Novel antioxidant compounds

The autoxidation process, mechanism of action of radical-trapping antioxidants and the problem of textile yellowing are described and reviewed. Structures implicit in the function of an antioxidant by promotion of radical stabihsation are identified and textile yellowing is attributed largely to reactions of antioxidants with NO2. The reaction of ethanolic solutions of 2,6-di-r-butyl-4-methylphenol (BHT) with several concentrations of gaseous NO2 are investigated. The main products are 2,6-dir-butyl-4-methyl-4-hydroxy-2,5-cyclohexadienone (MQOL) and 2,6-di-r-butyl-4-methyl-4-nitro-2,5-cyclohexadienone (MQN). Additional products are observed when lower- concentrations of BHT and NO2 are employed. The major product, MQN, is shown to be unstable in aqueous ethanohc solutions and the yellowing component of the reaction solutions is identified as 2,6-di-r-butyl-4-nitrophenol (NP).Two methods for screening potential compounds for antioxidant activity involving the inhibition of BHT product formation and the NO2-/NO3-ratio are described. They indicate that kojic acid, maltol and 2,5-dimethyl-4-hydroxyfuranone possess similar degrees of antioxidant activity to BHT. This is shown to be consistent with antioxidant function being promoted by the structural features identified.A quantitative NO2-yellowing test is described which allows rapid determination of the yellowing indices (OUYI) of test compounds. The results support the use of kojic acid and maltol as alternatives to BHT.An investigation of kojic acid indicates that it is both nitrosated by gaseous NO2, and undergoes a complicated series of reactions. Investigations with 3-methylcyclopentane-1,2-dione confirm that cychc 1,2-diones both reduce and trap gaseous NO2, a possible strategy for reducing yellowing.The foregoing studies indicate possible structural requirements for a NO2yellowing antioxidant and the synthesis of several N-(3,5-di-r-butyl-4-hydroxyphenyl) cyclic imides has been accomplished. This has provided a group of new compounds which show similar antioxidant activity to BHT, but are less prone to NO2-yellowing than 4-substituted hindered phenols possessing labile hydrogen atoms. Studies on the solvolysis of these cyclic imide compounds suggest that sufficient stability to obtain a commercially useful antioxidant may be imparted by the bulky alkyl substituents in the imide ring, as in the case of N-(3,5-di-f-butyl-4-hydroxyphenyl)-3,3-dimethylglutarimide and N-(3,5-di-tbutyl-4-hydroxyphenyl)-2,3-diethyl-2,3-dimethylsuccinimide which have been successfully prepared

The Role of Oxytocin in Antisocial Personality Disorders: A Systematic Review of the Literature

Background and aims: Antisocial personality disorder is an enduring mental disorder associated with significant disease burden and treatment difficulties. This is apparent within forensic populations. There is growing evidence to suggest that treatment with oxytocin could have some benefit in treating a range of psychiatric disorders. There are no reviews studying the use of oxytocin for patients with ASPD. We aim to present the first literature review on the use of oxytocin in patients with ASPD.Method: We searched relevant databases for original research on effect of oxytocin upon persons with a diagnosis of ASPD or healthy participants with symptoms seen in ASPD. Studies were included if they included healthy participants that evaluated the effect of oxytocin on symptoms relevant to ASPD, including empathy, inhibitory control, compliance, conformity, aggression, violence, and moral responsibility.Results: Thirty-six studies were included. There were a range of study designs, including randomized controlled trials, double blinded, single blinded, and unblinded controlled trials. The sample sizes in studies ranged from 20 to 259 participants. Studies looked at participants with a diagnosis of ASPD and participants with symptoms relevant to ASPD, including empathy, inhibitory control, compliance, conformity, aggression, violence, and moral responsibility. Oxytocin was found to demonstrate diversified effects, in most cases being associated with socially positive or non-criminogenic behaviors. However, some studies found opposite, and non-desirable, effects, e.g., an increase in violent inclinations to partners. The two studies looking at participants with ASPD had a number of limitations and had conflicting results on the impact that OT has on aggression in ASPD.Conclusions: This is the first systematic literature review exploring the potential use of oxytocin in managing ASPD and the symptoms of ASPD. It is apparent that there is a body of evidence addressing related symptoms in healthy individuals. There were diversified effects with oxytocin showing some benefits in promoting positive effects on symptoms of ASPD, but there were also studies showing non-desirable effects. It is difficult to draw any direct inferences from healthy control studies. Further high quality large sample studies are required to explore the effects of oxytocin in those with ASP

