[Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations].

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Urine phthalate levels were associated with skin barrier dysfunction and atopic sensitization in children.

OBJECTIVE: Phthalates can cause immunological disorders and aggravate allergic diseases. Thus, we investigated the relationship between urinary phthalate, skin barrier function, and atopic sensitization in children. PATIENTS AND METHODS: In total, 448 school children [334 with severe allergic disease; and 123 with severe atopic dermatitis (AD)] aged 10-12 years were enrolled in this study between June and July 2017. Four high-molecular-weight phthalates (HMWP) [Σ4HMWP] and three low-molecular-weight phthalates (LMWP) [Σ3LMWP] metabolites in urine samples, specific immunoglobulin E (IgE), and total eosinophil count were measured. Four-part trans epidermal water loss (TEWL) (cheek, leg, and upper/lower arm; Σ4TEWL) was measured to evaluate the skin barrier function. RESULTS: After adjusting for confounding variables, Σ4TEWL was significantly associated with the quartiles of urinary Σ4HMWP [adjusted ß=7.897, 95% confidence interval (CI): 0.636-15.158, p=0.033] and Σ3LMWP (adjusted ß=9.670, 95% CI: 2.422-16.919, p=0.009). The adjusted analyses revealed that the quartiles of urinary Σ4HMWP and Σ3LMWP were not significantly associated with total eosinophil count, atopic sensitization, and severe AD (p>0.05). According to the quartiles of urinary Σ4HMWP and Σ3LMWP, there were significant differences in the TEWL of the lower arm and leg (p<0.05) but not in cheek and upper arm. CONCLUSIONS: Exposure to HMWPs and LMWPs was significantly associated with skin barrier dysfunction but not with atopic sensitization. These results suggest that children exposed to phthalates may be more susceptible to fragile skin barrier function.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children.

OBJECTIVE: Previous studies on the relationship of bisphenol-A (BPA) with fractional exhaled nitric oxide (FeNO) had conflicting results, suggesting that other factors may modulate this relationship. Thus, we investigated the modulating effect of vitamin D on the relationship of BPA with FeNO in children. PATIENTS AND METHODS: This study recruited 432 children (10 to 12 years old) from the general pediatric population of Korea between June and July 2017. We conducted measurements of urinary BPA, serum vitamin D, specific serum IgE, FeNO, and data from impulse oscillometry (reactance area [AX], airway resistance at 5 Hz [Rrs5] and 20 Hz [Rrs10], and the difference of Rrs5 and Rrs20 [Rrs5-20]). RESULTS: Serum vitamin D (adjusted ß =- 0.014, p=0.002) and urinary BPA (ß = 0.006, p<0.001) level was significantly associated with FeNO. Urinary BPA level was significantly associated with FeNO in children with low vitamin D levels (≤23 ng/mL; αß = 0.006, p < 0.001), but not in children with high vitamin D levels (>23 ng/mL). The interaction of vitamin D and BPA had a significant effect on FeNO (pint = 0.005). There was no relationship with the airway lung function (Rrs5, AX, and Rrs5-20) to serum vitamin D and urinary BPA level. Vitamin D ameliorated the BPA-mediated increase of FeNO in children. CONCLUSIONS: These results suggest that children with low vitamin D levels may be more susceptible to airway inflammation due to BPA.

MiR-376a-3p alleviates the development of glioma through negatively regulating KLF15.

