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PubMed2000

Estrogen agonist (zeranol) treatment in a castrated male lamb model: effects on growth and bone mineral accretion.

The mechanism of estrogen's action on bone mineralization in children has received little attention. Our objective was to determine the effect of time (developmentally) and duration of exposure to an estrogen agonist (zeranol) on bone growth and mineralization using a castrated male lamb model. At birth, 40 male lambs were castrated and within 14 days of birth (day = 0) they were assigned (n = 10 per group) to age-matched control lambs (C-AGE) or to receive a 12.5-mg zeranol implant as follows: E-0, implanted on days 0, 45, 90, and 135; E-90, implanted on days 90 and 135; and E-0, 90, implanted on days 0, 90, and 135. Lambs were studied for 163 days. Serum was collected on days 28, 73, 118, 135, and 163 and analyzed for minerals (Ca, P, and Mg), markers of bone remodeling (bone alkaline phosphatase [ALP] and tartrate resistant acid phosphatase [TRAP]), 1,25-dihydroxyvitamin D [1,25(OH)2D], growth hormone (GH), and insulin-like growth factor I (IGF-I). Whole-body bone mineral content (BMC), bone mineral density (BMD), fat mass, and lean mass were determined by dual energy X-ray absorptiometry (DEXA) on days 28, 73, 118, and 163. There was a linear increase in growth at all time points. Whole-body BMC, weight, and lean mass of C-AGE and E-90 lambs were less than E-0, and E-0, 90 lambs at all time points. Whole-body BMD of C-AGE and E-90 lambs was less than E-0 and E-0, 90 lambs at 28 days and 73 days; however, after implantation at day 90 whole-body BMD of E-90 lambs was similar to E-0 and E-0, 90 lambs at day 118 and day 163 and all three were greater than C-AGE lambs. There was no effect of treatment on calcium absorption, serum minerals, hormones, or markers of bone remodeling. We conclude from these data that treatment of growing castrated lambs with an estrogen agonist from birth augments growth, whereas delaying estrogen agonist treatment does not facilitate growth but appears to augment bone mineral accretion. We suggest these observations may have clinical relevance, and deserve consideration when treating children with delays in growth and bone mineral accretion.

Animals↗
PubMed1998

Rates of change in spinal bone density among Japanese women.

To determine the rates of change in bone mineral density (BMD) at the spine in healthy Japanese women, longitudinal measurements of spinal BMD using dual X-ray absorptiometry were collected from 984 women over 17 years of age (mean age 51.6) at eight medical research centers. They were followed up for 20.9 months on average without any treatment influencing bone and calcium metabolism. Measurements of BMD obtained by two different scanners were converted into standardized BMD (sBMD) values. The multiple linear regression model predicts that spinal sBMD increases up to about 23 years of age: the estimated average rates of increases were 0.13%/year for women aged 20 years. After the age of 23, the sBMD began decreasing: the rates of loss increased by 0.045%/year for each year increase in age among premenopausal women. In perimenopausal women, the rate of loss was 2. 1%/year. In postnatural menopausal women, the rates of loss decreased exponentially with increasing years since menopause. The rates of loss increased by 0.04%/year for 1 kg decrease in body weight or by 0.1%/year for 1 kg/m2 decrease in body mass index. No significant differences in changes in sBMD were found between scanners and between centers after multiple adjustment. We conclude that the rates of change in spinal sBMD are associated with age in premenopausal women, and with years since menopause and weight or BMI in postmenopausal women. Caution is needed, however, when using data from different densitometers to evaluate rates in bone loss in multicenter trials.

Adolescent↗
PubMed2006

Reasons for condom use among young people in KwaZulu-Natal: prevention of HIV, pregnancy or both?