Newly qualified doctors' views about whether their medical school had trained them well: questionnaire surveys

A survey of newly qualified doctors in the UK in 2000/2001 found that 42% of them felt unprepared for their first year of employment in clinical posts. We report on how UK qualifiers' preparedness has changed since then, and on the impact of course changes upon preparedness. Methods Postal questionnaires were sent to all doctors who qualified from UK medical schools, in their first year of clinical work, in 2003 (n = 4257) and 2005 (n = 4784); and findings were compared with those in 2000/2001 (n = 5330). The response rates were 67% in 2000/2001, 65% in 2003, and 43% in 2005. The outcome measure was the percentage of doctors agreeing with the statement "My experience at medical school has prepared me well for the jobs I have undertaken so far". Results In the 2000/2001 survey 36.3% strongly agreed or agreed with the statement, as did 50.3% in the 2003 survey and 58.5% in 2005 (chi-squared test for linear trend: χ2 = 259.5; df = 1; p < 0.001). Substantial variation in preparedness between doctors from different medical schools, reported in the first survey, was still present in 2003 and 2005. Between 1998 and 2006 all UK medical schools updated their courses. Within each cohort a significantly higher percentage of the respondents from schools with updated courses felt well prepared. Conclusion UK medical schools are now training doctors who feel better prepared for work than in the past. Some of the improvement may be attributable to curricular change

The mental health expert patient: findings from a pilot study of a generic chronic condition self-management programme for people with mental illness

Author version made available in accordance with the publisher's policyBackground Less than optimal outcomes and escalating costs for chronic conditions including mental illness have prompted calls for innovative approaches to chronic illness management. Aims This study aimed to test the feasibility and utility of combining a generic, clinician administered and peer-led self-management group approach for people with serious mental illness. Method General practitioners and mental health case managers used a patient-centered care model (the Flinders Model) to assist 38 patients with serious mental illness to identify their self-management needs, and match these with interventions including Stanford peer-led, self-management groups and one-to-one peer support. Self-management and quality of life outcomes were measured and qualitative evaluation elicited feedback from all participants. Results Collaborative care planning, combined with a problems and goals focused approach, resulted in improved self-management and mental functioning at 3 to 6 months follow up. The Stanford self-management course was applicable and acceptable to patients with serious mental illnesses. Qualitative feedback was highly supportive of this approach. Conclusions Generic, structured assessment and care planning approaches, resulting in self-management education targeted to the individual, improved self-management and quality of life. Patients and service providers reported considerable gains despite the challenges associated with introducing a generic model within the mental health and general practice sector

The mental health expert patient: findings from a pilot study of a generic chronic condition self-management programme for people with mental illness

Author version made available in accordance with the publisher's policyBackground Less than optimal outcomes and escalating costs for chronic conditions including mental illness have prompted calls for innovative approaches to chronic illness management. Aims This study aimed to test the feasibility and utility of combining a generic, clinician administered and peer-led self-management group approach for people with serious mental illness. Method General practitioners and mental health case managers used a patient-centered care model (the Flinders Model) to assist 38 patients with serious mental illness to identify their self-management needs, and match these with interventions including Stanford peer-led, self-management groups and one-to-one peer support. Self-management and quality of life outcomes were measured and qualitative evaluation elicited feedback from all participants. Results Collaborative care planning, combined with a problems and goals focused approach, resulted in improved self-management and mental functioning at 3 to 6 months follow up. The Stanford self-management course was applicable and acceptable to patients with serious mental illnesses. Qualitative feedback was highly supportive of this approach. Conclusions Generic, structured assessment and care planning approaches, resulting in self-management education targeted to the individual, improved self-management and quality of life. Patients and service providers reported considerable gains despite the challenges associated with introducing a generic model within the mental health and general practice sector

Genome-based infection tracking reveals dynamics of Clostridium difficile transmission and disease recurrence

© 2015 The Authors. Published by Oxford University Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/cid/civ1031Background. Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain). Methods. We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards. Results. Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor–recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management. Conclusions. Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management.This work was supported by the Wellcome Trust (grant number 098051) and Medical Research Council UK (grant number PF451).Published versio

Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc

Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo. Results The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creERT2Apcflx/flx and BlgCreBrca2flx/flp53flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50–95% (P < 0.01) reduction in RNA and protein expression with SL7207/c-Myc targeted strains. In vivo, following establishment of tumour tissue, a single intra-peritoneal administration of 1 × 106 CFU of SL7207/c-Myc was sufficient to permit tumour colonisation and significantly extend survival with no overt toxicity in control animals. Conclusions In summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation

Occurrence of Typhoid Fever Complications and Their Relation to Duration of Illness Preceding Hospitalization: A Systematic Literature Review and Meta-analysis.

