Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.
Ko, Young-Jin;Kim, Ji Young;Lee, Joongyub;Song, Hong-Ji;Kim, Ju-Young;Choi, Nam-Kyong;Park, Byung-Joo
Journal of Preventive Medicine and Public Health
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v.47
no.1
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pp.36-46
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2014
Objectives: To evaluate the association between fracture risk and levothyroxine use in elderly women with hypothyroidism, according to previous osteoporosis history. Methods: We conducted a cohort study from the Korean Health Insurance Review and Assessment Service claims database from January 2005 to June 2006. The study population comprised women aged ${\geq}65$ years who had been diagnosed with hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who met any of the following criteria: previous fracture history, hyperthyroidism, thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow-up period <90 days. We categorized the daily levothyroxine doses into 4 groups: ${\leq}50{\mu}g/d$, 51 to $100{\mu}g/d$, 101 to $150{\mu}g/d$, and > $150{\mu}g/d$. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional hazard model, and subgroup analyses were performed according to the osteoporosis history and osteoporosis-specific drug prescription status. Results: Among 11 155 cohort participants, 35.6% had previous histories of osteoporosis. The adjusted HR of fracture for the > $150{\mu}g/d$ group, compared with the 51 to $100{\mu}g/d$ group, was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable osteoporosis subgroup, restricted to patients who were concurrently prescribed osteoporosis-specific drugs, the adjusted HR of fracture for the > $150{\mu}g/d$ group, compared with the 51 to 100 ${\mu}g/d$ group, was 1.93 (95% CI, 1.14 to 3.26). Conclusions: While further studies are needed, physicians should be concerned about potential levothyroxine overtreatment in elderly osteoporosis patients.
Intelligent systems(i.e., artificial intelligence), particularly deep learning, are machines able to mimic the cognitive functions of humans to perform tasks of problem-solving and learning. This field deals with computational models that can think and act intelligently, like the human brain, and construct algorithms that can learn from data to make predictions. Artificial intelligence is becoming important in radiology due to its ability to detect abnormalities in radiographic images that are unnoticed by the naked human eye. These systems have reduced radiologists' workload by rapidly recording and presenting data, and thereby monitoring the treatment response with a reduced risk of cognitive bias. Intelligent systems have an important role to play and could be used by dentists as an adjunct to other imaging modalities in making appropriate diagnoses and treatment plans. In the field of maxillofacial radiology, these systems have shown promise for the interpretation of complex images, accurate localization of landmarks, characterization of bone architecture, estimation of oral cancer risk, and the assessment of metastatic lymph nodes, periapical pathologies, and maxillary sinus pathologies. This review discusses the clinical applications and scope of intelligent systems such as machine learning, artificial intelligence, and deep learning programs in maxillofacial imaging.
Journal of the Korean Data and Information Science Society
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v.27
no.3
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pp.577-586
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2016
Hazardous air pollution caused by heavy metals in the air is at a serious level. Although manganese(Mn), one of the heavy metals, is a non-carcinogenic substance, it has a harmful influence on the human body. It is partially measured because automatic monitoring technologies have not yet be fully established. We introduced a statistical model for the daily concentration of manganese. Incorporating a linkage between Mn and meteorology, the proposed model is formulated in way to identify meteorological effects and to allow for seasonal trends, enabling not only accurate measurement of manganese concentration, but also information about the evaluation on a Hazard Quotient (non-cancer risk).
Recently, the results of vital tissue test showed that nitrosodimethylamine (NDMA) as a disinfection by-product (DBP), could be regarded as a carcinogen because a tumor was observed in organs. U.S.EPA indicated 0.7 ng/L as exposure concentration of NDMA based on a risk assessment target with a lifetime cancer risk of $10^{-6}$. Several recent studies have shown that UV oxidation could remove NDMA. However, UV oxidation is uneconomical and can reform NDMA after treating. In addition, the treatment mechanism of adsorption has not been founddue to the uncertainty of NDMA pathway. In addtion, NDMA has a radioisotope $^{14}C$-labeled which can be analyzed at low concentration of NDMA by Liquid Scintillation Counter (LSC). This study has investigated NDMA determination using LSC at an extremely low range from 1 to 100 ng/L and NDMA removal by powdered activated carbon (PAC) adsorption. For $^{14}C$-NDMA by LSC, the highest correlation over 99% between count number and NDMA concentrationwas obtained with possibility of $^{14}C$-NDMA concentration up to 1 ng/L. In the presence of PAC ranging from 50 to 10,000 mg/L, $^{14}C$-NDMA was removed from 18% to 97% for Sigma-Aldrich corporation (S-A co.) and from 9% to 93% by PAC for Daejung corporation (Dj co.). Hence it was found that the removal efficiency by PAC adsorption could vary depending on PAC types from different companies. For PAC adsorption capacity of $^{14}C$-NDMA using the Freundlich isotherm, $K_f$ and 1/n of PAC from S-A co. were $2.67\times10^{-3}$ ng/mg and 1.009, while those of PAC from Dj co. were $1.30\times10^{-3}$ ng/mg and 0.994, respectively. Thus, PAC from S-A co. showed twice higher adsorption capacity than Dj co.
