The synthesis of quinolone natural products from pseudonocardia sp.

Abstract The synthesis of four quinolone natural products from the actinomycete Pseudonocardia sp. is reported. The key step involved a sp2–sp3 Suzuki–Miyaura reaction between a common boronic ester lateral chain and various functionalised quinolone cores. The quinolones slowed growth of E. coli and S. aureus by inducing extended lag phases.The research leading to these results has received funding from the European Reserach Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC grant agreement no [279337/DOS]. Research in the DRS lab is also supported by the Engineering and Physical Sciences Research Council, Biotechnology and BiologicalSciences Research Council, Medical Research Council, Cancer Research UK, and the Wellcome Trust. Work in the MW lab is supported by the BBSRC and MRC. JTH was supported by Trinity College Cambridge. Data accessibility: all data supporting this study are provided as Supplementary Information accompanying this paper.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/ejoc.20150140

Chocolate consumption and incident heart failure

BACKGROUND: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.The EPIC-Norfolk study was supported by grants from the Medical Research Council and Cancer Research UK.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.numecd.2016.01.00

Absence of Staphylococcus aureus in Wild Populations of Fish Supports a Spillover Hypothesis

Staphylococcus aureus is a human commensal and opportunistic pathogen that also infects other animals. In humans and livestock, where S. aureus is most studied, strains are specialized for different host species. Recent studies have also found S. aureus in diverse wild animals. However, it remains unclear whether these isolates are also specialized for their hosts or whether their presence is due to repeated spillovers from source populations. This study focuses on S. aureus in fish, testing the spillover hypothesis in two ways. First, we examined 12 S. aureus isolates obtained from the internal and external organs of a farmed fish. While all isolates were from clonal complex 45, genomic diversity indicates repeated acquisition. The presence of a φSa3 prophage containing human immune evasion genes suggests that the source was originally human. Second, we tested for S. aureus in wild fish that were isolated from likely sources. In particular, we sampled 123 brown trout and their environment at 16 sites in the remote Scottish Highlands with variable levels of exposure to humans, birds, and livestock. This screen found no S. aureus infection in any of the wild populations or their environment. Together, these results support that the presence of S. aureus in fish and aquaculture is due to spillover from humans rather than specialization. Given the trends of increasing fish consumption, a better understanding of the dynamics of S. aureus spillover in aquaculture will mitigate future risks to fish and human health. IMPORTANCE Staphylococcus aureus is a human and livestock commensal but also an important pathogen responsible for high human mortality rates and economic losses in farming. Recent studies show that S. aureus is common in wild animals, including fish. However, we do not know whether these animals are part of the normal host range of S. aureus or whether infection is due to repeated spillover events from true S. aureus hosts. Answering this question has implications for public health and conservation. We find support for the spillover hypothesis by combining genome sequencing of S. aureus isolates from farmed fish and screens for S. aureus in isolated wild populations. The results imply that fish are unlikely to be a source of novel emergent S. aureus strains but highlight the prominence of the spillover of antibiotic-resistant bacteria from humans and livestock. This may affect both future fish disease potential and the risk of human food poisoning

External data required timely response by the Trial Steering-Data Monitoring Committee for the NALoxone InVEstigation (N-ALIVE) pilot trial

The prison-based N-ALIVE pilot trial had undertaken to notify the Research Ethics Committee and participants if we had reason to believe that the N-ALIVE pilot trial would not proceed to the main trial. In this paper, we describe how external data for the third year of before/after evaluation from Scotland's National Naloxone Programme, a related public health policy, were anticipated by eliciting prior opinion about the Scottish results in the month prior to their release as official statistics. We summarise how deliberations by the N-ALIVE Trial Steering-Data Monitoring Committee (TS-DMC) on N-ALIVE's own interim data, together with those on naloxone-on-release (NOR) from Scotland, led to the decision to cease randomization in the N-ALIVE pilot trial and recommend to local Principal Investigators that NOR be offered to already-randomized prisoners who had not yet been released

Evaluation of lymphatic vessel dilatations by anterior segment swept-source optical coherence tomography: Case report

Background: Conjunctival lymphangiectasia is a rare condition presumably caused by the obstruction of lymphatic channels or by an abnormal connection between conjunctival lymphatic and blood vessels. Diagnosis is based on clinical appearance and histology. We report a case of conjunctival lymphangiectasia in which anterior segment optical coherence tomography (OCT) was used to assist the diagnosis and the planning of the biopsy location. Case presentation: A 31-year-old woman was referred with repeated episodes of conjunctival "hemorrhages" and chemosis with extended recovery periods over the last months. Other symptoms were dryness, redness, burning sensation and itching. Photo documentation, anterior segment OCT, ultrasound, computer tomography (CT) and magnetic resonance imaging (MRI) of the brain were performed. MRI revealed dilated atypical Virchow-Robin space (VRS). Conjunctival biopsy was taken and the location of the biopsy was selected based on OCT findings. Based on the clinical appearance we suspected the case to be conjunctival lymphangiectasia or lymphangioma. Histology and immunhistochemistry confirmed the diagnosis of conjunctival lymphangiectasia. Conclusions: Anterior segment OCT is a non-invasive tool, useful in the evaluation of conjunctival lesions and planning surgery. © 2017 The Author(s)