BACKGROUND:Complications from typhoid fever disease have been estimated to occur in 10%-15% of hospitalized patients, with evidence of a higher risk in children and when delaying the implementation of effective antimicrobial treatment. We estimated the prevalence of complications in hospitalized patients with culture-confirmed typhoid fever and the effects of delaying the implementation of effective antimicrobial treatment and age on the prevalence and risk of complications. METHODS:A systematic review and meta-analysis were performed using studies in the PubMed database. We rated risk of bias and conducted random-effects meta-analyses. Days of disease at hospitalization (DDA) was used as a surrogate for delaying the implementation of effective antimicrobial treatment. Analyses were stratified by DDA (DDA <10 versus ≥10 mean/median days of disease) and by age (children versus adults). Differences in risk were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were evaluated with the I2 value and funnel plot analysis, respectively. RESULTS:The pooled prevalence of complications estimated among hospitalized typhoid fever patients was 27% (95% CI, 21%-32%; I2 = 90.9%, P < .0001). Patients with a DDA ≥ 10 days presented higher prevalence (36% [95% CI, 29%-43%]) and three times greater risk of severe disease (OR, 3.00 [95% CI, 2.14-4.17]; P < .0001) than patients arriving earlier (16% [95% CI, 13%- 18%]). Difference in prevalence and risk by age groups were not significant. CONCLUSIONS:This meta-analysis identified a higher overall prevalence of complications than previously reported and a strong association between duration of symptoms prior to hospitalization and risk of serious complications

Chest radiograph classification and severity of suspected COVID-19 by different radiologist groups and attending clinicians: multi-reader, multi-case study.

OBJECTIVES: To quantify reader agreement for the British Society of Thoracic Imaging (BSTI) diagnostic and severity classification for COVID-19 on chest radiographs (CXR), in particular agreement for an indeterminate CXR that could instigate CT imaging, from single and paired images. METHODS: Twenty readers (four groups of five individuals)-consultant chest (CCR), general consultant (GCR), and specialist registrar (RSR) radiologists, and infectious diseases clinicians (IDR)-assigned BSTI categories and severity in addition to modified Covid-Radiographic Assessment of Lung Edema Score (Covid-RALES), to 305 CXRs (129 paired; 2 time points) from 176 guideline-defined COVID-19 patients. Percentage agreement with a consensus of two chest radiologists was calculated for (1) categorisation to those needing CT (indeterminate) versus those that did not (classic/probable, non-COVID-19); (2) severity; and (3) severity change on paired CXRs using the two scoring systems. RESULTS: Agreement with consensus for the indeterminate category was low across all groups (28-37%). Agreement for other BSTI categories was highest for classic/probable for the other three reader groups (66-76%) compared to GCR (49%). Agreement for normal was similar across all radiologists (54-61%) but lower for IDR (31%). Agreement for a severe CXR was lower for GCR (65%), compared to the other three reader groups (84-95%). For all groups, agreement for changes across paired CXRs was modest. CONCLUSION: Agreement for the indeterminate BSTI COVID-19 CXR category is low, and generally moderate for the other BSTI categories and for severity change, suggesting that the test, rather than readers, is limited in utility for both deciding disposition and serial monitoring. KEY POINTS: • Across different reader groups, agreement for COVID-19 diagnostic categorisation on CXR varies widely. • Agreement varies to a degree that may render CXR alone ineffective for triage, especially for indeterminate cases. • Agreement for serial CXR change is moderate, limiting utility in guiding management

Oral literature in South Africa: 20 years on

I offer a retrospective on the field of orality and performance studies in South Africa from the perspective of 2016, assessing what has been achieved, what may have happened inadvertently or worryingly, what some of the significant implications have been, what remain challenges, and how we may think of, or rethink, orality and performance studies in a present and future that are changing at almost inconceivable pace.DHE