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1
Yajima, Takahiro, Hiroshi Takahashi, and Keigo Yasuda. "Comparison of Interstitial Fluid Glucose Levels Obtained by Continuous Glucose Monitoring and Flash Glucose Monitoring in Patients With Type 2 Diabetes Mellitus Undergoing Hemodialysis." Journal of Diabetes Science and Technology 14, no. 6 (October 18, 2019): 1088–94. http://dx.doi.org/10.1177/1932296819882690.
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Background: The accuracy of flash glucose monitoring (FGM, FreeStyle Libre Pro [FSL-Pro]) remains unclear in patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis. Methods: We assessed 13 patients with T2DM undergoing hemodialysis. They simultaneously underwent FGM, continuous glucose monitoring (CGM, iPro2), and self-monitoring blood glucose (SMBG). Results: Parkes error grid analysis against SMBG showed that 49.0% and 51.0% of interstitial fluid glucose (ISFG) levels measured using FGM and 93.3% and 6.7% of those measured using CGM fell into zones A and B, respectively. Mean absolute relative difference (MARD) against SMBG for FGM was significantly higher than that for CGM (19.5% ± 13.2% vs 8.1% ± 7.6%, P < .0001). Parkes error grid analysis of 2496 paired ISFG levels between FGM and CGM showed that 53.6%, 46.2%, and 0.2% of the plots fell into zones A, B, and C, respectively. Mean ISFG levels were lower with FGM than with CGM (143.7 ± 67.2 mg/dL vs 164.6 ± 58.5 mg/dL; P < .0001). Mean absolute relative difference of ISFG levels between FGM and CGM was 19.2% ± 13.8%. Among three groups classified according to CGM ISFG levels (hypoglycemia, <70 mg/dL; euglycemia, 70-180 mg/dL; and hyperglycemia, >180 mg/dL), the MARDs for hypoglycemia (31.9% ± 25.0%) and euglycemia (22.8% ± 14.6%) were significantly higher than MARD for hyperglycemia (13.0% ± 8.5%) ( P < .0001 in both). Conclusions: Flash glucose monitoring may be clinically acceptable. Average ISFG levels were lower with FGM than with CGM, and MARDs were higher for hypoglycemia and euglycemia in patients with T2DM undergoing hemodialysis.
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Wada, Eri, Takeshi Onoue, Tomoko Kobayashi, Tomoko Handa, Ayaka Hayase, Masaaki Ito, Mariko Furukawa, et al. "Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial." BMJ Open Diabetes Research & Care 8, no. 1 (June 2020): e001115. http://dx.doi.org/10.1136/bmjdrc-2019-001115.
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IntroductionThe present study aimed to evaluate the effects of flash glucose monitoring (FGM) and conventional self-monitoring of blood glucose (SMBG) on glycemic control in patients with non-insulin-treated type 2 diabetes.Research design and methodsIn this 24-week, multicenter, open-label, randomized (1:1), parallel-group study, patients with non-insulin-treated type 2 diabetes at five hospitals in Japan were randomly assigned to the FGM (n=49) or SMBG (n=51) groups and were provided each device for 12 weeks. The primary outcome was change in glycated hemoglobin (HbA1c) level, and was compared using analysis of covariance model that included baseline values and group as covariates.ResultsForty-eight participants in the FGM group and 45 in the SMBG group completed the study. The mean HbA1c levels were 7.83% (62.1 mmol/mol) in the FGM group and 7.84% (62.2 mmol/mol) in the SMBG group at baseline, and the values were reduced in both FGM (−0.43% (−4.7 mmol/mol), p<0.001) and SMBG groups (−0.30% (−3.3 mmol/mol), p=0.001) at 12 weeks. On the other hand, HbA1c was significantly decreased from baseline values in the FGM group, but not in the SMBG group at 24 weeks (FGM: −0.46% (−5.0 mmol/mol), p<0.001; SMBG: −0.17% (−1.8 mmol/mol), p=0.124); a significant between-group difference was also observed (difference −0.29% (−3.2 mmol/mol), p=0.022). Diabetes Treatment Satisfaction Questionnaire score was significantly improved, and the mean glucose levels, SD of glucose, mean amplitude of glycemic excursions and time in hyperglycemia were significantly decreased in the FGM group compared with the SMBG group.ConclusionsGlycemic control was better with FGM than with SMBG after cessation of glucose monitoring in patients with non-insulin-treated type 2 diabetes.Trial registration numberUMIN000026452, jRCTs041180082.
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Abdulah, Deldar Morad, Bewar Abdulaziz Sedo, and Angela Dawson. "Female Genital Mutilation in Rural Regions of Iraqi Kurdistan: A Cross-Sectional Study." Public Health Reports 134, no. 5 (July 31, 2019): 514–21. http://dx.doi.org/10.1177/0033354919860512.
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Objectives: Although female genital mutilation (FGM) is illegal in Iraqi Kurdistan, FGM continues to be performed frequently in Muslim communities in the region. The objectives of this study were to (1) determine the prevalence of FGM among females living in rural areas of Iraqi Kurdistan; (2) assess the attitudes toward FGM of mothers, village community leaders, and religious leaders; and (3) compare the prevalence of FGM by maternal education. Methods: In a cross-sectional, double-randomized study of rural areas in Iraqi Kurdistan, we used a semi-structured questionnaire to interview 1657 mothers of 5048 daughters, 192 mullahs (religious leaders), and 386 mokhtars (community leaders). We examined data on maternal education level, daughters’ ages, whether daughters had experienced FGM, and attitudes about FGM. Results: A total of 2361 of 5048 (46.8%) daughters had experienced FGM. Of 1643 mothers, 565 (34.4%) supported FGM for their daughters in the future, although 825 of 1652 (49.9%) mothers were aware that it was illegal. Eighty-six of 192 (44.8%) mullahs and 339 of 382 (88.7%) mokhtars supported abandoning the practice of FGM. Support for FGM was significantly higher among uneducated mothers than among educated mothers (prevalence ratio [PR] = 1.45; 95% confidence interval [CI], 1.22-1.72; P < .001) and significantly higher among mothers with ≤9 years of education than among mothers with >9 years of education (PR = 1.66; 95% CI, 1.17-2.35; P = .003). Conclusions: FGM continues to be prevalent in rural areas of Iraqi Kurdistan. Public health interventions in this region are needed to improve knowledge about the harmful effects of FGM, its illegality, and the importance of prevention, particularly targeting leaders and households with low education levels.
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Lehman, Chadwick P., Christopher T. Rota, and Joshua J. Millspaugh. "Nutritional condition and physiological stress levels of elk in the Black Hills, South Dakota." PeerJ 7 (June 27, 2019): e7185. http://dx.doi.org/10.7717/peerj.7185.
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Percent of body fat and physiological stress are important correlates to wildlife demographics. We studied winter percent of body fat and physiological stress levels for a declining elk (Cervus canadensis nelsoni) population in South Dakota, 2011–2013. We obtained percent of winter body fat, pregnancy status, lactation status, and physiological stress data from 58 adult females (2+ years old). We compared physiological stress level data from 2011 with data collected from this same herd when elk densities were much higher (1995–1997). Our objectives were to determine percent of body fat during winter, examine if winter body fat was correlated with pregnancy and lactation status, and quantify and compare physiological stress hormone values from elk in the mid-1990s. Probability of being pregnant increased with higher winter nutritional condition, or percent of body fat; whereas females with a higher probability of previously lactating were lower in winter body fat. Mean fecal glucocorticoid metabolite (FGM) levels in 2011 (mean = 47.78 ng/g, SE = 2.37) were higher during summer compared to data collected in 1995–1997 (mean = 34.21 ng/g, SE = 3.71); however, mean FGM levels during winter did not differ between the two time periods. Although summer levels of FGM have significantly increased since the mid-1990s, we caution against any interpretation of increased FGM levels on elk fitness, as it may not infer biological significance. Mean winter percent of body fat of elk was lower when compared to other populations in the west but this difference does not appear to be limiting vital rates and population growth for this elk herd. We recommend future research focus on summer/autumn data collection to provide a more comprehensive understanding of percent of body fat for elk in our region.
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Wang, Xinhua, Chengpeng Wan, Xiaoxia Feng, Fuyan Zhao, and Huiming Wang. "In Vivo and In Vitro Analyses of Titanium-Hydroxyapatite Functionally Graded Material for Dental Implants." BioMed Research International 2021 (April 30, 2021): 1–14. http://dx.doi.org/10.1155/2021/8859945.
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Purpose. The stress shielding effect caused due to the mechanical mismatch between the solid titanium and the surrounding bone tissue warrants the utilization of a mechanically and biologically compatible material such as the titanium-hydroxyapatite (Ti-HA) functionally graded material (FGM) for dental implants. This study is aimed at fabricating a Ti-HA FGM with superior mechanical and biological properties for dental implantation. Materials and Methods. We fabricated a Ti-HA FGM with different Ti volume fractions (VFs) using HA and Ti powders. Ti-HA was characterized by studying its mechanical properties. Cytotoxicity was examined using a Cell Counting Kit-8 assay and an LDH cell cytotoxicity assay. Scanning electron microscopy was performed on an XL30 environmental scanning electron microscope (ESEM). Alkaline phosphatase (ALP) and transforming growth factor (TGF-β1) expressions were quantitatively monitored using enzyme-linked immunosorbent assay (ELISA) kits. The expressions of TGF-β receptors and ALP genes were measured using real-time polymerase chain reaction. The Ti-HA FGM dental implants were placed in beagle dogs. Microcomputed tomography (CT) and hard tissue slices were performed to evaluate the bone-implant contact (BIC) and bone volume over total volume (BV/TV). Results. The density and mechanical properties of the Ti-HA exhibited various graded distributions corresponding to VF. Based on the results of the Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, the difference in cytotoxicity between the two groups was statistically nonsignificant ( P = 0.11 ). The ALP and TGF-β1 levels were slightly upregulated. The transcript levels of ALP and TGF-βRI were higher in the Ti-HA groups than in the Ti group at 7 days, whereas the transcript levels of TGF-βRII exhibited no obvious increase. The BIC did not exhibit significant differences between the Ti and Ti-HA FGM groups ( P = 0.0504 ). BV/TV showed the Ti-HA FGM group had better osteogenesis ( P = 0.04 ). Conclusion. Ti-HA FGM contributes to the osteogenesis of dental implants in vivo and in vitro.
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Stothart, Mason R., Colleen B. Bobbie, Albrecht I. Schulte-Hostedde, Rudy Boonstra, Rupert Palme, Nadia C. S. Mykytczuk, and Amy E. M. Newman. "Stress and the microbiome: linking glucocorticoids to bacterial community dynamics in wild red squirrels." Biology Letters 12, no. 1 (January 2016): 20150875. http://dx.doi.org/10.1098/rsbl.2015.0875.
