COVID-19 are just some of the mechanisms that may explain the pathogenesis of COVID-19-induced myocarditis. Here, we review the pathophysiological mechanisms underlying myocarditis associated with COVID-19 infection, with a particular focus on the involvement of ACE2 and Toll-like receptors (TLRs)

Loss of the xeroderma pigmentosum group B protein binding site impairs p210 BCR/ABL1 leukemogenic activity

Previous studies have demonstrated that p210 BCR/ABL1 interacts directly with the xeroderma pigmentosum group B (XPB) protein, and that XPB is phosphorylated on tyrosine in cells that express p210 BCR/ABL1. In the current study, we have constructed a p210 BCR/ABL1 mutant that can no longer bind to XPB. The mutant has normal kinase activity and interacts with GRB2, but can no longer phosphorylate XPB. Loss of XPB binding is associated with reduced expression of c-MYC and reduced transforming potential in ex-vivo clonogenicity assays, but does not affect nucleotide excision repair in lymphoid or myeloid cells. When examined in a bone marrow transplantation (BMT) model for chronic myelogenous leukemia, mice that express the mutant exhibit attenuated myeloproliferation and lymphoproliferation when compared with mice that express unmodified p210 BCR/ABL1. Thus, the mutant-transplanted mice show predominantly neutrophilic expansion and altered progenitor expansion, and have significantly extended lifespans. This was confirmed in a BMT model for B-cell acute lymphoblastic leukemia, wherein the majority of the mutant-transplanted mice remain disease free. These results suggest that the interaction between p210 BCR/ABL1 and XPB can contribute to disease progression by influencing the lineage commitment of lymphoid and myeloid progenitors