SummaryObjectives The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. Methods We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15 481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15 894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. Results The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. Conclusions In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.
Critical-sized bone defects are a difficult problem in both human and veterinary medicine. To address this issue, synthetic graft materials have been garnering attention. Abundant in vitro studies have proven the possibilities of poly(lactic-acid) (PLA) scaffolds and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) nanofibres for treating bone defects. The present study aimed at conducting an in vivo assessment of the biological performance of a three dimensional (3D)-printed PLA scaffold filled with a PLGA/HAp nanofibrous scaffold to estimate its potential applications in bone defect reconstruction surgery. Defects were created in a 20 mm-long region of the radius bone. The defects created on the right side in six Beagle dogs (n = 6) were left untreated (Group 1). The defects on the left side (n = 6) were filled with 3D-printed PLA scaffolds incorporated with PLGA/Hap nanofibres with gelatine (Group 2). The other six Beagle dog defects were made bilaterally (n = 12) and filled with the same material as that used in Group 2 along with recombinant bone morphogenetic protein 2 (rhBMP-2) (Group 3). Both the radiological and histological examinations were performed for observing the reaction of the scaffold and the bone. Micro-computed tomography (CT) was utilised for the evaluation of the bone parameters 20 weeks after the experiment. The radiological and histological results revealed that the scaffold was biodegradable and was replaced by new bone tissue. The micro-CT revealed that the bone parameters were significantly (P < 0.05) increased in Group 3. Based on these results, our study serves as a foundation for future studies on bone defect treatment using synthetic polymeric scaffolds.
Left ventricular ejection fraction at rest and during treadmill and isometric handgrip exercise were determined in 16 patients with essential hypertension (mean age 47.4 years) before and after therapy. The untreated hypertensive patient showed a linear correlation between mean blood pressure and LVEF (r =0.62, p < 0.01). The relation of sitting, resting LVEF with systolic blood pressure was highly significant (r =0.88, p < 0.001). Prior to therapy no significant change in LVEF in response to exercise was noted. After therapy with captopril, a normal isotonic exercise response occurred consisting of a highly significant increase in ejection fraction (p < 0.0025). Subjects receiving propranolol had a fall in LVEF with isometric stress (p < 0.0025). These data suggest an increased ejection fraction in patients with essential hypertension when all other parameters of the heart are normal and an abnormal response to isotonic exercise which may be reversed with therapy.
Introducing small genetic changes to study specific mutations or reverting clinical mutations to wild type has been an area of interest in precision genomics for several years. In fact, it has been found that nearly 90% of all human pathogenic mutations are caused by small genetic variations, and the methods to efficiently and precisely correct these errors are critically important. One common way to make these small DNA changes is to provide a single stranded DNA (ssDNA) donor containing the desired alteration together with a targeted double-strand break (DSB) at the genomic target. The donor is typically flanked by regions of homology that are often ~30-100bp in length to leverage the homology directed repair (HDR) pathway. Coupling a ssDNA donor with a CRISPR-Cas9 to produce a targeted DSB is one of the most streamlined approaches to introduce small changes. However, in many cell types this approach results in a low rate of incorporation of the desired alteration and has undesired imprecise repair at the 5' or 3' junction due to artifacts of the DNA repair process. We herein report a technology that couples the spatial temporal localization of an ssDNA repair template and leverages the nucleic acid components of the CRISPR-Cas9 system. We show that by direct fusion of an ssDNA template to the trans activating RNA (tracrRNA) to generate an RNA-DNA chimera, termed Donorguide, we recover precise integration of genetic alterations, with both increased integration rates and decreased imprecision at the 5' or 3' junctions relative to an ssODN donor in vitro in HEK293T cells as well as in vivo in zebrafish. Further, we show that this technology can be used to enhance gene conversion with other gene editing tools such as TALENs.
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