[Factors Influencing Oncofertility in Gynecological Cancer Patients: Application of Mixed Methods Study].

PURPOSE: This study aimed to identify factors influencing oncofertility and to explore the oncofertility experiences of patients with gynecological cancer using quantitative and qualitative methods, respectively. METHODS: An explanatory sequential mixed-methods study was conducted. The quantitative study involved 222 patients with gynecological cancer recruited from online cafes and hospitals. Data were analyzed using IBM SPSS Statistics 28. For qualitative research, eight patients with gynecological cancer were interviewed. Data were analyzed using theme analysis method. RESULTS: Oncofertility performance was quantitatively assessed in 40 patients (18.0%). Factors that significantly affected oncofertility were fertility preservation awareness (odds ratio [OR] = 14.97, 95% confidence interval [CI]: 4.22~53.08), number of children planned before cancer diagnosis (OR = 6.08, 95% CI: 1.89~19.62; OR = 5.04, 95% CI: 1.56~16.29), monthly income (OR= 3.29, 95% CI: 1.23~8.86), social support (OR = 1.08, 95% CI: 1.01~1.17), and anxiety (OR = 0.79, 95% CI: 0.66~0.95). Qualitative results showed three theme clusters and eight themes: (1) themes for determinant factors affecting oncofertility selection: 'desire to have children' and 'special meaning of the uterus and ovaries;' (2) themes for obstructive factors affecting oncofertility selection: 'fertility preservation fall behind priorities,' 'confusion caused by inaccurate information,' and 'my choice was not supported;' (3) themes for support factors affecting oncofertility selection: 'provide accurate and reasonable information about oncofertility,' 'addressing the healthcare gap,' and 'need financial support for oncofertility.' CONCLUSION: Financial support, sufficient information, social support, and anxiety-relief interventions are required for oncofertility in patients with gynecological cancer.

Suspected paroxysmal dyskinesia in four small-breed dogs: Clinical presentation, diagnosis, management and prognosis.

This case report details the clinical presentation, diagnosis, management and prognosis of paroxysmal dyskinesia (PD) in four small-breed dogs, each weighing under 6 kg: A 7-year-old spayed female Pomeranian, an 8-year-old female mixed breed, a 1-year-old female Pomeranian and a 9-year-old castrated male Poodle. These dogs were referred to our hospital due to movement disorders. Diagnosis was facilitated by video recordings of the episodes, assessing motor activity, consciousness, episode duration, any pre- or post-episodic behaviour as well as the presence of autonomic signs. Magnetic resonance imaging conducted on two of the dogs returned unremarkable results. Treatment trials included a gluten-free diet for all four dogs, with two also receiving acetazolamide. This intervention led to a decrease in the frequency of abnormal movement in all patients. Our findings suggest that PD in dogs can be effectively diagnosed through detailed symptom description using videos and questionnaires. Furthermore, once diagnosed, a combination of nutritional and medical management can be beneficial.

Sensitive Electrochemical and Thermal Detection of Human Noroviruses Using Molecularly Imprinted Polymer Nanoparticles Generated against a Viral Target.

Norovirus (NoV) is the predominant cause of foodborne illness globally; current detection methods are typically expensive, have inadequate sensitivities, and utilize biological receptors with poor stability. Therefore, accurate, cost-effective, and highly stable detection methods are needed to screen for NoV in foods. We developed molecularly imprinted polymer nanoparticles (nanoMIPs) to detect NoV using a small target epitope (12 amino acids) with a solid-phase synthesis approach. The performance of three batches of nanoMIPs with varying monomer compositions (nanoMIP-1, -2, and -3) were compared both experimentally and computationally. Surface plasmon resonance examined nanoMIP binding affinity to norovirus virus-like particles (NoV-LPs), whereby nanoMIP-1 had the lowest KD value of 0.512 µM. This is significant, as traditional targets for generation of norovirus ligands previously reported were generated against drastically larger norovirus capsid segments that have limitations in ease of production. Further, an electrochemical sensor was developed by covalently attaching the nanoMIPs to glassy carbon electrodes. In agreement with our predictions from density functional theory simulations, electrochemical impedance spectroscopy showed a sensitive response toward NoV-LPs for nanoMIP batches tested; however, nanoMIP-1 was optimal, with an excellent detection limit of 3.4 pg/mL (1.9 × 105 particles/mL). Due to its exceptional performance, nanoMIP-1 was immobilized to screen-printed electrodes and utilized within a thermal sensor, where it exhibited a low detection limit of 6.5 pg/mL (3.7 × 105 particles/mL). Crucially, we demonstrated that nanoMIP-1 could detect NoV in real food samples (romaine lettuce) by using electrochemical and thermal sensors. Consequently, the study highlights the exceptional potential of nanoMIPs to replace traditional biological materials (e.g., antibodies) as sensitive, versatile, and highly stable receptors within NoV sensors.

