Privacy-aware estimation of relatedness in admixed populations.

BACKGROUND: Estimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in third-party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization. RESULTS: Here, we present SIGFRIED, which makes use of existing reference panels with a projection-based approach that simplifies kinship estimation in the admixed populations. We use simulated and real datasets to demonstrate the accuracy and efficiency of kinship estimation. We present a secure federated kinship estimation framework and implement a secure kinship estimator using homomorphic encryption-based primitives for computing relatedness between samples in two different sites while genotype data are kept confidential. Source code and documentation for our methods can be found at https://doi.org/10.5281/zenodo.7053352. CONCLUSIONS: Analysis of relatedness is fundamentally important for identifying relatives, in association studies, and for estimation of population-level estimates of inbreeding. As the awareness of individual and group genomic privacy is growing, privacy-preserving methods for the estimation of relatedness are needed. Presented methods alleviate the ethical and privacy concerns in the analysis of relatedness in admixed, historically isolated and underrepresented populations. SHORT ABSTRACT: Genetic relatedness is a central quantity used for finding relatives in databases, correcting biases in genome wide association studies and for estimating population-level statistics. Methods for estimating genetic relatedness have high computational requirements, and occasionally do not consider individuals from admixed ancestries. Furthermore, the ethical concerns around using genetic data and calculating relatedness are not considered. We present a projection-based approach that can efficiently and accurately estimate kinship. We implement our method using encryption-based techniques that provide provable security guarantees to protect genetic data while kinship statistics are computed among multiple sites.

Evaluation of the Clinical Efficacy and Trust in AI-Assisted Embryo Ranking: Survey-Based Prospective Study.

BACKGROUND: Current embryo assessment methods for in vitro fertilization depend on subjective morphological assessments. Recently, artificial intelligence (AI) has emerged as a promising tool for embryo assessment; however, its clinical efficacy and trustworthiness remain unproven. Simulation studies may provide additional evidence, provided that they are meticulously designed to mitigate bias and variance. OBJECTIVE: The primary objective of this study was to evaluate the benefits of an AI model for predicting clinical pregnancy through well-designed simulations. The secondary objective was to identify the characteristics of and potential bias in the subgroups of embryologists with varying degrees of experience. METHODS: This simulation study involved a questionnaire-based survey conducted on 61 embryologists with varying levels of experience from 12 in vitro fertilization clinics. The survey was conducted via Google Forms (Google Inc) in three phases: (1) phase 1, an initial assessment (December 23, 2022, to January 22, 2023); (2) phase 2, a validation assessment (March 6, 2023, to April 5, 2023); and (3) phase 3 an AI-guided assessment (March 6, 2023, to April 5, 2023). Inter- and intraobserver assessments and the accuracy of embryo selection from 360 day-5 embryos before and after AI guidance were analyzed for all embryologists and subgroups of senior and junior embryologists. RESULTS: With AI guidance, the interobserver agreement increased from 0.355 to 0.527 and from 0.440 to 0.524 for junior and senior embryologists, respectively, thus reaching similar levels of agreement. In a test of accurate embryo selection with 90 questions, the numbers of correct responses by the embryologists only, embryologists with AI guidance, and AI only were 34 (38%), 45 (50%), and 59 (66%), respectively. Without AI, the average score (accuracy) of the junior group was 33.516 (37%), while that of the senior group was 35.967 (40%), with P<.001 in the t test. With AI guidance, the average score (accuracy) of the junior group increased to 46.581 (52%), reaching a level similar to that of the senior embryologists of 44.833 (50%), with P=.34. Junior embryologists had a higher level of trust in the AI score. CONCLUSIONS: This study demonstrates the potential benefits of AI in selecting embryos with high chances of pregnancy, particularly for embryologists with 5 years or less of experience, possibly due to their trust in AI. Thus, using AI as an auxiliary tool in clinical practice has the potential to improve embryo assessment and increase the probability of a successful pregnancy.

Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis.

