Evaluation of cosmetic outcomes in breast reconstruction patients undergoing radiotherapy using an anomaly generative adversarial network model.

Considering the rising prevalence of breast reconstruction followed by radiotherapy (RT), evaluating the cosmetic impact of RT is crucial. Currently, there are limited tools for objectively assessing cosmetic outcomes in patients who have undergone reconstruction. Therefore, we validated the cosmetic outcome using a previously developed anomaly Generative Adversarial Network (GAN)-based model and evaluated its utility. Between January 2016 and December 2020, we collected computed tomography (CT) images from 82 breast cancer patients who underwent immediate reconstruction surgery followed by radiotherapy. Among these patients, 38 received immediate implant insertion, while 44 underwent autologous breast reconstruction. Anomaly scores (AS) were estimated using an anomaly GAN model at pre-RT, 1st follow-up, 1-year (Post-1Y) and 2-year (Post-2Y) after RT. Subsequently, the scores were analyzed in a time-series manner, considering reconstruction types (implant versus autologous), RT techniques, and the incidence of major complications. The median age of the patients was 46 years (range 29-62). The AS between Post-1Y and Post-2Y demonstrated a positive relationship (coefficient 0.515, P < 0.001). The AS was significantly associated with objective cosmetic indices, namely Breast Contour Difference (P = 0.009) and Breast Area Difference (P = 0.004), at both Post-1Y and Post-2Y. Subgroup analysis stratified by type of breast reconstruction revealed significantly higher AS values in patients who underwent prosthetic implant insertion compared to those with autologous reconstruction at all follow-up time points (1st follow-up, P = 0.001; Post-1Y, P < 0.001; and Post-2Y, P < 0.001). A threshold AS of ≥ 1.9 was associated with a 10% predicted risk of developing major complications. The feasibility of an AS generated by a GAN model for predicting both cosmetic outcomes and the likelihood of complications following RT has been successfully validated. Further investigation involving a larger patient cohort is warranted.

Groundwater health risk assessment of North China Plain based on Monte Carlo model sensitivity analysis and morphological analysis: A case study of Shijiazhuang City.

The rapid development of the social economy and the influence of human activities can lead to aggravated groundwater pollution. Groundwater safety is the premise of residents' health. Therefore, studying the sustainable utilization and health risks of groundwater quality is important. The groundwater quality and potential health risks were evaluated in the Shijiazhuang area, which is located in the North China Plain in this paper. Based on 159 groundwater samples collected in the study area, the potential health risks of As, Cr6+, Ni, Pb, F-, and NO3 - to humans were evaluated from oral and skin contact. Results of the human health risk assessment showed that the average carcinogenic risk and non-carcinogenic risk of children are higher than those of adults. According to the spatial distribution of the total risk value, adults and children in the southwest of the study area face higher risks. Because of the uncertainty of USEPA, Monte Carlo simulation was used to calculate the probability of health risk assessment and prioritization of contaminant treatment. The results of the Monte Carlo simulation showed that the acceptable range for children is 6.82%, and the acceptable range for adults is 18.07%. According to the HRWM model, carcinogenic pollutants mainly include As, Cr6+, and Ni. The most important chemical species of As is HAsO4 2-, followed by H2AsO4 -. Similarly, CrO4 2- and Ni2+ are the main forms of Cr6+ and Ni. The results of this study can provide data support for the protection and management of groundwater quality in the North China Plain. PRACTITIONER POINTS: Children are more susceptible to carcinogenic risk than adults. After calculation, the main influencing elements are Ni and Cr. Metal morphology analysis was carried out, and the results showed that HAsO4 2-, CrO4 2-, and Ni2+ were the main types.

A molecular beacon design for a colorimetric loop-mediated isothermal amplification assay.

