SEARCH · Search PubMed

Results for “Dual Data Collection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources

PubMed2006

Longitudinal patterns of alcohol, drug, and mental health need and care in a national sample of U.S. adults.

OBJECTIVE: Use of longitudinal data can help clarify the extent of persistent need for services or persistent problems in gaining access to services. This study examined the level of transient and persistent need and unmet need over time among respondents to a national survey and whether need was met by provision of mental health services or resolved without treatment. METHODS: Data from the longitudinal Health Care for Communities (HCC) household telephone survey were used to produce joint distributions of need status and care for two periods (wave 1 data collected in 1997 to 1998 and wave 2 data collected in 2000 to 2001; N=6,659). Perceived need was measured as self-report of need for help with a mental or substance use problem. Probable clinical need was assessed with the Composite International Diagnostic Interview, the Alcohol Use Disorders Identification Test, and the 12-item Short Form Health Survey. RESULTS: High levels of persistent unmet need for care (44 to 52 percent) were found among respondents who had probable clinical need in wave 1. Although a majority of those with need received some care, an equal proportion (about 30 percent) of those with perceived need only or probable clinical need in wave 1 did not receive any care. A substantial portion of need (22 to 26 percent) appears to have resolved without treatment, which may suggest high levels of transient need. CONCLUSIONS: Persistent patterns of unmet need represent important targets for policy and programs that can improve utilization, including outreach, education, and improved insurance coverage.

Adolescent↗

PubMed1998

Cost-effectiveness of assertive community treatment versus standard case management for persons with co-occurring severe mental illness and substance use disorders.

OBJECTIVE: To determine the cost-effectiveness of Assertive Community Treatment (ACT) in comparison to Standard Case Management (SCM) for persons with severe mental illness and substance use disorders. DATA SOURCES AND STUDY SETTING: Original data on the effectiveness and social costs of ACT and SCM that were collected between 1989 and 1995. Seven community mental health centers in New Hampshire provided both types of treatment. STUDY DESIGN: Persons with schizophrenia, schizoaffective disorder, or bipolar disorder and a concurrent substance use disorder were randomly assigned to ACT or SCM and followed for three years. The primary variables assessed were substance use, psychiatric symptoms, functioning, quality of life, and social costs. DATA COLLECTION METHODS: Effectiveness data were obtained from interviews at six-month intervals with persons enrolled in treatment and with their service providers. Social cost and service utilization data came from client reports; interviews with informal caregivers; provider information systems and Medicaid claims; law enforcement agencies; courts; and community service providers. PRINCIPAL FINDINGS: Participants in both groups showed significant reductions in substance use over time. Focusing on quality of life and substance use outcomes, ACT and SCM were not significantly different in cost-effectiveness over the entire three-year study period. Longitudinal analyses showed that SCM tended to be more efficient during the first two years but that ACT was significantly more efficient than SCM during the final year of the study. CONCLUSIONS: In an adequately funded system, ACT is not more cost-effective than SCM. However, ACT efficiency appears to improve over time.

Adolescent↗

PubMed2005

Response of the alternative complement pathway to an oral fat load in first-degree relatives of subjects with type II diabetes.

OBJECTIVE: To investigate levels of components of the alternative pathway of complement, and of two activation products, ASP and Bb, in persons ranging in insulin resistance both fasting and following the consumption of a high-fat, low-carbohydrate meal. SUBJECTS: Healthy controls (n = 17) and normoglycaemic first-degree relatives of patients with type II diabetes (n = 15). MEASUREMENTS: All subjects had normal glucose tolerance. Blood was collected for the measurement of plasma glucose, insulin, triglycerides and free fatty acids. Body composition was assessed with dual energy X-ray absorptiometry (DEXA) and whole-body insulin sensitivity with a euglycaemic, hyperinsulinaemic clamp. Basal and postprandial values over 6 h were determined for plasma C3, B, D, Bb and ASP. Basal levels of C1q, C4 and CRP were also determined. RESULTS: Controls did not differ significantly from the relatives of patients with type II diabetes for any metabolic parameter except in their degree of insulin resistance and central fat (kg). Across all subjects, basal levels of C3, but no other complement protein, were correlated with insulin resistance. Native complement proteins, but not ASP or Bb, were correlated with body mass index and the amount (kg) of central fat. Basal levels of C3 and factor B were significantly higher in the relatives group, whereas factor D and the classical pathway proteins C1q and C4 did not differ between the two groups. Postprandially, levels of factor D were significantly reduced in both groups. ASP levels also fell postprandially, the decline achieving significance in the relatives group. CONCLUSIONS: Elevated levels of C3 and factor B in the diabetic relatives group may have resulted from increased synthesis by adipose tissue. There was no evidence of alternative pathway activation in response to a fat meal in terms of ASP or Bb production, or significant consumption of C3 and factor B. These data do not support an essential requirement of the hypothesis that ASP is produced in response to the intake of fat.

Adult↗

PubMedDate not supplied

New approach in the treatment of T2DM and metabolic syndrome (focus on a novel insulin sensitizer).

Peroxisome Proliferator-Activate Receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. The three PPARs (alpha, beta/delta, and gamma) are distributed differently in the different organs. PPARalpha is most common in the liver, but also found in kidney, gut, skeletal muscle and adipose tissue, while PPARbeta/delta, is fairly ubiquitous; it may be found in body tissues and brain (for myelination process and lipid metabolism in the brain). PPARgamma has 3 isoforms, such as PPARgamma 1, PPARgamma 2, and PPARgamma 3. The syndrome-X was firstly coined by Reaven in 1988 and then to be provided in 1999 by the name : the metabolic syndrome-X. This metabolic syndrome represents a "Cluster" of metabolic disorders and cardiovascular risk factors which has been collected and summarized by the author and such a cluster includes: insulin resistance/hyperinsulinemia, central obesity, glucose intolerance/DM, atherogenic dyslipidemia (increase TG, decrease HDL-cholesterol, increase Apo-B, increase small dense LDL), hypertension, prothrombotic state (increase PAI-1, increase F-VII, increase fibrinogen, increase vWF, increase adhesion molecules), endothelial dysfunction, hyperuricemia, and increased hsC-RP and cytokines. The metabolic syndrome-X may lead to the development of T2DM and coronary heart disease (CHD); insulin resistance plays pivotal roles in the progression of such a syndrome and cardiovascular diseases. Improvement of Insulin Resistance, therefore, is most likely to reduce the high cardiovascular event rate in T2DM. It has been generally accepted that Insulin Resistance (detected by HOMA-R) and Acute Insulin Response = AIR (by HOMA-B) are both usually present in T2DM. The Thiazolidinedions (TZDs) are Insulin Sensitizers (e.g Rosiglitazone = ROS, Pioglitazone = PIO) introduced into clinical practice in 1997; clinical evidence data showed that TZDs improved both HOMA-R, and HOMA-B. PPARgamma can be activated by TZDs and it appears to be fundamental to the pathophysiology of diabetes mellitus i.e increase GLUT-4, increase glucokinase, decrease PEPCK, increase GLUT-4, and decreases production by fat cell of several mediators that may cause insulin resistance, such as TNFalpha and resistin. PPARgamma also mediates increased production of Adiponectin and the insulin signaling intermediate PI3K, and both actions lead to increase insulin sensitivity. A "dual PPARgamma-PPARalpha agonists" (e.g PIO, but ROS poorly activate PPARalpha) might lower glucose and modulate lipids. Thus, PIO, as a stronger "dual PPARgamma-PPARalpha agonists", shows an important therapeutic pathway in diabetes mellitus and cardiovascular diseases, even in metabolic syndrome. Current evidence suggests a close relationship between activation of PPARgamma and restoration of insulin sensitivity by reductions in TNFalpha and FFAs, and the enhancement of insulin stimulation of PI3-K Pathway and also increase adiponectin & decrease resistin.

Diabetes Mellitus, Type 2↗

PubMed1995

Overexpression in Escherichia coli, folding, purification, and characterization of the first three short consensus repeat modules of human complement receptor type 1.