The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without endometriosis (EMS) during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control (CT; P-phase [pCT], n = 8; S-phase [sCT], n = 13) and 23 EMS patients (P-phase [pEMS], n = 13; S-phase [sEMS], n = 12). DElncRNAs and DEmRNAs were analyzed using total RNA-sequencing. In P-phase, expression of NONHSAG019742.2 and NONHSAT120701.2 was significantly higher in EMS than control patients, that of while NONHSAG048398.2 and NONHSAG016560.2 was lower in EMS patients. In S-phase, expression of NONHSAT000959.2, NONHSAT203423.1, and NONHSAG053769.2 was significantly increased in EMS patients, while that of NONHSAG012105.2 and NONHSAG020839.2 was lower. In addition, the expression of HSD11B2, THBS1, GPX3, and SHISA6 was similar to that of neighboring lncRNAs in both P- and S-phases. In contrast, ELP3 and NR4A1, respectively, were up- or downregulated in pEMS tissues. In sEMS, expression of LAMB3 and HIF1A was increased, while expression of PAM was reduced. Our findings on lncRNAs and mRNAs encourage not only exploration of the potential clinical applications of lncRNAs and mRNAs as prognostic or diagnostic biomarkers for EMS but also to gain valuable insights into its pathogenesis.

SVAT: Secure outsourcing of variant annotation and genotype aggregation.

BACKGROUND: Sequencing of thousands of samples provides genetic variants with allele frequencies spanning a very large spectrum and gives invaluable insight into genetic determinants of diseases. Protecting the genetic privacy of participants is challenging as only a few rare variants can easily re-identify an individual among millions. In certain cases, there are policy barriers against sharing genetic data from indigenous populations and stigmatizing conditions. RESULTS: We present SVAT, a method for secure outsourcing of variant annotation and aggregation, which are two basic steps in variant interpretation and detection of causal variants. SVAT uses homomorphic encryption to encrypt the data at the client-side. The data always stays encrypted while it is stored, in-transit, and most importantly while it is analyzed. SVAT makes use of a vectorized data representation to convert annotation and aggregation into efficient vectorized operations in a single framework. Also, SVAT utilizes a secure re-encryption approach so that multiple disparate genotype datasets can be combined for federated aggregation and secure computation of allele frequencies on the aggregated dataset. CONCLUSIONS: Overall, SVAT provides a secure, flexible, and practical framework for privacy-aware outsourcing of annotation, filtering, and aggregation of genetic variants. SVAT is publicly available for download from https://github.com/harmancilab/SVAT .

Evaluation of vicinity-based hidden Markov models for genotype imputation.

BACKGROUND: The decreasing cost of DNA sequencing has led to a great increase in our knowledge about genetic variation. While population-scale projects bring important insight into genotype-phenotype relationships, the cost of performing whole-genome sequencing on large samples is still prohibitive. In-silico genotype imputation coupled with genotyping-by-arrays is a cost-effective and accurate alternative for genotyping of common and uncommon variants. Imputation methods compare the genotypes of the typed variants with the large population-specific reference panels and estimate the genotypes of untyped variants by making use of the linkage disequilibrium patterns. Most accurate imputation methods are based on the Li-Stephens hidden Markov model, HMM, that treats the sequence of each chromosome as a mosaic of the haplotypes from the reference panel. RESULTS: Here we assess the accuracy of vicinity-based HMMs, where each untyped variant is imputed using the typed variants in a small window around itself (as small as 1 centimorgan). Locality-based imputation is used recently by machine learning-based genotype imputation approaches. We assess how the parameters of the vicinity-based HMMs impact the imputation accuracy in a comprehensive set of benchmarks and show that vicinity-based HMMs can accurately impute common and uncommon variants. CONCLUSIONS: Our results indicate that locality-based imputation models can be effectively used for genotype imputation. The parameter settings that we identified can be used in future methods and vicinity-based HMMs can be used for re-structuring and parallelizing new imputation methods. The source code for the vicinity-based HMM implementations is publicly available at https://github.com/harmancilab/LoHaMMer .

