Paging through history: parchment as a reservoir of ancient DNA for next generation sequencing.

Parchment represents an invaluable cultural reservoir. Retrieving an additional layer of information from these abundant, dated livestock-skins via the use of ancient DNA (aDNA) sequencing has been mooted by a number of researchers. However, prior PCR-based work has indicated that this may be challenged by cross-individual and cross-species contamination, perhaps from the bulk parchment preparation process. Here we apply next generation sequencing to two parchments of seventeenth and eighteenth century northern English provenance. Following alignment to the published sheep, goat, cow and human genomes, it is clear that the only genome displaying substantial unique homology is sheep and this species identification is confirmed by collagen peptide mass spectrometry. Only 4% of sequence reads align preferentially to a different species indicating low contamination across species. Moreover, mitochondrial DNA sequences suggest an upper bound of contamination at 5%. Over 45% of reads aligned to the sheep genome, and even this limited sequencing exercise yield 9 and 7% of each sampled sheep genome post filtering, allowing the mapping of genetic affinity to modern British sheep breeds. We conclude that parchment represents an excellent substrate for genomic analyses of historical livestock

Vitamin D-tour : cognition and depression: the role of vitamin D and its interplay with glucose homeostasis

According to recent estimations approximately 35.6 million people have dementia worldwide. Globally, 350 million people experience one or more depressive episodes during their life. As the therapeutic options for dementia and depression are limited, these conditions form a major challenge for public health and society. More and more researchers have initiated research on potential preventive factors for dementia and depression, including the potential effects of nutritional factors. The aim of this PhD-thesis was to study the role of vitamin D and its potential interplay with glucose homeostasis, in the development of cognitive decline and depression, using epidemiological data as well experimental animal data. Chapter 2 recapitulates a debate between vitamin D experts that was organized to make a step towards the harmonization on the formulation of optimal vitamin D intake levels and serum 25(OH)D concentrations across Europe. It was concluded that based on the current evidence-base 25(OH)D concentrations ≥50 nmol/L are sufficient with respect to optimal bone health. For health outcomes beyond bone health evidence was considered insufficient to formulate optimal levels. In order to achieve and maintain a 25(OH)D concentration ≥50 nmol/L, older adults aged ≥65 years were recommended to adhere to a vitamin D intake of 20 μg/day. Chapter 3 shows that there is a high prevalence of 25(OH)D inadequacy in a population of Dutch older adults that participated in the B-PROOF study (n=2857), namely 45% had 25(OH)D concentrations In chapter 4 the associations between 25(OH)D status and global cognitive performance (n=116), depressive symptoms (n=118), and surrogate markers of glucose intolerance (n=593) were evaluated using data of European adults aged 70-75 years. None of the associations reached significance. Studying the potential role of vitamin D in domain-specific cognitive performance and depression in 127 Dutch pre-frail and frail older adults aged ≥65 years (chapter 5), showed an association between 25(OH)D concentration and executive functioning, and a tendency towards an association with information processing speed. Stratification for ‘low’ and ‘high’ fasting glucose concentrations did not suggest an interaction between vitamin D and glucose homeostasis in the association with domain-specific cognitive performance. Moreover, adding fasting glucose or insulin did not substantially influence the associations between 25(OH)D status and domain-specific cognitive performance, and hence a mediation effect of glucose homeostasis was considered unlikely. We furthermore observed associations of 25(OH)D status with attention and working memory (n=787) (chapter 6), depression (n=2839) (chapter 7) and grey matter volume of the brain (n=217) (chapter 8) in a population community-dwelling Dutch older adults aged ≥65 years. Again, these studies did not provide evidence that the associations were modified or mediated by glucose intolerance. However, it should be emphasized that glucose intolerance in these three chapters was defined sub-optimally, specifically using blood samples that may have been collected in a non-fasting state, or by using self-reported diabetes data. Hence, the mediation and interaction effects should be interpreted cautiously. Finally, chapter 9 shows the results of a proof of principle study on the effect of a long-term vitamin D deficiency on cognitive decline and emotional reactivity in old C57BL/6j mice. Modest tendencies were shown for a relation between vitamin D and spatial learning, but these tendencies did not reach significance. Vitamin D deficiency did not affect recognition memory, spatial memory or emotional reactivity. Mice that received a higher dietary fat load, which was given to induce an impaired glucose tolerance, did not respond differently to a vitamin D deficiency than mice that received a low fat diet did. Overall, it is concluded that the evidence for an effect of vitamin D on cognitive performance/decline, depression or brain volume is insufficient to formulate disease specific cut-off values for vitamin D intake or 25(OH)D status. However, given the high prevalence of 25(OH)D concentrations <50 nmol/L we do call for a more active promotion of the current vitamin D intake recommendations.</p

