Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Aerobic Exercise Improves Radiation Therapy Efficacy in Non-Small Cell Lung Cancer: Preclinical Study Using a Xenograft Mouse Model.

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.

The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease.

OBJECTIVES: Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few studies on the MTX's effectiveness in thiopurine-naïve CD adult patients and children. This study aimed to evaluate the MTX's effectiveness and safety as first immunomodulator for maintenance therapy in pediatric CD. METHODS: This retrospective cohort study recruited 64 pediatric CD patients treated with MTX as a first-line immunomodulator. Clinical remission (CR) was assessed at weeks 14, 26, and 52. Mucosal healing (MH) was assessed at weeks 26 and 52. RESULTS: Of 64 patients who received MTX, CR was noted in 60.9% at week 14, 29.7% with MH in 68.0% at week 26, and 27.8% with MH in 81.8% at week 52. When comparing age subtypes according to the Paris classification, the CR rate was higher in A1a than in the other subtypes at week 26 (60.0% in A1a, 26.5% in A1b, 0% in A2; P = 0.038). There were no differences in disease location, behavior, or perianal involvement. Adverse effects were noted in 30 of 64 (46.9%) patients, including 1 patient who stopped MTX before 26 weeks owing to side effects; increased liver enzymes in 25 (39.0%) patients, leukopenia in 5 (7.8%), nausea in 5 (7.8%), skin erosion in 1 (1.6%), and headache in 1 (1.6%). CONCLUSION: MTX as a first-line immunomodulator may be an effective and safe maintenance therapy for pediatric CD patients.

The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.

This is the first guidelines for adenomyosis from the Asian Society of Endometriosis and Adenomyosis.

Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells.

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

Progression to prediabetes or diabetes in young Korean women with polycystic ovary syndrome: A longitudinal observational study.

OBJECTIVE: To investigate changes in glycaemic status in women with polycystic ovary syndrome (PCOS). DESIGN: Longitudinal observational study. PATIENTS: Women with PCOS who underwent baseline and follow-up screening tests for diabetes (n = 262). Four patients with type 2 diabetes (T2DM) at baseline and 6 patients who were taking drugs at the final follow-up were excluded. MEASUREMENTS: Changes in glycaemic classification based on fasting glucose, haemoglobin A1c and oral glucose tolerance test. RESULTS: The median length of follow-up was 2.9 years. The mean age and body mass index in the normoglycaemia group (n = 202) were 23.0 years and 21.6 kg/m2 , while it was 23.6 years and 22.9 kg/m2 in the prediabetes group (n = 50). In the normoglycaemia group, 38 (18.8%) and 2 (1.0%) developed prediabetes and T2DM, respectively. In the prediabetes group, 22 (44.0%) remained in the same category, 6 (12.0%) developed T2DM, while 22 (44.0%) achieved normoglycaemia. The incidence rate of T2DM was 9.3 per 1,000 person-years, which was significantly higher than that of the female population of similar age, and the incidence was higher in women with fasting glucose ≥ 5.6 mmol/L at baseline than in women with < 5.6 mmol/L. CONCLUSIONS: About 20% of normoglycaemic women had developed prediabetes or T2DM after a median time of 2.9 years. Meanwhile, nearly half of prediabetes women achieved normoglycaemia. Higher baseline fasting glucose levels were associated with an increased incidence of T2DM. Our results are the first to evaluate glycaemic status changes using all three parameters in patients with PCOS.

Nuclear localization of endothelial nitric oxide synthase and nitric oxide production attenuates aphidicolin-induced endothelial cell death.

