Rapid detection of nicotine and benzoic acid in e-liquids with surface-enhanced Raman scattering and artificial intelligence-assisted spectrum interpretation.

Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (e-liquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotine-containing e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5-4.4% and 4.4-8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1-2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives.

Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial.

BACKGROUND: Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life. METHODS: For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005. FINDINGS: Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred. INTERPRETATION: Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing. FUNDING: National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.

First insights on value-based healthcare of elders using ICHOM older person standard set reporting.

BACKGROUND: Clinical guidelines for specific conditions fragment care provision for elders. The International Consortium for Health Outcomes Measurement (ICHOM) has developed a global standard set of outcome measures for comprehensive assessment of older persons. The goal of this study was to report value-based health metrics in Taiwan using this ICHOM toolset. METHODS: The cross-sectional study of baseline data excerpted from a prospective longitudinal cohort, which recruited people ≥65 years old with ≥3 chronic medical conditions between July and December 2018. All participants received measurements of physical performance, anthropometric characteristics, health-related behaviors, Charlson Comorbidity Index, and Montreal Cognitive Assessment. The ICHOM toolset comprises three tiers: 1 includes frailty and having chosen a preferred place of death; 2 includes polypharmacy, falls, and participation in decision-making; and 3 includes loneliness, activities of daily living, pain, depression, and walking speed. These items were converted into a 0-10 point value-based healthcare score, with high value-based health status defined as ≥8/10 points. RESULTS: Frequencies of individual ICHOM indicators were: frail 11.7%, chose preferred place of death 14.4%, polypharmacy 31.5%, fell 17.1%, participated in decision-making 81.6%, loneliness 26.8%, limited activities of daily living 22.4%, pain 10.4%, depressed mood 13.0%, and slowness 38.5%. People with high disease burden (OR 0.40, 95% CI 0.21-0.76, p = 0.005) or cognitive impairment (OR 0.49, 95%CI 0.27-0.87, p = 0.014) were less likely to have high value-based healthcare status. CONCLUSIONS: The ICHOM Standard Set Older Person health outcome measures provide an opportunity to shift from a disease-centric medical paradigm to whole person-focused goals. This study identified advanced age, chronic disease burden and cognitive impairment as important barriers to achieving high value-based healthcare status.

Ultrasensitive Detection of Volatile Organic Compounds by a Freestanding Aligned Ag/CdSe-CdS/PMMA Texture with Double-Side UV-Ozone Treatment.

Volatile organic compounds (VOCs) are organic chemicals having a high vapor pressure at room temperature. Chronic exposure to VOC vapor can be potentially dangerous to human health. In this study, we build a high-performance freestanding aligned Ag/CdSe-CdS/poly(methyl methacrylate) (PMMA) texture to detect VOC vapors. The insight of this new VOC-sensing material is based on electrospinning techniques, ultraviolet (UV)/ozone treatments, and nano-optics. The incorporation of CdSe-CdS core-shell quantum rods (QR) and silver nanocrystals in the PMMA nanofibers amplifies the polarization response of long rods in VOC detection, thus increasing the sensitivity of VOC-sensing materials. Further, the uniaxial aligned Ag/QR/PMMA sensing material was treated by UV-ozone etching to increase surface absorption. The advanced double-sided UV-ozone etching on the uniaxial aligned Ag/QR/PMMA efficiently enhanced the extinction changes of VOCs. Two categories of solvents, typical VOCs and alcoholic VOCs, were put into practical tests for the Ag/QR/PMMA VOC-sensing materials. The Ag/QR/PMMA reached the detection limit for 100 ppm butanol within 1 min. The freestanding aligned Ag/CdSe-CdS/PMMA texture is a newly designed nanocomposite device for environmental risk monitoring. It can be accepted by the market compared to the other highly sensitive commercial VOC-sensing materials.

Comparison Between Acupuncture and Biofeedback as Adjunctive Treatments for Primary Insomnia Disorder.

