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Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates.
Dietary habits have been associated with alterations of the human gut resident microorganisms contributing to obesity, diabetes and cancer1. In Western diets, red meat is a frequently eaten food2, but long-term consumption has been associated with increased risk of disease3,4. Red meat is enriched in N-glycolylneuraminic acid (Neu5Gc) that cannot be synthesized by humans5. However, consumption can cause Neu5Gc incorporation into cell surface glycans6, especially in carcinomas4,7. As a consequence, an inflammatory response is triggered when Neu5Gc-containing glycans encounter circulating anti-Neu5Gc antibodies8,9. Although bacteria can use free sialic acids as a nutrient source10-12, it is currently unknown if gut microorganisms contribute to releasing Neu5Gc from food. We found that a Neu5Gc-rich diet induces changes in the gut microbiota, with Bacteroidales and Clostridiales responding the most. Genome assembling of mouse and human shotgun metagenomic sequencing identified bacterial sialidases with previously unobserved substrate preference for Neu5Gc-containing glycans. X-ray crystallography revealed key amino acids potentially contributing to substrate preference. Additionally, we verified that mouse and human sialidases were able to release Neu5Gc from red meat. The release of Neu5Gc from red meat using bacterial sialidases could reduce the risk of inflammatory diseases associated with red meat consumption, including colorectal cancer4 and atherosclerosis13
Determination of absorption of vitamin B<SUB>12</SUB> by a double isotope tracer technique
A new simple method for the study of vitamin B12 absorption involving the use of two tracers is described. Along with 58Co labeled vitamin B12 an unabsorbable marker in the form of 51Cr labeled chromic oxide is administered to the patients. The ratio of the activities of the two isotopes in the standard is compared with the ratio of the activies of these isotopes in an aliquot of a stool sample collected after 24 or 48 hours. The absorption of labeled vitamin B12 is estimated from the alteration in the ratio of absorbable and unabsorbable isotopes in the stool sample. The method compares well with other methods of estimating vitamin B12 absorption such as Schilling's test, total faecal collection and whole body counting
Delivering medical abortion at scale: a study of the retail market for medical abortion in Madhya Pradesh, India.
BACKGROUND: Medical abortion (mifepristone and misoprostol) has the potential to contribute to reduced maternal mortality but little is known about the provision or quality of advice for medical abortion through the private retail sector. We examined the availability of medical abortion and the practices of pharmacists in India, where abortion has been legal since 1972. METHODS: We interviewed 591 pharmacists in 60 local markets in city, town and rural areas of Madhya Pradesh. One month later, we returned to 359 pharmacists with undercover patients who presented themselves unannounced as genuine customers seeking a medical abortion. RESULTS: Medical abortion was offered to undercover patients by 256 (71.3%) pharmacists and 24 different brands were identified. Two thirds (68.5%) of pharmacists stated that abortion was illegal in India. Only 106 (38.5%) pharmacists asked clients the timing of the last menstrual period and 38 (13.8%) requested to see a doctor's prescription - a legal requirement in India. Only 59 (21.5%) pharmacists correctly advised patients on the gestational limit for medical abortion, 97 (35.3%) provided correct information on how many and when to take the tablets in a combination pack, and 78 (28.4%) gave accurate advice on where to seek care in case of complications. Advice on post-abortion family planning was almost nonexistent. CONCLUSIONS: The retail market for medical abortion is extensive, but the quality of advice given to patients is poor. Although the contribution of medical abortion to women's health in India is poorly understood, there is an urgent need to improve the practices of pharmacists selling medical abortion
Thyroid hormones And [<SUP>14</SUP>C] glucose metabolism in bacteria
The effects of triiodothyronine and thyroxine on metabolism and growth of bacteria were studied. It was observed that over a certain range of concentration thyroxine and triiodothyronine produced increase in 14CO2 release from [14C]-labeled glucose and also stimulated bacteria growth
Thyroid uptake studies in infectious hepatitis
Thyroid-function studies were done in 43 cases of infectious hepatitis with varying degree of liver damage as judged by serum bilirubin levels. A different pattern of thyroid uptakes was seen in patients with moderate liver damage and those with severe liver damage. A good correlation was observed between thyroid uptake and degree of liver damage
Synthesis of thyroglobulin in thyroid carcinoma patients after radioiodine therapy
Endogenously radioiodinated thyroglobulin (Tg) and the serum concentration of Tg have been measured in patients with metastatic thyroid carcinoma after therapeutic doses of radioiodine. Serial samples of blood were analyzed for both these parameters over a period of 10 to 22 days. The specific activity of Tg (cpm/ng) was calculated for each sample. Among the six patients studied, three showed constant specific activity. The specific activity of the other three fell, indicating the entering of newly synthesized Tg into the circulation. The respective amounts of Tg entering into the circulation in these three patients were 120, 852, and 20,935 ng/ml serum/day
Does consumer protection enhance disclosure credibility in reward crowdfunding?
We study how the interplay of disclosure and regulation shapes capital allocation in reward crowdfunding. Using data from Kickstarter, the largest online reward crowdfunding platform, we show that, even in the absence of clear regulation and enforcement mechanisms, disclosure helps entrepreneurs access capital for their projects and bolsters engagement with potential project backers, consistent with the notion that disclosure mitigates moral hazard. We further document that, subsequent to a change in Kickstarter’s terms of use that increases the threat of consumer litigation, the association between project funding and disclosure becomes stronger. This evidence suggests that consumer protection regulation enhances the perceived credibility of disclosure. We find the effect of the change in terms of use to be more pronounced in states with stricter consumer protection regulations. Taken together, our findings yield important insights on the role of disclosure, as well as on the potential effects of increased regulation on crowdfunding platforms
Diagnosis of hyperthyroidism by external liver counting : correlation between external scintillation counting of the liver and plasma protein-bound iodine<SUP>131</SUP>
External liver counting clearly distinguishes between euthyroid and hyperthyroid patients (t = 10.2); hyperthyroid and nontoxic goitre patients (t = 11.9). Individual values for these patients show a good separation between the groups. Correlation coefficient between liver counts and PBI131 in euthyroid and hyperthyroid patients was found to be 0.84 and correlation coefficient for hyperthyroid and nontoxic goitre patients was 0.76. The advantages of external liver counting as an alternative method to plasma PBI131 estimations are:
(a) simplicity of the techniques;
(b) no additional well scintillation assembly needed, and
(c) no errors in results due to contamination of glassware, chemicals, etc(a) simplicity of the techniques;
(b) no additional well scintillation assembly needed, and
(c) no errors in results due to contamination of glassware, chemicals, et
Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Improving the Study of Protein Glycosylation with New Tools for Glycopeptide Enrichment
High confidence methods are needed for determining the glycosylation profiles of complex biological samples as well as recombinant therapeutic proteins. A common glycan analysis workflow involves liberation of N-glycans from glycoproteins with PNGase F or O-glycans by hydrazinolysis prior to their analysis. This method is limited in that it does not permit determination of glycan attachment sites. Alternative proteomics-based workflows are emerging that utilize site-specific proteolysis to generate peptide mixtures followed by selective enrichment strategies to isolate glycopeptides. Methods designed for the analysis of complex samples can yield a comprehensive snapshot of individual glycans species, the site of attachment of each individual glycan and the identity of the respective protein in many cases. This chapter will highlight advancements in enzymes that digest glycoproteins into distinct fragments and new strategies to enrich specific glycopeptides
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