Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany

Background: Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. Objectives: To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. Methods: Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015-30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD-10-GM codes). Twelve-month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. Results: Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second-generation H1 -antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). Conclusions: In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes

Epidemiology, comorbidities, and healthcare utilization of patients with chronic urticaria in Germany

Abstract Background Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary. Objectives To investigate the epidemiology of CU, overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database. Methods Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin [InGef] (01 January 2015–30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD‐10‐GM codes). Twelve‐month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated. Results Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second‐generation H 1 ‐antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%). Conclusions In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes

Aspects of bovine herpesvirus-1 infection in dairy and beef herds in the Republic of Ireland

<p>Abstract</p> <p>Background</p> <p>Infection with bovine herpesvirus-1 (BHV-1) causes a wide range of disease manifestations, including respiratory disease and abortion, with world-wide distribution. The primary objective of the present study was to describe aspects of BHV-1 infection and control on Irish farms, including herd-level seroprevalence (based on pooled sera) and vaccine usage.</p> <p>Methods</p> <p>The characteristics of a diagnostic indirect BHV-1 antibody ELISA test when used on serum pools were evaluated using laboratory replicates for use in the seroprevalence study. The output from this indirect ELISA was expressed as a percentage positivity (PP) value. A proposed cut off (PCO) PP was applied in a cross-sectional study of a stratified random sample of 1,175 Irish dairy and beef cattle herds in 2009, using serum pools, to estimate herd seroprevalence. The study was observational, based primarily on the analysis of existing samples, and only aggregated results were reported. For these reasons, ethical approval was not required. Bulk milk samples from a subset of 111 dairy herds were analysed using the same ELISA. Information regarding vaccine usage was determined in a telephone survey.</p> <p>Results</p> <p>A PCO PP of 7.88% was determined to give 97.1% sensitivity and 100% specificity relative to the use of the ELISA on individual sera giving maximization of the prevalence independent Youden's index, on receiver operating characteristics analysis of replicate results. The herd-level BHV-1 seroprevalence was 74.9% (95% CI - 69.9%-79.8%), with no significant difference between dairy and beef herds. 95.5% agreement in herd classification was found between bulk milk and serum pools. Only 1.8 percent of farmers used BHV-1 marker vaccine, 80% of which was live while 75% of vaccinated herds were dairy.</p> <p>A significant association was found between herd size (quartiles) and seroprevalence (quartiles).</p> <p>Conclusions</p> <p>The results from this study indicate BHV-1 infection is endemic, although BHV-1 vaccines are rarely used, in the cattle population in Ireland.</p

The Thermal Structural Transition of α-Crystallin Inhibits the Heat Induced Self-Aggregation

-crystallin, the major constituent of human lens, is a member of the heat-shock proteins family and it is known to have a quaternary structural transition at . The presence of calcium ions and/or temperature changes induce supramolecular self-aggregation, a process of relevance in the cataractogenesis. Here we investigate the potential effect of the bovine -crystallin's structural transition on the self-aggregation process. Along all the temperatures investigated, aggregation proceeds by forming intermediate molecular assemblies that successively aggregate in clusters. The final morphology of the aggregates, above and below , is similar, but the aggregation kinetics are completely different. The size of the intermediate molecular assemblies, and their repulsive energy barrier show a marked increase while crossing . Our results highlight the key role of heat modified form of -crystallin in protecting from aggregation and preserving the transparency of the lens under hyperthermic conditions

Association of herd BRSV and BHV-1 seroprevalence with respiratory disease and reproductive performance in adult dairy cattle