Up-Regulation of the Long Noncoding RNA X-Inactive-Specific Transcript and the Sex Bias in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease. Increased expression and activity of the long-noncoding RNA X-inactive-specific transcript (Xist), essential for X-chromosome inactivation and dosage compensation of X-linked genes, may explain the sex bias of PAH. The present studies used a murine model of plexiform PAH, the intersectin-1s (ITSN) heterozygous knockout (KOITSN+/-) mouse transduced with an ITSN fragment (EHITSN) possessing endothelial cell proliferative activity, in conjunction with molecular, cell biology, biochemical, morphologic, and functional approaches. The data demonstrate significant sex-centered differences with regard to EHITSN-induced alterations in pulmonary artery remodeling, lung hemodynamics, and p38/ETS domain containing protein/c-Fos signaling, altogether leading to a more severe female lung PAH phenotype. Moreover, the long-noncoding RNA-Xist is up-regulated in the lungs of female EHITSN-KOITSN+/- mice compared with that in female wild-type mice, leading to sex-specific modulation of the X-linked gene ETS domain containing protein and its target, two molecular events also characteristic to female human PAH lung. More importantly, cyclin A1 expression in the S and G2/M phases of the cell cycle of synchronized pulmonary artery endothelial cells of female PAH patients is greater versus controls, suggesting functional hyperproliferation. Thus, Xist up-regulation leading to female pulmonary artery endothelial cell sexual dimorphic behavior may provide a better understanding of the origin of sex bias in PAH. Notably, the EHITSN-KOITSN+/- mouse is a unique experimental animal model of PAH that recapitulates most of the sexually dimorphic characteristics of human disease.

Etiology and Secular Trends in Primary Amenorrhea in 856 Patients: A 17-Year Retrospective Multicenter Study in Korea.

BACKGROUND: This study was performed to evaluate etiologies and secular trends in primary amenorrhea in South Korea. METHODS: This retrospective multi-center study analyzed 856 women who were diagnosed with primary amenorrhea between 2000 and 2016. Clinical characteristics were compared according to categories of amenorrhea (hypergonadotropic/hypogonadotropic hypogonadism, eugonadism, disorders of sex development) or specific causes of primary amenorrhea. In addition, we assessed secular trends of etiology and developmental status based on the year of diagnosis. RESULTS: The most frequent etiology was eugonadism (39.8%). Among specific causes, Müllerian agenesis was most common (26.2%), followed by gonadal dysgenesis (22.4%). Women with hypergonadotropic hypogonadism were more likely to have lower height and weight, compared to other categories. In addition, the proportion of cases with iatrogenic or unknown causes increased significantly in hypergonadotropic hypogonadism category, but overall, no significant secular trends were detected according to etiology. The proportion of anovulation including polycystic ovarian syndrome increased with time, but the change did not reach statistical significance. CONCLUSION: The results of this study provide useful clinical insight on the etiology and secular trends of primary amenorrhea. Further large-scale, prospective studies are necessary.

Effects of Ethanol on Expression of Coding and Noncoding RNAs in Murine Neuroblastoma Neuro2a Cells.

Excessive use of alcohol can induce neurobiological and neuropathological alterations in the brain, including the hippocampus and forebrain, through changes in neurotransmitter systems, hormonal systems, and neuroimmune processes. We aimed to investigate the effects of ethanol on the expression of coding and noncoding RNAs in a brain-derived cell line exposed to ethanol. After exposing Neuro2a cells, a neuroblastoma cell line, to ethanol for 24 and 72 h, we observed cell proliferation and analyzed up- and downregulated mRNAs and long noncoding RNAs (lncRNAs) using total RNA-Seq technology. We validated the differential expression of some mRNAs and lncRNAs by RT-qPCR and analyzed the expression of Cebpd and Rnu3a through knock-down of Cebpd. Cell proliferation was significantly reduced in cells exposed to 100 mM ethanol for 72 h, with 1773 transcripts up- or downregulated by greater than three-fold in ethanol-treated cells compared to controls. Of these, 514 were identified as lncRNAs. Differentially expressed mRNAs and lncRNAs were mainly observed in cells exposed to ethanol for 72 h, in which Atm and Cnr1 decreased, but Trib3, Cebpd, and Spdef increased. On the other hand, lncRNAs Kcnq1ot1, Tug1, and Xist were changed by ethanol, and Rnu3a in particular was greatly increased by chronic ethanol treatment through inhibition of Cebpd. Our results increase the understanding of cellular and molecular mechanisms related to coding and noncoding RNAs in an in vitro model of acute and chronic exposure to ethanol.

