Effects of ß-mannanase supplementation on intestinal health and growth of nursery pigs.

Two experiments were conducted using 120 pigs to test the hypothesis that supplementation of ß-mannanase could reduce digesta viscosity, enhance nutrient digestion, and improve intestinal health and growth of nursery pigs. In experiment 1, 48 crossbred barrows were randomly allotted to four treatments with increasing levels of ß-mannanase at 0, 200, 400, and 600 U/kg in feeds. All pigs were euthanized on day 12 to collect jejunal digesta to measure digesta viscosity and ileal digesta to measure apparent ileal digestibility (AID) of dry matter (DM), gross energy (GE), neutral detergent fiber (NDF), and acid detergent fiber (ADF). In experiment 2, 72 nursery pigs were randomly allotted to three treatments with increasing levels of ß-mannanase at 0, 400, and 600 U/kg in feeds. Plasma collected on day 9 was used to measure tumor necrosis factor-α (TNF-α), immunoglobulin G (IgG), malondialdehyde (MDA), and protein carbonyl (PC). All pigs were euthanized on day 10 to collect duodenal and jejunal tissues to evaluate the production of TNF-α, IL-6, and MDA, morphology, crypt cell proliferation, and expression of tight junction proteins in the jejunum. Data were analyzed using the MIXED procedure for polynomial contrasts and the NLMIXED procedure for broken-line analysis of SAS. In experiment 1, ß-mannanase supplementation tended to have quadratic effects on digesta viscosity (P = 0.085) and AID of GE (P = 0.093) in the pigs. In experiment 2, jejunal digesta viscosity of the pigs was reduced (P < 0.05) when ß-mannanase was supplemented at 360 U/kg of feed. ß-Mannanase supplementation linearly reduced (P < 0.05) TNF-α, IgG, MDA, and PC in the duodenum, and TNF-α, IgG, and MDA in the jejunum of the pigs. ß-Mannanase supplementation linearly increased (P < 0.05) villus height to crypt depth ratio and crypt cell proliferation in the jejunum. ß-Mannanase supplementation tended to linearly improve (P = 0.083) expression of zonula occludens-1 in the jejunum. In conclusion, supplementation of ß-mannanase at 360 U/kg reduced the digesta viscosity and up to 600 U/kg positively affected intestinal health and growth of pigs by reducing inflammation and oxidative stress whilst enhancing structure and barrier function in the jejunum.

Nursery pigs face challenges in digesting complex carbohydrates in their feeds, which can negatively affect their growth and intestinal health. In particular, ß-mannans can increase digesta viscosity and hinder nutrient digestion of nursery pigs. ß-Mannanase, an enzyme that breaks down ß-mannans, has been used in nursery feeds to alleviate negative impacts on nutrient utilization and intestinal health of nursery pigs. This study investigated the effects of increasing supplementation levels of ß-mannanase on intestinal health, nutrient utilization, and growth of nursery pigs. The results showed that supplementation of ß-mannanase at 360 U/kg in the feed reduced the digesta viscosity in the jejunum and up to 600 U/kg positively had beneficial effects on the intestinal health and growth of nursery pigs by reducing inflammation and oxidative stress through improving structure and barrier function in the jejunum.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Risk Factors for Treatment-Related Amenorrhea in Female Survivors of Childhood and Adolescent Cancer: 10-Year Experiences at Oncofertility Clinic in Korean Tertiary Center.

