Self-completed online contact tracing for COVID-19 is associated with reporting fewer contacts: an observational study.

Background: Contact tracing was central to England's approach to controlling coronavirus disease 2019 (COVID-19). England's COVID-19 contact tracing system included a step where cases were invited to provide information through an online 'self-service' portal. It is important to understand whether this had any effect on the numbers of contacts reported.

Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

Objectives: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018.

Study Design: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets.

High prevalence of malnutrition and frailty among older adults at admission to residential aged care.

INTRODUCTION Malnutrition is an under-recognised and under-treated problem often affecting older adults. AIM The aim of this study was to evaluate the prevalence of and factors associated with malnutrition and frailty among older adults at early admission to residential aged care. METHODS A cross-sectional study was undertaken among eligible older adults within the first week of admission to residential aged care.

Using hierarchical clustering to explore patterns of deprivation among English local authorities.

Background: The English Indices of Multiple Deprivation (IMD) is widely used as a measure of deprivation. However, similarly ranked areas can differ substantially in the underlying domains of deprivation. These domains contain a richer set of data that might be useful for classifying local authorities.

Welfare and well-being: towards mental health-promoting welfare systems.

By protecting vulnerable people from poverty and debt, welfare systems can be powerful tools for promoting mental health. However, the details of how welfare systems are implemented determine whether they also cause harm. Here, we review evidence and principles that might guide the development of mental health-promoting welfare systems.

Perceptions of health and healthcare in ex-Army residents of Tameside: a pilot qualitative study.

Background: Local authorities and other service providers need data on their local ex-military communities to be able to plan services. However, published research and data may not be applicable to the local population. Qualitative research offers a relatively low-cost way to get insights into the needs of local ex-military communities.

Health needs of ex-military personnel in the UK: a systematic review and qualitative synthesis.

Background: Despite all local authorities in England signing up to the Armed Forces Covenant, only a small proportion of Joint Strategic Needs Assessments (JSNAs) include detailed consideration of the health of the local ex-military population. This article supports improvements to JSNAs by systematically reviewing published research for evidence of differences in health between the ex-military population and the general public.

Methods: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology for qualitative synthesis of mixed study designs.

Region-specific deficits in dopamine, but not norepinephrine, signaling in a novel A30P α-synuclein BAC transgenic mouse.

Parkinson's disease (PD) is a neurodegenerative disorder classically characterized by the death of dopamine (DA) neurons in the substantia nigra pars compacta and by intracellular Lewy bodies composed largely of α-synuclein. Approximately 5-10% of PD patients have a familial form of Parkinsonism, including mutations in α-synuclein. To better understand the cell-type specific role of α-synuclein on DA neurotransmission, and the effects of the disease-associated A30P mutation, we generated and studied a novel transgenic model of PD.

Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model.

The pathological end-state of Parkinson disease is well described from postmortem tissue, but there remains a pressing need to define early functional changes to susceptible neurons and circuits. In particular, mechanisms underlying the vulnerability of the dopamine neurons of the substantia nigra pars compacta (SNc) and the importance of protein aggregation in driving the disease process remain to be determined. To better understand the sequence of events occurring in familial and sporadic Parkinson disease, we generated bacterial artificial chromosome transgenic mice (SNCA-OVX) that express wild-type α-synuclein from the complete human SNCA locus at disease-relevant levels and display a transgene expression profile that recapitulates that of endogenous α-synuclein.

Characterization and dating of blue ballpoint pen inks using principal component analysis of UV-Vis absorption spectra, IR spectroscopy, and HPTLC.

The ink of pens and ink extracted from lines on white photocopier paper of 10 blue ballpoint pens were subjected to ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR), and high-performance thin-layer liquid chromatography (HPTLC). The R(f) values and color tones of the bands separated by thin-layer chromatography (TLC) analysis used to classify the writing inks into three groups. The principal component analysis (PCA) investigates the pen responsible for a piece of writing, and how time affects spectroscopy of written ink.

5-substituted pyrimidine L-2'-deoxyribonucleosides: synthetic, quantum chemical, and NMR studies.

As a part of an ongoing medicinal chemistry, we report here the synthesis and structure evaluation of 1-(2-deoxy-3,5-di-O-acetylpentofuranosyl)-5-[(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4H-pyrazol-4-ylidene) pyrimidine-2,4(1H,3H)-dione 5 and 5-[bis(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4H-pyrazol-4-yl)methyl-1-(2-deoxy-3,5-di-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione 6 derived from 3',5'-di-O-acetyl-5-formyl-2'-deoxy-β-L-uridine 1. Base hydrolysis of compounds 1 and 6 furnished their deacetylated analogues in good yields, whereas hydrolysis of 5 was troublesome. Structural features of these molecules are discussed by NMR spectra analyses and density functional theory quantum chemical calculations.

QSTR of the toxicity of some organophosphorus compounds by using the quantum chemical and topological descriptors.

Quantum chemical and topological descriptors of some organophosphorus compounds (OP) were correlated with their toxicity LD(50) as a dermal. The quantum chemical parameters were obtained using B3LYP/LANL2DZdp-ECP optimization. Using linear regression analysis, equations were derived to calculate the theoretical LD(50) of the studied compounds.

A regio- and stereo-controlled approach to triazoloquinoxalinyl C-nucleosides.