Physiological Responses of Mesodinium major to Irradiance, Prey Concentration and Prey Starvation.

Ciliates within the Mesodinium rubrum/Mesodinium major species complex harbor chloroplasts and other cell organelles from specific cryptophyte species. Mesodinium major was recently described, and new studies indicate that blooms of M. major are just as common as blooms of M. rubrum. Despite this, the physiology of M. major has never been studied and compared to M. rubrum. In this study, growth, food uptake, chlorophyll a and photosynthesis were measured at six different irradiances, when fed the cryptophyte, Teleaulax amphioxeia. The results show that the light compensation point for growth of M. major was significantly higher than for M. rubrum. Inorganic carbon uptake via photosynthesis contributed by far most of total carbon uptake at most irradiances, similar to M. rubrum. Mesodinium major cells contain ~four times as many chloroplast as M. rubrum leading to up to ~four times higher rates of photosynthesis. The responses of M. major to prey starvation and refeeding were also studied. Mesodinium major was well adapted to prey starvation, and 51 d without prey did not lead to mortality. Mesodinium major quickly recovered from prey starvation when refed, due to high ingestion rates of > 150 prey/predator/d.

Vitamin D Status in Distinct Types of Ichthyosis: Importance of Genetic Type and Severity of Scaling.

Data on vitamin D status of patients with inherited ichthyosis in Europe is scarce and unspecific concerning the genetic subtype. This study determined serum levels of 25-hydroxyvitamin D3 (25(OH)D3) in 87 patients with ichthyosis; 69 patients were additionally analysed for parathyroid hormone. Vitamin D deficiency was pronounced in keratinopathic ichthyosis (n = 17; median 25(OH)D3: 10.5 ng/ml), harlequin ichthyosis (n = 2;7.0 ng/ml) and rare syndromic subtypes (n = 3; 7.0 ng/ml). Vitamin D levels were reduced in TG1-proficient lamellar ichthyosis (n = 15; 8.9 ng/ml), TG1-deficient lamellar ichthyosis (n = 12; 11.7 ng/ml), congenital ichthyosiform erythroderma (n = 13; 12.4 ng/ml), Netherton syndrome (n = 7; 10.7 ng/ml) and X-linked ichthyosis (n = 8; 13.9 ng/ml). In ichthyosis vulgaris 25(OH)D3 levels were higher (n = 10; 19.7 ng/ml). Parathyroid hormone was elevated in 12 patients. Low 25(OH)D3 levels were associated with high severity of scaling (p = 0.03) implicating scaling as a risk factor for vitamin D deficiency. Thus, this study supports our recent guidelines for ichthyoses, which recommend screening for and substituting of vitamin D deficiency.

Assessment of medical students' clinical performance using high-fidelity simulation: comparison of peer and instructor assessment.

BACKGROUND: High-fidelity simulators are highly useful in assessing clinical competency; they enable reliable and valid evaluation. Recently, the importance of peer assessment has been highlighted in healthcare education, and studies using peer assessment in healthcare, such as medicine, nursing, dentistry, and pharmacy, have examined the value of peer assessment. This study aimed to analyze inter-rater reliability between peers and instructors and examine differences in scores between peers and instructors in the assessment of high-fidelity-simulation-based clinical performance by medical students. METHODS: This study analyzed the results of two clinical performance assessments of 34 groups of fifth-year students at Ajou University School of Medicine in 2020. This study utilized a modified Queen's Simulation Assessment Tool to measure four categories: primary assessment, diagnostic actions, therapeutic actions, and communication. In order to estimate inter-rater reliability, this study calculated the intraclass correlation coefficient and used the Bland and Altman method to analyze agreement between raters. A t-test was conducted to analyze the differences in evaluation scores between colleagues and faculty members. Group differences in assessment scores between peers and instructors were analyzed using the independent t-test. RESULTS: Overall inter-rater reliability of clinical performance assessments was high. In addition, there were no significant differences in overall assessment scores between peers and instructors in the areas of primary assessment, diagnostic actions, therapeutic actions, and communication. CONCLUSIONS: The results indicated that peer assessment can be used as a reliable assessment method compared to instructor assessment when evaluating clinical competency using high-fidelity simulators. Efforts should be made to enable medical students to actively participate in the evaluation process as fellow assessors in high-fidelity-simulation-based assessment of clinical performance in situations similar to real clinical settings.

