Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021.

BACKGROUND: This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. METHODS: The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. RESULTS: Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. CONCLUSIONS: The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.

Piperine improves the health span of Drosophila melanogaster with age- and sex-specific effect.

Piperine, a dietary phytochemical isolated from the Piper species, has been used as a natural medicine for pain, flu, and fever in ancient China and India. Although the health benefits of piperine have been widely studied, research on its effect on aging is limited. This study aimed to determine whether piperine has the potential to mitigate aging-related changes in the fruit fly (Drosophila melanogaster), which is an excellent model organism for studies on aging. The experiments were conducted using the newly eclosed or 30-day-old D. melanogaster wild-type strain Cantonized-white. Piperine was dissolved in 99% ethanol and added to the sucrose-yeast medium at a final concentration of 10, 35, 70, or 100 µM. The study examined the effects of piperine supplementation on the lifespan of D. melanogaster and other physiological functions, such as fecundity, feeding, lipid content, and resistance to environmental stress. Log-rank tests, Shapiro-Wilk test, F-test, t-test, or Wilcoxon rank sum test were used to analyze the data. Piperine failed to change the lifespan and body weight, but increased the fecundity and decreased the feeding rate in one-week-old flies. However, when piperine was fed to 30-day-old flies, it increased the lifespan of male flies and the fecundity and feeding rate of female flies. These results indicate that piperine can improve the health of aged flies. The findings suggest that piperine has age-dependent and sex-specific anti-aging effects in fruit flies.

Betulinic Acid Increases the Lifespan of Drosophila melanogaster via Sir2 and FoxO Activation.

Betulinic acid (BetA), a triterpenoid derivative found abundantly in the plant kingdom, has emerged as a promising candidate for promoting longevity. Many research studies have shown its antioxidant, anti-inflammatory, antiviral, and anticancer activities, making it an interesting subject for investigating its potential influence on lifespan. This study aimed to investigate the effects of BetA on longevity and the mechanisms associated with it using the fruit fly Drosophila melanogaster as the organism model. The results showed that 50 µM BetA supplementation extended the mean lifespan of fruit flies by 13% in males and 6% in females without any adverse effects on their physiology, such as fecundity, feeding rate, or locomotion ability reduction. However, 50 µM BetA supplementation failed to increase the lifespan in mutants lacking functional silent information regulator 2 (Sir2) and Forkhead box O (FoxO)-null, implying that the longevity effect of BetA is related to Sir2 and FoxO activation. Our study contributes to the knowledge in the field of anti-aging research and inspires further investigations into natural compounds such as BetA to enhance organismal healthspan.

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy.

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

Depressed Mood as a Significant Risk Factor for Gynecological Cancer Aggravation.

BACKGROUND: The aim of this study was to evaluate the relationship between depressed mood and gynecological cancer outcomes, identifying risk factors for cancer aggravation. METHODS: This study was a retrospective analysis of gynecological cancer patients (January 2020-August 2022) at Korea University Anam Hospital using Patient Health Questionnaire-9 (PHQ-9). Patients were classified into non-depressed mood (NDM)- and depressed mood (DM)-based scores. Statistical analysis was performed using Student's t-test, chi-square test, Fisher's exact test, Kaplan-Meier analysis, and Cox regression analyzing using SPSS. RESULTS: Of the 217 participants, the NDM group comprised 129 patients, and the DM group comprised 88. The two-year disease-free survival (DFS) rates showed significant differences (NDM, 93.6%; DM 86.4%; p = 0.006), but overall survival (OS) did not (p = 0.128). Patients with stage 3 or higher cancer, undergoing five or more chemotherapies, experiencing post-chemotherapy side effects, and depressed mood had an increased risk of cancer aggravation. CONCLUSIONS: Appropriate treatment of depressed mood, as well as adequate treatment for advanced gynecological cancer patients, those with numerous CTx., and those with post-CTx. side effects, may contribute to reducing the risk of cancer aggravation.

Cationic nanoplastic causes mitochondrial dysfunction in neural progenitor cells and impairs hippocampal neurogenesis.

