Integrated pathway-genome databases and their role in drug discovery.

Integrated pathway-genome databases describe the genes and genome of an organism, as well as its predicted pathways, reactions, enzymes and metabolites. In conjunction with visualization and analysis software, these databases provide a framework for improved understanding of microbial physiology and for antimicrobial drug discovery. We describe pathway-based analyses of the genomes of a number of medically relevant microorganisms and a novel software tool that visualizes gene-expression data on a diagram showing the whole metabolic network of the microorganism.     

Pediatric manpower in Canada: a cross-country survey.

Health care costs and government cutbacks in Canadian training posts have caused concerns about physician manpower. To determine the present pediatric manpower situation a cross-country survey was undertaken of all pediatricians and their practice patterns. Of the 2060 recipients of a questionnaire 5% were found to not be pediatricians. Of the remaining 1960, 69% returned a completed questionnaire. Overall, 70% of the pediatricians were men, although among those less than 35 years of age 49% were women. Across Canada 37% of the pediatricians practised primary care, 25% secondary care and 38% tertiary care. There were wide regional differences in practice patterns, with large numbers of primary care pediatricians in Winnipeg, Toronto, Ottawa and the province of Quebec; few pediatricians in the Maritimes and the remainder of western Canada practised primary care. Non-Canadian graduates accounted for 33% of the pediatricians and represented a considerable proportion of tertiary care pediatricians. Cutbacks in numbers of pediatric training positions and restrictions on immigration of foreign pediatricians may lead to unexpected deficiencies in the availability of some types of pediatric practitioners, especially those in tertiary care.     

Nonsuicidal self-harm in youth: a population-based survey

Background

Nonsuicidal self-harm includes cutting, scratching, burning and minor overdosing. There have been few studies that have examined the rate of self-harm and mental-health correlates among community-based youth. We performed a population-based study to determine the prevalence of nonsuicidal self-harm, its mental-health correlates and help-seeking behaviour.

Methods

We used data from the Victoria Healthy Youth Survey, a population-based longitudinal survey of youth aged 14–21 in Victoria, British Columbia. The survey included questions about the history, method, frequency, age of onset and help-seeking for nonsuicidal self-harm. Youth were interviewed between February and June 2005. Univariable group differences were analyzed using students t test for continuous data and χ² for binary or categorical data. Multivariate analyses were conducted by use of multivariate analysis of variance and logistic regression.

Results

Ninety-six of 568 (16.9%) youth indicated that they had ever harmed themselves. Self-injuries such as cutting, scratching and self-hitting were the most common forms of nonsuicidal self-harm (83.2%). The mean age of onset was 15.2 years. Of those who reported nonsuicidal self-harm, 56% had sought help for this behaviour. Participants who reported 5 or more symptoms (out of 6) in a given symptom category were more likely than those who reported less than 5 symptoms to report nonsuicidal self-harm for the following categories: depressive mood (odds ratio [OR] 2.18, confidence interval [CI] 1.28–3.7) and problems with regulation of attention, impulsivity and activity (OR 2.24, CI 1.33–3.76).

Interpretation

We found a high lifetime prevalence of nonsuicidal self-harm. Many mental-health symptoms were associated with this behaviour, particularly those with depressive mood and attention-related problems. Just over half of youth reported seeking help for nonsuicidal self-harm. Clinicians who encounter youth should be vigilant to assess for this behaviour in youth who present with mental health issues.Nonsuicidal self-harm includes behaviours such as self-cutting, scratching and burning, done without the conscious intent to take one''s life. Onset typically occurs between 14 and 24 years of age.^1,2 The most common reasons for this type of harm are regulation of affect (e.g., to reduce tension or relieve dysphoric feelings), but reasons may also include self-punishment, interpersonal reasons, sensation seeking and anti-dissociation mechanisms.³ Factors associated with nonsuicidal self-harm include being female, awareness of self harm in peers, family members who self harm, drug misuse, depression, anxiety, impulsivity, disruptive disorders and low self-esteem.^4,5 Suicide ideation and attempts are more likely to be reported among those with repeated nonsuicidal self-harm.⁶A definition of “deliberate self-harm,” which does not distinguish between suicidal and nonsuicidal intent, has been proposed by the Child and Adolescent Self-Harm in Europe research group and has been used in several school-based surveys of adolescents.^4,7 The prevalence self-harm has been studied in school-based surveys of adolescents and young adults.^4–6,8 The results of these surveys are of limited generalizability because the samples were restricted to schools in large urban centres. Thus, we performed a population-based survey of youth in western Canada to investigate nonsuicidal self-harm. Our objectives were to determine the rate of nonsuicidal self-harm among Canadian youth; to determine the mental-health factors associated with nonsuicidal self-harm; and to examine the help-seeking patterns for this behaviour.     