We have developed a simple expression, isolation, and folding protocol for an SCR oligomer comprising the first three SCRs of complement receptor Type 1 (C3b/C4b receptor, CD35). A T7 RNA polymerase expression system in Escherichia coli was used to express the oligomer as inclusion bodies. The oligomer was recovered from solubilized inclusion bodies using batch adsorption on SP-Sepharose. The oligomer was folded by one-step dilution in 20 mM ethanolamine/1 mM EDTA supplemented with 1 mM GSH/0.5 mM GSSG. The folded material was processed to a concentrated (> 20 mg/ml), usable product of greater than 98% purity using a combination of ultrafiltration, ammonium sulfate treatment, hydrophobic interaction, and size-exclusion chromatography. The yield of folded material varied between 6 and 15 mg/liter culture. The oxidation states of the 12 cysteine residues in SCR(1-3) were identified by HPLC of peptide fragments from a tryptic digest using dual UV/fluorescence detection, collection of selected peaks, and N-terminal sequencing. This methodology confirmed the expected location of disulfide bridges. Equilibrium and velocity sedimentation studies are interpreted in terms of a single sedimenting species with molecular weights of 21,629 and 21,063 by these respective techniques. These values compare to the predicted molecular weight, from amino acid composition, of 21,817. The hydrodynamic properties of the molecule indicate that it is asymmetric with an axial ratio of 1:5.2 or equivalent dimensions of 21 x 110 A. SCR(1-3) has an unusual CD spectrum exhibiting a broad maximum at 220-230 nm and a minimum at 190 nm. There was little evidence of classical secondary structure. The product exhibited concentration-dependent inhibition of complement-mediated lysis of sensitized sheep red blood cells.

Amino Acid Sequence↗

PubMed1993

Generation of a human chromosome 18-specific YAC clone collection and mapping of 55 unique YACs by FISH and fingerprinting.

A yeast artificial chromosome (YAC) library was constructed from a somatic cell hybrid line in which the human chromosome content had been reduced by repeated subcloning to one or two copies of chromosome 18. Screening of 4700 primary yeast transformants generated 74 clones containing a YAC with a human DNA insert averaging 190 kb in size. The human YACs were localized to subregions of chromosome 18 by in situ hybridization of biotin-labeled Alu-PCR products obtained using total yeast DNA as a template. Comparisons of interspersed repetitive sequence-PCR and restriction fragment fingerprint patterns identified five sets of identical and three sets of overlapping YACs. Dual-label fluorescence in situ hybridization interphase mapping was used to determine the order of some nonoverlapping YACs. STS (sequence-tagged site) content mapping was carried out with PCR primers for 56 chromosome 18-specific markers. The identification of YACs containing four known genes--encoding the pituitary adenylate cyclase activating polypeptide (PA-CAP), the myelin basic protein (MBP), ferrochelatase (FECH), and SSAV1, an endogenous retroviral element related to the SSAV virus--provides a precise cytological map position for the respective loci. Our final collection of 55 randomly isolated, unique, and regionally localized YACs (D18S107-D18S161) is distributed over the entire chromosome and collectively covers approximately 12 Mb, i.e., 16% of the estimated 77 Mb of DNA in euchromatin of chromosome 18. These YACs provide reagents for the isolation of genes in these regions and represent nucleation points for the generation of STS to increase coverage of the chromosome by YAC contigs.

Adenylyl Cyclases↗

PubMed2004

Multiplexed fluorescence detection in microfabricated devices with both time-resolved and spectral-discrimination capabilities using near-infrared fluorescence.

We examined the feasibility of using a two-color time-resolved detection scheme with microdevices for DNA sequencing applications. A home-built dual-color optical-fiber-based time-resolved near-infrared (IR) fluorescence microscope successfully coupled lifetime discrimination with color discrimination, increasing fluorescence multiplexing capabilities. The instrument was constructed by using two pulsed-diode lasers (680/780-nm excitation) and two avalanche photodiodes as the basic building blocks. The data were processed using electronics configured in a time-correlated single-photon counting format. The use of near-IR fluorescence detection greatly simplified the hardware and allowed low detection limits (< 0.1nM). We examined the separation of a single-base tract on a microchip and compared the performance with that of conventional capillary gel electrophoresis. The microchip was fabricated in glass and contained an effective separation length of 7.0 cm. It was found that, without incorporating a solid-phase reversible immobilization cleanup procedure, the calculated lifetime of the dye label on the microchip was longer and the standard deviation was larger than those of the same sample analyzed using capillary electrophoresis. Using cleanup steps, the accuracy and precision of the measurements improved. Lifetimes of four near-IR dyes (AlexaFluor680, IRD700, IRD800, and IRD40) used in this study were determined to be 986 ps (RSD=2.1%), 1551 ps (RSD=1.8%), 520 ps (RSD=3.3%), and 788 ps (RSD=4.9%), respectively, in a microchannel filled with poly(dimethylacrylamide) (POP-6) gel. The lifetimes calculated using maximum likelihood estimators provided favorable precision on the microchip, where small numbers of photocounts were collected. An M13mp18 template was sequenced on the microchip using a two-color two-lifetime format with POP-6 as the sieving polymer. Read lengths of 294 bp with calling accuracies of 90.8 and 83.7% were achieved in each color channel. The relatively low calling accuracy and the short read length resulted primarily from the short separation channel, which yielded low electrophoretic resolution.

