Clinical Predictors of Sensorineural Hearing Loss and Cognitive Outcome in Infants with Symptomatic Congenital Cytomegalovirus Infection.

The objective of this study was to determine newborn clinical findings predictive of adverse clinical outcomes in infants with symptomatic congenital cytomegalovirus infection. Of 160 infants, significantly more children with central nervous system involvement had sensorineural hearing loss (P = 0.0007) and an IQ ≤70 (P < 0.

O2 Protonation Controls Threshold Behavior for N-Glycosidic Bond Cleavage of Protonated Cytosine Nucleosides.

IRMPD action spectroscopy studies of protonated 2'-deoxycytidine and cytidine, [dCyd+H](+) and [Cyd+H](+), have established that both N3 and O2 protonated conformers coexist in the gas phase. Threshold collision-induced dissociation (CID) of [dCyd+H](+) and [Cyd+H](+) is investigated here using guided ion beam tandem mass spectrometry techniques to elucidate the mechanisms and energetics for N-glycosidic bond cleavage. N-Glycosidic bond cleavage is observed as the major dissociation pathways resulting in competitive elimination of either protonated or neutral cytosine for both protonated cytosine nucleosides.

An audit of HIV treatment outcomes in a UK inner city cohort.

We describe the demographics and treatment outcomes of a HIV-infected cohort from Croydon University Hospital, London, UK. We showed that the Croydon Cohort had good viral load suppression (98.6% with viral load < 100 copies/ml and 99.

N3 Protonation Induces Base Rotation of 2'-Deoxyadenosine-5'-monophosphate and Adenosine-5'-monophosphate.

Infrared multiple photon dissociation (IRMPD) action spectroscopy experiments combined with theoretical calculations are performed to investigate the stable gas-phase conformations of the protonated adenine mononucleotides, [pdAdo+H](+) and [pAdo+H](+). Conformations that are present in the experiments are elucidated via comparative analyses of the experimental IRMPD spectra and the B3LYP/6-311+G(d,p) IR spectra predicted for the conformers optimized at this level of theory. N3 protonation is preferred as it induces base rotation, which allows a strong hydrogen bond to be formed between the excess proton of adenine and the phosphate moiety.

No Quick Fixes: A Mixed Methods Feasibility Study of an Urban Community Health Worker Outreach Program for Intimate Partner Violence.

Community health workers (CHWs) provide peer support in diverse health care settings, but few studies have evaluated CHW interventions for intimate partner violence (IPV). We assessed the feasibility, acceptability, and safety of CHW outreach in four urban community health clinics and characterized the experiences and barriers to providing safe and effective services for women experiencing IPV. CHWs successfully enrolled and engaged IPV victims, who indicated satisfaction and increased safety with program participation.

Quadrate lobe: a reliable landmark for bile duct anatomy during laparoscopic cholecystectomy.

Background: This investigation was undertaken to determine whether the shape of the inferior surface quadrate lobe (segment IV) can assist in defining a safe starting point for dissection during laparoscopic cholecystectomy.

Methods: Patients undergoing laparoscopic cholecystectomy were prospectively audited. Intraoperative cholangiograms and photographs of the quadrate lobe were reviewed measuring the angle between the cystic duct and common bile duct and its relationship to quadrate shape.

Individual Case Analysis of Postmortem Interval Time on Brain Tissue Preservation.

At autopsy, the time that has elapsed since the time of death is routinely documented and noted as the postmortem interval (PMI). The PMI of human tissue samples is a parameter often reported in research studies and comparable PMI is preferred when comparing different populations, i.e.

Cationic Noncovalent Interactions: Energetics and Periodic Trends.

In this review, noncovalent interactions of ions with neutral molecules are discussed. After defining the scope of the article, which excludes anionic and most protonated systems, methods associated with measuring thermodynamic information for such systems are briefly recounted. An extensive set of tables detailing available thermodynamic information for the noncovalent interactions of metal cations with a host of ligands is provided.

Interaction of Cu(+) with cytosine and formation of i-motif-like C-M(+)-C complexes: alkali versus coinage metals.

The Watson-Crick structure of DNA is among the most well-known molecular structures of our time. However, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or the presence of cations. Pairing of cytosine (C) bases induced by the sharing of a single proton (C-H(+)-C) may give rise to the so-called i-motif, which occurs primarily in expanded trinucleotide repeats and the telomeric region of DNA, particularly at low pH.

Longitudinal Analysis of the Effect of Inflammation on Voriconazole Trough Concentrations.

Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations.

Discriminating Properties of Alkali Metal Ions Towards the Constituents of Proteins and Nucleic Acids. Conclusions from Gas-Phase and Theoretical Studies.

Quantitative insight into the structures and thermodynamics of alkali metal cations interacting with biological molecules can be obtained from studies in the gas phase combined with theoretical work. In this chapter, the fundamentals of the experimental and theoretical techniques are first summarized and results for such work on complexes of alkali metal cations with amino acids, small peptides, and nucleobases are reviewed. Periodic trends in how these interactions vary as the alkali metal cations get heavier are highlighted.

