Accessing the discriminatory performance of FRAIL-NH in two-class and three-class frailty and examining its agreement with the frailty index among nursing home residents in mainland China.

BACKGROUND: FRAIL-NH has been commonly used to assess frailty in nursing home residents and validated in many ethnic populations; however, it has not been validated in mainland China, where such an assessment tool is lacking. This study aimed to (1) assess the discriminatory performance of FRAIL-NH in two-class frailty (non-frail+ pre-frail vs. frail) and three-class frailty (non-frail vs. pre-frail vs. frail), based on the Frailty Index (FI), (2) determine the appropriate cutoff points for FRAIL-NH that distinguish two-class and three-class frailty, and (3) examine the agreement in classification between FRAIL-NH and FI. METHODS: A cross-sectional study of 302 residents aged 60 years or older from six nursing homes in Changsha was conducted. The FRAIL-NH scale and 34-item FI were used to measure frailty. Two-way and three-way receiver operating characteristic (ROC) curves were used to estimate the performance of FRAIL-NH. Cohen's Kappa statistics were used to examine the agreement between these two measures. RESULTS: The agreement between FRAIL-NH and FI ranged from 0.33 to 0.55. Regardless of what FI cutoff points were based on, the volume under the ROC surface (VUS) for FRAIL-NH from the three-way ROC were higher than the VUS of a useless test (1/6), and the area under the ROC curve (AUC) for FRAIL-NH from the two-way ROC were higher than the clinically meaningless value (0.5). When using FI cutoff points of 0.20 for pre-frail and 0.45 for frail, FRAIL-NH cutoff points of 1 and 9 in classifying three-class frailty had the highest VUS and the largest correct classification rates. Whichever FI was chosen, the performance of FRAIL-NH in distinguishing between pre-frailty and frailty, and between non-frailty and pre-frailty was equivalent. According to FRAIL-NH, the proportion of individuals with frailty misclassified as pre-frailty was higher than that of individuals with non-frailty misclassified as pre-frailty. CONCLUSION: FRAIL-NH can be used as a preliminary frailty screening tool in nursing homes in mainland China. FI should be further used especially for those classified as pre-frailty by FRAIL-NH. It is not advisable to simply combine adjacent two classes of FRAIL-NH to create a new frailty variable in research settings.

Roles of partitioning-defective protein 6 (Par6) and its complexes in the proliferation, migration and invasion of cancer cells.

A pivotal regulator of cell polarity and homeostasis, partitioning-defective protein 6 (Par6) forms multicomponent complexes that not only regulate cell polarity and stabilize cell morphology, but have also been demonstrated to participate in the proliferation, migration and invasion of cancer cells. The transforming growth factor (TGF)-ß and extracellular signal-regulated kinase (Erk) 1/2 pathways are the most thoroughly studied pathways involving Par6 in many cancers. Aurothiomalate has been used to disrupt the interaction between Par6 and atypical protein kinase C within the multicomponent complexes, and has been shown to effectively block transformed growth and metastasis in vitro and/or in vivo in a variety of cancers, including pancreatic, prostate and lung cancers, as well as alveolar rhabdomyosarcoma. It is likely that with further revelations regarding the critical roles of Par6 in cancer initiation, progression and metastasis, targeted therapies against Par6 will be discovered and prove effective preclinically, and hopefully clinically, in cancer treatment.

Numerical Simulation Study on Impact Initiation on Shielded Charge Using Hypervelocity Composite-Structure Reactive Fragments.

In order to study the impact initiation process and mechanism of hypervelocity PTFE/Al composite structure reactive fragments on a shielded charge, first, an existing PTFE/Al reactive fragment hypervelocity collision experiment was numerically simulated using the SPH algorithm in ANSYS/AUTODYN 17.0 software. Then, the Lee-Tarver model was verified to describe the detonation reaction behavior and explosion damage effect of reactive materials. A numerical simulation analysis of the impact of two kinds of ultra-high-speed PTFE/Al composite-structure reactive fragments on a shielded charge was carried out using the SPH algorithm. These were steel-coated PTFE/Al and steel-semi-coated PTFE/Al fragments, and they were compared with the impact of steel fragments. The results indicate that the threshold velocities of the impact initiation of the two composite-structure reactive fragments on the shielded charge were both 2.6 km/s, while the threshold velocity of the steel fragment was 2.7 km/s. Under the threshold velocity condition, the two composite-structure reactive fragments increase the time and intensity of the compressed shock wave pulse in the explosive due to the impact energy release effect of the reactive materials, causing the shielded charge to detonate under the continuous long-term pulse loads. However, the mechanism of the steel fragment on the shielded charge belongs to the shock-detonation transition. The research results can provide scientific references for the design of hypervelocity reactive fragments and the study of their damage mechanism.

Mathematical modelling of the use of insecticide-treated nets for elimination of visceral leishmaniasis in Bihar, India.

Visceral leishmaniasis (VL) is a deadly neglected tropical disease caused by a parasite Leishmania donovani and spread by female sand flies Phlebotomus argentipes. There is conflicting evidence regarding the role of insecticide-treated nets (ITNs) on the prevention of VL. Numerous studies demonstrated the effectiveness of ITNs. However, KalaNet, a large trial in Nepal and India did not support those findings. The purpose of this paper is to gain insight into the situation by mathematical modelling. We expand a mathematical model of VL transmission based on the KalaNet trial and incorporate the use of ITNs explicitly into the model. One of the major contributions of this work is that we calibrate the model based on the available epidemiological data, generally independent of the KalaNet trial. We validate the model on data collected during the KalaNet trial. We conclude that in order to eliminate VL, the ITN usage would have to stay above 96%. This is higher than the 91% ITNs use at the end of the trial which may explain why the trial did not show a positive effect from ITNs. At the same time, our model indicates that asymptomatic individuals play a crucial role in VL transmission.

Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Potent Target for Breast Cancer Therapy.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) belongs to the EGF family and exhibits its activity after binding to its receptors in autocrine, paracrine, and juxtacrine interactions. HB-EGF plays important roles in several biological and pathological processes, such as wound healing, blastocyst implantation, atherosclerosis, and heart development. Clinical studies have shown that HB-EGF is closely correlated with tumorigenesis, metastasis, and drug resistance in breast cancer. Specifically, targeted inhibition of HB-EGF improves the therapeutic efficacy and suppresses the tumor progression. This review discusses the importance of HB-EGF in mammary carcinoma progression and the potential value of HB-EGF as a therapeutic target for breast cancer treatment.

Design and finite element analysis of a novel sliding rod microscrew implantation device for mandibular prognathism.

Tooth distalization is an effective approach for mandibular prognathism. Current distalization devices are bulky and clinically complicated. Here, we designed a novel molar distalization device by using a sliding rod and a microscrew and performed a mechanical analysis and finite element model (FEM) analysis of force distribution and displacement of the upper canine, first and second premolar and first molar. A 2D FEM was constructed using the Beam3 element and a 3D FEM was constructed of the mandibular teeth, the periodontal membrane, and the alveolar bones using the UG software. The upper first molar was divided into 12 points on the dental surface to facilitate stress analysis. Force analysis using the ANSYS WORKBECNH revealed that, both horizontally and vertically, the traction force causing distalization of the first molar decreased when the spring coil moved down the L shaped sliding rod. The 3D FEM force analysis revealed distomedial displacement of the upper first molar when the sliding rod microscrew implantation device caused distalization of the molar. These findings support further exploration for the use of the sliding rod microscrew implants as an anchorage for group distal movement of the teeth of patients with mandibular prognathism.