iBDecide: A web-based tool to promote engagement in shared decision-making among adolescents with ulcerative colitis.

BACKGROUND: Adolescents and young adults (AYAs) seek increased autonomy and self-efficacy. AYAs must learn to manage their medical care in preparation for transition to adult healthcare. Our team's research found that AYAs need more information about their disease and treatment OBJECTIVE: To develop and test the usability of a decision tool "iBDecide" to promote shared decision-making among AYAs with ulcerative colitis (UC) who are beginning to manage their treatment and medications METHODS: Using design thinking, 14 AYAs, 6 healthcare providers, 4 designers, a social worker, and a human factors researcher developed a shared decision-making tool. The System Usability Scale (SUS) assessed usability RESULTS: AYAs preferred an application with information on treatment, medication, nutrition, and symptom tracking. A web-based application, 'iBDecide', was developed to include these options. SUS results indicated that participants on average "agree" that: 'they would use iBDecide' and that 'it was easy to use and streamlined'. The mean SUS score was 78.25 (+/-12.91), range 70-90 DISCUSSION: Including AYAs in tool development helps ensure usability and improves engagement in shared decision-making. Co-designed tools may remove barriers for engagement and skill-building needed for the transition to adult care. CONCLUSION: iBDecide can stimulate AYA engagement in shared decision-making in treating UC.

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis.

Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.

Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a role in the modulation of food intake and mood. In rodents, the actions of MCH are mediated via the MCHR1 receptor. The goal of this study was to investigate the effects of acute (1 h) and chronic (28 days) p.o. dosing of a novel MCHR1 antagonist, N-[3-(1-{[4-(3,4-difluorophenoxy)-phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847), in three mouse models predictive of antidepressant/anxiolytic-like activity: novelty suppressed feeding (NSF) in 129S6/SvEvTac mice and light/dark paradigm (L/D) and forced swim test (FST) in BALB/cJ mice. A significant increase in the time spent in the light compartment of the L/D box was observed in response to acute and chronic treatment with SNAP 94847. An anxiolytic/antidepressant-like effect was found in the NSF test after acute and chronic treatment, whereas no effect was observed in the FST. Because neurogenesis in the dentate gyrus has been shown to be a requirement for the effects of antidepressants in the NSF test, we investigated whether neurogenesis was required for the effect of SNAP 94847. We showed that chronic treatment with SNAP 94847 stimulated proliferation of progenitors in the dentate gyrus. The efficacy of SNAP 94847 in the NSF test, however, was unaltered in mice in which neurogenesis was suppressed by X-irradiation. These results indicate that SNAP 94847 has a unique anxiolytic-like profile after both acute and chronic administration and that its mechanism of action is distinct from that of selective serotonin reuptake inhibitors and tricyclic antidepressants.

CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase.

Reactive microglia have been suggested to play a role in the Alzheimer's disease (AD) process, and previous studies have shown that expression of CD45, a membrane-bound protein-tyrosine phosphatase (PTP), is elevated in microglia in AD brain compared with controls. To investigate the possible role of CD45 in microglial responsiveness to beta-amyloid (Abeta) peptides, we first co-treated primary cultured microglia with a tyrosine phosphatase inhibitor [potassium bisperoxo (1,10-phenanthroline) oxovanadate (phen), 5 micrometer] and freshly solubilized Abeta peptides (1000 nm). Data show synergistic induction of microglial activation as evidenced by tumor necrosis factor alpha (TNF-alpha) production and nitric oxide (NO) release, both of which we show to be dependent on activation of p44/42 mitogen-activated protein kinase (MAPK). Furthermore, co-treatment with phen and Abeta peptides results in microglia-induced neuronal cell injury. Stimulation of microglial CD45 by anti-CD45 antibody markedly inhibits these effects via inhibition of p44/42 MAPK, suggesting that CD45 is a negative regulator of microglial activation. Accordingly, primary cultured microglia from CD45-deficient mice demonstrate hyper-responsiveness to Abeta, as evidenced by TNF-alpha release, NO production, and neuronal injury after stimulation with Abeta peptides. As a validation of these findings in vivo, brains from a transgenic mouse model of AD [transgenic Swedish APP-overexpressing (Tg APP(sw)) mice] deficient for CD45 demonstrate markedly increased production of TNF-alpha compared with Tg APP(sw) mice. Taken together, these results suggest that therapeutic agents that stimulate the CD45 PTP signaling pathway may be effective in suppressing microglial activation associated with AD.

Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10.

Recently, it has been demonstrated that the CD40 receptor is constitutively expressed on cultured microglia at low levels. Ligation of CD40 by CD40 ligand on these cells results in microglial activation, as measured by TNF-alpha production and neuronal injury. However, the intracellular events mediating this effect have yet to be investigated. We report that ligation of microglial CD40 triggers activation of p44/42 mitogen-activated protein kinase (MAPK). This effect is evident 30 min posttreatment, and progressively declines thereafter (from 30 to 240 min). Phosphorylated p38 MAPK is not observed in response to ligation of microglial CD40 across the time course examined. Inhibition of the upstream activator of p44/42 MAPK, mitogen-activated protein/extracellular signal-related kinase kinase 1/2, with PD98059, decreases phosphorylation of p44/42 MAPK and significantly reduces TNF-alpha release following ligation of microglial CD40. Furthermore, cotreatment of microglial cells with CD40 ligand and TGF-beta1 or IL-10, or both, inhibits CD40-mediated activation of p44/42 MAPK and production of TNF-alpha in a statistically interactive manner. Taken together, these data show that ligation of microglial CD40 triggers TNF-alpha release through the p44/42 MAPK pathway, an effect that can be opposed by TGF-beta1 and IL-10.

Incorporating digital imaging into dental hygiene practice.

The objective of this paper is to describe digital imaging technology: available modalities, scientific imaging process, advantages and limitations, and applications to dental hygiene practice. Advances in technology have created innovative imaging modalities for intraoral radiography that eliminate film as the traditional image receptor. Digital imaging generates instantaneous radiographic images on a display monitor following exposure. Advantages include lower patient exposure per image and elimination of film processing. Digital imaging enhances diagnostic capabilities and, therefore, treatment decisions by the oral healthcare provider. Utilization of digital imaging technology for intraoral radiography will advance the practice of dental hygiene. Although spatial resolution is inferior to conventional film, digital imaging provides adequate resolution to diagnose oral diseases. Dental hygienists must evaluate new technologies in radiography to continue providing quality care while reducing patient exposure to ionizing radiation.

Septicaemia in paediatric intensive-care patients at the Hospital for Sick Children, Great Ormond Street.

A review of nosocomial septicaemia in paediatric intensive care in a tertiary referral setting was undertaken for a 33-month period (1988-90). This involved six units: Cardiothoracic surgery; Neonatal surgery; general medical; Renal dialysis/transplant; Haematology/Oncology and Infectious disease/Immunology. The latter two units undertake bone marrow transplantation. During the study period, 10,719 admissions were made to these areas and 624 episodes of septicaemia were documented in 464 children. The frequency of septicaemia per 100 admissions ranged from 1.5 in the Renal Transplant Unit to 17.3 in the Haematology/Oncology unit. Over 60% of all septicaemic episodes occurred in children in the Haematology/Oncology and Cardiac Units. Gram-positive organisms were responsible for 66% of episodes, Gram-negative organisms for 17% and fungi for 3%. Polymicrobial episodes accounted for 13%. Coagulase-negative staphylococci were the most frequent isolates overall (43% of episodes in pure culture, and a further 6% in combination with other organisms). Staphylococcus aureus was associated with 10% of episodes, Enterobacteriaceae with 9% and Pseudomonas spp. 6% among which environmental pseudomonads predominated. Anaerobes and Haemophilus influenzae were each isolated in less than 1% of episodes.

Child abuse: a survey of ASDC members and a diagnostic-data-assessment for dentists.

Survey results on the subject of child abuse from the American Society of Dentistry for Children membership are reported. The survey results reflected the need of a documentation protocol for the dental office. A protocol is proposed which reviews the need of thorough assessment of orofacial lesions before concluding that child abuse exists. A data- and diagnostic-assessment form has been made using guidelines of the American Dental Association and other related referenced articles. The diagnostic-assessment form is presented to guide the practitioner through the documentation process and to develop a step-by-step decision on the probability of child abuse in any individual case.

