Estimating the total prevalence of PTSD among the UK police force: Formal comment on Stevelink et al. (2020).

Two recent surveys have reported widely differing prevalence rates for posttraumatic stress disorder (PTSD) within the U.K. police force.

Complete genome of the thermophilic purple sulfur Bacterium Thermochromatium tepidum compared to Allochromatium vinosum and other Chromatiaceae.

The complete genome sequence of the thermophilic purple sulfur bacterium Thermochromatium tepidum strain MC (DSM 3771) is described and contrasted with that of its mesophilic relative Allochromatium vinosum strain D (DSM 180) and other Chromatiaceae. The Tch. tepidum genome is a single circular chromosome of 2,958,290 base pairs with no plasmids and is substantially smaller than the genome of Alc.

Cultivation and characterization of snowbound microorganisms from the South Pole.

Little is known about microbial ecosystems of interior Antarctica, if indeed such ecosystems exist. Although considerable research has assessed microorganisms indigenous to coastal regions of Antarctica, particularly their lakes, ponds, and soils, to our knowledge only one characterized bacterium, a strain of Pseudomonas, has been isolated from South Pole ice or snow. Metagenomic community analyses described in this work and elsewhere reveal that a diversity of bacteria exists in inland polar snows, yet attempts to culture and characterize these microbes from this extreme environment have been few to date.

Large genome-wide association study identifies three novel risk variants for restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.

Posttraumatic stress disorder and complex posttraumatic stress disorder in UK police officers.

Background: We investigated work-related exposure to stressful and traumatic events in police officers, including repeated exposure to traumatic materials, and predicted that ICD-11 complex PTSD (CPTSD) would be more prevalent than posttraumatic stress disorder (PTSD). The effects of demographic variables on exposure and PTSD were examined, along with whether specific types of exposure were uniquely associated with PTSD or CPTSD.

Methods: An online survey covering issues about trauma management, wellbeing and working conditions was disseminated via social media and official policing channels throughout the UK.

Analysis of the Complete Genome of the Alkaliphilic and Phototrophic Firmicute Strain HH.

Despite significant interest and past work to elucidate the phylogeny and photochemistry of species of the , genomic analyses of heliobacteria to date have been limited to just one published genome, that of the thermophilic species (.) str. Ice1.

A shorter working week for everyone: How much paid work is needed for mental health and well-being?

There are predictions that in future rapid technological development could result in a significant shortage of paid work. A possible option currently debated by academics, policy makers, trade unions, employers and mass media, is a shorter working week for everyone. In this context, two important research questions that have not been asked so far are: what is the minimum amount of paid employment needed to deliver some or all of the well-being and mental health benefits that employment has been shown to bring? And what is the optimum number of working hours at which the mental health of workers is at its highest? To answer these questions, this study used the UK Household Longitudinal Study (2009-2018) data from individuals aged between 16 and 64.

Restless legs syndrome is associated with major comorbidities in a population of Danish blood donors.

Background: Restless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and is thus linked with psychosocial distress. Due to the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications.

Prevalence of restless legs syndrome and associated factors in an otherwise healthy population: results from the Danish Blood Donor Study.

Objective: Restless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by uncomfortable sensations in the legs. RLS often occurs as a comorbid condition. Besides an increased risk of iron deficiency, blood donors are considered to be generally healthy.

A novel method for the immunoquantification of UDP-glucuronosyltransferases in human tissue.

Glucuronidation is a major pathway of drug and xenobiotic metabolism that is catalyzed by members of the UDP-glucuronosyltransferase (UGT) family. Predicting the contribution of individual UGTs to drug metabolism would be of considerable value in drug development and would be greatly aided by the availability of detailed absolute expression levels of these proteins; this is hampered by the lack of purified protein standards because of the hydrophobic membrane-associated nature of UGTs and the consequential difficulties in expression and purification. Here we describe a novel solution to this problem by expressing UGTs in Escherichia coli as fusion proteins with ribonuclease S-peptide, targeted to the periplasm with the pelB leader sequence.

Validation of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey.

Background And Purpose: Epidemiological studies of restless legs syndrome (RLS) have been limited by lack of a well validated patient-completed diagnostic questionnaire that has a high enough specificity to provide a reasonable positive predictive value. Most of the currently used patient completed diagnostic questionnaires have neither been validated nor included items facilitating the differential diagnosis of RLS from conditions producing similar symptoms. The Cambridge-Hopkins diagnostic questionnaire for RLS (CH-RLSq) was developed with several iterations to include items covering the basic diagnostic features of RLS and to provide some basic differential diagnosis.

RLS and blood donation.

Background And Purpose: The link between brain iron deficiency and RLS is now well established. In a related observation, several conditions that can deplete iron stores have been linked to increased probability of RLS. Blood donation has been linked to iron deficiency.

Amino terminal domains of human UDP-glucuronosyltransferases (UGT) 2B7 and 2B15 associated with substrate selectivity and autoactivation.

Despite the important role of UDP-glucuronosyltransferases (UGT) in the metabolism of drugs, environmental chemicals and endogenous compounds, the structural features of these enzymes responsible for substrate binding and selectivity remain poorly understood. Since UGT2B7 and UGT2B15 exhibit distinct, but overlapping, substrate selectivities, UGT2B7-UGT2B15 chimeras were constructed here to identify substrate binding domains. A UGT2B7-15-7 chimera that incorporated amino acids 61-194 of UGT2B15 glucuronidated the UGT2B15 substrates testosterone and phenolphthalein, but not the UGT2B7 substrates zidovudine and 11alpha-hydroxyprogesterone.

Molecular and functional characterization of microsomal UDP-glucuronic acid uptake by members of the nucleotide sugar transporter (NST) family.

