Low-density lipoprotein modified by myeloperoxidase oxidants induces endothelial dysfunction

Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation and acceleration of lesion development by multiple pathways, including the induction of endothelial dysfunction. Thiocyanate (SCN-) ions are utilised by MPO to produce the oxidant hypothiocyanous acid (HOSCN), which reacts with LDL in a different manner to HOCl. Whilst the reactivity of HOCl-modified LDL has been previously studied, the role of HOSCN in the modification of LDL in vivo is poorly defined, although emerging evidence suggests that these particles have distinct biological properties. This is important because elevated plasma SCN- is linked with both the propagation and prevention of atherosclerosis. In this study, we demonstrate that both HOSCN- and HOCl-modified LDL inhibit endothelium-mediated vasorelaxation ex vivo in rat aortic ring segments. In vitro experiments with human coronary artery endothelial cells show that HOSCN-modified LDL decreases in the production of nitric oxide (NO•) and induces the loss of endothelial nitric oxide synthase (eNOS) activity. This occurs to a similar extent to that seen with HOCl-modified LDL. In each case, these effects are related to eNOS uncoupling, rather than altered expression, phosphorylation or cellular localisation. Together, these data provide new insights into role of MPO and LDL modification in the induction of endothelial dysfunction, which has implications for both the therapeutic use of SCN- within the setting of atherosclerosis and for smokers, who have elevated plasma levels of SCN-, and are more at risk of developing cardiovascular disease

The mysterious case of the missing half-ton of gold

A milling circuit in the concentrator processing ore at one of the gold mines managed by Johannesburg Consolidated Investments had apparently been losing a substantial part of the gold input to it for several months. At the time of investigation, the gold unaccounted for totalled nearly half a ton, worth some $5 million. A specially adapted distributed lag model was fitted to measurements made of the input and output, and far from confirming the apparent loss of gold, indicated that the plant's output balanced its input. The apparent contradiction between the total input and output and the more detailed accounting of the distributed lag model (which included variable time lags explicitly) gave rise to a closer investigation of the circuit which led to an explanation of the apparent discrepancies, and the actual location of a large amount of gold

Prevention of childhood poisoning in the home: overview of systematic reviews and a systematic review of primary studies

Unintentional poisoning is a significant child public health problem. This systematic overview of reviews, supplemented with a systematic review of recently published primary studies synthesizes evidence on non-legislative interventions to reduce childhood poisonings in the home with particular reference to interventions that could be implemented by Children's Centres in England or community health or social care services in other high income countries. Thirteen systematic reviews, two meta-analyses and 47 primary studies were identified. The interventions most commonly comprised education, provision of cupboard/drawer locks, and poison control centre (PCC) number stickers. Meta-analyses and primary studies provided evidence that interventions improved poison prevention practices. Twenty eight per cent of studies reporting safe medicine storage (OR from meta-analysis 1.57, 95% CI 1.22–2.02), 23% reporting safe storage of other products (OR from meta-analysis 1.63, 95% CI 1.22–2.17) and 46% reporting availability of PCC numbers (OR from meta-analysis 3.67, 95% CI 1.84–7.33) demonstrated significant effects favouring the intervention group. There was a lack of evidence that interventions reduced poisoning rates. Parents should be provided with poison prevention education, cupboard/drawer locks and emergency contact numbers to use in the event of a poisoning. Further research is required to determine whether improving poison prevention practices reduces poisoning rates

Intelligence and neuroticism in relation to depression and psychological distress: Evidence from two large population cohorts

BACKGROUND: Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined. METHODS: Associations and interactions between neuroticism and general intelligence (g) on MDD, self-reported depression, and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, n=19,200) and UK Biobank (n=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS. RESULTS: Neuroticism was strongly associated with increased risk for depression and higher psychological distress in both samples. Although intelligence conferred no consistent independent effects on depression, it did increase the risk for depression across samples once neuroticism was adjusted for. Results suggest that higher intelligence may ameliorate the association between neuroticism and self-reported depression although no significant interaction was found for clinical MDD. Intelligence was inversely associated with psychological distress across cohorts. A small interaction was found across samples such that lower psychological distress associates with higher intelligence and lower neuroticism, although effect sizes were small. CONCLUSIONS: From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on psychological distress. Intelligence does not confer protection against diagnosis of depression in those high in neuroticism

Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: phase I of the PRO-diGi study

Aim Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. Method Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). Results Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of ‘general recovery’ and ‘gastrointestinal symptoms’ were identified. General recovery included three themes: ‘life impact’, ‘mental impact’, including anxiety, and ‘physical impact’, including fatigue. Gastrointestinal symptoms included three themes: ‘abdominal symptoms’ such as pain, ‘diet and appetite’ and ‘expulsory function’, such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery—many of which lasted several weeks following discharge. Conclusion This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery