Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Dux facilitates post-implantation development, but is not essential for zygotic genome activation†.

Double homeobox genes are unique to eutherian mammals. It has been proposed that the DUXC clade of the double homeobox gene family, which is present in multicopy long tandem arrays, plays an essential role in zygotic genome activation (ZGA). We generated a deletion of the tandem array encoding the DUXC gene of mouse, Double homeobox (Dux), and found it surprisingly to be homozygous viable and fertile. We characterize the embryonic development and ZGA profile of knockout (KO) embryos, finding that zygotic genome activation still occurs, with only modest alterations in 2-cell embryo gene expression, no defect in in vivo preimplantation development, but an increased likelihood of post-implantation developmental failure, leading to correspondingly smaller litter sizes in the KO strain. While all known 2-cell specific Dux target genes are still expressed in the KO, a subset is expressed at lower levels. These include numerous genes involved in methylation, blastocyst development, and trophectoderm/placental development. We propose that rather than driving ZGA, which is a process common throughout the animal kingdom, DUXC genes facilitate a process unique to eutherian mammals, namely the post-implantation development enabled by an invasive placenta.

Microstructural white matter alterations in patients with drug induced parkinsonism.

Drug-induced parkinsonism (DIP) is the second most common etiology of parkinsonism. And yet, there is little information on structural imaging in DIP to elucidate the accurate underlying pathomechanisms. To investigate microstructural white matter (WM) in patients with DIP using diffusion tensor image and to determine its relationship to severity of parkinsonian motor symptoms and cognitive function. A total of 42 patients with DIP, 65 with Parkinson's disease, and 33 control subjects were recruited from a movement disorders outpatient clinic. We performed comparative analysis of fractional anisotropy (FA) and mean diffusivity (MD) values among groups using tract-based spatial statistics. Correlation analysis between WM integrity and parkinsonian motor symptoms and cognitive performance was also performed in DIP patients using voxel-wise statistical analysis. DIP patients had significantly lower FA and higher MD values over widespread WM areas than control subjects. The patients with DIP had poor cognitive performance relative to control subjects, which correlated well with WM properties. Additionally, the parkinsonian motor symptoms were negatively correlated with FA values. In contrast, exposure time to the offending drugs prior to the development of parkinsonism or duration of parkinsonism showed no significant association with FA or MD values. The present study demonstrates that disruption of the WM microstructure is extensive in patients with DIP, and it is correlated with clinical parameters of parkinsonism and cognitive performance. This suggests that DIP may be reflective of underlying abnormality of microstructural WM. Hum Brain Mapp 38:6043-6052, 2017. © 2017 Wiley Periodicals, Inc.

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration.

Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

Mammographic density defined by higher than conventional brightness threshold better predicts breast cancer risk for full-field digital mammograms.

INTRODUCTION: When measured using the computer-assisted method CUMULUS, mammographic density adjusted for age and body mass index predicts breast cancer risk. We asked if new mammographic density measures defined by higher brightness thresholds gave better risk predictions. METHODS: The Korean Breast Cancer Study included 213 women diagnosed with invasive breast cancer and 630 controls matched for age at full-field digital mammogram and menopausal status. Mammographic density was measured using CUMULUS at the conventional threshold (Cumulus), and in effect at two increasingly higher thresholds, which we call Altocumulus and Cirrocumulus, respectively. All measures were Box-Cox transformed and adjusted for age, body mass index, menopausal status and machine. We used conditional logistic regression to estimate the change in Odds PER standard deviation of transformed and Adjusted density measures (OPERA). The area under the receiver operating characteristic curve (AUC) was estimated. RESULTS: Corresponding Altocumulus and Cirrocumulus density measures were correlated with Cumulus measures (r approximately 0.8 and 0.6, respectively). Altocumulus and Cirrocumulus measures were on average 25% and 80% less, respectively, than the Cumulus measure. For dense area, the OPERA was 1.18 (95% confidence interval: 1.01-1.39, P = 0.03) for Cumulus; 1.36 (1.15-1.62, P < 0.001) for Altocumulus; and 1.23 (1.04-1.45, P = 0.01) for Cirrocumulus. After fitting the Altocumulus measure, the Cumulus measure was no longer associated with risk. After fitting the Cumulus measure, the Altocumulus measure was still associated with risk (P = 0.001). The AUCs for dense area was 0.59 for the Altocumulus measure, greater than 0.55 and 0.57 for the Cumulus and Cirrocumulus measures, respectively (P = 0.001). Similar results were found for percentage dense area measures. CONCLUSIONS: Altocumulus measures perform better than Cumulus measures in predicting breast cancer risk, and Cumulus measures are confounded by Altocumulus measures. The mammographically bright regions might be more aetiologically important for breast cancer, with implications for biological, molecular, genetic and epidemiological research and clinical translation.

Target genes involved in antiproliferative effect of modified ginseng extracts in lung cancer A549 cells.

Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Panax ginseng has long been used to treat cancer and other diseases worldwide. Most of the pharmacological actions of ginseng are attributed to a variety of ginsenosides, which are often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng was increased after enzymatic processing of ginseng saponin (50% inhibitory concentration, >70 µg/ml). To elucidate the mechanism by which modified ginseng extract (MGX) induced cell death in human lung cancer cells, the gene expression profiles of A549 cells regulated by MGX were assayed using Agilent PrimeView Human Gene Expression Arrays. The expression of 17 genes involved in the regulation of cell signaling, cell metabolism, transport, and cytoskeleton-regulation was up-regulated, whereas the expression of 16 genes implicated in invasion and metastasis and cellular metabolism was down-regulated in MGX-treated A549 cells. Moreover, nuclear staining with 4',6-diamidino-2-phenylindole revealed that MGX clearly caused nuclear condensation and fragmentation which are observed in apoptosis cell. These results elucidate crucial anticancer mechanisms of MGX and provide potential new targets for the assessment of anticancer activity of MGX.

Adaptive Formation Control of Electrically Driven Nonholonomic Mobile Robots With Limited Information.

We present a leader-follower-based adaptive formation control method for electrically driven nonholonomic mobile robots with limited information. First, an adaptive observer is developed under the condition that the velocity measurement is not available. With the proposed adaptive observer, the formation control part is designed to achieve the desired formation and guarantee the collision avoidance. In addition, neural network is employed to compensate the actuator saturation, and the projection algorithm is used to estimate the velocity information of the leader. It is shown, by using the Lyapunov theory, that all errors of the closed-loop system are uniformly ultimately bounded. Simulation results are presented to illustrate the performance of the proposed control system.

Nasopharyngeal electrodes in temporal lobe epilepsy: A reappraisal of their diagnostic utility.

OBJECTIVE: To compare electroencephalography (EEG) recordings with nasopharyngeal electrodes (NPEs) plus anterior temporal electrodes (ATEs) (NPE recordings) and those with only ATEs (non-NPE recordings) for the detection of interictal epileptiform discharges (IEDs) in patients with suspected temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed the initial EEGs of 229 patients that were recorded simultaneously with ATEs and NPEs in addition to the electrodes of the 10-20 system of electrode placement. Two data sets of NPE and non-NPE recordings were reviewed independently by three interpreters with differing degrees of experience. Discordant findings in the interpretation among the three interpreters were resolved by a consensus to yield final results. RESULTS: IEDs were detected in 76.4% of patients with NPE recordings compared to 55.5% with non-NPE recordings (p < 0.01). Bilateral independent IEDs were found in 26.2% and 11.4% of EEGs with NPE and non-NPE recordings (p < 0.01). The degree of agreement for the detection of IEDs among the three interpreters was higher with the NPE than with non-NPE recordings (κappa score, 0.70 vs. 0.54). The increased diagnostic yield of NPE recordings for the detection of IEDs was particularly prominent in patients with mesial and non-lesional TLEs. CONCLUSIONS: EEG recordings using NPEs are useful to improve the sensitivity and level of agreement among interpreters for the detection of IEDs in patients with TLE. SIGNIFICANCE: NPE recordings may be recommended in routine EEGs for the evaluation of patients with suspected TLE.

A survey to explore the psychological impact of the COVID-19 pandemic on radiation therapists in Norway and Canada: A tale of two countries.

INTRODUCTION: Several studies have demonstrated the psychological impact of the COVID-19 pandemic on health care providers. However, there is little known about how the COVID-19 pandemic has impacted radiation therapists (RTs) in Norway or Canada. The aim of this investigation was to study the psychological impact of working during the COVID-19 pandemic among RTs in Canada and Norway. METHODS: Online surveys were administered to a convenience sample of RTs and RT department managers. Approximately 2000 and 300 RTs were invited to participate from Canada and Norway, respectively. The RT survey collected information on demographics, work-related stressors, psychological impact, quality of life, and workplace support programmes. The RT manager survey collected information on departmental changes, patient volumes, staff shortages and redeployment, personal protective equipment, and infection control measures. Descriptive analysis, group comparisons and logistic regression were used to examine the impact of COVID-19 on RTs in the two countries, while open-ended questions were examined through thematic analysis. RESULTS: Work-related stress and anxiety were prevalent among Canadian (n = 155) and Norwegian RTs (n = 124), with Canadian RTs reporting higher levels. Fear of transmission, changes in PPE usage, and changes in staffing were reported as the most frequent work-related stressors. Themes related to working during the pandemic included: generalised anxiety; physical, emotional and cognitive symptoms of stress; and loneliness, as well as negative impact on health and quality of relationships. Survey findings from RT department managers in Canada (n = 12) and Norway (n = 13) suggest that the pandemic had an organisational impact on RT departments due to implemented infection control measures and changes in staffing. CONCLUSION: The COVID-19 pandemic has led to similar stressors amongst Canadian and Norwegian RTs but relatively higher levels of psychological impact among Canadian RTs. Findings demonstrate the importance of mental health support programmes in the workplace to mitigate the psychological impact of the COVID-19 pandemic on RTs.

Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia.

OBJECTIVE: To investigate whether adding rifampicin to vancomycin could cure more patients with nosocomial methicillin-resistant Staphylococcus aureus pneumonia compared with vancomycin-only. DESIGN: Prospective randomized open-label study. SETTING: Medical intensive care unit in Seoul, Korea. PATIENTS: Ninety-three of 183 patients with Gram-positive nosocomial pneumonia. INTERVENTIONS: The enrolled patients with subsequently documented methicillin-resistant Staphylococcus aureus pneumonia (modified intention-to-treat population) were treated with vancomycin (1 g intravenous every 12 hrs) plus rifampicin (300 mg twice daily by mouth) (n = 41) or with vancomycin-only (n = 42). The intended treatment (at least 5 days) was completed in 30 patients in the vancomycin plus rifampicin group and 34 patients in the vancomycin-only group (per protocol population). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the clinical cure rate on day 14 of treatment. The secondary outcomes were intensive care unit mortality on days 28 and 60, and microbiological eradication on day 14. The clinical cure rate in the modified intention-to-treat population was 53.7% (22 of 41) in the vancomycin plus rifampicin group, and 31.0% (13 of 42) in the vancomycin-only group (p = .047), and the respective rates in the per protocol population were 63.3% (19 of 30) and 38.2% (13 of 34) (p = .079). The respective mortality rates were nine (22.0%) of 41 and 16 (38.1%) of 42 on day 28 (p = .151), and 11 (26.8%) of 41 and 21 (50.0%) of 42 on day 60 (p = .042). The microbiological eradication rate did not differ between groups (p = .472). CONCLUSIONS: Vancomycin plus rifampicin seems to be more effective than vancomycin alone in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia.

Quality of life constructs of Chinese people living with HIV/AIDS.

