Baeyer-Villiger monooxygenases belong to a family of flavin-binding proteins that catalyze the Baeyer-Villiger (BV) oxidation of ketones to produce lactones or esters, which are important intermediates in pharmaceuticals or sustainable materials. Phenylacetone monooxygenase (PAMO) from Thermobifida fusca with moderate thermostability catalyzes the oxidation of aryl ketone substrates, but is limited by high specificity and narrow substrate scope. In the present study, we applied loop optimization by loop swapping followed by focused saturation mutagenesis in order to evolve PAMO mutants capable of catalyzing the regioselective BV oxidation of cyclohexanone and cyclobutanone derivatives with formation of either normal or abnormal esters or lactones. We further modulated PAMO to increase enantioselectivity. Crystal structure studies indicate that rotation occurs in the NADP-binding domain and that the high B-factor region is predominantly distributed in the catalytic pocket residues. Computational analyses further revealed dynamic character in the catalytic pocket and reshaped hydrogen bond interaction networks, which is more favorable for substrate binding. Our study provides useful insights for studying enzyme-substrate adaptations.
Continual semantic segmentation (CSS) based on incremental learning (IL) is a great endeavour in developing human- like segmentation models. However, current CSS approaches encounter challenges in the trade-off between preserving old knowledge and learning new ones, where they still need large-scale annotated data for incremental training and lack interpretability. In this paper, we present Learning at a Glance (LAG), an efficient, robust, human- like and interpretable approach for CSS. Specifically, LAG is a simple and model-agnostic architecture, yet it achieves competitive CSS efficiency with limited incremental data. Inspired by human- like recognition patterns, we propose a semantic-invariance modelling approach via semantic features decoupling that simultaneously reconciles solid knowledge inheritance and new-term learning. Concretely, the proposed decoupling manner includes two ways, i.e., channel- wise decoupling and spatial-level neuron-relevant semantic consistency. Our approach preserves semantic-invariant knowledge as solid prototypes to alleviate catastrophic forgetting, while also constraining sample-specific contents through an asymmetric contrastive learning method to enhance model robustness during IL steps. Experimental results in multiple datasets validate the effectiveness of the proposed method. Furthermore, we introduce a novel CSS protocol that better reflects realistic data-limited CSS settings, and LAG achieves superior performance under multiple data-limited conditions.
Behavioral changes or neuropsychiatric symptoms (NPSs) are common features in dementia and are associated with accelerated cognitive impairment and earlier deaths. However, how NPSs are intertwined with cognitive decline remains elusive. In this study, we identify that the basolateral amygdala (BLA) is a key brain region that is associated with mood disorders and memory decline in the AD course. During the process from pre- to post-onset in AD, the dysfunction of parvalbumin (PV) interneurons and pyramidal neurons in the amygdala leads to hyperactivity of pyramidal neurons in the basal state and insensitivity to external stimuli. We further demonstrate that serotonin (5-HT) receptors in distinct neurons synergistically regulate the BLA microcircuit of AD rather than 5-HT levels, in which both restrained inhibitory inputs by excessive 5-HT1AR signaling in PV interneurons and depolarized pyramidal neurons via upregulated 5-HT2AR contribute to aberrant neuronal hyperactivity. Downregulation of these two 5-HT receptors simultaneously enables neurons to resist ß-amyloid peptides (Aß) neurotoxicity and ameliorates the mood and cognitive defects. Therefore, our study reveals a crucial role of 5-HT receptors for regulating neuronal homeostasis in AD pathogenesis, and this would provide early intervention and potential targets for AD cognitive decline.
