Identifying Individuals at Risk for Fracture in Guatemala

INTRODUCTION: The FRAX calculator combines a set of clinical risk factors with country-specific incidence rates to determine the ten-year absolute risk of major osteoporotic fracture. However, regional or country-specific databases from Central American countries are not available. We compared the use of various FRAX databases and the Pluijm algorithm in determining risk of fracture. METHODS: We collected clinical risk factor data needed for the FRAX calculator and Pluijm algorithm of Hispanic women in Guatemala and calculated the FRAX absolute risk measures of major osteoporotic fracture and hip fracture. Subjects were postmenopausal women greater than age 40 with no history of using medication that affect bone. A random sample of 204 women in 34 different regions women in Guatemala City was visited in their homes to complete the surveys. The Pluijm risk score and FRAX risk score using the US Hispanic, Spain, and Mexican databases were calculated. RESULTS: We used the US NOF guidelines for treatment which suggest a treatment threshold for patients with a 10-year hip fracture probability ≥ 3% or a 10-year major osteoporotic fracture risk ≥ 20%. The number of patients meeting the suggested threshold limits for treatment using the Spain and Mexico calculators were identical. There was 100% conformity in threshold limits for both hip and major osteoporotic fracture risk. The mean conformity for any fracture risk between US Hispanic and the other two databases was 97.5%. Conformity was 99.0% based on major osteoporotic fracture and 97.5% based on risk of hip fracture. The Pluijm evaluation shows conformity of 87.2% and 83.3%, respectively, when compared to the US Hispanic and Spain/Mexico FRAX thresholds for risk of fracture. DISCUSSION: Although the different FRAX databases provide variations in the absolute risk of fracture, the overall conformity to treatment thresholds amongst the US Hispanic, Spain, and Mexico databases show the database used would have little effect as to the decision to treat. The Pluijm tool conforms to the FRAX thresholds and can be used as well. It does not matter which country-specific calculator or assessment tool is used, as there are a similar number of patients that would meet the intervention threshold

New occurrences of the White River Ash (east lobe) in Subarctic Canada and utility for estimating freshwater reservoir effect in lake sediment archives

The freshwater reservoir effect (FRE) in the Canadian Subarctic complicates development of high-resolution age-depth models based on radiocarbon dates from lake sediments. Volcanic ashfall layers (tephras) provide chronostratigraphic markers that can be used to estimate age offsets. We describe the first recorded occurrence of a visible tephra in a lacustrine sequence in the central Northwest Territories. The tephra, observed in Pocket Lake, near Yellowknife, is geochemically and stratigraphically attributed to the White River Ash east lobe (WRAe; 833–850 CE; 1117–1100 cal BP), which originated from an eruption of Mount Churchill, Alaska. We also observed the WRAe as a cryptotephra in Bridge Lake, 130 km to the NE, suggesting that records of this tephra are potentially widespread in CNT lakes. The identification of this tephra presents opportunities for use of the WRAe as a dating tool in the region and to quantify the magnitude of the FRE in order to correct radiocarbon age-depth models. Two well-dated sediment cores from Pocket Lake, containing a visible WRAe record, indicate a FRE of 200 years at the time of the ash deposition, which matches closely with the estimated FRE of 245 years at the lake sediment-water interface. Although additional results from other lakes in the region are required, this finding implies that FRE estimates for the late Holocene in the region, may be based either on down-core WRAe/radiocarbon age model offsets, or on radiocarbon dates obtained from the sediment-water interface

Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Tea and coffee consumption in relation to vitamin D and calcium levels in Saudi adolescents

Background Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents. Methods A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays. Results Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9–12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9–12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure. Conclusion This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively

Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study

<p>Abstract</p> <p>Background</p> <p>The use of honey as a natural product of <it>Apis </it>spp. for burn treatment has been widely applied for centuries. Tualang honey has been reported to have antibacterial properties against various microorganisms, including those from burn-related diagnoses, and is cheaper and easier to be absorbed by Aquacel dressing. The aim of this study is to evaluate the potential antibacterial properties of tualang honey dressing and to determine its effectiveness as a partial thickness burn wound dressing.</p> <p>Methods</p> <p>In order to quantitate the bioburden of the swabs, pour plates were performed to obtain the colony count (CFU/ml). Swabs obtained from burn wounds were streaked on blood agar and MacConkey agar for bacterial isolation and identification. Later, antibacterial activity of Aquacel-tualang honey, Aquacel-Manuka honey, Aquacel-Ag and Aquacel- plain dressings against bacteria isolated from patients were tested (<it>in-vitro</it>) to see the effectiveness of those dressings by zone of inhibition assays.</p> <p>Results</p> <p>Seven organisms were isolated. Four types of Gram-negative bacteria, namely <it>Enterobacter cloacae</it>, <it>Klebsiella pneumoniae</it>, <it>Pseudomonas </it>spp. and <it>Acinetobacter </it>spp., and three Gram-positive bacteria, namely <it>Staphylococcus aureus</it>, coagulase-negative <it>Staphylococcus aureus </it>(CONS) and <it>Streptococcus </it>spp., were isolated. Total bacterial count decreased on day 6 and onwards. In the <it>in-vitro </it>antibacterial study, Aquacel-Ag and Aquacel-Manuka honey dressings gave better zone of inhibition for Gram positive bacteria compared to Aquacel-Tualang honey dressing. However, comparable results were obtained against Gram negative bacteria tested with Aquacel-Manuka honey and Aquacel-Tualang honey dressing.</p> <p>Conclusions</p> <p>Tualang honey has a bactericidal as well as bacteriostatic effect. It is useful as a dressing, as it is easier to apply and is less sticky compared to Manuka honey. However, for Gram positive bacteria, tualang honey is not as effective as usual care products such as silver-based dressing or medical grade honey dressing.</p

Trypanosoma cruzi CYP51 Inhibitor Derived from a Mycobacterium tuberculosis Screen Hit

Enzyme sterol 14α-demethylase (CYP51) is a well-established target for anti-fungal therapy and is a prospective target for Chagas' disease therapy. We previously identified a chemical scaffold capable of delivering a variety of chemical structures into the CYP51 active site. In this work the binding modes of several second generation compounds carrying this scaffold were determined in high-resolution co-crystal structures with CYP51 of Mycobacterium tuberculosis. Subsequent assays against CYP51 in Trypanosoma cruzi, the agent of Chagas' disease, demonstrated that two of the compounds bound tightly to the enzyme. Both were tested for inhibitory effects against T. cruzi and the related protozoan parasite Trypanosoma brucei. One of the compounds had potent, selective anti–T. cruzi activity in infected mouse macrophages. This compound is currently being evaluated in animal models of Chagas' disease. Discrimination between T. cruzi and T. brucei CYP51 by the inhibitor was largely based on the variability of a single amino acid residue at a critical position in the active site. Our work is aimed at rational design of potent and highly selective CYP51 inhibitors with potential to become therapeutic drugs. Drug selectivity to prevent host–pathogen cross-reactivity is pharmacologically important, because CYP51 is present in human host

Androgen receptor expression in metastatic adenocarcinoma in females favors a breast primary

BACKGROUND: The differential diagnosis of metastatic mammary adenocarcinoma and adenocarcinomas from other primary sites can be challenging, particularly in tumors that are poorly differentiated and negative for Estrogen/Progesterone receptors (ER/PR). With progression of disease, Androgen receptors (AR) are preserved with higher frequency than ER/PR in metastatic mammary carcinoma. This study was undertaken to evaluate the diagnostic significance of AR expression in adenocarcinoma of breast and other morphologically similar adenocarcinomas. DESIGN: Formalin-fixed paraffin-embedded tissue sections of 113 primary adenocarcinoma of various sites [breast (34, all females), lung (23, M- 6, F-17), colon (9, M-2, F-7), stomach (6, M-4, F-2), liver and bile duct (11, M-5, F-6), pancreas (7, M-2, F-5), ovary (10), endometrium (7), and cervix (6)] were immunostained with monoclonal antibody for AR. Except for well differentiated lobular carcinoma of breast (5) and bronchoalveolar carcinoma of lung (10), majority of the tumors were moderately to poorly differentiated. Tumors immunoreactive for ≥ 10% of nuclei were considered AR positive. However, AR immunoreactivity in the cytoplasm only was also recorded. RESULTS: 56% (19/34) mammary carcinoma and 20% (2/10) adenocarcinoma of ovary were positive for AR. Remaining 69 adenocarcinomas did not show nuclear immunoreactivity for AR in ≥ 10% nuclei; however, 52% (36/69) showed variable cytoplasmic immunoreactivity. CONCLUSION: Significant proportion of mammary carcinomas and some ovarian carcinomas express AR in the nuclei of more than 10% tumor cells. If metastatic tumor with unknown primary in a female is AR positive, breast and ovary are the most likely primary sites. Cytoplasmic immunoreactivity alone without nuclear immunoreactivity for AR was non-specific for this differential diagnosis

lpxC and yafS are the Most Suitable Internal Controls to Normalize Real Time RT-qPCR Expression in the Phytopathogenic Bacteria Dickeya dadantii