Cho, Jae Won;Youn, Jiyoung;Choi, Min-Gew;Rha, Mi Young;Lee, Jung Eun
Korean Journal of Community Nutrition
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v.27
no.3
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pp.205-222
/
2022
Objectives: This study examined the characteristics of patients according to nutritional status assessed by five nutritional screening tools: Patient-Generated Subjective Global Assessment (PG-SGA), NUTRISCORE, Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) and to compare the agreement, sensitivity, and specificity of these tools. Methods: A total of 952 gastric cancer patients who underwent gastrectomy and chemotherapy from January 2009 to December 2012 were included. The patients were categorized into malnutrition and normal status according to five nutritional screening tools one month after surgery. The Spearman partial correlation, Cohen's Kappa coefficient, the area under the curve (AUC), sensitivity, and specificity of each two screening tools were calculated. Results: Malnutrition was observed in 86.24% of patients based on the PG-SGA and 85.82% based on the NUTRISCORE. When NRI or CONUT were applied, the proportions of malnutrition were < 30%. Patients with malnutrition had lower intakes of energy and protein than normal patients when assessed using the PG-SGA, NUTRISCORE, or NRI. Lower levels of albumin, hemoglobin, total lymphocyte count, and total cholesterol and longer postoperative hospital stays were observed among patients with malnutrition compared to normal patients when NRI, PNI, or CONUT were applied. Relatively high agreement for NUTRISCORE relative to PG-SGA was found; the sensitivity was 90.86%, and the AUC was 0.78. When NRI, PNI, and CONUT were compared, the sensitivities were 23.72% for PNI relative to NRI, 44.53% for CONUT relative to NRI, and 90.91% for CONUT relative to PNI. The AUCs were 0.95 for NRI relative to PNI and 0.91 for CONUT relative to PNI. Conclusions: NUTRISCORE had a high sensitivity compared to PG-SGA, and CONUT had a high sensitivity compared to PNI. NRI had a high specificity compared to PNI. This relatively high sensitivity and specificity resulted in 77.00% agreement between PNI and CONUT and 77.94% agreement between NRI and PNI. Further cohort studies will be needed to determine if the nutritional status assessed by PG-SGA, NUTRISCORE, NRI, PNI, and CONUT predicts the gastric cancer prognosis.
Background: Patients who are considered for major pulmonary resection are generally evaluated by spirometry and clinical assessment to predict morbidity and mortality. Despite this, none has yet proved to be a convenient and reliable estimate of risk. Material and Method: A retrospective analysis was performed in 167 patients who were diagnosed for lung cancer, bronchiectasis, pulmonary tuberculosis, and other benign pulmonary disease, and who underwent major lung resections. The relationship of 25 preoperative or postoperative variables to 19 postoperative events were classified into categories as operative mortality, pulmonary or cardiovascular morbidity, and other morbidity was assessed. Logistic regression analysis and $\chi$2 analysis were used to identify the relationship of the operative risk factors to the grouped postoperative complications. Result: The best single predictor of complications was the percent predicted postoperative diffusing capacity (pulmonary morbidity, p<0.009; cardiovascular morbidity, p<0.003: overall morbidity, p<0.004). Conclusion: The diffusing capacity of the lung for carbon monoxide was an important predictor of postoperative complications than the spirometry, and it usually should be a part of the evaluation of patients being considered for pulmonary resection.