CONTEXT: High levels of HIV/AIDS and unwanted pregnancy among young people are urgent public health problems in South Africa. Studies among youth have generally focused on protection against one or the other of these risks, but not both. METHODS: Data collected in 2001 from 2,067 sexually active men and women aged 15-24 in KwaZulu-Natal were examined in bivariate and multivariate analyses to assess reasons for condom use, and levels and determinants of use. RESULTS: Overall, 59% of respondents said that they used condoms at last sexual intercourse, including 6% who used them with another method. The main reason for use (cited by 64% of users) was protection against both pregnancy and HIV infection. Two-thirds of respondents thought that becoming or making someone pregnant in the next few weeks would be a big problem; fewer than one in five viewed their risk of HIV infection as medium or high. Among both sexes, young people who would consider a pregnancy highly problematic were more likely to use condoms than their counterparts who would view a pregnancy as no problem (odds ratios, 1.4-2.3). In sharp contrast, young men and women who perceived themselves as having a medium to high risk of HIV infection were less likely to use condoms than their counterparts who perceived themselves as being at no risk (0.2-0.3). CONCLUSION: Prevention programs could increase condom use in this population by increasing awareness of the twin risks of pregnancy and HIV infection, and by promoting condoms for protection against these dual risks.

Adolescent↗
PubMed1999

Purification and quantitation of tumor necrosis factor receptor immunoadhesin using a combination of immunoaffinity and reversed-phase chromatography.

The development of an automated, dual column assay to quantitate and recover the glycoprotein, tumor necrosis factor receptor immunoadhesin (TNFr-IgG) from monkey plasma, human serum, cell culture fluid and buffer samples is described. A combination of immunoaffinity and reversed-phase chromatographies are used. The targeted protein was captured using an anti-TNFr-1 monoclonal antibody immobilized on POROS resin. After non-specific adsorption had been reduced, the affinity column was placed in-line with a reversed-phase column and eluted with dilute acid. The reversed-phase column was subsequently eluted with an acetonitrile gradient and the TNFr-IgG collected and quantitated by comparison with peak areas of similarly treated standards. Detection was performed by measurement of absorbance at 214 nm. The dynamic range is from 0.5-15 microg total sample. Samples were quantitated and recovered from monkey and human pharmacokinetics samples, as well as from cell culture fluid and buffers. The lowest concentrations assayed were 100 ng ml(-1). Quantitation is reproducible, with a coefficient of variation of 2%. The procedure was used to develop a pharmacokinetic profile for the clearance of TNFr-IgG in humans and cynomolgus monkeys. Sufficient material was recovered such that the glycoforms could be identified. Additionally it has been used for process monitoring. The results compared favorably with data generated by ELISA. Optimization of the method and results are presented.

Animals↗
PubMed2002

Characterization of COX19, a widely distributed gene required for expression of mitochondrial cytochrome oxidase.

COX19, a nuclear gene of Saccharomyces cerevisiae, was cloned by transformation of a respiratory-deficient mutant from complementation group G188 of a pet mutant collection. The gene codes for an 11-kDa protein (Cox19p) required for expression of cytochrome oxidase. Because cox19 mutants are able to synthesize the mitochondrial and nuclear gene products of cytochrome oxidase, Cox19p probably functions post-translationally during assembly of the enzyme. Cox19p is present in the cytoplasm and mitochondria, where it exists as a soluble intermembrane protein. This dual location is similar to what was previously reported for Cox17p, a low molecular weight copper protein thought to be required for maturation of the CuA center of subunit 2 of cytochrome oxidase. The similarity in their subcellular distribution, combined with the presence of four cysteines in Cox19p that align with a subset of the cysteines in Cox17p, suggests that like the latter, Cox19p may function in metal transport to mitochondria.

Amino Acid Sequence↗
PubMed1998

Gonadotrophin storage patterns in the ewe during the oestrous cycle or after long-term treatment with a GnRH agonist.