OBJECTIVE: Inflammatory pain, is caused by lesions or diseases of the somatosensory tissue, is a prevalent chronic condition that profoundly impacts the quality of life. However, clinical treatment for this type of pain remains limited. Traditionally, the stimulation of microglia and subsequent inflammatory reactions are considered crucial elements to promote the worsening of inflammatory pain. Recent research has shown the crucial importance of the cGAS-STING pathway in promoting inflammation. It is still uncertain if the cGAS-STING pathway plays the role in the fundamental cause of inflammatory pain. We aim to explore the treatment of inflammatory pain by interfering with cGAS-STING signaling pathway. METHODS: In this study, we established an inflammatory pain model by CFA into the plantar of mice. Activation of microglia, various inflammatory factors and cGAS-STING protein in the spinal dorsal horn were evaluated. Immunofluorescence staining was used to observe the cellular localization of cGAS and STING. The cGAS-STING pathway proteins expression and mRNA expression of indicated microglial M1/M2 phenotypic markers in the BV2 microglia were detected. STING inhibitor C-176 was intrathecal injected into mice with inflammatory pain, and the pain behavior and microglia were observed. RESULTS: This research showed that injecting CFA into the left hind paw of mice caused mechanical allodynia and increased inflammation in the spine. Our research results suggested that the cGAS-STING pathway had a function in the inflammation mediated by microglia in the spinal cord dorsal horn. Blocking the cGAS-STING pathway using STING antagonists (C-176) led to reduced release of inflammatory factors and prevented M1 polarization of BV2 microglia in a laboratory setting. Additionally, intrathecal administration of C-176 reduced the allodynia in CFA treated mice. CONCLUSION: Our results suggest that inhibiting microglial polarization through the cGAS-STING pathway represents a potential novel therapeutic strategy for inflammatory pain.
The efficient design of Permanent Magnet Synchronous Motors (PMSMs) is crucial for their operational performance. A key design parameter, cogging torque, is significantly influenced by various structural parameters of the motor, complicating the optimization of motor structures. This paper proposes an optimization method for PMSM structures based on heuristic optimization algorithms, named the Permanent Magnet Synchronous Motor Self-Optimization Lift Algorithm (PMSM-SLA). Initially, a dataset capturing the efficiency of motors under various structural parameter scenarios is created using finite element simulation methods. Building on this dataset, a batch optimization solution aimed at PMSM structure optimization was introduced to identify the set of structural parameters that maximize motor efficiency. The approach presented in this study enhances the efficiency of optimizing PMSM structures, overcoming the limitations of traditional trial-and-error methods and supporting the industrial application of PMSM structural design.
Catnip (Nepeta cataria L.) plants produce a wide array of specialized metabolites with multiple applications for human health. The productivity of such metabolites, including nepetalactones, and natural insect repellents is influenced by the conditions under which the plants are cultivated. In this study, we assessed how field-grown catnip plants, transplanted after being propagated via either single-node stem cuttings or seeds, varied regarding their phytochemical composition throughout a growing season in two distinct environmental conditions (Pittstown and Upper Deerfield) in the state of New Jersey, United States. Iridoid terpenes were quantified in plant tissues via ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QqQ-MS), and phenolic compounds (phenolic acids and flavonoids) were analyzed via UHPLC with diode-array detection (UHPLC-DAD). The highest contents of total nepetalactones in Pittstown were found at 6 weeks after transplanting (WAT) for both seedlings and cuttings (1305.4 and 1223.3 mg/100 g, respectively), while in Upper Deerfield, the highest contents for both propagules were at 11 WAT (1247.7 and 997.1 mg/100 g, respectively) for seed-propagated and stem cuttings). The highest concentration of nepetalactones was associated with floral-bud to partial-flowering stages. Because plants in Pittstown accumulated considerably more biomass than plants grown in Upper Deerfield, the difference in nepetalactone production per plant was striking, with peak productivity reaching only 598.9 mg per plant in Upper Deerfield and 1833.1 mg per plant in Pittstown. Phenolic acids accumulated in higher contents towards the end of the season in both locations, after a period of low precipitation, and flavone glycosides had similar accumulation patterns to nepetalactones. In both locations, rooted stem cuttings reached their maximum nepetalactone productivity, on average, four weeks later than seed-propagated plants, suggesting that seedlings have, overall, better agronomic performance.
