Validation of Olfactory Questionnaire in Koreans: an Alternative for Conventional Psychophysical Olfactory Tests.

BACKGROUND: The patients with coronavirus disease 2019 (COVID-19), a worldwide pandemic infection, frequently complain of olfactory disorders. However, psychophysical olfactory tests performed by an examiner are very difficult in these highly infectious patients. This study aimed to develop and validate a questionnaire for olfactory function that can be readily used to evaluate olfactory loss. METHODS: Fourteen smell-related questions were created based on smells familiar to Koreans. Among them, questions with a κ value of 0.6 or higher were finally selected through a test-retest reliability analysis. The correlations between the scores of the olfactory questionnaire and those of olfactory function tests (Butanol Threshold Test [BTT] and Cross Cultural Smell Identification Test [CCSIT]) were analyzed. To evaluate the predictive ability of the questionnaire and elicit cutoff values, receiver operating characteristic (ROC) curves were generated. RESULTS: Out of the 14 questions in the questionnaire, 11 (κ > 0.6) were selected for the olfactory questionnaire. We analyzed 2,273 subjects, and there was a significant correlation between the total score of the olfactory questionnaire and the BTT (r = 0.643, P < 0.001) or CCSIT (r = 0.615, P < 0.001) scores. ROC curves for the olfactory questionnaire, BTT, and CCSIT all demonstrated high predictive power to discriminate anosmia and severe hyposmia from normosmia. Regarding mild to moderate hyposmia, however, ROC curve for the olfactory questionnaire alone showed high predictive power of discrimination from normosmia. Based on the results of ROC curves among the subclasses, we suggest the classification of the total score of the questionnaire as 0-4, 5-17, 18-27, 28-41, and 42-44, for anosmia, severe hyposmia, moderate hyposmia, mild hyposmia, and normosmia, respectively. CONCLUSION: The total scores of the questionnaires correlated with the BTT and CCSIT scores. The symptom questionnaire for olfactory dysfunction may be useful as an alternative tool for olfactory function testing, when unavailable.

A portable FRET analyzer for rapid detection of sugar content.

Fluorescence resonance energy transfer (FRET) is widely used as a core process in biometric sensors to detect small molecules such as sugars, calcium ions, or amino acids. However, FRET based biosensors with innate weak signal intensity require the use of expensive, high-sensitive equipment. In the present study, these shortcomings were overcome with the fabrication of a sensitive, inexpensive, and portable analyzer which provides quantitative detection of small molecules in a liquid sample. The usability of the developed analyzer was successfully tested by measuring sucrose and maltose contents in commercially available beverage samples, with better performance than the conventional monochromator-type spectrofluorometer. It is anticipated that miniaturization of the equipment and improving the FRET based biosensors will contribute to the practical use of this hand-held analyzer in conditions where high-end equipment is not available.

Endoplasmic reticulum stress induces epithelial-mesenchymal transition through autophagy via activation of c-Src kinase.

BACKGROUND: Endoplasmic reticulum (ER) stress has been implicated in inducing epithelial-mesenchymal transition (EMT). ER stress is also known to induce autophagy. However, it is unclear whether ER stress-induced autophagy contributes to EMT. We hypothesized that ER stress might induce EMT through autophagy via activation of c-Src kinase in tubular epithelial cells. METHOD: All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Immunofluorescence and small interfering RNA (siRNA) experiments were performed. RESULTS: Chemical ER stress inducers such as tunicamycin (TM, 0.2 µM) and thapsigargin (TG, 0.2 µM) induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ER stress inhibitors such as 4-PBA and salubrinal suppressed both TM- and TG-induced EMT. TM and TG also induced autophagy, as evidenced by upregulation of LC3-II and beclin-1, which were abolished by pretreatment with ER stress inhibitors. Transfection with siRNA targeting ER stress protein (IRE-1) blocked the TM- or TG-induced EMT and autophagy. Autophagy inhibitors such as 3-methyladenine and bafilomycin inhibited the TM- or TG-induced EMT. Transfection with siRNA targeting autophagy protein (beclin-1) also blocked the TM- or TG-induced EMT. Both TM and TG induced activation of c-Src kinase. Inhibitor of c-Src kinase (PP2) suppressed the TM- or TG-induced autophagy and EMT. CONCLUSION: ER stress by TM or TG induced EMT through autophagy via activation of c-Src kinase in tubular epithelial cells.