A subdivision of strains of Staphylococcus aureus in the 94,96 complex by means of experimental phages.

In order to facilitate epidemiological investigations a subdivision of Staphylococcus aureus strains belonging to the 94,96 complex by means of two experimental phages, 16 and 47A, was performed. These phages were selected from the nine experimental phages initially examined because they gave the greatest discrimination. On the basis of reactions with these two phages, 2199 isolates which reacted with phages 94 and 96, and 773 isolates which reacted with phage 96 alone, were each subdivided into two major and two minor groups. Strains with different phage patterns were in a few cases (2/64) isolated from the same deep body site in a patient, and lysogenisation experiments suggested that differences in phage patterns were determined by the presence of prophages. Strains with the phage patterns 94/96 and 96 were found to be unevenly distributed throughout Denmark. This regional distribution suggested that particular strains might predominate in some areas. The extended phage patterns with the experimental phages did not give any retrospectively useful epidemiological information. It is proposed that in future phages 16 and 47A be used for specific investigations into the sources and relatedness of strains involved in small incidents.

Problems in the investigation of an apparent outbreak of coagulase-negative staphylococcal septicaemia following cardiac surgery.

Two hundred and twenty-six hospital staff and patients were investigated for the carriage of gentamicin-resistant coagulase-negative staphylococci (CNS) during an apparent outbreak of infection after cardiac surgery. Of the four index strains from infected wounds, three were indistinguishable. The carriage of similar organisms was widespread, particularly among ITU staff (72%) and patients. Ninety-one of the 296 gentamicin-resistant isolates were further investigated, and of these 33 were indistinguishable from index strains even with the use of specialized techniques. Our experience indicates that in outbreaks of infection caused by gentamicin-resistant CNS, resources should be focused on the interruption of transmission and prevention of introduction of these organisms to susceptible patients.

Methicillin-resistant Staphylococcus aureus in the UK and Ireland. A questionnaire survey.

The results of a questionnaire survey of the distribution of methicillin-resistant Staphylococcus aureus (MRSA) in the UK and Ireland between 1982 and 1983 are reported. Information was obtained about the geographical distribution of MRSA, the units affected, the sites of isolation and the preventive measures employed. Serious clinical problems were confined to a small number of hospitals with high isolation rates of MRSA.

Bacteriological characters of strains of Staphylococcus aureus submitted to a reference laboratory related to methicillin resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) strains present an increasing clinical problem. Analysis of 2679 strains submitted to a reference laboratory in the first quarter of 1983 and 3050 strains submitted in summer 1984 showed 479 and 593 multi-resistant strains. The proportion of methicillin-resistant strains classified as epidemic rose from 5.9 to 10.2%. Other methicillin-resistant strains continued to occur but other methicillin-sensitive multi-resistant strains appeared to fall. A strain with defined characters could be recognized in the Thames regions.

Gram-negative endotoxins and staphylococcal toxic shock syndrome.

Strains of Staphylococcus aureus isolated from toxic shock syndrome (TSS) produce toxic shock syndrome toxin 1 (TSST1) which causes a shock-like illness in rabbits with many features similar to TSS in humans. TSST1 is lethal per se in rabbits and also acts synergistically with endotoxin to potentiate lethality. The mode of action of TSST1 is as yet unknown; it has been suggested that it may act by inhibiting the reticuloendothelial system thus allowing endotoxic shock to occur. Rabbits pretreated with polymyxin-B, which prevents the effect of endotoxin, were found to be protected from death by TSST1 indicating that endotoxin is indeed implicated in the pathogenesis of TSS. Specific pathogen-free rabbits which presumably have negligible levels of circulating LPS were susceptible to TSST1 suggesting that very small amounts of endotoxin are sufficient to potentiate lethality. The ways in which TSST1 may allow shock to occur is discussed.

Toxic shock syndrome in Britain--epidemiology and microbiology.