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Bacterial diversity within animals is emerging as an essential component of health, but it is unknown how stress may influence the microbiome. We quantify a proximate link between the oral microbiome and hypothalamic–pituitary–adrenal (HPA) axis activity using faecal glucocorticoid metabolites (FGM) in wild red squirrels ( Tamiasciurus hudsonicus ). Not only was bacterial diversity lower at higher levels of FGM, but also between capture periods a change in bacterial relative abundance was related to an increase in FGM. These linkages between the HPA axis and microbiome communities represent a powerful capacity for stress to have multi-dimensional effects on health.
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Cook, Kate. "Female Genital Mutilation in the UK Population." Journal of Criminal Law 80, no. 2 (April 2016): 88–96. http://dx.doi.org/10.1177/0022018316639092.
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This article considers the definition of female genital mutilation (FGM) in the context of United Nations work which aims to end this practice. The piece focuses on the prevalence of FGM in the UK and on legal provisions outlawing cutting in England and Wales. It argues that FGM is now relatively commonplace in the UK and ends with a call for greater public education about FGM and better support for survivors of mutilation. The article begins by looking at international ideas about FGM, drawing on knowledge from UNICEF and considering the realities of the practices carried out on young girls. It is acknowledged that there is a risk of alienating traditions that value cutting, inherent in the western view of FGM as child abuse. Nevertheless, the article argues that FGM must be eradicated. A review of information on the prevalence of FGM in UK populations follows, showing that there are many thousands of women and girl survivors now resident in Britain. FGM has been a criminal offence in England and Wales since the Prohibition of Female Circumcision Act 1985. However this legislation proved impractical and it has now been replaced by a Female Genital Mutilation Act in 2003 and that, in turn, is now amended by the Serious Crime Act 2015. An outline of the newer legislations suggests that there are signs of usefulness within the latest amendments. However the article ends with some warnings about the risks of criminalisation without appropriate levels of support and public discussion.
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Mancini, Giulia, Maria Berioli, Elisa Santi, Francesco Rogari, Giada Toni, Giorgia Tascini, Roberta Crispoldi, Giulia Ceccarini, and Susanna Esposito. "Flash Glucose Monitoring: A Review of the Literature with a Special Focus on Type 1 Diabetes." Nutrients 10, no. 8 (July 29, 2018): 992. http://dx.doi.org/10.3390/nu10080992.
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In people with type 1 diabetes mellitus (T1DM), obtaining good glycemic control is essential to reduce the risk of acute and chronic complications. Frequent glucose monitoring allows the adjustment of insulin therapy to improve metabolic control with near-normal blood glucose concentrations. The recent development of innovative technological devices for the management of T1DM provides new opportunities for patients and health care professionals to improve glycemic control and quality of life. Currently, in addition to traditional self-monitoring of blood glucose (SMBG) through a glucometer, there are new strategies to measure glucose levels, including the detection of interstitial glucose through Continuous Glucose Monitoring (iCGM) or Flash Glucose Monitoring (FGM). In this review, we analyze current evidence on the efficacy and safety of FGM, with a special focus on T1DM. FGM is an effective tool with great potential for the management of T1DM both in the pediatric and adult population that can help patients to improve metabolic control and quality of life. Although FGM might not be included in the development of an artificial pancreas and some models of iCGM are more accurate than FGM and preferable in some specific situations, FGM represents a cheaper and valid alternative for selected patients. In fact, FGM provides significantly more data than the intermittent results obtained by SMBG, which may not capture intervals of extreme variability or nocturnal events. With the help of a log related to insulin doses, meal intake, physical activity and stress factors, people can achieve the full benefits of FGM and work together with health care professionals to act upon the information provided by the sensor. The graphs and trends available with FGM better allow an understanding of how different factors (e.g., physical activity, diet) impact glycemic control, consequently motivating patients to take charge of their health.
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Katz, Itamar, Rachel Sanders, Maria Nadia Carvalho, Howard S. Friedman, Berhanu Legesse, William Winfrey, and Nafissatou Diop. "Cost and impact of scaling up female genital mutilation prevention and care programs: Estimated resource requirements and impact on incidence and prevalence." PLOS ONE 16, no. 1 (January 28, 2021): e0244946. http://dx.doi.org/10.1371/journal.pone.0244946.
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Purpose SDG 5.3 targets include eliminating harmful practices such as Female Genital Mutilation (FGM). Limited information is available about levels of investment needed and realistic estimates of potential incidence change. In this work, we estimate the cost and impact of FGM programs in 31 high burden countries. Methods This analysis combines program data, secondary data analysis, and population-level costing methods to estimate cost and impact of high and moderate scaleup of FGM programs between 2020 and 2030. Cost per person or community reached was multiplied by populations to estimate costs, and regression analysis was used to estimate new incidence rates, which were applied to populations to estimate cases averted. Results Reaching the high-coverage targets for 31 countries by 2030 would require an investment of US$ 3.3 billion. This scenario would avert more than 24 million cases of FGM, at an average cost of US$ 134 per case averted. A moderate-coverage scenario would cost US$ 1.6 billion and avert more than 12 million cases of FGM. However, average cost per case averted hides substantial variation based on country dynamics. The most cost-effective investment would be in countries with limited historic change in FGM incidence, with the average cost per case averted between US$ 3 and US$ 90. The next most effective would be those with high approval for FGM, but a preexisting trend downward, where cost per case averted is estimated at around US$ 240. Interpretation This analysis shows that although data on FGM is limited, we can draw useful findings from population-level surveys and program data to guide resource mobilization and program planning.
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Jones, Laura, Emma Danks, Joanne Clarke, Lailah Alidu, Benjamin Costello, Kate Jolly, Alison Byrne, Meg Fassam-Wright, Pallavi Latthe, and Julie Taylor. "Exploring the views of female genital mutilation survivors, their male partners and healthcare professionals on the timing of deinfibulation surgery and NHS FGM care provision (the FGM Sister Study): protocol for a qualitative study." BMJ Open 9, no. 10 (October 2019): e034140. http://dx.doi.org/10.1136/bmjopen-2019-034140.
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IntroductionFemale genital mutilation (FGM) is a significant global health concern and is likely to become an increasingly important healthcare challenge in destination countries such as the UK owing to rising levels of migration from FGM-affected countries. Currently, there is no consensus on the optimal timing of deinfibulation (opening) surgery for women who have experienced type 3 FGM and care provision remains suboptimal in the UK. This qualitative study aims to explore the views of survivors, male partners and healthcare professionals (HCPs) on the timing of deinfibulation and delivery of NHS FGM services.Methods and analysisA qualitative study, informed by the Sound of Silence conceptual framework, will be undertaken via two work packages (WPs). WP1 will explore views on timing preferences for deinfibulation and NHS FGM services through interviews and discussion groups with FGM survivors (n~50), male partners (n~10) and HCPs (n~50). WP2 will use established techniques via two workshops (community (n~20–25 participants) and national stakeholder (n~30–35 participants)) to synthesise qualitative research findings and inform best practice and policy recommendations around the timing of deinfibulation and NHS FGM care provision. Supported by trained interpreters, data collection will be audio recorded and transcribed. Data will be analysed using the framework method to facilitate a systematic mapping and exploration of qualitative data from multiple sources.Ethics and disseminationThe study has received ethical approval from the North West Greater Manchester East Research Ethics Committee (18/NW/0498). The outputs for this study will be recommendations for best practice and policy around FGM care provision that reflects the views and preferences of key stakeholders. The findings will be disseminated via conference presentations, peer-reviewed publications, patient groups, third sector organisations and social media.Trial registration numberISRCTN14710507.
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Liang, Mengjia, Edilberto Loaiza, Nafissatou J. Diop, and Berhanu Legesse. "Demographic perspectives of female genital mutilation." International Journal of Human Rights in Healthcare 9, no. 1 (March 14, 2016): 3–28. http://dx.doi.org/10.1108/ijhrh-05-2015-0017.
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Purpose – This publication aims to document the most relevant features of the practice of female genital mutilation (FGM) in 23 African and six Arab countries. The purpose of this paper is to provide a simple presentation of current levels; the main differences, according to background characteristics; and observed trends in the last 10-15 years. Considering past, current and future demographic dynamics helps identify possible scenarios for elimination. Design/methodology/approach – Data on FGM have been collected through Demographic Health Surveys since 1990, with about 50 surveys conducted in 23 countries with FGM concentrations, and through Multiple Indicator Cluster Surveys since 2000, with about 31 surveys conducted in 18 countries with prevalent FGM. Reliable data on the practice are now available for all African countries where the practice is concentrated, plus Iraq and Yemen. Statistical information is currently not available for countries where FGM has been newly identified, such as India and Indonesia. Findings – Approximately 130 million girls have undergone FGM in countries where the practice remains prevalent. If programmatic interventions and resources remain the same or decline, over 15.2 million girls will be subject to FGM. However if the 17 target countries attain their respective annual rates of reduction, four million girls will have been protected from FGM. Demographic analysis of FGM demonstrates that it is a practice that occurs within specific socio-cultural parameters, such as place of residence, and reproductive health and status. Interventions focusing on abandonment should take into consideration gender inequalities, how manifest, exacerbating high fertility and very young populations. Research limitations/implications – Gender equality has a catalytic effect on the achievement of inclusive and progressive human development, good governance, sustained peace, and harmonious dynamics between environments and human populations – all of which are at the centre of sustainable development and human rights. Practical implications – The case studies focusing on Burkina Faso and Guinea show that characteristics such as the mother’s educational level and whether or not she experienced FGM, religious background and ethnicity provide valuable information in determining who is subject to FGM and defining the milieu in which they live. This information corroborates other studies finding that ethnic and religious background are strong determinants. Social implications – Presented analysis strongly highlights the importance of data in understanding the context within which FGM programmes operate, especially those that target local communities. Djibouti, with a rapidly growing urban population, should focus on prevention programmes in cities. A highly rural country such as Guinea-Bissau will take a different approach, as only a few ethnic groups practice FGM. Originality/value – This is one of the first attempts to analyse and have a better understanding of the demographic, social and economic context of the practice. It aims to highlight the population and development issues surrounding the social norms of FGM.
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Xu, Yalan, Yu Qian, and Kongming Guo. "Statistical Identification of Parameters for Damaged FGM Structures with Material Uncertainties in Thermal Environment." Complexity 2018 (2018): 1–21. http://dx.doi.org/10.1155/2018/9034865.
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Considering that the statistic numerical characteristics are often required in the probability-based damage identification and safety assessment of functionally graded material (FGM) structures, an stochastic model updating-based inverse computational method to identify the second-order statistics (means and variances) of material properties as well as distribution of constituents for damaged FGM structures with material uncertainties is presented by using measurable modal parameters of structures. The region truncation-based optimization method is employed to simplify the computational process in stochastic model updating. In order to implement the forward propagation of uncertainties required in the stochastic model updating and avoid large error resulting in the nonconvergence of the iteration process, an algorithm is proposed to compute the covariance between the modal parameters and the identified parameters for damaged FGM structures. The proposed method is illustrated by a numerically simulated damaged FGM beam with continuous spatial variation of material properties and verified by comparing with the Monte-Carlo simulation (MCS) method. The influences of the levels and sources of measured data uncertainties as well as the boundary conditions on the identification results are investigated. The numerical simulation results show the efficiency and effectiveness of the presented method for the identification of material parameter variability by using the measurable modal parameters of damaged FGM structures.