In this study, a molecular beacon (MB) was designed for colorimetric loop-mediated isothermal amplification (cLAMP). The length of complementary bases on the MB, guanine and cytosine content (GC content), and hybridization sites of complementary bases were investigated as key factors affecting the design of the MB. We designed MBs consisting of 10, 15, and 20 complementary bases located at both ends of the HRPzyme. In the case of the long dumbbell DNA structure amplified from the hlyA gene of Listeria monocytogenes, possessing a flat region (F1c-B1) of 61 base pairs (bp), an MB was designed to intercalate into the flat region between the F1c and B1 regions of the LAMP amplicons. In the case of the short dumbbell DNA structure amplified from the bcfD gene of Salmonella species possessing a flat region (F1c-B1) length of 6 bp, another MB was designed to intercalate into the LoopF or LoopB regions of the LAMP amplicons. The results revealed that the hybridization site of the MB on the LAMP amplicons was not crucial in designing the MB, but the GC content was an important factor. The highest hybridization efficiencies for LAMP amplicons were obtained from hlyA gene-specific and bcfD gene-specific MBs containing 20- and 15-base complementary sequences, respectively, which exhibited the highest GC content. Therefore, designing MBs with a high GC content is an effective solution to overcome the low hybridization efficiency of cLAMP assays. The results obtained can be used as primary data for designing MBs to improve cLAMP accessibility.

A nationwide study of breast reconstruction after mastectomy in patients with breast cancer receiving postmastectomy radiotherapy: comparison of complications according to radiotherapy fractionation and reconstruction procedures.

BACKGROUND: We examined the patterns of breast reconstruction postmastectomy in breast cancer patients undergoing postmastectomy radiotherapy (PMRT) and compared complications based on radiotherapy fractionation and reconstruction procedures. METHODS: Using National Health Insurance Service (NHIS) data (2015-2020), we analysed 4669 breast cancer patients with PMRT and reconstruction. Using propensity matching, cohorts for hypofractionated fractionation (HF) and conventional fractionation (CF) were created, adjusting for relevant factors and identifying grade ≥3 complications. RESULT: Of 4,669 patients, 30.6% underwent HF and 69.4% CF. The use of HF has increased from 19.4% in 2015 to 41.0% in 2020. Immediate autologous (32.9%) and delayed two-stage implant reconstruction (33.9%) were common. Complication rates for immediate (N = 1286) and delayed two-stage (N = 784) reconstruction were similar between HF and CF groups (5.1% vs. 5.4%, P = 0.803, and 10.5% vs. 10.7%, P = 0.856, respectively) with median follow-ups of 2.5 and 2.6 years. HF showed no increased risk of complications across reconstruction methods. CONCLUSION: A nationwide cohort study revealed no significant difference in complication rates between the HF and CF groups, indicating HF for reconstructed breasts is comparable to CF. However, consultation regarding the fractionation for reconstructed breast cancer patients may still be necessary.

The impact of the new ESTRO-ACROP target volume delineation guidelines for postmastectomy radiotherapy after implant-based breast reconstruction on breast complications.

The European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) updated a new target volume delineation guideline for postmastectomy radiotherapy (PMRT) after implant-based reconstruction. This study aimed to evaluate the impact on breast complications with the new guideline compared to the conventional guidelines. In total, 308 patients who underwent PMRT after tissue expander or permanent implant insertion from 2016 to 2021 were included; 184 received PMRT by the new ESTRO-ACROP target delineation (ESTRO-T), and 124 by conventional target delineation (CONV-T). The endpoints were major breast complications (infection, necrosis, dehiscence, capsular contracture, animation deformity, and rupture) requiring re-operation or re-hospitalization and any grade ≥2 breast complications. With a median follow-up of 36.4 months, the cumulative incidence rates of major breast complications at 1, 2, and 3 years were 6.6%, 10.3%, and 12.6% in the ESTRO-T group, and 9.7%, 15.4%, and 16.3% in the CONV-T group; it did not show a significant difference between the groups (p = 0.56). In multivariable analyses, target delineation is not associated with the major complications (sHR = 0.87; p = 0.77). There was no significant difference in any breast complications (3-year incidence, 18.9% vs. 23.3%, respectively; p = 0.56). Symptomatic RT-induced pneumonitis was developed in six (3.2%) and three (2.4%) patients, respectively. One local recurrence occurred in the ESTRO-T group, which was within the ESTRO-target volume. The new ESTRO-ACROP target volume guideline did not demonstrate significant differences in major or any breast complications, although it showed a tendency of reduced complication risks. As the dosimetric benefits of normal organs and comparable oncologic outcomes have been reported, further analyses with long-term follow-up are necessary to evaluate whether it could be connected to better clinical outcomes.