A secure system for genomics clinical decision support.

We developed a prototype genomic archiving and communications system to securely store genome data and provide clinical decision support (CDS). This system operates on a client-server model. The client encrypts the data, and the server stores data and performs the computations necessary for CDS. Computations are directly performed on encrypted data, and the client decrypts results. The server cannot decrypt inputs or outputs, which provides strong guarantees of security. We have validated our system with three genomics-based CDS applications. The results demonstrate that it is possible to resolve a long-standing dilemma in genomic data privacy and accessibility, by using a principled cryptographical framework and a mathematical representation of genome data and CDS questions.

Plasma levels of polychlorinated biphenyl, genetic polymorphisms, and the risk of advanced stage endometriosis.

Both environmental and genetic factors interact and play a critical role in the pathogenesis of endometriosis. We analyzed the plasma levels of 12 polychlorinated biphenyl (PCB) congeners with genetic polymorphisms of glutathione-S-transferase M1 (GSTM1), glutathione-S-transferase T1 (GSTT1), and aryl hydrocarbon receptor repressor (AhRR) codon 185. Total sum of the 12 congeners was significantly higher in the controls compared with endometriosis group. Women without C/C genotype in AhRR codon 185 had a significantly increased risk of endometriosis compared with those with C/C genotype. Total sum of the 12 congeners was significantly higher in women without C/C genotype compared with those with C/C genotype. Adjusting for age and AhRR codon 185 genotype, there was no significant association between exposure to PCBs and the risk of endometriosis. These findings suggest a possible presence of gene-environment interaction, however, we could not see any clear association between exposure to PCBs and the risk of endometriosis.

Effectiveness of simulation-based interprofessional education for medical and nursing students in South Korea: a pre-post survey.

BACKGROUND: Effective collaboration and communication among health care team members are critical for providing safe medical care. Interprofessional education aims to instruct healthcare students how to learn with, from, and about healthcare professionals from different occupations to encourage effective collaboration to provide safe and high-quality patient care. The purpose of this study is to confirm the effectiveness of Interprofessional education by comparing students' attitudes toward interprofessional learning before and after simulation-based interprofessional education, the perception of teamwork and collaboration between physicians and nurses, and the self-reported competency differences among students in interprofessional practice. METHODS: The survey responses from 37 5th-year medical students and 38 4th-year nursing students who participated in an interprofessional education program were analyzed. The Attitude Towards Teamwork in Training Undergoing Designed Educational Simulation scale, the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration, and the Interprofessional Education Collaborative competency scale were used for this study. The demographic distribution of the study participants was obtained, and the perception differences before and after participation in interprofessional education between medical and nursing students were analyzed. RESULTS: After interprofessional education, student awareness of interprofessional learning and self-competency in interprofessional practice improved. Total scores for the Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration did not change significantly among medical students but increased significantly among nursing students. Additionally, there was no significant change in the perception of the role of other professions among either medical or nursing students. CONCLUSIONS: We observed an effect of interprofessional education on cultivating self-confidence and recognizing the importance of interprofessional collaboration between medical professions. It can be inferred that exposure to collaboration situations through Interprofessional education leads to a positive perception of interprofessional learning. However, even after their interprofessional education experience, existing perceptions of the role of other professional groups in the collaboration situation did not change, which shows the limitations of a one-time short-term program. This suggests that efforts should be made to ensure continuous exposure to social interaction experiences with other professions.

Relationships Between Perspective-Taking, Empathic Concern, and Self-rating of Empathy as a Physician Among Medical Students.

