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ObjectiveTo evaluate the feasibility and clinical usefulness of deep learning (DL)-accelerated turbo spin echo (TSEDL) sequences relative to standard TSE sequences (TSES) for acute radius fracture patients wearing a splint.MethodsThis prospective consecutive study investigated 50 patients' preoperative wrist MRI scans acquired between July 2021 and January 2022. Examinations were performed at 3 Tesla MRI with body array coils due to the wrist splint. Besides TSES obtained according to the routine protocol, TSEDL sequences for axial T2-, coronal T1-, and coronal PD-weighted TSE sequences were scanned for comparison. For quantitative assessment, the relative signal-to-noise ratio (rSNR), the relative contrast-to-noise ratio (rCNR), and the relative contrast ratio (rCR) were measured. For qualitative assessment, all images were assessed by two independent musculoskeletal radiologists in terms of perceived SNR, image contrast, image sharpness, artifacts disturbing evaluation, overall image quality and diagnostic confidence for injuries using a four- or five-point Likert scale.ResultsThe scan time was shortened approximately by a factor of two for TSEDL compared to TSES. TSEDL images showed significantly better rSNR, rCNR, and rCR values for all sequences, and scored significantly better in terms of both image quality and diagnostic confidence for both readers than TSES images (all p < .05). Interrater reliabilities were in almost perfect agreement.ConclusionThe DL-accelerated technique proved to be very helpful not only to reduce scan time but also to improve image quality for acute painful fracture patients wearing a splint despite using body array coils instead of a wrist-specific coil. Based on our study, the DL-accelerated technique can be very useful for MRI of any part of the extremities in trauma settings just with body array coils.

Although non-prescription anthelmintics are used by many patients as cancer treatment in South Korea, data regarding the experiences or perceptions of these drugs are lacking. This study aimed to investigate the repercussions of non-prescription anthelmintics for cancer treatment and evaluate their perceived effectiveness and adverse effects. This survey included 86 cancer patients, aged 19 years and older, who underwent anthelmintic therapy for cancer. They were recruited from two online communities in South Korea through a structured questionnaire that was provided online. Cancer patients under non-prescription anthelmintic therapy for cancer in South Korea were mostly in their advanced stages and had started the treatment in 2019. About half of the cancer patients had taken non-prescription anthelmintics during their chemotherapy, and 96.5% of them did not inform the clinicians. These participants had a positive perception (79.1%) toward the effectiveness of anthelmintics, as they felt it improved their physical condition. Data on the adverse effects of anthelmintics showed that more than two-third of the participants did not report experiencing any adverse effects. Communication between the clinicians and cancer patients regarding the use of non-prescription anthelmintics should be enhanced to prevent adverse effects.

Although non-prescription anthelmintics are used by many patients as cancer treatment in South Korea, data regarding the experiences or perceptions of these drugs are lacking. This study aimed to investigate the repercussions of non-prescription anthelmintics for cancer treatment and evaluate their perceived effectiveness and adverse effects. This survey included 86 cancer patients, aged 19 years and older, who underwent anthelmintic therapy for cancer. They were recruited from two online communities in South Korea through a structured questionnaire that was provided online. Cancer patients under non-prescription anthelmintic therapy for cancer in South Korea were mostly in their advanced stages and had started the treatment in 2019. About half of the cancer patients had taken non-prescription anthelmintics during their chemotherapy, and 96.5% of them did not inform the clinicians. These participants had a positive perception (79.1%) toward the effectiveness of anthelmintics, as they felt it improved their physical condition. Data on the adverse effects of anthelmintics showed that more than two-third of the participants did not report experiencing any adverse effects. Communication between the clinicians and cancer patients regarding the use of non-prescription anthelmintics should be enhanced to prevent adverse effects.