Cross sectional survey of multicentre clinical databases in the United Kingdom

Objectives To describe the multicentre clinical databases that exist in the United Kingdom, to report on their quality, to explore which organisational and managerial features are associated with high quality, and to make recommendations for improvements.Design Cross sectional survey, with interviews with database custodians and search of electronic bibliographic database (PubMed).Studies reviewed 105 clinical databases across the United Kingdom.Results Clinical databases existed in all areas of health care, but their distribution was uneven—cancer and surgery were better covered than mental health and obstetrics. They varied greatly in age, size, growth rate, and geographical areas covered. Their scope (and thus their potential uses) and the quality of the data collected also varied. The latter was not associated with any organisational characteristics. Despite impressive achievements, many faced substantial financial uncertainty. Considerable scope existed for improvements: greater use of nationally approved codes; more support from relevant professional organisations; greater involvement by nurses, allied health professionals, managers, and laypeople in database management teams; and more attention to data security and ensuring patient confidentiality. With some notable exceptions, the audit and research potential of most databases had not been realised: half the databases had each produced only four or fewer peer reviewed research articles.Conclusions At least one clinical database support unit is needed in the United Kingdom to provide assistance in organisation and management, information technology, epidemiology, and statistics. Without such an initiative, the variable picture of databases reported here is likely to persist and their potential not be realised.     

Current situation and future usage of anticancer drug databases

Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type of anticancer drugs with their own emphases on different aspects, such as drug–target interactions, the relationship between mutations in drug targets and drug resistance/sensitivity, drug–drug interactions, natural products with anticancer activity, anticancer peptides, synthetic lethality pairs and histone deacetylase inhibitors. We focus on a holistic view of the current situation and future usage of databases related to anticancer drugs and further discuss their strengths and weaknesses, in the hope of facilitating the discovery of new anticancer drugs with better clinical outcomes.     

A morbillivirus antibody survey of Atlantic walrus, narwhal and beluga in Canada

A longitudinal serologic survey was conducted for morbillivirus antibodies in Atlantic walruses (Odobenus rosmarus rosmarus), narwhal (Monodon monoceros), and beluga (Delphinapterus leucas) from the Northwest Territories, Nunavut and the St. Lawrence estuary (Canada). Sixty-five of 131 (50%) walruses sampled between 1984 and 1993 had detectable morbillivirus neutralizing antibodies. Positive walrus were identified from four of five Arctic sampling sites, to as far back as 1984. Prevalence of morbillivirus neutralizing antibodies in walruses from Foxe Basin ranged from a high of 76% (n = 21) in 1993 to a low of 22% (n = 28) in 1984. Limitations in sample acquisition may have produced underestimates for the 1984 data. There are no reports of clinical morbillivirus infection in walruses. Our results are consistent with the hypothesis that a morbillivirus similar or identical to phocine distemper virus (PDV) has circulated among walrus populations of the eastern Canadian Arctic, at least since the early 1980s. No narwhal (n = 79) or beluga (n = 445) from Arctic waters were identified as having antibodies to dolphin morbilivirus (DMV) above the threshold serum dilution of log2 4. Also, none of the beach-cast cetacean carcasses (n = 28) from the Gulf of St. Lawrence and the St. Lawrence estuary were positive for antibodies to DMV. This indicates that Gulf of St. Lawrence, St. Lawrence estuary, and Arctic cetaceans either have not been exposed to DMV or an antigenically related morbillivirus, or are not susceptible to infection.     