Multiphasic analysis of whole exome sequencing data identifies a novel mutation of ACTG1 in a nonsyndromic hearing loss family.

BACKGROUND: The genetic heterogeneity of sensorineural hearing loss is a major hurdle to the efficient discovery of disease-causing genes. We designed a multiphasic analysis of copy number variation (CNV), linkage, and single nucleotide variation (SNV) of whole exome sequencing (WES) data for the efficient discovery of mutations causing nonsyndromic hearing loss (NSHL). RESULTS: From WES data, we identified five distinct CNV loci from a NSHL family, but they were not co-segregated among patients. Linkage analysis based on SNVs identified six candidate loci (logarithm of odds [LOD] >1.5). We selected 15 SNVs that co-segregated with NSHL in the family, which were located in six linkage candidate loci. Finally, the novel variant p.M305T in ACTG1 (DFNA20/26) was selected as a disease-causing variant. CONCLUSIONS: Here, we present a multiphasic CNV, linkage, and SNV analysis of WES data for the identification of a candidate mutation causing NSHL. Our stepwise, multiphasic approach enabled us to expedite the discovery of disease-causing variants from a large number of patient variants.

Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy.

Pyruvate is an endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of ethyl pyruvate (EP) against the development and progression of diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-glucose (HG; 50 mM) or normal-glucose (NG; 5 mM) conditions and with or without pyruvate. Pyruvate-treated diabetic rats exhibited decreased albuminuria and attenuated NADPH-dependent reactive oxygen species generation. Immunohistochemistry showed reduced laminin, type IV collagen, and fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue mRNA and protein expression levels of monocyte chemoattractant protein-1, transforming growth factor-ß1, laminin, fibronectin, and type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that pyruvate protects against kidney injury via NADPH oxidase inhibition. The present study established that activation of NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular hypertrophy, and ECM molecule expression. Pyruvate exhibited a renoprotective effect in the progression of experimental diabetic nephropathy. Future research is warranted to investigate the protective mechanism of pyruvate more specifically in relation to NADPH oxidase in diabetic nephropathy.

[Korean Clinical Practice Guidelines for Adverse Reactions to Intravenous Iodinate and MRI-Gadolinium Contrast Agents: Revised Clinical Consensus and Recommendations (3rd Edition, 2022)]. / 주사용 요오드화 ì¡°ì˜ì œ 및 MRI용 가돌리늄 ì¡°ì˜ì œ ìœ í•´ë°˜ì‘ì— 대한 한국 임상진료지침: ê°œì •ëœ ìž„ìƒì  합의 및 ê¶Œê³ ì•ˆ(2022ë „ ì œ3판).

The Korean Society of Radiology and Medical Guidelines Committee amended the existing 2016 guidelines to publish the "Korean Clinical Practice Guidelines for Adverse Reactions to Iodide Contrast for Injection and Gadolinium Contrast for MRI: The Revised Clinical Consensus and Recommendations (2022 Third Edition)." Expert members recommended and approved by the Korean Society of Radiology, the Korean Academy of Asthma, Allergy and Clinical Immunology, and the Korean Nephrology Society participated together. According to the expert consensus or systematic literature review, the description of the autoinjector and connection line for the infection control while using contrast medium, the acute adverse reaction, and renal toxicity to iodized contrast medium were modified and added. We would like to introduce the revised contents.

Comparison of vascular calcification scoring systems using plain radiographs to predict vascular stiffness in peritoneal dialysis patients.