BackgroundIntraoperative hypertension and blood pressure (BP) fluctuation are known to be associated with negative patient outcomes. During robotic lower abdominal surgery, the patient's abdominal cavity is filled with CO2, and the patient's head is steeply positioned toward the floor (Trendelenburg position). Pneumoperitoneum and the Trendelenburg position together with physiological alterations during anesthesia, interfere with predicting BP changes. Recently, deep learning using recurrent neural networks (RNN) was shown to be effective in predicting intraoperative BP. A model for predicting BP rise was designed using RNN under special scenarios during robotic laparoscopic surgery and its accuracy was tested.MethodsDatabases that included adult patients (over 19 years old) undergoing low abdominal da Vinci robotic surgery (ovarian cystectomy, hysterectomy, myomectomy, prostatectomy, and salpingo-oophorectomy) at Soonchunhyang University Bucheon Hospital from October 2018 to March 2021 were used. An RNN-based model was designed using Python3 language with the PyTorch packages. The model was trained to predict whether hypertension (20% increase in the mean BP from baseline) would develop within 10 minutes after pneumoperitoneum.ResultsEight distinct datasets were generated and the predictive power was compared. The macro-average F1 scores of the datasets ranged from 68.18% to 72.33%. It took only 3.472 milliseconds to obtain 39 prediction outputs.ConclusionsA prediction model using the RNN may predict BP rises during robotic laparoscopic surgery.

BackgroundA high false-negative rate has been reported for the diagnosis of ossification of the posterior longitudinal ligament (OPLL) using plain radiography. We investigated whether deep learning (DL) can improve the diagnostic performance of radiologists for cervical OPLL using plain radiographs.Materials and methodsThe training set consisted of 915 radiographs from 207 patients diagnosed with OPLL. For the test set, we used 200 lateral cervical radiographs from 100 patients with cervical OPLL and 100 patients without OPLL. An observer performance study was conducted over two reading sessions. In the first session, we compared the diagnostic performance of the DL-model and the six observers. The diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC) at the vertebra and patient level. The sensitivity and specificity of the DL model and average observers were calculated in per-patient analysis. Subgroup analysis was performed according to the morphologic classification of OPLL. In the second session, observers evaluated the radiographs by referring to the results of the DL-model.ResultsIn the vertebra-level analysis, the DL-model showed an AUC of 0.854, which was higher than the average AUC of observers (0.826), but the difference was not significant (p = 0.292). In the patient-level analysis, the performance of the DL-model had an AUC of 0.851, and the average AUC of observers was 0.841 (p = 0.739). The patient-level sensitivity and specificity were 91% and 69% in the DL model, and 83% and 68% for the average observers, respectively. Both the DL-model and observers showed decreases in overall performance in the segmental and circumscribed types. With knowledge of the results of the DL-model, the average AUC of observers increased to 0.893 (p = 0.001) at the vertebra level and 0.911 (p < 0.001) at the patient level. In the subgroup analysis, the improvement was largest in segmental-type (AUC difference 0.087; p = 0.002).ConclusionsThe DL-based OPLL detection model can significantly improve the diagnostic performance of radiologists on cervical radiographs.

Standardized instruments are often used to monitor one's progress in tinnitus relief although they were developed to screen and diagnose tinnitus. The need for the development for a tinnitus outcome assessment tool is high in the field of audiology and otolaryngology. The purpose of this study was to develop a tinnitus outcome questionnaire for sound management (listening to sound stimuli for tinnitus relief) and assess its content validity. A total of 32 questions with six domains (Tinnitus characteristics, the impact of tinnitus, tinnitus and hearing issues, handedness, tinnitus management, and sound management outcome) were generated after closely investigating major tinnitus questionnaires used worldwide (i.e. Tinnitus Handicap Inventory and Tinnitus Handicap Questionnaire) as well as literature. Ten healthcare professionals evaluated the appropriateness of the questionnaire items on a five-point Likert scale, where 1 is strongly inappropriate and 5 is strongly appropriate. Content relevance was assessed by computing the content validity index with the cut-off value of 0.75. Each response was first weighted as follows: 1 = 0; 2 = 0.25; 3 = 0.5; 4 = 0.75; and 5 = 1.0. The weighted average was then calculated. Items with a content validity index less than 0.75 were discarded and some items were revised according to the experts' feedback. As a result, 31 out of the 32 items had the content validity index higher than 0.75, indicating that the items are appropriate to obtain information about the six domains. Reflecting the experts' feedback, some questions were revised to be more specific. The study provides a baseline structure regarding potential questions to be included in a tinnitus outcome questionnaire for sound management. Development and standardization of such questionnaire would be a pathway to validating tinnitus relief via sound therapy.