Nanoplastics (NPs) exposure to humans can occur through various routes, including the food chain, drinking water, skin contact, and respiration. NPs are plastics with a diameter of less than 100 nm and have the potential to accumulate in tissues, leading to toxic effects. This study aimed to investigate the neurotoxicity of polystyrene NPs on neural progenitor cells (NPCs) and hippocampal neurogenesis in a rodent model. Toxicity screening of polystyrene NPs based on their charge revealed that cationic amine-modified polystyrene (PS-NH3+) exhibited cytotoxicity, while anionic carboxylate-modified polystyrene (PS-COO-) and neutral NPs (PS) did not. NPCs treated with PS-NH3+ showed a significant reduction in growth rate due to G1 cell cycle arrest. PS-NH3+ increased the expression of cell cycle arrest markers p21 and p27, while decreasing cyclin D expression in NPCs. Interestingly, PS-NH3+ accumulated in mitochondria, leading to mitochondrial dysfunction and energy depletion, which caused G1 cell cycle arrest. Prolonged exposure to PS-NH3+ in C17.2 NPCs increased the expression of p16 and senescence-associated secretory phenotype factors, indicating cellular senescence. In vivo studies using C57BL/6 mice demonstrated impaired hippocampal neurogenesis and memory retention after 10 days of PS-NH3+ administration. This study suggests that NPs could deplete neural stem cell pools in the brain by mitochondrial dysfunction, thereby adversely affecting hippocampal neurogenesis and neurocognitive functions.

Pivotal Clinical Study to Evaluate the Efficacy and Safety of Assistive Artificial Intelligence-Based Software for Cervical Cancer Diagnosis.

Colposcopy is the gold standard diagnostic tool for identifying cervical lesions. However, the accuracy of colposcopies depends on the proficiency of the colposcopist. Machine learning algorithms using an artificial intelligence (AI) system can quickly process large amounts of data and have been successfully applied in several clinical situations. This study evaluated the feasibility of an AI system as an assistive tool for diagnosing high-grade cervical intraepithelial neoplasia lesions compared to the human interpretation of cervical images. This two-centered, crossover, double-blind, randomized controlled trial included 886 randomly selected images. Four colposcopists (two proficient and two inexperienced) independently evaluated cervical images, once with and the other time without the aid of the Cerviray AI® system (AIDOT, Seoul, Republic of Korea). The AI aid demonstrated improved areas under the curve on the localization receiver-operating characteristic curve compared with the colposcopy impressions of colposcopists (difference 0.12, 95% confidence interval, 0.10-0.14, p < 0.001). Sensitivity and specificity also improved when using the AI system (89.18% vs. 71.33%; p < 0.001, 96.68% vs. 92.16%; p < 0.001, respectively). Additionally, the classification accuracy rate improved with the aid of AI (86.40% vs. 75.45%; p < 0.001). Overall, the AI system could be used as an assistive diagnostic tool for both proficient and inexperienced colposcopists in cervical cancer screenings to estimate the impression and location of pathologic lesions. Further utilization of this system could help inexperienced colposcopists confirm where to perform a biopsy to diagnose high-grade lesions.

Cadmium-treatment efficiency and membrane fouling during electrodialysis of wastewater discharged from zinc smelting.

Zinc smelting wastewater contains high concentrations of Cd. Here, the treatment efficiency of Cd using electrodialysis was evaluated. In addition, scale accumulation of ion-exchange membrane (IEM) was analyzed, and fouling control was studied. The results showed that spacers effectively improved the limiting current density but accelerated foulant accumulation. The Cd-treatment efficiency improved to 85.4% without a spacer. Dissolved organic carbon (DOC) and hydrophobic DOC levels in diluted water decreased by 0.65 mg L-1 and 2.1 mg L-1, respectively; in contrast, hydrophilic DOC level increased by 1.45 mg L-1. Some of the hydrophobic DOC in the diluted water was converted to hydrophilic DOC and subsequently to low-molecular-weight (LMW) DOC. DOC level in the concentrated water did not change substantially, but the LMW fraction of the hydrophilic DOC increased. In the cation-exchange membrane, a material composed of calcium sulfate accumulated in the bottom layer, and hydroxides of divalent and trivalent ions accumulated on top of it. In contrast, the anion-exchange membrane was fouled by humic substances. In terms of fouling control, physical and acid cleaning of IEMs was more effective than the reversal operation.

Probiotic Limosilactobacillus Reuteri (Lactobacillus Reuteri) Extends the Lifespan of Drosophila Melanogaster through Insulin/IGF-1 Signaling.

