Correlates of substance use in a large naturalistic cohort of young people with early and emerging psychosis.

BACKGROUND: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). METHODS: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. RESULTS: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. CONCLUSION: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes.

Tobacco smoking in young people seeking treatment for mental ill-health: what are their attitudes, knowledge and behaviours towards quitting?

INTRODUCTION: Tobacco smoking is a leading cause of preventable death and disease worldwide. Adults with mental ill-health smoke tobacco at substantially higher rates than other adults, with public health approaches effective in the population overall having less impact on those with mental ill-health. However, less is known about the tobacco smoking behaviours, attitudes and knowledge of young people with mental ill-health, despite this being the peak period of onset for both mental illness and cigarette smoking. METHODS: Young people attending a youth mental health centre (providing both primary and specialist care) in Melbourne, Australia were approached by youth peer researchers and asked to complete a survey about smoking behaviours, attitudes and knowledge. We examined smoking and associated attitudes in the sample overall, and as a function of the services accessed. RESULTS: In total, 114 young people completed the survey, with 56.3% reporting lifetime cigarette smoking, 42.0% smoking in the last 12 months and 28.6% in the past week. Of current regular smokers, 75.0% acknowledged they should quit in the future; however, only 23.5% planned to do so in the next month, with 44.4% confident that they could quit. Participants lacked knowledge about interactions between tobacco smoking, mental and physical health. CONCLUSIONS: Youth presenting for mental ill-health had high rates of cigarette smoking relative to population rates. Presentation at youth mental health services may represent a critical window for early intervention to reduce the lifetime impacts of cigarette smoking in mental ill-health. Interventions to support smoking cessation in this group are urgently needed.

First and Second Metatarsophalangeal Joint Open Dislocations: A Case Report.

Dislocation of multiple metatarsophalangeal joint is an uncommon injury. The mechanism of injury is a high energy force distal to proximal with foot in hyperextension at the metatarsophalangeal (MTP) joint. The acute hyperextension of the toe at the moment of injury causes avulsion of the plantar part of the capsule from the junction of head and neck of the metatarsal. If the collateral ligaments remain intact, they maintain the locked fibrocartilaginous plate over the dorsum of the head of the metatarsal, making closed reduction impossible. We report a case of simultaneous 1st and 2nd MTP joint open dislocation. In the present case, we chose the plantar approach utilizing the already present plantar wound. At 18 months post-operative follow-up, there was no instance of redislocations or signs of avascular necrosis of head of metatarsal.

Evaluation of factors contributing to excessive nitrate accumulation in fodder crops leading to ill-health in dairy animals.

A study was conducted to estimate nitrate content in commonly used fodder crops, viz., berseem (Trifolium alexandrinum), bajra (Pennisetum glaucum), maize (Zea mays), oats (Avena sativa), sorghum (Sorghum vulgare) and toriya (Brassica napus), collected from the fields of different villages of Punjab and farms of the university, and to evaluate the factors associated with nitrate accumulation in these crops. The nitrate level was highest in sorghum on dry matter basis, followed by oats and toriya, berseem, maize and bajra. The nitrate content was also determined in fodder samples harvested from young and mature stages and in different parts of plants. The stem part of forages had higher content than leaves; however, concentrations were low in mature crops as compared to immature ones. The environmental and soil factors associated with it are discussed and correlated with the experimental findings.

Ecstasy (MDMA) and high prevalence psychiatric symptomatology: somatic anxiety symptoms are associated with polydrug, not ecstasy, use.

Although previous studies have examined anxiety and depression in ecstasy (+/-3,4-methylenedioxymethamphetamine; MDMA) users, it remains unclear whether symptoms are associated specifically with ecstasy or with polydrug use in general. We compared mean symptomatology and clinically significant symptoms in 45 ecstasy polydrug, 48 cannabis polydrug and 40 legal drug users, who completed standardised self-report anxiety and depression symptom measures. We further examined whether group differences were secondary to increased somatic symptom reporting, which may reflect acute/subacute drug effects. Anxiety and depression scores were higher in polydrug than legal drug users, with no difference between ecstasy and cannabis groups. There was no difference in numbers meeting criteria for clinically significant depression or 'moderate' or 'severe' anxiety, but the polydrug group contained more individuals reporting at least 'mild' anxiety symptoms than the legal drug control. Multivariate analyses indicated that anxiety alone was sufficient to discriminate groups. Polydrug users reported more somatic anxiety symptoms than legal drug users, but endorsed equivalent numbers of non-somatic symptoms. High prevalence psychiatric symptomatology in ecstasy polydrug users may be associated with polydrug rather than ecstasy use. Higher ratings in polydrug users appear to be secondary to increased somatic symptom reporting, suggesting possible impacts of drug effects on symptom endorsement.