Reconstructing Failure: Assessing Surgical and Patient Reported Outcomes Following Loss of Initial Breast Reconstruction.

BACKGROUND: Breast reconstruction failure, defined as the removal of a prosthetic device or flap without immediate replacement, can be traumatic for patients. We aim to describe the progression of patients who experience tissue expander (TE), implant, or autologous breast reconstructive failure and assess the patient reported outcomes (PROs) among patients who undergo additional reconstruction. METHOD: Patients undergoing TE, implant, or autologous breast reconstruction between 2017 and 2022 were included, and patients with reconstructive failures were identified. Outcomes of interests included (1) receipt of additional reconstruction and (2) BREAST-Q scores 1-year after reconstructive failure. We also performed a propensity-matched analysis between patients who undergo secondary reconstruction and patients who had an uncomplicated reconstruction. RESULTS: 4,258 TE, 4,420 implant, and 1,545 autologous breast reconstruction patients were included. Of patients who experienced reconstructive failures, 49.5% of TE, 4.8% of implant, and 53.8% of autologous patients underwent secondary reconstruction. Age, psychiatric diagnosis, chemotherapy, radiation, and mastectomy type were associated with increased likelihood of secondary reconstruction. Between patients with and without additional reconstruction, higher Psychosocial Well-being trended towards the former cohort (61 [Interquartile Range: 56, 80] vs 50 [46, 65], p=0.085). Propensity-matched analysis demonstrated comparable PROs at 1-year after definite reconstruction. CONCLUSION: Less than half of reconstructive failure patients undergo an additional reconstruction. Patients with secondary reconstruction may have improved Psychosocial Well-being than those who do not and comparable PROs to those who had uncomplicated initial reconstruction. Surgeons should counsel patients with reconstructive failures that although traumatizing, secondary reconstruction may be beneficial.

ECM stiffness regulates calcium influx into mitochondria via tubulin and VDAC1 activity.

Calcium ions (Ca2+) play pivotal roles in regulating numerous cellular functions, including metabolism and growth, in normal and cancerous cells. Consequently, Ca2+ signaling is a vital determinant of cell fate and influences both cell survival and death. These intracellular signals are susceptible to modulation by various factors, including changes in the extracellular environment, which leads to mechanical alterations. However, the effect of extracellular matrix (ECM) stiffness variations on intracellular Ca2+ signaling remains underexplored. In this study, we aimed to elucidate the mechanisms of Ca2+ regulation through the mitochondria, which are crucial to Ca2+ homeostasis. We investigated how Ca2+ regulatory mechanisms adapt to different levels of ECM stiffness by simultaneously imaging the mitochondria and endoplasmic reticulum (ER) in live cells using genetically encoded biosensors. Our findings revealed that the uptake of mitochondrial Ca2+ through Voltage-Dependent Anion Channel 1 (VDAC1), facilitated by intracellular tubulin, is influenced by ECM stiffness. Unraveling these Ca2+ regulatory mechanisms under various conditions offers a novel perspective for advancing biomedical studies involving Ca2+ signaling.

Inner retinal layer thickness alterations in adult and pediatric patients with neurofibromatosis 1.