Purpose: This study investigates the impact of gonadotoxic cancer treatment on treatment-related amenorrhea (TRA) and hormonal status in pediatric and adolescent females who underwent fertility preservation (FP) consultation. Methods: A retrospective review was conducted on 143 females under 21 with cancer referred to the FP clinic at Seoul National University Hospital between 2011 and 2022. We analyzed variables, including age, menarche status, cancer type, and treatment. Subsequently, subjects were evaluated to identify clinical factors affecting TRA at 1-year intervals following the completion of treatment. Upon cancer diagnosis, all patients received FP counseling and underwent semiannual evaluations for menstrual resumption and hormonal status. Results: The median age at diagnosis was 15; menarche was reported in 76.9%. Bone sarcoma (16.1%) and acute lymphoblastic leukemia (14.7%) were predominant. Most consultations (74.8%) occurred pretreatment. After FP consultations, 9.8% of patients underwent oocyte cryopreservation, and 99.3% used gonadotropin-releasing hormone agonists during systemic chemotherapy. One year after treatment completion, TRA was shown in 29.4% of this cohort. Cyclophosphamide-equivalent dose >4000 mg/m2 (adjusted odds ratio [aOR], 2.279; 95% confidence interval [CI]; 1.018-5.105, p = 0.045) and pelvic irradiation (aOR, 16.271; 95% CI, 1.545-171.408; p = 0.020) were independent clinical factors predicting TRA. Conclusion: The study delineates the clinical factors affecting TRA in pediatric and adolescent cancer survivors, revealing the significant impact of specific treatment. The data highlight the critical role of personalized oncofertility consultations in this demographic, offering valuable insights for designing targeted FP strategies at tertiary centers.

Effects of Cetrorelix on Ovary and Endometrium Prior to Anti-PD-L1 Antibody in Murine Model.

BACKGROUND: Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration. METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. RESULTS: Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. CONCLUSION: Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PD-L1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.

Current Position of Oncofertility in Adolescent Female Cancer Patients: A Comparative Review on Society Guidelines.

Fertility preservation (FP) in pediatric and adolescent oncology patients presents a complex interplay between cancer treatment imperatives and reproductive aspirations, demanding a multi-disciplinary approach. Essential guidelines emphasize the importance of early referrals to FP specialists, ensuring timely counseling on oocyte and ovarian tissue cryopreservation options. Proper patient selection and risk assessment, considering intrinsic and extrinsic factors, is crucial for judicious resource utilization and optimal outcomes. Gonadotoxic effects of cancer treatments pose significant threats to reproductive capabilities. Oocyte cryopreservation (OC) is preferred in post-pubertal adolescents without partners. Cultural and religious concerns, especially regarding hymenal integrity, influence FP decisions, necessitating culturally sensitive consent processes. Ovarian tissue cryopreservation (OTC) offers an alternative for those unfit for OC. Despite its experimental label in some societies, emerging data support the efficacy of OTC, with ovarian tissue transplantation (OTT) showing promise in restoring ovarian function. However, the reintroduction of potentially malignant cells during transplantation remains a concern. Overall, while FP offers hope for future parenthood, the intricacies of decision-making and the potential medical, ethical, and cultural challenges underscore the importance of a personalized, multi-disciplinary approach. In this review, guidelines from various societies have been comprehensively reviewed and analyzed to provide insight into the clinical practice of oncofertility.

Enhancing Supplemental Effects of Acute Natural Antioxidant Derived from Yeast Fermentation and Vitamin C on Sports Performance in Triathlon Athletes: A Randomized, Double-Blinded, Placebo-Controlled, Crossover Trial.

This study investigated the acute effects of natural antioxidants, derived from yeast fermentation containing glutathione and dietary vitamin C supplementation, on metabolic function, skeletal muscle oxygenation, cardiac function, and antioxidant function during submaximal exercise in middle-aged triathlon athletes. Twelve participants (aged 49.42 ± 5.9 years) completed 90 min submaximal cycling trials corresponding to 70% maximal oxygen uptake with either vitamin C and glutathione (VitC+Glu), vitamin C (VitC), glutathione (Glu) supplementation, or placebo. Metabolic function (minute ventilation, oxygen uptake, carbon dioxide output [VCO2], respiratory exchange ratio [RER], oxygen pulse [O2pulse], carbohydrate oxidation, fat oxidation, and energy expenditure), skeletal muscle oxygenation (oxidized hemoglobin and myoglobin in skeletal muscle tissue, total hemoglobin and myoglobin in skeletal muscle tissue [tHb]), cardiac function (heart rate [HR], stroke volume [SV], cardiac output, end-diastolic volume, end-systolic volume, and ejection fraction), and antioxidant function parameters (blood lactate, superoxide dismutase, catalase, glutathione peroxidases, glutathione [GSH], diacron reactive oxygen metabolite [dROM], and biological antioxidant potential [BAP]) were measured during submaximal exercise and recovery. VCO2, RER, HR, blood lactate after exercise, and dROM were significantly lower, and O2pulse, tHb, and BAP were significantly higher for VitC+Glu than for the other trials (p < 0.05). In conclusion, combined vitamin C and glutathione supplementation was more effective in improving metabolic function, skeletal oxygenation, cardiac function, and antioxidant function during prolonged submaximal exercise in middle-aged triathletes.