The storage pattern of gonadotrophins in the ewe pituitary was investigated during the oestrous cycle and after desensitization to GnRH using long-term treatment with a GnRH agonist, buserelin. Oestrous cycles in ewes were synchronized with progestagen sponges. Animals were allocated to two experiments. In the first, ewes were killed 36 h (before the preovulatory surge, n = 4), 48 h (end of the preovulatory surge, n = 5), 72 h (post-ovulation, n = 4) and 240 h (luteal phase, n = 3) after sponge removal. In the second experiment, another progestagen sponge was inserted in ewes 84 h after removal of the first sponge. Four ewes were infused continuously with buserelin (50 micrograms/day) for 15 days before killing. A further four ewes received no buserelin (controls). Pituitaries were collected and processed for immunocytochemistry to detect monohormonal (LH or FSH) and multihormonal (LH/FSH) cells. The percentages of LH or FSH immunoreactive cells in the pituitary were lower at the end of the preovulatory surge (7.4 +/- 0.3% and 1.2 +/- 0.3% respectively) compared with the other stages (11.4 +/- 0.5% and 5.4 +/- 0.7% respectively). Analysis of dual immunostaining showed the existence of monohormonal cells for LH and multihormonal cells (LH/FSH). No monohormonal cell for FSH was detected except at the end of the preovulatory surge when a few monohormonal FSH cells appeared (0.1 +/- 0.01% of pituitary cells). The percentage of monohormonal LH cells in the pituitary gland was similar in all studied stages of the oestrous cycle, whereas the percentage of multihormonal cells was lower at the end of the surge. In agonist-treated ewes, the percentages of LH or FSH immunoreactive cells (5.3 +/- 0.5% and 1.5 +/- 0.8% respectively) were decreased compared with controls (9.4 +/- 1% and 7.5 +/- 1.1% respectively). Analysis of the double immunostaining revealed a few monohormonal FSH cells (0.2 +/- 0.01% of pituitary cells) in agonist-treated ewes but not in controls. The percentage of monohormonal LH cells in the pituitary gland increased from 1.9 +/- 0.2% in controls to 3.8 +/- 0.3% in agonist-treated ewes, whereas multihormonal cells dropped from 7.5 +/- 1.1% to 1.3 +/- 0.7%. Our data suggest, therefore, that multihormonal cells contribute to gonadotrophin secretion, either during the preovulatory surge of the oestrous cycle or during the 'flare-up' effect initially induced by a GnRH agonist. Moreover, the appearance of monohormonal FSH cells in some conditions reflects a differential regulation of LH and FSH.

Animals↗
PubMed2006

Remission of psychiatric symptoms among drug misusers after drug dependence treatment.

The study investigates changes in psychiatric symptoms after drug dependence treatment, and relationships between pretreatment problems, illicit drug use, treatment retention, and changes in psychiatric symptoms. The sample comprised 662 drug-dependent adults recruited at admission to treatment in residential rehabilitation programs (15 agencies) or outpatient methadone treatment (16 methadone maintenance programs and 15 methadone reduction programs). Using a longitudinal, prospective cohort design, data were collected by structured interviews at intake to treatment and at 1-month and 6-month follow-ups. Reductions were found in a range of psychiatric symptoms after admission to drug dependence treatment and among patients treated in outpatient and in residential programs. These reductions occurred rapidly (during the first month) and were maintained at subsequent follow-up. At intake to treatment, 39% of the residential sample met criteria for psychiatric caseness. This figure dropped to 3% at both 1-month and 6-month follow-up. Among methadone patients, 15% met criteria for psychiatric caseness at intake, and this dropped to 5% at 1 month and 3% at 6 months. Improvement in psychiatric symptoms was positively related to treatment retention. Some of the psychiatric symptoms presented by drug-dependent patients at admission to treatment are associated with drug misuse and show rapid remission after substance misuse treatment.

Adolescent↗
PubMed1994

The pre-registration year. It's time for job reprofiling.