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to detect the associations between bovine herpesvirus 1 (BHV-1) status of a herd and respiratory disease (BRD) occurrence and reproductive performance in pregnant heifers and cows. The association between management-related factors and higher BRD occurrence was also estimated.</p> <p>Methods</p> <p>Serum samples, collected from cows and youngstock from 103 dairy cattle herds, were analyzed for antibodies against BHV-1, bovine respiratory syncytial virus (BRSV), bovine viral diarrhoea virus (BVDV), and <it>Mycoplasma bovis</it>. A questionnaire was used to collect data concerning herd management factors and reproductive performance, as well as the occurrence of clinical signs of respiratory disease in the last two years, as evaluated by the veterinarian or farm manager. Multiple correspondence analysis (MCA) and logistic regression analysis were performed to identify and quantify the risk factors.</p> <p>Results</p> <p>A low to moderate prevalence (1-49%) of BRSV antibodies among youngstock was associated with a high occurrence of respiratory disease (OR = 6.2, p = 0.010) in cows and in-calf heifers. Employees of the farm may participate in the spread of such disease. Larger herd size, loose-housing of cows, housing youngstock separately from cows until pregnancy, and purchasing new animals were factors possibly related to a high occurrence of respiratory disease symptoms in pregnant heifers and cows. The highest risk of abortions (> 1.3%) and increased insemination index (number of inseminations per pregnancy) (> 1.9) occurred in herds with a moderate prevalence of BHV-1 antibodies (1-49%) in cows.</p> <p>Conclusions</p> <p>BHV-1 was not associated with acute respiratory disease in adult dairy cattle, however was significantly related to reproductive performance. BRSV possesses the main role in respiratory disease complex in adult dairy cattle.</p

The Leukemia-Associated Mllt10/Af10-Dot1l Are Tcf4/β-Catenin Coactivators Essential for Intestinal Homeostasis

The leukemia-associated Mllt10/Af10 and its partner the histone methyltransferase Dot1l are identified as Tcf4/β-catenin co-activators and shown to be essential for Wnt-driven endogenous gene expression, intestinal development and homeostasis

γCOP Is Required for Apical Protein Secretion and Epithelial Morphogenesis in Drosophila melanogaster

Background: There is increasing evidence that tissue-specific modifications of basic cellular functions play an important role in development and disease. To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the γCOP gene, which encodes a subunit of the COPI coatomer complex. Principal Findings: We found that γCOP is essential for the viability of the Drosophila embryo. In the absence of zygotic γCOP activity, embryos die late in embryogenesis and display pronounced defects in morphogenesis of the embryonic epidermis and of tracheal tubes. The coordinated cell rearrangements and cell shape changes during tracheal tube morphogenesis critically depend on apical secretion of certain proteins. Investigation of tracheal morphogenesis in γCOP loss-of-function mutants revealed that several key proteins required for tracheal morphogenesis are not properly secreted into the apical lumen. As a consequence, γCOP mutants show defects in cell rearrangements during branch elongation, in tube dilation, as well as in tube fusion. We present genetic evidence that a specific subset of the tracheal defects in γCOP mutants is due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we identified a critical target protein of COPI-dependent secretion in epithelial tube morphogenesis. Conclusions/Significance: These studies highlight the role of COPI coatomer-mediated vesicle trafficking in both general and tissue-specific secretion in a multicellular organism. Although COPI coatomer is generally required for protein secretion, we show that the phenotypic effect of γCOP mutations is surprisingly specific. Importantly, we attribute a distinct aspect of the γCOP phenotype to the effect on a specific key target protein

Function of the Active Site Lysine Autoacetylation in Tip60 Catalysis

The 60-kDa HIV-Tat interactive protein (Tip60) is a key member of the MYST family of histone acetyltransferases (HATs) that plays critical roles in multiple cellular processes. We report here that Tip60 undergoes autoacetylation at several lysine residues, including a key lysine residue (i.e. Lys-327) in the active site of the MYST domain. The mutation of K327 to arginine led to loss of both the autoacetylation activity and the cognate HAT activity. Interestingly, deacetylated Tip60 still kept a substantial degree of HAT activity. We also investigated the effect of cysteine 369 and glutamate 403 in Tip60 autoacetylation in order to understand the molecular pathway of the autoacetylation at K327. Together, we conclude that the acetylation of K327 which is located in the active site of Tip60 regulates but is not obligatory for the catalytic activity of Tip60. Since acetylation at this key residue appears to be evolutionarily conserved amongst all MYST proteins, our findings provide an interesting insight into the regulatory mechanism of MYST activities