Exogenous lactate intake immediately after endurance exercise increases time to exhaustion in VO2max measurements in mice.

PURPOSE: The purpose of the study was to investigate the effects of 4 weeks of lactate intake immediately after endurance exercise on maximal oxygen uptake (VO2max) in exercise performance. METHODS: Seven-week-old mice from the Institute of Cancer Research (ICR) were randomly divided into four groups: vehicle intake (SE/CON), lactate intake (SE/LAC), endurance exercise with vehicle intake (EX/ CON), and lactate intake with endurance exercise (EX/ LAC). Mice were subjected to 60-70% VO2max endurance exercise with or without oral lactate intake 5 days/ week for 4 weeks. VO2max measurements (VO2max, time to exhaustion (TTE), respiratory exchange rate, fat oxidation, and carbohydrate oxidation) were recorded at the end of the study period. After 48 h of VO2max measurement, the mice were sacrificed, and three different abdominal fat samples (epididymal, perirenal, and mesenteric) were collected. RESULTS: Body weight and abdominal fat mass did not differ between the groups. When measuring VO2max, endurance exercise raised VO2max, and lactate intake after endurance exercise increased TTE. The change in energy substrate utilization during VO2max measurement demonstrated that although the respiratory exchange rate and fat oxidation were enhanced by lactate intake, there were no synergistic effects of lactate intake and endurance exercise. CONCLUSION: Lactate intake immediately after endurance exercises can improve exercise performance, indicating the benefit of long-term exogenous lactate intake as an exercise supplement.

Efficacy of Feed Additive Containing Bentonite and Enzymatically Hydrolyzed Yeast on Intestinal Health and Growth of Newly Weaned Pigs under Chronic Dietary Challenges of Fumonisin and Aflatoxin.

This study aimed to investigate the efficacy of a feed additive containing bentonite and enzymatically hydrolyzed yeast on the intestinal health and growth of newly weaned pigs under chronic dietary exposure to fumonisin and aflatoxin. Newly weaned pigs were randomly allotted to one of four possible treatments: a control diet of conventional corn; a diet of corn contaminated with fumonisin and aflatoxin; a diet of mycotoxin-contaminated corn with 0.2% of feed additive; and a diet of mycotoxin contaminated corn with 0.4% of feed additive. We observed lower average weight gain and average daily feed intake in pigs that were fed only mycotoxin-contaminated corn compared to the control group. Feed additive supplementation linearly increased both average weight gain and feed intake, as well as tumor necrosis factor-alpha. In the jejunum, there was an observed decrease in immunoglobulin A and an increase in claudin-1. Additionally, feed additive supplementation increased the villus height to crypt depth ratio compared to the control. In conclusion, feed additives containing bentonite and enzymatically hydrolyzed yeast could mitigate the detrimental effects of mycotoxins on the growth performance of newly weaned pigs by improving intestinal integrity and positively modulating immune response.

Deep learning proton beam range estimation model for quality assurance based on two-dimensional scintillated light distributions in simulations.