Discrimination in Medical Settings across Populations: Evidence From the All of Us Research Program.

INTRODUCTION: Discrimination in medical settings (DMS) contributes to healthcare disparities in the United States, but few studies have determined the extent of DMS in a large national sample and across different populations. This study estimated the national prevalence of DMS and described demographic and health-related characteristics associated with experiencing DMS in seven different situations. METHODS: Survey data from 41,875 adults participating in the All of Us Research Program collected in 2021-2022 and logistic regression were used to examine the association between sociodemographic and health-related characteristics and self-reported DMS among adults engaged with a healthcare provider within the past 12 months. Statistical analysis was performed in 2023-2024. RESULTS: About 36.89% of adults reported having experienced at least one DMS situation. Adults with relative social and medical disadvantages had higher prevalence of experiencing DMS. Compared to their counterparts, respondents with higher odds of experiencing DMS in at least one situation identified as female, non-Hispanic Black, having at least some college, living in the South, renter, having other living arrangement, being publicly insured, not having a usual source of care, having multiple chronic conditions, having any disability, and reporting fair or poor health, p<0.05. CONCLUSIONS: The findings indicate a high prevalence of DMS, particularly among some population groups. Characterizing DMS may be a valuable tool for identifying populations at risk within the healthcare system and optimizing the overall patient care experience. Implementing relevant policies remains an essential strategy for mitigating the prevalence of DMS and reducing healthcare disparities.

Barriers and Facilitators to Establishing Partnerships for Substance Use Disorder Care Transitions Between Safety-Net Hospitals and Community-Based Organizations.

BACKGROUND: The effectiveness of hospital-based transitional opioid programs (TOPs), which aim to connect patients with substance use disorders (SUD) to ongoing treatment in the community following initiation of medication for opioid use disorder (MOUD) treatment in the hospital, hinges on successful patient transitions. These transitions are enabled by strong partnerships between hospitals and community-based organizations (CBOs). However, no prior study has specifically examined barriers and facilitators to establishing SUD care transition partnerships between hospitals and CBOs. OBJECTIVE: To identify barriers and facilitators to developing partnerships between hospitals and CBOs to facilitate care transitions for patients with SUDs. DESIGN: Qualitative study using semi structured interviews conducted between November 2022-August 2023. PARTICIPANTS: Staff and providers from hospitals affiliated with four safety-net health systems (n=21), and leaders and staff from the CBOs with which they had established partnerships (n=5). APPROACH: Interview questions focused on barriers and facilitators to implementing TOPs, developing partnerships with CBOs, and successfully transitioning SUD patients from hospital settings to CBOs. KEY RESULTS: We identified four key barriers to establishing transition partnerships: policy and philosophical differences between organizations, ineffective communication, limited trust, and a lack of connectivity between data systems. We also identified three facilitators to partnership development: strategies focused on building partnership quality, strategic staffing, and organizing partnership processes. CONCLUSIONS: Our findings demonstrate that while multiple barriers to developing hospital-CBO partnerships exist, stakeholders can adopt implementation strategies that mitigate these challenges such as using mediators, cross-hiring, and focusing on mutually beneficial services, even within resource-limited safety-net settings. Policymakers and health system leaders who wish to optimize TOPs in their facilities should focus on adopting implementation strategies to support transition partnerships such as inadequate data collection and sharing systems.

Hospital use of common Z-codes for Medicare fee-for-service beneficiaries, 2017-2021.