Nepeta , Seasons , Nepeta/chemistry , Chromatography, High Pressure Liquid , Phytochemicals/chemistry , Phytochemicals/analysis , Flavonoids/analysis , Flavonoids/chemistry , Cyclopentane Monoterpenes , Seeds/chemistry , Seeds/growth & development , Plant Extracts/chemistry , Iridoids/chemistry , Pyrones
This study employs five UV-AOPs (PMS, PDS, H2O2, NaClO and NaClO2) to produce radicals (â¢OH, SO4â¢-, ClOâ¢, O2â¢- and 1O2) and further comparatively studies their activity sequence and activity difference cause in toluene degradation. The toluene mineralization efficiency as a descending order is 73 % (UV-PMS) > 71 % (UV-PDS) > 70 % (acidified-UV-NaClO) > 55 % (UV-H2O2) > 36 % (UV-NaClO) > 35 % (UV-NaClO2); that of conversion efficiency is 99 % (acidified-UV-NaClO) > 95 % (UV-PMS) > 90 % (UV-PDS) > 74 % (UV-H2O2) > 44 % (UV-NaClO) > 41 % (UV-NaClO2). Acidic pretreatment significantly boosts the reactivity of UV-NaClO. ESR combined with radical quenching tests reveals the radicals' generation and evolution, and their contribution rates to toluene conversion, i.e. ClO⢠> SO4â¢- > O2â¢- > 1O2 > â¢OH. Theoretical calculations further unveil the ring-opening reaction routes and the nature of the activity difference of different radicals. The minimum energy required for ring-opening reaction is 116.77, 150.63, 168.29 and 191.92 kJ/mol with respect to ClOâ¢, SO4â¢-, 1O2 and â¢OH, and finding that the ClOâ¢-HO⢠pair is the best for toluene mineralization. The difficulty for eliminating typical VOCs by using UV-AOPs method is determined as toluene > chlorobenzene > benzene > ethyl acetate.
CeO2, particularly in the shape of rod, has recently gained considerable attention for its ability to mimic peroxidase (POD) and haloperoxidase (HPO). However, this multi-enzyme activities unavoidably compete for H2O2 affecting its performance in relevant applications. The lack of consensus on facet distribution in rod-shaped CeO2 further complicates the establishment of structure-activity correlations, presenting challenges for progress in the field. In this study, the HPO-like activity of rod-shaped CeO2 is successfully enhanced while maintaining its POD-like activity through a facile post-calcination method. By studying the spatial distribution of these two activities and their exclusive H2O2 activation pathways on CeO2 surfaces, this study finds that the increased HPO-like activity originated from the newly exposed (111) surface at the tip of the shortened rods after calcination, while the unchanged POD-like activity is attributed to the retained (110) surface in their lateral area. These findings not only address facet distribution discrepancies commonly reported in the literature for rod-shaped CeO2 but also offer a simple approach to enhance its antibacterial performance. This work is expected to provide atomic insights into catalytic correlations and guide the design of nanozymes with improved activity and reaction specificity.
To systematically evaluate the effects of quality nursing care on wound pain and anxiety in burn patients. Computerised searches of PubMed, Google Scholar, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure databases randomised controlled trials (RCTs) on the application of quality nursing care to burn patients were carried out from database inception to October 2023. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs and 1115 burn patients were included, including 563 and 552 in the quality care and routine care groups. It was found that, compared with routine care, burn patients who implemented quality care had significantly less wound pain (SMD: -1.79, 95% CI: -2.22 to -1.36, p < 0.001), anxiety (SMD: -2.71. 95% CI: -3.49 to -1.92, p < 0.001) and depression (SMD: -1.74, 95% CI: -2.35 to -1.14, p < 0.001) levels were significantly reduced post-trauma.