BACKGROUND: Many studies have utilized optical camera systems with volumetric scintillators for quality assurances (QA) to estimate the proton beam range. However, previous analytically driven range estimation methods have the difficulty to derive the dose distributions from the scintillation images with quenching and optical effects. PURPOSE: In this study, a deep learning method utilized to QA was used to predict the beam range and spread-out Bragg peak (SOBP) for two-dimensional (2D) map conversion from the scintillation light distribution (LD) into the dose distribution in a water phantom. METHODS: The 2D residual U-net modeling for deep learning was used to predict the 2D water dose map from a 2D scintillation LD map. Monte Carlo simulations for dataset preparation were performed with varying monoenergetic proton beam energies, field sizes, and beam axis shifts. The LD was reconstructed using photons backpropagated from the aperture as a virtual lens. The SOBP samples were constructed based on monoenergetic dose distributions. The training set, including the validation set, consisted of 8659 image pairs of LD and water dose maps. After training, dose map prediction was performed using a 300 image pair test set generated under random conditions. The pairs of simulated and predicted dose maps were analyzed by Bragg peak fitting and gamma index maps to evaluate the model prediction. RESULT: The estimated beam range and SOBP width resolutions were 0.02 and 0.19 mm respectively for varying beam conditions, and the beam range and SOBP width deviations from the reference simulation result were less than 0.1 and 0.8 mm respectively. The simulated and predicted distributions showed good agreement in the gamma analysis, except for rare cases with failed gamma indices in the proximal and field-marginal regions. CONCLUSION: The deep learning conversion method using scintillation LDs in an optical camera system with a scintillator is feasible for estimating proton beam range and SOBP width with high accuracy.

Effect of topical estrogen cream compared with observation in prepubertal girls with labial adhesions.

BACKGROUND: Topical estrogen treatment has been considered the first-line treatment of labial adhesions in prepubertal girls. However, the effect of topical estrogen cream is different according to studies, and no study compared estrogen cream to observation. OBJECTIVE: This study aims to investigate the efficacy of topical estrogen cream treatment compared with observation in prepubertal girls with labial adhesions. STUDY DESIGN: The medical records of prepubertal girls diagnosed with labial adhesions from April 2005 to June 2019 were retrospectively analyzed. Baseline characteristics such as age at diagnosis and initial symptoms were collected. The primary outcome was the resolution of labial adhesion. Secondary outcomes were recurrence and side effects. RESULTS: A total of 114 patients were enrolled and divided into two groups, topical estrogen cream (n = 94), and observation (n = 20). Girls who were treated with estrogen cream had older age (24.6 ± 19.0 vs. 16.7 ± 15.3 months, p = 0.037) and higher resolution rate than the observation group (100.0% vs. 85.0%, respectively, p = 0.005). Girls younger than 23.3 months showed a significantly higher resolution rate to topical estrogen treatment (100% vs. 86.7%, p = 0.043). Side effects and recurrences occurred exclusively in children treated with topical estrogen therapy without significant differences compared to the observation group. CONCLUSION: Topical estrogen therapy showed a higher resolution rate than observation for the treatment of prepubertal girls with labial adhesions, especially in younger girls.

Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance.

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.

A study of quantitative indicators for slice sorting in cine-mode 4DCT.

The uncertainties of four-dimensional computed tomography (4DCT), also called as residual motion artefacts (RMA), induced from irregular respiratory patterns can degrade the quality of overall radiotherapy. This study aims to quantify and reduce those uncertainties. A comparative study on quantitative indicators for RMA was performed, and based on this, we proposed a new 4DCT sorting method that is applicable without disrupting the current clinical workflow. In addition to the default phase sorting strategy, both additional amplitude information from external surrogates and the quantitative metric for RMA, investigated in this study, were introduced. The comparison of quantitative indicators and the performance of the proposed sorting method were evaluated via 10 cases of breath-hold (BH) CT and 30 cases of 4DCT. It was confirmed that N-RMSD (normalised root-mean-square-deviation) was best matched to the visual standards of our institute's regime, manual sorting method, and could accurately represent RMA. The performance of the proposed method to reduce 4DCT uncertainties was improved by about 18.8% in the averaged value of N-RMSD compared to the default phase sorting method. To the best of our knowledge, this is the first study that evaluates RMA indicators using both BHCT and 4DCT with visual-criteria-based manual sorting and proposes an improved 4DCT sorting strategy based on them.

Soy protein concentrate replacing animal protein supplements and its impacts on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs.

