Breast cancer risk assessment can inform the use of screening and prevention modalities. We investigated the performance of the Breast Cancer Surveillance Consortium (BCSC) risk model in combination ...with a polygenic risk score (PRS) comprised of 83 single nucleotide polymorphisms identified from genome-wide association studies. We conducted a nested case–control study of 486 cases and 495 matched controls within a screening cohort. The PRS was calculated using a Bayesian approach. The contributions of the PRS and variables in the BCSC model to breast cancer risk were tested using conditional logistic regression. Discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve (AUROC). Increasing quartiles of the PRS were positively associated with breast cancer risk, with OR 2.54 (95 % CI 1.69–3.82) for breast cancer in the highest versus lowest quartile. In a multivariable model, the PRS, family history, and breast density remained strong risk factors. The AUROC of the PRS was 0.60 (95 % CI 0.57–0.64), and an Asian-specific PRS had AUROC 0.64 (95 % CI 0.53–0.74). A combined model including the BCSC risk factors and PRS had better discrimination than the BCSC model (AUROC 0.65 versus 0.62,
p
= 0.01). The BCSC-PRS model classified 18 % of cases as high-risk (5-year risk ≥3 %), compared with 7 % using the BCSC model. The PRS improved discrimination of the BCSC risk model and classified more cases as high-risk. Further consideration of the PRS’s role in decision-making around screening and prevention strategies is merited.
Axillary lymph node (LN) metastasis is the most important predictor of overall recurrence and survival in patients with breast cancer, and accurate assessment of axillary LN involvement is an ...essential component in staging breast cancer. Axillary management in patients with breast cancer has become much less invasive and individualized with the introduction of sentinel LN biopsy (SLNB). Emerging evidence indicates that axillary LN dissection may be avoided in selected patients with node-positive as well as node-negative cancer. Thus, assessment of nodal disease burden to guide multidisciplinary treatment decision making is now considered to be a critical role of axillary imaging and can be achieved with axillary US, MRI, and US-guided biopsy. For the node-positive patients treated with neoadjuvant chemotherapy, restaging of the axilla with US and MRI and targeted axillary dissection in addition to SLNB is highly recommended to minimize the false-negative rate of SLNB. Efforts continue to develop prediction models that incorporate imaging features to predict nodal disease burden and to select proper candidates for SLNB. As methods of axillary nodal evaluation evolve, breast radiologists and surgeons must work closely to maximize the potential role of imaging and to provide the most optimized treatment for patients.
Intracellular pH (pHi) is an important parameter associated with cellular behaviors and pathological conditions. Sensing pHi and monitoring its changes in live cells are essential but challenging due ...to the lack of effective probes. We herein report a pH-sensitive fluorogen for pHi sensing and tracking. The dye is a tetraphenylethene–cyanine adduct (TPE-Cy). It is biocompatible and cell-permeable. Upon diffusing into cells, it responds sensitively to pHi in the entire physiological range, visualizing the acidic and basic compartments with intense red and blue emissions, respectively. The ratiometric signal of the red and blue channels can thus serve as an indicator for local proton concentration. The utility of TPE-Cy in pHi imaging and monitoring is demonstrated with the use of confocal microscopy, ratiometric analysis, and flow cytometry.
Fluorescent biosensors are powerful analytical tools for studying biological events in living systems. Luminescent materials with aggregation-induced emission (AIE) attributes have attracted much ...research interest and have been identified as a novel class of luminogens to develop fluorescent turn-on biosensors with superior sensitivity. In this Tutorial Review, we present an overview of the AIE phenomenon and its mechanism. We summarize the structural design and working principle of AIE biosensors developed recently. Typical examples of AIE biosensors are presented.
Objective To evaluate the effectiveness of an empowerment intervention in reducing intimate partner violence (IPV) and improving health status.
Design Randomised controlled trial.
Setting ...Antenatal clinic in a public hospital in Hong Kong.
Sample One hundred and ten Chinese pregnant women with a history of abuse by their intimate partners.
Methods Women were randomised to the experimental or control group. Experimental group women received empowerment training specially designed for Chinese abused pregnant women while the control group women received standard care for abused women. Data were collected at study entry and six weeks postnatal.
Main outcomes measures IPV on the Conflict Tactics Scale (CTS), health‐related quality of life (SF‐36) and postnatal depression Edinburgh Postnatal Depression Scale (EPDS).
