Discovery of Multiple Effects of Reactive Oxygen Species on Lung Adenocarcinoma at the Single-cell and Bulk Tissue Levels.

BACKGROUND: Reactive oxygen species (ROS) are potential targets for treating malignant tumors. AIMS: The aim of this study was to probe into the mechanisms of disease development and treatment in lung adenocarcinoma (LUAD). OBJECTIVE: This study investigated the impact of ROS on the progression of LUAD at different transcriptomic levels and analyzed key molecules involved in the regulation of LUAD. METHODS: Single-cell RNA-seq (scRNA-seq) data of LUAD were clustered and annotated to determine cell types. Scissor cells based on LUAD bulk transcriptome and epithelial scRNA-seq data were used to classify subsets associated with ROS phenotypes. Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analyses were performed between the Scissor-positive and Scissor-negative epithelial cells to select key differentially expressed genes (DEGs) for developing a ROS-related signature. RESULTS: The ROS score was significantly negatively correlated with the overall survival (OS) of LUAD. Seven cell types from the LUAD tissues were identified. The ROS-related gene signature was significantly correlated with metabolism, tumor microenvironment (TME) indicators, and the half-maximal inhibitory concentration (IC50) values of 10 drugs. The gene signature was verified as an independent indicator for LUAD prognosis. CONCLUSION: The current study provided novel insights into the impact of ROS on LUAD pathology at both single-cell and bulk-tissue levels, facilitating the prognostic evaluation and drug therapy development for patients with LUAD.

Microbial community and gene dynamics response to high concentrations of gadolinium and sulfamethoxazole in biological nitrogen removal system.

The impact of high antibiotic and heavy metal pollution levels on biological nitrogen removal in wastewater treatment plants (WWTPs) remains poorly understood, posing a global concern regarding the issue spread of antibiotic resistance induced by these contaminants. Herein, we investigated the effects of gadolinium (Gd) and sulfamethoxazole (SMX), commonly found in medical wastewater, on biological nitrogen removal systems and microbial characteristics, and the fate of antibiotic resistance genes (ARGs), metal resistance genes (MRGs), and mobile genetic elements (MGEs). Our findings indicated that high SMX and Gd(III) concentrations adversely affected nitrification and denitrification, with Gd(III) exerting a strong inhibitory effect on microbial activity. Metagenomic analysis revealed that high SMX and Gd(III) concentrations could reduce microbial diversity, with Thauera and Pseudomonas emerging as dominant genera across all samples. While the relative abundance of most ARGs decreased under single Gd(III) stress, MRGs increased, and nitrification functional genes were inhibited. Conversely, combined SMX and Gd(III) pollution increased the relative abundance of intl1. Correlation analysis revealed that most genera could host ARGs and MRGs, indicating co-selection and competition between these resistance genes. However, most denitrifying functional genes exhibited a positive correlation with MRGs. Overall, our study provides novel insights into the impact of high concentrations of antibiotics and heavy metal pollution in WWTPs, and laying the groundwork for the spread and proliferation of resistance genes under combined SMX and Gd pollution.

[Chloroplast genomic characterization and phylogenetic analysis of Castanopsis hystrix].

The structure and size of the chloroplast genome of Castanopsis hystrix was determined by Illumina HiSeq 2500 sequencing platform to understand the difference between C. hystrix and the chloroplast genome of the same genus, and the evolutionary position of C. hystrix in the genus, so as to facilitate species identification, genetic diversity analysis and resource conservation of the genus. Bioinformatics analysis was used to perform sequence assembly, annotation and characteristic analysis. R, Python, MISA, CodonW and MEGA 6 bioinformatics software were used to analyze the genome structure and number, codon bias, sequence repeats, simple sequence repeat (SSR) loci and phylogeny. The genome size of C. hystrix chloroplast was 153 754 bp, showing tetrad structure. A total of 130 genes were identified, including 85 coding genes, 37 tRNA genes and 8 rRNA genes. According to codon bias analysis, the average number of effective codons was 55.5, indicating that the codons were highly random and low in bias. Forty-five repeats and 111 SSR loci were detected by SSR and long repeat fragment analysis. Compared with the related species, chloroplast genome sequences were highly conserved, especially the protein coding sequences. Phylogenetic analysis showed that C. hystrix is closely related to the Hainanese cone. In summary, we obtained the basic information and phylogenetic position of the chloroplast genome of red cone, which will provide a preliminary basis for species identification, genetic diversity of natural populations and functional genomics research of C. hystrix.

Ti3C2@Bi2O3 nanoaccordion for electrochemical determination of miRNA-21.

Based on a dual signal amplification strategy of novel accordion-like Bi2O3-decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction (HCR), an ultra-sensitive electrochemical biosensor was constructed for miRNA-21 detection. By etching Ti3AlC2 with HF, Ti3C2 with an accordion-like structure was first obtained and subsequently covered by Bi2O3 nanoparticles (NPs), forming Ti3C2@Bi2O3. A layer of Au NPs was electrodeposited on the glassy carbon electrode coated with Ti3C2@Bi2O3, which not only significantly improved the electron transport capacity of the electrode but also greatly increased its surface active area. Upon the immobilization of the thiolated capture probe (SH-CP) on the electrode, the target miRNA-21 specifically hybridized with SH-CP and thus opened its hairpin structure, triggering HCR to form a long double strand with the primers H1 and H2. A large number of the electrochemical indicator molecules were thus embedded inside the long double strands to produce the desirable electrochemical signal at a potential of - 0.19 V (vs. Ag/AgCl). Such dual signal amplification strategy successfully endowed the biosensor with ultra-high sensitivity for miRNA-21 detection in a wide linear range from 1 fM to 100 pM with a detection limit as low as 0.16 fM. The excellent detection of miRNA-21 in human blood plasma displayed a broad prospect in clinical diagnosis. An ultra-sensitive electrochemical biosensor was successfully constructed for miRNA-21 detection in human blood plasma based on the dual signal amplification strategy of novel accordion-like Bi2O3 decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction.

Development and validation of a nursing home mortality index to identify nursing home residents nearing the end of life in dental clinics.

BACKGROUND: Nursing home (NH) residents seek care at dental offices, yet many of them are at the end of life. The uncertain life expectancy further complicates the care of NH residents. This study aimed to develop and validate a Nursing Home Mortality Index (NHMI) to identify NH residents in the last year of life. METHODS: Logistic modeling was used to develop predictive models for death within 1 year after initial appointment by utilizing the new patient examination data and mortality data of 903 Minnesota NH residents. The final model was selected based on areas under the curve (AUC) and then validated using data from 586 Iowa NH residents. Based on the final model, the NHMI was developed with the estimated 1-year mortality for the low, medium and high risk group. RESULTS: One-year mortalities were 21% and 26% in the development and validation cohorts, respectively. Predictors included age, gender, communication capacity, physical mobility, congestive heart failure, peripheral vascular disease, cancer, cerebrovascular disease, chronic renal disease and liver disease. AUCs for the development and validation models were 0.73 and 0.68, respectively. For the validation cohort, the sensitivity and specificity were 0.79 and 0.53, respectively. The estimated 1-year mortality risks for three risk groups were 0%-10%, 11%-19%, and ≥20%, respectively CONCLUSION: The high mortality rate of NH residents following a dental exam highlighted a need to incorporate patients' prognoses in treatment planning along with normative needs and patients' preferences. The NHMI provides a practical way to guide treatment decisions for end-of-life NH residents.

Tooth Agenesis Patterns in Orofacial Clefting Using Tooth Agenesis Code: A Meta-Analysis.

Individuals with orofacial clefting (OFC) have a higher prevalence of tooth agenesis (TA) overall. Neither the precise etiology of TA, nor whether TA occurs in patterns that differ by gender or cleft type is yet known. This meta-analysis aims to identify the spectrum of tooth agenesis patterns in subjects with non-syndromic OFC and controls using the Tooth Agenesis Code (TAC) program. An indexed search of databases (PubMed, EMBASE, and CINAHL) along with cross-referencing and hand searches were completed from May to June 2019 and re-run in February 2022. Additionally, unpublished TAC data from 914 individuals with OFC and 932 controls were included. TAC pattern frequencies per study were analyzed using a random effects meta-analysis model. A thorough review of 45 records retrieved resulted in 4 articles meeting eligibility criteria, comprising 2182 subjects with OFC and 3171 controls. No TA (0.0.0.0) was seen in 51% of OFC cases and 97% of controls. TAC patterns 0.2.0.0, 2.0.0.0, and 2.2.0.0 indicating uni- or bi-lateral missing upper laterals, and 16.0.0.0 indicating missing upper right second premolar, were more common in subjects with OFC. Subjects with OFC have unique TA patterns and defining these patterns will help increase our understanding of the complex etiology underlying TA.

