Impact of 5 years of hepatitis C testing and treatment in the North East of England prisons.

Hepatitis C virus infection (HCV) is prevalent in prisons. Therefore, effective prison HCV services are critical for HCV elimination programmes. We aimed to evaluate the efficacy of a regional HCV prison testing and treatment programme.

Hydrogen sulfide production during early yeast fermentation correlates with volatile sulfur compound biogenesis but not thiol release.

Yeasts undergo intensive metabolic changes during the early stages of fermentation. Previous reports suggest the early production of hydrogen sulfide (H2S) is associated with the release of a range of volatile sulfur compounds (VSCs), as well as the production of varietal thiol compounds 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHA) from six-carbon precursors, including (E)-hex-2-enal. In this study, we investigated the early H2S potential, VSCs/thiol output, and precursor metabolism of 11 commonly used laboratory and commercial Saccharomyces cerevisiae strains in chemically defined synthetic grape medium (SGM) within 12 h after inoculation.

Enantioselective Total Synthesis of ()-Blumenol B and d-()-Blumenol B.

C-norisoprenoids are of particular importance to grapes and wines, as these molecules influence wine aroma and have been shown to significantly contribute to the distinct character of various wine varieties. Blumenol B is a putative precursor to a number of important wine aroma compounds, including the well-known compounds theaspirone and vitispirane. The enantioselective synthesis of (,)-blumenol B from commercially available 4-oxoisophorone was achieved using a short and easily scaleable route, which was then successfully applied to the synthesis of poly-deuterated d9-blumenol B.

Determining the frequency and characteristics of Hepatitis C reinfections in North East England.

Hepatitis C virus infection (HCV) is common, and injecting drug use is the major risk factor for acquisition. Understanding HCV reinfection following treatment is an important consideration for HCV elimination programmes. The aim of this work was to assess the frequency and patterns of HCV reinfection in our region to develop avoidance strategies.

A single run liquid chromatography-tandem mass spectrometry method for the analysis of varietal thiols and their precursors in wine.

This research details the development of a novel LC-MS/MS method involving a QuEChERS-based extraction that, for the first time, achieves the fast and concurrent analysis of both free varietal thiols (3-sulfanylhexan-1-ol, 3-sulfanylhexyl acetate, and 4-methyl-4-sulfanylpentan-2-one) and their S-glutathionylated/S-cysteinylated precursors in wine samples. Limits of detections for the free thiols were comparable to or lower than those obtained with previously reported more laborious methods. Repeatability for the free thiols ranged between 3-19% and from 0.

First use of grape waste-derived building blocks to yield antimicrobial materials.

Grape marc is an underutilised waste material that poses significant environmental issues. This study offers the first proof-of-concept investigation into the polymerisation of both crude and purified Sauvignon blanc grape marc extracts using the diacyl chlorides terephthaloyl chloride, succinyl chloride, adipoyl chloride, sebacoyl chloride, and the tartaric acid derivative (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dicarbonyl dichloride to obtain new materials, in what to the best of our knowledge is the first reported example of a direct polymerisation of an agricultural waste extract. A total of 26 novel materials were prepared.

Metabolite characterization of fifteen by-products of the coffee production chain: From farm to factory.

Approximately 11.4 million tonnes of solid by-products and an increased amount of waste water will be generated during the 2020/21 coffee harvest. There are currently no truly value-adding uses for these potentially environmentally threatening species.

Does HO Really Act as a Ligand in the Solid State?

The evidence for the existence of metal complexes containing HO as a ligand in the solid state is examined. Each of the 68 examples in the Cambridge Structural Database in which HO is bound to a transition metal, lanthanoid, actinoid, or main group metal ion is detailed and critically appraised. It is concluded that none of the reported examples of complexes containing coordinated HO have been unequivocally characterized and that they result from either curation errors or misinterpretations of the crystallographic data.

Five-coordinate transition metal complexes and the value of : observations and caveats.

The τ5 parameter, first proposed by Addison and coworkers, is the principal measure of the geometry of five-coordinate transition metal complexes, with τ5 = 0 said to describe a perfect square pyramidal geometry and τ5 = 1 a perfect trigonal pyramidal geometry. Therefore, the geometries of all five-coordinate complexes are assumed to lie on a continuum between these two extremes. Herein we show that there are a significant number of examples of transition metal complexes having τ5 > 1, leading to an equatorially distorted trigonal bipyramidal geometry with the transition metal ion lying out of the plane of the equatorial donor atoms.

Identification of potent, highly constrained CGRP receptor antagonists.

A novel series of potent CGRP receptor antagonists containing a central quinoline ring constraint was identified. The combination of the quinoline constraint with a tricyclic benzimidazolinone left hand fragment produced an analog with picomolar potency (14, CGRP K(i)=23 pM). Further optimization of the tricycle produced a CGRP receptor antagonist that exhibited subnanomolar potency (19, CGRP K(i)=0.

Previous trauma exposure and PTSD symptoms as predictors of subjective and biological response to stress.

Objective: The immediate and long-term effects of traumatic exposure and subsequent posttraumatic stress reactions in people in high-risk occupations are well-documented. What is less evident is the impact of this traumatic exposure and subsequent traumatic stress symptoms on workers' response to acute stress situations. This study aimed to examine the association between prior traumatic exposure related to policing, current posttraumatic stress symptoms and biological markers of stress, and subjective appraisal of stress before, during, and after exposure to acutely stressful stimuli.