DNA↗

PubMed1994

Relation between growth hormone and cortisol spontaneous secretion in children.

OBJECTIVE: Dual effects of corticoids upon GH release in man have been described: a rapid, potentiating effect and a delayed suppressive one. Many investigators have used pharmacological doses of glucocorticoids in an attempt to detect this interaction of corticoids and GH. The aim of the present study was to determine the relationship between GH and cortisol spontaneous secretion in children under physiological conditions. DESIGN AND PATIENTS: Nine children aged 7.5-13.5 years with different growth rates were evaluated over a 24-hour period. Four were of normal stature (+/- 2 SD) and five were below 2 SD (familial or constitutional short stature). Blood samples were obtained at 20-minute intervals over a 24-hour period. MEASUREMENTS: GH and cortisol concentrations were measured by radioimmunoassay in each of the 73 samples collected. RESULTS: A significant correlation was obtained between mean 24-hour cortisol concentration and mean 24-hour GH concentration (r = 0.83; P < 0.01), the sum of 24-hour GH pulse amplitudes (r = 0.85; P < 0.01) and the highest 24-hour GH concentration (r = 0.88; P < 0.01). A significant positive correlation was also detected between mean 24-hour cortisol concentration and the number of GH pulses over a 24-hour period (r = 0.70; P < 0.05). However, there was no significant correlation between mean 24-hour GH concentration and number of cortisol pulses over a 24-hour period. The correlation between number of cortisol pulses and number of GH pulses was also non-significant. CONCLUSION: These data suggest an interplay of spontaneous GH and cortisol secretion in children. Physiological plasma cortisol levels may play a role in brain-pituitary regulatory mechanisms of GH secretion.

Adolescent↗

PubMed2001

Antecedents of opioid dependence and personality disorder: attention-deficit/hyperactivity disorder and conduct disorder.

Both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) were explored as possible antecedents of opioid dependence and personality disorder. One hundred adult opioid-dependent, treatment-seeking male inpatients were explored; an extended clinical semistructured interview to collect sociodemographic, drug use related, and clinical data and the Structured Clinical Interview for DSM-IV personality disorders SCID-II were carried out. Four groups of patients, namely ADHD alone (4 patients), ADHD + CD (7 patients), CD alone (47 patients) and no ADHD/no CD (42 patients) were identified and compared with each other. The results indicate that ADHD alone does not predispose to the development of opioid dependence in male inpatients. Childhood ADHD may nevertheless be found more frequently in male opioid addicts due to its comorbidity with CD, which was identified in more than half of our sample. Patients with ADHD history seemed to go through the drug abuse career earlier and to develop more frequently histrionic and obsessive-compulsive personality disorder. Over half of the CD patients developed borderline and/or antisocial personality disorder; both ADHD and CD predispose significantly to the PD development. Early substance use preventive measures are necessary in children and adolescents suffering from CD and from ADHD comorbid with CD.

Adolescent↗

PubMed1997

Resistance to insecticides in insect vectors of disease: est alpha 3, a novel amplified esterase associated with amplified est beta 1 from insecticide resistant strains of the mosquito Culex quinquesfasciatus.