OBJECTIVE: The purpose of this study was to uncover the role of microRNA-376a-3p (miR-376a-3p) in mediating migratory and invasive capacities of glioma, as well as the underlying mechanism. PATIENTS AND METHODS: MiR-376a-3p levels in 39 collected glioma tissues were detected. After collecting clinical data of included glioma patients, the relationship between miR-376a-3p level and clinical features of glioma was analyzed. Next, regulatory effects of miR-376a-3p on proliferative and metastatic capacities of U251 and T98-G cells were assessed. Downstream genes of miR-376a-3p were searched by bioinformatics approach. At last, the involvement of KLF15 in the development of glioma regulated by miR-376a-3p was explored. RESULTS: It was found that miR-376a-3p was lowly expressed in glioma tissues. Low level of miR-376a-3p was linked to high metastasis rate and poor prognosis in glioma. Besides, overexpression of miR-376a-3p suppressed proliferative and metastatic capacities of glioma cells. KLF15, the downstream gene binding miR-376a-3p, was highly expressed in glioma, and displayed a negative correlation to miR-376a-3p. Notably, KLF15 was able to abolish the regulatory effects of miR-376a-3p on phenotypes of glioma cells. CONCLUSIONS: MiR-376a-3p is related to lymphatic metastasis and distant metastasis of glioma, and alleviates metastasis of glioma by negatively regulating KLF15.

Global land-water nexus: Agricultural land and freshwater use embodied in worldwide supply chains.

As agricultural land and freshwater inextricably interrelate and interact with each other, the conventional water and land policy in "silos" should give way to nexus thinking when formulating the land and water management strategies. This study constructs a systems multi-regional input-output (MRIO) model to expound global land-water nexus by simultaneously tracking agricultural land and freshwater use flows along the global supply chains. Furthermore, land productivity and irrigation water requirements of 160 crops in different regions are investigated to reflect the land-water linkage. Results show that developed economies (e.g., USA and Japan) and major large developing economies (e.g., mainland China and India) are the overriding drivers of agricultural land and freshwater use globally. In general, significant net transfers of these two resources are identified from resource-rich and less-developed economies to resource-poor and more-developed economies. For some crops, blue water productivity is inversely related to land productivity, indicating that irrigation water consumption is sometimes at odds with land use. The results could stimulus international cooperation for sustainable land and freshwater management targeting on original suppliers and final consumers along the global supply chains. Moreover, crop-specific land-water linkage could provide insights for trade-off decisions on minimizing the environmental impacts on local land and water resources.

Expression of heat shock protein 70 in transport-stressed broiler pectoralis major muscle and its relationship with meat quality.

Omics research has indicated that heat shock protein 70 (HSP70) is a potential biomarker of meat quality. However, the specific changes and the potential role of HSP70 in postmortem meat quality development need to be further defined. In this study, Arbor Acres broiler chickens (n=126) were randomly categorized into three treatment groups of unstressed control (C), 0.5-h transport (T) and subsequent water shower spray following transport (T/W). Each treatment consisted of six replicates with seven birds each. The birds were transported according to a designed protocol. The pectoralis major (PM) muscles of the transport-stressed broilers were categorized as normal and pale, soft and exudative (PSE)-like muscle samples according to L* and pH24 h values to test the expression and location of HSP70. Results revealed that the activities of plasma creatine kinase and lactate dehydrogenase increased significantly (P<0.05) in normal and PSE-like muscle samples after transportation. The mRNA expression of HSP70 in normal muscle samples increased significantly (P<0.05) compared with that in the controls after stress. The protein expression of HSP70 increased significantly in normal muscle samples and decreased significantly (P<0.05) in PSE-like muscles. Immuno-fluorescence showed that HSP70 was present in the cytoplasm and on surface membranes of PM muscle cells in the normal samples following stress. Meanwhile, HSP70 was present on the surface membranes and extracellular matrix but was barely visible in the cytoplasm of the PSE-like samples. Principal component analysis showed high correlations between HSP70 and meat quality and stress indicators. In conclusion, this research suggests that the variation in HSP70 expression may provide a novel insight into the pathways underlying meat quality development.

Precipitation and ultimate pH effect on chemical and gelation properties of protein prepared by isoelectric solubilization/precipitation process from pale, soft, exudative (PSE)-like chicken breast meat1.