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Di Francesco, Juliette, Gabriela F. Mastromonaco, Janice E. Rowell, John Blake, Sylvia L. Checkley, and Susan Kutz. "Fecal glucocorticoid metabolites reflect hypothalamic–pituitary–adrenal axis activity in muskoxen (Ovibos moschatus)." PLOS ONE 16, no. 4 (April 14, 2021): e0249281. http://dx.doi.org/10.1371/journal.pone.0249281.
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Muskoxen (Ovibos moschatus), a taxonomically unique Arctic species, are increasingly exposed to climate and other anthropogenic changes. It is critical to develop and validate reliable tools to monitor their physiological stress response in order to assess the impacts of these changes. Here, we measured fecal glucocorticoid metabolite (FGM) levels in response to the administration of adrenocorticotropic hormone (ACTH) in the winter (1 IU/kg) and summer (2 IU/kg) using two enzyme immunoassays, one targeting primarily cortisol and the other targeting primarily corticosterone. Fecal cortisol levels varied substantially within and among individuals, and none of the animals in either challenge showed an increase in fecal cortisol following the injection of ACTH. By contrast, two of six (winter) and two of five (summer) muskoxen showed a clear response in fecal corticosterone levels (i.e., maximal percentage increase as compared to time 0 levels > 100%). Increases in fecal corticosterone post-ACTH injection occurred earlier and were of shorter duration in the summer than in the winter and fecal corticosterone levels were, in general, lower during the summer. These seasonal differences in FGM responses may be related to the use of different individuals (i.e., influence of sex, age, social status, etc.) and to seasonal variations in the metabolism and excretion of glucocorticoids, intestinal transit time, voluntary food intake, and fecal output and moisture content. Results from this study support using FGMs as a biomarker of hypothalamic–pituitary–adrenal axis activity in muskoxen, advance our understanding of the physiological adaptations of mammals living in highly seasonal and extreme environments such as the Arctic, and emphasize the importance of considering seasonality in other species when interpreting FGM levels.
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Al Hayek, Ayman A., Asirvatham A. Robert, and Mohamed A. Al Dawish. "Evaluation of FreeStyle Libre Flash Glucose Monitoring System on Glycemic Control, Health-Related Quality of Life, and Fear of Hypoglycemia in Patients with Type 1 Diabetes." Clinical Medicine Insights: Endocrinology and Diabetes 10 (January 1, 2017): 117955141774695. http://dx.doi.org/10.1177/1179551417746957.
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Background/objectives: In the current era of modern technology and the development of smart devices such as the flash glucose monitoring (FGM) systems, patients can easily monitor their glucose levels more frequently without any inconvenience. In this study, we evaluate the effect of FreeStyle Libre FGM system on glycemic control, hypoglycemia, health-related quality of life (QoL), and the fear of hypoglycemia (FOH) among children and young people with type 1 diabetes (T1D). Design and methods: A prospective study was conducted at the Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between January 2017 and May 2017 on 47 (aged 13-19 years) registered patients with T1D who used conventional finger-pricking method for self-testing the glucose. At baseline visit, the FGM sensors were placed on each participant by a trained diabetes educator. The data collected from the sensors were computed to generate the respective ambulatory glucose profiles so as to determine the total number of scans conducted during the study period. At the baseline and at 3 months of the experiment, a trained interviewer administered the questionnaire Hypoglycemia Fear Survey-Child Version (HFS-C) and PedsQL 3.0 (QoL questionnaire) to each patient. The age, sex, weight, height, adjusted body mass index, duration of diabetes, treatment modality, and glycosylated hemoglobin A1c (HbA1c) levels of each patient were recorded. Results: As compared with the baseline, a significant improvement was noted in the behavior of FOH ( P = .0001), worry ( P = .0001), QoL ( P = .002), HbA1c level ( P = .008), and hypoglycemia ( P = .023) at 3 months. Significant improvement was noted in the behavior ( P = .0001), worry ( P = .0001), QoL ( P = .003), HbA1c level ( P = .014), and hypoglycemia ( P = .001) among the multiple-dose insulin injection–treated patients as compared with baseline. Significant improvement was noted in the behavior ( P = .0001), worry ( P = .0001), and hypoglycemia ( P = .001) among the insulin pump–treated patients as compared with baseline. A positive correlation was recorded in the behavior ( r = .47; P < .001), QoL ( r = .70; P < .001), and the mean number of FGM scans. A negative correlation was recorded in the worry ( r = −.43; P = .002), HbA1c level ( r = −.58; P < .001), hypoglycemia ( r = −.65; P < .001), and the mean number of FGM scans. Conclusions: The frequent use of FGM scanning reduced the frequency of hypoglycemia, HbA1c level, and worry and increased the behavior and QoL. As compared with self-testing by the conventional finger-pricking method, the use of FGM increased the frequency of self-testing and thus diabetes control.
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Moura de Sousa, Jorge A., João Alpedrinha, Paulo R. A. Campos, and Isabel Gordo. "Competition and fixation of cohorts of adaptive mutations under Fisher geometrical model." PeerJ 4 (August 2, 2016): e2256. http://dx.doi.org/10.7717/peerj.2256.
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One of the simplest models of adaptation to a new environment is Fisher’s Geometric Model (FGM), in which populations move on a multidimensional landscape defined by the traits under selection. The predictions of this model have been found to be consistent with current observations of patterns of fitness increase in experimentally evolved populations. Recent studies investigated the dynamics of allele frequency change along adaptation of microbes to simple laboratory conditions and unveiled a dramatic pattern of competition between cohorts of mutations, i.e., multiple mutations simultaneously segregating and ultimately reaching fixation. Here, using simulations, we study the dynamics of phenotypic and genetic change as asexual populations under clonal interference climb a Fisherian landscape, and ask about the conditions under which FGM can display the simultaneous increase and fixation of multiple mutations—mutation cohorts—along the adaptive walk. We find that FGM under clonal interference, and with varying levels of pleiotropy, can reproduce the experimentally observed competition between different cohorts of mutations, some of which have a high probability of fixation along the adaptive walk. Overall, our results show that the surprising dynamics of mutation cohorts recently observed during experimental adaptation of microbial populations can be expected under one of the oldest and simplest theoretical models of adaptation—FGM.
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Yan, Rengna, Huiqin Li, Xiaocen Kong, Xiaofang Zhai, Maoyuan Chen, Yixuan Sun, Lei Ye, Xiaofei Su, and Jianhua Ma. "The Accuracy and Precision of the Continuously Stored Data from Flash Glucose Monitoring System in Type 2 Diabetes Patients during Standard Meal Tolerance Test." International Journal of Endocrinology 2020 (January 4, 2020): 1–6. http://dx.doi.org/10.1155/2020/5947680.
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Background. The purpose of this study was to investigate the accuracy of the continuously stored data from the Abbott FreeStyle Libre flash glucose monitoring (FGM) system in Chinese diabetes patients during standard meal tests when glucose concentrations were rapidly changing. Subjects and Methods. Interstitial glucose levels were monitored for 14 days in 26 insulin-treated patients with type 2 diabetes using the FGM system. Standard meal tests were conducted to induce large glucose swings. Venous blood glucose (VBG) was tested at 0, 30, 60, and 120 min after standard meal tests in one middle day of the first and second weeks, respectively. The corresponding sensor glucose values were obtained from interpolating continuously stored data points. Assessment of accuracy was according to recent consensus recommendations with median absolute relative difference (MARD) and Clarke and Parkes error grid analysis (CEG and PEG). Results. Among 208 paired sensor-reference values, 100% were falling within zones A and B of the Clarke and Parkes error grid analysis. The overall MARD was 10.7% (SD, 7.8%). Weighted least squares regression analysis resulted in high agreement between the FGM sensor glucose and VBG readings. The overall MTT results showed that FGM was lower than actual VBG, with MAD of 22.1 mg/dL (1.2 mmol/L). At VBG rates of change of -1 to 0, 0 to 1, 1 to 2, and 2 to 3 mg/dl/min, MARD results were 11.4% (SD, 8.7%), 9.4% (SD, 6.5%), 9.9% (SD, 7.5%), and 9.5% (SD, 7.7%). At rapidly changing VBG concentrations (>3 mg/dl/min), MARD increased to 19.0%, which was significantly higher than slow changing BG groups. Conclusions. Continuously stored interstitial glucose measurements with the FGM system were found to be acceptable to evaluate VBG in terms of clinical decision during standard meal tests. The continuously stored data from the FGM system appeared to underestimate venous glucose and performed less well during rapid glucose changes.
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A. Mitwaly, Abo Bakr, Diaa Eldeen Mohamed Abd El Aal, Peter A. Aziz, Ahmed I. Hassanin, and Ahmed M. Abbas. "A recent look for the implication and attitude of practicing female genital mutilation in upper Egypt: a cross sectional study." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 6, no. 10 (September 23, 2017): 4224. http://dx.doi.org/10.18203/2320-1770.ijrcog20174398.
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Background: Female genital mutilation (FGM) was defined as the partial or total removal of the female external genitalia for non-medical reasons The Demographic and Health Survey in Egypt in 2000 showed that 97% of married women included in the survey had experienced female genital mutilation.Methods: This is a cross sectional study to evaluate the current prevalence of FGM, current attitude of our society towards it after illegalization of it as a cross sectional survey of Upper Egypt. The most important point in this study is our evaluation of intention of these women whom exposed to FGM toward mutilation of their daughters or not and reasons for that. Statistical analysis was done using SPSS software version 21.Results: The study included 1175 women, from whom 89.1% were circumcised. Type 1 FGM was the most prevalent type practiced in about 58% of participants. Immediate complications occurred in 42.5% of women. Primary hemorrhage during circumcision was the most commonly reported immediate complication among 38.5% of them. Sexual problems were found in 40.5% of participants. Sixty-four women reported occurrence of hepatitis virus infection after the procedure. Moreover, 44 women were suffered from infertility and 72 women had an episode or chronic PID. Women who intend to circumcise their daughters are mostly those coming from rural areas (p=0.000) and housewives (p=0.000). Most of women (45.8%) who have the intent to circumcise their daughters claiming that it is religious based.Conclusions: The prevalence of FGM did not differ between urban and rural or between house wives and employee, lastly did not differ between different educational levels as most of them were encourage it thinking that it is of traditional, religious base and protect the girl from any abnormal sexual excitation. The women who intent not circumcise their daughters were from low educational level in its highest percentage and this was explained by occurrence of higher percentage of complications in spite of the highest percentage of operator was physician.
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Al Hayek, Ayman A., Asirvatham A. Robert, and Mohamed A. Al Dawish. "Acceptability of the FreeStyle Libre Flash Glucose Monitoring System: The Experience of Young Patients With Type 1 Diabetes." Clinical Medicine Insights: Endocrinology and Diabetes 13 (January 2020): 117955142091012. http://dx.doi.org/10.1177/1179551420910122.