Vector control programmes in many countries face the dual problems of parasite drug resistance and insecticide resistance in the insect vectors of the disease. Here we report for the first time a new esterase-based insecticide resistance mechanism in the filariasis vector Culex quinquefasciatus. The field collected COL strain of C. quinquefasciatus from Columbia was heterogeneous for organophosphorus insecticide resistance. On native polyacrylamide gels it had an elevated beta-naphthyl acetate specific esterase with the same Rf as that for the Est beta 1s involved in insecticide resistance in other strains of this mosquito species. After five generations of temephos insecticide selection, both the esterase specific activity with p-nitrophenyl acetate and the temephos LC50 values were increased, suggesting that elevation of esterase activity was the underlying mechanism of resistance. Western blots with antisera raised to Est alpha 2(1) and Est beta 2(1) from C. quinquefasciatus indicated that the COL strain had an elevated Est alpha 3 enzyme which co-migrated on native gels with Est beta 1. Southern blots indicated that an est alpha 3 gene was amplified in the COL strain and a Cuban mosquito strain (MRes), although the restriction digest patterns of the est beta 1 genes in these two strains are different. In contrast, the Californian TEMR strain, with the amplified est beta 1(1) gene, had no associated elevated Est alpha. Restriction digest patterns for COL and TEMR DNA suggest that they contain an identical est beta 1(1) gene, but our data suggest that the est alpha 3 gene occurs on the same amplicon as an est beta 1 gene although the genes are probably > 10 kb apart. Hence, either the COL strain has two est beta 1 genes or the est beta 1(1) amplicon in TEMR has been disrupted at some stage during the long colonisation of this strain and the amplified est alpha has been lost.

Animals↗

PubMed1996

Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator.

The availability of gene-targeted mice deficient in the urokinase-type plasminogen activator (uPA), urokinase receptor (uPAR), tissue-type plasminogen activator (tPA), and plasminogen permits a critical, genetic-based analysis of the physiological and pathological roles of the two mammalian plasminogen activators. We report a comparative study of animals with individual and combined deficits in uPAR and tPA and show that these proteins are complementary fibrinolytic factors in mice. Sinusoidal fibrin deposits are found within the livers of nearly all adult mice examined with a dual deficiency in uPAR and tPA, whereas fibrin deposits are never found in livers collected from animals lacking uPAR and rarely detected in animals lacking tPA alone. This is the first demonstration that uPAR has a physiological role in fibrinolysis. However, uPAR-/-/tPA-/- mice do not develop the pervasive, multi-organ fibrin deposits, severe tissue damage, reduced fertility, and high morbidity and mortality observed in mice with a combined deficiency in tPA and the uPAR ligand, uPA. Furthermore, uPAR-/-/tPA-/- mice do not exhibit the profound impairment in wound repair seen in uPA-/-/tPA-/- mice when they are challenged with a full-thickness skin incision. These results indicate that plasminogen activation focused at the cell surface by uPAR is important in fibrin surveillance in the liver, but that uPA supplies sufficient fibrinolytic potential to clear fibrin deposits from most tissues and support wound healing without the benefit of either uPAR or tPA.

Animals↗

PubMed2001

Assessing predictive factors for extended hospitalization at acute psychiatric admission.

OBJECTIVE: This study examined whether information obtained early in the hospitalization process can be used to assess a patient's need for extended care. METHODS: A sample of 2,430 inpatients who were admitted to a state psychiatric facility during a one-year index period (January through December 1997) were randomly assigned to a primary sample or a replication sample. Data were collected on demographic characteristics and history of previous hospitalization. The Brief Psychiatric Rating Scale-Anchored Version (BPRS-A) was administered to patients within 48 hours of admission, and four new subscales derived from ratings of newly admitted patients were calculated. Univariate and multivariate analyses were conducted to identify factors associated with whether a patient was discharged to the community or transported to another hospital for extended care. RESULTS: A discriminant analysis of the data correctly identified 70 percent of the patients who were referred for continued hospitalization and 80 percent of the patients who were discharged to the community. The main correlates of the need for extended inpatient services were, in descending order, scores on the BPRS-A resistance subscale, the number of previous referrals for extended hospitalizations, and scores on the BPRS-A positive symptoms and psychological discomfort scales. CONCLUSIONS: BPRS-A subscale scores should be considered to be at least as good as more traditional measures in predicting length of hospitalization.

Adult↗

PubMed2004

A mutation in the nuclear-encoded plastid ribosomal protein S9 leads to early embryo lethality in maize.

