Exploring the relationship between marital quality and cognitive function: A systematic review.

Cognitive function is an important indicator of healthy aging as it is central to maintaining functional independence, performing job-related tasks, decision-making, and improving quality of life. Therefore, researchers seek to identify biopsychosocial factors that can help preserve cognitive function in aging individuals. One such factor is the maintenance of good quality marital relationships.

3D-Printed Tumor Phantoms for Assessment of In Vivo Fluorescence Imaging Analysis Methods.

Purpose: Interventional fluorescence imaging is increasingly being utilized to quantify cancer biomarkers in both clinical and preclinical models, yet absolute quantification is complicated by many factors. The use of optical phantoms has been suggested by multiple professional organizations for quantitative performance assessment of fluorescence guidance imaging systems. This concept can be further extended to provide standardized tools to compare and assess image analysis metrics.

Predicting the role of touchless technologies within diagnostic radiography: Results of an international survey.

Introduction: The evolution of technology within healthcare is continuing at a rapid rate. Touchless technologies (i.e.

Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion.

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC of 1.

Modifications to mobile chest radiography technique during the COVID-19 pandemic - implications of X-raying through side room windows.

Introduction: Modifications to common radiographic techniques have resulted from the challenges presented by the COVID-19 pandemic. Reports exist regarding the potential benefits of undertaking mobile radiography through side room windows. The aim of this study was to evaluate the impact on image quality and exposure factors when undertaking such examinations.

A Randomized, Placebo-Controlled, Respiratory Syncytial Virus Human Challenge Study of the Antiviral Efficacy, Safety, and Pharmacokinetics of RV521, an Inhibitor of the RSV-F Protein.

Effective treatments for respiratory syncytial virus (RSV) infection are lacking. Here, we report a human proof-of-concept study for RV521, a small-molecule antiviral inhibitor of the RSV-F protein. In this randomized, double-blind, placebo-controlled trial, healthy adults were challenged with RSV-A Memphis-37b.

Clostridium difficile has a single sortase, SrtB, that can be inhibited by small-molecule inhibitors.

Background: Bacterial sortases are transpeptidases that covalently anchor surface proteins to the peptidoglycan of the Gram-positive cell wall. Sortase protein anchoring is mediated by a conserved cell wall sorting signal on the anchored protein, comprising of a C-terminal recognition sequence containing an "LPXTG-like" motif, followed by a hydrophobic domain and a positively charged tail.

Results: We report that Clostridium difficile strain 630 encodes a single sortase (SrtB).

Combinatorial Domain Hunting: solving problems in protein expression.

Modern drug discovery demands large amounts of high-quality protein and, therefore, begins by expressing target genes in heterologous systems such as bacteria or insect cells. However, some of the most attractive drug targets have proven challenging to clone and express. A technology called Combinatorial Domain Hunting has been developed to express regions or domains of proteins in a non-aggregated form.

Clustering of Pseudomonas aeruginosa transcriptomes from planktonic cultures, developing and mature biofilms reveals distinct expression profiles.

Background: Pseudomonas aeruginosa is a genetically complex bacterium which can adopt and switch between a free-living or biofilm lifestyle, a versatility that enables it to thrive in many different environments and contributes to its success as a human pathogen.

Results: Transcriptomes derived from growth states relevant to the lifestyle of P. aeruginosa were clustered using three different methods (K-means, K-means spectral and hierarchical clustering).

Nucleoside analogs as anti-HBV agents.

Chronic hepatitis B virus (HBV) infection affects about 400 million people worldwide. The development of nucleoside analogs that inhibit HBV polymerase provides an important approach for treating HBV infection. The approval of lamivudine, adefovir and entecavir represents a cornerstone of hepatitis B therapy.

Transcriptome analysis of Pseudomonas aeruginosa growth: comparison of gene expression in planktonic cultures and developing and mature biofilms.

The transcriptomes of logarithmic- and stationary-phase Pseudomonas aeruginosa planktonic cultures and static biofilms of different stages of development were compared. Developing and confluent biofilm transcriptomes were found to be related to those of logarithmic- and stationary-phase planktonic cultures, respectively. In addition, a number of novel genes were up-regulated in developing and confluent biofilms, including genes encoding putative solute transport proteins and transcriptional regulators, respectively.

Achievements and challenges in antiviral drug discovery.

The last 40 years have seen the development of several antiviral drugs with therapeutic value in treating life-threatening or debilitating diseases such as those caused by HIV, hepatitis B virus, herpesviruses (such as herpes simplex virus and varicella zoster virus) and influenza virus. These relatively recent advances have been due to technical breakthroughs in the cultivation of viruses in the laboratory, identification of viral enzymes and, more recently, their molecular biology. We describe here the antecedence of several of the existing antivirals and their strengths and weaknesses.

The past, present and future of antiviral drug discovery.

A review of the history, development and current status of antiviral chemotherapy is presented from its origins in the 1960s until the present day. Key issues in the development of novel antivirals are the emergence of resistant virus, safety and side effects. This review describes the current therapeutic status of the herpes viruses, HIV, hepatitis viruses and respiratory viruses, and outlines the current limitations in the field together with the future compounds likely to emerge to address these needs.

Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells.

The efficacies of ganciclovir (GCV), penciclovir (PCV) and acyclovir (ACV) in inducing cell death in the herpes simplex virus thymidine kinase (HSVTK) system were compared. HSVTK-transformed baby hamster kidney cells treated with GCV, PCV or ACV were monitored for growth by viable count, and for death by TUNEL assay, propidium iodide staining, detection of phosphatidyl serine translocation and detection of DNA laddering. All compounds delayed growth or reduced viability of HSVTK-transformed cells.

Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues.