Aphidicolin represses DNA replication by inhibiting DNA polymerase α and δ, which leads to cell cycle arrest and cell damage. Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays an essential role in maintenance of endothelial integrity including endothelial cell (EC) survival. Previously, we reported that aphidicolin increases NO production in bovine aortic ECs (BAECs). However, the role of aphidicolin-induced NO on EC viability and its molecular mechanism remain to be elucidated. Treatment with 20 µM aphidicolin for 24 h reduced BAEC viability by ~40%, which was accompanied by increased NO production, phosphorylation of eNOS at Ser1179 (p-eNOS-Ser1179), and eNOS protein expression. The aphidicolin-increased eNOS expression and p-eNOS-Ser1179 were not altered by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (BAPTA-AM), a cell permeable and specific intracellular Ca2+ chelator. Co-treatment with 2-phenyl-4, 4, 5, 5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), an NO scavenger, or Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), a NOS inhibitor, exacerbated aphidicolin-stimulated BAEC death. Knockdown of eNOS gene expression using siRNA aggravated aphidicolin-induced BAEC death. However, exogenous NO donors including S-nitroso-l-glutathione (GSNO) or diethylenetriamine NONOate (DETA NO) had no effect on aphidicolin-decreased BAEC viability and aggravated BAEC viability at higher doses. Interestingly, aphidicolin accumulated eNOS protein in the active form, p-eNOS-Ser1179, in the nucleus. When cells were ectopically transfected with a wild-type (WT)-eNOS gene, aphidicolin induced significant localization of the protein product in the nucleus. Additionally, aphidicolin-elicited cell death was significantly reversed in WT-eNOS gene-transfected BAECs. Furthermore, overexpression of the eNOS gene containing nuclear localization signal (NLS) but not nuclear export signal (NES) significantly attenuated aphidicolin-induced BAEC death. When G2A-eNOS mutant lacking myristoylation at Gly2 was transfected, its intracellular distribution became diffuse and included the nucleus. Finally, expression of N-myristoyltransferase 2 (NMT2) but not NMT1 significantly decreased in aphidicolin-treated BAECs. Taken together, our results suggest that aphidicolin attenuates BAEC death in part by increasing nuclear eNOS localization and NO production.

Association Between Polycystic Ovary Syndrome and the Polymorphisms of Aryl Hydrocarbon Receptor Repressor, Glutathione-S-transferase T1, and Glutathione-S-transferase M1 Genes.

OBJECTIVE: To investigate the association between the aryl hydrocarbon receptor repressor (AhRR) C/G polymorphisms and glutathione-S-transferase M1 (GSTM1) and GSTT1 null mutation and the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS: This was a case-control study of 478 women with PCOS and 376 aged-matched healthy controls. Genotyping of the AhRR C/G polymorphism and GSTM1 and GSTT1 were performed using real-time PCR analysis and multiplex PCR, respectively. RESULTS: The genotype distribution of the AhRR C/G polymorphisms and GSTM1/GSTT1 null mutations did not differ between women with PCOS and controls. Using the wild-type combined AhRR CC and GSTT1 present genotype as a reference, the odds that a woman had PCOS were 1.54 (95% CIs 1.04-2.29) times higher if she had a combined AhRR CG or GG and GSTT1 null genotype. The odds that a woman had PCOS was 1.48 (95% CIs 1.08-2.04) times higher if she had a combined GSTM1/GSTT1 null genotype compared with the wild-type combined GSTM1/GSTT1 present genotype. However, there were no significant associations between the risk of PCOS and any combined AhRR and GSTM1. CONCLUSIONS: Our data suggest that a combined AhRR CG or GG and GSTT1 null genotype or a combined GSTT1/GSTM1 null genotype might be associated with an increased risk of PCOS.

The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer.

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.Impact StatementWhat is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo. Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group.What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles.What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.

Anionic Redox Chemistry as a Clue for Understanding the Structural Behavior in Layered Cathode Materials.

The anionic redox chemistries of layered cathode materials have been in focus recently due to an intriguing phenomenon that cannot be described by the number of electrons of transition metal ions. However, even though several studies have investigated the anionic redox chemistry of layered materials in terms of the charge compensation, the relationship between the origin of the structural behavior and anionic redox chemistry in layered materials remains poorly understood. In addition, a simultaneous redox process of transition metal ions could occur through the d bands interaction. Here, it is demonstrated that the anionic redox chemistry is associated with the anisotropic structural behavior of the layered cathode materials albeit without providing additional capacities exceeding the theoretical values. These findings will provide a foundation of a new chapter in the understanding of the properties of materials.

Impact of the newly recommended antral follicle count cutoff for polycystic ovary in adult women with polycystic ovary syndrome.