Rapid electrochemical detection of MiRNA-21 facilitated by the excellent catalytic ability of Pt@CeO2 nanospheres.

Pt@CeO2 nanospheres (NSs) were first synthesized by simply mixing Ce(NO3)3 and K2PtCl4 under the protection of pure argon at 70 °C for 1 h, which exhibited excellent catalytic ability toward hydrogen peroxide (H2O2). An electrochemical biosensor was successfully developed using Pt@CeO2 NSs as a capture probe for the ultra-sensitive and fast detection of miRNA-21, a new type of biomarker for disease diagnostics, especially for cancer. During the step-by-step construction process of the RNA sensor, Pt@CeO2 NSs were functionalized with streptavidin (SA) to obtain SA-Pt@CeO2 NSs through amide bonds. Gold nanoparticles (Au NPs) were electrodeposited on the surface of the glassy carbon electrode to improve the transmission capacity of electrons and provided Au atoms for fixing the thiolated capture probe (SH-CP) with a hairpin structure on the electrode via forming Au-S bonds. The target miRNA-21 specifically hybridized with SH-CP and opened the hairpin structure to form a rigid duplex so as to activate the biotin at the end of the capture probe. SA-Pt@CeO2 NSs were thus specially attached to the electrode surface through the biotin-streptavidin affinity interaction, finally leading to the significant signal amplification. The ultra-sensitive and rapid detection of miRNA-21 was finally realized as expected benefiting from the excellent catalytic ability of Pt@CeO2 NSs toward H2O2 in a wide linear concentration range from 10 fM to 1 nM with the detection limit as low as 1.41 fM. The results achieved with this new RNA sensor were quite satisfactory during the blood sample analysis.

Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma.

BACKGROUND: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) improve outcomes for non-small-cell lung cancer (NSCLC) patients with ALK fusions. Nevertheless, ALK TKI resistance will inevitably occur. Histological transformation is one of the causes of TKI resistance in NSCLC. Reports of ALK-rearranged adenocarcinoma with histological transformation are limited. CASE PRESENTATION: A case of an invasive lung adenocarcinoma patient with ALK rearrangement who experienced histological transformation into sarcomatoid carcinoma after ALK TKI resistance is reported, and ALK fusion, MET amplification and TP53 mutation were detected after transformation. CONCLUSIONS: This case first reported a patient with invasive lung adenocarcinoma harboring ALK rearrangement who underwent histological transformation into sarcomatoid carcinoma after ALK TKI resistance, and MET amplification might represent the cause. After transformation, the patient benefited from targeted therapy combined with chemotherapy, which represents a promising option for patients with sarcomatoid carcinoma transformation.

How Do Bismuth-Based Nanomaterials Function as Promising Theranostic Agents for the Tumor Diagnosis and Therapy?

The complexity of the tumor microenvironment and the diversity of tumors seriously affect the therapeutic effect, the focus, therefore, has gradually been shifted from monotherapy to combination therapy in clinical research in order to improve the curative effect. The synergistic enhancement interactions among multiple monotherapies majorly contribute to the birth of the multi-mode cooperative therapy, whose effect of the treatment is clearly stronger than that of any single therapy. In addition, the accurate diagnosis of the tumour location is also crucial to the treatment. Bismuth-based nanomaterials (NMs) hold great properties as promising theranostic platforms based on their many unique features that include low toxicity, excellent photothermal conversion efficiency as well as the high ability of X-ray computed tomography imaging and photoacoustic imaging. In this review, we will introduce briefly the main features of the tumor microenvironment first and its effect on the mechanism of nanomedicine actions and present the recent advances of bismuth-based NMs for diagnosis and photothermal therapy-based combined therapies using bismuth-based NMs are presented, which may provide a new way for overcoming drug resistance and hypoxia. In the end, further challenges and outlooks regarding this promising field are discussed accompanied with some design tips for bismuth- based NMs, hoping to provide researchers some inspiration to design safe and effective nanotherapeutic agents for clinical treatments of cancers.

Three-dimensional finite element analysis with different internal fixation methods through the anterior approach.