Levels of bystander death occurring in herpes simplex virus type 1 (HSV-1)-infected mouse brain stems were studied, as well as the extent to which bystander death is influenced by guanosine nucleoside analogue treatment. Consecutive sections from brain stems of HSV-1-infected mice were stained alternately for (i) viral infection and (ii) cell death (TUNEL assay). Virus antigen was detectable in brain stems on day 3 of infection, while TUNEL staining was comparatively lower.

Antibodies to Epstein-Barr virus thymidine kinase: a characteristic marker for the serological detection of nasopharyngeal carcinoma.

Patients suffering from nasopharyngeal carcinoma (NPC) generally exhibit elevated serum IgA antibody titres to Epstein-Barr virus (EBV) early antigen (EA) and virus capsid antigen (VCA). This property is frequently used as a diagnostic aid. Preliminary experiments suggested that an ELISA for IgA antibodies against the EBV-encoded thymidine kinase (TK) could form the basis of a more reliable diagnostic test.

Indolocarbazoles: potent, selective inhibitors of human cytomegalovirus replication.

In our search for new, safer anti-HCMV agents, we discovered that the natural product Arcyriaflavin A (la) was a potent inhibitor of HCMV replication in cell culture. A series of analogues (symmetrical indolocarbazoles) was synthesised to investigate structure activity relationships in this series against a range of herpes viruses (HCMV, VZV, HSV1, and 2). This identified a number of novel, selective and potent inhibitors of HCMV, 12,13-dihydro-2,10-difluoro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazol e-5,7-(6H)-dione (1d) being the best example (IC50=40 nM, therapeutic index > 1450).

Synthesis and anti-herpes virus activity of 2'-deoxy-4'-thiopyrimidine nucleosides.

A series of 5-substituted 2'-deoxy-4'-thiopyrimidine nucleosides was synthesized and evaluated as potential antiviral agents. A number of analogues such as 2'-deoxy-5-propyl-4'-thiouridine (3ii), 2'-deoxy-5-isopropyl-4'-thiouridine (3iii), 5-cyclopropyl-2'-deoxy-4'-thiouridine (3iv), 2'-deoxy-4'-thio-5-vinyluridine (3viii), and 5-(2-chloroethyl)-2'-deoxy-4'-thiouridine (3xx) were found to be highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) in vitro with no significant cytotoxicity. The compound with the broadest spectrum of activity was 2'-deoxy-5-ethyl-4'-thiouridine (3i) which showed significant activity against HSV-1, HSV-2, and VZV.

The cloning, sequencing and expression of a major antigenic region from the feline calicivirus capsid protein.

RNA purified from the feline calicivirus (FCV) F9 vaccine strain was used to prepare a cDNA library in the expression vector lambda gt11. The library was screened for expression of FCV antigen using a rabbit antiserum prepared against purified FCV. A 330 bp cDNA clone was identified and used as a probe to obtain a larger overlapping clone of 1369 bp.

Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir.

Human cytomegalovirus (HCMV, a betaherpes virus) is the cause of serious disease in immunologically compromised individuals, including those with acquired immunodeficiency syndrome. One of the compounds used in the chemotherapy of HCMV infections is the nucleoside analogue 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (ganciclovir). The mechanism of action of this drug is dependent on the formation of the nucleoside triphosphate, which is a strong inhibitor of the viral DNA polymerase.

32P-postlabelling of alkylated thymidines using Epstein-Barr virus encoded thymidine kinase.

Alkylated nucleotides have been detected by 32P-postlabelling using the enzyme T4 polynucleotide kinase which phosphorylates the 3'-mononucleotides to give the 3',[5'-32P]bisphosphates. These may then be separated by two-dimensional TLC as the bisphosphates or the [5'-32P]monophosphates. We describe here an alternative approach using the Epstein-Barr virus (EBV) encoded thymidine kinase (TK) to directly phosphorylate adducted nucleosides to give the [5'-32P]monophosphates.

Diagnosis of nasopharyngeal carcinoma by means of recombinant Epstein-Barr virus proteins.

The immune response of patients with nasopharyngeal carcinoma to Epstein-Barr virus (EBV) antigens is diagnostic of the tumour. Existing tests use EBV antigens produced in EBV-infected lymphoblastoid cells, but the virus replicates poorly in these cells. Serum samples from 18 patients diagnosed as having nasopharyngeal carcinoma were screened by western blot analysis, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence tests for antibodies to the EBV-coded alkaline deoxyribonuclease (DNase), thymidine kinase, and membrane antigen (gp340/220) produced in recombinant baculovirus or bovine papillomavirus systems.

High-level expression of the Epstein-Barr virus alkaline deoxyribonuclease using a recombinant baculovirus: application to the diagnosis of nasopharyngeal carcinoma.

The Epstein-Barr virus (EBV) alkaline deoxyribonuclease (DNase) was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV). Infection of the insect cell line Spodoptera frugiperda (SF9) with the recombinant virus led to the expression of an enzymatically active alkaline DNase. The recombinant EBV alkaline DNase was highly soluble, and the recombinant baculovirus produced approximately 10-20 mg of EBV DNase per 1 X 10(9) cells.

Immunological studies on the Epstein-Barr virus encoded alkaline deoxyribonuclease found in virus-producing lymphoblastoid cells.

Antisera were raised against a purified recombinant form of the Epstein-Barr virus (EBV) alkaline deoxyribonuclease (DNase) expressed in Escherichia coli. These sera were shown to be reactive with lymphoblastoid cells expressing EBV antigens (B95-8, P3HR-1 and Raji). Immunostaining studies of cells expressing EBV antigens revealed that the DNase was a component of the restricted early antigen complex of EBV.