We present a case of a 47-year-old female with a history of diagnosed KD and autoimmune hepatitis 13 years ago who presented with recurrent fevers and a desquamative rash on the lower extremities. Patient has elevated ASMA titer, and a subsequent liver biopsy confirmed the diagnosis of autoimmune hepatitis
Biobutanol produced in acetone-butanol-ethanol fermentation at batch mode cannot compete with chemically derived butanol because of the low reactor productivity. Continuous fermentation can dramatically enhance productivity and lower capital and operating costs but are rarely used in industrial fermentation because of increased risks in culture degeneration, cell washout, and contamination. In this study, cells of the asporogenous Clostridium acetobutylicum ATCC55025 were immobilized in a single-pass fibrous-bed bioreactor (FBB) for continuous production of butanol from glucose and butyrate at various dilution rates. Butyric acid in the feed medium helped maintaining cells in the solventogenic phase for stable continuous butanol production. At the dilution rate of 1.88 h -1, butanol was produced at 9.55 g/L with a yield of 0.24 g/g and productivity of 16.8 g/L∙h, which was the highest ever achieved for biobutanol fermentation and an 80-fold improvement over the conventional ABE fermentation. The extremely high productivity was attributed to the high density of viable cells (~100 g/L at >70% viability) immobilized in the fibrous matrix, which also enabled the cells to better tolerate butanol and butyric acid. The FBB was stable for continuous operation for an extended period of over one month.
Prenatal diagnosis of hypoplastic aortic arch and coarctation of aorta is still challenging and remains one of the most difficult cardiac defect to diagnose. The results reveal significant improvement of prenatal diagnosis of hypoplastic arch and coactation of aorta. The data also shows the significant overlapping of fetal aortic isthmus z score between the infants who need the arch procedure and those who do not.
Cationic helical peptides play a crucial role in applications such as anti-microbial and anti-cancer activity. The activity of these peptides directly correlates with their helicity. In this study, we have performed extensive all-atom molecular dynamics simulations of 25 Lysine-Leucine co-polypeptide sequences of varying charge density ( λ ) and patterns. Our findings showed that an increase in the charge density on the peptide leads to a gradual decrease in the helicity up to a critical charge density λ c . Beyond, λ c a complete helix to coil transition was observed. The decrease in the helicity correlated with the increased number of water molecules in first solvation shell, solvent-exposed surface area, and a higher value of the radius of gyration of the peptide.
A man in his 50s with no significant past medical history developed subarachnoid hemorrhage due to ruptured left middle cerebral artery aneurysm. 9th hospital day, he experienced a ruptured visceral aneurysm with segmental arterial mediolysis, and we successfully treated with transarterial embolization using metallic coils.
DNA extraction and preservation bias is a recurring topic in DNA sequencing-based microbial ecology. Different methodologies can lead to distinct outcomes, which has been demonstrated especially in studies investigating prokaryotic community composition. Eukaryotic microbes are ubiquitous, diverse, and increasingly a subject of investigation in addition to bacteria and archaea. However, little is known about how the choice of DNA preservation and extraction methodology impacts perceived eukaryotic community composition. In this study, we compared the effect of two DNA preservation protocols and 6 DNA extraction methods on the community profiles of both eukaryotes and prokaryotes in phototrophic biofilms on seagrass (Zostera marina) leaves from the Baltic Sea. We found that, whereas DNA preservation and extraction method caused significant bias in perceived community composition for both eukaryotes and prokaryotes, extraction bias was more pronounced for eukaryotes than prokaryotes. Especially soft-bodied or hard-shelled eukaryotes like nematodes and diatoms were differentially abundant depending on the extraction method. We conclude that careful consideration of DNA preservation and extraction methodology is crucial to achieving representative community profiles of eukaryotes in marine biofilms, and likely all other habitats containing diverse eukaryotic microbial communities.
Based on Carpentier’s classification and principles, the techniques for mitral valve repair continue to evolve. We herein report our experience with the morpho-functional echocardiographic analysis of single mitral leaflets, as different anatomic features, even if conflicting, may coexist not only in the two leaflets, but in the same leaflet as well. A classification is proposed, based on the length (normal, short, or long) and mobility (normal, restricted, or excessive) of mitral leaflets. The surgical techniques adopted for mitral valve repair are the direct consequence of this analysis.