A range of quality of life (QOL) measurements specific for people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) are available. They were, however, developed before or at about the time of introducing highly active antiretroviral therapy (HAART) and there has been very little measurement developed from a Chinese perspective. A study was therefore undertaken and we report our findings of the first phase, in which Chinese people living with HIV/AIDS in Hong Kong were asked to explain their perceptions of QOL so as to identify their construct of QOL using a qualitative approach. Thirty-six participants, thirty males and six females, of mixed demographic and disease-related characteristics were recruited through purposive sampling. Following thematic analysis, nine QOL constructs emerged which included perceptions of adaptation and coping, physical health, stigmatization and discrimination, HIV care services, antiretroviral therapy, sexual relationships, relationships with family and friends, work and money, and pleasure and contentment. When comparing these constructs with those of Western populations, they contain more components on focusing psychosocial and spiritual aspects but less on functional status and HIV-related symptoms. The differences may not be attributed by cultural variations alone but also by the dynamic nature of QOL. Since there has been a rapid evolution of HIV medicine, instrument developers may need to regularly review and update measures of QOL. The subjective perceptions and experiences of targeted population should be addressed. Our findings also suggest the need of maintaining tailor-made psychosocial support services for HIV-infected people despite general reduction of morbidity and mortality from HAART.

Safety of antimicrobial de-escalation for culture-negative severe pneumonia.

PURPOSE: This study investigated the outcomes of antimicrobial de-escalation (ADE) based on mortality and the incidence of multi-drug resistant (MDR) pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis and septic shock. MATERIALS AND METHODS: We retrospectively analyzed patients diagnosed with severe pneumonia requiring intensive care unit (ICU) admission and possessing negative microbiological culture results at a tertiary referral hospital in South Korea from March 2008 to July 2018. RESULTS: We identified 107 patients with culture-negative pneumonia. The Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) mean scores were 20.3 ±â€¯8.6 and 9.6 ±â€¯3.3, respectively. Among the patients, 40 (37.4%) underwent ADE. The APACHE II, SOFA, and follow-up SOFA scores did not differ significantly between the groups, and no differences were found in ICU mortality and MDR pathogen occurrence (27.5% vs 41.8%, P = .137 and 15.0% vs 16.9% P = .794, respectively). CONCLUSIONS: We observed similar ICU mortality and MDR pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis/shock regardless of whether they received ADE. Additionally, ADE lowered the antimicrobial burden.

Trends in Palate Surgery for Obstructive Sleep Apnea in Korea Over the Past 12 Years

Background and Objectives@#In the past, palate surgery, such as uvulopalatopharyngoplasty (UPPP), was widely performed to treat obstructive sleep apnea (OSA). However, since the introduction of reimbursement for positive airway pressure (PAP) therapy in 2018, it is believed that the frequency of these operations has significantly declined. Despite this, there are currently no definitive data to support this assertion. @*Methods@#We examined the number of palate operations conducted by utilizing medical statistical data from the Health Insurance Review and Assessment Service (HIRA) Bigdata Open portal. Within this system, we queried UPPP (Q2196), UPPP_complex (Q2195), and uvulectomy (Q2197), and collected data spanning from 2010 to 2021. The data were then analyzed according to hospital type, sex, and age groups. @*Results@#In total, 2,728 palate operations were performed in 2010; this number peaked at 4,330 cases in 2014, and then steadily decreased to 3,096 cases in 2021. Of the operations in 2010, 1,892 were conducted in general hospitals, while 836 took place in primary hospitals and clinics. However, by 2021, the number of operations performed in general hospitals had decreased to 1,002, while those performed in primary hospitals and clinics had increased to 2,093. The most common age group for these operations was 30–39 for men and 40–49 for women. Since 2019, the proportion of palate operations relative to the number of OSA patients has decreased. @*Conclusion@#The frequency of palate surgery in Korea started to decrease after 2014. Despite this, there was an increase in the number of these operations performed in hospitals and clinics, with middle-aged patients being the primary recipients. The ratio of palate operations to OSA patients has shown a notable decrease after the introduction of reimbursement of polysomnography and PAP therapy.

Professional self-concept, self-leadership, job stress and fatigue on clinical competence of dental hygienists / 대한구강보건학회지

