Natural zeolite (chabazite/phillipsite) dietary supplementation influences faecal microbiota and oxidant status of working dogs

We evaluated whether chabazite/phillipsite dietary supplementation might affect the faecal microbiota, oxidant and antioxidant status of working dogs at rest undergone to a trial test. Forty English Setter dogs were involved in two replicate trials. At each replicate, dogs were divided into two homogeneous groups (10 dogs/group). During a period of 28 days, diet was supplemented (Z group) or not supplemented (C group) with chabazite/phillipsite at the dose of 5 g/head/day. On day 29, dogs were subjected to a trial test. Faecal characteristics were assessed at 0 and 29 days (within two hours from the end of the trial test). Faecal consistency was not affected by dietary supplementation (p > .05). On day 29, Lactobacillus spp. and Enterococcus spp. counts were higher and Enterobacteriaceae were lower in Z than in C group (p  .05). Our results suggest that chabazite/phillipsite dietary supplementation, improves the intestinal microbiota ecosystem and may counteract the oxidative damage caused by physical stress in hunting dogs at the beginning of the working season

Brexit’s Effect on Citizens, Human Rights & Immigration

This report records the roundtable on “Brexit’s Effect on Citizens, Human Rights and Immigration” organised by Dr Adrienne Yong on 11 June 2019 at City, University of London funded by the Higher Education Innovation Fund (HEIF) 2018/19. Speakers included: • Hannah Wilkins (House of Commons Library) • Blanca Grey (Home Office)1 • Paul Erdunast (Immigration Law Practitioner’s Association - ILPA) • Christopher Desira (Seraphus Solicitors) • Nicole Masri (Rights of Women) • Ollie Persey (Public Law Project) • Katarzyna Zagrodniczek (East European Resource Centre) • Mihai Calin Bica (Roma Support Group) • Dr Adrienne Yong (City, University of London) • Dr Michaela Benson (Goldsmiths, University of London) • Madeleine Sumption (Migration Observatory) • Sheona York (Kent Law Clinic) A host of unique legal questions were raised in the aftermath of the UK’s referendum result where the electorate voted in favour of leaving the EU on the 23 June 2016. Opinion has been split as to whether the UK and EU have indeed struck a fair deal for citizens, with arguments that citizens have been used as bargaining chips throughout the process to achieve a deal. As negotiations progressed towards the original mandated date of withdrawal, 29 March 2019, various schemes emerged to handle post-Brexit immigration of EU citizens in the UK and reciprocal arrangements for British citizens in the EU. This is now reflected in the EU Settlement Scheme, the Immigration and Social Security Co-ordination Bill, and the reciprocity agreed with EU Member States as to British citizens in the EU. These issues and more were discussed at the roundtable

ADAPT Identifies an ESCRT Complex Composition That Discriminates VCaP From LNCaP Prostate Cancer Cell Exosomes

Libraries of single-stranded oligodeoxynucleotides (ssODNs) can be enriched for sequences that specifically bind molecules on naïve complex biological samples like cells or tissues. Depending on the enrichment strategy, the ssODNs can identify molecules specifically associated with a defined biological condition, for example a pathological phenotype, and thus are potentially useful for biomarker discovery. We performed ADAPT, a variant of SELEX, on exosomes secreted by VCaP prostate cancer cells. A library of ∼1011 ssODNs was enriched for those that bind to VCaP exosomes and discriminate them from exosomes derived from LNCaP prostate cancer cells. Next-generation sequencing (NGS) identified the best discriminating ssODNs, nine of which were resynthesized and their discriminatory ability confirmed by qPCR. Affinity purification with one of the sequences (Sequence 7) combined with LC-MS/MS identified its molecular target complex, whereof most proteins are part of or associated with the multiprotein ESCRT complex participating in exosome biogenesis. Within this complex, YBX1 was identified as the directly-bound target protein. ADAPT thus is able to differentiate exosomes from cancer cell subtypes from the same lineage. The composition of ESCRT complexes in exosomes from VCaP versus LNCaP cells might constitute a discriminatory element between these prostate cancer subtypes

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

Epitope mapping and characterization of 4-hydroxy-2-nonenal modified-human serum albumin using two different polyclonal antibodies

Lipids are susceptible to damage by reactive oxygen species, and from lipid oxidation reactions many short chain lipid peroxidation products can be formed. 4-Hydroxy-2-nonenal (HNE) is one of the most abundant and cytotoxic lipid oxidation products and is known to form covalent adducts with nucleophilic amino acids of proteins. HNE-modified proteins have value as biomarkers and can be detected by antibody-based techniques, but most commercially available antibodies were raised against HNE-keyhole limpet hemocyanin. We used HNE-treated human serum albumin (HSA) to raise sheep antiserum and report for the first time the use of covalently modified peptide arrays to assess epitope binding of antibodies (Abs). Peptide arrays covering the sequence of HSA and treated post peptide synthesis with HNE were used to compare the different binding patterns of a commercial polyclonal antibody (pAb) raised against HNE-treated KLH and an in-house anti-HNE enriched pAb. The results were correlated with analysis of HNE-modified HSA by high-resolution tandem mass spectrometry. Both anti-HNE pAbs were found to bind strongly to eight common peptides on the HNE-treated HSA membranes, suggesting that HNE adducts per se induced an immune response in both cases even though different immunogens were used. Both antibodies bound with the highest affinity to the peptide 365DPHECYAKVFDEFKPLV381, which contains K378 and was also shown to be modified by the mass spectrometry analysis. Overall, the commercial anti-HNE pAb showed better specificity, recognizing nine out of the eleven adducts found by MS/MS, while the in-house enriched pAb only recognizes six. Nevertheless, the in-house pAb recognized specific peptides that were not recognized by the commercial pAb, which suggests the presence of clones uniquely specific to HNE adducts on HSA

Factors considered by medical students when formulating their specialty preferences in Japan: findings from a qualitative study

<p>Abstract</p> <p>Background</p> <p>Little research addresses how medical students develop their choice of specialty training in Japan. The purpose of this research was to elucidate factors considered by Japanese medical students when formulating their specialty choice.</p> <p>Methods</p> <p>We conducted qualitative interviews with 25 Japanese medical students regarding factors influencing specialty preference and their views on roles of primary versus specialty care. We qualitatively analyzed the data to identify factors students consider when developing specialty preferences, to understand their views about primary and subspecialty care, and to construct models depicting the pathways to specialization.</p> <p>Results</p> <p>Students mention factors such as illness in self or close others, respect for family member in the profession, preclinical experiences in the curriculum such as labs and dissection, and aspects of patient care such as the clinical atmosphere, charismatic role models, and doctor-patient communication as influential on their specialty preferences. Participating students could generally distinguish between subspecialty care and primary care, but not primary care and family medicine. Our analysis yields a "Two Career" model depicting how medical graduates can first train for hospital-based specialty practice, and then switch to mixed primary/specialty care outpatient practice years later without any requirement for systematic training in principles of primary care practice.</p> <p>Conclusion</p> <p>Preclinical and clinical experiences as well as role models are reported by Japanese students as influential factors when formulating their specialty preferences. Student understanding of family medicine as a discipline is low in Japan. Students with ultimate aspirations to practice outpatient primary care medicine do not need to commit to systematic primary care training after graduation. The Two Career model of specialization leaves the door open for medical graduates to enter primary care practice at anytime regardless of post-graduate residency training choice.</p

Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis

<p>Abstract</p> <p>Background</p> <p>Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group.</p> <p>Methods</p> <p>Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen^®) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6.</p> <p>Results</p> <p>Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups.</p> <p>Conclusions</p> <p>Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.</p