Pale, soft, exudative (PSE)-like chicken breast is considered deteriorated raw material in the poultry meat industry that has inferior processing ability. The chemical and gelation properties of PSE-like chicken breast meat paste were studied. These pastes were prepared by the pH adjustment method and protein isolation using the isoelectric solubilization/precipitation (ISP) process from PSE-like chicken meat. The ISP-isolated samples were solubilized at pH 11.0 and recovered at pH 5.5 and 6.2. The ultimate pH of the ISP-isolated protein and meat paste was adjusted to 6.2 and 7.0. The ultimate pH in this article referred to the final pH of the extracted protein and meat paste. Higher reactive sulfhydryl content and surface hydrophobicity were found in the precipitation at pH 6.2 than at pH 5.5. However, various ultimate pH values showed no significant influence on the surface hydrophobicity. The hardness of gel, as measured by textural profile analysis, was improved using 6.2 as the precipitation pH compared with pH 5.5. The viscoelastic modulus (G΄) of gel pastes prior to the thermal gelation was higher with ISP treatment. However, lower G΄ was seen after thermal gelation compared with the control. Dynamic rheological measurement demonstrated a different gel-forming mechanism for protein precipitated at pH values of 5.5 and 6.2 compared with the meat paste. The cooking loss showed that the recovered protein failed to form a gel with good water-retention capacity unless the ultimate pH was adjusted to 7.0. Gels made from protein extracted by the ISP method had higher yellowness and lower redness values, probably due to protein denaturation. Precipitation at pH 6.2 formed a harder gel with lower water-retention ability than that at pH 5.5, and this result was possibly due to higher surface hydrophobicity and S-S bridge formation. Overall, network characteristics of ISP-treated protein gels were strongly dependent on precipitation pH and ultimate pH.

Evaluation of parameters obtained from the Sysmex XN-2000 for predicting the recovery of the absolute neutrophil count and platelets after hematopoietic stem cell transplantation.

INTRODUCTION: We analyzed abilities of parameters from Sysmex XN-2000 (Sysmex, Kobe, Japan) to predict absolute neutrophil count (ANC) and platelet recovery after hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. METHODS: We prospectively analyzed 911 follow-up peripheral blood samples from 44 HSCT-performed patients and evaluated the performances of the following parameters: WBC, immature granulocyte (IG), hematopoietic stem and progenitor cells (HPC), immature reticulocyte fraction (IRF), immature platelet fraction (IPF), platelet distribution width (PDW), mean platelet volume (MPV), and platelet larger cell ratio (P-LCR). RESULTS: When compared to four other parameters, the identification of initiation in IG (%)/HPC (%) increase enabled earlier prediction of ANC recovery to >500/µL and >1000/µL with more time benefit of 3.5-6.5 days/2.0-5.0 days and 3.0-6.0 days/2.0-5.0 days, respectively. When compared to IPF (%), the identification of initiation in PDW, MPV, and P-LCR (%) increase enabled earlier prediction of platelet recovery to >20 000/µL and >50 000/µL with more time benefit of 2.5-3.5 days and 2.0-3.0 days, respectively. However, the standard deviation of time benefit obtained from IG (%)/HPC (%)/PDW/MPV/P-LCR (%) was consistently large (3.0-4.3 days). CONCLUSIONS: There is a systematic pattern where a rise in most of the studied parameters can be observed in most patients before ANC/platelet recovery. However, the interindividual variation between the time of rise of these parameters and ANC/platelet recovery is large, and therefore, using these parameters to predict recovery in the individual patient is probably not meaningful in the clinical setting.

Origin of photovoltaic effect in superconducting YBa2Cu3O6.96 ceramics.