Objectives@#This study examines the relationship of dental hygienists’ professional self-concept, self-leadership, job stress, and fatigue with their clinical competence in order to identify factors that can improve clinical competence. This study is intended to provide basic information to develop educational programs for dental hygienist’s clinical competence. @*Methods@#The self-administered questionnaire survey was conducted with 243 dental hygienists working at dental clinics in Gwangju and Jeonnam from August 14, 2017 to September 9, 2017.The data regarding the general characteristics, professional self-concept, self-leadership, job stress and fatigue, and clinical competence were collected, and analyzed through independent t-tests, one-way analysis of variance (ANOVA), Pearson’s correlation coefficient, and multiple regression analysis using the SPSS Windows ver. 22.0. @*Results@#High professional self-concept (r=0.54) and self-leadership(r=0.48) were associated with high clinical competence. High self-leadership (r=0.53) was associated with high professional selfconcept. High fatigue(r=―0.21) was associated with low professional self-concept(P<0.01). The highest factor influencing clinical competence was professional self-concept, followed by selfleadership, total clinical experience, education level, and fatigue (P<0.05). @*Conclusions@#Based on the findings, it is necessary to develop educational programs which can improve autonomy and develop professionalism to enhance clinical competence in consideration of work experience and educational levels in dental hygienists.

Weight Loss for Obstructive Sleep Apnea: Pharmacological and Surgical Management

Obstructive sleep apnea (OSA) is a relatively common sleep disorder characterized by repetitive narrowing or obstruction of the upper airway, including the nasal cavity, pharynx, and larynx, during sleep. OSA can cause a variety of symptoms and/or complications, such as excessive daytime sleepiness, reduced concentration, hypertension, type II diabetes, and stroke. Accordingly, an accurate diagnosis and appropriate treatments are required for OSA. Obesity is an important risk factor for OSA and is characterized by the abnormal accumulation of fat in the body, including the upper airway. When the body weight increases, adipose tissue accumulates in the pharynx, which can narrow the diameter of the upper airway and lead to dysfunction of the pharynx dilator muscles. These changes caused by weight gain can cause or exacerbate OSA. Various therapeutic options exist for patients with overweight or obesity, including diet, behavioral modifications, exercise, pharmacological treatments, and surgical procedures. Of these, diet, behavioral modifications, and exercise constitute the first-line management for obesity. However, their results are relatively unsatisfactory, and pharmacotherapy and bariatric surgery are generally implemented in obese patients with OSA. Therefore, the purpose of this paper is to review pharmacological and surgical management strategies for obesity that are currently commonly used in overweight or obese adult patients with OSA.

Image fusion technique using flat panel detector rotational angiography for transvenous embolization of intracranial dural arteriovenous fistula

Precise evaluation of the feeders, fistulous points, and draining veins plays a key role for successful embolization of intracranial dural arteriovenous fistulas (DAVF). Digital subtraction angiography (DSA) is a gold standard diagnostic tool to assess the exact angioarchitecture of DAVFs. With the advent of new image postprocessing techniques, we lately have been able to apply image fusion techniques with two different image sets obtained with flat panel detector rotational angiography. This new technique can provide additional and better pretherapeutic information of DAVFs over the conventional 2D and 3D angiographies. In addition, it can be used during the endovascular treatment to help the accurate and precise navigation of the microcatheter and microguidwire inside the vessels and identify the proper location of microcatheter in the targeted shunting pouch. In this study, we briefly review the process of an image fusion technique and introduce our clinical application for treating DAVFs, especially focused on the transvenous embolization.

A Refractory Livedoid Vasculopathy Accompanied by Methylene Tetrahydrofolate Reductase Gene Polymorphism Successfully Treated with Hyperbaric Oxygen Therapy

Livedoid vasculopathy (LV) is a chronic coagulation disorder characterized by recurrent, painful ulcers on the lower extremities. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphism is associated with coagulopathy. Therapeutic options usually include anti-inflammatory or immunosuppressive agents. However, the condition is still highly challenging to manage and no consensus over the first-line treatment for LV exists. Furthermore, when LV is accompanied with MTHFR gene polymorphism, clinical presentations could be more severe and resistant to treatment. We report a case of refractory LV accompanied by MTHFR gene polymorphism, which was successfully treated with hyperbaric oxygen therapy (HBOT). A 63-year-old female patient presented with multiple painful ulcers, atrophie blanches, and retiform purpura on both lower legs and feet. Histopathologic findings were compatible with LV. LV was diagnosed based on these clinicopathological findings. Following the diagnosis, we treated the patient with pentoxifylline, aspirin, systemic corticosteroid, antihistamine, and antibiotics. In spite of six-month treatment, the skin lesions did not improve; hence, HBOT was performed. It was performed at 2.0 absolute atmosphere for 120 minutes each time, three times a week. After 4 sessions, the ulcers began to heal and after 13 sessions, the skin lesions almost healed. During the eight-month followup period, the skin ulcers did not recur and the symptoms remained stable. Additionally, it was confirmed that she had MTHFR gene polymorphism after a genetic test. In conclusion, we wish to provide evidence regarding the effectiveness of HBOT and suggest that HBOT might be a considerable treatment option in refractory LV.