AIM: Vascular stiffness is associated with cardiovascular mortality in dialysis patients and related with vascular calcification and microvascular inflammation. The objective of this study is to compare predictability of two different vascular calcification scoring systems using plain radiographs in peritoneal dialysis (PD) patients. METHODS: Vascular stiffness was represented by heart-to-femoral pulse wave velocity (hfPWV) in our 79 PD patients. Peripheral vascular calcification score (PVCS) and abdominal aortic calcification score (AACS) were measured from plain radiographs. Microvascular inflammation was represented by peritoneal protein clearance (PPC). Regression analysis and the receiver operating characteristic (ROC) curve analysis were used for analysis. RESULTS: The hfPWV revealed correlation with PVCS and AACS independently. In the ROC curve analysis, area under the curve (AUC) of PVC score was 0.7119 (P = 0.006), and AUC of AACS were 0.6960 (P = 0.011). After multiple linear regression analysis, PVCS remained as a predictor of vascular stiffness (R(2) = 0.579, ß = 0.210, P = 0.038). The combination of PVCS and PPC exhibited a trend toward better predictability for vascular stiffness (AUC 0.7738, P = 0.001) than any of the two parameters alone. CONCLUSION: It is assumed that the PVCS system is more predictable for vascular stiffness in our study. Moreover, the combination of PVCS and PPC might be more useful as a screening test for vascular stiffness.

A decline in renal function is associated with loss of bone mass in Korean postmenopausal women with mild renal dysfunction.

This study was conducted to assess the relationship between estimated glomerular filtration rate (eGFR) and bone mineral density (BMD) in Korean postmenopausal women with mild renal dysfunction. A total of 328 postmenopausal women who underwent BMD measurement during health check-up was investigated. BMD was measured in lumbar spine (L1-L4), femoral neck, total proximal femur and femoral trochanteric areas by dual energy radiography absorptiometry and renal function was estimated by eGFR using Cockcroft-Gault equation. Of the 328 subjects, 317 (96.6%) had an eGFR ≥60 mL/min/1.73 m(2). By using simple linear regression analysis, age, height, weight and eGFR were significantly associated with BMD for the 4 aforementioned anatomic sites, while serum levels of creatinine and blood urea nitrogen did not influence BMD. When multiple regression analyses were applied, age and body weight still had significant associations with BMD at 4 different anatomic sites (P < 0.001). A significant association of eGFR with BMD remained in the lumbar spine, femoral neck and proximal total femur (P < 0.05) but not in the trochanteric area (P = 0.300). Our study suggests that a decline of renal function is associated with lower BMD in the lumbar spine, femoral neck and total proximal femur areas in Korean menopausal women with mild renal dysfunction.

High dose vitamin D3 attenuates the hypocalciuric effect of thiazide in hypercalciuric rats.

Thiazide is known to decrease urinary calcium excretion. We hypothesized that thiazide shows different hypocalciuric effects depending on the stimuli causing hypercalciuria. The hypocalciuric effect of hydrochlorothiazide (HCTZ) and the expression of transient receptor potential vanilloid 5 (TRPV5), calbindin-D(28K), and several sodium transporters were assessed in hypercalciuric rats induced by high calcium diet and vitamin D(3). Urine calcium excretion and the expression of transporters were measured from 4 groups of Sprague-Dawley rats; control, HCTZ, high calcium-vitamin D, and high calcium-vitamin D with HCTZ groups. HCTZ decreased urinary calcium excretion by 51.4% in the HCTZ group and only 15% in the high calcium-vitamin D with HCTZ group. TRPV5 protein abundance was not changed by HCTZ in the high calcium-vitamin D with HCTZ group compared to the high calcium-vitamin D group. Protein abundance of NHE3, SGLT1, and NKCC2 decreased in the hypercalciuric rats, and only SGLT1 protein abundance was increased by HCTZ in the hypercalciuric rats. The hypocalciuric effect of HCTZ is attenuated in high calcium and vitamin D-induced hypercalciuric rats. This attenuation seems to have resulted from the lack of HCTZ's effect on protein abundance of TRPV5 in severe hypercalciuric condition induced by high calcium and vitamin D.

