Hyponatremia during hospitalization and in-hospital mortality in patients hospitalized from heart failure

BackgroundTo date, the majority of studies on hyponatremia focussed on hyponatremia at admission, and came from developed countries. This study aimed to identify the prevalence of hyponatremia during hospitalization in patients hospitalized for HF and its association with in-hospital mortality.MethodsThis was an observational study using retrospective data from patients’ records between 2010–2013. It focused on those patients carrying an ICD-10 code of 150.0(Congestive Heart Failure) as their primary diagnosis.Hyponatremia during hospitalization was defined as serum sodium level lower than 135 mEq/L obtained from a blood chemistry measurement on the next days after admission. Patients’ characteristics were examined and the association between hyponatremia during hospitalization and in-hospital mortality was analyzed.ResultsAmong 464 patients hospitalized for HF, hyponatremia during hospitalization was observed in 22 % of patients with 44 % of this group had normal serum sodium level on admission.Hyponatremia during hospitalization was associated with lower blood pressure on admission, both systolic and diastolic, peripheral oedema, ascites and fatigue. Patients having history of hospitalization for cardiac diseases and renal failure were higher in patients developing hyponatremia during hospitalization. In this group, amiodarone, heparin, insulin and antibiotics were administered more frequently. Factors potentially increase the risk of hyponatremia during hospitalization include history of fatigue (OR = 3.23, 95 % CI 1.79–5.82), presence of ascites (4.14, 1.84–9.31), and administration of heparin (3.85, 1.78–8.31) and antibiotics (3.08, 1.71–5.53). Length of hospital stay was significantly longer in patients with hyponatremia during hospitalization and in-hospital mortality was also higher compared to non-hyponatremic patients, 7.7 % and 29.1 %, respectively.ConclusionThis study found that the prevalence of hyponatremia during hospitalization in patients hospitalized for HF was almost the same as hyponatremia on admission and administration of heparin and antibiotics can potentially worsen hyponatremia during hospitalization. In this study population, hyponatremia during hospitalization was found to be associated with in-hospital mortality

JANUS KINASE ENZYME (JAK) INHIBITORS AND RHEUMATOID ARTHRITIS: A REVIEW OF THE LITERATURE

Cytokines play an essential role in normal cell growth and the regulation of immune function. The emergence of Janus Kinase Enzyme inhibitors promises the start of a revolution in the treatment of several chronic diseases. Their efficacy and safety profile have been demonstrated in multiple trials and they have been licensed for the treatment of a number of diseases including RA and PsA. Moreover, the use of highly selective Janus Kinase Enzyme inhibitors is currently being studied aiming to reduce side effects compared with traditional JAKinibs, an example of that would be the recent FDA approved upadacitinib. The Janus Kinase Enzyme inhibitorsmay supplant the classical biologic agents in the treatment of autoimmune diseases, since they exhibitthe advantages of oral administration, simultaneous blockade of multiple cytokines, reversibility and the lack of immunogenicity

From Low-Distortion Norm Embeddings to Explicit Uncertainty Relations and Efficient Information Locking

The existence of quantum uncertainty relations is the essential reason that some classically impossible cryptographic primitives become possible when quantum communication is allowed. One direct operational manifestation of these uncertainty relations is a purely quantum effect referred to as information locking. A locking scheme can be viewed as a cryptographic protocol in which a uniformly random n-bit message is encoded in a quantum system using a classical key of size much smaller than n. Without the key, no measurement of this quantum state can extract more than a negligible amount of information about the message, in which case the message is said to be "locked". Furthermore, knowing the key, it is possible to recover, that is "unlock", the message. In this paper, we make the following contributions by exploiting a connection between uncertainty relations and low-distortion embeddings of L2 into L1. We introduce the notion of metric uncertainty relations and connect it to low-distortion embeddings of L2 into L1. A metric uncertainty relation also implies an entropic uncertainty relation. We prove that random bases satisfy uncertainty relations with a stronger definition and better parameters than previously known. Our proof is also considerably simpler than earlier proofs. We apply this result to show the existence of locking schemes with key size independent of the message length. We give efficient constructions of metric uncertainty relations. The bases defining these metric uncertainty relations are computable by quantum circuits of almost linear size. This leads to the first explicit construction of a strong information locking scheme. Moreover, we present a locking scheme that is close to being implementable with current technology. We apply our metric uncertainty relations to exhibit communication protocols that perform quantum equality testing.Comment: 60 pages, 5 figures. v4: published versio