This study compared the thickness of each intraretinal layer in patients with neurofibromatosis 1 (NF1) and controls to analyze the association between intraretinal layer thickness and visual function. The macular spectral-domain optical coherence tomography volumetric dataset obtained from 68 eyes (25 adult eyes, 43 pediatric eyes) with NF1 without optic glioma and 143 control eyes (100 adult eyes, 43 pediatric eyes) was used for image auto-segmentation. The intraretinal layers segmented from the volumetric data included the macular retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer. Cases and controls were compared after adjusting for age, sex, refractive error, and binocular use. The association between retinal layer thickness and visual acuity was also analyzed. The GCIPL was significantly thinner in both adult and pediatric patients with NF1 compared with healthy controls. Average RNFL and GCIPL thicknesses were associated with visual acuity in adult patients with NF1. In pediatric patients, average GCIPL thickness was associated with visual acuity. These results suggest that changes in the inner retinal layer could be a biomarker of the structural and functional status of patients with NF1.

National Trends in the Prevalence of Unmet Health Care and Dental Care Needs During the COVID-19 Pandemic: Longitudinal Study in South Korea, 2009-2022.

BACKGROUND: Although previous studies have investigated trends in unmet health care and dental care needs, most have focused on specific groups, such as patients with chronic conditions and older adults, and have been limited by smaller data sets. OBJECTIVE: This study aims to investigate the trends and relative risk factors for unmet health care and dental care needs, as well as the impact of the COVID-19 pandemic on these needs. METHODS: We assessed unmet health care and dental care needs from 2009 to 2022 using data from the Korea Community Health Survey (KCHS). Our analysis included responses from 2,750,212 individuals. Unmet health care or dental care needs were defined as instances of not receiving medical or dental services deemed necessary by experts or desired by patients. RESULTS: From 2009 to 2022, the study included 2,700,705 individuals (1,229,671 men, 45.53%; 673,780, 24.95%, aged 19-39 years). Unmet health care needs decreased before the COVID-19 pandemic; however, during the pandemic, there was a noticeable increase (ßdiff 0.10, 95% CI 0.09-0.11). Unmet dental care needs declined before the pandemic and continued to decrease during the pandemic (ßdiff 0.23, 95% CI 0.22-0.24). Overall, the prevalence of unmet dental care needs was significantly higher than that for unmet health care needs. While the prevalence of unmet health care needs generally decreased over time, the ß difference during the pandemic increased compared with prepandemic values. CONCLUSIONS: Our study is the first to analyze national unmet health care and dental care needs in South Korea using nationally representative, long-term, and large-scale data from the KCHS. We found that while unmet health care needs decreased during COVID-19, the decline was slower compared with previous periods. This suggests a need for more targeted interventions to prevent unmet health care and dental care needs.

Triplet Energy Transfer (EnT)-Promoted 1,3-Dipolar Cycloaddition Reactions of N-(Trimethylsilyl)methylphthalimide with Electron-Deficient Alkynes and Alkenes.

Triplet energy transfer (EnT)-promoted photochemical pathways, arisen by visible light and its photosensitizers, have gained significant attention as a complementary strategy for initiating organic transformations in photochemical reactions that are unlikely to occur through a single electron transfer (SET) process. In the present study, we investigated the triplet EnT-promoted 1,3-dipolar cycloaddition reactions of N-(trimethylsilyl)methylphthalimide with electron-deficient alkynyl and alkenyl dipolarophiles. The triplet excited state of N-(trimethylsilyl)methylphthalimide, promoted by the triplet EnT from thioxanthone (TXA) photosensitizer, underwent sequential intramolecular SET and carbon-to-oxygen migration of the silyl group to form azomethine ylide. This generated ylide cycloadded to alkynes or alkenes to regioselectively and stereospecifically produce a nitrogen-containing benzopyrrolizidine scaffold with multiple stereogenic centers. Crucially, the stereoselectivity of these cycloaddition reactions (i.e., endo versus exo addition) was influenced by the nature of the dipolarophiles.

Titania-Cored Janus Multipods as UV-Protective Pickering Emulsifiers for Sunscreens.