Context • Insomnia affects from 5% to 35% of the general population worldwide. Primary insomnia disorder is the most frequently diagnosed, sleep-related disorder. Pharmacological treatments remain the most widely used treatments for insomnia. Nonpharmacological treatments for primary insomnia disorder have been found to be effective. Objective • This study intended to determine the appropriateness of acupuncture and biofeedback as adjuncts to medication for primary insomnia disorder. Design • The research team designed a randomized, controlled study. Setting • The study took place in a psychosomatic clinic at a regional general hospital in southern Taiwan. Participants • Participants were patients at the clinic with primary insomnia disorder who had never received prior hypnotic medication or alternative treatments. Intervention • All participants received 10 mg of zolpidem. The participants were divided into 3 groups: (1) acupuncture adjunctive to zolpidem (AAZ) group- 18 patients received 1 acupuncture session weekly; (2) biofeedback adjunctive to zolpidem (BAZ) group- 17 patients received 1 biofeedback session weekly; and (3) control (OZ) group-14 patients received only zolpidem. Patients visited the clinic 1 ×/wk for 4 wk, at baseline and on days 7, 14, and 21 of the intervention. Outcome Measures • The Pittsburgh Sleep Quality Index (PSQI) was used to measure outcomes. Treatment success was defined as a final PSQI score of ≤5. The generalized estimating equation (GEE) was used for statistical analysis. Results • Using analysis of variance, the reduction in the PSQI scores were (1) 3.72 for the AAZ group, (2) 2.00 for the BAZ group, and (3) 2.29 for the OZ group (P = .28). The GEE analysis indicated no differences in the therapeutic effects among the 3 groups: P = .37 for the AAZ group vs the OZ group and P = .07 for the BAZ group vs the OZ group, when the PSQI of the OZ group was set to 0. The AAZ group had a significantly higher score than the OZ group for the sleep duration domain (B = 3.01, P < .001), whereas the BAZ group had a significantly higher score than the OZ group on the sleep disturbance domain (B = 6.78, P < .001). Higher scores indicate more difficulty in a domain. Conclusions • The change in the PSQI score and the success rate were better in the acupuncture group. The heterogeneity in primary insomnia disorder might mean that different therapeutic compositions are needed.

Herb-drug interaction of Epimedium extract on the pharmacokinetic of dapoxetine in rats.

The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10mg/kg, i.v.); (2) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, i.v.); (3) dapoxetine alone (10mg/kg, p.o.); (4) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500ng/mL with the R(2)=0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats.

Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy.

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.

Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment.

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 µM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.

Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have investigated the comparative pharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment. MATERIALS AND METHODS: The comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats was studied by liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug-metabolizing genes after SHXXT treatment was investigated by microarray analysis and real-time polymerase chain reaction (RT-PCR). RESULTS: A validated LC-MS/MS method was applied to investigate the comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats. The pharmacokinetic results demonstrate that the loperamide-induced constipation reduced the absorption of rhein. Cmax significantly reduced by 2.5-fold, the AUC decreased by 27.8%; however, the elimination half-life (t1/2) was prolonged by 1.6-fold. Tmax and mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold, respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of microarray analysis on gene expression indicate that five drug-metabolizing genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the SHXXT (0.5 g/kg) treatment. CONCLUSION: The loperamide-induced constipation reduced the absorption of rhein. Since among the 25,338 genes analyzed, there were five genes significantly altered by SHXXT treatment. Thus, information on minor drug-metabolizing genes altered by SHXXT treatment indicates that SHXXT is relatively safe for clinical application.

Determination of bioactive components in Chinese herbal formulae and pharmacokinetics of rhein in rats by UPLC-MS/MS.

Rhein (4,5-dihydroxy-9,10-dioxoanthracene-2-carboxylic acid, cassic acid) is a pharmacological active component found in Rheum palmatum L. the major herb of San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have determined multiple bioactive components in SHXXT and investigated the comparative pharmacokinetics of rhein in rats. A sensitive and specific method combining liquid chromatography with electrospray ionization tandem mass spectrometry has been developed and validated to simultaneously quantify six active compounds in the pharmaceutical herbal product SHXXT to further study their pharmacokinetics in rats. Multiple reaction monitoring (MRM) was employed for quantification with switching electrospray ion source polarity between positive and negative modes in a single run. There were no significant matrix effects in the quantitative analysis and the mean recovery for rhein in rat plasma was 91.6%±3.4%. The pharmacokinetic data of rhein demonstrate that the herbal formulae or the single herbal extract provide significantly higher absorption rate than the pure compound. This phenomenon suggests that the other herbal ingredients of SHXXT and rhubarb extract significantly enhance the absorption of rhein in rats. In conclusion, the herbal formulae (SHXXT) are more efficient than the single herb (rhubarb) or the pure compound (rhein) in rhein absorption.

Comparative oral bioavailability of geniposide following oral administration of geniposide, Gardenia jasminoides†Ellis fruits extracts and Gardenia herbal formulation in rats.

OBJECTIVE: The aim of this study was to compare the oral bioavailability and pharmacokinetic data between pure compound of the major active component, single herbal extract and complex herbal formulation by determining bioavailability of geniposide in each group following intravenous and oral administrations. METHODS: A conscious and freely moving rat model was used in this experiment to avoid the stress caused by restraint or anaesthesia. The pure compound of geniposide, Gardenia fruits (Chinese name: Zhi-Zi), and extracts of a Gardenia herbal formulation (Chinese name: Zhi-Zi-Chi-Tang) were administered at doses of 200 mg/kg, 4.69 g/kg and 10.82 g/kg for oral administration and fed by gavages to rats, respectively. The earlier doses are equivalent to geniposide administration dose of 200 mg/kg. KEY FINDINGS: The results show that after oral administration of geniposide, Gardenia fruits and Gardenia herbal formulation, the bioavailability were 4.23%, 32.32% and 27.17%, respectively. The results of oral bioavailability of geniposide also suggest that Gardenia fruits extract, single herb, is a more efficient way for geniposide, pure compound, absorption than traditional herbal formulation administration and direct pure compound administration. CONCLUSIONS: The conclusion reveals that herbal ingredient-ingredient or herb-herb interaction may affect the oral absorption of geniposide-related herbal formulation.