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Background: In the current era of modern technology, the development of smart devices such as the flash glucose monitoring (FGM) systems helps patients with diabetes to effortlessly monitor their glucose levels more frequently. In this study, we determine the user acceptability of FGM among young patients with type 1 diabetes (T1D). Methods: A cross-sectional study was performed among 67 young patients with T1D in the age group of 13 to 19 years and who were managed on the FGM method for self-testing the glucose levels for a minimum of 6 months. The participants acceptability measures that were collected with a standard questionnaire and where they rated their experience with the system on a scale of 1 (strongly agree/painless) to 5 (strongly disagree/severe pain). In addition to the demographic and clinical parameters, a closed/structured questionnaire was administered, in order to record the prior and present skin issues, over a 6-month period. Results: From the patient statements regarding sensor application, 95.5% of the study population strongly agreed that the sensor application caused less pain than the routine finger-stick. Similarly, 85% of the users strongly agreed that using the sensor was comfortable, while 94% strongly agreed that they found the small size of the FGM made it easy to wear, 47.8% strongly agreed that wearing the sensor did not attract attention, 70.1% reported no discomfort under the skin, 80.6% stated that the sensor could be scanned without anyone noticing it, 89.6% felt that the sensor did not affect their daily activities, 91% strongly agreed that the sensor was very compatible with their lifestyle, 79.1% reported ease with taking a glucose reading with the scan, 89.6% reported that taking glucose readings with this system would not disrupt their daily activities, and 76.1% participants were excited to share with other individuals their experiences with this system. A comparison of the self-monitoring of blood glucose and freestyle techniques demonstrated that 83.6% participants strongly agreed that it was less painful to get glucose readings from the freestyle sensor, and that it was a more discreet (83.6%), more comfortable (85.1%), easier (95.5%), faster (82.1%), simpler (79.1%), more private (88.1%), and less stressful (77.6%) method, with minimal hassle (74.6%). It is notable here that 86.6% of the participants reported absolutely no pain when the freestyle sensor was applied; also, the majority of the participants (91%) reported no pain symptoms when scanning the sensor. Conclusion: The findings of this study clearly showed that the study population had a high level of acceptability of the FGM.
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Massa, Guy G., Inge Gys, Anniek Op ‘t Eyndt, Esmiralda Bevilacqua, Anne Wijnands, Peter Declercq, and Renate Zeevaert. "Evaluation of the FreeStyle® Libre Flash Glucose Monitoring System in Children and Adolescents with Type 1 Diabetes." Hormone Research in Paediatrics 89, no. 3 (2018): 189–99. http://dx.doi.org/10.1159/000487361.
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Background/Aims: The FreeStyle® Libre Flash Glucose Monitoring System (FGM, Abbott) measures glucose concentrations in the interstitial fluid for up to 14 days. It has been approved for use in children aged > 4 years in January 2016. Experience in children is still limited. We evaluated the accuracy and usability of the FGM in children with type 1 diabetes mellitus (DM). Methods: 67 children with type 1 DM (35 girls), aged 4–18 years, were included. Subjects wore a sensor on the back of their upper arm. For the first 14 days, they regularly measured capillary blood glucose (BG) with their usual BG meter (Accu-Chek® Mobile [ACM], Roche [n = 24]; Contour® Next Link [CNL], Bayer [n = 26]; OneTouch® Verio® IQ [OTV], LifeScan [n = 17]) followed by a sensor glucose (SG) scanning. SG readings were compared to BG measurements by consensus error grid (CEG) analysis; the mean difference (MD), the mean relative difference (MRD), the mean absolute difference (MAD), and the mean absolute relative difference (MARD) were calculated. After 14 days, subjects were asked to fill in a questionnaire on the usability of the FGM. Results: 2,626 SG readings were paired with BG results. FGM readings were highly correlated with BG (r = 0.926, p < 0.001). 80.3% of the data pairs were in zone A (= no effect on clinical action) and 18.4% were in zone B (= altered clinical action with little or no effect on the clinical outcome) of the CEG. Overall MD was +7.5 mg/dL; MD varied with the BG meter: ACM +10.4 mg/dL, CNL +14.2 mg/dL, OTV –3.6 mg/dL (p < 0.001). Overall, MARD was 16.7%. We observed a large interindividual variability in the accuracy parameters. MD and MRD were inversely related to BMI (r = –0.261 [p < 0.05]; r = –0.266 [p < 0.05], respectively). MARD was inversely related to age (r = –0.266 [p < 0.05]). Twenty-nine patients (43.3%) reported sensor problems, mainly early detachment of the sensor. Nonetheless, the usability questionnaire indicated high levels of satisfaction. Conclusions: Our results showed a reasonable agreement between the FGM SG readings and capillary BG measurements in children. There was, however, a large interindividual variability. The wearing of the sensor requires special attention. Further studies in children are imperative in order to document the accuracy and safety of the FGM in the paediatric population.
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Evans, Catrin, Ritah Tweheyo, Julie McGarry, Jeanette Eldridge, Carol McCormick, Valentine Nkoyo, and Gina Marie Awoko Higginbottom. "What are the experiences of seeking, receiving and providing FGM-related healthcare? Perspectives of health professionals and women/girls who have undergone FGM: protocol for a systematic review of qualitative evidence." BMJ Open 7, no. 12 (December 2017): e018170. http://dx.doi.org/10.1136/bmjopen-2017-018170.
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IntroductionFemale genital mutilation (FGM) is an issue of global concern. High levels of migration mean that healthcare systems in higher-income western countries are increasingly being challenged to respond to the care needs of affected communities. Research has identified significant challenges in the provision of, and access to, FGM-related healthcare. There is a lack of confidence and competence among health professionals in providing appropriate care, suggesting an urgent need for evidence-based service development in this area. This study will involve two systematic reviews of qualitative evidence to explore the experiences, needs, barriers and facilitators to seeking and providing FGM-related healthcare in high-income (Organisation for Economic Cooperation and Development) countries, from the perspectives of: (1) women and girls who have undergone FGM and (2) health professionals.Review methodsTwelve databases including MEDLINE, EMBASE, PsycINFO, ASSIA, Web of Science, ERIC, CINAHL, and POPLINE will be searched with no limits on publication year. Relevant grey literature will be identified from digital sources and professional networks.Two reviewers will independently screen, select and critically appraise the studies. Study quality will be assessed using the Joanna Briggs Institute Qualitative Assessment and Review Instrument appraisal tool. Findings will be extracted into NVivo software. Synthesis will involve inductive thematic analysis, including in-depth reading, line by line coding of the findings, development of descriptive themes and re-coding to higher level analytical themes. Confidence in the review findings will be assessed using the CERQual approach. Findings will be integrated into a comprehensive set of recommendations for research, policy and practice.DisseminationThe syntheses will be reported as per the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement. Two reviews will be published in peer-reviewed journals and an integrated report disseminated at stakeholder engagement events.PROSPERO registration numberCRD42015030001: 2015 and CRD42015030004: 2015.
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Shin, Ki Hoon, and Seong Kyun Cheong. "FEA-Based Design and Fabrication of Functionally Graded Materials." Key Engineering Materials 326-328 (December 2006): 1681–84. http://dx.doi.org/10.4028/www.scientific.net/kem.326-328.1681.
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Functionally Graded Materials (FGMs) are composite materials that have continuous material variation along with geometry. This paper introduces a method for FEA-based design and layered manufacturing (LM) of FGMs. An FGM solid model is first created by referring to the libraries of primary materials and composition functions. The model is then discretized into an object model onto which appropriate material properties are mapped. Next, the object model is adaptively meshed and converted into an FE model. FEA using ANSYS is finally performed to estimate stress levels. This FEA-based design cycle is repeated until a satisfactory solution is obtained. The object model is then fed to the fabrication system where a process planning is performed to create instructions for LM machines. As a laser-based LM method, Direct Metal Deposition (DMD) at the University of Michigan is briefly described. A specific example (FGM pressure vessel) is shown to illustrate the entire FEA-based design and DMD fabrication cycle.
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Marealle, Wilfred N., Grethe Stavik Eggen, and Eivin Røskaft. "Faecal Glucocorticoids Metabolite Response in Giraffes (Giraffa camelopardalis tippelskirchi) in Relation to Protected Area Management Objectives in Tanzania." East African Journal of Forestry and Agroforestry 2, no. 1 (April 26, 2020): 47–58. http://dx.doi.org/10.37284/eajfa.2.1.142.
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The increase in the human population and the demand for natural resources and recreational activities poses insurmountable threats to the welfare and survival of wildlife. Human disturbance negatively impacts wildlife populations. A prospective way of determining wildlife welfare is to assess stress. To manage and conserve giraffes, it is vital to understand their stress factors and their responses to stressors. This study used a non-invasive (faecal collection) technique to evaluate the Faecal Glucocorticoid Metabolite (FGM) levels of giraffes depending on the protected area type, poaching risk, group size, age and sex. The study took place at the Serengeti National Park and Selous Game Reserve where a total of 63 faecal samples were randomly collected from 272 giraffe groups. A significant difference in the FGM levels between the sexes was found, as females had higher concentrations compared to males. In addition, a significant difference was found in relation to group size and age; however, protection type and poaching risk did not have any significant effect. Stressful conditions when prolonged can result in deteriorating animal welfare especially in calves and young animals thus their survival. However, the level of impaired FGMs and the amount of time required to produce damage are not known. In this regard, conservation strategies should seek to minimize the occurrence of stressful events in protected areas.
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Volfová, Martina, Zuzana Machovcová, Franz Schwarzenberger, Eva Voslářová, Iveta Bedáňová, and Vladimír Večerek. "The effects of transport stress on the behaviour and adrenocortical activity of the black-and-white ruffed lemur (Varecia variegata)." Acta Veterinaria Brno 88, no. 1 (2019): 85–92. http://dx.doi.org/10.2754/avb201988010085.
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The aim of this study was to assess behavioural and glucocorticoid changes in black-and-white ruffed lemur females transported for breeding purposes between Czech ZOOs. The frequency of the presented behaviour elements was recorded via direct observation. The faecal samples were collected from the floor and subsequently the faecal glucocorticoid values were determined using specifically designed assays for faecal glucocorticoid metabolite (FGM) analysis. While the frequency of certain comfort behaviour patterns decreased (P < 0.05) in response to transport and change of the environment, grooming, resting, sleeping as well as playful behaviour (chasing, climbing) were not affected (P > 0.05). No changes were found in the frequency of behaviour connected to metabolic events with the exception of defecation. Lemur females defecated more frequently (P < 0.05) in their new environment. The frequency of neither fear nor exploratory behaviour differed (P > 0.05) before and after transport. The positive effect of the novelty was shown by the reduction (P < 0.01) of behavioural signs of frustration and stereotypical behaviour after transport. In response to transport, a significant (P < 0.05) increase of FGM levels was found the second day after the transport, reaching peak levels in the morning and starting to decline to baseline levels in the afternoon. The results of both behaviour and adrenocortical activity analysis suggest that despite some presented changes in the monitored indices prior and after transport, the transportation under the studied conditions presented only a mild stressor with limited behavioural and glucocorticoid responses.