Characteristics of hard seltzer and their effect on the tooth surface / 대한구강보건학회지

Objectives@#To investigate the effect of commercially available hard seltzer on the tooth enamel surface. @*Methods@#Some commercially available hard seltzer were purchased at the market and the characteristics of the beverages were surveyed. Subsequently, Cloud hard seltzer mango was selected for the hard seltzer group (group 4), Jeju Samdasoo for the mineral water group (group 1), Coca-Cola for the cola group (group 2), and Cloud Original for the beer group (group 3). The specimens were immersed in the experimental beverage for 30 minutes, then the surface microhardness and surface condition of the specimens were evaluated. @*Results@#The average pH of the twelve types of hard seltzer in this study were 3.51±0.01 (before stirring) and 3.46±0.01 (after stirring). The pH of experimental beverage were 7.92±0.03 (group 1), 2.55±0.01 (group 2), 4.41±0.01 (group 3), and 3.31±0.01 (group 4). Paired t-test of the surface microhardness of enamel before and after beverage immersion found no significant difference in group 1 (P>0.05), but a significant difference was observed in groups 2, 3, and 4 (P<0.05). One way ANOVA of the surface microhardness change values (∆VHN, before - after immersion) among groups found a statistically significant difference between groups 1 and 3 (9.20±34.82 ∆VHN and 20.20±6.52 ∆VHN) and groups 2 and 4 (82.90±18.08 ∆VHN and 67.10±18.27 ∆VHN) (P<0.05).On scanning electron microscopy, hard seltzer group showed rough and ruined surface condition. @*Conclusions@#This study found a risk of dental erosion due to the low pH of hard seltzer. Therefore, it is suggested that when ingesting hard seltzer, dental erosion should be considered for oral health.

Molecular basis and genetic testing strategies for diagnosing 21-hydroxylase deficiency, including CAH-X syndrome

Congenital adrenal hyperplasia (CAH) is a group of autosomally recessive disorders that result from impaired synthesis of glucocorticoid and mineralocorticoid. Most cases (~95%) are caused by mutations in the CYP21A2 gene, which encodes steroid 21-hydroxylase. CAH patients manifest a wide phenotypic spectrum according to their degree of residual enzyme activity. CYP21A2 and its pseudogene (CYP21A1P) are located 30 kb apart in the 6q21.3 region and share approximately 98% of their sequences in the coding region. Both genes are aligned in tandem with the C4, SKT19, and TNX genes, forming 2 segments of the RCCX modules that are arranged as STK19-C4A-CYP21A1P-TNXA-STK19B-C4B-CYP21A2-TNXB. The high sequence homology between the active gene and pseudogene leads to frequent microconversions and large rearrangements through intergenic recombination. The TNXB gene encodes an extracellular matrix glycoprotein, tenascin-X (TNX), and defects in TNXB cause Ehlers-Danlos syndrome. Deletions affecting both CYP21A2 and TNXB result in a contiguous gene deletion syndrome known as CAH-X syndrome. Because of the high homology between CYP21A2 and CYP21A1P, genetic testing for CAH should include an evaluation of copy number variations, as well as Sanger sequencing. Although it poses challenges for genetic testing, a large number of mutations and their associated phenotypes have been identified, which has helped to establish genotype-phenotype correlations. The genotype is helpful for guiding early treatment, predicting the clinical phenotype and prognosis, and providing genetic counseling. In particular, it can help ensure proper management of the potential complications of CAH-X syndrome, such as musculoskeletal and cardiac defects. This review focuses on the molecular pathophysiology and genetic diagnosis of 21-hydroxylase deficiency and highlights genetic testing strategies for CAH-X syndrome.