OBJECTIVE: The aim of this study was to ascertain the relationships between perspective-taking, empathic concern, and self-rating of empathy as a physician among medical students. METHODS: This study analyzed the questionnaire responses of 152 medical students enrolled in Ajou University School of Medicine, Suwon, Republic of Korea, in 2018. As measurement instruments, the authors applied the Interpersonal Reactivity Index (IRI) and Korean Student Version of the Jefferson Scale of Physician Empathy (Korean JSPE-S), and then examined participant characteristic variables based on the obtained data and conducted subsequent correlation analyses of subscales, one-way ANOVA, and regression analyses. RESULTS: Medical students with clinical clerkship experience demonstrated higher levels of perspective-taking and empathy as physicians than did students without experience. Moreover, perspective-taking and empathic concern were significant predictors of medical students' empathy as physicians in the regression model. CONCLUSIONS: Medical students with higher scores in perspective-taking and empathic concern demonstrated higher levels of perception regarding the necessity and importance of empathy as a physician in patient-physician relationships. Therefore, in actual medical situations with patient-centered therapy, to enhance the levels of physician empathy, medical education should focus on the understanding of other persons' opinions and interpersonal interactions accompanied by empathic concern.

Changes in Medical Students' Self-Assessments of Clinical Communication Skills after Clinical Practice and Standardized Patient Feedback.

OBJECTIVE: In this study, the authors aimed to analyze the effects of clinical practice and Standardized Patient (SP) feedback on medical students' self-assessments of their clinical communication skills (CCS). METHODS: The authors analyzed questionnaire responses from 43 fifth-year medical students enrolled in the Ajou University School of Medicine, Suwon, Republic of Korea, in 2019, and used the Communication Assessment Tool (CAT) scale to measure the study's variables. A descriptive statistical analysis and paired t test focused on the distribution of and changes in CCS before and after clinical practice and after receiving SP feedback. RESULTS: After clinical practice, the students' perceptions of their own CCS were positively increased, but after the receipt of SP feedback, they significantly decreased. Scores for the item on interpersonal relationships with the patient from the perspective of the patient were significantly lower after the SP feedback was obtained. CONCLUSIONS: SP feedback emerged as an important educational method, allowing students to assess their CCS more objectively and view their CCS as physicians from the patient's perspective. SP feedback is necessary, as is providing students with the experience of receiving direct SP feedback, on clinical performance to increase patient-centered care competencies.

Growth and Chloroplast Replacement of the Benthic Mixotrophic Ciliate Mesodinium coatsi.

While the ecophysiology of planktonic Mesodinium rubrum species complex has been relatively well studied, very little is known about that of benthic Mesodinium species. In this study, we examined the growth response of the benthic ciliate Mesodinium coatsi to different cryptophyte prey using an established culture of this species. M. coatsi was able to ingest all of the offered cryptophyte prey types, but not all cryptophytes supported its positive, sustained growth. While M. coatsi achieved sustained growth on all of the phycocyanin-containing Chroomonas spp. it was offered, it showed different growth responses to the phycoerythrin-containing cryptophytes Rhodomonas spp., Storeatula sp., and Teleaulax amphioxeia. M. coatsi was able to easily replace previously ingested prey chloroplasts with newly ingested ones within 4 d, irrespective of prey type, if cryptophyte prey were available. Once retained, the ingested prey chloroplasts seemed to be photosynthetically active. When fed, M. coatsi was capable of heterotrophic growth in darkness, but its growth was enhanced significantly in the light (14:10 h light:dark cycle), suggesting that photosynthesis by ingested prey chloroplast leads to a significant increase in the growth of M. coatsi. Our results expand the knowledge of autecology and ecophysiology of the benthic M. coatsi.

Professional self-concept and burnout among medical school faculty in South Korea: a cross-sectional study.