BACKGROUND: With the modernization of society and transportation in the last decades in China, the incidence of high-energy trauma increased sharply in China, including that of acetabular fractures. AIM: To establish different finite element models for acetabular posterior column fractures involving the quadrilateral area of the acetabulum. METHODS: The three-dimensional models of the normal and fractured pelvis and the five internal fixations were established using the computed tomography data of the pelvis of a living volunteer. After the vertebral body model was inserted in the way of origin matching and all cancellous bones were copied using the duplicated cancellous bone model as the subtractive entity, the Boolean operation was performed on the pelvis model to obtain the model of the complete pelvis cortical and cancellous bones. RESULTS: In the standing position, the maximum stress was 46.21 MPa. In the sitting position, the sacrum bore the simulated gravity load at the upper end. When comparing the five fixations, there were no significant differences in the stress mean values among groups (sitting: P = 0.9794; standing: P = 0.9741). In terms of displacement, the average displacement of the internal iliac plate group was smaller than that of the spring plate group (P = 0.002), and no differences were observed between the other pairs of groups (all P > 0.05). In the standing position, there were no significant differences in the mean value of displacement among the groups (P = 0.2985). It can be seen from the stress nephogram of the internal fixations in different positions that the stress of the internal fixation was mainly concentrated in the fracture segment. CONCLUSION: There were no significant differences among the fixations for acetabular posterior column fractures involving the quadrilateral area of the acetabulum.

Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy.

Metal organic-frameworks (MOFs) are novel materials that have attracted increasing attention for applications in a wide range of research, owing to their unique advantages including their small particle size, porous framework structure and high specific surface area. Because of their adjustable size, nanoscale MOFs (nano-MOFs) can be prepared as carriers of biotherapy drugs, thus enabling biotherapeutic applications. Nano-MOFs' metal ion catalytic activity and organic group functional characteristics can be exploited in biological treatments. Furthermore, the applications of nano-MOFs can be broadened by hybridization with other materials to form composites. This review focuses on the preparation and recent advances in nano-MOFs as drug carriers, therapeutic materials and functionalized materials in drug delivery and tumor therapy based on the single/multiple stimulus response of drug release to achieve the targeted therapy, offering a comprehensive reference for drug carrier design. At the end, the current challenges and prospects are discussed to provide significant insight into the design and applications of nano-MOFs in drug delivery and tumor therapy.

How accurate is the assessment of certified nursing assistants on resident's oral self-care function in three North Carolina assisted-living facilities?

AIMS: To examine the association between the assessments of certified nursing assistants (CNAs) on resident's oral self-care function and resident's oral hygiene outcomes in three North Carolina assisted-living (AL) facilities. METHODS AND RESULTS: Sixty-five dentate AL residents were included in this secondary analysis. CNAs were asked to rate the AL residents' overall oral self-care function using a 6-point Likert scale. Their assessments were then compared with the objective, performance-based Dental Activities Test and the oral hygiene and gingival health measures. The analysis showed that nearly 90% of the participants presented with at least one untreated decayed or broken tooth. On average, nearly two-thirds of the surfaces were covered by soft deposits (Debris Index = 1.83, SD = 0.60). Generalized mild to moderate inflammation (Gingival Index = 1.51, SD = 0.53) commonly presented on residents' gingiva. CNAs were able to accurately identify the residents with substantial impairment in oral self-care function, yet they tended to overestimate the oral self-care function of residents with mild to moderate impairment. CNAs assessments were also not significantly correlated with residents' oral hygiene measures. CONCLUSION: CNAs failed to identify and provide assistance to AL residents with impaired oral self-care function, contributing to poor oral oral hygiene in these vulnerable individuals.

Retraction Note: miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2.

A Retraction to this paper has been published and can be accessed via a link at the top of the paper.

Flexible, rule-based dose escalation: The cohort-sequence design.