The pre-registration house officers' year has a dual purpose. On the one hand, there is the basic service requirement for long hours of routine assistance to senior medical staff. On the other hand, there is the educational component of the job as seen in the GMC and post-graduate deans' objectives. Reports on a study which shows there is considerable tension between these two objectives. Examines the extent and nature of this divergence. Suggests that there are two problems to be addressed: how best to generate a sense of ownership and affinity to the trust hospital, and even more fundamental, requires a strategic audit and reappraisal of the purpose of the pre-registration year and strongly suggests the desirability of reprofiling it in order to provide a rich working experience and learning environment.

Data Collection↗
PubMed2005

Multilocus sequence typing of Staphylococcus aureus isolated from high-somatic-cell-count cows and the environment of an organic dairy farm in the United Kingdom.

An outbreak of Staphylococcus aureus intramammary infections on an organic dairy farm was monitored for 10 months. Environmental and milk samples were collected from a total of 26 cows and a group of 21 purchased heifers about to be introduced into the milking herd. There was variation in the rate of isolation of S. aureus (9.5 to 43.8%) from individual mammary quarters, although no S. aureus isolates were detected in the milk samples collected from the heifers. One hundred ninety-one S. aureus isolates were detected from cow milk samples (n = 182), milking machine clusters (n = 4), farm personnel (n = 4), and the environment (n = 1). Multilocus sequence typing (MLST) had a typeability of 100% when it was applied to the 191 isolates. Among the 191 isolates there was limited strain diversity, with seven sequence types (STs) dominated by two strains with closely related STs that differed at a single locus. Within individual mammary quarters there were naturally occurring dual infections, although this was identified in only 0.4% of milk samples. Different strains were associated with variable persistence within quarters. MLST is clearly a very suitable tool for the differentiation and analysis of S. aureus populations detected on dairy cattle farms.

Animals↗
PubMed2005

Simple and straightforward construction of a mouse gene targeting vector using in vitro transposition reactions.

In a gene targeting experiment, the generation of a targeting construct often requires complex DNA manipulations. We developed a set of cassettes and plasmids useful for creating targeting vectors to modify the mammalian genome. A positive selection marker cassette (PGK/EM7p-npt), which included dual prokaryotic and eukaryotic promoters to permit consecutive selection for recombination in Escherichia coli and then in mouse embryonic stem cells, was flanked by two FRT-loxP sequences. The PGK/EM7p-npt cassette was placed between the minimum regions of a Tn7 transposable element for insertion into another DNA by means of Tn7 transposase in vitro. We also constructed a plasmid having a loxP-Zeo-loxP cassette between the modified Tn5 outer elements. These cassettes can be integrated randomly into a given genomic DNA through the in vitro transposition reaction, thus producing a collection of genomic segments flanked by loxP sites (floxed) at various positions without the use of restriction enzymes and DNA ligase. We confirmed that this system remarkably reduced the time and labor for the construction of complex gene targeting vectors.

Alleles↗
PubMed2001

1998 survey of cardiac pacing in South Africa--report of the working group on registries of the cardiac arrhythmia society of South Africa (CASSA).

BACKGROUND: Permanent pacemakers provide effective relief of symptoms and are life-saving in patients with symptomatic heart block. Since pacemakers are only implanted by cardiologists or cardiothoracic surgeons in tertiary hospitals, the rates of pacemaker implantation provide a readily auditable measure of tertiary health care. METHODS: A survey was conducted of pacemaker implantation in South Africa in 1998, using questionnaires completed by implanters and information on the total number of pacemakers sold during the period, supplied by pacemaker distributors. RESULTS: A total of 1,643 new pacemakers were implanted in 1998 by 112 doctors working in 31 institutions (9 public and 22 private). The annual implant rate per million population was 39, compared with 31/million in 1995, an increase of 25.8%. Public hospitals accounted for 31.7% of primary pacemaker implants in 1998 as opposed to 37% in 1995. Practice in the public sector differed from that in the private sector in that atrioventricular (AV) block was the major indication for pacing in 75.3% versus 45.3%, whereas sinus node dysfunction accounted for 34.9% of private patients, as opposed to 16.2% of public hospital patients. Simple VVI single-chamber pacemakers accounted for 49.5% of public hospital implants versus only 9.6% in private patients. The reverse was true for dual-chamber implants (12.1% v. 42.3%). Severe cost constraints in the public sector have resulted in increasing use of cheaper single-chamber pacemakers for more stringent indications (predominantly AV block). The overall implant rate remains low compared with a median of 283/million in Europe. Large discrepancies persist between race groups (232/million whites, as opposed to 8.8/million blacks) and regions (89.3/million in the Western Cape versus 10.8/million in the four provinces without pacemaker implanters). CONCLUSION: It is likely that socio-economic factors play a major role in the unequal distribution of this highly effective treatment for potentially lethal bradyarrhythmias. The changing trends in pacemaker implantations indicate a shift of tertiary health care resources from the public to the private sectors.