Seeds of the lethal embryo 1 (lem1) mutant in maize (Zea mays) display a non-concordant lethal phenotype: whereas the embryo aborts very early, before the transition stage, the endosperm develops almost normally. The mutant was identified in a collection of maize lines that carried the transposon Activation (Ac) at different locations in the genome. Co-segregation and reversion analysis showed that lem1 was tagged by Ac. The lem1 gene encodes a protein that is highly similar to the rice plastid 30S ribosomal protein S9 (PRPS9). lem1 maps to chromosome 1L and appears to be the only copy of prps9 in the maize genome. Green fluorescent protein (GFP) fusion constructs containing only the putative transit peptide (TP) of LEM1 localize exclusively to the plastids, confirming that the LEM1 protein is a PRP. In contrast, GFP fusion constructs containing the entire LEM1 protein co-localize to the plastids and to the nucleus, suggesting a possible dual function for this protein. Two alternative, although not mutually exclusive, explanations are considered for the lem phenotype of the lem1 mutant: (i) functional plastids are required for normal embryo development; and (ii) the PRPS9 has an extra-ribosomal function required for embryogenesis.

Amino Acid Sequence↗

PubMed2003

Revision augmentation mastopexy: indications, operations, and outcomes.

In the absence of any published information on the indications, frequency, and outcomes of revision augmentation/mastopexy, an 8-year retrospective review was undertaken of all patients undergoing revision of a previous augmentation/mastopexy in the senior author's practice. The data collected included original implant type, location and mastopexy type, indication for revision, interval from original surgery, new implant type, location, and associated corrective surgical procedures. A simultaneous review was also performed of all primary augmentation/mastopexies done during the same period. Twenty patients underwent revision of 34 previously performed augmentation/mastopexies. Five patients underwent revisions of a prior revision. Fourteen were bilateral, while 6 were unilateral, for a total of 34 breasts. Forty patients underwent primary augmentation/mastopexy during the same period. Among the revisions, 10 implants were originally subglandular, while 24 were either partly or totally submuscular. Twelve of the previous mastopexies were periareolar, 2 were vertical, and 20 were of the inverted T-type. The indications for revision included capsular contracture in 11 of 20 (55%) patients, nipple ptosis in 11 of 20 (55%) patients, implant malposition in 7 of 20 (35%) patients, dissatisfaction with implant size in 6 of 20 (30%) patients, poor scar in 5 of 20 (25%) patients, breast ptosis in 4 of 20 (20%) patients, nipple malposition in 2 of 20 (10%) patients, and patient preference in 1 of 20 (5%) patients. Most patients had 2 or more indications for revision. The average duration to revision was 7 years. In 13 of 20 (65%) patients, no change in implant type was made. The remainder had exchanges to a different type. In 12 of 20 (60%) patients, no change in implant location was made, whereas 8 of 20 (40%) patients had a change to the subpectoral or dual plane position. In 18 of 20 (90%) patients, the revision included the same type of mastopexy, while in 2 of 20 (10%) patients, the type of mastopexy was changed. Corrective surgical procedures performed included repeat mastopexy, capsulectomy, change of implant type, change of implant location, change of implant size, capsulotomy, capsulorrhaphy, and scar revision. To date, all of the patients are satisfied with their appearance. Follow-up ranged from 2 months to 4 years. Revision augmentation mastopexy is not an uncommon procedure, occurring half as often as primary augmentation/mastopexy in our series. There were 8 common indications for revision, with capsular contracture and recurrent ptosis being the most common. Eight surgical procedures, in various combinations, were performed during revision, with repeat mastopexy being the most common.

Adult↗

PubMed2000

Treatment programmes for people with both severe mental illness and substance misuse.

BACKGROUND: Substance misuse in the context of severe mental illness can have detrimental effects. A variety of treatments exist, but the drive has been to provide programmes integrating treatment of both substance misuse and severe mental illness. Such programmes require additional resources and may require radical redesign of service delivery systems. OBJECTIVES: To evaluate the effectiveness of treatment programmes within psychiatric care for people with problems of both substance misuse and serious mental illness. SEARCH STRATEGY: Biological Abstracts (1985-1998), CINAHL (1982-1998), The Cochrane Library (Issue 3, 1998), The Cochrane Schizophrenia Group's Register of trials (August 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1998) and Sociofile (1974-1998) were comprehensively searched. Citations of all trials were searched and further studies sought from published trials and their authors. SELECTION CRITERIA: All randomised trials of any programme of substance misuse treatment for people with serious mental illness and current problems of substance misuse. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. For homogeneous dichotomous data the Peto odds ratio (OR), and 95% confidence intervals (CI) were calculated on an intention-to-treat basis. MAIN RESULTS: Six relevant studies, four of which were small, were identified. In general, the quality of design and reporting was not high. Clinically important outcomes such as relapse of severe mental illness, violence to others, patient or carer satisfaction, social functioning and employment were not reported. There is no clear evidence supporting an advantage of any type of substance misuse programme for those with serious mental illness over the value of standard care. No one programme is clearly superior to another. REVIEWER'S CONCLUSIONS: The problems posed by substance misuse in the context of severe mental illness will not go away. The current momentum for integrated programmes is not based on good evidence. Implementation of new specialist substance misuse services for those with serious mental illnesses should be within the context of simple, well designed controlled clinical trials.