Periodogram Connectivity of EEG Signals for the Detection of Dyslexia

Electroencephalography (EEG) signals provide an important source of information of brain activity at different areas. This information can be used to diagnose brain disorders according to different activation patterns found in controls and patients. This acquisition technology can be also used to explore the neural basis of less evident learning disabilities such as Developmental Dyslexia (DD). DD is a specific difficulty in the acquisition of reading skills not related to mental age or inadequate schooling, whose prevalent is estimated between 5% and 12% of the population. In this paper we propose a method to extract discriminative features from EEG signals based on the relationship among the spectral density at each channel. This relationship is computed by means of different correlation measures, inferring connectivity-like markers that are eventually selected and classified by a linear support vector machine. The experiments performed shown AUC values up to 0.7, demonstrating the applicability of the proposed approach for objective DD diagnosis

Quality and Safety Aspects of Infant Nutrition

Quality and safety aspects of infant nutrition are of key importance for child health, but oftentimes they do not get much attention by health care professionals whose interest tends to focus on functional benefits of early nutrition. Unbalanced diets and harmful food components induce particularly high risks for untoward effects in infants because of their rapid growth, high nutrient needs, and their typical dependence on only one or few foods during the first months of life. The concepts, standards and practices that relate to infant food quality and safety were discussed at a scientific workshop organized by the Child Health Foundation and the Early Nutrition Academy jointly with the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, and a summary is provided here. The participants reviewed past and current issues on quality and safety, the role of different stakeholders, and recommendations to avert future issues. It was concluded that a high level of quality and safety is currently achieved, but this is no reason for complacency. The food industry carries the primary responsibility for the safety and suitability of their products, including the quality of composition, raw materials and production processes. Introduction of new or modified products should be preceded by a thorough science based review of suitability and safety by an independent authority. Food safety events should be managed on an international basis. Global collaboration of food producers, food-safety authorities, paediatricians and scientists is needed to efficiently exchange information and to best protect public health. Copyright (C) 2012 S. Karger AG, Base

Overdiagnosis and overtreatment of breast cancer: Is overdiagnosis an issue for radiologists?

Overdiagnosis is diagnosis of cancers that would not present within the life of the patient and is one of the downsides of screening. This applies to low-grade ductal carcinoma in situ and some small grade 1 invasive cancers. Radiologists are responsible for cancer diagnosis, but at the time of diagnosis they cannot determine whether a particular low-grade diagnosis is one to which the definition of overdiagnosis applies. Overdiagnosis is likely to be driven by technological developments, including digital mammography, computer-aided detection and improved biopsy techniques. It is also driven by the patient's fear that cancer will be missed and the doctor's fear of litigation. It is therefore an issue of importance for radiologists, presenting them with difficult fine-tuned decisions in every assessment clinic that are ultimately counted later by those who evaluate their screening

Identification of Zoonotic Genotypes of Giardia duodenalis

Giardia duodenalis, originally regarded as a commensal organism, is the etiologic agent of giardiasis, a gastrointestinal disease of humans and animals. Giardiasis causes major public and veterinary health concerns worldwide. Transmission is either direct, through the faecal-oral route, or indirect, through ingestion of contaminated water or food. Genetic characterization of G. duodenalis isolates has revealed the existence of seven groups (assemblages A to G) which differ in their host distribution. Assemblages A and B are found in humans and in many other mammals, but the role of animals in the epidemiology of human infection is still unclear, despite the fact that the zoonotic potential of Giardia was recognised by the WHO some 30 years ago. Here, we performed an extensive genetic characterization of 978 human and 1440 animal isolates, which together comprise 3886 sequences from 4 genetic loci. The data were assembled into a molecular epidemiological database developed by a European network of public and veterinary health Institutions. Genotyping was performed at different levels of resolution (single and multiple loci on the same dataset). The zoonotic potential of both assemblages A and B is evident when studied at the level of assemblages, sub-assemblages, and even at each single locus. However, when genotypes are defined using a multi-locus sequence typing scheme, only 2 multi-locus genotypes (MLG) of assemblage A and none of assemblage B appear to have a zoonotic potential. Surprisingly, mixtures of genotypes in individual isolates were repeatedly observed. Possible explanations are the uptake of genetically different Giardia cysts by a host, or subsequent infection of an already infected host, likely without overt symptoms, with a different Giardia species, which may cause disease. Other explanations for mixed genotypes, particularly for assemblage B, are substantial allelic sequence heterogeneity and/or genetic recombination. Although the zoonotic potential of G. duodenalis is evident, evidence on the contribution and frequency is (still) lacking. This newly developed molecular database has the potential to tackle intricate epidemiological questions concerning protozoan diseases