Octreotide acetate, the active pharmaceutical ingredient in the long-acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide ...hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous
H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear
C,
N, and aromatic
H nuclei are available. Here, using state-of-the-art 1D and 2D homo- and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for
CO and
NH of F1,
NH of C2, and
NζHζ of K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D
H/
C/
N solid-state NMR (SSNMR) spectra showing the potential applicability of
C/
N SSNMR for octreotide drug product characterization.
Recent advancements in radiation detection and computer vision have enabled small unmanned aerial systems (sUASs) to produce 3-D radiation maps, for example, composed of gamma rays and neutrons, in ...real time. Currently, these state-of-the-art systems require two operators: one to pilot the sUAS and another operator to monitor the detected radiation. In this work, we present a system that integrates real-time 3-D radiation visualization with semi-autonomous sUAS control. Our virtual reality (VR) interface enables a single operator to define trajectories using waypoints to abstract complex flight control and utilize the semi-autonomous maneuvering capabilities of the sUAS. The interface also displays a fused radiation visualization and environment map, thereby enabling simultaneous remote operation and radiation monitoring by a single operator. This interface and its underlying framework serves as the basis for development of a single system that can deploy and autonomously control a fleet of radiation-mapping sUASs.
Since December 2019, the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - Corona Virus-2) has been spreading rapidly in the sense of a global pandemic. This poses significant ...challenges for clinicians and hospitals and is placing unprecedented strain on the healthcare systems of many countries. The majority of patients with Coronavirus Disease 2019 (COVID-19) present with only mild symptoms such as cough and fever. However, about 6 % require hospitalization. Early clarification of whether inpatient and, if necessary, intensive care treatment is medically appropriate and desired by the patient is of particular importance in the pandemic. Acute hypoxemic respiratory insufficiency with dyspnea and high respiratory rate (> 30/min) usually leads to admission to the intensive care unit. Often, bilateral pulmonary infiltrates/consolidations or even pulmonary emboli are already found on imaging. As the disease progresses, some of these patients develop acute respiratory distress syndrome (ARDS). Mortality reduction of available drug therapy in severe COVID-19 disease has only been demonstrated for dexamethasone in randomized controlled trials. The main goal of supportive therapy is to ensure adequate oxygenation. In this regard, invasive ventilation and repeated prone positioning are important elements in the treatment of severely hypoxemic COVID-19 patients. Strict adherence to basic hygiene, including hand hygiene, and the correct wearing of adequate personal protective equipment are essential when handling patients. Medically necessary actions on patients that could result in aerosol formation should be performed with extreme care and preparation.
Introduction
The relation between rheumatoid arthritis (RA) and periodontitis (PD) has been investigated ever since the discovery of the citrullinating enzyme peptidyl arginine deaminase presents in ...the oral bacterium
Porphyromonas gingivalis
. Recently, we demonstrated the presence of RA autoantibodies, especially of IgA anti-citrullinated protein antibody (ACPA), in gingival crevicular fluid (GCF) of Indonesian patients with and without RA or PD which might indicate the local formation of RA antibodies in the periodontium.
Aim
The purpose of this study was to assess whether the subgingival microbiome is related to the presence of IgA ACPA in the GCF of healthy individuals with or without PD.
Patients and Methods
Healthy individuals with a known periodontal status and high IgA ACPA (>0.1 U/ml) in GCF (
n
= 27) were selected and matched for age, gender, periodontal status, and smoking status with 27 healthy individuals without IgA ACPA in their GCF. Taxonomic profiling of the subgingival microbiome was based on bacterial 16S rRNA gene sequencing. Downstream analyses were performed to assess compositional differences between healthy subjects with or without IgA ACPA in GCF and with or without PD.
Results
Between groups with or without PD, or with or without IgA ACPA in GCF, no differences in alpha diversity were seen. Beta diversity was different between groups with or without PD (
p
< 0.0001), and a trend was seen in subjects with PD between subjects with or without IgA ACPA in GCF (
p
= 0.084). Linear discriminant analysis effect size (LEfSe) revealed no significant differences in the total population between subjects with IgA ACPA compared to subjects without IgA ACPA in GCF. Although
Porphyromonas
was not identified by LEfSe, its relative abundance was significantly higher in healthy individuals with high IgA ACPA in GCF compared to individuals without IgA ACPA in GCF (
p
= 0.0363). Zooming in on the subgroup with PD, LEfSe revealed that species
Neisseriaceae, Tannerella
, and
Haemophilus
were more abundant in the subjects with IgA ACPA in GCF compared to subjects without IgA ACPA in GCF.
Conclusion
Periodontitis and certain taxa, including
Porphyromonas
, seem to be associated with the local presence of ACPA in the periodontium.
A particular role for Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) has been suggested in periodontitis and rheumatoid arthritis (RA), as these bacteria could initiate ...the formation of rheumatoid factor (RF) and anticitrullinated protein autoantibodies (ACPA). We assessed whether serum antibodies against Pg and Aa in RA patients and non-RA controls reflect the subgingival presence of Pg and Aa, and evaluated the relationship of these antibodies to the severity of periodontal inflammation and RA-specific serum autoantibodies. In 70 Indonesian RA patients and 70 non-RA controls, the subgingival presence of Pg and Aa was assessed by bacterial 16S rRNA gene sequencing, and serum IgG levels specific for Pg and Aa were determined. In parallel, serum levels of ACPA (ACPA:IgG,IgA) and RF (RF:IgM,IgA) were measured. The extent of periodontal inflammation was assessed by the periodontal inflamed surface area. In both RA patients and the controls, the presence of subgingival Pg and Aa was comparable, anti-Pg and anti-Aa antibody levels were associated with the subgingival presence of Pg and Aa, and anti-Pg did not correlate with ACPA or RF levels. The subgingival Pg and Aa were not related to RA. No noteworthy correlation was detected between the antibodies against Pg and Aa, and RA-specific autoantibodies.