Comorbidity↗

PubMed2026

Dual β-lactam therapy against high-risk Pseudomonas aeruginosa isolates: a dynamic in-vitro infection model study integrating population genomics with quantitative systems pharmacology modelling and simulations.

BACKGROUND: Pseudomonas aeruginosa has an extraordinary capacity for resistance emergence during treatment, even with newer antipseudomonals. There is a gap in understanding how resistance mechanisms affect the time-course of bacterial response to these newer agents. Traditional approaches for predicting pathogen response to an antibiotic do not apply to combination therapy. We aimed to develop a modelling framework to predict treatment response based on resistome information, using isolates of the worldwide-disseminated high-risk clone sequence type (ST) 235 and β-lactam antibiotics as the example. METHODS: In this hollow-fibre in-vitro infection study, we used three extensively drug-resistant ST235 clinical isolates from the national collection of the Clinical Microbiology Department of the Hospital Son Espases (Palma de Mallorca, Spain) that were hospital-acquired, were isolated following routine microbiological procedures from different patients between 2017 and 2022, were susceptible to ceftolozane-tazobactam, and had different levels of meropenem resistance. The selected isolates (ST235-05, ST235-09, and ST235-10) showed classical β-lactam resistance mechanisms pre-treatment. The isolates were investigated in 240-h dynamic hollow-fibre in-vitro infection models (HFIMs). The studies exposed the isolates to pharmacokinetic profiles of ceftolozane-tazobactam (simulating 1 g of ceftolozane and 0·5 g of tazobactam as a 3-h infusion every 8 h) and meropenem (simulating 6 g per day continuous infusion) as observed in hospitalised patients, as monotherapy and in combination. Treatment response was assessed through the quantification of the time-courses of viable total and resistant bacteria. Whole-genome sequencing identified the mechanisms of emerging resistance. A quantitative systems pharmacology (QSP) approach was used to model total and resistant bacterial counts and corresponding pharmacokinetic data from the HFIM. Monte Carlo simulations were used to predict treatment responses in 1000 virtual infected patients treated with ceftolozane-tazobactam and meropenem as monotherapies or in combination over 10 days. FINDINGS: In the HFIMs, each antibiotic alone amplified resistance by approximately 48 h for all isolates; that is, monotherapies resulted in a higher concentration of resistant bacteria compared with the control treatment at the respective time, except ceftolozane-tazobactam against ST235-10. Combination of ceftolozane-tazobactam and meropenem was synergistic (bacterial counts ≥2 log10 colony forming units [CFU] per mL lower than the best performing monotherapy and initial inoculum) against all isolates and suppressed resistance. Against ST235-10, ceftolozane-tazobactam monotherapy reduced counts to less than 1 log10 CFU per mL from 192 h onwards, whereas the combination reached less than 1 log10 CFU per mL by 24 h. Across strains, population genomics confirmed monotherapy failures were associated with emerging resistance mechanisms (ceftolozane-tazobactam: ampC Ω-loop mutations; meropenem: ftsl mutation). The developed QSP model incorporated baseline resistance mechanisms and those emerging in resistant mutant subpopulations. The model explained and predicted the monotherapy failures involving amplification of these subpopulations, and synergistic killing and resistance suppression by the combination. Simulations using the model predicted bacterial regrowth above the initial inoculum for more than 90% of patients after 0 to approximately 3 days for meropenem monotherapy across all strains and for ceftolozane-tazobactam monotherapy against ST235-05 and ST235-09. For ceftolozane-tazobactam monotherapy against ST235-10, regrowth was predicted for approximately 30% of patients. In contrast, the simulations predicted sustained bacterial killing of at least 2 log10 CFU per mL compared with the initial inoculum by the combination for more than 89% of patients across all strains. INTERPRETATION: To our knowledge, this model is the first to characterise and predict the time-course of responses of clinical isolates to antibiotics only by the resistance mechanisms present and their complex interplay, representing a step towards pathogen-specific, personalised medicine. FUNDING: Australian National Health and Medical Research Council.