This study was to evaluate the effects of soy protein concentrate (SPC) supplementation replacing animal protein supplements on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs. Thirty-two newly weaned pigs at 21 d of age with 6.4 ± 0.4 kg body weight (BW) were allotted to four treatments in a randomized complete block design with initial BW and sex as blocks. Pigs were fed for 35 d in three phases. Dietary treatments were SPC 0% (diets with fish meal 4/2/1%, poultry meal 10/8/4%, blood plasma 4/2/1%, and crude protein 24.6/22.6/20.9% for phase 1/2/3, respectively), SPC 33%, SPC 66%, and SPC 100% (SPC 0% diets with SPC replacing 33/66/100% of animal protein supplements, respectively). Pigs were euthanized on day 35 to collect jejunal mucosa and tissues to evaluate intestinal immune status, intestinal oxidative stress status, intestinal morphology, and mucosa-associated microbiota in the jejunum. Titanium dioxide was added in phase three diets as an indigestible marker. Ileal digesta was collected to measure apparent ileal digestibility (AID) of nutrients. Data were analyzed using MIXED and NLMIXED procedures of SAS. Increasing SPC supplementation by replacing animal protein supplements linearly decreased (P < 0.05) the BW, ADG, and ADFI of pigs during the overall period, and linearly increased (P < 0.05) peptide tyrosine tyrosine (PYY) in jejunum. Increasing SPC supplementation linearly decreased (P < 0.05) feed cost per weight gain. In the exponential model, SPC can replace animal protein supplements up to 10.5% and 16.5% without reducing the ADG and ADFI of pigs, respectively. The SPC 100% decreased (P < 0.05) Helicobacteraceae, Campylobacteraceae, alpha diversity, and changed beta diversity of microbiota in the jejunal mucosa. In conclusion, SPC supplementation replacing animal protein supplements reduced growth performance by reducing feed intake, which might be related to increased PYY. However, 10.5% and 16.8% of animal protein supplements can be replaced by SPC without affecting BW gain and feed intake of nursery pigs, respectively. Complete removal of animal protein supplements by SPC supplementation modulated the composition of jejunal mucosa-associated microbiota by reducing Helicobacteraceae and Campylobacteraceae, whereas without affecting the intestinal immune status, intestinal oxidative stress status, intestinal morphology, and AID of nutrients in nursery pigs.

Due to the high-quality nutrients and functional compounds, animal protein supplements are generally included in nursery pig diets to relieve the negative impacts caused by weaning stress. However, the high cost, short supply, and potential safety issues of animal protein supplements limit their use. Soybean meal is commonly used in swine diets due to the high nutritional values and competitive cost, however, antinutritional factors in soybean meal have been shown to impair the health and growth of nursery pigs. Soy protein concentrate is processed from soybean meal by ethanol extraction and efficiently removes the anti-nutritional factors. The aim of this study was to investigate the effects of soy protein concentrate replacing animal protein supplements at various levels on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, and growth performance of nursery pigs. The use of soy protein concentrate completely replacing animal protein supplements showed benefits on modulating the bacterial ecosystem on the mucosal lining of the small intestine by decreasing potentially harmful bacteria, whereas without affecting intestinal immune status, intestinal oxidative stress status, intestinal morphology, and nutrient digestibility. However, excessive use of soy protein concentrate replacing animal protein supplements decreased the weight gain of nursery pigs due to reduced feed intake.

The impact of sex steroids on osteonecrosis of the jaw.