BackgroundPhysicians can find it challenging to decide whether confirmative digital subtraction angiography (DSA) should be performed in patients who present with "suspicious small aneurysm-like structures" on magnetic resonance angiography (MRA). Factors associated with "false positive aneurysms on MRA" (FPAMs)," which are finally confirmed as negative on DSA, have rarely been reported. This study aimed to identify the clinical or radiologic clues indicative of FPAM on DSA.MethodsPatients who had undergone DSA between 2016 and 2019 for suspicious aneurysm-like structures < 5 mm in size on MRA were enrolled. Patient demographics and the details regarding the geometry of the structures were retrospectively reviewed. Univariate and multivariate logistic regression analyses were conducted to identify the associated factors. Receiver operating characteristic curve analysis was performed to assess the clinical implications.ResultsOf the 107 suspicious structures, 46 were indicated as being false positive on DSA (42.96%). Location (positive on C7 and negative on C5-6 ICA) and lower dome to neck ratio were found to be significant parameters in the multivariate analysis. The dome to neck ratio threshold value was 0.99.ConclusionSuspicious aneurysm-like structures located not on C5-6 but on C7 ICA and having wide neck morphologies (dome to neck ratio < 0.99) are highly likely to be negative on DSA.

We propose a machine learning (ML)-based model for predicting cochlear dead regions (DRs) in patients with hearing loss of various etiologies. Five hundred and fifty-five ears from 380 patients (3,770 test samples) diagnosed with sensorineural hearing loss (SNHL) were analyzed. A threshold-equalizing noise (TEN) test was applied to detect the presence of DRs. Data were collected on sex, age, side of the affected ear, hearing loss etiology, word recognition scores (WRS), and pure-tone thresholds at each frequency. According to the cause of hearing loss as diagnosed by the physician, we categorized the patients into six groups: 1) SNHL with unknown etiology; 2) sudden sensorineural hearing loss (SSNHL); 3) vestibular schwannoma (VS); 4) Meniere's disease (MD); 5) noise-induced hearing loss (NIHL); or 6) presbycusis or age-related hearing loss (ARHL). To develop a predictive model, we performed recursive partitioning and regression for classification, logistic regression, and random forest. The overall prevalence of one or more DRs in test ears was 20.36% (113 ears). Among the 3,770 test samples, the overall frequency-specific prevalence of DR was 6.7%. WRS, pure-tone thresholds at each frequency, disease type (VS or MD), and frequency information were useful for predicting DRs. Sex and age were not associated with detecting DRs. Based on these results, we suggest possible predictive factors for determining the presence of DRs. To improve the predictive power of the model, a more flexible model or more clinical features, such as the duration of hearing loss or risk factors for developing DRs, may be needed.

This study directly compared the performance of a contralateral routing of signal (CROS)/bilateral routing of signal (BiCROS) and a soft-band bone-anchored hearing aid (BAHA) in patients with unilateral sensorineural hearing loss (SNHL) and assessed the relationship between hearing aid benefits and personal factors. Participants with unilateral SNHL were prospectively enrolled in the study and were tested under the following three conditions: unaided, with CROS/BiCROS, and with soft-band BAHA. Sound localization, consonant, hearing in noise, and psychoacoustic tests were performed. Pseudobinaural benefits (e.g., squelch, summation, and head shadow effect) were obtained in both the CROS/BiCROS and soft-band BAHA conditions and compared to the unaided condition. Sound localization ability was not improved in either the CROS/BiCROS condition or soft-band BAHA condition. Rather, sound localization ability was significantly decreased in the CROS/BiCROS setting. A CROS/BiCROS hearing aid and a soft-band BAHA provided additional benefit for speech-in-noise perception when target speech was directed to the impaired ear side. The CROS/BiCROS hearing aid was superior to the soft-band BAHA one in decreasing the head shadow effect, but it appeared to have a negative effect when the noise was delivered to the better ear. The positive and negative effects of CROS/BiCROS for localization and speech perception were significantly correlated with personal factors such as age, hearing threshold in the better ear, and unaided psychoacoustic performances. Despite the lack of device acclimatization, we believe that this study provides counseling information for hearing aid clinics to use in the context of patients with unilateral SNHL.