We report remarkable photovoltaic effect in YBa2Cu3O6.96 (YBCO) ceramic between 50 and 300 K induced by blue-laser illumination, which is directly related to the superconductivity of YBCO and the YBCO-metallic electrode interface. There is a polarity reversal for the open circuit voltage Voc and short circuit current Isc when YBCO undergoes a transition from superconducting to resistive state. We show that there exists an electrical potential across the superconductor-normal metal interface, which provides the separation force for the photo-induced electron-hole pairs. This interface potential directs from YBCO to the metal electrode when YBCO is superconducting and switches to the opposite direction when YBCO becomes nonsuperconducting. The origin of the potential may be readily associated with the proximity effect at metal-superconductor interface when YBCO is superconducting and its value is estimated to be ~10(-8) mV at 50 K with a laser intensity of 502 mW/cm(2). Combination of a p-type material YBCO at normal state with an n-type material Ag-paste forms a quasi-pn junction which is responsible for the photovoltaic behavior of YBCO ceramics at high temperatures. Our findings may pave the way to new applications of photon-electronic devices and shed further light on the proximity effect at the superconductor-metal interface.

Reduced functionality of PSE-like chicken breast meat batter resulting from alterations in protein conformation.

The objectives of this study were to evaluate protein thermal stability, water-protein interaction, microstructure, and protein conformation between PSE-like and normal chicken breast meat batters. Sixty pale, soft, and exudative (PSE)-like (L*>53, pH24 h<5.7) and 60 normal (46

Sepsis affects most routine and cell population data (CPD) obtained using the Sysmex XN-2000 blood cell analyzer: neutrophil-related CPD NE-SFL and NE-WY provide useful information for detecting sepsis.

INTRODUCTION: The Sysmex XN-2000 analyzer can assess 36 routine and 57 cell population data (CPD) items. In this study, we evaluated these items as sepsis biomarkers. METHODS: We enrolled 280 normal control (NC) and 130 sepsis patients. The sepsis patients were classified as uncomplicated or complicated sepsis. Routine and CPD items were determined, and the results were compared at between the NC and sepsis groups, uncomplicated and complicated sepsis groups, and survivors and nonsurvivors. RESULTS: For the detection of sepsis, CPD items NE-SFL [defined as the fluorescent light intensity of the neutrophil area on the WDF (white blood cell differential) scattergram] and NE-WY (defined as the fluorescent light distribution width of the neutrophil area on the WDF scattergram) showed comparative or higher AUC of 0.909 and 0.905, respectively, when compared with routine items such as hematocrit, hemoglobin, RBC, RDW, immature granulocytes count, lymphocytes count, and neutrophils count. For the discrimination of sepsis severity, only platelet-related items showed higher AUC (0.723 - 0.748) than lactic acid (0.695). For the prediction of 28-day mortality, only CV and SD of RDW showed higher AUC (0.766 and 0.732 each) than lactic acid (0.712). CONCLUSIONS: Sepsis patients demonstrated significant changes in routine and CPD items related to RBC, neutrophils, lymphocytes, and platelets when compared to NCs. Increase in CPD items NE-SFL and NE-WY, which may indicate neutrophil immaturity or activation, could be useful for the detection of sepsis patients, in conjunction with currently used surrogate sepsis biomarkers. However, these items did not efficiently contribute to the discrimination of sepsis severity or predict mortality.

Detection of common deafness mutation by maternal plasma cell-free DNA.

OBJECTIVES: The aim is to investigate the use of the ligase detection reaction (LDR) microarray to examine the difference of the single nucleotide between the pregnant woman and the fetus by cell-free DNA in the maternal plasma in congenital deafness. MATERIALS AND METHODS: The proband and the couples' venous blood samples and the amniotic fluid/ chorionic villi collected from seven deafness families for prenatal diagnosis were analyzed. The cell-free DNA from maternal plasma was examined to determine if they carried the mutations of GJB2 235delC. RESULTS: Three samples were found to carry the mutation of GJB2 235delC. It is in agreement with the sequencing results. The affected fetuses were suggested to take invasive procedure for confirmation. CONCLUSIONS: The chip may be a potential method to screen for congenital deafness based on maternal plasma DNA.