STUDY QUESTION: What is the impact of the newly recommended antral follicle count (AFC) cutoff for polycystic ovary (PCO) on the diagnostic status of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Among patients with phenotypes requiring the presence of PCO for diagnosis, approximately half (48.2%) were excluded from having PCOS based on the new AFC cutoff, although these excluded women had worse metabolic and hormonal profiles than the controls and were indistinguishable from the remaining patients with regard to major hormonal and metabolic parameters. WHAT IS KNOWN ALREADY: In the Rotterdam criteria, PCO is defined as either 12 or more follicles measuring 2-9 mm in diameter or an increased ovarian volume >10 cm3. Recently, an international PCOS guideline development group recommended an AFC threshold for PCO of ≥20 in adult women when using transducers with a high-resolution frequency, including 8 MHz. STUDY DESIGN, SIZE, DURATION: The current study used a case control design. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was diagnosed according to the Rotterdam criteria. Ultrasonography examinations were conducted with wide band frequency (5-9 MHz) transvaginal transducers and the centre frequency was 8 MHz. In patients who show both irregular menstruation and hyperandrogenism (HA), a diagnosis of PCOS can be made irrespective of the ovarian criteria change. Patients who were diagnosed according to HA and PCO (n = 86) or irregular menstruation and PCO (n = 443) were initially included among a total of 1390 adult women with PCOS (aged 20-40 years). Regardless of the AFC, if the ovarian volume is ≥10 cm3, a diagnosis of PCO can still be made. Thus, only patients who had an ovarian volume of <10 cm3 were analysed. Subjects who had an AFC of 12-19 and an ovarian volume <10 cm3 were designated as the 'low AFC group' (n = 255) and were the main focus of the study because they were excluded from having PCOS based on the new cutoff. Subjects with an AFC ≥20 and an ovarian volume <10 cm3 were designated as the 'high AFC group' (n = 101). A total of 562 premenopausal women without PCOS were enrolled as controls. MAIN RESULTS AND THE ROLE OF CHANCE: Among patients with irregular menstruation and PCO or HA and PCO phenotypes, approximately half (48.2%, 255/529) were excluded from having PCOS, which corresponded to one-fifth (18.3%, 255/1390) of the total adult patients. However, compared to the control group, these excluded women had worse metabolic profiles and were more androgenised. Notably, they were indistinguishable from the 'high AFC group' with regard to major hormonal and metabolic parameters (BMI and diabetic classification status, and the prevalence of insulin resistance, metabolic syndrome and HA). LIMITATIONS, REASONS FOR CAUTION: We cannot exclude the possibility of inter- and intraobserver variation in the evaluation of AFC. WIDER IMPLICATIONS OF THE FINDINGS: With the newly recommended follicle count cutoff, a substantial proportion of women with PCOS might be classified as not having PCOS despite visiting a hospital due to irregular menstruation or hyperandrogenic symptoms. A practical approach to them would involve controlling the menstrual or hyperandrogenic symptoms in hand and regularly evaluating them regarding newly developed or worsening PCOS-related symptoms or metabolic abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Seoul National University Hospital Research Fund (No. 2520140090), Republic of Korea. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: Not applicable.

Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review.

Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have been widely used in various research applications, yet there are limitations such as invasiveness of obtaining samples, low yield and proliferation rate, and questions regarding their practicality in clinical applications. Some have suggested that MSCs from other sources, specifically those derived from palatine tonsil tissues, that is, tonsil-derived MSCs (TMSCs), could be considered as a new potential therapeutic tool in regenerative medicine due to their superior proliferation rate and differentiation capabilities with low immunogenicity and ease of obtaining. Several studies have determined that TMSCs have differentiation potential not only into the mesodermal lineage but also into the endodermal as well as ectodermal lineages, expanding their potential usage and placing them as an appealing option to consider for future studies in regenerative medicine. In this review, the differentiation capacities of TMSCs and their therapeutic competencies from past studies are addressed. Stem Cells 2019;37:1252-1260.

Successful Pregnancy and Delivery with Intracytoplasmic Sperm Injection in HIV-Serodiscordant Couple: the First Case in Korea.

With highly active antiretroviral therapy, human immunodeficiency virus (HIV) infection is considered to be a manageable chronic disease. The improved prognosis increases the desire of individuals with HIV to have biological offspring. With the establishment of washing protocol, no HIV transmission has been reported among more than 11,000 assisted reproduction technology (ART) cycles. Although the Acquired Immunodeficiency Syndrome Prevention Act in Korea prevents the use of HIV-infected blood, organs, tissues and semen, we recently obtained the authentic approval from the Korea Centers for Disease Control and Prevention for the practice of ART in HIV-serodiscordant couples. We report a 32-year-old HIV-seronegative female with her husband who was HIV-1 seropositive. After semen washing was performed by means of a density gradient and the swim-up technique, HIV-1 ribonucleic acid was not detected in the semen. An aliquot of processed semen was cryopreserved before ART. None of 3 cycles of intrauterine insemination was successful. After the third frozen-thawed embryo transfer following two cycles of intracytoplasmic sperm injection, an intrauterine singleton pregnancy was identified. She gave birth to a normal healthy male baby at full term by Cesarean section. She and her baby were tested for HIV during pregnancy and after delivery and the results were negative. Semen washing may be a safe ART method for HIV-serodiscordant couples who desire to have a baby in Korea.