BACKGROUND: Medical school faculty members have been reported to be highly likely to suffer burnout. Research is being conducted on professional self-concepts as a factor that relieves burnout in many professions. However, there is a paucity of data on the relationship between professional self-concept and burnout among medical school faculty. Professional self-concept means a perception of oneself as a member of the profession. It influences an individual's thoughts, actions, and emotions. The more positive the professional self-concept, the higher is the self-esteem in the profession, which can contribute to reducing burnout. This study aimed to investigate the professional self-concept and incidence of burnout among medical school clinical faculty members, and to ascertain the factors that affect professional self-concept with respect to burnout. METHODS: A total of 68 clinical faculty members at the Ajou University School of Medicine completed a modified form of the professional self-concept scale and the Maslach Burnout Inventory. We undertook the following statistical analyses: a descriptive analysis to understand the distribution of participants, correlation analysis to indicate associations between variables and a multiple regression analysis to examine the influence of gender, position, and specialty on professional self-concept and burnout, and the effect of each subscale of professional self-concept on burnout. RESULTS: As professional self-concept increases, burnout decreases. There was no significant difference between professional self-concept and burnout with respect to gender or field of medical specialty, while a significant difference was observed across faculty position levels. Additionally, the professional self-concept subscale, which included satisfaction and communication skill, was found to significantly affect burnout. CONCLUSIONS: This study shows that professional self-concept affects burnout. Through these results, we can infer that professional self-concept functioned to protect medical school faculty from burnout. This may be a strategy that fortifies the professional identity of medical school faculty, and it is suggested that educational programs that are directed toward this goal be established.

Alcohol-mediated miR-34a modulates hepatocyte growth and apoptosis.

MicroRNAs (miRs) have been recently shown to be heavily involved in the development of alcoholic liver disease (ALD) and suggested as a potential therapeutic target in ALD. The miR-34a was consistently reported to be significantly elevated in several ALD rodent models, but it remains unclear how miR-34a modulates the cellular behaviours of hepatocytes in ALD development and progression. This study aims to characterize alcohol-induced miR-34a impact on hepatocytes growth and apoptosis. The miRNA array was performed to assess changes in miRNA after chronic alcohol feeding. Liver and blood samples were used to examine ALD progression. The miR-34a was overexpressed in human hepatocytes to evaluate its impact on cell growth and apoptosis. Real-time quantitative PCR and Western blot were used to determine the growth and apoptosis molecular signalling pathways associated with miR-34a. Alcohol feeding significantly promoted fatty liver progression, serum ALT levels, apoptosis and miR-34a expression in rat liver. Overexpression of miR-34a in human hepatocytes suppressed cell growth signallings, including c-Met, cyclin D1 and cyclin-dependent kinase 6 (CDK6). The miR-34a might also inhibit the expression of sirtuin 1 (Sirt1) and its target, B-cell lymphoma 2. Interestingly, the expression of miR-34a reverses the suppressive effects of ethanol on cell growth. But, miR-34a promotes hepatocyte senescence and apoptosis. Although the miR-34a-mediated down-regulation of cell growth-associated genes may contribute to cell growth retardation, other miR-34a targets, such as Sirt1, may reverse this phenotype. Future studies will be needed to clarify the role of miR-34a in ALD progression.

Effect of insemination timing on pregnancy outcome in association with female age, sperm motility, sperm morphology and sperm concentration in intrauterine insemination.

AIM: We investigated the effect of insemination timing on pregnancy outcomes in intrauterine insemination (IUI) cycles. METHODS: This is a retrospective study of 411 IUI cycles performed with a diagnosis of unexplained infertility and male factor infertility. The cycles were divided according to the interval between insemination and ovulation: ≤36 h, 36-37 h, 37-38 h and >38 h. The overall pregnancy rate, chemical pregnancy rate and clinical pregnancy rate were compared. We also analyzed the association between pregnancy outcomes and clinical characteristics, including age, duration of infertility, sperm concentration, body mass index (BMI), anti-Müllerian hormone (AMH) and number of mature follicles at ovulation. RESULTS: There were no differences regarding age, duration of infertility, BMI, AMH, sperm concentration and number of mature follicles between different IUI timing groups. Sperm morphology was significantly lower in ≤36 h group (5.3 ± 1.4) compared to 36-37 h, 37-38 h and >38 h (6.3 ± 2.5 vs 6.5 ± 2.7 vs 6.5 ± 3.5, P = 0.004) groups. The ≤36 h group showed lowest total pregnancy rate (5.0%) compared to other IUI timings (21.8% vs 24.8% vs 20.0%, P = 0.05). Multivariate analysis showed that sperm morphology was associated with pregnancy in 36-37 h (odd ratio 1.42, 95% confidence interval 1.03-1.95, P = 0.02). CONCLUSION: Insemination at least 36 h after ovulation is associated with increased pregnancy rate compared to IUIs performed ≤36 h following ovulation.