Sex steroid hormones play a major role in bone homeostasis. Therefore, the use of sex hormones or drugs may increase the risk of osteonecrosis of the jaw (ONJ), a complication caused by damaged bone homeostasis. However, few are known the impact of medications changing sex hormone levels on ONJ. The pathophysiology of ONJ is not clearly understood and many hypotheses exist: cessation of bone remodeling caused by its anti-resorptive effect on osteoclasts; compromised microcirculation due to medication affecting angiogenesis, including bisphosphonate; and impairment of defense mechanism toward local infection. The use of high-dose intravenous bisphosphonate in cancer patients is associated with a high prevalence of ONJ. Exogenous estrogen or androgen replacement was reported to be associated with ONJ. Polycystic ovarian syndrome (PCOS) patients demonstrate an androgen excess status, and androgen overproduction serves as a protective factor in the bone mineral density of young women. To date, there are no reports of ONJ occurrence due to androgen overproduction. In contrast, few reports on the occurrence of ONJ due to estrogen deficiency induced by drugs, such as selective estrogen receptor modulator (SERM), aromatase inhibitors, and gonadotropin-releasing hormone (GnRH) agonists, are available. Thus, the role of sex steroids in the development of ONJ is not known. Further studies are required to demonstrate the exact role of sex steroids in bone homeostasis and ONJ progression. In this review, we will discuss the relationship between medication associated with sex steroids and ONJ.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Synergistic Promoting Effects of X-Linked Inhibitor of Apoptosis Protein and Matrix on the In Vitro Follicular Maturation of Marmoset Follicles.

BACKGROUND: In vitro follicular maturation (IVFM) of ovarian follicles is an emerging option for fertility preservation. Many paracrine factors and two-dimensional or three-dimensional (3D) environments have been used for optimization. However, since most studies were conducted using the murine model, the physiological differences between mice and humans limit the interpretation and adaptation of the results. Marmoset monkey is a non-human primate (NHPs) with more similar reproductive physiology to humans. In this study, we attempted to establish a 3D matrix (Matrtigel)-based IVFM condition for marmoset ovarian follicles in combination with anti-apoptotic factor, X-linked inhibitor of apoptosis protein (XIAP). METHODS: Marmoset follicles were isolated as individual follicles and cultured in a single drop with the addition of 0, 10, and 100 µg/mL of XIAP molecules. Matured oocytes and granulosa cells from mature follicles were collected and analyzed. The average number of isolated follicles was less than 100, and primordial and antral follicles were abundant in the ovaries. RESULTS: IVFM of marmoset follicles in 3D matrix conditions with XIAP increased the rates of survival and in vitro follicle development. Furthermore, oocytes from the 3D cultures were successfully fertilized and developed in vitro. The addition of XIAP increased the secretion of estradiol and aromatase. Furthermore, expression of granulosa-specific genes, such as bone morphogenetic protein 15, Oct4, and follicle-stimulating hormone receptor were upregulated in the in vitro-matured follicles than in normal, well-grown, and atretic follicles. Apoptosis-related B-cell lymphoma-2 was highly expressed in the atretic follicles than in the XIAP-treated follicles, and higher caspase-3 was localized in the XIAP-treated follicles. CONCLUSION: In this study, we attempted to establish a 3D-matrix-based marmoset IVFM condition and demonstrated the synergistic effects of XIAP. The use of a 3D matrix may be applied as an optimal culture condition for marmoset ovarian follicles.

Effects of Yarrowia lipolytica supplementation on growth performance, intestinal health and apparent ileal digestibility of diets fed to nursery pigs.

OBJECTIVE: The objective was to evaluate the efficacy of increasing supplementation of Yarrowia lipolytica (YL) up to 3.0% replacing 1.6% poultry fat and 0.9% blood plasma for growth performance, intestinal health and nutrient digestibility of diets fed to nursery pigs. METHODS: Twenty-four pigs weaned at 24 d of age (initial body weight at 7.2±0.6 kg) were allotted to three dietary treatments (n = 8) based on the randomized complete block. The diets with supplementation of YL (0.0%, 1.5%, and 3.0%, replacing poultry fat and blood plasma up to 1.6% and 0.9%, respectively) were fed for 21 d. Feed intake and body weight were recorded at d 0, 10, and 21. Fecal score was recorded at every odd day from d 3 to 19. Pigs were euthanized on d 21 to collect proximal and distal jejunal mucosa to measure intestinal health markers including tumor necrosis factor-alpha, interleukin-8, immunoglobulin A and immunoglobulin G. Ileal digesta was collected for apparent ileal digestibility (AID) of nutrients in diets. Data were analyzed using Proc Mixed of SAS. RESULTS: Supplementation of YL (1.5% and 3.0%) replacing poultry fat and blood plasma did not affect growth performance, fecal score and intestinal health. Supplementation of YL at 1.5% did not affect nutrient digestibility, whereas supplementation of YL at 3.0% reduced AID of dry matter (40.2% to 55.0%), gross energy (44.0% to 57.5%), crude protein (52.1% to 66.1%), and ether extract (50.8% to 66.9%) compared to diets without supplementation. CONCLUSION: Yarrowia lipolytica can be supplemented at 1.5% in nursery diets, replacing 0.8% poultry fat and 0.45% blood plasma without affecting growth performance, intestinal health and nutrient digestibility. Supplementation of YL at 3.0% replacing 1.6% poultry fat and 0.9% blood plasma did not affect growth performance and intestinal health, whereas nutrient digestibility was reduced.

