ENZYME ENGINEERING AT ALMAC: Case studies of enzyme discovery and engineering

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Safeguarding children in dentistry: 1. Child protection training, experience and practice of dental professionals with an interest in paediatric dentistry

* Few dental professionals with child protection training have experience of making referrals. * There is a wide gap in practice between recognising signs of child abuse and neglect and responding effectively. * This may indicate missed opportunities to save children from continuing abuse. * There is a need for improved child protection information, support and training for dental professionals. Abstract Following several highly publicised inquiries into the deaths of children from abuse and neglect, there has been much recent interest in the role and responsibility of all health professionals to protect children at risk of maltreatment. The findings of a postal questionnaire, sent in March 2005 to 789 dentists and dental care professionals with an interest in paediatric dentistry working in varied settings in the UK, are presented in a two-part report and discussed in the context of current multi-agency good practice in safeguarding and promoting the welfare of children. This first part explores reported child protection training, experience and practice. There was a significant gap between recognising signs of abuse and responding effectively: 67% of respondents had suspected abuse or neglect of a child patient at some time in their career but only 29% had ever made a child protection referral. The dental profession is alerted to the need to ensure necessary appropriate action to safeguard children is always taken when child abuse or neglect are suspected

Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol

Background: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness. Methods: We will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity. Discussion: This review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium. Systematic review registration: PROSPERO CRD42019118808.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted versio

National study of adverse reactions after vaccination with bacille Calmette-Guerin

Few large prospective studies of adverse reactions after bacille Calmette-Guérin (BCG) vaccination are available. In a prospective national study of such adverse reactions among 918 subjects (aged 1 day to 54 years) over a 14-month period, 45 vaccinees (5%) reported 53 adverse reactions (23 injection-site abscesses, 14 severe local reactions, 10 cases of lymphadenitis, and 6 other reactions). Only 1% of vaccinees required medical attention. Reactions, particularly lymphadenitis, were significantly less common in infants <6 months old (but not in subjects aged 6 months) vaccinated by trained (vs. untrained) providers (relative risk [RR], 0.24; 95% confidence interval [CI], 0.090.68). Injection-site abscesses (RR, 2.96; 95% CI, 1.117.90) and severe local reactions (RR, 4.93; 95% CI, 1.1121.90) were significantly more common in older vaccinees. Local reactions were more frequently reported by adult females than by adult males (RR, 7.18; 95% CI, 1.5932.45). Adverse reactions were not significantly associated with any currently available vaccine batch, previous receipt of BCG vaccine, or concomitant administration of other vaccines.F. M. Turnbull, P. B. McIntyre, H. M. Achat, H. Wang, R. Stapledon, M. Gold, and M. A. Burges

Human-computer interaction to human-computer-context interaction : towards a conceptual framework for conducting user studies for shifting interfaces

Computer interfaces have been diversifying: from mobile and wearable technologies to the human body as an interface. Moreover, new sensing possibilities have allowed input to interfaces to go beyond the traditional mouse- and keyboard. This has resulted in a shift from manifest to latent interactions, where interactions between the human and the computer are becoming less visible. Currently, there is no framework available that fully captures the complexity of the multidimensional, multimodal, often latent interactions with these constantly shifting interfaces. In this manuscript, the Hu-man-Computer-Context Interaction (HCCI) framework is proposed. This framework defines 5 relevant interaction levels to be considered during user research in all stages of the new product development process in order to optimize user experience. More specifically, the interaction context is defined in terms of user-object, user-user, user-content, user-platform and user-context interactions. The HCCI framework serves as a concrete tool to use in a new product development process by HCI researchers, design-ers, and developers and aims to be technology independent and future-proof. This framework is a preliminary suggestion to be matched against other innovation devel-opment projects and needs to be further validated

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Should digestion assays be used to estimate persistence of potential allergens in tests for safety of novel food proteins?

Food allergies affect an estimated 3 to 4% of adults and up to 8% of children in developed western countries. Results from in vitro simulated gastric digestion studies with purified proteins are routinely used to assess the allergenic potential of novel food proteins. The digestion of purified proteins in simulated gastric fluid typically progresses in an exponential fashion allowing persistence to be quantified using pseudo-first-order rate constants or half lives. However, the persistence of purified proteins in simulated gastric fluid is a poor predictor of the allergenic status of food proteins, potentially due to food matrix effects that can be significant in vivo. The evaluation of the persistence of novel proteins in whole, prepared food exposed to simulated gastric fluid may provide a more correlative result, but such assays should be thoroughly validated to demonstrate a predictive capacity before they are accepted to predict the allergenic potential of novel food proteins

Dopaminergic and Serotonergic Drug Use: A Nationwide Register-Based Study of Over 1 300 000 Older People

Objective: To investigate the use of dopaminergic and serotonergic drugs in elderly people. Methods: We analyzed data on age, sex and dispensed drugs for individuals aged $65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81$65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these. Results: Dopaminergic and serotonergic drugs were used by 5.6 % and 13.2 % the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern. Conclusion: Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed fo