Effects of sucrose on the extracellular matrix of plaque-like biofilm formed in vivo, studied by proteomic analysis.

Previous studies have shown that sucrose promotes changes in the composition of the extracellular matrix (ECM) of plaque-like biofilm (PLB), but its effect on protein expression has not been studied in vivo. Therefore, the protein compositions of ECM of PLB formed with and without sucrose exposure were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). For this purpose, a crossover study was conducted during two phases of 14 days each, during which a volunteer wore a palatal appliance containing eight enamel blocks for PLB accumulation. In each phase, a 20% sucrose solution or distilled and deionized water (control) were extraorally dripped onto the blocks 8x/day. On the 14th day, the PLB were collected, the ECM proteins were extracted, separated by two-dimensional gel electrophoresis, digested by in-gel trypsin and MALDI-TOF MS analyzed. In the ECM of PLB formed under sucrose exposure, the following changes compared with the control PLB were observed: (1) the presence of upregulated proteins that may be involved in bacterial response to environmental changes induced by sucrose and (2) the absence of calcium-binding proteins that may partly explain the low inorganic concentration found in ECM of PLB formed under sucrose exposure. The findings showing that sucrose affected the ECM protein composition of PLB in vivo provide further insight into the unique cariogenic properties of this dietary carbohydrate.

Management of blood loss in periacetabular osteotomy.

The aim of this study was to determine the efficacy and cost-effectiveness of the use of predonation of autologous blood for the periacetabular osteotomy. We carried out a retrospective single surgeon series study looking at patient demographics, intraoperative blood loss, volume of red cells returned (by cell salvage and allogenic/autologous transfusion), and comparing pre- and postoperative haemoglobin levels in those that predonated and those that did not. One hundred and twenty-two procedures were performed on 107 patients between 1996 and 2005. An initial audit (22 procedures) revealed high wastage (45% returned) of allogenic blood. A predonation protocol was initiated and subsequently 100 procedures in 91 patients were performed. In 82 procedures, the patients were eligible for predonation. A total of 226 units of autologous blood were predonated and 92% was used. Only 13 of these patients (16%) required additional allogenic transfusion for unforeseen excessive blood loss intraoperatively. A set protocol for predonation reduces the need for allogenic transfusion and involves minimal wastage. In a procedure which has significant blood loss, we suggest that preoperative autologous donation is a safe and cost effective method of managing blood loss.

Metamemory in recreational ecstasy polydrug users: what do self-reports of memory failures mean?

Previous research has found relationships between self-rated memory and ecstasy use, such that heavier users report worse function. These findings have been interpreted in terms of objective memory capacity. However, research on metamemory suggests that self-reported memory may be only weakly related to objective function, with demographics, mood, and memory-related beliefs and feelings also contributing to ratings. This study examined relationships between ecstasy/other drug use and self-reported memory, controlling for effects of demographic factors and mood. Associations between self-reported memory, memory-related beliefs and feelings, and objectively-measured cognitive function were also examined. Forty-five ecstasy polydrug, 48 cannabis polydrug, and 40 legal drug users completed a battery of neuropsychological tests and questionnaire measures of metamemory, including memory-related control beliefs, memory-related anxiety, and self-reported prospective and general/retrospective memory. The combined polydrug groups reported more general/retrospective memory failures. Covariance analysis, however, suggested that this finding was confounded by general anxiety levels. A combination of objective cognitive measures contributed to prediction of self-rated prospective memory, with demographics, mood, and memory-related anxiety also contributing to variability. However, associations between objective and self-reported memory were not strong. Self-report may not be a specific methodology with which to assess objective memory capacities in ecstasy and other drug users.

Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds.

BACKGROUND: Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds. METHOD: A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed. RESULTS: It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1-6% of variance in cognitive scores. CONCLUSIONS: Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

Lipid peroxidation and the levels of antioxidant enzymes in coronary artery disease.