Background : The 2015 American thyroid association (ATA) guidelines greatly expanded section on risk stratification of thyroid cancer. Definition of "Low risk of recurrence" has expanded, by inclusion of small volume lymph node involvement, such as less than 5 lymph node metastases each smaller than 2mm in central compartment. Purpose : We evaluated the number of positive nodes, Positive node ratio (PNR), recurrence, and radioablation therapy. Also, evaluated the safety of omitting strategy of radioablation after total thyroidectomy with PTC, especially on low-PNR N1a patients compared with high-PNR N1a patients. Methods : Consecutive 147 N1a and 216 N0 patients who underwent total thyroidectomy with central neck dissection between 2003 and 2004 were enrolled. We divided 147 N1a patients into two groups, such as 96 high-PNR versus 51 low-PNR group according to 50% of PNR, and compared these two groups with N0 group. Results: 7.2% (26/363) recurrences were occurred, and 21/147 (14.3 %) recurrences were on N1a patients, and 5/216 (2.3 %) were on N0 patients. Of these 21 recurrences in N1a stage patients, 20 (95.2 %) recurrences were occurred in high-PNR N1a group and only 1 (4.8 %) recurrence was in low-PNR N1a group. The recurrence of low-PNR N1a group was significantly lower than high-PNR N1a group (Log-rank p value = 0.003), but significantly not different from N0 group (Log-rank p value = 0.889). Although this study was a retrospective non-randomized trial with small number of patients, the 10-year recurrence of omitting RAI in low-PNR N1a patients with less than 50% of PNR were shown to be comparable with 216 N0 low risk patients. Conclusion : Positive node ratio could be a useful predictor of recurrence and useful guidance postoperative management -rather than absolute number of positive node.
The number of CT scans is increasing every year due to the improvement of the medical standards of the public, and thus the annual dose of medical radiation is also increasing. In this study, we evaluated the effective dose of the human body exposed to CT scans and estimated LAR. First, five region were selected from the CT diagnostic reference level guideline, and the effective dose of human body exposed to each examination was evaluated by clinical CT device. Second, the human organs and effective dose were calculated using the ALARA-CT program under the same conditions. Third, lifetime attributable risk (LAR) estimated by the effective dose exposed through the previous CT scan was estimated. As a result, the most effective dose was 21.18 mSv during the abdomen 4 phase scan, and the dose level was below DRL for all other tests except for the abdominal examination. As a result of evaluating effective dose using a dose calculation program under the same conditions, the results showed about 1.1 to 1.9 times higher results for each examination. In the case of organ dose, the closer the organ to the scan site, the higher the scattering ray. The lifetime attributable risk to CT radiation dose in adults was gradually decreased with age, and the results were somewhat different according to gender.
Journal of Korean Society of Occupational and Environmental Hygiene
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v.24
no.2
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pp.122-129
/
2014
Objectives: Because of its properties such as resistance to heat, chemicals and corrosion; tensile strength; sound absorption; and affordable price, asbestos has been widely used as a building material, fire resistant and retardant, thermal and heat insulator, soundproofing material, and electrical insulation. Since the prolonged inhalation of asbestos can cause serious illnesses such as lung cancer, mesothelioma, and asbestosis after an incubation period of 20 to 40 years, the mineral was classified as a Group 1 carcinogen by the International Agency for Research on Cancer, an intergovernmental agency forming part of the World Health Organization. Children and infants are more at risk than are adults if they are exposed to carcinogens, due to aweaker immunity that has not yet been fully developed. Most childcare centers are operated all day and children tend to spend a great amount of time in the centers. This is why it is important for them to be systematically isolated from environments that may expose them to asbestos. Materials: In order to understand both indoor and outdoor hazards to which children may have been exposed, the study focused on actual surveys of asbestos used in childcare centers, paying special attention to slate-roofed buildings in the vicinity of the centers. Results: A survey of a total of 211 childcare centers showed that the buildings of 18.1% of the centers contained asbestos, with 60.53% of the material being found in classroom ceilings. "Tex" was the most used material for ceilings, making up 89.47% of all ceilings. An outdoor survey showed that childcare centers in Daegu Metropolitan City had an average of 143 slate-roof buildings within a distance of 1km. Conclusions: Buildings housing mainly toddlers, children, teenagers and others more vulnerable to the toxicity of asbestos are not subject to asbestos investigation by law. A legal and practical basis for asbestos control is required for such buildings. In particular, housing materials which contain asbestos in day care centers require asbestos control. GIS should be used to identify the location of buildings with slate roofing materials in the vicinity of daycare centers in order to gauge toxicity of exposure to asbestos caused by potential asbestos friability possibility in outdoor conditions.
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