Anxiety , Burns , Humans , Anxiety/etiology , Anxiety Disorders , Pain , Burns/complications , Burns/therapy , China , Randomized Controlled Trials as Topic
OBJECTIVE: With the recent exponential increase in express deliveries across China, the number of patients with flame burns caused by electric bicycle battery chargers (BEBBC) has markedly increased in burn units. In this study, we aimed to characterize BEBBC to systematically explore measures to prevent their occurrence. METHODS: We performed a retrospective chart review of patients with flame burns who visited the Burn Department of Rui Jin Hospital between January 2015 and December 2021. RESULTS: Sixty-three patients with BEBBC and 1412 with types of other flame burn were included in this study. Fifty-six of the 63 BEBBC cases occurred between 9 pm and 7 am. BEBBC incidents involved a higher incidence of group burn in which multiple individuals were affected. Non-local patients with BEBBC were significantly younger than their local counterparts. BEBBC had a higher mortality than types of other flame burn. CONCLUSIONS: The rising incidence of BEBBC calls for greater attention because of the associated high mortality and heavy burden on society. Enacting related legislation, disseminating information to the public, and improving treatment to control infection can help prevent BEBBC, increase its cure rate, and reduce patient mortality.
Bicycling , Hospitals , Humans , Retrospective Studies , China/epidemiology
Glomalin-related soil protein (GRSP) is a significant component in the sequestration of heavy metal in soils, but its mechanisms for metal adsorption are poorly known. This study combined spectroscopic data with molecular docking simulations to reveal metal adsorption onto GRSP's surface functional groups at the molecular level. The EXAFS combined with FTIR and XPS analyses indicated that the adsorption of Cd(II), Sr(II), and Ni(II) by GRSP occurred mainly through the coordination of -OH and -COOH groups with the metal. The -COOH and -OH groups bound to the metal as electron donors and the electron density of the oxygen atom decreased, suggesting that electrostatic attraction might be involved in the adsorption process. Two-dimensional correlation spectroscopy revealed that preferential adsorption occurred on GRSP for the metal in sequential order of -COOH groups followed by -OH groups. The presence of the Ni-C shell in the Ni EXAFS spectrum suggested that Ni formed organometallic complexes with the GRSP surface. However, Sr-C and Cd-C were absent in the second shell of the Sr and Cd spectra, which was attributed to the adsorption of Sr and Cd ions with large hydration ion radius by GRSP to form outer-sphere complexes. Through molecular docking simulations, negatively charged residues such as ASP151 and ASP472 in GRSP were found to provide electrostatic attraction and ligand combination for the metal adsorption, which was consistent with the spectroscopic analyses. Overall, these findings provided new insights into the interaction mechanisms between GRSP and metals, which will help deepen our understanding of the ecological functions of GRSP in metal sequestration.
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immune homeostasis in multiple sclerosis (MS). Hence, we aimed to explore the therapeutic efficacy and safety of adoptive cell therapy (ACT) utilizing induced antigen-specific Tregs in an animal model of MS, that is, in an experimental autoimmune encephalomyelitis (EAE) model. B cells from EAE model that were activated with soluble CD40L were used as antigen-presenting cells (APCs) to induce the differentiation of antigen-specific Tregs from naïve CD4 precursors, and then, a stepwise isolation of CD4+CD25highCD127low Tregs was performed using a flow sorter. All EAE mice were divided into Treg-treated group (2 × 104 cells in 0.2 mL per mouse, n = 14) and sham-treated group (0.2 mL normal saline (NS), n = 20), which were observed daily for clinical assessment, and for abnormal appearance for 6 weeks. Afterward, histological analysis, immunofluorescence and real-time PCR were performed. Compared to sham-treated mice, Treg-treated mice exhibited a significant decrease in disease severity scores and reduced inflammatory infiltration and demyelination in the spinal cord. Additionally, Tregs-treated mice demonstrated higher CCN3 protein and mRNA levels than sham-treated mice. The results of this preclinical study further support the therapeutic potential of this ACT approach in the treatment of MS.