Phase I oncology trials seek to acquire preliminary information on the safety of novel treatments. In current practice, most such trials employ rule-based designs that determine whether to escalate the dose using data from the current dose only. The most popular of these, the 3 + 3, is simple and familiar but inflexible and inefficient. We propose a rule-based design that addresses these deficiencies. Our method, which we denote the cohort-sequence design, is defined by a sequence of J increasing cohort sizes n = ( n 1 , … , n J ) and corresponding critical values b = ( b 1 , … , b J ) . The idea is to begin with a small cohort size n 1 and escalate through the planned doses, increasing the cohort size when we encounter toxicities. By selection of J and a safety threshold tuning parameter θ, one can create a design that will efficiently identify a target toxicity rate, potentially including a built-in dose-expansion cohort. We compared our designs to the 3 + 3 under a range of toxicity scenarios, observing that our approach generally rapidly identifies an MTD without enrolling patients unnecessarily at low doses where both toxicity and response rates are likely to be low. We have implemented the design in the R package cohortsequence.

Comparison of Dako HercepTest and Ventana PATHWAY Anti-HER2 (4B5) Tests and Their Correlation With Fluorescent In Situ Hybridization in Breast Carcinoma.

OBJECTIVES: We compared the performance of two Food and Drug Administration-approved HER2 immunohistochemistry (IHC) tests: HercepTest (Dako) and PATHWAY anti-HER2 (4B5) (Ventana). MATERIALS AND METHODS: In total, 180 invasive breast carcinomas previously tested by both HercepTest and fluorescent in situ hybridization (FISH) were retested with 4B5. Three pathologists scored the HER2 IHC using the 2013 American Society of Clinical Oncology/College of American Pathologists guidelines. The HER2 IHC results were correlated with FISH. RESULTS: Among 135 equivocal cases by HercepTest, 100 (74.1%) were negative by 4B5. Among 45 positive HercepTest cases 9 (20%) were equivocal by 4B5. Among 135 equivocal HercepTest results, 100 (74.1%) were nonamplified, 18 (13.3%) equivocal, and 17 (12.6%) amplified by FISH. Among the 45 positive results with HercepTest, 2 (4.5%) were nonamplified and 1 (2.2%) was equivocal by FISH. All 37 positive and 3 negative by 4B5 cases were amplified by FISH. The absolute interobserver agreement was high for both tests (Fleiss kappa=0.838 for HercepTest and 0.771 for 4B5). CONCLUSIONS: PATHWAY anti-HER2 (4B5) significantly reduced the number of equivocal results that require additional testing. Although HercepTest was positive in a small number of HER2 nonamplified cases, 4B5 failed to detect 3 cases that were interpreted as positive by FISH, all with nonclassic or low levels of amplification.

Radiation-Induced DNA Damage Cooperates with Heterozygosity of TP53 and PTEN to Generate High-Grade Gliomas.

Glioblastomas are lethal brain tumors that are treated with conventional radiation (X-rays and gamma rays) or particle radiation (protons and carbon ions). Paradoxically, radiation is also a risk factor for GBM development, raising the possibility that radiotherapy of brain tumors could promote tumor recurrence or trigger secondary gliomas. In this study, we determined whether tumor suppressor losses commonly displayed by patients with GBM confer susceptibility to radiation-induced glioma. Mice with Nestin-Cre-driven deletions of Trp53 and Pten alleles were intracranially irradiated with X-rays or charged particles of increasing atomic number and linear energy transfer (LET). Mice with loss of one allele each of Trp53 and Pten did not develop spontaneous gliomas, but were highly susceptible to radiation-induced gliomagenesis. Tumor development frequency after exposure to high-LET particle radiation was significantly higher compared with X-rays, in accordance with the irreparability of DNA double-strand breaks (DSB) induced by high-LET radiation. All resultant gliomas, regardless of radiation quality, presented histopathologic features of grade IV lesions and harbored populations of cancer stem-like cells with tumor-propagating properties. Furthermore, all tumors displayed concomitant loss of heterozygosity of Trp53 and Pten along with frequent amplification of the Met receptor tyrosine kinase, which conferred a stem cell phenotype to tumor cells. Our results demonstrate that radiation-induced DSBs cooperate with preexisting tumor suppressor losses to generate high-grade gliomas. Moreover, our mouse model can be used for studies on radiation-induced development of GBM and therapeutic strategies. SIGNIFICANCE: This study uncovers mechanisms by which ionizing radiation, especially particle radiation, promote GBM development or recurrence.

Author Correction: miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2.

Change history: In this Letter, the citation to 'Fig. 4e, f' in the main text should be 'Fig. 3e, f'. This has not been corrected online.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases.