The term probiotic refers to bacteria that provide a beneficial effect to the host. Limosilactobacillus reuteri (Lactobacillus reuteri) is a probiotic isolated from human breast milk. Although L. reuteri has antimicrobial and anti-inflammatory activities occasionally linked to anti-aging effects, there are no reports of the effects of L. reuteri on longevity. This study evaluated the anti-aging effects of L. reuteri on the lifespan and physiology of Drosophila melanogaster. L. reuteri increased the mean lifespan of fruit flies significantly without reducing the reproductive output, food intake, or locomotor activity. Furthermore, the data suggested that the longevity effect of L. reuteri is mediated by the reduction of the insulin/IGF-1 signaling pathway and the action of reuterin, an antimicrobial compound produced by L. reuteri. These results show that L. reuteri can be used as a probiotic that acts as a dietary restriction mimetic with anti-aging effects.

Effects of Parental Dietary Restriction on Offspring Fitness in Drosophila melanogaster.

Dietary restriction (DR) is a well-established strategy to increase lifespan and stress resistance in many eukaryotic species. In addition, individuals fed a restricted diet typically reduce or completely shut down reproduction compared to individuals fed a full diet. Although the parental environment can lead to changes epigenetically in offspring gene expression, little is known about the role of the parental (F0) diet on the fitness of their offspring (F1). This study investigated the lifespan, stress resistance, development, body weight, fecundity, and feeding rate in offspring from parental flies exposed to a full or restricted diet. The offspring flies of the parental DR showed increases in body weight, resistance to various stressors, and lifespan, but the development and fecundity were unaffected. Interestingly, parental DR reduced the feeding rate of their offspring. This study suggests that the effect of DR can extend beyond the exposed individual to their offspring, and it should be considered in both theoretical and empirical studies of senescence.

Comparison of Surgical Outcomes between Single-Port Laparoscopic Surgery and Da Vinci Single-Port Robotic Surgery.

BACKGROUND: The aim of this study is to compare the surgical outcomes of single-port laparoscopic surgery (SPLS) and single-port robotic surgery (SPRS). METHODS: We retrospectively analyzed patients who underwent a hysterectomy, ovarian cystectomy, or myomectomy with SPLS or SPRS from January 2020 to July 2022. Statistical analyses were performed using the SPSS chi-square test and student's t-test. RESULTS: A total of 566 surgeries including single-port laparoscopic hysterectomy (SPLH; n = 148), single-port robotic hysterectomy (SPRH; n = 35), single-port laparoscopic ovarian cystectomy (SPLC; n = 207), single-port robotic ovarian cystectomy (SPRC; n = 108), single-port laparoscopic myomectomy (SPLM; n = 12), and single-port robotic myomectomy (SPRM; n = 56). The SPRH, SPRC, and SPRM groups had a shorter operation time than the SPLS group, although the results were not statistically significant (SPRH vs. SPLH, p = 0.134; SPRC vs. SPLC, p = 0.098; SPRM vs. SPLM, p = 0.202). Incisional hernia occurred as a postoperative complication in two patients only in the SPLH group. Postoperative Hb changes were lower in the SPRC and SPRM groups than in the SPLC and SPLM groups (SPRC vs. SPLC, p = 0.023; SPRM vs. SPLM, p = 0.010). CONCLUSIONS: Our study demonstrated that the SPRS had comparable surgical outcomes when compared to the SPLS. Therefore, the SPRS should be considered a feasible and safe option for gynecologic patients.

Trends in Gynecologic Carcinosarcoma Based on Analysis of the Surveillance Epidemiology End Result (SEER) Database.

Carcinosarcomas (malignant mixed Mullerian tumors) of a female genital organ are rare tumors associated with a poor survival. The purpose of this study was to identify site-specific differences in the incidence and prognosis in carcinosarcomas originating in the uterus, cervix, or ovary. The data of patients with gynecologic carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2016. The characteristics of gynecologic carcinosarcomas were compared using Pearson X2 and Fisher's exact tests. Kaplan-Meier models were used for cause-specific survival (CSS) analysis. The cohort included 7086 females, including 5731 cases of uterine carcinosarcoma, 161 cervical carcinosarcomas, and 1193 ovarian carcinosarcomas. The age-adjusted incidence rates of uterine, cervical, and ovarian carcinosarcoma were 3.9, 0.1, and 0.6 per 1,000,000, respectively. In the distribution of carcinosarcoma incidence by race, compared with the uterus or cervix, those originating from the ovary were unequally distributed in Caucasians (84.4% versus 69.6%, 67.7%; p < 0.001). The incidence of uterine carcinosarcoma steadily increased over time, from 2.2 in 2000 to 5.5 in 2016 (per 1,000,000), while cervical or ovarian carcinosarcoma showed no significant difference in incidence. The five-year CSS rates based on the site of origin (uterus, cervix, and ovary) were 39.9%, 33.1%, and 25.8%, respectively. The incidence rates of gynecologic carcinosarcoma, especially uterine carcinosarcoma, are gradually increasing. Although uterine carcinosarcoma is associated with a higher incidence than the others, it has a better prognosis compared with ovarian and cervical carcinosarcoma. The survival rates were worst in ovarian carcinosarcoma.