Loss of abcd4 in zebrafish leads to vitamin B12-deficiency anemia.

ABCD4, a member of the ATP-binding cassette transporter superfamily, is associated with the transport of vitamin B12 which is crucial for the development of red blood cells (RBCs) and may also be involved in its metabolism. However, the molecular function of ABCD4 during RBC development in zebrafish is mostly unknown. Using a morpholino-based knockdown approach, we found that abcd4-knockdown resulted in abnormal RBCs of irregular shapes and various sizes. o-Dianisidine staining, as an indicator of hemoglobin in RBCs, further confirmed that abcd4 morphants possessed fewer hemoglobinized cells and impaired blood circulation. Multiple protein sequence alignment revealed that the amino acid sequence for residues 13-292, which is the domain of vitamin B12 transport, of the zebrafish Abcd4 was highly conserved compared to that of other species. Accordingly, the abcd4 morphants can be rescued with human ABCD4, demonstrating a conserved role of ABCD4 in vertebrates. Notably, the vitamin B12-deficient phenotype in abcd4 morphants, which causes anemia, was recapitulated in the newly-established abcd4 mutant, indicating the possibility that the abcd4 mutant could be used as a disease model of vitamin B12-deficiency anemia. Our study provides an insight that the analysis of the newly-established abcd4 mutant may contribute to understanding its roles in ABCD4-related vitamin B12-deficiency anemia and the associated pathogeneses in humans.

Phenotype and genotype of polycystic ovary syndrome in Asia: Ethnic differences.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, and ethnic diversity has been reported in its manifestation. This review addressed phenotype and genetic studies in Asian women with PCOS. Generally, East Asians are less hirsute, and the hirsutism score cutoff is lower than the Caucasian counterpart. It is not clear whether there are any significant differences in the prevalence or severity of irregular menstruation (IM) or characteristics of polycystic ovary (PCO) across ethnicities. Interestingly, the IM/PCO subgroup is a relatively common phenotype in East Asian patients but not in Caucasian patients. The prevalence of insulin resistance in PCOS patients varies depending on the index used and the cutoff, but women with PCOS showed a higher degree of insulin resistance than those of controls across ethnicities. Lower body mass index (BMI) and lower prevalence of metabolic syndrome were reported in East Asian patients, but despite lower BMI, a comparative study reported that Asian women with PCOS were more likely to have diabetes compared with Caucasian patients, suggesting they also have metabolic complications. Unlike East Asian patients, South Asian patients showed an increased degree of hirsutism, early onset of symptoms, and severe insulin resistance and metabolic risks compared with Caucasians. Genetic components play important roles in the pathogenesis of PCOS, and genome-wide association studies of PCOS suggest that similar genetic risk factors exist between Asian and Caucasian patients. Continuous comparative studies are needed to standardize the diagnosis and management of PCOS across different ethnicities.

Arterial stiffness measured by cardio-ankle vascular index in Korean women with polycystic ovary syndrome.

Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. The aim of this study was to evaluate arterial stiffness by CAVI in PCOS patients (n = 26) and in the age-matched controls (n = 59). The CAVI was measured by a single medical professional. The mean age of the women with PCOS was 33.3 (±6.6) years, and that of the matched controls was 33.1 (±5.9) years (p = .861). The mean CAVIs were similar between the patients and controls (6.49 ± 0.41 and 6.39 ± 0.65, respectively, p = .452). The CAVI increased linearly with age in both groups, but in the women with PCOS, CAVI showed relatively strong negative correlations with body mass index (BMI) in both the unadjusted (r = -0.537, p = .005) and adjusted models (r = -0.474, p = .003 after age and BMI adjustment and r = -0.604, p = .033 after age, BMI, sitting auscultatory systolic BP and square root hs-CRP adjustment). In conclusion, relatively young women with PCOS may not have increased arterial stiffness. A negative correlation between CAVI and BMI in women with PCOS requires further study to determine whether vascular adaptation to adiposity occurred in these women. Impact Statement What is already known on this subject? Increased arterial stiffness is one of the earliest adverse structural and functional alterations in blood vessels, potentially leading to later cardiovascular disease. Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. What do the results of this study add? The CAVIs were similar between the women with PCOS and the age-matched controls. The CAVI increased linearly with age in both groups, but in women with PCOS, CAVI showed a relatively strong negative correlation with the body mass index (BMI). What are the implications of these findings for clinical practice and/or further research? Relatively young women with PCOS may not have increased arterial stiffness. However, CAVI showed a negative correlation with BMI only in the women with PCOS, suggesting that adiposity itself is associated with the decreased arterial stiffness in these women. This finding requires a replication, and whether adaptation to the hemodynamic consequences of adiposity occurred in the PCOS patients remains to be established. Further longitudinal studies are needed to verify the relationships among vascular stiffness, adiposity and PCOS.