Voriconazole Therapeutic Drug Monitoring Practices in Intensive Care.

Background: Routine therapeutic drug monitoring of voriconazole seems to be beneficial. This study investigated the therapeutic drug monitoring practices in intensive care to derive possible recommendations for improvement.

Methods: A retrospective chart review was performed for patients aged ≥18 years who started treatment with voriconazole, which lasted for at least 3 days while being admitted to an intensive care unit to assess possible differences between the patients with and without voriconazole trough concentrations measured.

Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems.

Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate for human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a propagation method that utilizes a commercially available medium to produce UV tolerant B.

The Clinical and Cost Effectiveness of Ustekinumab for the Treatment of Psoriatic Arthritis: A Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ustekinumab (Janssen) to submit evidence for the clinical and cost effectiveness of ustekinumab for the treatment of active psoriatic arthritis (PsA) as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Appraisal Group at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the ERG review of the manufacturer's evidence submission, and summarises the NICE Appraisal Committee's final guidance (TA340) issued in June 2015.

A genetic and physical study of the interdomain linker of E. Coli AraC protein--a trans-subunit communication pathway.

Genetic experiments with full length AraC and biophysical experiments with its dimerization domain plus linker suggest that arabinose binding to the dimerization domain changes the properties of the inter-domain linker which connects the dimerization domain to the DNA binding domain via interactions that do not depend on the DNA binding domain. Normal AraC function was found to tolerate considerable linker sequence alteration excepting proline substitutions. The proline substitutions partially activate transcription even in the absence of arabinose and hint that a structural shift between helix and coil may be involved.

Mechanisms and energetics for N-glycosidic bond cleavage of protonated 2'-deoxyguanosine and guanosine.

Experimental and theoretical investigations suggest that hydrolysis of N-glycosidic bonds generally involves a concerted SN2 or a stepwise SN1 mechanism. While theoretical investigations have provided estimates for the intrinsic activation energies associated with N-glycosidic bond cleavage reactions, experimental measurements to validate the theoretical studies remain elusive. Here we report experimental investigations for N-glycosidic bond cleavage of the protonated guanine nucleosides, [dGuo+H](+) and [Guo+H](+), using threshold collision-induced dissociation (TCID) techniques.

2,4-Dihydroxy and O2 Protonated Tautomers of dThd and Thd Coexist in the Gas Phase: Methylation Alters Protonation Preferences versus dUrd and Urd.

The gas-phase structures of protonated thymidine, [dThd + H](+), and its modified form, protonated 5-methyluridine, [Thd + H](+), are examined by infrared multiple photon dissociation (IRMPD) action spectroscopy combined with electronic structure calculations. IRMPD action spectra are measured over the ranges extending from ~600 to 1900 cm(-1) and ~2800 to 3800 cm(-1) using the FELIX free electron laser and an optical parametric oscillator/amplifier (OPO/OPA) laser system, respectively. Comparisons between the B3LYP/6-311+G(d,p) linear IR spectra calculated for the stable low-energy conformers and the measured IRMPD spectra are used to determine the most favorable tautomeric conformations of [dThd + H](+) and [Thd + H](+) and to identify those populated in the experiments.

Structural Analysis of Multi-Helical RNAs by NMR-SAXS/WAXS: Application to the U4/U6 di-snRNA.

NMR and SAXS (small-angle X-ray scattering)/WAXS (wide-angle X-ray scattering) are highly complementary approaches for the analysis of RNA structure in solution. Here we describe an efficient NMR-SAXS/WAXS approach for structural investigation of multi-helical RNAs. We illustrate this approach by determining the overall fold of a 92-nt 3-helix junction from the U4/U6 di-snRNA.

Conformational dynamics of stem II of the U2 snRNA.

The spliceosome undergoes dramatic changes in both small nuclear RNA (snRNA) composition and structure during assembly and pre-mRNA splicing. It has been previously proposed that the U2 snRNA adopts two conformations within the stem II region: stem IIa or stem IIc. Dynamic rearrangement of stem IIa into IIc and vice versa is necessary for proper progression of the spliceosome through assembly and catalysis.

Posttranslational Modification of HOIP Blocks Toll-Like Receptor 4-Mediated Linear-Ubiquitin-Chain Formation.

Unlabelled: Linear ubiquitination is an atypical posttranslational modification catalyzed by the linear-ubiquitin-chain assembly complex (LUBAC), containing HOIP, HOIL-1L, and Sharpin. LUBAC facilitates NF-κB activation and inflammation upon receptor stimulation by ligating linear ubiquitin chains to critical signaling molecules. Indeed, linear-ubiquitination-dependent signaling is essential to prevent pyogenic bacterial infections that can lead to death.

Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.

Lipids are necessary for every step in the replication cycle of hepatitis C virus (HCV) and dengue virus (DENV), members of the family Flaviviridae. Recent studies have demonstrated that discrete steps in the replication cycles of these viruses can be inhibited by pharmacological agents that target host factors mediating lipid synthesis, metabolism, trafficking, and signal transduction. Despite this, targeting host lipid metabolism and trafficking as an antiviral strategy by blockade of entire pathways may be limited due to host toxicity.