Recognizing the impact of the social determinants of health (SDOH) on health outcomes, in 2016, the Centers for Medicare and Medicaid Services recommended the use of International Classification of Diseases, 10th Revision (ICD-10), Z-codes to capture patients' health-related social needs. We examined changes in Z-code utilization to document health-related social needs for Medicare fee-for-service recipients among US hospitals between 2017 and 2021 across 5 common SDOH domains. We found that, while 56.9% of hospitals had at least 1 Z-code recorded in at least 1 patient per year, apart from those referring to housing needs, rates of Z-code adoption were low. Additionally, hospitals that were general medical, part of a teaching institution, affiliated with larger health systems, and of medium to large size had greater odds of utilizing Z-codes. Findings from this study highlight the need for continued efforts in promoting the consistent use of standardized SDOH capturing methods like Z-code documentation, such as provider training.

Examining the relationship between social determinants of health, measures of structural racism and county-level overdose deaths from 2017-2020.

INTRODUCTION: Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020. METHODS: This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure. RESULTS: In our multivariate model, higher per capita fine and forfeiture revenue (5.76; CI: 4.76, 6.78), households receiving food stamps (1.15; CI: 0.77, 1.53), residents that are veterans (1.07; CI: 0.52, 1.63), substance use treatment availability (4.69; CI: 3.03, 6.33) and lower population density (-0.002; CI: -0.004, -0.001) and percent of Black residents (-0.7`; CI: -1.01, -0.42) were significantly associated with higher overdose death rates. There was a significant additive interaction between the fines and forfeitures measure (0.10; CI: 0.03, 0.17) and the percent of Black residents. CONCLUSIONS: Our findings suggest that structural racism, along with other SDOH, is associated with overdose deaths. Future research should focus on connecting individual-level data on fines and forfeitures to overdose deaths and other health outcomes, include measures of justice-related fines, such as court fees, and assess whether interventions aimed at increasing economic vitality in disadvantaged communities impact overdose deaths in a meaningful way.

Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model.

BACKGROUND: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. METHODS: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects. RESULTS: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%. CONCLUSIONS: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life.

Clinical characteristics and salivary biomarkers of burning mouth syndrome.

OBJECTIVES: To investigate the clinical characteristics and salivary biomarkers in each type of burning mouth syndrome (BMS) patients. MATERIALS AND METHODS: Ninety-eight postmenopausal female patients with BMS were included. Fifty and 21 patients were assigned to the primary and secondary groups, respectively. Twenty-seven patients with both primary and secondary characteristics were assigned to the intermediate group. Comprehensive clinical characteristics and salivary biomarkers were analyzed. RESULTS: Significant differences in age, proportion of hyposalivator patients based on unstimulated whole saliva (UWS), symptom distribution, severties of burning sensation and effect of oral complaints in daily life (Eff-life), and positive symptom distress index (PSDI) were observed among the three groups. The primary group had significant higher UWS flow rate, fewer UWS hyposalivator proportions, and lesser severity of Eff-life than the secondary group. The intermediate group had significantly greater intensities of burning sensation and Eff-life and higher PSDI score than did the primary group. The primary group had significantly higher cortisol and dehydroepiandrosterone (DHEA) levels in stimulated whole saliva than did the secondary group. CONCLUSIONS: This study's findings show that clinical characteristics differentiate each BMS type. Cortisol and DHEA levels are potential salivary biomarkers for discriminating between the primary and secondary types of BMS.

Comparing Rates of Undiagnosed Hypertension and Diabetes in Patients With and Without Substance Use Disorders.