Coronary Artery Disease is the major cause of mortality and morbidity worldwide. Traditional risk factors account for only half of the morbidity and mortality from coronary artery disease. There is substantial evidence that oxidative stress plays the major role in the atherosclerotic process. The present study was undertaken to evaluate the level of lipid peroxidation (by measuring malondialdehyde) and antioxidant enzymes (ceruloplasmin, glutathione, superoxide dismutase) in coronary artery disease. Serum malondialdehyde levels and serum ceruloplasmin levels were significantly raised in all the subgroups of study group as compared to control group (p<0.001). Whole blood glutathione levels and hemolysate superoxide dismutase activity was significantly decreased in all the subgroups of study group as compared to control group (p<0.001). Above results suggests that the patients of coronary artery disease show increased oxidative stress and decreased levels of antioxidant enzymes. So it is recommended that the management protocol for coronary artery disease patients should include antioxidant supplementation along with simultaneous lowering of lipid peroxidation.

The role of sucrose in cariogenic dental biofilm formation--new insight.

Dental caries is a biofilm-dependent oral disease, and fermentable dietary carbohydrates are the key environmental factors involved in its initiation and development. However, among the carbohydrates, sucrose is considered the most cariogenic, because, in addition to being fermented by oral bacteria, it is a substrate for the synthesis of extracellular (EPS) and intracellular (IPS) polysaccharides. Therefore, while the low pH environment triggers the shift of the resident plaque microflora to a more cariogenic one, EPS promote changes in the composition of the biofilms' matrix. Furthermore, it has recently been shown that the biofilm formed in the presence of sucrose presents low concentrations of Ca, P(i), and F, which are critical ions involved in de- and remineralization of enamel and dentin in the oral environment. Thus, the aim of this review is to explore the broad role of sucrose in the cariogenicity of biofilms, and to present a new insight into its influence on the pathogenesis of dental caries.

Unreamed femoral nail with spiral blade in subtrochanteric fractures: experience of 55 cases.

OBJECTIVE: To evaluate the use of the unreamed femoral nail with spiral blade (UFN-SB) in the treatment of subtrochanteric femoral fractures. DESIGN: A retrospective review of a consecutive series of 55 fractures. Fourteen patients had metastatic disease (four had prophylactic nailing). RESULTS: In five fractures, the UFN-SB failed: there was migration in three cases and breakage of the spiral blade in two cases, with breakage of the nail in two cases. Revision surgery was necessary in four cases. Five out of seven complications related to the spiral blade were seen in patients with a Seinsheimer fracture Type IIC or V. All other fractures healed within 1 year including those that needed revision surgery. In two cases the end result was THR. CONCLUSIONS: No complication was observed in pathological fractures, which may be because of a high mortality in the first 4 months after surgery due to co morbidity. The main advantage of the nail seems to be its ease of use. It can be inserted through a small incision. The options in spiral blade angle insertion make it a very versatile implant. The implant should probably not be used in Type IIC or V (Seinsheimer) fractures.

Design and validation of a surrogate humerus for biomechanical testing.

At present biomechanical testing of fracture plating strategies is conducted using animal or cadaveric whole bone models. This may introduce experimental error into these studies. This communication summarises the design and validation of a novel bone and fibre-reinforced plastic construct conceived to minimise intra-experimental error. A tubular surrogate humerus was produced with dimension and strength matched to that of the human humerus. Bone inserts placed into the wall of the tube allow for the fixation of the plates with bone screws. Three-point bending tests of the flexural rigidity of the surrogate humerus (EI=100.1 (SD 6.0)Nm(2)) showed it to be comparable to the human humerus. Further, pull-out tests of the screws showed that the bone slots adequately mimicked the whole bone scenario. This testing construct will be used for a comparative study of humeral plating techniques.

Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB.

TRAIL (tumour-necrosis factor-related apoptosis ligand or Apo2L) triggers apoptosis through engagement of the death receptors TRAIL-R1 (also known as DR4) and TRAIL-R2 (DR5). Here we show that the c-Rel subunit of the transcription factor NF-kappaB induces expression of TRAIL-R1 and TRAIL-R2; conversely, a transdominant mutant of the inhibitory protein IkappaBalpha or a transactivation-deficient mutant of c-Rel reduces expression of either death receptor. Whereas NF-kappaB promotes death receptor expression, cytokine-mediated activation of the RelA subunit of NF-kappaB also increases expression of the apoptosis inhibitor, Bcl-xL, and protects cells from TRAIL. Inhibition of NF-kappaB by blocking activation of the IkappaB kinase complex reduces Bcl-x L expression and sensitizes tumour cells to TRAIL-induced apoptosis. The ability to induce death receptors or Bcl-xL may explain the dual roles of NF-kappaB as a mediator or inhibitor of cell death during immune and stress responses.