Burkholderia pseudomallei is an environmental bacterium that causes melioidosis, a major community-acquired infection in tropical regions. Melioidosis presents with a range of clinical symptoms, is often characterized by a robust inflammatory response, may relapse after treatment, and results in high mortality rates. Lipopolysaccharide (LPS) of B. pseudomallei is a potent immunostimulatory molecule comprised of lipid A, core, and O-polysaccharide (OPS) components. Four B. pseudomallei LPS types have been described based on SDS-PAGE patterns that represent the difference of OPS-type A, type B, type B2 and rough LPS. The majority of B. pseudomallei isolates are type A. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) followed by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QqTOF MS) and gas chromatography to characterize the lipid A of B. pseudomallei within LPS type A isolates. We determined that B. pseudomallei lipid A is represented by penta- and tetra-acylated species modified with 4-amino-4-deoxy-arabinose (Ara4N). The MALDI-TOF profiles from 171 clinical B. pseudomallei isolates, including 68 paired primary and relapse isolates and 35 within-host isolates were similar. We did not observe lipid A structural changes when the bacteria were cultured in different growth conditions. Dose-dependent NF-κB activation in HEK cells expressing TLR4 was observed using multiple heat-killed B. pseudomallei isolates and corresponding purified LPS. We demonstrated that TLR4-dependent NF-κB activation induced by heat-killed bacteria or LPS prepared from OPS deficient mutant was significantly greater than those induced by wild type B. pseudomallei. These findings suggest that the structure of B. pseudomallei lipid A is highly conserved in a wide variety of clinical and environmental circumstances but that the presence of OPS may modulate LPS-driven innate immune responses in melioidosis.

BACKGROUND:A wider angle between the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) has been suggested to induce plaque formation in the arterial system via changes in shear stress. However, the relationship between the left main coronary artery (LM)-LAD angle and LAD stenosis has not been investigated. Therefore, we aimed to evaluate the associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS:Coronary computed tomography angiographies (CTAs) of 201 patients with suspected coronary artery disease were analyzed. Angle measurements were performed twice by experts using CTA images, and the values were averaged. The patients were divided into two groups, based on the presence of significant LAD stenosis (luminal diameter narrowing ≥50%) on CTA. RESULTS:The mean LM-LAD and LAD-LCX angles were 37.46° and 63.04°, respectively. The LM-LAD and LAD-LCX angles of the group with significant LAD stenosis were significantly wider than that of the group with nonsignificant LAD stenosis (P

MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulosa cell. In each case, mRNAs were up or down-regulated after treatments with miR-146a C or G and miR-196a2 T or C. We found that miR-146a led to a significantly altered regulation of the mRNA levels of FOXO3, FOXL2 and CCND2 compared to controls. We also found that the polymorphisms of miR-146a led to a significantly altered regulation of CCND2 and FOXO3. Our results suggest that miR-146aC>G and miR-196a2T>C can regulate the levels of many of their target transcripts. In addition, specific target genes of miR-146aC>G polymorphisms may be involved in granulosa cell regulation.

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats.

Several natural products containing tannins are used as traditional medicines for treatment of constipation; however, their pharmacological mechanism is not well understood. The laxative effects of gallotannin-enriched extract isolated from Galla Rhois (GEGR) were investigated using a constipation model induced by loperamide (Lop) injection. After analysis for antioxidant activity of GEGR, alterations in the excretion parameters, histological structure, mucin secretion, and related protein levels were measured in the transverse colon of Sprague Dawley (SD) rats with Lop-induced constipation following treatment with 250, 500 and 1,000 mg/ml of GEGR. The number and weight of feces increased significantly by 48-79% and 128-159%, respectively, in the Lop+GEGR treated group relative to the Lop+vehicle treated group, while food intake and water consumption were maintained at a constant level. The thickness of mucosa, muscle and flat luminal surface, as well as the number of goblet cells and crypt of lieberkuhn were enhanced in the Lop+GEGR treated group. Moreover, mucin secretion increased significantly in a dose dependent manner in the Lop+GEGR treated group. Furthermore, the downstream signaling pathway of the muscarinic acetylcholine receptors (mAChR) M2 and M3 was recovered by GEGR treatment, although the expression level varied. The levels of Gα expression and inositol triphosphate (IP3) concentration were also recovered in the Lop+GEGR treated group relative to the Lop+vehicle treated group. The results of the present study provide strong evidence that tannins distributed in various medicinal plants are important candidates for improving chronic constipation induced by Lop treatment in animal models.