Does posttraumatic stress disorder (PTSD) affect performance?

Research has increasingly identified alarming levels of traumatic stress symptoms in individuals working in emergency services and other high stress jobs. This study examined the effects of prior critical incident exposure and current posttraumatic symptoms on the performance of a nonpatient population, police recruits, during an acutely stressful event. A stressful policing situation was created through the use of a video simulator room that was responsive to actions of participants.

3-Substituted gem-cyclohexane sulfone based gamma-secretase inhibitors for Alzheimer's disease: conformational analysis and biological activity.

Previously, chemistry effort on the gem-cyclohexane series of gamma-secretase inhibitors has focused on the 4-position of the cyclohexane ring. Recently chemistry has been directed towards the 3-position and substitution here has also provided compounds with high gamma-secretase activity.

NK1 antagonists based on seven membered lactam scaffolds.

A new class of high affinity hNK1R antagonists based on seven-membered ring cores has been identified. This series, with relatively simple, compact structures, includes compounds with high affinity, good selectivity, and promising in vivo properties.

The impact of high risk human papillomavirus testing in an inner London colposcopy clinic.

This is an audit of a new technique to improve the colposcopy service. Samples were tested for high risk HPV DNA using Digene Hybrid Capture II. Sixty-four percent of the sampled women under 30 had detectable high risk HPV DNA, decreasing to 44% in 30--39 year olds and to 27% in women over 40.

Detection of persistent high risk human papillomavirus infections with hybrid capture II and SPF10/LiPA.

Background: HPV infection in young women is common. However only a certain number of HPV genotypes are oncogenic. It is necessary for high risk HPV infection to persist at the cervix for a considerable time before oncogenesis occurs.

Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site.

The identification of a novel series of 7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines as GABA(A)alpha5 inverse agonists, which have both binding and functional (efficacy) selectivity for the benzodiazepine binding site of alpha5- over alpha1-, alpha2-, and alpha3-containing GABA(A) receptor subtypes, is described. Binding selectivity was determined to a large part by the degree of planarity of the fused ring system whereas functional selectivity was dependent on the nature of the heterocycle at the 3-position of the triazolopyridazine ring. 3-Furan and 5-methylisoxazole were shown to be optimal for GABA(A)alpha5 functional selectvity.

Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers.

Nonselective inverse agonists at the gamma-aminobutyric acid(A) (GABA-A) benzodiazepine binding site have cognition-enhancing effects in animals but are anxiogenic and can precipitate convulsions. Herein, we describe novel GABA-A alpha5 subtype inverse agonists leading to the identification of 16 as an orally active, functionally selective compound that enhances cognition in animals without anxiogenic or convulsant effects. Compounds of this type may be useful in the symptomatic treatment of memory impairment associated with Alzheimer's disease and related dementias.

Synthesis and conformational dynamics of tricyclic pyridones containing a fused seven-membered ring.

A new synthetic approach to tricyclic pyridones bearing a fused seven-membered ring is described. These compounds exhibit atropisomerism and exist in enantiomeric forms. Chiral HPLC separation of the enantiomers has allowed the rates of racemization to be measured and hence the free energy barrier for flipping the seven-membered ring to be deduced.

Personality Perceptions of Medical School Applicants.

Purpose To examine the extent to which medical school interviewers consider perceptions of applicant personality traits during a semi-structured panel interview, the interrater reliability of assessments, and the impact of such perceptions on individual admission decisions. Method Semi-structured panel interviews were conducted with applicants to the Doctor of Medicine Program at the University of Western Ontario in London, Canada. Interviewers also provided voluntary, "research only" ratings of applicants on nine relevant personality traits.

A randomized comparison of psychological (cognitive behavior therapy), medical (fluoxetine) and combined treatment for women with premenstrual dysphoric disorder.

This study examines the relative effectiveness of cognitive behavior therapy (CBT) (ten sessions), fluoxetine (20 mg daily) and combined therapy (CBT plus fluoxetine) in women with premenstrual dysphoric disorder (PMDD). This was a randomized pragmatic treatment trial with three treatment cells. Treatment lasted for 6 months; a naturalistic follow-up was undertaken 1 year post-treatment.

Medical (fluoxetine) and psychological (cognitive-behavioural therapy) treatment for premenstrual dysphoric disorder: a study of treatment processes.

Objectives: To investigate (i) the differential changes in premenstrual symptoms, mood, cognitions, and coping strategies during two treatments [cognitive-behavioural therapy (CBT) and fluoxetine] for premenstrual dysphoric disorder (PMDD) and (ii) the characteristics of those with good vs. poor outcome post treatment and at 1 year follow-up.

Methods: Premenstrual symptoms, mood (Hospital Anxiety and Depression Scale, HADS), causal attributions, and use of cognitive and behavioural coping strategies were examined during 6 months of both treatments.

Detection and genotyping of human papillomavirus DNA by SPF10 and MY09/11 primers in cervical cells taken from women attending a colposcopy clinic.

Human papillomavirus (HPV) is the main etiological agent of cervical cancer. There is a large number of HPV genotypes and therefore a need to distinguish the high risk HPV genotypes associated with invasive cancer from the low risk. Because persistence of high risk HPV infection is necessary for progression of a pre-invasive cervical change one needs to identify the individual genotype to see if it persists.