Pseudomonas aeruginosa↗

PubMed2005

Mycorrhizal impact on drought stress tolerance of rose plants probed by chlorophyll a fluorescence, proline content and visual scoring.

Micropropagated rose plants (Rosa hybrida L., cv. New Dawn) were inoculated with the arbuscular mycorrhizal (AM) fungus Glomus intraradices (Schenk and Smith) and subjected to different drought regimens. The dual objectives of these experiments were to investigate the mechanism and the extent to which AM can prevent drought damages and whether physiological analyses reveal enhanced drought tolerance of an economically important plant such as the rose. In a long-term drought experiment with four different water regimens, visual scoring of wilt symptoms affirmed that AM in a selected host-symbiont combination increased plant performance. This effect was mostly expressed if moderate drought stress was constantly applied over a long period. In a short-term experiment in which severe drought stress was implemented and plants were allowed to recover after 4 or 9 days, no visual differences between mycorrhizal and non-mycorrhizal roses were observed. Therefore, the early physiological steps conferring drought tolerance were prone to investigation. Proline content in leaves proved to be an unsuitable marker for AM-induced drought tolerance, whereas analysis of chlorophyll a fluorescence using the JIP test (collecting stress-induced changes of the polyphasic O-J-I-P fluorescence kinetics in a non-destructive tissue screening) was more explanatory. Parameters derived from this test could describe the extent of foliar stress response and help to differentiate physiological mechanisms of stress tolerance. AM led to a more intense electron flow and a higher productive photosynthetic activity at several sites of the photosynthetic electron transport chain. A K step, known as a stress indicator of general character, appeared in the fluorescence transient only in drought-stressed non-mycorrhizal plants; conversely, the data elucidate a stabilising effect of AM on the oxygen-evolving complex at the donor site of photosystem (PS) II and at the electron-transport chain between PS II and PS I. If drought stress intensity was reduced by a prolonged and milder drying phase, these significant tolerance features were less pronounced or missing, indicating a possible threshold level for mycorrhizal tolerance induction.

Adaptation, Physiological↗

PubMed2003

A substance P receptor (NK1) antagonist enhances the widespread osteoporotic effects of sciatic nerve section.

The long-term effects of sciatic nerve section on bone mineral density (BMD) were studied using dual-energy X-ray absorptiometry (DEXA) in skeletally mature rats. Unilateral sciatic neurectomy caused the rapid loss of cancellous bone in the proximal and distal femur and tibia in the ipsilateral hindlimb and, to a lesser extent, in the contralateral intact hindlimb. The reduction in BMD rapidly progressed for 4 weeks after sciatic section and then gradually stabilized with no evidence of recovery at 12 weeks. The development of osteoporosis in the contralateral intact hindlimb was a novel finding. There was no evidence of disuse in the normal contralateral hindlimb after unilateral sciatic section; grid-crossing activity over a 24-h interval was unchanged and there was no reduction in weight bearing on the contralateral normal hindpaw during the stance phase of ambulation. Unilateral peripheral nerve lesions have well-documented effects on substance P content and function in the corresponding contralateral intact nerve. We hypothesized that after sciatic section a reduction in substance P signaling might contribute to bone loss in the contralateral hindlimb. Daily administration of the substance P receptor (NK1) antagonist LY303870 for 2 weeks caused significant loss of cancellous bone in the denervated and the contralateral hindlimb, evidence that substance P signaling sustained bone density after nerve section. After sciatic neurectomy there was a 33% reduction in sciatic nerve stimulation-evoked extravasation in the contralateral intact hindlimb, indicating transmedian inhibition of substance P signaling after nerve injury. Furthermore, there was a 50% reduction in the substance P content in both tibias after unilateral sciatic section. Collectively, these data support the hypothesis that a widespread reduction in substance P content in bone contributes to the osteoporotic effects of sciatic neurectomy and that residual substance P signaling maintains bone integrity after nerve section in both the denervated and contralateral intact hindlimb.

Absorptiometry, Photon↗