Application of Immune Checkpoint Inhibitors in Gynecological Cancers: What Do Gynecologists Need to Know before Using Immune Checkpoint Inhibitors?

Standard treatments for gynecological cancers include surgery, chemotherapy, and radiation therapy. However, there are limitations associated with the chemotherapeutic drugs used to treat advanced and recurrent gynecological cancers, and it is difficult to identify additional treatments. Therefore, immune checkpoint inhibitor (ICI) therapy products, including PD-1/PD-L1 inhibitors and CTLA-4 inhibitors, are in the spotlight as alternatives for the treatment of advanced gynecological cancers. Although the ICI monotherapy response rate in gynecological cancers is lower than that in melanoma or non-small cell lung cancer, the response rates are approximately 13-52%, 7-22%, and 4-17% for endometrial, ovarian, and cervical cancers, respectively. Several studies are being conducted to compare the outcomes of combining ICI therapy with chemotherapy, radiation therapy, and antiangiogenesis agents. Therefore, it is critical to determine the mechanism underlying ICI therapy-mediated anti-tumor activity and its application in gynecological cancers. Additionally, understanding the possible immune-related adverse events induced post-immunotherapy, as well as the appropriate management of diagnosis and treatment, are necessary to create a quality environment for immunotherapy in patients with gynecological cancers. Therefore, in this review, we summarize the ICI mechanisms, ICIs applied to gynecological cancers, and appropriate diagnosis and treatment of immune-related side effects to help gynecologists treat gynecological cancers using immunotherapy.

Factors associated with cervical cancer screening behaviors among young married female (aged 20-29) immigrants in South Korea.

OBJECTIVE: To identify factors that affect the participation of female immigrants in their 20s in the national cervical cancer screening programs. METHODS: Data were obtained from the National Health Insurance Services from 2016 to 2017. A total of 17,730 women who agreed to undergo cervical cancer screening during 2016-2017 were included in the study. RESULTS: Of the 17,730 women, 8,149 (46%) participated in cervical cancer screening, whereas, 9,581 (54%) did not. Logistic regression analysis of factors related to cervical cancer screening showed that the odds ratio (OR) of screening was higher in short duration of stay (OR, 1.18; 95% confidence interval [CI], 1.03-1.35), Chinese nationality (OR, 1.43; 95% CI, 1.28-1.59), unemployment (OR, 1; 95% CI, reference), participation in general health screening (OR, 4.16; 95% CI, 3.24-5.33), and comorbidities (OR, 1.16; 95% CI, 1.09-1.24) when compared to the other populations. The highest OR was associated with participation in general health screening. CONCLUSION: Appropriate programs should be developed to increase participation of socially vulnerable groups in cervical cancer screening. Such programs will improve awareness regarding cervical cancer screening and reduce disparities in healthcare.

The necessity of continuing cervical cancer screening of elderly Korean women aged 65 years or older.