Impact of BRCA mutations and hormone receptor status on reproductive potential in breast cancer patients undergoing fertility preservation.

OBJECTIVE: To identify whether the BRCA mutations and hormone receptor status affect the ovarian reserve and ovarian stimulation outcomes in breast cancer patients undergoing fertility preservation. METHODS: A total of 117 women diagnosed with breast cancer who were referred to the fertility preservation clinics at Seoul National University Bundang Hospital and Seoul National University Hospital between September 2012 and July 2019 undergone ovarian stimulation for oocyte retrieval. Basal characteristics including age, BMI, basal AMH, basal FSH, and fertility preservation outcomes such as the number of retrieved oocytes and mature oocytes were compared retrospectively. RESULTS: BRCA1 mutation was noted in 25 women, and BRCA2 mutation was observed in 35 women. Positive estrogen receptor status was noted in 87 women, and positive progesterone receptor status was noted in 69 women. HER2 was positive in 55 women, and 19 women were diagnosed with triple-negative breast cancers. The number of total oocytes retrieved was lower in patients with BRCA mutation (8.3 ± 5.4 vs. 15.3 ± 8.7, p = .002). The number of mature oocytes retrieved was also lower in BRCA carriers (4.7 ± 4.2 vs. 8.7 ± 7.9, p = .025). Triple-negative breast cancer (TNBC) patients were younger than non-TNBC patients (30.3 ± 4.8 vs. 33.9 ± 5.0, p = .007). The rate of mature oocyte rate was higher in TNBC patients (68.6%±20.6 vs. 52.5%±29.7, p = .037). CONCLUSIONS: Our study demonstrated that BRCA carriers with breast cancer had comparable ovarian reserve to non-carriers but the response to ovarian stimulation was lower. We also observed that oocyte maturity was higher in TNBC patients, however age might be a confounding factor of this result.

The association between hyperuricemia and cardiovascular disease history: A cross-sectional study using KoGES HEXA data.

This cross-sectional study examines the association between hyperuricemia and cardiovascular diseases (CVDs). Data from the Korean Genome and Epidemiology Study from 2004 to 2016 were analyzed. Among the 173,209 participants, we selected 11,453 patients with hyperuricemia and 152,255 controls (non-hyperuricemia). We obtained the history of CVDs (stroke and ischemic heart disease [IHD]) from all participants. Crude and adjusted odds ratios (aORs) (age, income group, body mass index, smoking, alcohol consumption, anthropometry data, and nutritional intake) for CVDs were analyzed using a logistic regression model. Participants with hyperuricemia reported a significantly higher prevalence of stroke (2.4% vs 1.3%) and IHD (5.6% vs 2.8%) than controls did (P < .001). Participants with hyperuricemia had a significantly higher aOR for CVD than the controls. The aOR of hyperuricemia for stroke was 1.22 (95% confidence interval = 1.07-1.39, P = .004). When analyzed by subgroup according to age and sex, this result was only persistent in women. The aOR of hyperuricemia for IHD was 1.45 (95% confidence interval = 1.33-1.59, P < .001). In the subgroup analyses, the results were similar, except in young men. Hyperuricemia was significantly associated with CVD in the Korean population.