Pickering emulsifiers have gained significant interest as alternatives for conventional surfactants in various applications that includes pharmaceutics, food, homecare products, and cosmetics. However, their function is primarily focused on enhancing emulsion stability of which still remains to be resolved. Herein, Janus multipods are presented that simultaneously shield UV while offering high emulsion stability. These particles are prepared by growing multiple silicon dioxide (SiO2) nanopods using sol-gel method on a spherical titanium dioxide (TiO2) core with a thin SiO2 shell. The incorporation of high refractive index TiO2 in the core is shown to effectively shield UV while the SiO2 shell suppresses the photocatalytic activity. Moreover, by utilizing wax colloidosomes as templates, these multipod nanoparticles are further modified to exhibit Janus characteristics. This leads to strong adsorption of the Janus multipods at the oil/water emulsion interface where the multipod feature additionally reinforces the interfacial stabilization by interdigitation and interlocking of the Janus multipods to suppress detachment of the highly dense particles from the interface. As these Janus multipods offer effective UV protection as well as excellent emulsion stability, it is envisioned that they have great potential in advanced cosmetic formulations which require both enhanced sunscreen performance and better feeling in skincare products.

Natural product anticipation via chemical synthesis: Discovery of two new securinega alkaloids.

The isolation of a natural product conventionally precedes its chemical synthesis. Often, the isolation and structure determination of a natural product present in minute quantities in its natural source pose formidable challenges, akin to finding "a needle in a haystack." On the other hand, leveraging plausible biosynthetic insights and biomimetic synthetic expertise would allow for the prior synthesis of presumed natural products, followed by their verification in natural sources. In this study, we unveil two novel securinega alkaloids, securingines H and I, employing the natural product anticipation through synthesis approach. Structural analysis of securingines H and I suggests that they are biosynthetic derivatives of secu'amamine E and securinol A, respectively. We posit that this "synthesis first" strategy represents a valuable approach to the discovery of new natural products.

Erratum: Prevalence of Severe Atopic Dermatitis and Comorbid Chronic Systemic Diseases Is Increasing in Korean Children and Adolescents.

This corrects the article on p. 300 in vol. 16, PMID: 38910287.

Late-Onset Slowly Progressing Cone/Macular Dystrophy in Patients With the Biallelic Hypomorphic Variant p.Arg1933Ter in RP1.

Purpose: Homozygous hypomorphic variants of the RP1 gene, including c.5797C>T, p.Arg1933Ter, have traditionally been considered non-pathogenic. This study aimed to elucidate the clinical manifestations of late-onset, slowly progressive cone/macular dystrophy in patients homozygous for p.Arg1933Ter in the RP1 gene. Methods: Five patients with biallelic p.Arg1933Ter in RP1 were retrospectively recruited, and their clinical profiles were analyzed. Copy number variation analysis and Alu insertion assessment of genes associated with inherited retinal diseases were conducted. The results of comprehensive ophthalmological examinations, multimodal imaging, and full-field electroretinogram tests were analyzed. Results: No specific sequencing errors or structural variations associated with the clinical phenotypes were identified. Alu element insertion in RP1 was not detected. The mean ± SD age at the first visit was 62.2 ± 9.8 years, with symptoms typically starting between 45 and 50 years of age. Two patients exhibited a mild form of cone/macular dystrophy, characterized by a relatively preserved fundus appearance and blurring of the ellipsoid zone on optical coherence tomography. Three patients had late-onset cone/macular dystrophy with significant atrophy. Conclusions: To our knowledge, this study is the first to report that a homozygous hypomorphic variant of RP1, previously considered non-pathogenic, leads to cone/macular dystrophy. Translational Relevance: The study introduces novel possibilities suggesting that the homozygous hypomorphic variant of RP1 may be linked to variant pathogenicity.

Coating Robust Layers on Ni-Rich Cathode Active Materials while Suppressing Cation Mixing for All-Solid-State Lithium-Ion Batteries.

This study focused on addressing the challenges associated with the incompatibility between sulfide solid electrolytes and Ni-rich cathode active materials (CAMs) in all-solid-state lithium-ion batteries. To resolve these issues, protective layers have been explored for Ni-rich materials. Lithium lanthanum titanate (LLTO), a perovskite-type material, is recognized for its excellent chemical stability and ionic conductivity, which render it a potential protective layer in CAMs. However, traditional methods of achieving the perovskite structure involve temperatures exceeding 700 °C, resulting in challenges such as LLTO agglomeration, secondary phase formation between LLTO and CAM, and cation mixing within the CAM. In this study, a rapid technique known as flash-light sintering (FLS) was employed to fabricate a uniform and pure perovskite protective layer without inducing cation mixing within the CAM. The LLTO-coated LiNi0.8Co0.1Mn0.1O2 (NCM811) with FLS treatment demonstrated minimal cation mixing and formed a fully covered dense layer. This resulted in a high initial capacity and effectively addressed the incompatibility issues between the sulfide electrolytes and CAM. The rapid FLS method not only streamlines the fabrication of LLTO-coated NCM811 but also provides opportunities for its broader application to materials that were previously deemed impractical because of high sintering temperatures.