Although intensive statin therapy is recommended for high risk patients, evidence of its benefit in patients with stable coronary artery disease (CAD) and very low low-density lipoprotein-cholesterol (LDL-C) has been very rare. In this study, we investigated whether higher statin intensity reduces cardiovascular risks in this population.In this retrospective study, a total of 5234 patients with stable CAD were screened at three tertiary hospitals in Korea; 449 patients (mean age: 65 years, male: 69%) with LDL-C

Evidence of visual-auditory cross-modal plasticity in deaf individuals has been widely reported. Superior visual abilities of deaf individuals have been shown to result in enhanced reactivity to visual events and/or enhanced peripheral spatial attention. The goal of this study was to investigate the association between visual-auditory cross-modal plasticity and speech perception in post-lingually deafened, adult cochlear implant (CI) users. Post-lingually deafened adults with CIs (N = 14) and a group of normal hearing, adult controls (N = 12) participated in this study. The CI participants were divided into a good performer group (good CI, N = 7) and a poor performer group (poor CI, N = 7) based on word recognition scores. Visual evoked potentials (VEP) were recorded from the temporal and occipital cortex to assess reactivity. Visual field (VF) testing was used to assess spatial attention and Goldmann perimetry measures were analyzed to identify differences across groups in the VF. The association of the amplitude of the P1 VEP response over the right temporal or occipital cortex among three groups (control, good CI, poor CI) was analyzed. In addition, the association between VF by different stimuli and word perception score was evaluated. The P1 VEP amplitude recorded from the right temporal cortex was larger in the group of poorly performing CI users than the group of good performers. The P1 amplitude recorded from electrodes near the occipital cortex was smaller for the poor performing group. P1 VEP amplitude in right temporal lobe was negatively correlated with speech perception outcomes for the CI participants (r = -0.736, P = 0.003). However, P1 VEP amplitude measures recorded from near the occipital cortex had a positive correlation with speech perception outcome in the CI participants (r = 0.775, P = 0.001). In VF analysis, CI users showed narrowed central VF (VF to low intensity stimuli). However, their far peripheral VF (VF to high intensity stimuli) was not different from the controls. In addition, the extent of their central VF was positively correlated with speech perception outcome (r = 0.669, P = 0.009). Persistent visual activation in right temporal cortex even after CI causes negative effect on outcome in post-lingual deaf adults. We interpret these results to suggest that insufficient intra-modal (visual) compensation by the occipital cortex may cause negative effects on outcome. Based on our results, it appears that a narrowed central VF could help identify CI users with poor outcomes with their device.

Uncoordinated 51-like kinase 2 (ULK2), a member of the serine/threonine kinase family, plays an essential role in the regulation of autophagy in mammalian cells. Given the role of autophagy in normal cellular homeostasis and in multiple diseases, improved mechanistic insight into this process may result in the development of novel therapeutic approaches. Here, we present evidence that ULK2 associates with karyopherin beta 2 (Kapβ2) for its transportation into the nucleus. We identify a potential PY-NLS motif ((774)gpgfgssppGaeaapslRyvPY(795)) in the S/P space domain of ULK2, which is similar to the consensus PY-NLS motif (R/K/H)X(2-5)PY. Using a pull-down approach, we observe that ULK2 interacts physically with Kapβ2 both in vitro and in vivo. Confocal microscopy confirmed the co-localization of ULK2 and Kapβ2. Localization of ULK2 to the nuclear region was disrupted by mutations in the putative Kapβ2-binding motif (P794A). Furthermore, in transient transfection assays, the presence of the Kapβ2 binding site mutant (the cytoplasmic localization form) was associated with a substantial increase in autophagy activity (but a decrease in the in vitro serine-phosphorylation) compared with the wild type ULK2. Mutational analysis showed that the phosphorylation on the Ser1027 residue of ULK2 by Protein Kinase A (PKA) is the regulatory point for its functional dissociation from Atg13 and FIP 200, nuclear localization, and autophagy. Taken together, our observations indicate that Kapβ2 interacts with ULK2 through ULK2's putative PY-NLS motif, and facilitates transport from the cytoplasm to the nucleus, depending on its Ser1027 residue phosphorylation by PKA, thereby reducing autophagic activity.

To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported. Anti-globular-head-domain antibodies block either influenza virus receptor binding to the host cell or progeny virion release from the host cell. Anti-stem region antibodies hinder the membrane fusion process or induce antibody-dependent cytotoxicity to infected cells. In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody. This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