Clinical features and outcomes of abdominal tuberculosis in southeastern Korea: 12 years of experience.

BACKGROUND: Abdominal tuberculosis (TB) is an uncommon form of infection with Mycobacterium tuberculosis in Korea. In this study, we aimed to highlight the clinical features, diagnostic methods, and outcomes of abdominal TB over 12 years in Southeastern Korea. METHODS: A total of 139 patients diagnosed as having abdominal TB who received anti-TB medication from January 2005 to June 2016 were reviewed. Among them, 69 patients (49.6%) had luminal TB, 28 (20.1%) had peritoneal TB, 7 (5.0%) had nodal TB, 23 (16.5%) had visceral TB, and 12 (8.6%) had mixed TB. RESULTS: The most frequent symptoms were abdominal pain (34.5%) and abdominal distension (21.0%). Diagnosis of abdominal TB was confirmed using microbiologic and/or histologic methods in 76 patients (confirmed diagnosis), while the remaining 63 patients were diagnosed based on clinical presentation and radiologic imaging (clinical diagnosis). According to diagnostic method, frequency of clinical diagnosis was highest in patients with luminal (50.7%) or peritoneal (64.3%) TB, while frequency of microscopic diagnosis was highest in patients with visceral TB (68.2%), and frequency of histologic diagnosis was highest in patients with nodal TB (85.2%). Interestingly, most patients, except those with nodal TB, showed a good response to anti-TB agents, with 84.2% showing a complete response. The mortality rate was only 1.4% in the present study. CONCLUSIONS: Most patients responded very well to anti-TB therapy, and surgery was required in only a minority of cases of suspected abdominal TB.

A successful live birth with in vitro fertilization and thawed embryo transfer after conservative treatment of recurrent endometrial cancer.

Estrogen-dependent early stage endometrial cancer is relatively common in young women of reproductive age. The standard treatment is hysterectomy and bilateral salpingo-oophorectomy (BSO), even in early stage well-differentiated endometrial cancer patients. This surgical option results in permanent loss of fertility. There have been some reports of live births using in vitro fertilization after conservative management of endometrial cancer with high-dose progestin for the purpose of fertility preservation. However, most were not recurrent cases and pregnancy was achieved through conventional in vitro fertilization, which usually raises serum estradiol levels and may lead to the recurrence of endometrial cancer. To date, it is hard to find a case that can be referred for any possible different approach needed for the patients who experience recurrence. Here we report a successful live birth with in vitro fertilization using letrozole to maintain physiological levels of estradiol, and subsequent thawed embryo transfer after elective cryopreservation of embryos in a patient with recurrent endometrial cancer. There has been no evidence of disease recurrence at one year after delivery.

Relationship between serum anti-Mullerian hormone with vitamin D and metabolic syndrome risk factors in late reproductive-age women.

The relationship between serum anti-Mullerian hormone (AMH) with vitamin D (25OH-D) and metabolic syndrome (MetS) risk was evaluated in healthy, late reproductive-age (35-49 years) women with regular menstrual cycles. Among the 291 participants (mean age = 42.5 years), most (76.6%, n = 223) were serum vitamin D insufficient (<20 ng/ml). Mean serum levels of AMH and vitamin D were 2.04 ng/mL and 15.9 ng/mL, respectively. There was no correlation between AMH and 25OH-D after adjustment for age (r = -0.093, p = 0.113). Subjects with higher MetS score, higher waist circumference, and higher diastolic blood pressure had significantly higher serum AMH levels when adjusted for age, but the association attenuated when BMI was included. There was no significant correlation between MetS risk components with serum level of AMH or vitamin D. In conclusion, there was no association between AMH with serum 25OH-D or MetS risk factors in this population.

Prolactin receptor gene polymorphism and the risk of recurrent pregnancy loss: a case-control study.

Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student's t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss. Impact statement What is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and recurrent miscarriage, no replication study has been performed. What the results of this study add: The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent miscarriage group did not differ from that in the control group. What the implications are of these findings: Our study may be useful in that it is the first replication study since the initial report of the association of prolactin receptor gene polymorphism with recurrent miscarriage. Although no association was found, the potential role of prolactin in pregnancy loss needs to be further investigated because prolactin and its receptor have been postulated to play an important role in the maintenance of normal pregnancy.