Data Collection↗
PubMed1999

The ecological role of the prehensile tail in white-faced capuchins (Cebus capucinus).

Prehensile tails appear to have evolved at least twice in platyrrhine evolution. In the atelines, the tail is relatively long and possesses a bare area on the distal part of its ventral surface that is covered with der-matoglyphs and richly innervated with Meissner's corpuscles. In contrast, the prehensile tail of Cebus is relatively short, fully haired, and lacks specialized tactile receptors. Little is currently known regarding tail function in capuchins, and whether their prehensile tail serves a greater role in feeding or traveling. In this paper we examine patterns of positional behavior, substrate preference, and tail use in wild white-faced capuchins (Cebus capucinus) inhabiting a wet tropical forest in northeastern Costa Rica. Observational data were collected over the course of 3 months on adult capuchins using an instantaneous focal animal time sampling technique. Differences in the frequency and context of tail use, and the estimated amount of weight support provided by the tail relative to other appendages during feeding/foraging and traveling were used as measures of the ecological role of this specialized organ in capuchin positional behavior. During travel, quadrupedal walking, leaping, and climbing dominated the capuchin positional repertoire. The capuchin tail provided support in only 13.3% of travel and was principally employed during below branch locomotor activities. In contrast, tail-assisted postures accounted for 40.6% of all feeding and foraging records and occurred primarily in two contexts. The tail was used to suspend the individual below a branch while feeding, as well as to provide leverage and weight support in above-branch postures associated with the extraction of prey from difficult to search substrates. A comparison of tail use in Cebus, with published data on the atelines indicates that both taxa possess a grasping tail that is capable of supporting the animal's full body weight. In capuchins and howling monkeys, the tail appears to be used more frequently and serves a greater weight-bearing role during feeding than during traveling. In Ateles, and possibly Brachyteles, and Lagothrix, however, the prehensile tail serves a dual role in both feeding and forelimb suspensory locomotion. Additional relationships between white-faced capuchin feeding, positional behavior, extractive foraging techniques, and prehensile tail use are discussed.

Animals↗
PubMed1999

Methods of changing patterns of substance use among individuals with co-occurring schizophrenia and substance use disorder.

Individuals with a severe mental illness and substance use disorder tend to have medical and social problems and to make slower progress in treatment than those who have either disorder alone. Nevertheless, little attention has been paid to the discovery of effective methods of modifying substance use in the severely mentally ill (SMI). The purpose of this study was to collect qualitative data as a way to help identify techniques that might help to change patterns of substance use in the SMI. The participants were 21 men and women who were psychiatric clinic outpatients and who had a current schizophrenia spectrum diagnosis. A total of 18 participants had a lifetime diagnosis of alcohol abuse or dependence, and 21 lifetime other drug diagnoses were recorded for the sample. These individuals participated in focus group discussions about topics related to substance use and people's experiences with trying to quit. The results showed that participants identified several therapeutic and extratherapeutic factors that helped them to initiate and maintain changes in their substance use, as well as factors that hindered change. The findings are related to knowledge about the effectiveness of substance use disorder treatment techniques in general, and implications of the data are discussed for the conduct of integrated treatment of individuals with severe mental illness and a substance use disorder.