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Canecki Varzic, Silvija, Kristina Steiner, Maja Gradinjan Centner, Mladen Grgurevic, Maja Cigrovski Berkovic, Sanja Klobucar Majanovic, Maja Radman, Tanja Milicevic, Dario Rahelic, and Ines Bilic Curcic. "Assessment of FreeStyle Libre Flash Glucose Monitoring System Implementation in Real Life Clinical Setting: A Prospective Observational Study." Diagnostics 11, no. 2 (February 13, 2021): 305. http://dx.doi.org/10.3390/diagnostics11020305.
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Background: In this study, we investigated the effectiveness of FreeStyle Libre Flash Glucose Monitoring (FGM) implementation in a real life clinical setting with the emphasis on the effect of initial education on the use of the FGM system. Methods: This prospective observational study included 425 diabetes type 1 subjects followed up for 3 to 12 months (320 were followed up to 3 months, 267 up to 6 months and 147 up to period of one year). An FGM sensor was placed at study entry and all participants were educated through a period of 5 days on sensor usage and self-management of glycemia with follow up visits every 3 months. Results: HbA1c values significantly decreased from baseline (T0) to 3 months (T3) (p < 0.001), with a drop from 7.48% ± 0.1% to 7.30 ± 0.1%. There was no change in time spent in hypoglycemia from T3 to T12, although there was a decreasing trend present. The change in HbA1c values in the entire cohort was driven by change in the subgroup of patients with HbA1c ≥7% with a drop from 8.22% ± 1.14% to 7.68% ± 1.26% (p < 0.0001) in the first 3 months. Also, in individuals performing SMBG less than 5 times per day, there was a steady decrease in HbA1c levels up to 6 months (p < 0.05 and p < 0.001, respectively) as opposed to those who performed SMBG ≥5 times per day. Conclusions: The improvement in HbA1c was mainly driven by the increase in the number of scans per day. The subjects with poorer glycemic control and those who seldom performed SMBG benefited the most.
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Schoustra, Sijmen, Sungmin Hwang, Joachim Krug, and J. Arjan G. M. de Visser. "Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus." Proceedings of the Royal Society B: Biological Sciences 283, no. 1837 (August 31, 2016): 20161376. http://dx.doi.org/10.1098/rspb.2016.1376.
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Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.
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Castellana, Marco, Claudia Parisi, Sergio Di Molfetta, Ludovico Di Gioia, Annalisa Natalicchio, Sebastio Perrini, Angelo Cignarelli, Luigi Laviola, and Francesco Giorgino. "Efficacy and safety of flash glucose monitoring in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis." BMJ Open Diabetes Research & Care 8, no. 1 (June 2020): e001092. http://dx.doi.org/10.1136/bmjdrc-2019-001092.
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IntroductionFlash glucose monitoring (FGM) is a factory-calibrated sensor-based technology for the measurement of interstitial glucose. We performed a systematic review and meta-analysis to assess its efficacy and safety in patients with type 1 and type 2 diabetes.Research design and methodsPubMed, CENTRAL, Scopus and Web of Science were searched in July 2019. Twelve studies with a follow-up longer than 8 weeks, evaluating 2173 patients on prandial insulin, multiple daily insulin injections or continuous subcutaneous insulin infusion were included. The following data were extracted: HbA1c, time in range, time above 180 mg/dL, time below 70 mg/dL, frequency of hypoglycemic events, number of self-monitoring of blood glucose (SMBG) measurements, total daily insulin dose, patient-reported outcomes, adverse events, and discontinuation rate. A comparison with SMBG was conducted.ResultsFGM use was associated with a reduction in HbA1c (−0.26% (−3 mmol/mol); p=0.002) from baseline to the last available follow-up, which correlated with HbA1c levels at baseline (−0.4% (−4 mmol/mol) for each 1.0% (11 mmol/mol) of HbA1c above 7.2% (55 mmol/mol)). Also, a decrease in time below 70 mg/dL was found (−0.60 hours/day; p=0.04). Favorable findings in patient-reported outcomes and no device-related serious adverse events were reported. When compared with SMBG, FGM was characterized by no statistically different change in HbA1c (p=0.09), with lower number of SMBG measurements per day (−3.76 n/day; p<0.001) and risk of discontinuation (relative risk=0.42; p=0.001). A limited number of studies, with a heterogeneous design and usually with a short-term follow-up and without specific training, were found.ConclusionsThe present review provides evidence for the use of FGM as an effective strategy for the management of diabetes.
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Karaarslan, ES, ZC Özmen, F. Aytac, AA Bicakci, M. Buldur, L. Aydogan, F. Hologlu, and BBC Özkocak. "Evaluation of biochemical changes in dental tissues after different office bleaching methods." Human & Experimental Toxicology 38, no. 4 (December 9, 2018): 389–97. http://dx.doi.org/10.1177/0960327118817103.
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The color of the teeth is an important topic for many people and can be influenced by intrinsic and extrinsic stains. There is an increasing demand for whitening of the teeth year by year. The most popular way of whitening is “bleaching,” which is the result of the breakdown of pigments located in the enamel and/or the dentin, caused by reactive oxygen species (ROS) released from bleaching agents. These bleaching agents could increase matrix metalloproteinase (MMP)-mediated collagen degradation in dentin. The aim of this study was to compare biochemical changes and oxidative stress levels of the human premolar dentin–pulp complex after three different bleaching methods containing hydrogen peroxide (H2O2) bleaching agents. Individuals, whose first four premolars were extracted for orthodontic purposes, included into the study. Group 1—Laser: bleaching gel containing 46% H2O2 (LaserWhite20 whitening gel, Biolase Technology Inc., San Clemente, CA, USA) and a diode laser activation (Ezlase 940 nm system). Group 2: 35% H2O2 containing whitening gel (Whiteness HP Maxx, FGM) and halogen light source activation (Optilux 501, Kerr, Orange, CA, USA). Group 3: 35% H2O2 containing whitening gel (Whiteness HP Maxx, FGM). Group 4—Control: No whitening treatment. According to the test results, there were no significant differences among groups in the values of cathepsin B and MMP proteolytic activities ( p > 0.05). The total ROS values released from the dentin tissue were higher than those obtained from the pulp tissue ( p < 0.05). There were significant differences among the bleaching groups in the ROS values released from the dentin tissue.
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Arantes, Vera Lúcia, Leonardo Grajales Agudelo, and Pedro Luiz di Lorenzo. "Characterization of Composites Based on 316 Stainless Steel and Zirconia for Use as Functionally Graded Materials." Materials Science Forum 802 (December 2014): 120–24. http://dx.doi.org/10.4028/www.scientific.net/msf.802.120.
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Functionally graded materials (FGM) based on stainless steel and ceramic materials have inspired researchers to combine properties and features which are not present in conventional composites, and are considered to be an alternative in the production of motors parts, cutting tools and coatings for reactors. The addition of metal and ceramic in a graded structure allows the integration of distinct properties that combine advantages of metallic and ceramic materials. Ceramic components withstand high temperatures and present high corrosion resistance, while metallic ones provide higher mechanical resistance, in particular ultimate tensile strength and fracture toughness. In this work, composites with variable levels of 316 Stainless Steel and Ytria-stabilized Zirconia, were prepared and characterized, in order to determine the thermal behavior of each composition, aiming the optimization of sintering of pieces with chemical composition gradation.
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Khan, Atif Maqbool, and Magdalena Osińska. "How to Predict Energy Consumption in BRICS Countries?" Energies 14, no. 10 (May 11, 2021): 2749. http://dx.doi.org/10.3390/en14102749.
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Brazil, Russia, China, India, and the Republic of South Africa (BRICS) represent developing economies facing different energy and economic development challenges. The current study aims to predict energy consumption in BRICS at aggregate and disaggregate levels using the annual time series data set from 1992 to 2019 and to compare results obtained from a set of models. The time-series data are from the British Petroleum (BP-2019) Statistical Review of World Energy. The forecasting methodology bases on a novel Fractional-order Grey Model (FGM) with different order parameters. This study contributes to the literature by comparing the forecasting accuracy and the predictive ability of the FGM1,1 with traditional ones, like standard GM1,1 and ARIMA1,1,1 models. Moreover, it illustrates the view of BRICS’s nexus of energy consumption at aggregate and disaggregates levels using the latest available data set, which will provide a reliable and broader perspective. The Diebold-Mariano test results confirmed the equal predictive ability of FGM1,1 for a specific range of order parameters and the ARIMA1,1,1 model and the usefulness of both approaches for energy consumption efficient forecasting.
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Khan, Tehmina nafees sonia, Arshi Naz, Arjit Biswas, Anne Goodeve, Nisar Ahmed, Shariq Ahmed, Tahir Shamsi, and Johannes Oldenburg. "Identification of Novel Mutations with Molecular Modelling of Missense Mutations of Congenital Afibrinogenemia Patients in Pakistan." Blood 126, no. 23 (December 3, 2015): 4664. http://dx.doi.org/10.1182/blood.v126.23.4664.4664.
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Abstract Background: Congenital afibrinogenemia (OMIM #202400) is a rare coagulation disorder which was first described in 1920. It is transmitted as an autosomal recessive trait characterized by absent levels of fibrinogen (factor I) in plasma. Consanguinity in Pakistan and its neighboring countries has resulted in higher cases of congenital fibrinogen deficiency in their respective populations. Aims: This study focuses on the detection of mutations in the fibrinogen genes by DNA sequencing and molecular modeling of missense mutations in all three genes (Fibrinogen gene alpha (FGA), beta (FGB) and gamma (FGG) in Pakistani patients. Methods: This descriptive and cross sectional study was conducted in Karachi and Lahore and fully complied with the Declaration of Helsinki. Patients with fibrinogen deficiency (tested by Fibrinogen functional assay from Laboratoire Stago, Asnieres, France) were screened for mutations in the Fibrinogen gene alpha (FGA), beta (FGB) and gamma (FGG) genes by direct sequencing. Molecular modeling was performed to predict the putative structure functional impact of the missense mutations identified in this study Results: Ten patients had FGA mutations, four have FGB mutations and one mutation was detected in FGG. Thirteen of these mutations were novel. The missense mutations are predicted to result in loss of stability since they (a) break ordered regions (b) cause clashes in the hydrophobic core of the protein. Conclusion: Congenital afibrinogenemia is a rapid growing problem in countries such as Pakistan where consanguinity is frequently practiced. This study illustrates the fact that mutations in FGA are relatively more common in our population than those in FGB where as FGG mutations appear rarer. Disclosures Oldenburg: SOBI: Consultancy.
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Hammond, Talisin T., Minnie Vo, Clara T. Burton, Lisa L. Surber, Eileen A. Lacey, and Jennifer E. Smith. "Physiological and behavioral responses to anthropogenic stressors in a human-tolerant mammal." Journal of Mammalogy 100, no. 6 (September 11, 2019): 1928–40. http://dx.doi.org/10.1093/jmammal/gyz134.