BACKGROUND: Individuals with substance use disorders (SUDs) have increased risk for developing chronic conditions, though few studies assess rates of diagnosis of these conditions among patients with SUDs. OBJECTIVE: To compare rates of undiagnosed hypertension and diabetes among patients with and without an SUD. DESIGN: Cross-sectional analysis using electronic health record (EHR) data from 58 primary care clinics at a large, urban, healthcare system in New York. PARTICIPANTS: Patients who had at least two primary care visits from 2019-2022 were included in our patient sample. Patients without an ICD-10 hypertension diagnosis or prescribed hypertension medications and with at least two blood pressure (BP) readings ≥ 140/90 mm were labeled 'undiagnosed hypertension,' and patients without a diabetes diagnosis or prescribed diabetes medications and with A1C/hemoglobin ≥ 6.5% were labeled 'undiagnosed diabetes.' MAIN MEASURES: We calculated the mean number of patients with and without an ICD-10 SUD diagnosis who were diagnosed and undiagnosed for each condition. We used multivariate logistic regression to assess the association between being undiagnosed for each condition, and having an SUD diagnosis, patient demographic characteristics, clinical characteristics (body mass index, Elixhauser comorbidity count, diagnosed HIV and psychosis), the percentage of visits without a BP screening, and the total number of visits during the time period. KEY RESULTS: The percentage of patients with undiagnosed hypertension (2.74%) and diabetes (22.98%) was higher amongst patients with SUD than patients without SUD. In multivariate models, controlling for other factors, patients with SUD had significantly higher odds of having undiagnosed hypertension (OR: 1.81; 95% CI: 1.48, 2.20) and undiagnosed diabetes (OR: 1.93; 1.72, 2.16). Being younger, female, and having an HIV diagnosis was also associated with significantly higher odds for being undiagnosed. CONCLUSIONS: We found significant disparities in rates of undiagnosed chronic diseases among patients with SUDs, compared with patients without SUDs.

Isolation of Murine Adipose-Derived Stromal/Stem Cells for Adipogenic and Osteogenic Differentiation or Flow Cytometry-Based Analysis.

Murine models of obesity or reduced adiposity are a valuable resource for understanding the role of adipocyte dysfunction in metabolic disorders. Adipose tissue stromal vascular cells or primary adipocytes derived from murine adipose tissue and grown in culture are essential tools for studying the mechanisms underlying adipocyte development and function. Herein, we describe methods for the isolation, expansion, and long-term storage of murine adipose-derived stromal/stem cells, along with protocols for inducing adipogenesis to white or beige adipocytes in this cell population and osteogenic differentiation. Isolation of the adipose stromal vascular fraction cells for flow cytometric analysis is also described.

Assessment of lymph node area coverage with total marrow irradiation and implementation of total marrow and lymphoid irradiation using automated deep learning-based segmentation.

BACKGROUND: Total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI) have the advantages. However, delineating target lesions according to TMI and TMLI plans is labor-intensive and time-consuming. In addition, although the delineation of target lesions between TMI and TMLI differs, the clinical distinction is not clear, and the lymph node (LN) area coverage during TMI remains uncertain. Accordingly, this study calculates the LN area coverage according to the TMI plan. Further, a deep learning-based model for delineating LN areas is trained and evaluated. METHODS: Whole-body regional LN areas were manually contoured in patients treated according to a TMI plan. The dose coverage of the delineated LN areas in the TMI plan was estimated. To train the deep learning model for automatic segmentation, additional whole-body computed tomography data were obtained from other patients. The patients and data were divided into training/validation and test groups and models were developed using the "nnU-NET" framework. The trained models were evaluated using Dice similarity coefficient (DSC), precision, recall, and Hausdorff distance 95 (HD95). The time required to contour and trim predicted results manually using the deep learning model was measured and compared. RESULTS: The dose coverage for LN areas by TMI plan had V100% (the percentage of volume receiving 100% of the prescribed dose), V95%, and V90% median values of 46.0%, 62.1%, and 73.5%, respectively. The lowest V100% values were identified in the inguinal (14.7%), external iliac (21.8%), and para-aortic (42.8%) LNs. The median values of DSC, precision, recall, and HD95 of the trained model were 0.79, 0.83, 0.76, and 2.63, respectively. The time for manual contouring and simply modified predicted contouring were statistically significantly different. CONCLUSIONS: The dose coverage in the inguinal, external iliac, and para-aortic LN areas was suboptimal when treatment is administered according to the TMI plan. This research demonstrates that the automatic delineation of LN areas using deep learning can facilitate the implementation of TMLI.

Telehealth use during the early COVID-19 public health emergency and subsequent health care costs and utilization.

Telehealth utilization increased during the COVID-19 pandemic, yet few studies have documented associations of telehealth use with subsequent medical costs and health care utilization. We examined associations of telehealth use during the early COVID-19 public health emergency (March-June 2020) with subsequent total medical costs and health care utilization among people with heart disease (HD). We created a longitudinal cohort of individuals with HD using MarketScan Commercial Claims data (2018-2022). We used difference-in-differences methodology adjusting for patients' characteristics, comorbidities, COVID-19 infection status, and number of in-person visits. We found that using telehealth during the stay-at-home order period was associated with a reduction in total medical costs (by -$1814 per person), number of emergency department visits (by -88.6 per 1000 persons), and number of inpatient admissions (by -32.4 per 1000 persons). Telehealth use increased per-person per-year pharmacy prescription claims (by 0.514) and average number of days' drug supply (by 0.773 days). These associated benefits of telehealth use can inform decision makers, insurance companies, and health care professionals, especially in the context of disrupted health care access.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Effects of Zinc Compounds on the Enzymatic Activities of Lysozyme and Peroxidase and Their Antifungal Activities.

This study aimed to investigate the effects of zinc compounds on the enzymatic activities of lysozyme, peroxidase, and the glucose oxidase-mediated peroxidase (GO-PO) system and their antifungal activities. Four different zinc compounds (zinc chloride, gluconate, lactate, and sulfate) were incubated with hen egg-white lysozyme (HEWL), bovine lactoperoxidase (bLPO), the GO-PO system, and human unstimulated whole saliva in solution and on a hydroxyapatite surface. Enzymatic activities of lysozyme, peroxidase, and the GO-PO system were measured through the hydrolysis of Micrococcus lysodeikticus, oxidation of fluorogenic 2',7'-dichlorofluorescin, and glucose assay, respectively. Interactions between zinc and enzymes were analyzed by surface plasmon resonance (SPR). The minimum inhibitory concentration (MIC) and candidacidal activities of zinc compounds were examined against three Candida albicans strains. Zinc gluconate and sulfate significantly increased the enzymatic activities of salivary lysozyme in the solution assay and of HEWL and salivary lysozyme on the hydroxyapatite surface. However, all examined zinc compounds significantly decreased the enzymatic activities of bLPO and salivary peroxidase in solution and on the surface. SPR analyses revealed binding of zinc to lysozyme and peroxidase, with affinity differing according to the zinc compounds. The MIC of zinc compounds against C. albicans was 1.0-2.4 mM. Candidacidal activities were 17.7-38.8% and 23.7-47.0% at 1.0 and 10 mM concentrations, respectively. In conclusion, zinc compounds enhanced lysozyme activity but inhibited peroxidase activity. Zinc compounds exhibited concentration-dependent candidacidal activity against C. albicans. Zinc compounds are potential therapeutic agents for oral health, especially for geriatric patients.

Roles of breast cancer resistance protein and organic anion transporting polypeptide 2B1 in gastrointestinal toxicity induced by SN-38 under inflammatory conditions.

Drug transporters are among the factors that determine the pharmacokinetic profiles after drug administration. In this study, we investigated the roles of drug transporters involved in transport of SN-38, which is an active metabolite of irinotecan, in the intestine under inflammatory conditions in vitro and determined their functional consequences. The expression alterations of breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 2B1 were determined at the mRNA and protein levels, and the subsequent functional alterations were evaluated via an accumulation study with the representative transporter substrates [prazosin and dibromofluorescein (DBF)] and SN-38. We also determined the cytotoxicity of SN-38 under inflammatory conditions. Decreased BCRP expression and increased OATP2B1 expression were observed under inflammatory conditions in vitro, which led to altered accumulation profiles of prazosin, DBF, and SN-38, and the subsequent cytotoxic profiles of SN-38. Treatment with rifampin or novobiocin supported the significant roles of BCRP and OATP2B1 in the transport and cytotoxic profile of SN-38. Collectively, these results suggest that BCRP and OATP2B1 are involved in the increased cytotoxicity of SN-38 under inflammatory conditions in vitro. Further comprehensive research is warranted to completely understand SN-38-induced gastrointestinal cytotoxicity and aid in the successful treatment of cancer with irinotecan.