Cloning and characterization of a ninth member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9.

We have cloned, expressed and characterized the gene encoding a ninth member of the mammalian UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGaNTase) family, termed ppGaNTase-T9. This type II membrane protein consists of a 9-amino acid N-terminal cytoplasmic region, a 20-amino acid hydrophobic/transmembrane region, a 94-amino acid stem region, and a 480-amino acid conserved region. Northern blot analysis revealed that the gene encoding this enzyme is expressed in a broadly distributed manner across many adult tissues. Significant levels of 5- and 4.2-kilobase transcripts were found in rat sublingual gland, testis, small intestine, colon, and ovary, with lesser amounts in heart, brain, spleen, lung, stomach, cervix, and uterus. In situ hybridization to mouse embryos (embryonic day 14.5) revealed significant hybridization in the developing mandible, maxilla, intestine, and mesencephalic ventricle. Constructs expressing this gene transiently in COS7 cells resulted in no detectable transferase activity in vitro against a panel of unmodified peptides, including MUC5AC (GTTPSPVPTTSTTSAP) and EA2 (PTTDSTTPAPTTK). However, when incubated with MUC5AC and EA2 glycopeptides (obtained by the prior action of ppGaNTase-T1), additional incorporation of GalNAc was achieved, resulting in new hydroxyamino acid modification. The activity of this glycopeptide transferase is distinguished from that of ppGaNTase-T7 in that it forms a tetra-glycopeptide species from the MUC5AC tri-glycopeptide substrate, whereas ppGaNTase-T7 forms a hexa-glycopeptide species. This isoform thus represents the second example of a glycopeptide transferase and is distinct from the previously identified form in enzymatic activity as well as expression in embryonic and adult tissues. These findings lend further support to the existence of a hierarchical network of differential enzymatic activity within the diversely regulated ppGaNTase family, which may play a role in the various processes governing development.

The association of basic proline-rich peptides from human parotid gland secretions with caries experience.

To address whether there are associations between the peptide composition of human parotid saliva and dental decay (caries) experience, we have characterized the peptides from parotid ductal saliva collected from nine adults who have remained free from dental caries (mean age = 59.2; Decayed Missing Filled Surfaces index [DMFS] = 0) and nine individuals who have experienced caries (mean age = 51.2; mean DMFS = 38.4). Ethanol-soluble peptides were size-fractionated on columns of Bio-Gel P-2; the salivary peptides derived from caries-susceptible subjects appeared larger than those found in the saliva of caries-free subjects. Peptides were then resolved into 19 species by cation exchange HPLC. Sequence analysis identified 18 peptides that appear to be proteolytic cleavage products of the basic proline-rich proteins IB-4, IB-5, IB-7, IB-8b, and P-B. The peptides that were more abundant in saliva obtained from the caries-free group differed from those isolated from the caries-susceptible group. The median peptide concentration of one possible precursor protein, IB-7, was found to be higher in saliva collected from caries-free individuals than in that from caries-susceptible individuals. Although differences were found in the phenotypes of proline-rich proteins expressed by these groups of caries-free and caries-susceptible subjects, no statistically significant associations were observed among proline-rich phenotypes and the level of any peptide. Collectively, our results indicate that proteolytic processing of parotid salivary proteins differs among individuals who have remained caries-free and those who have experienced dental decay.

The reliability of the American Knee Society Score.

We have investigated the reliability of the American Knee Society Score (AKS), a widely used functional outcome score for knee arthroplasty. 29 subjects were assessed in random order by 6 observers, each patient seen twice by each observer. The interobserver reference intervals were 16 points for the Knee Score (0-100 points) and 21 points for the Function Score (0-100 points). The intraobserver reference intervals were smaller, 11 points and 13 points for the Knee Score and the Function Score, respectively. The presence of arthritis in other joints and general debility did not affect the reliability of the scores. The more experienced observers had greater intraobserver reproducibility. Notably, we found moderate agreement between observers in the subjective variables, while the objective variables produced lower levels of agreement. The high inter- and intraobserver variations of the AKS makes estimation of score change questionable. Reliable use of the AKS would necessitate repeated evaluation by an experienced observer.