Do newly built homes affect rhinitis in children? The ISAAC phase III study in Korea.

BACKGROUND: As Korea has experienced rapid economic development, the lifestyles of Koreans have become more Westernized, in terms of urbanization and dietary habits. Also, the prevalences of allergic diseases, such as rhinitis, asthma, and dermatitis, have increased rapidly. This study aimed to identify the factors influencing the symptoms of rhinitis conditions, including rhinitis, allergic rhinitis, overlapped rhinitis, and overlapped allergic rhinitis, among Korean children aged 6-7 years. METHODS: The study subjects were drawn from participants in the International Study of Asthma and Allergies in Childhood (ISAAC) study in 2010 and were aged 6-7 years. We analysed data for a total of 3804 children. RESULTS: The prevalences of symptoms suggestive of rhinitis and allergic rhinitis in the previous 12 months were 43.4% and 22.1%, respectively. For overlapped rhinitis and overlapped allergic rhinitis, only 2.5% and 1.9% of the children had overlapping symptoms, having rhinitis with asthma and eczema simultaneously. Gender, a parental history of allergic disease, mould or dampness at home, and the risk factors for 'sick building syndrome' (SBS) were risk factors influencing rhinitis diseases. In particular, a history of moving to a newly built home in the child's infancy was strongly associated with symptoms of all the rhinitis diseases examined. CONCLUSIONS: This study identified patterns of the prevalence of rhinitis conditions among Korean children that were similar to those reported in Western countries. We confirmed that a history of moving to a newly built home during infancy was associated with a considerable risk of rhinitis conditions.

Quantitative analysis on the urban flood mitigation effect by the extensive green roof system.

Extensive green-roof systems are expected to have a synergetic effect in mitigating urban runoff, decreasing temperature and supplying water to a building. Mitigation of runoff through rainwater retention requires the effective design of a green-roof catchment. This study identified how to improve building runoff mitigation through quantitative analysis of an extensive green-roof system. Quantitative analysis of green-roof runoff characteristics indicated that the extensive green roof has a high water-retaining capacity response to rainfall of less than 20 mm/h. As the rainfall intensity increased, the water-retaining capacity decreased. The catchment efficiency of an extensive green roof ranged from 0.44 to 0.52, indicating reduced runoff comparing with efficiency of 0.9 for a concrete roof. Therefore, extensive green roofs are an effective storm water best-management practice and the proposed parameters can be applied to an algorithm for rainwater-harvesting tank design.

Effects of catchment, first-flush, storage conditions, and time on microbial quality in rainwater harvesting systems.

Rainwater collected from a rooftop rainwater harvesting (RWH) system is typically not considered suitable for potable uses, primarily because of poor microbial quality. The quality of stored rainwater, however, can be improved through basic design and maintenance practices during the construction and operation of an RWH system. This paper presents the microbial analysis of rainwater in two RWH systems installed at the Seoul National University Campus in South Korea. Rainwater samples were collected at different locations within each system and analyzed for total and fecal coliforms, Escherichia coli, and heterotrophic plate count bacteria. Within their storage tanks, water quality improved horizontally from inlet to outlet points, and higher quality was observed at the supply point (located about 0.5 m from the base of the tank) than at the surface or bottom of the tank. First-flush rainwater was found to be highly contaminated but rainwater quality improved following about 1 mm of precipitation. The catchment surface also had a significant effect on the quality of rainwater; samples collected from a rooftop exhibited better microbial quality than from a terrace catchment. Better water quality in underground tanks (dark storage conditions) compared to open weirs/ filters (exposed to natural light) demonstrated the importance of storage conditions. Water quality also improved with longer storage, and a decrease of 70% to 90% in microbial concentrations was observed after about 1 week of storage time. The findings of this study demonstrate that the microbial quality of harvested rainwater can be improved significantly by the adoption of proper design and maintenance guidelines such as those discussed in this paper.