Various post translational modifications like hyper phosphorylation, O-GlycNAcylation, and acetylation have been attributed to induce the abnormal folding in tau protein. Recent in vitro studies revealed the possible involvement of N–glycosylation of tau protein in the abnormal folding and tau aggregation. Hence in this study, we performed microsecond long all atom molecular dynamics simulation to gain insights into the effects of N-glycosylation on Asn-359residue which forms part of the microtubule binding region. Trajectory analysis of the stimulations coupled with essential dynamics and free energy landscape analysis suggested that tau, in its N-glycosylated form tend to exist in a largely folded conformation having high beta sheet propensity as compared to unmodified tau which exists in a large extended form with very less beta sheet propensity. Residue interaction network analysis of the lowest energy conformations further revealed that Phe378 and Lys353 are the functionally important residues in the peptide which helped in initiating the folding process and Phe378, Lys347&Lys370 helped maintaining the stability of the protein in the folded state.
Herein, we report a case of VAIHS with atypical clinical presentation of perianal abscess, fistula fever and bicytopenia including pathogenic ADA2 mutation suggesting that ADA2 deﬁciency be considered as a differential diagnosis of enlarging cutaneous abscess with no evidence of wound healing in the setting of leukopenia and neutropenia.
Open dislocation of the ankle and Epstein's superior type of hip dislocation are rare orthopedic injuries. We reported a case of 50 years gentleman with a combination of these two rare orthopedic emergencies without any associated fracture with the newly reported mechanism and management to save limb and its function.
A narrative review based on the case of a patient presenting an atypical symptomatology of an atraumatic splenic rupture induced by rivaroxaban. An emergency splenectomy had to be performed. This complication is rare but increasing since the popularity of direct oral anticoagulants and the diagnosis is often delayed.
Crimean-Congo haemorrhagic fever (CCHF) is an emerging tick-borne human disease in Spain. Understanding the spatiotemporal dynamics and exposure risk determinants of CCHF virus (CCHFV) in animal models is essential to predict the time and areas of highest transmission risk. With this goal, we designed a longitudinal survey in two wild ungulate species, the red deer ( Cervus elaphus) and the Eurasian wild boar ( Sus scrofa), in Doñana National Park, a protected Mediterranean biodiversity hotspot with high ungulate and CCHFV vector abundance, and which is also one of the main stopover sites for migratory birds between Africa and western Europe. Both ungulates are hosts to the main CCHFV vector in Spain, Hyalomma lusitanicum. We sampled wild ungulates annually from 2005 to 2020 and analysed the frequency of exposure to CCHFV by a double-antigen ELISA. The annual exposure risk was modelled as a function of environmental traits in an approach to understand exposure risk determinants that allow us to predict the most likely places and years for CCHFV transmission. The main findings show that H. lusitanicum abundance is a major driver of the fine-scale spatial CCHFV transmission risk, while inter-annual variations in the risk are conditioned by virus/vector hosts, by host community structure and by weather variations. The most relevant conclusion of the study is that the emergence of CCHF in Spain might have been associated with recent wild ungulate population changes promoting higher vector abundance. Decreasing wild ungulate population densities could reduce vector abundance and thus virus prevalence and the risk of CCHFV transmission to humans.
RP7214 is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This paper describes the results from a Phase 1 study that evaluated safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy subjects. Target engagement of DHODH was also evaluated. A randomized, double-blind, placebo-controlled trial of single-dose (100, 200, and 400 mg QD) and multiple doses (200 and 400 mg BID for 7 days) followed by food effect at a single dose of 200 mg was conducted. A total of 18 healthy volunteers (HVs) (6 subjects in each of three cohorts) in the SAD part, 12 (6 subjects each in two cohorts) in the MAD part, and 12 in the food effect study were enrolled. RP7214 was well tolerated at all dose levels. None of the subjects reported any RP7214-related adverse events. RP7214 showed dose-proportional pharmacokinetics after single and multiple dosing. Steady-state concentrations were reached within about 3–6 days. The mean plasma half-life of RP724 at steady-state was approximately 13h. RP7214 showed accumulation on multiple dosing.. Food did not impact the absorption of RP7214. RP7214 showed dose-dependent inhibition of DHODH as measured by analyzing accumulating DHO levels, confirming target engagement. The rapid absorption and high systemic exposure of RP724 with a favorable safety profile shows the potential for the development of RP7214 in SARS-CoV-2 infection and acute myeloid leukemia. (NCT04680429). Keywords: RP7214, dihydroorotate dehydrogenase, SAD, MAD, HV
Background: Irinotecan and temozolmide achieve objective responses in patients with Ewing sarcoma which recurrences after initial therapy. Optional dose schedules have not been defined. Procedure: We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma which recurred after initial therapy. We compared objective response rates for patients who received 5 day irinotecan treatment schedules to response rates for patients who achieved 10 day irinotecan treatment schedules. Results: Among 94 patients treated with a 10 day irinotecan schedule there were 48 objective responses (51%). Among 218 patients treated with a 5 day irinotecan schedule there were 65 responses (30%). Conclusion: When we use irinotecan to treat Ewing sarcoma we should administer 10 days of treatment.