Metal-insulator transition-induced adsorption-resistant behavior of small Au nanoparticles.

Smaller nonmetallic nanoparticles are more inert: Metal-insulator transition of Au nanoparticles on silica is closely related to the metal-support charge transfer, which has a strong influence on chemisorption reactivity of Au. Smaller nonmetallic Au nanoparticles are more resistant towards butanethiol chemisorption [picture and graph: see text].The size-dependent variation of the electronic and chemical properties of Au nanoparticles formed on native Si oxide surfaces is investigated using synchrotron radiation photoemission spectroscopy and ultraviolet photoelectron spectroscopy. The adsorption reactivity toward butanethiol adsorption initially increases with decreasing particle size; however, the reactivity of Au nanoparticles becomes gradually lower below a size of approximately 0.8 nm. The photoemission spectral changes suggest a metal-insulator transition, accompanied by negative charge transfer from the nanoparticles to the support, which may be the source of the chemical inertness of small Au nanoparticles.

Genetic interactions between the donor and the recipient for susceptibility to acute rejection in kidney transplantation: polymorphisms of CCR5.

BACKGROUND: Acute rejection (AR) contributes to the development of chronic allograft nephropathy that is the major cause of graft failure. We analyzed the 59029G>A polymorphism and an internal 32 bp deletion (CCR5 32) of CCR chemokine receptor 5 (CCR5) Delta and tried to prove the hypothesis that genetic interactions between the donor and the recipient influence the development of AR. METHODS: We detected genetic polymorphisms by the TaqMan(R) method and by sizing PCR amplicons (n = 486). The primary outcomes were early acute rejection (EAR) and repeated early acute rejection (RR). We defined EAR as the occurrence of a biopsy-proven AR within 3 months after transplantation. RESULTS: The development of EAR was dependent on the number of A alleles in recipients and showed a dose-response relationship (P = 0.002). When we combined the number of A alleles in both donor and recipient, episodes of EAR and RR were more prevalent as the allelic number increased (A allelic number 0 & 1, 2 versus 3 & 4, P = 0.048; 0 & 1 versus 3 & 4, P = 0.006). Statistical significance was preserved after multivariate analysis of sex, HLA mismatch and type of donor with the recipient's age as the continuous term. Also, graft survival was different according to the presence of the A allele, i.e. recipients carrying A allele (+) grafts showed poor graft survival (P = 0.008 by a log-rank test). Again, the number of A alleles affected graft survival as the recipients who carried more A alleles had poor graft survival (A allele number 0 & 1 versus 2 versus 3 & 4, P = 0.011; 0 & 1 versus 3 & 4, P = 0.08; 0 & 1 versus 2, P = 0.002; by a log-rank test). All of the participants were wild-type homozygotes for CCR5Delta32. CONCLUSIONS: The A allele of CCR5 59029G>A was a risk factor for EAR and RR. As the number of A alleles increased, episodes of EAR were more frequently observed.

The removal of estrogenic activity and control of brominated by-products during ozonation of secondary effluents.

The purposes of this study were to investigate the behavior of brominated by-products, such as bromate ion and total organic bromide, formed during ozonation for the removal of estrogenic activity in sewage effluents and to propose operation parameters for the ozonation process. It is necessary to reduce the E(2) equivalent concentration of estrogenic activity in secondary effluent treated by 90% of the initial one. To do so, ozonation until dissolved ozone concentration increased to 0.1mg/L (which corresponds to approximately 1mg O(3)/mg DOC(0) [consumed ozone per initial DOC] of consumed ozone for the effluent in this study) is proposed as an operation parameter for ozonation without the formation of brominated by-products.

Changes in Resting Calcaneal Stance Position Angle Following Insole Fitting in Children With Flexible Flatfoot.