BACKGROUND: Although the incidence of cervical cancer has decreased since the 1980s in Korea, it remains high among the elderly women. This study evaluated the suitability of cervical cancer screening for elderly Korean women aged ≥65 years according to recommendations by the American Society of Cytopathology and American Society for Colposcopy and Cervical Pathology. METHODS: We retrospectively reviewed the records of patients who underwent cervical cancer screening, followed by liquid-based Pap test, human papillomavirus (HPV) test, and colposcopic punch biopsy at two academic hospitals from May 2008 to May 2018. The participants were divided into two groups <65 and ≥65 years old. Logistic regression analysis was performed to evaluate the association between cytology tests, HPV tests and the occurrence of high-risk lesions, ≥cervical intraepithelial neoplasia2 (CIN2). RESULTS: The mean patient age was 49.02 ± 15.437 (range 15-91) years. No patients aged <25 years showed atypical squamous cell-cannot exclude high grade (ASC-H), squamous cell carcinoma (SCC), or adenocarcinoma (ADC). The incidence of high-grade squamous intraepithelial lesion (HISL) (39.7%) and ≥CIN 3 (40.2%) was significantly higher in patients ≥65 years of age than in other age groups. However, patients ≥65 years showed increased HSIL and HPV negativity and ASC-H, HSIL, and HPV positivity in those with ≥CIN 2 (both p = .043). CONCLUSION: Korean women aged ≥65 years should undergo cervical cancer screening. The relevance of HPV or Cytology test alone or co-test for screening should be evaluated in this population.

Analysis of the Relationship between Socioeconomic Status and Incidence of Hysterectomy Using Data of the Korean Genome and Epidemiology Study (KoGES).

Hysterectomy remains a frequent gynecologic surgery, although its rates have been decreasing. The aim of this study was to investigate whether socioeconomic status affected the risk of hysterectomy in Korean women. This prospective cohort study used epidemiologic data from 2001 to 2016, from the Korean Genomic and Epidemiology Study (KoGES). Multivariate logistic regression analyses were performed to estimate the association between household income or education level and hysterectomy. Among 5272 Korean women aged 40−69 years, 720 who had a hysterectomy and 4552 controls were selected. Variable factors were adjusted using logistic regression analysis (adjusted model). Adjusted odds ratios (aORs) for insurance type and hysterectomy were not statistically significant. The aOR was 1.479 (95% confidence interval (CI): 1.018−2.146, p < 0.05) for women with education of high school or lower compared to college or higher. Women whose monthly household income was

Field test of water-net based wastewater treatment for nutrient removal and bioethanol production.

In this study, an open pond constructed in Myanmar, a region with tropical climate and favorable environmental conditions for algae growth, was considered to conduct field experiments on sewage inflow river water. The nutrient removal efficiency and productivity of Hydrodictyon reticulatum (H. reticulatum) were analyzed, and the maximum fermentation limit concentration for bioethanol production was determined. Three ponds were operated in batch mode to investigate the effect of light intensity. Photoinhibition was caused due to excessive light intensity in summer season in the region with tropical climate resulting in reduced facility efficiency in the absence of shade. For light blocking, a transparent film was found to be more effective than a translucent film. In the transparent film shading facility, the nitrogen and phosphorus removal efficiencies were maintained above 76% and 81%, respectively, and the productivity of H. reticulatum was 2.27 g m-2 d-1. For a raceway open pond facility shaded with transparent film, the performance was evaluated based on hydraulic retention time (HRT), and the productivity of algae was found to increase with increasing supply of nitrogen and phosphorous. Maximum biomass production of 3.21 g m-2 d-1 was observed with an HRT of 3 d, suggesting the possibility of long-term operation. As a result of evaluating the ethanol production based on the initial concentration of H. reticulatum, the yield of bioethanol at the initial reducing sugar content of 120 g L-1 was 89.4%, but bioethanol production was only 8.9 g L-1.

The Increased Abundance of Commensal Microbes Decreases Drosophila melanogaster Lifespan through an Age-Related Intestinal Barrier Dysfunction.

BACKGROUND: Commensal microbiota live in their host with a symbiotic relationship that affects the host's health and physiology. Many studies showed that microbial load and composition were changed by aging and observed that increasing the abundance and changing the composition of commensal microbes had detrimental effects on host lifespan. We hypothesized that dysbiosis of the intestinal microbiota leads to systemic effects in aging flies as a result of the increased intestinal permeability. METHODS: We used the fruit fly, Drosophila melanogaster, laboratory strains w1118, as a model system with many advantages for microbe-host studies. RESULTS: The incidence of intestinal dysfunction was increased with age, and intestinal dysfunction increased the permeability of the fly intestine to resident microbes. The lifespan of flies with an intestinal barrier dysfunction was increased by removal of the microbes. Interestingly, some bacteria were also found in the hemolymph of flies with intestinal barrier dysfunction. CONCLUSION: Our findings suggest the possibility that, as the host ages, there is an increase in intestinal permeability, which leads to an increased intestinal microbial load and a reduction in the host lifespan. Our data therefore indicate a connection between commensal microbes and host lifespan.