Novel functional hepatitis C virus glycoprotein isolates identified using an optimised viral pseudotype entry assay

Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, pre-clinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from individual patient quasispecies were discovered to behave very differently in this entry model. Empirical optimisation of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterised as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) were also sensitive to the amount, and ratio, of plasmids used, and that protocols for optimal production of these pseudoviruses is dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilising pseudoviruses to conduct empirical optimisation of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping

A literature review of the Janus kinase inhibitors used in the treatment of auto-immune dermatological conditions

© 2022 The Authors. Published by Archives of Pharmacy Practice. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.51847/RHmIzdv54FThe signal transducer and activator of transcription (STAT) families and Janus kinase group (JAK) are important intracellular signalling components that affect more than 50 cytokines and growth elements. JAK inhibitors target distinct receptor-associated kinases, inhibiting the activation of inflammatory signals. With the expanding body of evidence supporting the use of targeted medicines, numerous JAK inhibitors, both topical and systemic, have been tested in the treatment of atopic dermatitis, with varying mechanisms of action, effectiveness, and safety. The efficacy and safety of JAK inhibitors used to treat inflammatory and atopic skin diseases are examined in this review study. Their application in the mentioned fields has been characterized by some excellent clinical responses, but wide variability in responses and some serious and even life-threatening side effects. While JAK inhibitors are now beneficial to many patients, further study is needed to better understand this complicated mechanism to improve treatment outcomes and minimize side effects.Published versio

Flexible and rapid construction of viral chimeras applied to Hepatitis C Virus

A novel and broadly applicable strategy combining site directed mutagenesis and DNA assembly for constructing seamless viral chimeras is described using Hepatitis C Virus as an exemplar. Full-length HCV genomic cloning cassettes, which contained flexibly situated restriction endonuclease sites, were prepared via a single site-directed mutagenesis reaction and digested to receive PCR amplified virus envelope genes by In-Fusion cloning. Using this method we were able to construct gene-shuttle cassettes for generation of cell culture-infectious JFH-1-based chimeras containing genotype 1-3 E1E2 genes. Importantly, using this method we also show that E1E2 clones that were not able to support cell entry in the HCV pseudoparticle assay did confer entry when shuttled into the chimeric cell culture chimera system. This method can be easily applied to other genes of study and other viruses and, as such, will greatly simplify reverse genetics studies of variable viruses

Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells

Immunization with a synthetic consensus hepatitis C virus E2 glycoprotein ectodomain elicits virus-neutralizing antibodies

Global eradication of hepatitis C virus (HCV) infection will require an efficacious vaccine capable of eliciting protective immunity against genetically diverse HCV strains. Natural spontaneous resolution of HCV infection is associated with production of broadly neutralizing antibodies targeting the HCV glycoproteins E1 and E2. As such, production of cross-neutralizing antibodies is an important endpoint for experimental vaccine trials. Varying success generating cross-neutralizing antibodies has been achieved with immunogens derived from naturally-occurring HCV strains. In this study the challenge of minimising the genetic diversity between the vaccine strain and circulating HCV isolates was addressed. Two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) were derived from consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains. These two synthetic sequences differed in their relative positions in the overall genotype 1a/1b phylogeny. Expression of these constructs in Drosophila melanogaster S2 cells resulted in high yields of correctly-folded, monomeric E2 protein, which were recognised by broadly neutralizing monoclonal antibodies. Immunization of guinea pigs with either of these consensus immunogens, or a comparable protein representing a circulating genotype 1a strain resulted in high titres of cross-reactive anti-E2 antibodies. All immunogens generated antibodies capable of neutralizing the H77 strain, but NotC1 elicited antibodies that more potently neutralized virus entry. These vaccine-induced antibodies neutralized some viruses representing genotype 1, but not strains representing genotype 2 or genotype 3. Thus, while this approach to vaccine design resulted in correctly folded, immunogenic protein, cross-neutralizing epitopes were not preferentially targeted by the host immune response generated by this immunogen. Greater immunofocussing by vaccines to common epitopes is necessary to successfully elicit broadly neutralizing antibodies