Adult↗
PubMed2006

Effect of Social Security payments on substance abuse in a homeless mentally ill cohort.

OBJECTIVES: To determine whether receipt of social supplemental security income (SSI) or Social Security disability income (SSDI) disability payments is associated with increased drug and alcohol use. DATA SOURCES/STUDY SETTING: Secondary analysis of data from 6,199 participants in the Access to Community Care and Effective Social Supports and Services demonstration for the homeless mentally ill. DESIGN: Observational, 12-month, cohort study completed over 4 years. Substance abuse and other outcomes were compared between the participants who did not receive SSI or SSDI during the 12-month study, those newly awarded benefits, and those without benefits throughout the 12 months. DATA COLLECTION METHODS: Social Security administrative records were used to corroborate Social Security benefit status. Drug and alcohol use were measured by self-report and clinician ratings. PRINCIPAL FINDINGS: Participants who did not receive benefits significantly reduced their substance use over time. In generalized estimating equations models that adjusted for potentially confounding covariates, participants who newly received Social Security benefits showed no greater drug use than those without benefits but had significantly more days housed and fewer days employed. Participants whose benefits antedated the demonstration and continued during the 12 months had more clinician-rated drug use over time than those without benefits. CONCLUSIONS: In this vulnerable population, participants with newly awarded benefits did not have any different drug use changes than those without benefits, and had relatively more days housed. The hypothesis that Social Security benefits facilitate drug use was not supported by longitudinal data in this high-risk population.

Adult↗
PubMed2004

Integrated radiotherapy imaging system (IRIS): design considerations of tumour tracking with linac gantry-mounted diagnostic x-ray systems with flat-panel detectors.

The design of an integrated radiotherapy imaging system (IRIS), consisting of gantry mounted diagnostic (kV) x-ray tubes and fast read-out flat-panel amorphous-silicon detectors, has been studied. The system is meant to be capable of three main functions: radiographs for three-dimensional (3D) patient set-up, cone-beam CT and real-time tumour/marker tracking. The goal of the current study is to determine whether one source/panel pair is sufficient for real-time tumour/marker tracking and, if two are needed, the optimal position of each relative to other components and the isocentre. A single gantry-mounted source/imager pair is certainly capable of the first two of the three functions listed above and may also be useful for the third, if combined with prior knowledge of the target's trajectory. This would be necessary because only motion in two dimensions is visible with a single imager/source system. However, with previously collected information about the trajectory, the third coordinate may be derived from the other two with sufficient accuracy to facilitate tracking. This deduction of the third coordinate can only be made if the 3D tumour/marker trajectory is consistent from fraction to fraction. The feasibility of tumour tracking with one source/imager pair has been theoretically examined here using measured lung marker trajectory data for seven patients from multiple treatment fractions. The patients' selection criteria include minimum mean amplitudes of the tumour motions greater than 1 cm peak-to-peak. The marker trajectory for each patient was modelled using the first fraction data. Then for the rest of the data, marker positions were derived from the imager projections at various gantry angles and compared with the measured tumour positions. Our results show that, due to the three dimensionality and irregular trajectory characteristics of tumour motion, on a fraction-to-fraction basis, a 'monoscopic' system (single source/imager) is inadequate for consistent real-time tumour tracking, even with prior knowledge. We found that, among the seven patients studied with peak-to-peak marker motion greater than 1 cm, five cases have mean localization errors greater than 2 mm and two have mean errors greater than 3 mm. Because of this uncertainty associated with a monoscopic system, two source/imager pairs are necessary for robust 3D target localization. Dual orthogonal x-ray source/imager pairs mounted on the linac gantry are chosen for the IRIS. We further studied the placement of the x-ray sources/panel based on the geometric specifications of the Varian 21EX Clinac. The best configuration minimizes the localization error while maintaining a large field of view and avoiding collisions with the floor/ceiling or couch.