Potential Inflammatory Markers Related to the Conversion to Alzheimer's Disease in Female Patients With Late-Life Depression.

Background: Inflammation has been postulated as a mediating factor in the development of Alzheimer's disease (AD) pathology. We investigated candidate inflammatory markers related to conversion to AD among patients with depression. Methods: A longitudinal study was conducted with older women with depression who were at least 55 years of age, with a mean follow-up period of 5.73 years. At baseline, 9 inflammatory cytokines were measured using the immunoreactivity method. During follow-up, patients with depression who complained of cognitive impairment were evaluated and diagnosed with AD conversion. Association of the cytokines with conversion to AD was analyzed using multivariable Cox proportional hazards regression with adjusting covariates. For clinical applicability, the optimal cutoff value was determined using the minimum p value approach for the conversion to AD and was used to plot an AD-free survival curve. Results: Among 132 participants, 34 patients with depression (25.76%) developed AD during their follow-up period. Higher levels of interleukin (IL) 1ß at baseline (hazard ratio = 3.30 [95% CI, 1.11-9.78], p = .031) and lower levels of IL-10 (p < .001) were significantly associated with an increased risk of progression to AD. The survival curve plotted by the cutoff value of ≥0.25 pg/mL for IL-1ß and ≤0.15 pg/mL for IL-10 suggested adjusted hazard ratios of 8.96 (95% CI, 3.48-23.09; p < .001) for IL-1ß and 10.99 (p < .001) for IL-10, respectively. Conclusions: This study demonstrated that IL-1ß and IL-10 were associated with conversion to AD among patients with late-life depression, suggesting their potential as predictive markers of the transition to AD from depression.

Many patients with depression, more than expected, have been observed to be converted to Alzheimer's disease (AD) in the real world. We investigated potential inflammatory blood surrogate markers regarding progression from depression in late life to AD in 132 older Korean women with depression over a period of 1 to 18 years. Higher levels of the proinflammatory cytokine IL-1ß and lower levels of the anti-inflammatory cytokine IL-10 were associated with a higher risk of transition from depression to AD. These findings suggest that these markers could serve to predict the onset of AD in individuals with depression.

Synthesis and Structure Revision of Securingine E.

Chemical synthesis plays a crucial role in confirming and revising the structures of natural products. Through meticulous synthetic efforts, NMR spectroscopic and single-crystal X-ray diffraction analyses, DFT calculations, and mass spectrometric investigations, we revised the structure of securingine E. The revised structure of securingine E was unambiguously confirmed by its chemical synthesis.

Collagenase and Tyrosinase Inhibitory Compounds from Fish Gut Bacteria Ruegeria atlantica and Pseudoalteromonas neustonica.

Ruegeria atlantica and Pseudoalteromonas neustonica are fish gut bacteria that have been isolated from the guts of Pagrus major and Acanthopagrus schlegelii, respectively. A total of 22 compounds (1-22) were isolated from these two bacteria; 16 compounds (1-16) from R. atalantica and 6 compounds (17-22) from P. neustonica. Their chemical structures were elucidated by spectroscopic and spectrometric data analysis and chemical synthesis. Compounds 11 and 13 showed strong collagenase inhibitory activity, with 31.91% and 36.43% at 20 µM, respectively, comparable to or surpassing that of the positive control epigallocatechin gallate (EGCG, 34.66%). Also, compounds 11 and 14 exhibited a mild tyrosinase inhibitory effect of 6.73% and 13.68%, respectively. All of the tested compounds displayed no significant antibacterial activity against Escherichia coli and Bacillus subtilis up to 100 µM. The collagenase- and tyrosinase-inhibitory compound 11, cyclo(l-Pro-d-Leu), was found to be stable under heat (50 °C) and UV light (254 and 365 nm) for up to 6 days. These results indicate that compound 11 could be developed into a cosmeceutical with antiaging effects.

It is challenging to reproduce both anatomical and functional aspects of anterolateral reconstruction: postoperative 3D-CT analysis of the femoral tunnel position.

BACKGROUND: This study aimed to evaluate the femoral tunnel position and fiber length of the anterolateral ligament (ALL) reconstruction compared with the natural anatomy of the ALL. We also evaluated whether the femoral tunnel position would affect residual pivot shift. METHODS: This study was a retrospective review of 55 knees that underwent ALL reconstruction considering the anatomical and functional aspects, during primary anterior cruciate ligament (ACL) reconstruction in the presence of a high-grade pivot shift or revisional ACL reconstruction. We determined the position of the femoral tunnel and the length of graft using a three-dimensional (3D)-computed tomography (CT) model after ALL reconstruction. We also measured graft excursion during surgery and examined pivot shift 2 years after surgery. We conducted a subgroup analysis of femoral tunnel position, fiber length, isometricity, and residual pivot shift depending on whether the tunnel was anterior or posterior to the lateral epicondyle (LE). We also performed a subgroup analysis depending on whether the ACL reconstruction was primary or revisional. RESULTS: The mean femoral tunnel position was 2.04 mm posterior and 14.5 mm proximal from the center of the LE. The mean lengths of the anterior and posterior fibers were 66.6 and 63.4 mm, respectively. The femoral tunnel was positioned more proximally than the anatomical position, and both anterior and posterior ALL fibers were longer than the natural anatomy. The anteroposterior femoral tunnel position was significantly correlated with anterior (p = 0.045) and posterior (p = 0.037) fiber excursion. In the subgroup analysis, there was no significant difference in the residual pivot shift between the posterior and anterior tunnel positions. However, there were significant differences for proximal position (p < 0.001) and fiber length (p = 0.006). There was no significant difference between primary and revisional ACL regarding femoral tunnel position and fiber lengths. CONCLUSION: It is challenging to reproduce both anatomical and functional aspects of ALL reconstruction in both primary and revision ACL reconstruction. Especially for functional reconstruction, the femoral tunnel tended to be positioned more proximally than the anatomical position. However, the femoral tunnel position did not affect functional clinical outcomes at the 2-year follow-up. LEVEL OF EVIDENCE: Level IV Case series.

Predicting Postoperative Satisfaction with Breasts: How Important is the Preoperative BREAST-Q Score?

BACKGROUND: The role that preoperative Satisfaction with Breast plays in a patient's postoperative course after postmastectomy breast reconstruction (PMBR) is not understood. The aim of this study is to understand the impact of the preoperative score on postoperative outcome as an independent variable. METHODS: We examined patients who underwent PMBR between 2017 and 2021 and who completed the BREAST-Q Satisfaction with Breasts at 1 year postoperatively. Two multiple linear regression models (Model 1 with the preoperative Satisfaction with Breasts score and Model 2 without the preoperative score), likelihood ratio tests, simple t-statistics, and sample patient dataset to predict the 1 year score were performed. Multiple imputation was used to account for missing preoperative scores. RESULTS: Overall, 2324 patients were included. Model 1 showed that the preoperative score is significantly associated with the postoperative score (ß = 0.09, 95% confidence interval 0.04-0.14; p < 0.001). Comparing Model 1 and Model 2 demonstrated that including preoperative Satisfaction with Breasts in a regression significantly improves model fit (test statistic = 10.04; p = 0.0021). Using the absolute value of the t-statistics as a measure of variable importance in linear regression, the importance of the preoperative score was quantified as 3.39-more important than neoadjuvant radiation, mastectomy weight, body mass index, bilateral prophylactic mastectomy, and race, but less than adjuvant radiation, reconstruction type, and psychiatric diagnoses. CONCLUSION: Preoperative Satisfaction with Breasts scores are an important independent predictor of postoperative satisfaction after PMBR. Just as vital sign and work-up are carefully documented before surgery, preoperative scores should be collected to pre-emptively gauge patients' satisfaction and optimize postoperative outcomes.