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Abstract As humans continue to alter natural habitats, many wild animals are facing novel suites of environmental stimuli. These changes, including increased human–wildlife interactions, may exert sublethal impacts on wildlife such as alterations in stress physiology and behavior. California ground squirrels (Otospermophilus beecheyi) occur in human-modified as well as more pristine environments, where they face a variety of anthropogenic and naturally occurring threats. This makes this species a valuable model for examining the effects of diverse challenges on the physiology and behavior of free-living mammals. To explore potential sublethal effects of habitat modification on O. beecheyi, we compared body masses, behaviors, and fecal glucocorticoid metabolite (FGM) levels for free-living squirrels in human-disturbed versus undisturbed habitats. Prior to these analyses, we validated the use of FGMs in this species by exposing captive O. beecheyi to pharmacological and handling challenges; both challenges produced significant increases in FGMs in the study animals. While FGM responses were repeatable within captive individuals, responses by free-living animals were more variable, perhaps reflecting a greater range of life-history traits and environmental conditions within natural populations of squirrels. Animals from our human-disturbed study site had significantly higher FGMs, significantly lower body masses, and were significantly less behaviorally reactive to humans than those from our more pristine study site. Thus, despite frequent exposure of California ground squirrels to human impacts, anthropogenic stressors appear to influence stress physiology and other phenotypic traits in this species. These findings suggest that even human-tolerant mammalian species may experience important sublethal consequences due to human modifications of natural habitats.
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Apalak, M. Kemal, and M. Didem Demirbas. "Improved Mathematical Models of Thermal Residual Stresses in Functionally Graded Adhesively Bonded Joints: A Critical Review." Reviews of Adhesion and Adhesives 7, no. 4 (December 1, 2019): 367–416. http://dx.doi.org/10.7569/raa.2019.097313.
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Functionally graded material (FGM) concept has been applied successfully in order to improve/design heat transfer, electric and electronic conductivity, static and dynamic strengths of adhesive joints by reliving stress distributions in both adhesive and adherend materials. This new approach relies on tailoring material composition of adhesive and adherends along one or more coordinate directions. Thermal residual stresses in adhesive joints are a vital issue in terms of the joint strength. FGM concept also allows to relieve/control thermal residual stresses encountered in adhesive joints due to mismatches between coefficients of thermal expansion of adhesive and adherend materials. Mathematical models and solutions on the thermal residual stress analysis have been continuously improved. This paper reviews the current status of mathematical models, and offers an improved mathematical model and numerical solution method by considering two-dimensional thermal stress and deformation states of adhesively bonded bi-directional functionally graded clamped plates subjected to an in-plane heat flux along one of the ceramic edges. This mathematical model assumes the material properties of the functionally graded plates to vary with a power law along two in-plane directions and not through the plate thickness direction, in particular, considers the spatial derivatives of thermal and mechanical properties of the material, and enables the investigation of the effects of the bi-directional composition variations and spatial derivative terms on the displacement, strain and stress distributions. The heat conduction and Navier equations describing the twodimensional thermo-elastic problem are discretized using finite-difference method, and the set of linear equations are solved using the pseudo singular value method. The functionally graded plates relieve both stress and strain distributions and levels in the adhesive layer and in the plates even though the adhesive layer is still ungraded. The spatial derivatives of mechanical and thermal properties of the local material become more effective on the strain and stress distributions of the plates and adhesive layer. The model, disregarding these derivative terms, exhibits sensitivity to small changes in the compositional gradients (n, m) by adjusting the variations of ceramic volume fraction along the x - and y-directions, respectively, and instability in the calculation of stress and strain distributions and levels. However, the improved model with material derivatives, which considers the effects of these derivative terms, predicts stress and strain distributions and levels complying with changes in the compositional gradient exponents.
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Vallat, C., I. Dandouras, M. Dunlop, A. Balogh, E. Lucek, G. K. Parks, M. Wilber, E. C. Roelof, G. Chanteur, and H. Rème. "First current density measurements in the ring current region using simultaneous multi-spacecraft CLUSTER-FGM data." Annales Geophysicae 23, no. 5 (July 28, 2005): 1849–65. http://dx.doi.org/10.5194/angeo-23-1849-2005.
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Abstract. The inner magnetosphere's current mapping is one of the key elements for current loop closure inside the entire magnetosphere. A method for directly computing the current is the multi-spacecraft curlometer technique, which is based on the application of Maxwell-Ampère's law. This requires the use of four-point magnetic field high resolution measurements. The FGM experiment on board the four Cluster spacecraft allows, for the first time, an instantaneous calculation of the magnetic field gradients and thus a measurement of the local current density. This technique requires, however, a careful study concerning all the factors that can affect the accuracy of the J estimate, such as the tetrahedral geometry of the four spacecraft, or the size and orientation of the current structure sampled. The first part of this paper is thus providing a detailed analysis of the method accuracy, and points out the limitations of this technique in the region of interest. The second part is an analysis of the ring current region, which reveals, for the first time, the large latitudinal extent of the ring current, for all magnetic activity levels, as well as the latitudinal evolution of the perpendicular (and parallel) components of the current along the diffuse auroral zone. Our analysis also points out the sharp transition between two distinct plasma regions, with the existence of high diamagnetic currents at the interface, as well as the filamentation of the current inside the inner plasma sheet. A statistical study over multiple perigee passes of Cluster (at about 4 RE from the Earth) reveals the azimuthal extent of the partial ring current. It also reveals that, at these distances and all along the evening sector, there isn't necessarily a strong dependence of the local current density value on the magnetic activity level. This is a direct consequence of the ring current morphology evolution, as well as the relative positioning of the spacecraft with respect to the bulk of the ring current. It also proves the existence of a substantial ring current at these distances, all over the evening and the post-midnight sector. Keywords. Magnetospheric physics (Current systems; Energetic particles, trapped; Magnetospheric configuration and dynamics)
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Fish, Richard J., and Marguerite Neerman-Arbez. "A novel regulatory element between the human FGA and FGG genes." Thrombosis and Haemostasis 108, no. 09 (2012): 427–34. http://dx.doi.org/10.1160/th12-04-0274.
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SummaryHigh circulating fibrinogen levels correlate with cardiovascular disease (CVD) risk. Fibrinogen levels vary between people and also change in response to physiological and environmental stimuli. A modest proportion of the variation in fibrinogen levels can be explained by genotype, inferring that variation in genomic sequences that regulate the fibri-nogen genes (FGA, FGB and FGG) may affect hepatic fibrinogen production and perhaps CVD risk. We previously identified a conserved liver enhancer in the fibrinogen gene cluster (CNC12), between FGB and FGA. Genome-wide Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that transcription factors which bind fibrinogen gene promoters also interact with CNC12, as well as two potential fibrinogen enhancers (PFE), between FGA and FGG. Here we show that one of the PFE sequences has potent hepatocyte enhancer activity. Using a luciferase reporter gene system, we found that PFE2 enhances minimal promoter- and FGA promoter-driven gene expression in hepatoma cells, regardless of its orientation with respect to the promoters. A region within PFE2 bears a short series of conserved nucleotides which maintain enhancer activity without flanking sequence. We also demonstrate that PFE2 is a liver enhancer in vivo, driving enhanced green fluorescent protein expression in transgenic zebrafish larval livers. Our study shows that combining public domain ChIP-seq data with in vitro and in vivo functional tests can identify novel fibrinogen gene cluster regulatory sequences. Variation in such elements could affect fibrinogen production and influence CVD risk.
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Fokkert, Marion, Peter R. van Dijk, Mireille A. Edens, Alberto Díez Hernández, Robbert Slingerland, Rijk Gans, Elías Delgado Álvarez, and Henk Bilo. "Performance of the Eversense versus the Free Style Libre Flash glucose monitor during exercise and normal daily activities in subjects with type 1 diabetes mellitus." BMJ Open Diabetes Research & Care 8, no. 1 (August 2020): e001193. http://dx.doi.org/10.1136/bmjdrc-2020-001193.
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IntroductionAccurate blood glucose measurements are important in persons with diabetes during normal daily activities (NDA), even more so during exercise. We aimed to investigate the performance of fluorescence sensor-based and glucose oxidase-based interstitial glucose measurement during (intensive) exercise and NDA.Research design and methodsProspective, observational study in 23 persons with type 1 diabetes when mountain biking for 6 days, followed by 6 days of NDA. Readings of the Eversense (fluorescence-based continuous glucose monitoring (CGM); subcutaneously implanted) and of the Free Style Libre (FSL; glucose oxidase-based flash glucose monitoring (FGM); transcutaneously placed) were compared with capillary glucose levels (Free Style Libre Precision NeoPro strip (FSLCstrip)).ResultsMean average differences (MAD) and mean average relative differences (MARD) were significantly different when comparing exercise with NDA (reference FSLCstrip); Eversense MAD 25±19 vs 17±6 mg/dL (p<0.001); MARD 17±6 vs 13%±6% (p<0.01) and FSL MAD 32±17 vs 18±8 mg/dL (p<0.01); MARD 20±7 vs 12%±5% (p<0.001).When analyzing the data according to the Integrated Continuous Glucose Monitoring Approvals (class II–510(K) guidelines), the overall performance of interstitial glucose readings within 20% of the FSLCstrip during exercise compared with NDA was 69% vs 81% for the Eversense and 59% vs 83% for the FSL, respectively. Within 15% of the FSLCstrip was 59% vs 70% for the Eversense and 46% vs 71% for the FSL.ConclusionsDuring exercise, both fluorescence and glucose oxidase-based interstitial glucose measurements (using Eversense and FSL sensors) were less accurate compared with measurements during NDA. Even when acknowledging the beneficial effects of CGM or FGM, users should be aware of the risk of diminished accuracy of interstitial glucose readings during (intensive) exercise.
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Khonmee, Jaruwan, Thanat Wathirunwong, Terdsak Yano, Chaleamchat Somgird, Janine L. Brown, and Panuwat Yamsakul. "Effect of Artificial Piglet Suckling Sounds on Behavior and Performance of Piglets and Adrenal Responses of Sows." Veterinary Medicine International 2018 (October 22, 2018): 1–7. http://dx.doi.org/10.1155/2018/2762153.
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Operation of the farrowing house is essential to the productivity of a swine farm, requiring not only good management but also knowledge of the behavior of sows and piglets. Stress can negatively affect production in farm animals and could be a factor in production indexes. The objective of this study was to investigate the effect of artificial sucking sounds on the behavior of piglets and fecal glucocorticoid (FGM) concentrations of sows. A total of 30 sows were divided into two groups: a treatment group (15 sows) was exposed to artificial sucking sounds and a control group (15 sows) was not. Both groups received the same management; the two open-house system locations were separated by a distance of about 270 meters. The study had three key objectives: to compare farrowing indexes and to observe the sucking behavior of piglets using CCTV cameras. Fecal samples were collected daily for 21 days from the period after parturition to weaning to assess adrenal activity. The treatment group had a significantly higher average number of times piglets came to a sow’s udder, and sows had a shorter onset time for the first piglet to come to the sow’s udder than the control group (bothP<0.05). The patterns and levels of FGM between the two groups were not different (bothP<0.05), but the treatment group had better farrowing indexes than the control group (P>0.05), particularly for litter weight gain and percent preweaning mortality. In addition, the weaning to first service interval of the treatment group was shorter than the control group (P<0.05). This indicates that the artificial suckling sound probably has no adverse effect on adrenal responses of pig; however, it improves production indexes of postparturition sows.