OBJECTIVE: To clarify the relationship of the initial radiologic and a biomechanical parameter at first clinical visit, and define the effectiveness of modified insole, following insole fitting in children with flexible flatfoot. METHODS: Children aged less than 13 years with flexible flatfoot were enrolled. The total number of subjects was 66 (33 boys, 33 girls). The subjects were divided into 5 subgroups, based on age: 1-2, 3-4, 5-6, 7-9, and 10-12 years. The mean time period between the initial & final examination for their resting calcaneal stance position angle (RCSPA) was 24 months. Radiography quantified the deformity by measuring angles, including the talometatarsal angle, the metatarsal angle, and the calcaneal pitch angle. RESULTS: From the angles measured on radiographs, only the talometatarsal angle showed a statistically significant correlation to the initial RCSPA (r=-0.578 for right side, r=-0.524 for left side; p<0.01). The mean RCSPA improved in all subgroups of subjects following insole fitting. Moreover, in children younger than 7 years, the improvement in RCSPA from the insole fitting was greater compared to children aged 7 years and older. CONCLUSION: The insole has additionally beneficial effects in all populations younger than 13 years. However, there might exist a hidden effect of normal structural pedal alignment during growth accompanied with bony maturation and developmental process. To date, it is controversial whether the treatment of flexible flatfoot is necessary in the vast majority of cases, or simple observation and advice to parents would suffice.

Falsely Elevated Postvoid Residual Urine Volume in Uterine Myoma.

Precise measurement of postvoid residual (PVR) urine volume is a key factor in assessing patients with voiding dysfunction, including those with lower urinary tract problems. The safe and noninvasive ultrasound bladder scan is the preferred mode to measure PVR volume. However, this procedure has a false-positive rate up to 9%, in the presence of ovarian cysts, renal cysts, ascites, or uterine myoma with cystic degeneration. Until now, cystic lesions are known to cause false positivity in ultrasound bladder scanner. However, we encountered falsely-elevated PVR in two cases of non-cystic uterine myomas. We present these cases with detailed radiologic images and volume measurement data.

Optimal use of CT imaging in pediatric congenital cholesteatoma.

OBJECTIVE: This study aimed to determine the radiation dose of temporal bone computed tomography (TBCT) to detect pediatric congenital cholesteatoma (CC), and suggests strategy for lowering perioperative radiation dose. METHODS: Fifty-three CC patients followed up for more than 12 months after surgery. Perioperative clinical findings and the effective radiation dose (ERD) of TBCT were investigated. Patients' mean age at initial TBCT was 60 months; the mean follow-up period was 43 months. RESULTS: In 33 (62.3%) of 53 patients, only one TBCT was performed postoperatively. Postoperative CT imaging was performed to evaluate before second-stage ossiculoplasty, due to suspicion of CC recurrence on examinations, or as part of follow-up. When TBCT was performed on more than two occasions after surgery as a part of follow-up, there was no difference in the distribution of stage or type of CC compared to patients subjected to TBCT on less than three occasions (p=0.093 and p=0.744, respectively). During the most-recent follow-up of these 53 cases, there was no CC recurrence. The mean ERD of a single TBCT was 1.2mSv, and the mean cumulative ERD of TBCT was 2mSv per patient. CONCLUSION: Mean and cumulative ERD of TBCT performed in CC cases was not too high to consider radiation hazard. However, efforts to minimize the number of CT scans should be taken basically.

Removal of endocrine-disrupting chemicals by ozonation in sewage treatment.

Treatment experiments by two laboratory scale semi-batch reactors and a demonstration scale process were both carried out to evaluate endocrine disrupting chemical removal characteristics by ozonation in sewage treatment. In the semi-batch mode experiments, secondary effluent and primary effluen of sewage treatment plants were ozonated respectively. Behaviour of brominated by-products was also evaluated. The results based on these studies indicated that estrogenicity in wastewater can be removed by ozonation effectively. The condition of ozonation until dissolved ozone concentration increased to 0.1 mg/L, which corresponded to 1 mgO3/mgC and 0.4 mgO3/mgC of ozone consumption per initial DOC for secondary effluent and primary effluent, respectively, is proposed as an appropriate operational condition for efficient removal of EDCs as well as UV254 and SUVA without production of brominated by-products.