Herb-drug interaction of Epimedium sagittatum (Sieb. et Zucc.) maxim extract on the pharmacokinetics of sildenafil in rats.

Epimedium sagittatum (Sieb. et Zucc.) Maxim is one of the herbs used to treat erectile dysfunction in Traditional Chinese Medicine. Sildenafil is a phosphodiesterase 5 inhibitor used to treat erectile dysfunction in Western Medicine. This study evaluates the herbal-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil in rats by ultra-performance liquid chromatography. The rat plasma was sampled from each anesthetized rat after pretreatment with 3-days Epimedium sagittatum extract (1/2 g/kg/day) and intravenous injection with sildenafil (10/30 mg/kg). The pharmacokinetic data demonstrate that the area under the concentration-time curve (AUC) of sildenafil (10 mg/kg) was significantly decreased in groups that received a high dose of Epimedium sagittatum extract. In conclusion, the study demonstrates that there was significant herb-drug interaction of Epimedium sagittatum extract on the pharmacokinetics of sildenafil at low and high daily doses, suggesting co-administration use of Epimedium sagittatum extract and sildenafil in clinical practice should be prevented due to possible herb-drug interactions.

Ionic versus nonionic contrast media solvents used with an epirubicin-based agent for transarterial chemoembolization of hepatocellular carcinoma.

PURPOSE: To compare the stability of epirubicin-iodized oil emulsions prepared with ionic or nonionic contrast medium and to compare the efficacy of these emulsions in a prospective, randomized, controlled trial of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Epirubicin-iodized oil emulsions prepared with ionic and nonionic contrast media was evaluated for stability with light microscopy and magnetic resonance imaging. One hundred ninety-seven patients with inoperable HCC were randomized to receive TACE with epirubicin, prepared either with ionic (control group, n = 99) or nonionic (experimental group, n = 98) contrast medium. Tumor response was graded according to iodized oil retention (grade 1 = >90% retention, grade 2 = 50%-90% retention, and grade 3 = <50% retention), as characterized with computed tomography. Survival probabilities were calculated with the Kaplan-Meier method. RESULTS: The epirubicin-iodized oil emulsions prepared with ionic contrast medium were less stable, exhibiting rapid separation of the oil and aqueous phases, compared with emulsions prepared with nonionic medium. Ninety-one patients in the control group and 87 in the experimental group underwent follow-up CT. Thirty-seven of the 91 patients in the control group (41%) had grade 1 tumors, 41 (45%) had grade 2 tumors, and 13 (14%) had grade 3 tumors. Forty-eight of the 87 patients in the experimental group (55%) had grade 1 tumors, 22 (25%) had grade 2 tumors, and 17 (20%) had grade 3 tumors. The number of patients with grade 1 tumors was significantly higher in the experimental group than in the control group (P = .02); however, there was no difference in patient survival (P = .94). CONCLUSIONS: Epirubicin-iodized oil emulsions prepared with nonionic contrast medium are more stable and are associated with lower tumor grade in patients with inoperable HCC. The choice of solvent, however, does not appear to have an effect on patient survival.

Areca nut extract treatment elicits the fibroblastoid morphological changes, actin re-organization and signaling activation in oral keratinocytes.

BACKGROUND: Areca (named as betel) is an important etiological factor linked with the high prevalence of oral squamous cell carcinoma (OSCC) in South-Asian countries. This in vitro study investigated the cellular changes and signaling activation in oral keratinocytes in response to areca nut extract (ANE) treatment. METHODS: Normal human oral keratinocyte (NHOK) and oral epidermoid carcinoma cell, Meng-1 (OECM-1) OSCC cell line were treated with variable dosages of ripen ANE. The morphological and cytoskeletal changes, as well as the activation of GTPase proteins and signaling kinases, were analyzed. RESULTS: Most NHOK cells in culture were polygonal, with only <5% cells exhibiting fibroblastoid morphology. However, 10 microg/ml ANE elicited fibroblastoid morphological change, genesis of lamellipodia, loss of subcortical actin, and stress-fiber formation in approximately 25% cultivated NHOK cells. Similar morphological changes were observed in nearly all OECM-1 cells following the ANE treatment. The activation of Rac and Rho GTPase, together with the prominent phosphorylation of a stress-activated kinases, particularly JNK1, was identified in treated OECM-1 cells. CONCLUSION: The novel evidences from the study that ANE impairs the actin organization and activates the signals in oral keratinocytes might bestow further insight into the impacts of ANE in oral pathogenesis.