Humans↗
PubMed2006

Subchronic urinary bladder effects of muraglitazar in male rats.

Muraglitazar, a PPARalpha/gamma dual agonist, was dosed orally to rats once daily for 13 weeks to evaluate urinary and urothelial changes of potential relevance to urinary bladder tumorigenesis. Groups of 17 young or aged rats per sex were fed a normal or 1% NH4Cl-supplemented diet and were dosed with 0, 1, or 50 mg/kg muraglitazar. Lithogenic ions and sediment were profiled from freshly voided urine samples collected 24 h after dosing, and drug exposures were measured. Urinary citrate, oxalate, and epidermal growth factor (EGF) were assayed from 18-h urine collections. Urothelium was assessed by light microscopy, scanning electron microscopy, and BrdU and TUNEL immunohistochemistry. When fed a normal diet, urine pH was higher in males (above 6.5). Urine volume/body weight was greater in females. Urine soluble/total calcium and magnesium and phosphorus/creatinine ratios were lower in male rats fed a normal diet. Urine citrate levels were decreased and oxalate was increased in young male rats treated with 50 mg/kg muraglitazar compared to age/sex/diet-matched controls. No changes in urine sediment were detected 24 h after dosing. In young male rats treated with 50 mg/kg on normal diet, multifocal urothelial necrosis and proliferation were observed, whereas urothelial apoptosis and urine EGF levels were unchanged compared to age/sex/diet-matched controls. Urothelial necrosis and proliferation were not correlated to systemic or urinary drug exposures and were prevented by dietary acidification. These data suggest that muraglitazar-associated changes in urine composition predispose to urothelial cytotoxicity and proliferation in the urinary bladder of young male rats and that urine sediment must be profiled at multiple daily timepoints to fully qualify drug-induced changes in urine composition.

Age Factors↗
PubMed2000

Psychoactive substance use diagnoses among psychiatric in-patients.

OBJECTIVE: To estimate the prevalence and possible under-diagnosing of substance use disorders and to consider factors that might influence diagnosing of substance use disorders. METHOD: Data collected from case records and PSE interviews of psychiatric in-patients from 12 psychiatric departments in Denmark admitted during October 1996 were compared with data from the Danish Psychiatric Register. RESULTS: A substantially lower prevalence of substance use diagnoses were found in the register (26.1%) than in the research data (50.0%). A high prevalence of co-occurrence between substance use disorders and mental disorders other than substance use disorders was found (37.3%). In the majority of cases knowledge of the substance use disorders was present in the case records, although they had not resulted in a diagnosis. CONCLUSION: The under-diagnosis of substance use disorders is due not only to concealed diagnostic signs and symptoms but also to an under-diagnosis by the psychiatrists, in spite of the fact that information on the substance use was accessible.

Adult↗
PubMed1998

Mechanistic studies of initiator-initiator interaction and replication initiation.

Unlike the chromosome of Escherichia coli that needs only one replication initiator protein (origin recognition protein) called DnaA, many plasmid replicons require dual initiators: host-encoded DnaA and a plasmid-encoded origin recognition protein, which is believed to be the major determinant of replication control. Hitherto, the relative mechanistic roles of dual initiators in DNA replication were unclear. Here, we present the first evidence that DnaA communicates with the plasmid-encoded pi initiator of R6K and contacts the latter at a specific N-terminal region. Without this specific contact, productive unwinding of plasmid ori gamma and replication is abrogated. The results also show that DnaA performs different roles in host and plasmid replication as revealed by the finding that the ATP-activated form of DnaA, while indispensable for oriC replication, was not required for R6K replication. We have analyzed the accessory role of the DNA bending protein, integration host factor (IHF), in promoting initiator-origin interaction and have found that IHF significantly enhances the binding of DnaA to its cognate site. Collectively, the results further advance our understanding of replication initiation.

Bacterial Proteins↗