A survey of Clostridium perfringens enterotoxin antibody in human and animal sera in western Canada

Sera from human, cattle, sheep, swine, and horse populations in western Canada were tested for the presence of Clostridium perfringens enterotoxin antibody by the passive hemagglutination (PHA) test, supplemented by an immunodiffusion test and by counterimmunoelectrophoresis. A total of 224 human, 345 cattle, 165 sheep, 620 swine, and 768 horse serum samples were examined. Low-titer reactions in the PHA test were detected in human, cattle, horse, and swine sera, in that order, with no titers demonstrated in sheep. The titers in human sera ranged up to 1:128 and three of these samples were also positive in the other two serological tests. The significance of this antibody is not clear, but it is suggested that the low prevalence of the antibody may reflect a low prevalence of enterotoxigenic C. perfringens strains in western Canada. Such serological surveys may be applicable to epidemiological studies involving enterotoxigenic C perfringens.     

A population-based survey on gastrointestinal tract symptoms and Helicobacter pylori infection in children and adolescents

Background. Helicobacter pylori infection is a frequent infection mainly acquired in childhood. Even if the infection is almost invariably associated with mild to severe gastro‐duodenal lesions, no specific clinical picture has been identified. The aim of this study was to evaluate the presence of dyspeptic symptoms and their relationship with the presence of H. pylori infection in the first two decades of life. Materials and Methods. A school‐population sample size of 808 subjects from 6‐ to 19‐year‐olds was investigated for the presence of gastrointestinal tract symptoms and evaluated by a ¹³C‐urea breath test for H. pylori infection. The relationship between clinical findings and H. pylori infection was evaluated by χ² statistic or Fisher's exact test, as appropriate. Results. Symptoms of dyspepsia were identified in 45% of subjects, while the picture of ulcer‐like and dysmotility‐like forms were present in 3–4%. H. pylori infection was demonstrated in 95 (11.8%) subjects, 49.5% of them without symptoms. Severe epigastric pain and ulcer‐like dyspepsia were significantly associated with H. pylori infection, while recurrent abdominal pain or dysmotility‐like dyspepsia were not. Conclusions. Dyspeptic symptoms are frequent in children, and its association with H. pylori infection is more evident than with recurrent abdominal pain. The age at which the infection is acquired seems to be under 6 years of age.     

Access to adult liver transplantation in Canada: a survey and ethical analysis.

OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and because the primary limiting factor is organ supply, increased organ acquisition efforts are needed.     

Bioinformatics models in drug abuse and Neuro-AIDS: Using and developing databases

The magnitude of the problems of drug abuse and Neuro-AIDS warrants the development of novel approaches for testing hypotheses in diagnosis and treatment ranging from cell culture models to developing databases. In this study, cultured neurons were treated with/without HIV-TAT, ENV, or cocaine in a 2x2x2 expression study design. RNA was purified, labeled, and expression data were produced and analyzed using ANOVA. Thus, we identified 35 genes that were significantly expressed across treatment conditions. A diagram is presented showing examples of molecular relationships involving a significantly expressed gene in the current study (SOX2). Also, we use this information to discuss examples of gene expression interactions as a means to portray significance and complexity of gene expression studies in Drug Abuse and Neuro-AIDS. Furthermore, we discuss here that critical interactions remain undetected, which may be unravelled by developing robust database systems containing large datasets and gleaned information from collaborating scientists . Hence, we are developing a public domain database we named The Agora database , that will served as a shared infrastructure to query, deposit, and review information related to drug abuse and dementias including Neuro-AIDS. A workflow of this database is also outlined in this paper.