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Volfova, Martina, Zuzana Machovcova, Eva Voslarova, Iveta Bedanova, and Vladimir Vecerek. "Comparison of the Glucocorticoid Concentrations between Three Species of Lemuridae Kept in a Temporary Housing Facility." Animals 10, no. 6 (June 10, 2020): 1013. http://dx.doi.org/10.3390/ani10061013.
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We compared the glucocorticoid concentrations in response to various types of potential stressors present during standard operation of a temporary housing facility between three species, namely, ring-tailed lemurs, collared brown lemurs and white-headed lemurs. The levels of faecal glucocorticoid metabolites (FGMs) were measured non-invasively on a daily basis during a 30-day period. A total of 510 faecal samples were collected. Concentrations of immunoreactive glucocorticoid hormone metabolites were measured in the obtained extracts by using an enzyme immunoassay. The polyclonal antibodies used in this assay were directed against the metabolite 11-oxo-etiocholanolone I. We found all three monitored lemur species to respond to specific potentially stressful situations by increasing (p < 0.05) the FGM levels within one to two days after the event. Although housed in the same room, differences in response to potentially stressful situations were found in white-headed lemurs compared to ring-tailed lemurs. Increased mean levels of the FGMs were found more frequently in white-headed lemurs than in ring-tailed lemurs. The results suggest that this species may be more sensitive to changes in its surroundings. In general, the levels of the FGMs showed a similar pattern during 30 days of monitoring suggesting that all groups of lemurs responded in a similar manner to the same events. However, we recorded the differences in the absolute values of glucocorticoid concentrations between the monitored species likely due to the differences in sex ratios in the groups and presence of lactating females in the ring-tailed lemurs.
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Acaralp-Rehnberg, Lydia K., Grahame J. Coleman, Michael J. L. Magrath, Vicky Melfi, Kerry V. Fanson, and Ian M. Bland. "The Effect of Behind-The-Scenes Encounters and Interactive Presentations on the Welfare of Captive Servals (Leptailurus serval)." Animals 10, no. 4 (April 24, 2020): 743. http://dx.doi.org/10.3390/ani10040743.
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The serval (Leptailurus serval) is a small African felid that is well represented in zoos and often serves as an animal ambassador in encounter programs with zoo visitors. The impact on serval welfare in relation to such programs has not been investigated to date, and the aim of this study was to assess short-term welfare effects of varying levels of visitor interaction in two captive servals. Weekly blocks of four different treatments were imposed three times on each animal over 12 weeks, and the treatments involved (1) Presentations (serval undertaking a routine training session in a designated presentation space, typically attracting high visitor numbers), (2) Behind-the-scenes (BTS, a close encounter allowing a small group of visitors to interact closely with the cat in its enclosure), (3) Presentations and BTS combined, and (4) No visitor interaction. Serval activity budgets as well as behavioural diversity were created from behaviours observed from Close Circuit Television (CCTV) footage during four daily recording sessions per animal over three consecutive days per treatment, using instantaneous scan sampling every 60 s. Individual faecal samples were collected daily to monitor changes in faecal glucocorticoid metabolite (FGM) concentration. Results indicate that the mean number of scans with stereotypic pacing was significantly reduced (p = 0.01) during Treatments 1 and 3, when cats participated in presentations only, or the two activities combined. Conversely, a significant reduction in behavioural diversity (p < 0.001) was observed when cats participated in Treatment 3, i.e., cats expressed fewer behaviours when interaction with visitors was more frequent. FGM concentrations did not vary significantly with treatment (p > 0.05). Given the reduction in stereotypic pacing, these findings suggest that involvement in an encounter program appears to exert an overall positive short-term welfare effect on the individual servals in this study. Although a reduction in behavioural diversity was not considered a negative welfare effect in the short term, potential long-term negative welfare effects resulting from a more frequent encounter program could not be ruled out in the present study.
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Neerman-Arbez, Marguerite, Dung Vu, Bassam Abu-Libdeh, Isabelle Bouchardy, and Michael A. Morris. "Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense mutation in the FGB gene in a Palestinian family." Blood 101, no. 9 (May 1, 2003): 3492–94. http://dx.doi.org/10.1182/blood-2002-10-3116.
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Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease, homozygous deletions of approximately 11 kb of the fibrinogen alpha chain gene (FGA). Subsequent analyses revealed that most afibrinogenemia alleles are truncating mutations of FGA, although mutations in all 3 fibrinogen genes, FGG, FGA andFGB have been identified. In this study, we performed the first prenatal diagnosis for afibrinogenemia. The causative mutation in a Palestinian family was a novel nonsense mutation in theFGB gene, Trp467Stop (W467X). Expression of the Trp467Stop mutant FGB cDNA in combination with wild-typeFGA and FGG cDNAs showed that fibrinogen molecules containing the mutant beta chain are not secreted into the media. The fetus was found to be heterozygous for the Trp467Stop mutation by direct sequencing and by linkage analysis, a result that was confirmed in the newborn by intermediate fibrinogen levels.
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Chen, Yu Liang, and Chin Yu Huang. "Effect of Varied Layer-Content/Thickness on Ballistic Performance of a Functionally Graded Al2O3/ZrO2 Material." Materials Science Forum 928 (August 2018): 243–48. http://dx.doi.org/10.4028/www.scientific.net/msf.928.243.
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This study compared the ballistic performance of alumina (Al2O3)/ zirconia (ZrO2) functionally graded material (FGM) specimens with various levels of thickness and ZrO2 content and a pure Al2O3 single-layer ceramic composite (PCM). Ballistic tests were conducted with 0.3-inch armor-piercing (AP) projectiles, and finite element code LS-DYNA was used to examine energy absorption, stress distribution, and ceramic cone failure in the specimens. The findings are as follows: First, regarding energy absorption per unit of areal density, the 5% FGMs had the highest ballistic performance, which increased by up to 8%. By contrast, the ballistic performance of the 15% FGMs declined significantly to lower than that of the PCM. Second, the capability of the ceramic cone to withstand stress damage and projectiles was significantly greater in the 5% FGMs than in the 15% FGMs. Third, the wave impedance variations increased with the ZrO2 content in each layer, thereby enhancing the interactions between impact waves and aggravating ceramic damage. Thus, the intensities of transmission and reflection waves in the 15% FGMs increased, thereby causing reductions in its ballistic performance.
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Solari, A., N. Acquarone, E. Pucci, V. Martinelli, M. G. Marrosu, M. Trojano, C. Borreani, and M. Messmer Uccelli. "Communicating the diagnosis of multiple sclerosis - a qualitative study." Multiple Sclerosis Journal 13, no. 6 (February 9, 2007): 763–69. http://dx.doi.org/10.1177/1352458506074689.
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Studies on communicating the diagnosis of multiple sclerosis (MS) are few, and all reveal communication and information deficits. We explored the personal experience of diagnosis communication of people with MS and health professionals, using a qualitative methodology. Data were obtained from two sets of focus group meetings (FGM) with people with MS (total 23; 16 females; age range: 23-70) and one FGMs with health professionals (four neurologists, three psychologists, two nurses). The methods of framework analysis were applied to meeting transcripts to identify key topics and categories. The experience of communicating/receiving an MS diagnosis was highly varied; all patients reported the moment as powerfully evocative and unforgettable. Very poor levels of support and information were sometimes given. Although diagnosis communication had improved in more recent experience, all felt it should be further improved with appropriate setting (privacy, no interruptions, sufficient time), information tailored to the individual, and continuity of care. Such improvements imply a more meaningful patientneurologist relationship, and also structural and organisational changes. Multiple Sclerosis 2007; 13: 763-769. http://msj.sagepub.com
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Simurda, Tomas, Rui Vilar, Jana Zolkova, Eliska Ceznerova, Zuzana Kolkova, Dusan Loderer, Marguerite Neerman-Arbez, et al. "A Novel Nonsense Mutation in FGB (c.1421G>A; p.Trp474Ter) in the Beta Chain of Fibrinogen Causing Hypofibrinogenemia with Bleeding Phenotype." Biomedicines 8, no. 12 (December 13, 2020): 605. http://dx.doi.org/10.3390/biomedicines8120605.
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Congenital hypofibrinogenemia is a rare bleeding disorder characterized by a proportional decrease of functional and antigenic fibrinogen levels. Hypofibrinogenemia can be considered the phenotypic expression of heterozygous loss of function mutations occurring within one of the three fibrinogen genes (FGA, FGB, and FGG). Clinical manifestations are highly variable; most patients are usually asymptomatic, but may appear with mild to severe bleeding or thrombotic complications. We have sequenced all exons of the FGA, FGB, and FGG genes using the DNA isolated from the peripheral blood in two unrelated probands with mild hypofibrinogenemia. Coagulation screening, global hemostasis, and functional analysis tests were performed. Molecular modeling was used to predict the defect of synthesis and structural changes of the identified mutation. DNA sequencing revealed a novel heterozygous variant c.1421G>A in exon 8 of the FGB gene encoding a Bβ chain (p.Trp474Ter) in both patients. Clinical data from patients showed bleeding episodes. Protein modelling confirmed changes in the secondary structure of the molecule, with the loss of three β sheet arrangements. As expected by the low fibrinogen levels, turbidity analyses showed a reduced fibrin polymerisation and imaging difference in thickness fibrin fibers. We have to emphasize that our patients have a quantitative fibrinogen disorder; therefore, the reduced function is due to the reduced concentration of fibrinogen, since the Bβ chains carrying the mutation predicted to be retained inside the cell. The study of fibrinogen molecules using protein modelling may help us to understand causality and effect of novel genetic mutations.
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Nemeth, Matthias, Elisabeth Pschernig, Bernard Wallner, and Eva Millesi. "Non-invasive cortisol measurements as indicators of physiological stress responses in guinea pigs." PeerJ 4 (January 18, 2016): e1590. http://dx.doi.org/10.7717/peerj.1590.
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Non-invasive measurements of glucocorticoid (GC) concentrations, including cortisol and corticosterone, serve as reliable indicators of adrenocortical activities and physiological stress loads in a variety of species. As an alternative to invasive analyses based on plasma, GC concentrations in saliva still represent single-point-of-time measurements, suitable for studying short-term or acute stress responses, whereas fecal GC metabolites (FGMs) reflect overall stress loads and stress responses after a species-specific time frame in the long-term. In our study species, the domestic guinea pig, GC measurements are commonly used to indicate stress responses to different environmental conditions, but the biological relevance of non-invasive measurements is widely unknown. We therefore established an experimental protocol based on the animals’ natural stress responses to different environmental conditions and compared GC levels in plasma, saliva, and fecal samples during non-stressful social isolations and stressful two-hour social confrontations with unfamiliar individuals. Plasma and saliva cortisol concentrations were significantly increased directly after the social confrontations, and plasma and saliva cortisol levels were strongly correlated. This demonstrates a high biological relevance of GC measurements in saliva. FGM levels measured 20 h afterwards, representing the reported mean gut passage time based on physiological validations, revealed that the overall stress load was not affected by the confrontations, but also no relations to plasma cortisol levels were detected. We therefore measured FGMs in two-hour intervals for 24 h after another social confrontation and detected significantly increased levels after four to twelve hours, reaching peak concentrations already after six hours. Our findings confirm that non-invasive GC measurements in guinea pigs are highly biologically relevant in indicating physiological stress responses compared to circulating levels in plasma in the short- and long-term. Our approach also underlines the importance of detailed investigations on how to use and interpret non-invasive measurements, including the determination of appropriate time points for sample collections.