Travel-related schistosomiasis, strongyloidiasis, filariasis, and toxocariasis: the risk of infection and the diagnostic relevance of blood eosinophilia

<p>Abstract</p> <p>Background</p> <p>This study prospectively assessed the occurrence of clinical and subclinical schistosomiasis, strongyloidiasis, filariasis, and toxocariasis, and the screening value of eosinophilia in adult short-term travelers to helminth-endemic countries.</p> <p>Methods</p> <p>Visitors of a pre-travel health advice centre donated blood samples for serology and blood cell count before and after travel. Samples were tested for eosinophilia, and for antibodies against schistosomiasis, strongyloidiasis, filariasis, and toxocariasis. Previous infection was defined as seropositivity in pre- and post-travel samples. Recent infection was defined as a seroconversion. Symptoms of parasitic disease were recorded in a structured diary.</p> <p>Results</p> <p>Previous infection was found in 112 of 1207 subjects: schistosomiasis in 2.7%, strongyloidiasis in 2.4%, filariasis in 3.4%, and toxocariasis in 1.8%. Recent schistosomiasis was found in 0.51% of susceptible subjects at risk, strongyloidiasis in 0.25%, filariasis in 0.09%, and toxocariasis in 0.08%. The incidence rate per 1000 person-months was 6.4, 3.2, 1.1, and 1.1, respectively. Recent infections were largely contracted in Asia. The positive predictive value of eosinophilia for diagnosis was 15% for previous infection and 0% for recent infection. None of the symptoms studied had any positive predictive value.</p> <p>Conclusion</p> <p>The chance of infection with schistosomiasis, strongyloidiasis, filariasis, and toxocariasis during one short-term journey to an endemic area is low. However, previous stay leads to a cumulative risk of infection. Testing for eosinophilia appeared to be of no value in routine screening of asymptomatic travelers for the four helminthic infections. Findings need to be replicated in larger prospective studies.</p

Performance measures for upper gastrointestinal endoscopy:A European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative

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A prospective study of the importance of enteric fever as a cause of non-malarial febrile illness in patients admitted to Chittagong Medical College Hospital, Bangladesh

BACKGROUND: Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common. METHODS: Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.0 °C were investigated using a blood smear for malaria, a blood culture, real-time PCR to detect Salmonella Typhi, S. Paratyphi A and other pathogens in blood and CSF and an NS1 antigen dengue ELISA. RESULTS: We enrolled 300 febrile patients with a negative malaria smear between January and June 2012: 156 children (aged ≤15 years) and 144 adults with a median (interquartile range) age of 13 (5-31) years and median (IQR) illness duration before admission of five (2-8) days. Clinical enteric fever was diagnosed in 52 patients (17.3 %), lower respiratory tract infection in 48 (16.0 %), non-specific febrile illness in 48 (16.0 %), a CNS infection in 37 patients (12.3 %), urinary sepsis in 23 patients (7.7 %), an upper respiratory tract infection in 21 patients (7.0 %), and diarrhea or dysentery in 21 patients (7.0 %). Malaria was still suspected in seven patients despite a negative microscopy test. S. Typhi was detected in blood by culture or PCR in 34 (11.3 %) of patients. Of note Rickettsia typhi and Orientia tsutsugamushi were detected by PCR in two and one patient respectively. Twenty-nine (9 %) patients died during their hospital admission (15/160 (9.4 %) of children and 14/144 (9.7 %) adults). Two of 52 (3.8 %) patients with enteric fever, 5/48 (10.4 %) patients with lower respiratory tract infections, and 12/37 (32.4 %) patients with CNS infection died. CONCLUSION: Enteric fever was confirmed in 11.3 % of patients admitted to this hospital in Bangladesh with non-malaria fever. Lower respiratory tract and CNS infections were also common. CNS infections in this location merit more detailed study due to the high mortality

Viral Etiology of Encephalitis in Children in Southern Vietnam: Results of a One-Year Prospective Descriptive Study

Viral encephalitis is associated with high morbidity and mortality in Vietnam. However little is known about the causes of the disease due to a lack of diagnostic facilities in this relatively resource-poor setting. Knowledge about the etiologies and clinical outcome of viral encephalitis is necessary for future design of intervention studies targeted at improvement of clinical management, treatment and prevention of the disease. We report the viral agents, clinical outcome and prognostic factors of mortality of encephalitis in children admitted to a referral hospital for children in southern Vietnam. We show that about one third of the enrolled patients die acutely, and that mortality is independently associated with patient age and Glasgow Coma Scale on admission. Japanese encephalitis, dengue virus and enterovirus (including enterovirus 71) are the major viruses detected in our patients. However, more than half of the patients remain undiagnosed, while mortality in this group is as high as in the diagnosed group. This study will benefit clinicians and public health in terms of clinical management and prevention of childhood encephalitis in Vietnam