Background: Quantitative RT-PCR is the method of choice for studying, with both sensitivity and accuracy, the expression of genes. A reliable normalization of the data, using several reference genes, is critical for an accurate quantification of gene expression. Here, we propose a set of reference genes, of the phytopathogenic bacteria Dickeya dadantii and Pectobacterium atrosepticum, which are stable in a wide range of growth conditions. [br/] Results: We extracted, from a D. dadantii micro-array transcript profile dataset comprising thirty-two different growth conditions, an initial set of 49 expressed genes with very low variation in gene expression. Out of these, we retained 10 genes representing different functional categories, different levels of expression (low, medium, and high) and with no systematic variation in expression correlating with growth conditions. We measured the expression of these reference gene candidates using quantitative RT-PCR in 50 different experimental conditions, mimicking the environment encountered by the bacteria in their host and directly during the infection process in planta. The two most stable genes (ABF-0017965 (lpxC) and ABF-0020529 (yafS) were successfully used for normalization of RT-qPCR data. Finally, we demonstrated that the ortholog of lpxC and yafS in Pectobacterium atrosepticum also showed stable expression in diverse growth conditions. [br/] Conclusions: We have identified at least two genes, lpxC (ABF-0017965) and yafS (ABF-0020509), whose expressions are stable in a wide range of growth conditions and during infection. Thus, these genes are considered suitable for use as reference genes for the normalization of real-time RT-qPCR data of the two main pectinolytic phytopathogenic bacteria D. dadantii and P. atrosepticum and, probably, of other Enterobacteriaceae. Moreover, we defined general criteria to select good reference genes in bacteria

Stakeholder involvement in systematic reviews:a scoping review

Abstract Background There is increasing recognition that it is good practice to involve stakeholders (meaning patients, the public, health professionals and others) in systematic reviews, but limited evidence about how best to do this. We aimed to document the evidence-base relating to stakeholder involvement in systematic reviews and to use this evidence to describe how stakeholders have been involved in systematic reviews. Methods We carried out a scoping review, following a published protocol. We searched multiple electronic databases (2010–2016), using a stepwise searching approach, supplemented with hand searching. Two authors independently screened and discussed the first 500 abstracts and, after clarifying selection criteria, screened a further 500. Agreement on screening decisions was 97%, so screening was done by one reviewer only. Pre-planned data extraction was completed, and the comprehensiveness of the description of methods of involvement judged. Additional data extraction was completed for papers judged to have most comprehensive descriptions. Three stakeholder representatives were co-authors for this systematic review. Results We included 291 papers in which stakeholders were involved in a systematic review. Thirty percent involved patients and/or carers. Thirty-two percent were from the USA, 26% from the UK and 10% from Canada. Ten percent (32 reviews) were judged to provide a comprehensive description of methods of involving stakeholders. Sixty-nine percent (22/32) personally invited people to be involved; 22% (7/32) advertised opportunities to the general population. Eighty-one percent (26/32) had between 1 and 20 face-to-face meetings, with 83% of these holding ≤ 4 meetings. Meetings lasted 1 h to ½ day. Nineteen percent (6/32) used a Delphi method, most often involving three electronic rounds. Details of ethical approval were reported by 10/32. Expenses were reported to be paid to people involved in 8/32 systematic reviews. Discussion/conclusion We identified a relatively large number (291) of papers reporting stakeholder involvement in systematic reviews, but the quality of reporting was generally very poor. Information from a subset of papers judged to provide the best descriptions of stakeholder involvement in systematic reviews provide examples of different ways in which stakeholders have been involved in systematic reviews. These examples arguably currently provide the best available information to inform and guide decisions around the planning of stakeholder involvement within future systematic reviews. This evidence has been used to develop online learning resources. Systematic review registration The protocol for this systematic review was published on 21 April 2017. Publication reference: Pollock A, Campbell P, Struthers C, Synnot A, Nunn J, Hill S, Goodare H, Watts C, Morley R: Stakeholder involvement in systematic reviews: a protocol for a systematic review of methods, outcomes and effects. Research Involvement and Engagement 2017, 3:9. https://doi.org/10.1186/s40900-017-0060-4