By 30 June 1984, only 99 confirmed and probable cases of toxic shock syndrome (TSS) had been reported in the British Isles. Sixty-three were related to menstruation in women aged 14 to 54 years who used tampons of various brands and absorbencies; 33 (52%) of these cases were in girls under 20. Five women died (8%) and 19 (30%) reported at least one other possible episode. Thirty-six cases associated with a variety of clinical conditions occurred in men aged 17 to 74 years (9), women aged 20 to 54 years (15) and 12 children aged 10 months to 10 years; six patients (17%) died. Strains of Staphylococcus aureus which produced toxic shock syndrome toxin 1 (TSST-1) were isolated from 53 of 58 (91%) menstrual, but only from 18 of 33 (54%) non-menstrual patients. The frequency of toxin production was highest (93%) for 56 vaginal isolates and lowest (33%) for 9 isolates from blood culture. Ninety-six percent (68 of 71) of strains that were TSST-1-positive were sensitive to lytic-group I phages at one of the three concentrations tested; 82% were lysed by phage 29. Nineteen percent of 339 strains from a variety of sources other than TSS, produced TSST-1, and 35% of the strains lysed by group I phages were positive. Antibody to TSST-1 was detected by enzyme-linked immunosorbent assay at a serum dilution of 1:100, in 232 of 320 (82%) healthy individuals aged 14 to 56 years, but in acute-phase sera from only four of 37 (18%) TSS patients. A rise in antibody levels during convalescence was noted in two menstrual and 5 non-menstrual patients. These results show that the epidemiology of TSS is similar in Britain and the United States and provide further evidence of the importance of TSST-1-producing strains in the aetiology of the disease.

Waardenburg syndrome in South Africa. Part II. Is there founder effect for type I?

Three South African families of Afrikaner descent with the Waardenburg syndrome (WS) type I have been traced back for 12 generations. The families may be related through a French Huguenot couple who came to the Cape in 1683. Although the number of families in this study is small and the information incomplete and, although the earliest known family member with WS was born in 1842, the findings suggest that founder effect for the gene for WS type I may possibly exist in the Afrikaner population of South Africa.

Waardenburg syndrome in South Africa. Part I. An evaluation of the clinical findings in 11 families.

The clinical findings in 11 families with 52 members affected with the Waardenburg syndrome (WS) are presented and compared with the findings from other studies. The families are assigned to WS type I (7 families containing 31 affected individuals), or type II (4 families with 21 affected members), depending on the presence or absence of dystopia canthorum, and the differences between the two types are discussed. The hypothesis that the features of WS are explicable on the basis of a neural crest defect is supported. Attention is drawn to the finding of spina bifida in 2 unrelated WS type I patients, and of delayed milestones or poor school performance necessitating special schooling in 9 different unrelated patients. Deafness has previously been considered to be the most disabling characteristic of the condition, but if there is an increased incidence of spina bifida or mental retardation associated with WS, the approach to genetic counselling might need to be altered.

Characters of coagulase-negative staphylococci and micrococci from cases of endocarditis.

Strains of coagulase-negative staphylococci and micrococci submitted to a reference laboratory from 137 cases of endocarditis over a 5 year period were reviewed. Staphylococcus epidermidis biotype 1 (SII) was the commonest biotype in all groups of patients but exceeded 80 per cent in the 61 patients who had undergone prosthetic valve surgery and the 16 patients who had undergone other forms of surgery. Biotype 4 (SVI) was recovered from 10 of the 34 patients without surgery. Strains from prosthetic valve endocarditis were frequently resistant to many antibiotics while strains from natural valve endocarditis were frequently sensitive to all, or resistant only to penicillin. The value of bacteriophage typing was confirmed.

The Aarskog (facio-digital-genital) syndrome in South Africa. A report of three families.

Aarskog's syndrome comprises facial, digital and genital anomalies associated with short stature. Six affected males from three families were examined, and their clinical features are discussed. The presence of cleft lip in 1 of the patients supports the suggestion that cleft lip and cleft palate may well be a feature of the syndrome. Analysis of the pedigrees of the three families supports an X-linked recessive mode of inheritance with minimal expression in female carriers. The ultimate prognosis for affected individuals is good.