Results Following the training, the experimental group had significantly higher physical functioning and had significantly improved role limitation due to physical problems and emotional problems. They also reported less psychological (but not sexual) abuse, minor (but not severe) physical violence and had significantly lower postnatal depression scores. However, they reported more bodily pain.
Conclusion An empowerment intervention specially designed for Chinese abused pregnant women was effective in reducing IPV and improving the health status of the women.
A luminogen with aggregation‐induced emission characteristics is reported for bacterial imaging and antibiotics screening studies. The luminogen can light up bacteria in a wash‐free manner, which ...simplifies the imaging process and increases its accuracy in bacterial detection. It can also be applied to high‐throughput screening of antibiotics and fast evaluation of bacterial susceptibility, giving reliable results in less than 5 h.
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the early 1960s. The increasing resistance of pathogens to currently used antibiotics requires the urgent discovery of new ...antimicrobials effective in combating drug-resistant bacteria. From past to present, medicinal plants are useful to cure human diseases. Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), commonly found in Phyllanthus species, exerts potentiating effect on β-lactams against MRSA. However, its biological effect may not be fully utilized. Therefore, incorporating microencapsulation technology with the delivery of corilagin would be more effective in utilizing the potential effect on biomedical applications. This work reports the development of a safe micro-particulate system which combined agar with gelatin as wall matrix materials for topical delivery of corilagin in order to eliminate the potential toxicity of the crosslinker formaldehyde. The optimal parameters for microsphere preparation were identified and the particle size of optimal microspheres was 20.11 μm ± 3.58. Antibacterial studies revealed that micro-trapped corilagin (minimum bactericidal concentration, MBC = 0.5 mg/mL) possessed a higher potency against MRSA than free corilagin (MBC = 1 mg/mL). The in vitro skin cytotoxicity showed the safety of the corilagin-loaded microspheres for topical applications, with approximately 90 % of HaCaT cell viability. Our results demonstrated the potential of corilagin-loaded gelatin/agar microspheres for the applicable bio-textile products to treat drug-resistant bacterial infections.
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•We report corilagin-loaded microspheres prepared by a non-toxic gelatin/agar-based system.•Micro-entrapped corilagin showed a stronger antibacterial activity against MRSA than the free drug.•Micro-entrapped corilagin showed lower HaCaT cytotoxicity than the free drug.•Micro-entrapped corilagin with enhanced anti-MRSA activity would be applied to bio-textiles to treat bacterial infections.
We investigated antibacterial activity of ZnO nanorods prepared by a hydrothermal method against a gram-negative bacterium
Escherichia coli and a gram-positive bacterium
Bacillus atrophaeus. ...Antibacterial activity of ZnO nanorod coatings was studied on solid substrates covered with nutrient agar, as well as in liquid nutrient broth for different concentrations of ZnO nanorods, nanoparticles, and powder. ZnO exhibited antibacterial activity against both
E. coli and
B. atrophaeus, but it was considerably more effective in the latter case (at 15 mM vs. 5 mM concentration, respectively, showing zero viable cell count). For both organisms, damage of the cell membranes was found, and the effect was more pronounced for
B. atrophaeus. Chemiluminescence analysis has been used to detect the release of hydrogen peroxide from ZnO structures, and the effect of H
2O
2 on the
E. coli and
B. atrophaeus was studied. Since significant differences were observed in the effect of ZnO nanostructures and H
2O
2 on
B. atrophaeus, it can be concluded that there are other mechanisms contributing to the antibacterial activity of ZnO nanostructures.
Abstract Background The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional–fractionation radiotherapy plus concurrent–adjuvant chemotherapy as ...recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors. Methods Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RTi group: 218 patients) or chemoradiotherapy (CRTi group: 223 patients) using cisplatin (100 mg/m2 ) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2 ) plus fluorouracil (1000 mg/m2 /day for 4 days) for three cycles. The median follow-up was 6.1 years. Findings Comparison by intention-to-treat showed that the CRTi group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival ( p ⩽ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant ( p ⩾ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRTa versus RTa group: 72% versus 63% at 5-year, p = 0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0–1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively. Interpretation Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200 mg/m2 in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.
Background Current practice of adding concurrent–adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. ...However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. Methods Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m2) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg per m2 per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. Results The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). Conclusions Adding concurrent–adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
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