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis , Mice , Animals , T-Lymphocytes, Regulatory , Spinal Cord/pathology , Antigen-Presenting Cells , Mice, Inbred C57BL
BACKGROUND: A reduction in total lumbar range of motion (ROM) after lumbar fusion may offset the increase in intradiscal pressure (IDP) and facet joint force (FJF) caused by the abnormally increased ROM at adjacent segments. This study aimed to determine a relative total lumbar ROM rather than an ideal adjacent segment ROM to guide postoperative waist activities and further delay adjacent segment degeneration (ASD). METHODS: An intact L1-S1 finite element model was constructed and validated. Based on this, a surgical model was created to allow the simulation of L4/5 transforaminal lumbar interbody fusion (TLIF). Under the maximum total L1-S1 ROM, the ROM, IDP, and FJF of each adjacent segment between the intact and TLIF models were compared to explore the biomechanical influence of lumbar fusion on adjacent segments. Subsequently, the functional relationship between total L1-S1 ROM and IDP or total L1-S1 ROM and FJF was fitted in the TLIF model to calculate the relative total L1-S1 ROMs without an increase in IDP and FJF. RESULTS: Compared with those of the intact model, the ROM, IDP, and FJF of the adjacent segments in the TLIF model increased by 12.6-28.9%, 0.1-6.8%, and 0-134.2%, respectively. As the total L1-S1 ROM increased, the IDP and FJF of each adjacent segment increased by varying degrees. The relative total L1-S1 ROMs in the TLIF model were 11.03°, 12.50°, 12.14°, and 9.82° in flexion, extension, lateral bending, and axial rotation, respectively. CONCLUSIONS: The relative total L1-S1 ROMs after TLIF were determined, which decreased by 19.6-29.3% compared to the preoperative ones. Guiding the patients to perform postoperative waist activities within these specific ROMs, an increase in the IDP and FJF of adjacent segments may be effectively offset, thereby alleviating ASD.
Lumbar Vertebrae , Spinal Fusion , Humans , Finite Element Analysis , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/adverse effects , Range of Motion, Articular , Computer Simulation
Vanillin is a valuable natural product that can be used as a fragrance and additive. Recent research in the biosynthesis of vanillin has brought attention to a key enzyme, carboxylic acid reductase (CAR), which catalyzes the reduction of vanillic acid to vanillin. Nevertheless, the biosynthesis of vanillin is hampered by the low activity and stability of CAR. As such, a rational design campaign was conducted on a well-documented carboxylic acid reductase from Segniliparus rugosus (SrCAR), using vanillic acid as the model substrate. After combined active site saturation and iterative site-specific mutagenesis, the best quadruple mutant N292H/K524S/A627L/E1121W (M3) was successfully obtained. In comparison to the wildtype SrCAR, M3 demonstrated a 4.2-fold increase in catalytic efficiency (kcat/Km), and its half-life (t1/2) was enhanced by 3.8 times up to 385.08â¯minutes at 40⯰C. In silico docking and molecular dynamics simulation provided insights into the improved activity and stability. In the subsequent preparative-scale reaction with 100â¯mM (16.8â¯gâ¯L-1) vanillic acid, the whole cell catalysis utilizing M3 produced 10.15â¯g·L-1 of vanillin and 1.11â¯g·L-1 of vanillyl alcohol, respectively. This work demonstrates a dual improvement in the activity and thermal stability of SrCAR, thereby potentially facilitating the application of carboxylic acid reductase in the biosynthesis of vanillin.
Oxidoreductases , Vanillic Acid , Oxidoreductases/chemistry , Benzaldehydes
Correction for 'A Y1 receptor ligand synergized with a P-glycoprotein inhibitor improves the therapeutic efficacy of multidrug resistant breast cancer' by Yinjie Wang et al., Biomater. Sci., 2019, 7, 4748-4757, https://doi.org/10.1039/C9BM00337A.