PURPOSE: To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. METHODS AND MATERIALS: Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20 Gy delivered to the gross disease and 14 Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1 month after spine SABR. The primary endpoint was pain response at 3 months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1 month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. RESULTS: Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P < .0001). The local control with a median follow-up of 9.6 months was 92%. The freedom from VCF was 90% at 1 year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. CONCLUSIONS: Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

NQO1-dependent, Tumor-selective Radiosensitization of Non-small Cell Lung Cancers.

PURPOSE: Development of tumor-specific therapies for the treatment of recalcitrant non-small cell lung cancers (NSCLC) is urgently needed. Here, we investigated the ability of ß-lapachone (ß-lap, ARQ761 in clinical form) to selectively potentiate the effects of ionizing radiation (IR, 1-3 Gy) in NSCLCs that overexpress NAD(P)H:Quinone Oxidoreductase 1 (NQO1). EXPERIMENTAL DESIGN: The mechanism of lethality of low-dose IR in combination with sublethal doses of ß-lap was evaluated in NSCLC lines in vitro and validated in subcutaneous and orthotopic xenograft models in vivo. Pharmacokinetics and pharmacodynamics (PK/PD) studies comparing single versus cotreatments were performed to validate therapeutic efficacy and mechanism of action. RESULTS: ß-Lap administration after IR treatment hyperactivated PARP, greatly lowered NAD+/ATP levels, and increased double-strand break (DSB) lesions over time in vitro. Radiosensitization of orthotopic, as well as subcutaneous, NSCLCs occurred with high apparent cures (>70%), even though 1/8 ß-lap doses reach subcutaneous versus orthotopic tumors. No methemoglobinemia or long-term toxicities were noted in any normal tissues, including mouse liver that expresses the highest level of NQO1 (∼12 units) of any normal tissue. PK/PD responses confirm that IR + ß-lap treatments hyperactivate PARP activity, greatly lower NAD+/ATP levels, and dramatically inhibit DSB repair in exposed NQO1+ cancer tissue, whereas low NQO1 levels and high levels of catalase in associated normal tissue were protective. CONCLUSIONS: Our data suggest that combination of sublethal doses of ß-lap and IR is a viable approach to selectively treat NQO1-overexpressing NSCLC and warrant a clinical trial using low-dose IR + ß-lap against patients with NQO1+ NSCLCs.

The pathway from cognitive impairment to caries in older adults: A conceptual model.

BACKGROUND: Caries significantly increases in people with cognitive impairment (PWCI). However, the interrelationships among cognitive impairment, dentally related function (DRF), oral hygiene, and caries remain unclear, increasing difficulties to care appropriately for PWCI. In this study, the researchers tested a conceptual model in which impaired DRF acts as a mediator between cognitive impairment and poor oral hygiene, which then leads to caries. METHODS: The researchers recruited 68 older adult dentate participants with normal to severely impaired cognition from 3 assisted-living communities in North Carolina. Within 1 week of a calibrated oral examination performed by a geriatric dentist, a trained examiner blinded to the oral examination results conducted cognitive and functional assessments. The researchers conducted statistical analyses to examine the mediating effect of DRF on the relationship between cognitive impairment and oral hygiene or caries. RESULTS: Cognitive impairment (ß = 0.05; standard error [SE], 0.02; P = .017) and DRF (ß = -0.07; SE, 0.02; P = .005) were significantly associated with oral hygiene. However, the association between cognitive impairment and oral hygiene was greatly reduced and became nonsignificant after controlling for DRF (ß = 0.01; SE, 0.03; P = .430), suggesting that the effect of cognitive impairment on oral hygiene was mediated by DRF. DRF accounted for 80% of the total effect of cognitive impairment on oral hygiene. The ratio of the indirect effect to the total effect was .8. Associations between either cognitive impairment or DRF and caries were not significant, but oral hygiene was significantly associated with caries (ß = 0.87; SE, 0.28; P < .001). CONCLUSIONS: DRF mediated the association between cognitive impairment and oral hygiene. It accounted for 80% of the total impact of cognitive impairment on oral hygiene, which was associated with increased caries in PWCI. PRACTICAL IMPLICATIONS: As a result of cognitive impairment, impaired DRF plays a critical role in the pathway from cognitive impairment to oral health decline. Therefore, DRF assessment should be a standard component of geriatric dental assessment. A functionally-tailored oral hygiene intervention is essential to improve oral health for persons with cognitive impairment.