Exploring reliable electrolytes for aluminum ion batteries requires an in-depth understanding of the behavior of aluminum ions in ethereal-organic solvents. Electrolytes comprised of aluminum ...trifluoromethanesulfonate (Al-triflate) in tetrahydrofuran (THF) were investigated computationally and experimentally. Optimized geometries, redox potentials and vibrational frequencies of species likely to be present in the electrolyte were calculated by DFT and then measured spectroscopically and electrochemically. Aluminum appears to be electrochemically active in THF with a reduction onset near 0 V vs. Al/Al3+. Spectroscopic measurements reveal explicit evidence for the presence of two concentration-dependent ionic environments for the triflate anions; outer shell ligands and Al-bound triflates. Additionally, ionic conductivities of around 2.5 mS/cm have been measured for these electrolytes around 0.8M.
Apoptosis signaling is involved in both physiological tissue homeostasis and acute and chronic diseases. The role of regulatory apoptosis signaling molecules and their organ-specific functions are ...less defined. Therefore, we investigated the loss of the anti-apoptotic cellular FLICE-inhibitory protein (cFLIP) and the mechanisms of the resulting lethal organ failure in vivo using inducible knockout mice. These were generated by crossing floxed cFLIP mice to a tamoxifen inducible Rosa26-creERT2 mouse strain. Death following global loss of cFLIP resulted from liver failure, accumulation of M1-polarized macrophages and accompanying hepatic cell death and inflammation. Apoptosis was also prominent in immune cells, the kidney and intestinal epithelial cells (IECs) but not in cardiomyocytes. Cellular injury led to the release of damage-associated molecular patterns (DAMPs) and the induction of innate immune receptors including toll-like receptors (TLRs) 4 and 9, and stimulator of interferon genes (STING). Transplantation of bone marrow with intact cFLIP or depletion of macrophages prevented the phenotype of acute liver failure. Interestingly, compound deletion of cFLIP in bone marrow-derived cells and hepatocytes did not promote organ failure. Thus, cFLIP exerts a critical role in tissue homeostasis by preventing the activation of monocytic cells and innate immunity, which causes cell death and inflammation in susceptible tissues. These results encourage the development of organ-specific anti-apoptotic and anti-inflammatory therapies in acute organ failure.
Lessons to be learned from periodontitis Janssen, Koen M J; Vissink, Arjan; de Smit, Menke J ...
Current opinion in rheumatology
25, Številka:
2
Journal Article
Odprti dostop
This article reviews the link between periodontitis and rheumatoid arthritis (RA) with regard to similarities in genetic risk factors and immunopathogenesis. Emphasis is paid to the potential role of ...the periodontal pathogen Porphyromonas gingivalis in the etiopathogenesis of both periodontitis and RA, in particular by post-translational modification of arginine into citrulline.
P. gingivalis, a major periodontal pathogen, is presently known as the only bacterium in the oral flora which contains a peptidyl arginine deiminase enzyme (PAD). This enzyme is necessary for citrullination. As a result, citrullinated proteins and P. gingivalis PAD, PAD2 and PAD4 (expressed by infiltrating neutrophils) are found in periodontal tissues. Autoantibodies directed to citrullinated proteins, so-called anticitrullinated protein antibodies (ACPAs), are found to be present in gingival crevicular fluid originating from inflamed gingival tissue. Furthermore, treatment studies have revealed that nonsurgical periodontal treatment, that is removal of sub-gingival calculus and biofilm deposits, is accompanied by a reduction in the severity of RA.
In this study the similarities in immune response and tissue degradation between RA and periodontitis are reviewed. It is shown that the two diseases share the same environmental and genetic risk factors, apart from the fact that there is a link between both diseases via citrullination of proteins by human PAD and P. gingivalis PAD.
The K-SF-42 Figueredo, Aurelio José; Garcia, Rafael Antonio; Menke, J. Michael ...
Evolutionary psychology,
01/2017, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The purpose of the present article is to propose an alternative short form for the 199-item Arizona Life History Battery (ALHB), which we are calling the K-SF-42, as it contains 42 items as compared ...with the 20 items of the Mini-K, the short form that has been in greatest use for the past decade. These 42 items were selected from the ALHB, unlike those of the Mini-K, making direct comparisons of the relative psychometric performance of the two alternative short forms a valid and instructive exercise. A series of secondary data analyses were performed upon a recently completed five-nation cross-cultural survey, which was originally designed to assess the role of life history strategy in the etiology of interpersonal aggression. Only data from the ALHB that were collected in all five cross-cultural replications were used for the present analyses. The single immediate objective of this secondary data analysis was producing the K-SF-42 such that it would perform optimally across all five cultures sampled, and perhaps even generalize well to other modern industrial societies not currently sampled as a result of the geographic breadth of those included in the present study. A novel method, based on the use of the Cross-Sample Geometric Mean as a criterion for item selection, was used for generating such a cross-culturally valid short form.
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