Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Evaluation of multi-dimensional effects on the ecology of goat farming in Turkey: The case of Adana province

Goats are inseparable part of Mediterranean ecosystem determined by flora, land conditions and climatic conditions. The effects of goat grazing on ecology have not been studied for a long time. But the existing of positive or negative effects of goat grazing on ecology has been debated. The determination of effects of goat farming on ecology from aspects of different institutions is the aim of this study. Also the strengths and weaknesses of goat farming, the threats and opportunities were revealed via SWOT Analysis method. For obtaining data, survey method was used. Among the people interviewed 71.11% expressed opinion that goats are not a threat for ecology, and 28.89% had view that goats are a threat. When looking from institutions’ aspect, 92.31% of people from Environment Engineering, 73.53% of people from Environment and Forests Directorate of the City, 65.52% of people from Agricultural Faculty and 57.14% of people from Municipality expressed that goats are not a threat for ecology. Considering this result, almost half of municipality employees expressed that goat farming is a threat for ecology. Almost all of the people we interviewed from Department of Environment Engineering expressed that the goat is not a threat for ecology. The most important result which we can deduce about goat farming from the study is that the goat farmers must be trained how to choose consciously where to let the goats graze in order to minimize the negative effects on ecology. © 2016, National Centre for Agrarian Sciences. All rights reserved

Determination of technical efficiency in cotton growing farms in Turkey: A case study of Cukurova region

This paper analyses technical efficiency of cotton farms in Çukurova region in Turkey. Data was collected from cotton farms through a questionnaire study. Data collection was carried out following 2004-2005 growing seasons. Technical efficiency of cotton farms was estimated by using the Data Envelopment Analysis (DEA) and technical efficiency scores were calculated employing an input oriented DEA. Tobit regression analysis was used to identify determinants of technical efficiency. Results indicate that cotton farmers can save inputs by at least 20% while remaining at the same production level. Factors strongly affecting efficiency level of the farmers were found to be farmers' age, education level and groups of cotton growing areas. © 2009 Academic Journals

Identifying technical efficiency of dairy cattle management in rural areas through a non-parametric Method: A case study for the east Mediterranean in Turkey

There are many aspects regarding the success of dairy cattle management and productivity. In this study, amount and kinds of feed, costs of veterinary consultancy, herd size, labor and capital were utilized to estimate technical efficiency of dairy cattle management in small scale farms in the east Mediterranean region of Turkey. A non-parametric efficiency analysis was used for the data obtained through face-to-face interviews in 100 small scale farms. We used tobit regression analysis to determine the effectiveness of possible factors affecting production performances of the farms. The results suggested that the average technical efficiency is unsatisfactory since Constant Returns to Scale (CRS) and Variable Returns to Scale (VRS) values are relatively <1 (0.59 and 0.83, respectively). Only 13 and 46% of the farms were found to be efficient in terms of CRS and VRS, respectively. Data Envelopment Analysis (DEA) showed that the farms had excess input usage ranging from 10-22%. To increase efficiency scores in subsidiary profit farms in semi-arid east Mediterranean conditions, farmers should adopt new methodologies, which decrease the costs and excess input usage in such semi-pasture management systems. © Medwell Journals, 2009

Children with breakthrough varicella infection requiring hospitalization in Turkey (VARICOMP Study 2008-2013)

PubMed ID: 26133048Introduction: Varicella in previously immunized individuals, known as "breakthrough varicella". While the majority of breakthrough cases are mild, some may be severe, requiring hospitalization in previously healthy children or children with an underlying condition. Methods: This report, as a part of the prospective national pediatric varicella hospitalizations study (including 29 centers, represent 50% of pediatric population) in Turkey, is aimed to evaluate breakthrough varicella infection requiring hospitalization before the routine use of single-dose live varicella vaccine in national program from 2008 to 2013 (<10% of the pediatric age group received a single-dose vaccine). Results: In the time period, 1939 children were hospitalized due to varicella infection in Turkey; 36 children (20 boys, 16 girls, mean age 68.0 + 37.6 months, all received single dose live varicella vaccine) with breakthrough varicella infection. Breakthrough varicella infection might be severe in previously healthy children (61.1%) and children with immune-compromising conditions (38.9%). The time elapsed between vaccination and hospitalization was approximately 5 years, and neurological complications, mainly encephalitis and meningitis, were the most common reason for hospitalization in previously healthy children. Conclusion: Pediatric breakthrough varicella requiring hospitalization have been seen in Turkey, is mainly observed in previously healthy children at 5 years after a single-dose varicella vaccine. The varicella vaccine has been implemented as part of the National Immunization Program in Turkey in 2013 (a single dose at age 12 months). Further surveillance in the same settings could evaluate the effectiveness of national immunization with single-dose varicella vaccine at 12 months of age and potential need for second dose of vaccine. © 2015 Elsevier Ltd

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: A nationwide survey during the pre-vaccine era (VARICOMP study)

PubMed ID: 22170238Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15 years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5 years of age, and 29.5% were in children under 1 year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15 years of age in Turkey, 21.7 to 28 per 100,000 children under 1 year of age, 9.8-13.8 per 100,000 children under 5 years of age, 3.96-6.52 per 100,000 children between 5 and 10 years of age and 0.42 to 0.71 per 100,000 children between 10 and 15 years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p<0.001) and neurological complications (p<0.001) were significantly more common in previously healthy children, whereas hematological complications (p<0.001) were more commonly observed in children with underlying conditions. The median length of the hospital stay was 6 days, and it was longer in children with underlying conditions (<0.001). The median cost of hospitalization per patient was $338 and was significantly higher in children with underlying conditions (p<0.001). The estimated direct annual cost (not including the loss of parental work time and school absence) of varicella-related hospitalization in children under the age of 15 years in Turkey was$856,190 to $1,407,006. According to our estimates, 882 to 1,450 children are hospitalized for varicella each year, reflecting a population-wide occurrence of 466-768 varicella cases per 100,000 children. In conclusion, this study confirms that varicella-related hospitalizations are not uncommon in children, and two thirds of these children are otherwise healthy. The annual cost of hospitalization for varicella reflects only a small part of the overall cost of this disease, as only a very few cases require hospital admission. The incidence of this disease was higher in children <1 year of age, and there are no prevention strategies for these children other than population-wide vaccination. Universal vaccination is therefore the only realistic option for the prevention of severe complications and deaths. The surveillance of varicellaassociated complications is essential for monitoring of the impact of varicella immunization. © Springer-Verlag 2011