Functional analysis of the bovine beta- and kappa casein gene promoters using homologous mammary gland derived cell line

Abstract. Bovine casein gene cluster belongs to the best studied regions of the bovine genome. However, molecular basis of the regulation of casein gene expression is still of great interest for the advancement of milk production. Identification of crucial regulatory regions governing casein gene expression would provide valuable information for marker assisted selection in dairy cattle. In our study we performed comparative analysis of the bovine beta- and kappa casein gene promoter sequences with the regulatory sequences from some other species. In addition, we used homologous mammary gland derived cell culture and luciferase reporter gene system to confirm the functionality of the proximal beta and kappa casein promoters. The longer kappa casein promoter (2064 bp) showed the highest expression level, followed by the short kappa casein promoter (925 bp) and beta casein promoter (1692 bp). Here we demonstrate the suitability of the bovine mammary gland derived cell line BME UV1 for transient gene expression under transcriptional control of the bovine casein gene promoters and compare functionality of different fragments of bovine beta- and kappa casein gene promoters using homologous in vitro system

The EHA Research Roadmap:Platelet Disorders

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1 to 2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cellbased Immune Therapies; and Gene Therapy

Population structure and genetic history of Tibetan Terriers

International audienceAbstractBackgroundTibetan Terrier is a popular medium-sized companion dog breed. According to the history of the breed, the western population of Tibetan Terriers includes two lineages, Lamleh and Luneville. These two lineages derive from a small number of founder animals from the native Tibetan Terrier population, which were brought to Europe in the 1920s. For almost a century, the western population of Tibetan Terriers and the native population in Tibet were reproductively isolated. In this study, we analysed the structure of the western population of Tibetan Terriers, the original native population from Tibet and of different crosses between these two populations. We also examined the genetic relationships of Tibetan Terriers with other dog breeds, especially terriers and some Asian breeds, and the within-breed structure of both Tibetan Terrier populations.ResultsOur analyses were based on high-density single nucleotide polymorphism (SNP) array (Illumina HD Canine 170 K) and microsatellite (18 loci) genotypes of 64 Tibetan Terriers belonging to different populations and lineages. For the comparative analysis, we used 348 publicly available SNP array genotypes of dogs from other breeds. We found that the western population of Tibetan Terriers and the native Tibetan Terriers clustered together with other Asian dog breeds, whereas all other terrier breeds were grouped into a separate group. We were also able to differentiate the western Tibetan Terrier lineages (Lamleh and Luneville) from the native Tibetan Terrier population.ConclusionsOur results reveal the relationships between the western and native populations of Tibetan Terriers and support the hypothesis that Tibetan Terrier belongs to the group of ancient dog breeds of Asian origin, which are close to the ancestors of the modern dog that were involved in the early domestication process. Thus, we were able to reject the initial hypothesis that Tibetan Terriers belong to the group of terrier breeds. The existence of this native population of Tibetan Terriers at its original location represents an exceptional and valuable genetic resource

Alcohol use as a risk factor for tuberculosis – a systematic review

<p>Abstract</p> <p>Background</p> <p>It has long been evident that there is an association between alcohol use and risk of tuberculosis. It has not been established to what extent this association is confounded by social and other factors related to alcohol use. Nor has the strength of the association been established. The objective of this study was to systematically review the available evidence on the association between alcohol use and the risk of tuberculosis.</p> <p>Methods</p> <p>Based on a systematic literature review, we identified 3 cohort and 18 case control studies. These were further categorized according to definition of exposure, type of tuberculosis used as study outcome, and confounders controlled for. Pooled effect sizes were obtained for each sub-category of studies.</p> <p>Results</p> <p>The pooled relative risk across all studies that used an exposure cut-off level set at 40 g alcohol per day or above, or defined exposure as a clinical diagnosis of an alcohol use disorder, was 3.50 (95% CI: 2.01–5.93). After exclusion of small studies, because of suspected publication bias, the pooled relative risk was 2.94 (95% CI: 1.89–4.59). Subgroup analyses of studies that had controlled for various sets of confounders did not give significantly different results and did not explain the significant heterogeneity that was found across the studies.</p> <p>Conclusion</p> <p>The risk of active tuberculosis is substantially elevated in people who drink more than 40 g alcohol per day, and/or have an alcohol use disorder. This may be due to both increased risk of infection related to specific social mixing patterns associated with alcohol use, as well as influence on the immune system of alcohol itself and of alcohol related conditions.</p

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

<p>Abstract</p> <p>Background</p> <p>In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.</p> <p>Methods</p> <p>A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.</p> <p>Results</p> <p>There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.</p> <p>Conclusion</p> <p>The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.</p

Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression

BACKGROUND: Hundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy. METHODOLOGY/PRINCIPAL FINDINGS: We identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36-1.00) and the pooled specificity was 0.97 (range 0.54-1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy. CONCLUSIONS/SIGNIFICANCE: The sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries

Clinical targets for continuous glucose monitoring data interpretation : recommendations from the international consensus on time in range

Improvements in sensor accuracy, greater convenience and ease of use, and expanding reimbursement have led to growing adoption of continuous glucose monitoring (CGM). However, successful utilization of CGM technology in routine clinical practice remains relatively low. This may be due in part to the lack of clear and agreed-upon glycemic targets that both diabetes teams and people with diabetes can work toward. Although unified recommendations for use of key CGM metrics have been established in three separate peer-reviewed articles, formal adoption by diabetes professional organizations and guidance in the practical application of these metrics in clinical practice have been lacking. In February 2019, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address this issue. This article summarizes the ATTD consensus recommendations for relevant aspects of CGM data utilization and reporting among the various diabetes populations

Consensus recommendations for the use of automated insulin delivery technologies in clinical practice

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage