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This study aimed to determine nursing students’ perceptions of dementia and patients with dementia. Specifically, this study sought to illuminate the essential meaning of dementia among nursing students to uncover insights useful for developing patient-centered care rooted in empathy for patients with dementia. This study used a descriptive phenomenological research method. Between August and September 2023, semi-structured interviews were conducted with 15 nursing students. Colaizzi’s method was used for the manual analysis. After analyzing the interview data on nursing students’ awareness of dementia, four categories, nine theme clusters, and 28 formulated meanings were derived. The four categories were “View of dementia”, “Feelings about dementia”, “Efforts made regarding dementia”, and “Dementia as a nursing student”. Although nursing students’ perceptions of dementia resulted in negative perspectives and emotions, by looking into coping methods and wishes for dementia, this study also confirmed that nursing students had an awareness of caring for patients with dementia.

Abstract The neural circuits of the infant brain are rapidly established near 6 months of age, but neurodevelopmental disorders can be diagnosed only at the age of 2–3 years using existing diagnostic methods. Early diagnosis is very important to alleviate life-long disability in patients through appropriate early intervention, and it is imperative to develop new diagnostic methods for early detection of neurodevelopmental disorders. We examined the serum level of secretogranin II (SCG2) in pediatric patients to evaluate its potential role as a biomarker for neurodevelopmental disorders. A plasmonic immunosensor performing an enzyme-linked immunosorbent assay (ELISA) on a gold nanodot array was developed to detect SCG2 in small volumes of serum. This nanoplasmonic immunosensor combined with tyramide signal amplification was highly sensitive to detect SCG2 in only 5 μL serum samples. The analysis using the nanoplasmonic immunosensor revealed higher serum SCG2 levels in pediatric patients with developmental delay than in the control group. Overexpression or knockdown of SCG2 in hippocampal neurons significantly attenuated dendritic arborization and synaptic formation. These results suggest that dysregulated SCG2 expression impairs neural development. In conclusion, we developed a highly sensitive nanoplasmonic immunosensor to detect serum SCG2, a candidate biomarker for the early diagnosis of neurodevelopmental disorders.

Abstract KIF1A is a brain-specific anterograde motor protein that transports cargoes towards the plus-ends of microtubules. Many variants of the KIF1A gene have been associated with neurodegenerative diseases and developmental delay. Homozygous mutations of KIF1A have been identified in a recessive subtype of hereditary spastic paraplegia (HSP), SPG30. In addition, KIF1A mutations have been found in pure HSP with autosomal dominant inheritance. Here we report the first case of familial complicated HSP with a KIF1A mutation transmitted in autosomal dominant inheritance. A heterozygous p.T258M mutation in KIF1A was found in a Korean family through targeted exome sequencing. They displayed phenotypes of mild intellectual disability with language delay, epilepsy, optic nerve atrophy, thinning of corpus callosum, periventricular white matter lesion, and microcephaly. A structural modeling revealed that the p.T258M mutation disrupted the binding of KIF1A motor domain to microtubules and its movement along microtubules. Assays of peripheral accumulation and proximal distribution of KIF1A motor indicated that the KIF1A motor domain with p.T258M mutation has reduced motor activity and exerts a dominant negative effect on wild-type KIF1A. These results suggest that the p.T258M mutation suppresses KIF1A motor activity and induces complicated HSP accompanying intellectual disability transmitted in autosomal dominant inheritance.

Purpose: This study investigated prediction of North Korean refugees' adaptation to the South Korean society and verified the goodness of fit between a hypothetical model and actual data in order to suggest the best model. Methods: This survey was conducted with 445 North Korean refugees living in a metropolitan area. Data were collected from September 1st to November 20th, 2012, and analyzed using SPSS Windows 18.0 and AMOS 17.0. Results: Traumatic experiences of North Korean refugees increased self-efficacy and psychological trauma. Acculturation stress decreased self-efficacy and increased passive coping. Self-efficacy affected active and passive coping, decreased psychological trauma, and increased resilience. Resilience is successful adaptation and refers to North Korean refugees' abilities to adapt effectively to stress. In particular, self-efficacy as the main parameter affecting resilience was confirmed. Conclusions: The results suggest that resilience can be improved through self-efficacy. It was the most significant factor decreasing psychological trauma and increasing resilience. Therefore, we need to develop programs for self-efficacy. The results also provide basic data for policy making for North Korean refugees.

Background Cerebrospinal fluid (CSF) leakage may cause intracranial hypotension and postural headache. Secondary intracranial hypotension may result from an iatrogenic dural puncture or traumatic injury associated with pain procedures. Case A 45-year-old male developed a headache 26 days after spinal pain procedure. Headache was characterized as postural, worsening with standing or sitting and improving while lying down. The pain did not resolve despite the administration of oral and intravenous analgesics. A spinal magnetic resonance imaging revealed epidural venous congestion and a suspicious CSF leak around the left L4/5 level. The patient received an epidural blood patch (EBP), the headache improved dramatically, and the patient was discharged. Conclusions Delayed postural headaches may not be directly related to pain management. Nevertheless, intracranial hypotension related to pain management should be suspected even in this case. If confirmed, quickly applying an EBP is an effective treatment option.

Transcranial doppler ultrasonography (TCD) applies a low frequency of 2 MHz to measure the blood flow velocity and waveform within the skull. Medical technologists at several hospitals are conducting these examinations, and education is being imparted in many schools and academic societies. However, the skill of the tester is of utmost importance when performing TCD. Technicians who are conducting the procedure for the first time have trouble locating the blood vessels, and some experienced personnel are worried because too many blood vessels are present. Since this procedure does not directly look at and measure blood vessels, there are several limitations and difficulties. Therefore, this study aims to provide some help by introducing precautions and suggestions for TCD technicians conducting the test.

Abstract Osteoclasts degrade bone and osteoclast differentiation has been implicated in bone destruction in rheumatoid arthritis. The dairy bacterium Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk inhibits osteoclast differentiation and ameliorates collagen-induced arthritis. This study aimed to investigate the inhibitory effect of the surface proteins of MJ2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and explain the underlying mechanism. The murine macrophage cell line RAW 264.7 was used to study the inhibition of osteoclast differentiation. The surface proteins significantly inhibited RANKL-induced osteoclast differentiation in a protein concentration-dependent manner by inhibiting the expression of genes and proteins related to osteoclast differentiation. RNA microarray analysis showed that the surface proteins significantly upregulated lipocalin-2 (lcn2) expression. In addition, they downregulated c-fos and NFATc1 and inhibited the expression of NFATc1-downstream genes Atp6v0d2, Calcr, and Ctsk. siRNA silencing of lcn2 decreased the extent of surface protein inhibition on osteoclast differentiation, suggesting that lcn2 plays an important role in the inhibition of RANKL-induced osteoclast differentiation. In conclusion, surface proteins of MJ2 show inhibitory effects on RANKL-induced osteoclast differentiation by upregulating lcn2 expression, in turn downregulating NFATc1, leading to the inhibition of NFATc1-downstream osteoclastogenesis-related gene expression.

In this paper, a high gain circularly-polarized antenna array with a flat panel structure for low Earth orbit (LEO) satellite communication systems is proposed. This new CP structure can efficiently achieve high directivity and can easily be integrated with beamforming ICs (BFIC) when designing an antenna module, resulting in a good candidate for Ka-band satellite communications. Furthermore, the proposed FPAA can easily be extended to a larger scale array from a base unit in a 2 × 2 sub-array structure. Each sub-array is configured by four high-gain planar segmented antenna (PSA) elements with a sequentially rotating arrangement, where a single 4-channel BFIC can drive CP radiation. Unlike previously reported PSA elements that have limited CP performance, the proposed PSA-CP configuration adopts additional conductors and ground-via structures to further improve the CP gain, axial-ratio (AR), and cross-polarization (XPD) characteristics. To verify the performance of the proposed PSA-CP, a 2 × 2 left-hand circular polarization (LHCP) sub-array was fabricated at 28 GHz and tested with a BFIC. The measured 10-dB impedance and 3-dB AR bandwidths of the proposed 2 × 2 array were 13.92% and 12.5%, respectively. In addition, the measured peak gain was 15.2 dBic at 28.5 GHz with an XPD level of less than 15 dB.

Abstract cGMP-dependent protein kinase I-α (PKG1α) is a target for pulmonary arterial hypertension due to its role in the regulation of smooth muscle function. While most work has focused on regulation of cGMP turnover, we recently described several small molecule tool compounds which were capable of activating PKG1α via a cGMP independent pathway. Selected molecules were crystallized in the presence of PKG1α and were found to bind to an allosteric site proximal to the low-affinity nucleotide binding domain. These molecules act to displace the switch helix and cause activation of PKG1α representing a new mechanism for the activation and control of this critical therapeutic path. The described structures are vital to understanding the function and control of this key regulatory pathway.

Abstract The present study evaluated the potential of carrot (Daucus carota L.) leaf, a non-edible part of carrots, which are among the most consumed vegetables worldwide. The antioxidant activities of 70% ethanol extract (EEC) and hot water extract (HEC) of carrot leaves were compared. The results revealed that the total polyphenol content, total flavonoid content, and DPPH and ABTS radical scavenging activities were higher in EEC than in HEC. Both extracts protected the cells against H2O2-induced toxicity and markedly reduced the levels of reactive oxygen species in RAW 264.7 cells. Moreover, pretreatment of RAW 264.7 cells with EEC and HEC prior to H2O2 (500 μM) exposure increased superoxide dismutase and glutathione peroxidase activities in these cells. Notably, EEC and HEC increased intracellular catalase activity by 36.77 and 6.39 times, respectively. Compared to HEC, EEC remarkably inhibited the production of lipopolysaccharide-induced nitric oxide and reduced the gene expression of IL-6, IL-1β, iNOS, COX-2, and TNF-α. Comparative analysis of the composition of the extracts using HPLC–UV suggested notably higher contents of catechin, chlorogenic acid, caffeic acid, rutin, quercetin, and cynaroside in EEC than in HEC. Collectively, these results imply that carrot leaves are a potentially beneficial natural source of antioxidants and anti-inflammatory compounds in functional foods.

Abstract The genotype–phenotype correlation of the X-linked Alport syndrome (XLAS) has been well elucidated in males, whereas it remains unclear in females. In this multicenter retrospective study, we analyzed the genotype–phenotype correlation in 216 Korean patients (male:female = 130:86) with XLAS between 2000 and 2021. The patients were divided into three groups according to their genotypes: the non-truncating group, the abnormal splicing group, and the truncating group. In male patients, approximately 60% developed kidney failure at the median age of 25.0 years, and kidney survival showed significant differences between the non-truncating and truncating groups (P

Abstract Background Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. Methods Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. Results During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10–5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted

Abstract Epigenetic influence plays a role in the association between exposure to air pollution and attention deficit hyperactivity disorder (ADHD); however, research regarding sulfur dioxide (SO2) is scarce. Herein, we investigate the associations between prenatal SO2 exposure and ADHD rating scale (ARS) at ages 4, 6 and 8 years repeatedly in a mother–child cohort (n = 329). Whole blood samples were obtained at ages 2 and 6 years, and genome-wide DNA methylation (DNAm) was analyzed for 51 children using the Illumina Infinium HumanMethylation BeadChip. We analyzed the associations between prenatal SO2 exposure and DNAm levels at ages 2 and 6, and further investigated the association between the DNAm and ARS at ages 4, 6 and 8. Prenatal SO2 exposure was associated with ADHD symptoms. From candidate gene analysis, DNAm levels at the 6 CpGs at age 2 were associated with prenatal SO2 exposure levels. Of the 6 CpGs, cg07583420 (INS-IGF2) was persistently linked with ARS at ages 4, 6 and 8. Epigenome-wide analysis showed that DNAm at 6733 CpG sites were associated with prenatal SO2 exposure, of which 58 CpGs involved in Notch signalling pathway were further associated with ARS at age 4, 6 and 8 years, persistently. DNAm at age 6 was not associated with prenatal SO2 exposure. Changes in DNAm levels associated with prenatal SO2 exposure during early childhood are associated with increases in ARS in later childhood.

A bronchial stump blow-out is a serious complication following pneumonectomy/lobectomy. A blown-out stump requires well-vascularized tissue for healing and successful closure. We illustrate the use of the free anterolateral thigh flap in two patients. For patient 1, a chimeric anterolateral thigh flap was used to seal the bronchial stump following an upper lobectomy for tuberculous bronchiectasis. For patient 2, an anterolateral thigh flap was used to seal the main bronchial stump that had blown-out following pneumonectomy for actinomyces lung abscess. The latissimus dorsi muscle was unavailable in both cases due to a previous thoracotomy. Patient 1 had a persistent bronchial leak post-operatively, which resolved after anti-tuberculous treatment. Patient 2 recovered uneventfully and was discharged 14-days post-operatively. Their follow-ups were 13 years and 4 months respectively. In conclusion, the free anterolateral thigh flap is an alternative option to seal a blown-out bronchial stump in the absence of the latissimus dorsi muscle flap.

Background The entanglement of multiple central venous catheters is a rare and serious complication. The Swan-Ganz catheter is a responsible for various cases. Case A 66-year-old male patient was under general anesthesia for a coronary artery bypass graft surgery. As he had a pre-existing Perm catheter in the right subclavian vein, a Swan-Ganz catheter was inserted into the left internal jugular vein. Chest radiograph after catheter placement revealed that the Perm catheter had migrated to the left brachiocephalic vein. The surgeon attempted to reposition it manually, but postoperative radiograph showed that it had rolled into a loop. On postoperative day 1, radiological intervention was performed to untangle the loop, which was successful. Conclusions After placing a Swan-Ganz catheter in patients with a pre-existing central venous catheter, the presence of entanglement should be assessed. In such cases, radiology-guided correction is recommended, as a blind attempt to disentangle can aggravate the condition.

Background: With recent advances in cardiac surgery through minimal access, mini-thoracotomy has emerged as an excellent alternative for cardiac myxoma resection. This study analyzed the surgical results of this approach, focusing on postoperative cerebral embolism and tumor recurrence. Methods: We retrospectively reviewed 64 patients (mean age, 56.0±12.1 years; 40 women) who underwent myxoma resection through mini-thoracotomy from October 2008 to July 2020. We conducted femoral cannulation and antegrade cardioplegic arrest in all patients. Patient characteristics and perioperative data, including brain diffusion-weighted magnetic resonance imaging (DWI) findings, were collected. Medium-term echocardiographic follow-up was performed. Results: Thirteen patients (20.3%) had a history of preoperative stroke, and 7 (11.7%) had dyspnea with New York Heart Association functional class III or IV. Sixty-one cases (95.3%) had myxomas in the left atrium. The mean cardiopulmonary bypass and cardiac ischemic times were 69.0±28.6 and 34.1±15.0 minutes, respectively. Sternotomy conversion was not performed in any case, and 50 patients (78.1%) were extubated in the operating room. No early mortality or postoperative clinical stroke occurred. Postoperative DWI was performed in 32 (53%) patients, and 7 (22%) showed silent cerebral embolisms. One patient underwent reoperation for tumor recurrence during the study period; in that patient, a genetic study confirmed the Carney complex. Conclusion: Mini-thoracotomy for cardiac myxoma resection showed acceptable clinical and neurological outcomes. In the medium-term echocardiographic follow-up, reliable resection was proven, with few recurrences. This approach is a promising alternative for cardiac myxoma resection.

Abstract Cardiac amyloidosis is a debilitating disease associated with poor long‐term survival. Medical or palliative treatment is the usual course of therapy, but patients are often intolerant of conventional heart failure treatment. The current standard of care of sequential heart and bone marrow transplant is usually not feasible for ill or frail patients or in countries with limited organ donors or without transplant programmes. Left ventricular assist devices (LVAD) are not usually offered to these patients due to high peri‐operative risks and risks of suction events with the LVAD in a small left ventricle. We report the 2 year outcome and discuss the challenges faced in the management of our patient with end‐stage heart failure due to cardiac amyloidosis, who was successfully supported with an LVAD using a modified left atrium to aorta implantation technique.

Background Delayed emergence from general anesthesia is associated with life-threatening conditions with pharmacological, neurological, metabolic, and rarely, psychiatric causes. This case report was presented to report psychogenic coma after recovery from anesthesia with remimazolam and remifentanil. Case An elderly woman was unresponsive after recovery from anesthesia with remimazolam and remifentanil. Physical examination, laboratory testing, and radiographic imaging did not reveal any obvious organic causes. Pharmacological or metabolic abnormalities were not found. Absence of those causes strongly suggests that prolonged unconsciousness is related to psychiatric origin. The patient spontaneously regained consciousness after 48 h without any neurological complications. Conclusions Anesthesiologists should be aware of the possibility of psychogenic coma for patients with unexplained delay in emergence from anesthesia after the exclusion of other causes.

Background: In this study, we present recent trends in heart valve surgery in Korea through analyses of data from the Korea Heart Valve Surgery Registry (KHVSR). Methods: We enrolled 8,981 patients who were registered in the KHVSR from 2017 to 2020. Yearly trends in patients’ baseline characteristics, surgical profiles, and early mortality rates were explored. The observed/expected mortality ratio (O/E ratio), calculated from the actual mortality in the KHVSR and the predicted mortality estimated using the EuroSCORE II, was also analyzed. Results: The proportion of aortic valve surgery significantly increased from 56.8% in 2017 to 60.3% in 2020. The proportion of all combined procedures and minimally invasive surgery significantly increased over the 4-year study period. The operative mortality rate was 2.9% in the entire cohort, while mitral valve repair showed the lowest mortality risk (0.9%). The mortality rates of isolated aortic valve replacement (AVR) significantly decreased from 2.1% in 2017 to 0.8% in 2020 (p=0.016). Overall, the O/E ratio was 0.784 (95% confidence interval [CI], 0.677–0.902) demonstrating significantly lower actual mortality risks than expected based on the EuroSCORE II. In particular, the O/E ratios were as low as 0.364 (95% CI, 0.208–0.591) for isolated AVR. Conclusion: The recent data from the KHVSR showed increasing trends for complex procedures and minimally invasive surgery in heart valve surgery in Korea, and demonstrated remarkably low risks of operative mortality.

Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using

Background: Climate change is suspected to cause adverse health effects, and increased ozone concentration is one of the proposed pathways. We examined the mediation of ozone on the association between temperature and daily mortality and estimated excess mortality due to climate change. Methods: Daily mean temperature, 8-hour maximum ozone concentration, and daily number of non-accidental deaths from 7 metropolitan cities in Korea (Seoul, Busan, Daegu, Incheon, Daejeon, Gwangju, and Ulsan) between January 1, 2006 and December 31, 2019 were analyzed. A mediation analysis using a linear regression model for temperature and ozone and a Poisson regression model for temperature and mortality adjusting for ozone was conducted on days with temperature higher than or lower than city specific minimum mortality temperature. We calculated excess mortality due to direct and indirect effects of daily temperature exceeding average daily temperature from 1960 to 1990. Results: The daily mean temperature from 2006 to the end of 2019 was 1.15 ± 2.94 °C higher than the average daily temperature from 1960 to 1990. The pooled relative risk (for a 1 °C increment) of indirect effects through increased ozone were 1.0002 [95% confidence interval (CI): 0.9999, 1.0004] and 1.0003 (95% CI: 1.0002, 1.0005) in days with higher than or lower than minimum mortality temperature, respectively. The numbers of excess deaths during the study period were 2072.5 (95% CI: 1957.1, 2186.5) due to direct effects in days with higher than minimal mortality temperature, and 94.6 (95% CI: 84.3, 101.7) and 268.5 (95% CI: 258.4, 289.1) due to indirect effects in days with higher than and lower than minimal mortality temperature, respectively. Conclusion: We observed a mediating effect of ozone between temperature and daily mortality. There has been excess deaths due direct effect of temperature and indirect effects through ozone.

ABSTRACT Fragility fractures, resulting from low‐energy trauma, occur in approximately 1 in 10 Danish women aged 50 years or older. Bilateral oophorectomy (surgical removal of both ovaries) may increase the risk of fragility fractures due to loss of ovarian sex steroids, particularly estrogen. We investigated the association between bilateral oophorectomy and risk of fragility fracture and whether this was conditional on age at time of bilateral oophorectomy, hormone therapy (HT) use, hysterectomy, physical activity level, body mass index (BMI), or smoking. We performed a cohort study of 25,853 female nurses (≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from age 50 years or entry into the cohort, whichever came last, until date of first fragility fracture, death, emigration, or end of follow‐up on December 31, 2018, whichever came first. Cox regression models with age as the underlying time scale were used to estimate the association between time‐varying bilateral oophorectomy (all ages,

BackgroundA high rate of locoregional recurrence is one of the major difficulties in successful treatment of retroperitoneal sarcoma (RPS). Although pre-operative radiation therapy (RT) is considered a potential way to improve local recurrence, concerns about the associated treatment toxicity and risk of peri-operative complications need to be addressed. Hence, this study investigates the safety of pre-operative RT (preRTx) for RPS.MethodsA cohort of 198 patients with RPS who had undergone both surgery and RT was analyzed for peri-operative complications. They were divided into three groups according to the RT scheme: (1) preRTx group, (2) post-operative RT without tissue expander, and (3) post-operative RT with tissue expander.ResultsThe preRTx was overall well tolerated and did not affect the R2 resection rate, operative time, and severe post-operative complications. However, the preRTx group was associated with higher incidence of post-operative transfusion and admission to intensive care unit (p = 0.013 and p = 0.036, respectively), where preRTx was an independent risk factor only for the post-operative transfusion (p = 0.009) in multivariate analysis. The median radiation dose was the highest in preRTx group, although no significant difference was demonstrated in overall survival and local recurrence rate.ConclusionThis study suggests that the preRTx does not add significant post-operative morbidity to the patients with RPS. In addition, radiation dose elevation is achievable with the pre-operative RT. However, a meticulous intra-operative bleeding control is recommended in those patients, and further high-quality trials are warranted to evaluate the long-term oncological outcomes.

Abstract Background Forests are atmospheric carbon sinks, whose natural growth can contribute to climate change mitigation. However, they are also affected by climate change and various other phenomena, for example, the low growth of coniferous forests currently reported globally, including in the Republic of Korea. In response to the implementation of the Paris Agreement, the Korean government has proposed 2030 greenhouse gas roadmap to achieve a Nationally Determined Contribution (NDC), and the forest sector set a sequestration target of 26 million tons by 2030. In this study, the Korean forest growth model (KO-G-Dynamic model) was used to analyze various climate change and forest management scenarios and their capacity to address the NDC targets. A 2050 climate change adaptation strategy is suggested based on forest growth and CO2 sequestration. Results Forest growth was predicted to gradually decline, and CO2 sequestration was predicted to reach 23 million tons per year in 2050 if current climate and conditions are maintained. According to the model, sequestrations of 33 million tCO2 year−1 in 2030 and 27 million tCO2 year−1 in 2050 can be achieved if ideal forest management is implemented. It was also estimated that the current forest management budget of 317 billion KRW (264 million USD) should be twice as large at 722 billion KRW (602 million USD) in the 2030s and 618 billion KRW (516 million USD) in the 2050s to achieve NDC targets. Conclusions The growth trend in Korea's forests transitions from young-matured stands to over-mature forests. The presented model-based forest management plans are an appropriate response and can increase the capacity of Korea to achieve its NDC targets. Such a modeling can help the forestry sector develop plans and policies for climate change adaptation.

Background/Aims The long-term effect of Helicobacter pylori eradication on the metabolic syndrome or diabetes are unclear. The aim of this study was to evaluate the effect of H. pylori eradication on glycemic control in type 2 diabetes mellitus (T2DM) or prediabetes mellitus (preDM). Methods A total of 124 asymptomatic subjects with T2DM or preDM were divided into H. pylori-negative (n = 40), H. pylori-positive with non-eradicated (n = 34), and eradicated (n = 50) groups. We measured H. pylori status (culture, histology, and rapid urease test) and glycated hemoglobin A1c (A1C) levels and followed-up at the 1st year and the 5th year of follow-up. Results The A1C levels significantly decreased in the eradicated group compared to the negative group and the non-eradicated groups (at the 1st year, p = 0.024; at the 5th year, p = 0.009). The A1C levels decreased in male, and/or subjects < 65 years of age in subgroup analyses (in male subjects, p = 0.047 and p = 0.020 at the 1st and the 5th year; in subjects < 65 years of age, p = 0.028 and p = 0.006 at the 1st and the 5th year; in male subjects < 65 years of age, p = 0.039 and p = 0.032 at the 1st and the 5th year). The eradication of H. pylori was related to the decrease in A1C values throughout the follow-up period, compared to the non-eradicated group (p = 0.017). Conclusions H. pylori eradication was related to the decreasing of A1C levels in patients with T2DM or preDM over a long-term follow-up period, especially in male and subjects < 65 years of age.

Introduction: Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. Materials and methods: This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. Results: In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. Conclusions: The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice. [ABSTRACT FROM AUTHOR]

Background/Aims: We investigated how interactions between humans and computer-aided detection (CADe) systems are influenced by the user’s experience and polyp characteristics. Methods: We developed a CADe system using YOLOv4, trained on 16,996 polyp images from 1,914 patients and 1,800 synthesized sessile serrated lesion (SSL) images. The performance of polyp detection with CADe assistance was evaluated using a computerized test module. Eighteen participants were grouped by colonoscopy experience (nurses, fellows, and experts). The value added by CADe based on the histopathology and detection difficulty of polyps were analyzed. Results: The area under the curve for CADe was 0.87 (95% confidence interval [CI], 0.83 to 0.91). CADe assistance increased overall polyp detection accuracy from 69.7% to 77.7% (odds ratio [OR], 1.88; 95% CI, 1.69 to 2.09). However, accuracy decreased when CADe inaccurately detected a polyp (OR, 0.72; 95% CI, 0.58 to 0.87). The impact of CADe assistance was most and least prominent in the nurses (OR, 1.97; 95% CI, 1.71 to 2.27) and the experts (OR, 1.42; 95% CI, 1.15 to 1.74), respectively. Participants demonstrated better sensitivity with CADe assistance, achieving 81.7% for adenomas and 92.4% for easy-to-detect polyps, surpassing the standalone CADe performance of 79.7% and 89.8%, respectively. For SSLs and difficult-to-detect polyps, participants' sensitivities with CADe assistance (66.5% and 71.5%, respectively) were below those of standalone CADe (81.1% and 74.4%). Compared to the other two groups (56.1% and 61.7%), the expert group showed sensitivity closest to that of standalone CADe in detecting SSLs (79.7% vs 81.1%, respectively). Conclusions: CADe assistance boosts polyp detection significantly, but its effectiveness depends on the user’s experience, particularly for challenging lesions [ABSTRACT FROM AUTHOR]

A widely used method for estimating fine scale long-term spatial variation in air pollution, especially for epidemiology studies, is land use regression (LUR) modeling using fixed off-road monitors. More recently, LUR models have been developed using data from mobile monitors that repeatedly measure road pollutants and mixed-effects modeling. Here, nitrogen dioxide (NO2) and black carbon (BC) predictions from two independent models were compared across streets (defined as 30–60 m road segments) (N = 30,312) and residences (N = 76,752) in Copenhagen, Denmark. The first model was Google Street View (GSV)-based mixed-effects LUR models (Google-MM) that predicted 2019 mean NO2 and BC levels, and the second was European-wide (EUW) LUR models that predicted annual mean 2010 levels at 100 m spatial resolution. Across street segments, the Spearman correlation coefficient between the 2019 NO2 from Google-MM-LUR and 2010 NO2 from EUW-LUR was 0.66, while at residences, this was 0.60. For BC, these were 0.51 across street segments and 0.40 at the residential level. The ratio of percentile 97.5 to 2.5 for NO2 across the study area streets using Google-MM NO2 was 4.5, while using EUW-LUR, this was 2.1. These NO2 ratios at residences were 3.1 using Google-MM LUR, and 1.7 using EUW-LUR. Such ratios for BC across street segments were 3.4 using Google-MM LUR and 2.3 using EUW-LUR, while at the residential level, they were 2.4 and 1.9, respectively. In conclusion, Google-MM-LUR NO2 for 2019 was moderately correlated with EUW-LUR NO2 developed in 2010 across Copenhagen street segments and residences. For BC, while Google-MM-LUR was moderately correlated with EUW-LUR across Copenhagen streets, the correlation was lower at the residential level. Overall, Google-MM-LUR revealed larger spatial contrasts than EUW-LUR.

Blood–brain barrier (BBB) models are important tools for studying CNS drug delivery, brain development, and brain disease. In vitro BBB models have been obtained from animals and immortalized cell lines; however, brain microvascular endothelial cells (BMECs) derived from them have several limitations. Furthermore, obtaining mature brain microvascular endothelial-like cells (BME-like cells) from human pluripotent stem cells (hPSCs) with desirable properties for establishing BBB models has been challenging. Here, we developed an efficient method for differentiating hPSCs into BMECs that are amenable to the development and application of human BBB models. The established conditions provided an environment similar to that occurring during BBB differentiation in the presence of the co-differentiating neural cell population by the modulation of TGF-β and SHH signaling. The developed BME-like cells showed well-organized tight junctions, appropriate expression of nutrient transporters, and polarized efflux transporter activity. In addition, BME-like cells responded to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance. Moreover, the BME-like cells exhibited an immune quiescent property of BBB endothelial cells by decreasing the expression of adhesion molecules. Therefore, our novel cellular platform could be useful for drug screening and the development of brain-permeable pharmaceuticals.

Forests are essential for sustaining ecosystems, regulating the climate, and providing economic benefits to human society. However, activities such as commercial practices, fuelwood collection, and land use changes have resulted in severe forest degradation and deforestation. Timor-Leste, a small island nation, faces environmental sustainability challenges due to land use changes, limited infrastructure, and agricultural practices. This study proposes a simplified and highly accessible approach to assess deforestation (SHAD) nationally using limited human and non-human resources such as experts, software, and hardware facilities. To assess deforestation in developing countries, we utilize open-source software (Dryad), employ the U-Net deep learning algorithm, and utilize open-source data generated from the Google Earth Engine platform to construct a time-series land cover classification model for Timor-Leste. In addition, we utilize the open-source land cover map as label data and satellite imagery as model training inputs, and our model demonstrates satisfactory performance in classifying time-series land cover. Next, we classify the land cover in Timor-Leste for 2016 and 2021, and verified that the forest classification achieved high accuracy ranging from 0.79 to 0.89. Thereafter, we produced a deforestation map by comparing the two land cover maps. The estimated deforestation rate was 1.9% annually with a primary concentration in the northwestern municipalities of Timor-Leste with dense population and human activities. This study demonstrates the potential of the SHAD approach to assess deforestation nationwide, particularly in countries with limited scientific experts and infrastructure. We anticipate that our study will support the development of management strategies for ecosystem sustainability, climate adaptation, and the conservation of economic benefits in various fields.

Screening campaigns, especially those aimed at modulating enzyme activity, often rely on measuring substrate→product conversions. Unfortunately, the presence of endogenous substrates and/or products can limit one's ability to measure conversions. As well, coupled detection systems, often used to facilitate optical readouts, are subject to interference. Stable isotope labeled substrates can overcome background contamination and yield a direct readout of enzyme activity. Not only can isotope kinetic assays enable early screening, but they can also be used to follow hit progression in translational (pre)clinical studies. Herein, we consider a case study surrounding lipid biology to exemplify how metabolic flux analyses can connect stages of drug development, caveats are highlighted to ensure reliable data interpretations. For example, when measuring enzyme activity in early biochemical screening it may be enough to quantify the formation of a labeled product. In contrast, cell-based and in vivo studies must account for variable exposure to a labeled substrate (or precursor) which occurs via tracer dilution and/or isotopic exchange. Strategies are discussed to correct for these complications. We believe that measures of metabolic flux can help connect structure-activity relationships with pharmacodynamic mechanisms of action and determine whether mechanistically differentiated biophysical interactions lead to physiologically relevant outcomes. Adoption of this logic may allow research programs to (i) build a critical bridge between primary screening and (pre)clinical development, (ii) elucidate biology in parallel with screening and (iii) suggest a strategy aimed at in vivo biomarker development.

BackgroundAdequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea.MethodsA total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient (< 100 μg/L), adequate (100–199 μg/L), more than adequate (200–299 μg/L), mild excessive (300–999 μg/L), and severe excessive (≥ 1000 μg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated.ResultsThe median TSH level was 2.3 μIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 μg/L, with higher levels in boys (684 μg/L vs. 545 μg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (β = − 0.04, p = 0.032 for mild excess; β = − 0.04, p = 0.042 for severe excess) and T3 levels (β = − 8.12, p = 0.009 for mild excess; β = − 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (β = 0.04, p = 0.046).ConclusionExcess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation.

PurposeThis study aimed to assess the feasibility of contrast-enhanced ultrasound (CEUS) for the diagnosis of acute pyelonephritis (APN) in pediatric patients with febrile urinary tract infection (UTI).Materials and methodsBetween March 2019 and January 2021, study participants with suspected UTI were assessed for APN using ultrasound. Parenchymal echogenicity changes, renal pelvis dilatation, and the presence of a focal suspected lesion were assessed using conventional grayscale ultrasound. The presence and location of a decreased perfusion area were evaluated using color Doppler ultrasound (CDUS) and CEUS. Agreement between each ultrasound examination and a 99mTc‒dimercaptosuccinic acid (DMSA) scan was assessed using the κ value, and the most visible period of the lesion was evaluated using CEUS.ResultsThis study enrolled 21 participants (median age, 8.0 months; range, 2.0-61.0 months) with isolated urinary tract pathogens. Five increased parenchymal echotextures (11.9%) and 14 renal pelvic dilatations (33.3%) were confirmed, but no focal lesions were detected on the grayscale images. CDUS and CEUS showed decreased local perfusion suggestive of APN in two and five kidneys, respectively. DMSA scan showed substantial agreement with CEUS findings (κ = 0.80, P = 0.010), but other grayscale and CDUS findings did not agree with DMSA scan results (P > 0.05). All lesions were best observed in the late parenchymal phase on CEUS.ConclusionCEUS can reveal renal perfusion defects in pediatric patients with suspected APN without radiation exposure or sedation; therefore, CEUS may be a feasible and valuable diagnostic technique.

Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson’s Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, often accompanied by extra-skeletal calcification in adult patients. As increased vascular calcification is predicted to increase cardiovascular mortality and morbidity, the revised Kidney Disease: Improving Global Outcomes guidelines recommend avoiding calcium-containing phosphate chelators. However, extra-skeletal calcification is less commonly noticed in pediatric patients. Here, we report our experience of such a complication in pediatric patients receiving maintenance peritoneal dialysis. Extra-skeletal calcification was noticed at the corneas, pelvic cavity, and soft tissues of the lower leg in 4 out of 32 patients on maintenance peritoneal dialysis. These patients experienced the aggravation of extra-skeletal calcifications during peritoneal dialysis, and 2 of them underwent excisional operations. It is required to monitor extra-skeletal calcifications in children on kidney replacement therapy.

Purpose Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness. Methods We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency. Results A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required. Conclusions The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

Background: Ambient air pollution is a pervasive and ubiquitous hazard, which has been linked to premature morbidity and a growing number of morbidity endpoints. Air pollution may be linked to neurodegeneration, and via this or other pathways, to neurodegenerative diseases. Emerging evidence suggests that air pollution may contribute to neurodegenerative diseases such as dementia, Parkinson’s Disease (PD), Multiple Sclerosis (MS) and Motor Neuron Diseases (MND), although this evidence remains inconsistent and very limited for MS and MND. In addition, this evidence base is rapidly emerging and would benefit from a wide and critical synthesis, including a better understanding of heterogeneity. Objectives: In this paper, we present a protocol for a systematic review and meta-analysis and specify our methods a priori. The main aim of the planned systematic review is to answer the question of whether long-term exposure (>1 year) to ambient (outdoor) air pollution (exposure, compared to lower exposure) increases the risk of adult (population) incidence of neurodegenerative diseases (outcomes) in epidemiological observational studies (study design). Another aim is to meta-analyze the associations between long-term exposure to ambient air pollutants and the risk of the selected outcomes and assess the shape of exposure–response functions. To set the stage for the proposed work, we also overview the existing epidemiological evidence in this protocol, but do not critically evaluate it, as these results will be fully presented in the planned systematic review. Search and study eligibility: We will search the electronic databases Medline (via Ovid), Embase (via Ovid), Cochrane Library, Cinahl (via Ebscohost), Global Health (via Ebscohost), PsycINFO (via Ebscohost), Scopus, Web of Science (Core Collection), from inception to October 2022. Eligible studies must contain primary research investigating the link between 1-year + exposure to any outdoor air pollutant, from any source, and dementia, PD, MS, and MND, or dementia subtypes: Alzheimer’s Disease, vascular dementia, and mixed dementia. The search strategy and eligibility criteria are pre-determined and described in full in this protocol. Study appraisal and synthesis methods: Articles will be stored and screened using Rayyan QCRI. Title and abstract screening, full text review, data extraction, risk of bias assessment and data preparation for statistical analysis will be conducted independently by two reviewers using pre-defined forms and criteria, described in this protocol. All these steps will also be piloted and the forms and/or methods adapted if issues arise. Meta-analysis and assessment of the shape of the exposure–response functions will be conducted if four independent exposure-outcomes pairs are available, and the remainder of results will be synthesized in the forms of tables and via a narrative summary. Certainty in the body of evidence will be assessed using the OHAT approach. This protocol describes the planned analysis and synthesis a priori and serves to increase transparency and impact of this systematic review and meta-analysis.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10−5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.

Purpose This study evaluated the diagnostic performance of contrast-enhanced voiding urosonography (ce-VUS) using a second-generation ultrasound contrast agent for the diagnosis of vesicoureteral reflux (VUR) and intrarenal reflux (IRR), and compared it with that of standard fluoroscopic voiding cystourethrography (VCUG). Methods Thirty-two consecutive children from April to October 2019 were included in this study. ce-VUS and VCUG were performed simultaneously by two operators with intravesical infusion of a mixture of ultrasound contrast medium, iodinated contrast medium and water. Two pediatric radiologists independently reviewed the ce-VUS and VCUG images and reported the presence and degree of VUR (grades I-V), and the presence and type of IRR. Results Twenty-seven of 63 urinary systems showed VUR. Interobserver agreement for VUR grading was very good for both examinations (κ=0.87; 95% confidence interval [CI], 0.82 to 0.92 for ce-VUS and κ=0.92; 95% CI, 0.87 to 0.96 for VCUG). The detection rate of VUR showed no significant difference between the two examinations (P=0.370). Four cases of VUR were missed on ce-VUS, while one case of VUR was missed on VCUG. All four false-negative cases on ce-VUS were grade 1 VUR. The two examinations showed very good agreement regarding VUR grading (κ =0.89; 95% CI, 0.81 to 0.96). IRR was more frequently detected with ce-VUS than with VCUG (10 cases with ce-VUS vs. 3 cases with VCUG, P=0.016). Conclusion ce-VUS showed very good agreement with VCUG for detecting grade 2 VUR and above, while grade 1 VUR was sometimes missed with ce-VUS. IRR was more frequently detected with ce-VUS than with VCUG.

Microbiota-derived short-chain fatty acids (SCFAs) are known to stimulate mucin expression in the intestine, which contributes to the gut mucosal immune responses, and the gut mucosal immune system extends to the brain and other organs through several axes. Hypoxia-inducible factors (HIFs), especially HIF-1α, are known to act as the master regulator of mucin expression, however, underlying mechanism of mucin expression during hypoxia by SCFAs remains unclear. In this study, we investigated the mechanism of MUC2 expression by propionate, an SCFA, in intestinal goblet cells. The real time oxygen consumption rate (OCR) and ATPase activity were measured to investigate the induction of hypoxia by propionate. Using 2-dimensional electrophoresis (2-DE), microarray analysis, and siRNA-induced gene silencing, we found that propionate is metabolized via a β-oxidation-like pathway instead of the vitamin B12-dependent carboxylation pathway (also known as the methylmalonyl pathway). We verified the results by analyzing several intermediates in the pathway using LC-MS and GC-MS. Propionate metabolism via the β-oxidation-like pathway leads to the depletion of oxygen and thereby induces hypoxia. Analysis of HIFs revealed that HIF-2α is the primary HIF whose activation is induced by propionate metabolism in a hypoxic environment and that HIF-2α regulates the expression of MUC2. Thus, hypoxia induced during propionate metabolism via a β-oxidation-like pathway specifically activates HIF-2α, stimulating MUC2 production in LS 174 T goblet cells. Our findings show that propionate-induced selective HIF-2α stimulation contributes to intestinal mucosal defense.