A culture-based colony counting method is the most widely used analytical technique for monitoring bioaerosols in both indoor and outdoor environments. However, this method requires several days for colony formation. In this study, our goal was fast monitoring (Sampling: 3 min, Detection: < 1 min) of indoor bioaerosol concentrations with ATP bioluminescence assay using a bioaerosol sampler. For this purpose, a novel hand-held electrostatic rod-type sampler (110 mm wide, 115 mm long, and 200 mm tall) was developed and used with a commercial luminometer, which employs the Adenosine triphosphate (ATP) bioluminescence method. The sampler consisted of a wire-rod type charger and a cylindrical collector, and was operated with an applied voltage of 4.5 kV and a sampling flow rate of 150.7 lpm. Its performance was tested using Staphylococcus epidermidis which was aerosolized with an atomizer. Bioaerosol concentrations were measured using ATP bioluminescence method with our sampler and compared with the culture-based method using Andersen cascade impactor under controlled laboratory conditions. Indoor bioaerosol concentrations were also measured using both methods in various indoor environments. A linear correlation was obtained between both methods in lab-tests and field-tests. Our proposed sampler with ATP bioluminescence method may be effective for fast monitoring of indoor bioaerosol concentrations.

Spectrotemporal modulation (STM) detection performance was examined for cochlear implant (CI) users. The test involved discriminating between an unmodulated steady noise and a modulated stimulus. The modulated stimulus presents frequency modulation patterns that change in frequency over time. In order to examine STM detection performance for different modulation conditions, two different temporal modulation rates (5 and 10 Hz) and three different spectral modulation densities (0.5, 1.0, and 2.0 cycles/octave) were employed, producing a total 6 different STM stimulus conditions. In order to explore how electric hearing constrains STM sensitivity for CI users differently from acoustic hearing, normal-hearing (NH) and hearing-impaired (HI) listeners were also tested on the same tasks. STM detection performance was best in NH subjects, followed by HI subjects. On average, CI subjects showed poorest performance, but some CI subjects showed high levels of STM detection performance that was comparable to acoustic hearing. Significant correlations were found between STM detection performance and speech identification performance in quiet and in noise. In order to understand the relative contribution of spectral and temporal modulation cues to speech perception abilities for CI users, spectral and temporal modulation detection was performed separately and related to STM detection and speech perception performance. The results suggest that that slow spectral modulation rather than slow temporal modulation may be important for determining speech perception capabilities for CI users. Lastly, test-retest reliability for STM detection was good with no learning. The present study demonstrates that STM detection may be a useful tool to evaluate the ability of CI sound processing strategies to deliver clinically pertinent acoustic modulation information.

PURPOSE:The purpose of this study was to compare the diagnostic performance of SPECT/CT and MRI in patients with ankle and foot pain, with regard to the lesion types. MATERIALS AND METHODS:Fifty consecutive patients with ankle and foot pain, who underwent 99mTc-MDP SPECT/CT and MRI, were retrospectively enrolled in this study. Symptomatic lesions were determined based on clinical examination and response to treatment. On MRI and SPECT/CT, detected lesions were classified as bone, ligament/tendon, and joint lesions. Uptake on SPECT/CT was assessed using a 4-grade system. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of SPECT/CT and MRI were evaluated in all detected lesions and each lesion type. Diagnostic value of uptake grade was analyzed using receiver-operating characteristics (ROC) curve analysis, and diagnostic performance was compared using Chi-square or McNemar tests. RESULTS:In overall lesions, the sensitivity, PPV and NPV of SPECT/CT for symptomatic lesions were 93%, 56%, 91%, and they were 98%, 48%, 95% for MRI. There was no significant difference between SPECT/CT and MRI. However, the specificity of SPECT/CT was significantly higher than that of MRI (48% versus 24%, P = 0.016). Uptake grade on SPECT/CT was significantly higher in symptomatic lesions (P < 0.001), and its area under curve on ROC analysis was 0.787. In the analysis of each lesion type, the specificity of SPECT/CT was poor in joint lesions compared with other lesion types and MRI (P < 0.001, respectively). MRI exhibited lower specificity than SPECT/CT in bone lesions (P = 0.004) and ligament/tendon lesions (P < 0.001). CONCLUSIONS:SPECT/CT has MRI-comparable diagnostic performance for symptomatic lesions in ankle and foot pain patients. SPECT/CT and MRI exhibit different diagnostic specificity in different lesion types. SPECT/CT may be used as a complementary imaging method to MRI for enhancing diagnostic specificity.

To prospectively evaluate the changes in fatty acid concentration after administrating a 60% high-fat diet to a non-alcoholic fatty liver disease rat model and to perform a correlation analysis between fatty acid with molecular diffusion (Dtrue), perfusion-related diffusion (Dfast), and perfusion fraction (Pfraction).This prospective study was approved by the appropriate ethics committee. Ten male Sprague-Dawley rats were fed a 60% high-fat diet until the study was finished. Point-resolved spectroscopy sequence 1H-MRS with TR = 1,500 msec, TE = 35 msec, NEX = 64, and 8×8×8 mm3 voxel was used to acquire magnetic resonance spectroscopy (MRS) data. Diffusion-weighted imaging was performed on a two-dimensional multi-b value spin echo planar image with the following parameters: repetition time msec/echo time msec, 4500 /63; field of view, 120×120 msec2; matrix, 128×128; section thickness, 3 mm; number of repetition, 8; and multiple b value, 0, 25, 50, 75, 100, 200, 500, 1000 sec/mm2. Baseline magnetic resonance imaging and magnetic resonance spectroscopy data (control) were acquired. 1H proton MRS and diffusion-weighted imaging were obtained every 2 weeks for 8 weeks. The individual contributions of the true molecular diffusion and the incoherent motions of water molecules in the capillary network to the apparent diffusion changes were estimated using a least-square nonlinear fitting in MatLab. A Wilcoxon signed-rank test with the Kruskal-Wallis test was used to compare each week's fatty acid mean quantification. Spearman's correlation coefficient was used to evaluate the correlation between each fatty acid (e.g., total lipid (TL), total saturated fatty acid (TSFA), total unsaturated fatty acid (TUSFA), total unsaturated bond (TUSB), and polyunsaturated bond (PUSB)) and intravoxel incoherent motion (IVIM) mapping images (e.g., Dtrue, Dfast, and Pfraction).The highest mean TL value was at week 8 (0.278 ± 0.10) after the administration of the 60% high-fat diet, followed by weeks 6, 4, 2, and 0. The concentration level (16.99±2.29) of TSFA at week 4 was the highest. No significant differences in the concentrations of TUSFA, TUSB, or PUSB were observed in different weeks.After the administration of the 60% high-fat diet in nonalcoholic fatty liver disease model, TL and TSFA depositions had significant changes. The mean concentrations of TUSFA, TUSB, PUSB did not significantly change. Total unsaturated fatty acid and polyunsaturated bond showed positive correlations with Dtrue and Pfraction.

To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats.

Grape seed proanthocyanidin extract (GSPE) is a natural flavonoid that exerts anti-inflammatory properties. Obesity is an inflammatory condition and inflammatory cells and their secretion of pro-inflammatory molecules contribute to the pathogenesis of obesity. Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by inflammation of joints lined by synovium. Previously, we demonstrated that obesity augmented arthritis severity in collagen induced arthritis (CIA), a murine model of human RA. Here, we investigated whether oral administration of GSPE showed antiobesity and anti-arthritic effects in high-fat diet-induced obese (DIO) mice and in obese CIA mice, respectively. The pathophysiologic mechanisms by which GSPE attenuates weight gain and arthritis severity in vivo were also investigated. In DIO mice, GSPE administration significantly inhibited weight gain, reduced fat infiltration in liver and improved serum lipid profiles. The antiobesity effect of GSPE was associated with increased populations of regulatory T (Treg) cells and those of decreased Th17 cells. Decrease of Th17 cells was associated with significant inhibition of their key transcriptional factors, pSTAT3(Tyr705) and pSTAT3(Ser727). On the contrary, GSPE-induced Treg induction was associated with enhanced pSTAT5 expression. To identify the anti-arthritis effects of GSPE, GSPE was given orally for 7 weeks after type II collagen immunization. GSPE treatment significantly attenuated the development of autoimmune arthritis in obese CIA model. In line with DIO mice, GSPE administration decreased Th17 cells and reciprocally increased Treg cells by regulating STAT proteins in autoimmune arthritis model. The expressions of pro-inflammatory cytokines and nitrotyrosine in synovium were significantly inhibited by GSPE treatment. Taken together, GSPE functions as a reciprocal regulator of T cell differentiation - suppression of Th17 cells and induction of Tregs in both DIO and obese CIA mice. GSPE may act as a therapeutic agent to treat immunologic diseases related with enhanced STAT3 activity such as metabolic disorders and autoimmune diseases.

Autosomal dominant non-syndromic hearing loss (AD-NSHL) is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES) and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP) chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A) in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15) described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3(rd) alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL.

OBJECTIVE: To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA). MATERIALS AND METHODS: OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry. RESULTS: Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment. CONCLUSION: CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.