Synthesis of 2D/2D Structured Mesoporous Co3O4 Nanosheet/N-Doped Reduced Graphene Oxide Composites as a Highly Stable Negative Electrode for Lithium Battery Applications.

Mesoporous Co3O4 nanosheets (Co3 O4 -NS) and nitrogen-doped reduced graphene oxide (N-rGO) are synthesized by a facile hydrothermal approach, and the N-rGO/Co3O4 -NS composite is formulated through an infiltration procedure. Eventually, the obtained composites are subjected to various characterization techniques, such as XRD, Raman spectroscopy, surface area analysis, X-ray photoelectron spectroscopy (XPS), and TEM. The lithium-storage properties of N-rGO/Co3O4 -NS composites are evaluated in a half-cell assembly to ascertain their suitability as a negative electrode for lithium-ion battery applications. The 2D/2D nanostructured mesoporous N-rGO/Co3O4 -NS composite delivered a reversible capacity of about 1305 and 1501 mAh g(-1) at a current density of 80 mA g(-1) for the 1st and 50th cycles, respectively. Furthermore, excellent cyclability, rate capability, and capacity retention characteristics are noted for the N-rGO/Co3O4 -NS composite. This improved performance is mainly related to the existence of mesoporosity and a sheet-like 2D hierarchical morphology, which translates into extra space for lithium storage and a reduced electron pathway. Also, the presence of N-rGO and carbon shells in Co3O4 -NS should not be excluded from such exceptional performance, which serves as a reliable conductive channel for electrons and act as synergistically to accommodate volume expansion upon redox reactions. Ex-situ TEM, impedance spectroscopy, and XPS, are also conducted to corroborate the significance of the 2D morphology towards sustained lithium storage.

Corrigendum: Determinants of Conductive Hearing Loss in Tympanic Membrane Perforation: Correction of the Sixth Author Name.

[This corrects the article on p. 92 in vol. 8, PMID: 26045905.].

Concomitant acute transverse myelitis and sensory motor axonal polyneuropathy in two children: two case reports.

Acute transverse myelitis (ATM) is an upper motor neuron disease of the spinal cord, and concomitant association of peripheral polyneuropathy, particularly the axonal type, is rarely reported in children. Our cases presented with ATM complicated with axonal type polyneuropathy. Axonal type polyneuropathy may be caused by acute motor-sensory axonal neuropathy (AMSAN) or critical illness polyneuropathy and myopathy (CIPNM). These cases emphasize the need for nerve and muscle biopsies to make the differential diagnosis between AMSAN and CIPNM in patients with ATM complicated with axonal polyneuropathy.

Successful conservative treatment: multiple atypical fractures in osteoporotic patients after bisphosphate medication: a unique case report.

Bisphosphonates have been commonly used for the treatment of osteoporosis. However, there have been recent case reports of atypical fractures citing their long-term use, which inhibits the turnover of bone components. A 64-year-old woman visited the outpatient clinic with pain in her right thigh and ambulation difficulty. We found fractures at both pedicles of L4 vertebra. subtrochanteric region of right femur, and left femoral shaft upon a radiologic examination. She had taken intravenous ibandronic sodium for osteoporosis over 3 years. We changed the bishophonates to a parathyroid hormone because it was suspected that the multiple fractures were caused by the medication. Further, rehabilitation, including progressive weight bearing, was started. After 3 months of the conservative treatment, she was able to walk independently. In conclusion, it is necessary to evaluate the possibility of atypical fractures in osteoporotic patients when they complain of lower extremity pain and to consider alternative treatments instead of bisphosphonates.