The synthesis of a new series of acyclic triazoloquinoxalinyl C-nucleosides and their transformation to their cyclic analogs are described following protection, activation, and deprotection with subsequent intramolecular nucleophilic substitution protocol. The antibacterial potency of the new compounds was determined using an inhibition zone diameter test. The results show that 3a and 2b exhibit good activity against Escherichiacoli and Candidaalbicans.

Physiological transgene regulation and functional complementation of a neurological disease gene deficiency in neurons.

The microtubule-associated protein tau (MAPT) and alpha-synuclein (SNCA) genes play central roles in neurodegenerative disorders. Mutations in each gene cause familial disease, whereas common genetic variation at both loci contributes to susceptibility to sporadic neurodegenerative disease. Here, we demonstrate exquisite gene regulation of the human MAPT and SNCA transgene loci and functional complementation in neuronal cell cultures and organotypic brain slices using the herpes simplex virus type 1 (HSV-1) amplicon-based infectious bacterial artificial chromosome (iBAC) vector to express complete loci >100 kb.

Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice lacking both alpha-synuclein and gamma-synuclein.

Alpha-synuclein is intimately involved in the pathogenesis of Parkinson's disease, and has been implicated in the regulation of synthesis, release and reuptake of dopamine (DA). However, mice lacking members of the synuclein family have been reported to display no overt behavioural phenotype. This may be a result of compensatory upregulation of other synucleins during development.

Synthesis and biological evaluation of a C5-biphenyl thiolactomycin library.

Fifteen novel C5 analogues of thiolactomycin (13 biphenyl analogues and two biphenyl mimics) have been synthesised and assessed for their in vitro mtFabH and whole cell Mycobacterium bovis BCG activity, respectively. Analysis of the 15 compounds revealed that six possessed enhanced in vitro activity in a direct mtFabH assay. Encouragingly analogues 11, 12 and 13 gave a significant enhancement in in vitro activity against mtFabH.

Herpes simplex virus type 1 amplicon vectors for the infectious delivery and expression of genomic DNA loci.

A wide range of viral gene transfer technologies has been developed for gene therapy and functional genetic purposes. Different viral vectors vary in transgene capacity, range of infectivity and stability of expression. It is now becoming increasingly apparent that there are distinct advantages in using a complete genomic locus as a transgene to produce physiological levels of tissue-specific, sustained expression.

Acetylene-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme.

Analogues of the natural antibiotic thiolactomycin, with acetylene-based side chains, have the highest recorded in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-[3-(4-acetyl-phenyl)-prop-2-ynyl]-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited more than an 18-fold increased potency, compared to thiolactomycin, against this key condensing enzyme, involved in M. tuberculosis mycolic acid biosynthesis.

Biphenyl-based analogues of thiolactomycin, active against Mycobacterium tuberculosis mtFabH fatty acid condensing enzyme.

Analogues of the antibiotic thiolactomycin, with biphenyl-based 5-substituents, were found to have excellent in vitro inhibitory activity against the recombinant Mycobacterium tuberculosis beta-ketoacyl-ACP synthase mtFabH condensing enzyme. In particular, 5-(4'-benzyloxy-biphen-4-ylmethyl)-4-hydroxy-3,5-dimethyl-5H-thiophen-2-one exhibited approximately a 4-fold increased potency against this key condensing enzyme involved in M. tuberculosis mycolic acid biosynthesis, compared to thiolactomycin.

Catecholase activity associated with copper-S100B.

This study addresses the spectroscopic properties and reactivity associated with the copper-loaded form of S100B isolated from bovine brain. Copper(II)-S100B displays EPR features typical of a type II copper center and is shown here to exhibit catecholase activity, the two-electron oxidation of catechols. The steady-state kinetics associated with the oxidation of several catecholamines has been probed in order to further characterize this activity.

Analogues of thiolactomycin: potential drugs with enhanced anti-mycobacterial activity.

Analogues of the antibiotic thiolactomycin (TLM) have been synthesized and have been shown to have enhanced activity against whole cells of Mycobacterium tuberculosis H37Rv and against mycolic acid biosynthesis in cell extracts of Mycobacterium smegmatis. TLM has a methyl-branched butadienyl side chain attached at position 5 on a 'thiolactone' ring, namely 4-hydroxy-3,5-dimethyl-5H-thiophen-2-one. Various combinations of strong bases were explored to create a reactive anion at position 5 on the thiolactone ring which could react with halides to produce 5-substituted derivatives; the best reagent was two equivalents of lithium-bis-(trimethylsilyl)amide in tetrahydrofuran.

Membrane interactions of the putative fusion peptide (MF alpha P) from fertilin-alpha, the mouse sperm protein complex involved in fertilization.

Mammalian fertilization depends upon successful binding and fusion between the membranes of the spermatozoon and the oocyte. These processes are thought to be mediated by a series of protein-protein interactions in which sperm antigens known as fertilins are thought to play a key role. Using a recently developed fluorescence technique, the interactions of the oligopeptide sequence corresponding to the fusogenic domain of mouse fertilin-alpha (MF alpha P) and phospholipid vesicles have been investigated.

Gastric emptying and intestinal transit of pancreatic enzyme supplements in cystic fibrosis.

Objective: To investigate gastric emptying and intestinal transit of pelleted pancreatin in relation to food boluses.

Methods: Dual isotope scintigraphy combined with breath hydrogen sampling was used to track the concurrent gastric emptying and intestinal transit of 111indium labelled microspheres and a 99mtechnetium labelled tin colloid test meal. Twelve pancreatic insufficient cystic fibrosis patients aged 5 to 38 years performed the study.