OBJECTIVE: This study evaluates an AI assistant developed using OpenAI's GPT-4 for interpreting pharmacogenomic (PGx) testing results, aiming to improve decision-making and knowledge sharing in clinical genetics and to enhance patient care with equitable access. MATERIALS AND METHODS: The AI assistant employs retrieval-augmented generation (RAG), which combines retrieval and generative techniques, by harnessing a knowledge base (KB) that comprises data from the Clinical Pharmacogenetics Implementation Consortium (CPIC). It uses context-aware GPT-4 to generate tailored responses to user queries from this KB, further refined through prompt engineering and guardrails. RESULTS: Evaluated against a specialized PGx question catalog, the AI assistant showed high efficacy in addressing user queries. Compared with OpenAI's ChatGPT 3.5, it demonstrated better performance, especially in provider-specific queries requiring specialized data and citations. Key areas for improvement include enhancing accuracy, relevancy, and representative language in responses. DISCUSSION: The integration of context-aware GPT-4 with RAG significantly enhanced the AI assistant's utility. RAG's ability to incorporate domain-specific CPIC data, including recent literature, proved beneficial. Challenges persist, such as the need for specialized genetic/PGx models to improve accuracy and relevancy and addressing ethical, regulatory, and safety concerns. CONCLUSION: This study underscores generative AI's potential for transforming healthcare provider support and patient accessibility to complex pharmacogenomic information. While careful implementation of large language models like GPT-4 is necessary, it is clear that they can substantially improve understanding of pharmacogenomic data. With further development, these tools could augment healthcare expertise, provider productivity, and the delivery of equitable, patient-centered healthcare services.
Axially chiral aldehydes have emerged recently as a unique class of motifs for drug design. However, few biocatalytic strategies have been reported to construct structurally diverse atropisomeric aldehydes. Herein, we describe the characterization of alcohol dehydrogenases to catalyze atroposelective desymmetrization of the biaryl dialdehydes. Investigations into the interactions between the substrate and key residues of the enzymes revealed the distinct origin of atroposelectivity. A panel of 13 atropisomeric monoaldehydes was synthesized with moderate to high enantioselectivity (up to >99% ee) and yields (up to 99%). Further derivatization allows enhancement of the diversity and application potential of the atropisomeric compounds. This study effectively expands the scope of enzymatic synthesis of atropisomeric aldehydes and provides insights into the binding modes and recognition mechanisms of such molecules.
Antibiotic exist in various states after entering agricultural soil through the application of manure, including the aqueous state (I), which can be directly absorbed by plants, and the auxiliary organic extraction state (III), which is closely associated with the pseudo-permanence of antibiotics. However, effective analytical methods for extracting and affecting factors on fractions of different antibiotic states remain unclear. In this study, KCl, acetonitrile/Na2EDTA-McIlvaine buffer, and acetonitrile/water were successively used to extract states I, II, and III of 21 antibiotics in soil, and the recovery efficiency met the quantitative requirements. Random forest classification and variance partitioning analysis revealed that dissolved organic matter, pH, and organic matter were important factors affecting the recovery efficiency of antibiotic in states I, II, and III, respectively. Additionally, 65-day spiked soil experiments combined with Mantel test analysis suggested that pH, organic acids, heavy metals, and noncrystalline minerals differentially affected antibiotic type and state. Importantly, a structural equation model indicated that organic acids play a crucial role in the fraction of antibiotic states. Overall, this study reveals the factors influencing the fraction of different antibiotic states in soil, which is helpful for accurately assessing their ecological risk.
Metals, Heavy , Soil Pollutants , Soil/chemistry , Anti-Bacterial Agents , Metals, Heavy/analysis , Agriculture , Organic Chemicals/analysis , Acetonitriles , Soil Pollutants/analysis
BACKGROUND: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. METHODS: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y-V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. RESULTS: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y-V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (pï¼0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (pï¼0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. CONCLUSION: Constricted posterior fourchette seriously affects the quality of life. Y-V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.
Patient Satisfaction , Plastic Surgery Procedures , Surgical Flaps , Vulva , Humans , Female , Adult , Vulva/surgery , Vulva/abnormalities , Plastic Surgery Procedures/methods , Treatment Outcome , Middle Aged , Follow-Up Studies , Young Adult , Gynecologic Surgical Procedures/methods