Transport of the co-substrate UDPGA (UDP-glucuronic acid) into the lumen of the endoplasmic reticulum is an essential step in glucuronidation reactions due to the intraluminal location of the catalytic site of the enzyme UGT (UDP-glucuronosyltransferase). In the present study, we have characterized the function of several NSTs (nucleotide sugar transporters) and UGTs as potential carriers of UDPGA for glucuronidation reactions. UDPGlcNAc (UDP-N-acetylglucosamine)-dependent UDPGA uptake was found both in rat liver microsomes and in microsomes prepared from the rat hepatoma cell line H4IIE.

Identification of the human liver UDP-glucuronosyltransferase involved in the metabolism of p-ethoxyphenylurea (dulcin).

Dulcin (DL), now banned, was once a widely used artificial sweetener. DL possesses an ureido group that is metabolized by direct glucuronidation in rabbit liver microsomes. Dulcin N-glucuronide (DNG) is the only type of ureido N-glucuronide known to date; ureido glucuronidation in humans has not been previously reported.

Glucuronidation of SN-38 and NU/ICRF 505 in human colon cancer and adjacent normal colon.

Background: Glucuronidation represents a novel mechanism of intrinsic drug resistance in colon cancer cells. To safely reverse this mechanism in vivo, it is essential to identify which isoforms of UDP-glucuronosyltransferases are responsible for catalysing this drug metabolism in tumour tissue.

Materials And Methods: LC-MS was applied to measure rates of glucuronidation of two anticancer compounds (SN-38 and NU/ICRF 505) by patient colon cancer biopsies and paired normal colon.

Substrate specificity of human hepatic udp-glucuronosyltransferases.

Five human hepatic UDP-glucuronosyltransferases (UGTs) catalyze the facilitated excretion of more than 90% of drugs eliminated by glucuronidation. The substrate specificity of these UGTs has been examined using cloned expressed enzymes and liquid chromatography-mass spectrometry assays to determine the intrinsic clearance of drug glucuronidation in vitro. Specific substrates for the five individual UGTs have been identified.

Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily.

Several novel UDP glycosyltransferase (UGT) genes, mainly UDP glucuronosyltransferases, have been identified in the human, mouse and rat genomes and in other mammalian species. This review provides an update of the UGT nomenclature to include these new genes and prevent the confusion that arises when the same gene is given different names. The new genes are named following previously established recommendations, taking into consideration evolutionary relatedness and the names already in general usage in the literature.

Application of high-performance liquid chromatography-electrospray ionization-mass spectrometry to measure microsomal membrane transport of glucuronides.

A primary reason for poor characterization of microsomal transport to date is the limitations of the measurement techniques used. Radiodetection provides sufficient sensitivity, but it can be applied only when labeled analogue is available. In this article, we report the novel application of high-performance liquid chromatography and electrospray tandem mass spectrometry (LC-MS/MS) in "rapid filtration" transport assays.

Identification of the rabbit liver UDP-glucuronosyltransferase catalyzing the glucuronidation of 4-ethoxyphenylurea (dulcin).

Dulcin (DL), 4-ethoxyphenylurea, a synthetic chemical about 200 times as sweet as sucrose, has been proposed for use as an artificial sweetener. DL is excreted as a urinary ureido-N-glucuronide after oral administration to rabbits. The phenylurea N-glucuronide is the only ureido conjugate with glucuronic acid known at present; therefore, DL is interesting as a probe to search for new functions of UDP-glucuronosyltransferases (UGTs).

Assessment of catechol induction and glucuronidation in rat liver microsomes.

Catechols are substances with a 1,2-dihydroxybenzene group from natural or synthetic origin. The aim of this study was to determine whether catechols (4-methylcatechol, 4-nitrocatechol, 2,3-dihydroxynaphthalene) and the antiparkinsonian drugs, entacapone and tolcapone, at doses 150 to 300 mg/kg/day, for 3 days, are able to enhance their own glucuronidation. The induction potency of catechols on rat liver UDP-glucuronosyltransferases (UGTs) was compared with that of a standard polychlorinated biphenyl (PCB) inducer, Aroclor 1254.

Evidence for multiple glucuronide transporters in rat liver microsomes.

The transport of glucuronides across the endoplasmic reticulum membrane is an important step in the overall process of biotransformation, although the mechanism remains unclear and the participating transporters are unidentified. Using a rapid filtration assay in combination with liquid chromatography-mass spectrometry, we measured the transport of a variety of beta-D-glucuronides in rat liver microsomes and investigated the substrate specificity of the participating transporter(s) by inhibition studies. Time-dependent and bi-directional transport of phenolphthalein glucuronide was detected and the kinetic parameters for transport were determined.

Farnesol is glucuronidated in human liver, kidney and intestine in vitro, and is a novel substrate for UGT2B7 and UGT1A1.

Farnesol is an isoprenoid found in many aromatic plants and is also produced in humans, where it acts on numerous nuclear receptors and has received considerable attention due to its apparent anticancer properties. Although farnesol has been studied for over 30 years, its metabolism has not been well characterized. Recently, farnesol was shown to be metabolized by cytochromes P450 in rabbit; however, neither farnesol hydroxylation nor glucuronidation in humans have been reported to date.

N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7.

Carbamazepine (CBZ) is one of the most widely prescribed anticonvulsants despite a high incidence of idiosyncratic side effects. Metabolism of CBZ is complex, and of the more than 30 metabolites identified, one of the most abundant is CBZ N-glucuronide. To date the uridine diphosphate glucuronosyltransferase (UGT) isoform responsible for the N-glucuronidation of CBZ has not been identified.