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Nowak-Göttl, Ulrike, Hartmut Weiler, Irene Hernandez, Sabine Thedieck, Tanja Seehafer, Thomas Schulte, and Monika Stoll. "Fibrinogen α and γ genes and factor VLeiden in children with thromboembolism: results from 2 family-based association studies." Blood 114, no. 9 (August 27, 2009): 1947–53. http://dx.doi.org/10.1182/blood-2009-04-218727.
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Previous case-control studies showed that genetic variation in the fibrinogen γ gene (FGG) increased the risk for deep vein thrombosis (VT) in adults. We investigated the association between the fibrinogen α (FGA) and FGG haplotypes, the factor VLeiden-mutation, and pediatric VT and thromboembolic stroke (TS) in 2 independent study samples. Association analysis revealed that the FGA-H1 and FGG-H2 haplotypes were significantly overtransmitted to VT patients (FGA-H1, P = .05; FGG: H2, P = .032). In contrast, the FGG-H3 haplotype was undertransmitted (P = .022). In an independent study sample, FGA-H1 (P = .008) and FGG-H2 (P = .05) were significantly associated with TS. The association of FGA and FGG haplotypes with VT was more pronounced in FVLeiden-negative families (FGA-H1, P = .001; FGG-H2, P = .001), indicating a genetic interaction between both risk factors. The risk-conferring FGG-H2 and the protective FGG-H3 haplotypes correlated with low (FGG-H2) and high (FGG-H3) levels of the γ′ chain variant, respectively. These results provide independent and novel evidence that FGA-H1 and FGG-H2 variants are associated with an increased risk of VT and TS in children. The observed negative correlation of genetic VT risk with the plasma levels of the fibrinogen γ′ variant suggests that FGG-H2 and -H3 haplotypes modify thrombosis risk by controlling the level of this FGG splice isoform.
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Monaldini, Luca, Rosanna Asselta, Stefano Duga, Flora Peyvandi, Mehran Karimi, Massimo Malcovati, and Maria Tenchini. "Mutational screening of six afibrinogenemic patients: Identification and characterization of four novel molecular defects." Thrombosis and Haemostasis 97, no. 04 (2007): 546–51. http://dx.doi.org/10.1160/th06-12-0743.
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SummaryCongenital afibrinogenemia (CAF) is a rare coagulation disorder characterized by very low or unmeasurable levels of functional and immunoreactive fibrinogen in plasma, associated with a hemorrhagic phenotype of variable severity. It is transmitted as an autosomal recessive trait (prevalence 1:1,000,000) and is invariantly associated with mutations affecting one of the three fibrinogen genes (FGA, FGB, and FGG, coding for Aα, Bβ, and γ chain, respectively). Fibrinogen is secreted by hepatocytes as a hexamer composed of two copies of each chain; the lack of one chain has been demonstrated to prevent its secretion. Most genetic defects causing afibrinogenemia are point mutations, where- as only three large deletions have been identified so far, all affecting the FGA gene. We here report the molecular characterization of six unrelated afibrinogenemic patients leading to the identification of eight different mutations, four hitherto unknown: a 4.1-Kb large deletion involving exon 1 of FGA (AC107385:g. 65682_69828del), two nonsense mutations (p.Trp229X in FGA and p.Trp266X in FGB), and an ins-del mutation (g.1787_ 1789del3ins12) in FGA. The molecular characterization of CAFcausing genetic defects increases our understanding on the genetic basis of this disease and might be helpful for prenatal screening purposes, as also demonstrated during this study.
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Uitte de Willige, Shirley, Marieke C. H. de Visser, Jeanine J. Houwing-Duistermaat, Frits R. Rosendaal, Hans L. Vos, and Rogier M. Bertina. "Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen γ′ levels." Blood 106, no. 13 (December 15, 2005): 4176–83. http://dx.doi.org/10.1182/blood-2005-05-2180.
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We investigated the association between haplotypes of fibrinogen alpha (FGA), beta (FGB), and gamma (FGG), total fibrinogen levels, fibrinogen γ′ (γA/γ′ plus γ′/γ′) levels, and risk for deep venous thrombosis. In a population-based case-control study, the Leiden Thrombophilia Study, we typed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) in this gene cluster. None of these haplotypes was associated with total fibrinogen levels. In each gene, one haplotype increased the thrombosis risk approximately 2-fold. After adjustment for linkage disequilibrium between the genes, only FGG-H2 homozygosity remained associated with risk (odds ratio [OR], 2.4; 95% confidence interval [95% CI], 1.5-3.9). FGG-H2 was also associated with reduced fibrinogen γ′ levels and reduced ratios of fibrinogen γ′ to total fibrinogen. Multivariate analysis showed that reduced fibrinogen γ′ levels and elevated total fibrinogen levels were both associated with an increased risk for thrombosis, even after adjustment for FGG-H2. A reduced fibrinogen γ′ to total fibrinogen ratio (less than 0.69) also increased the risk (OR, 2.4; 95% CI, 1.7-3.5). We propose that FGG-H2 influences thrombosis risk through htSNP 10034C/T [rs2066865] by strengthening the consensus of a CstF site and thus favoring the formation of γA chain above that of γ′ chain. Fibrinogen γ′ contains a unique high-affinity, nonsubstrate binding site for thrombin, which seems critical for the expression of the antithrombin activity that develops during fibrin formation (antithrombin 1).
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Nowak-Gottl, Ulrike, Hartmut Weiler, Sabine Thedieck, Tanja Seehafer, and Monika Stoll. "Fibrinogen Alpha and Gamma Genes and Factor VLeiden in Children with Thromboembolism: Results from Two Family-Based Association Studies." Blood 112, no. 11 (November 16, 2008): 3816. http://dx.doi.org/10.1182/blood.v112.11.3816.3816.
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Abstract Background: Fibrinogen, the precursor of fibrin, is an essential component of the hemostatic system. A previous large case-control study showed that genetic variation in the fibrinogen gamma gene (FGG) increased the risk for VT in adults. We investigated the association of haplotypes comprising the fibrinogen alpha (FGA) and gamma (FGG) genes, carriership of the Factor VLeiden-mutation and risk for VT in two large family-based study samples for pediatric thromboembolism. Methods: We genotyped 7 single nucleotide polymorphisms in FGA and FGG, and the G1691A Factor VLeiden polymorphism in 244 pediatric VT and 268 thrombo-embolic stroke families. Association was assessed using the Transmission Disequilibrium Test (TDT) and corrected for multiple testing. Results: Association analysis revealed that the FGA-H1 haplotype, and the FGG-H2 and -H3 haplotypes, were significantly associated with VT (FGA-H1, P=0.05; FGG: H2, P=0.032; H3, P=0.0216). In an independent study sample, FGA-H1 (P=0.0085) and FGG-H2 (P=0.05) were significantly associated with TS. When stratifying for FVLeiden carriership, the association between FGA and FGG and VT was more pronounced in FVLeiden-negative families (FGA-H1, P=0.0006; FGG-H2, P=0.0005). Homozygous carriership of the FGG-H2 risk haplotype resulted in the lowest fibrinogen γ′ content (γ′ levels: 22.7±13.7 vs. 26.8±12.0, P=0.013; % γ′: 7.63±3.05 vs. 9.46±3.17, P=2.3×10−5), with increasing concentrations of fibrinogen γ′ in heterozygote H2 carriers. Compound heterozygote carriers of one FGG-H2 risk and one FGG-H3 protective haplotype, showed significant increase in fibrinogen γ′ (P=0.000032), while fibrinogen levels remained unchanged. In contrast, homozygote carriers of the protective FGG-H3 haplotype showed the highest concentration of fibrinogen γ′ content (% γ′: 9.21±3.09, P=0.0031) with decreased total fibrinogen levels. Conclusion: Our results support an important role of genetic variants in FGA and FGG in thromboembolism in children and adults. Our data further suggest that the genetic architecture of VT is complex and involves subtle influences through susceptibility and protective haplotypes in FGG and a genetic interaction with the FVLeiden-mutation.
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Yu, Ziqiang, Lijuan Cao, Wei Zhang, Xia Bai, Changgeng Ruan, Jian Zhang, Xiaojuan Zhao, and Zhaoyue Wang. "A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia." Thrombosis and Haemostasis 110, no. 07 (2013): 76–82. http://dx.doi.org/10.1160/th12-12-0934.
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SummaryCongenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.
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Wassel, Christina L., Leslie A. Lange, Brendan J. Keating, Kira C. Taylor, Andrew D. Johnson, Cameron Palmer, Lindsey A. Ho, et al. "Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe)." Blood 117, no. 1 (January 6, 2011): 268–75. http://dx.doi.org/10.1182/blood-2010-06-289546.
Full textAbstract:
Abstract Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23 634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47 539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk.
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Kolz, Melanie, Jens Baumert, Henning Gohlke, Harald Grallert, Angela Döring, Annette Peters, Erich Wichmann, Thomas Illig, and Wolfgang Koenig. "Association study between variants in the fibrinogen gene cluster, fibrinogen levels and hypertension: Results from the MONICA/ KORA study." Thrombosis and Haemostasis 101, no. 02 (2009): 317–24. http://dx.doi.org/10.1160/th08-06-0411.
Full textAbstract:
SummaryPrevious studies reported a gender-specific association between plasma fibrinogen concentrations and incident hypertension. We systematically analysed polymorphisms and haplotypes across the fibrinogen gene cluster with fibrinogen levels and assessed their contribution to prevalent hypertension in 2,200 men and 2,159 women from the population-based MONICA/KORA Augsburg study. Eleven tagging single nucleotide polymorphisms (SNPs) were systematically selected in the three fibrinogen genes and haplotypes were reconstructed. The minor alleles of two SNPs, rs2227401 (FGB) and rs2070016 (FGA) and the haplotypes tagged by those variants, were significantly associated with higher fibrinogen concentrations in both, men and women, explaining 1% of the total variance of fibrinogen concentrations. In addition, a FGG haplotype, tagged by rs1049636, was associated with lower concentrations of fibrinogen in women, but not in men. Regarding hypertension, we detected a significant association with a FGA promoter variant (rs2070008) in women only, whereas fibrinogen haplotypes were not associated with hyper-tension after correction for multiple comparisons in either men or women. In conclusion, our results suggest that variants in all three fibrinogen genes are significantly associated with differences in fibrinogen concentrations with modest contribution to phenotypic variance. It is likely that other genetic variants outside the fibrinogen gene loci are involved in the regulation of fibrinogen concentrations. In addition, one FGA promoter variant was significantly associated with hypertension in women. Confirmation of these findings by future studies is warranted.