Assessment of the Effect of Rehmannia glutinosa Leaf Extract in Maintaining Skin Health: A Proof-of-Concept, Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Purpose: A double-blind, placebo-controlled, randomized, proof-of-concept trial aimed to evaluate the efficacy and safety of VerbasnolTM [Rehmannia glutinosa Libosch leaf-based extract (RGLE)] in females, with moderate to severe acne vulgaris. Participants and Methods: Twenty-two females aged 18 to 35 years having moderate to severe acne with Global Acne Grading System (GAGS) scores of 19 to 38 were included in the study and were randomized in a 1:1 ratio to receive either one capsule (100 mg/day) of RGLE or placebo orally after breakfast for 56 days. The primary outcome was a change in acne severity measured by the GAGS compared to the placebo on day 56. The secondary outcomes were changes in the number of inflammatory acne lesions, facial sebum secretion, quality of life, local pain and itching, skin wrinkle severity, and other skin characteristics, including radiance, luminosity, smoothness, texture, firmness, and hydration. Additionally, the percentage of responders and global tolerability and efficacy were evaluated. Results: The mean GAGS score was reduced by 21.72% and 14.20% on day 28 in RGLE (n=10) and placebo groups (n=12), respectively, which further reduced in both groups on day 56. The RGLE group reported better improvement in other skin characteristics on day 56. No safety or tolerability concerns were reported for the extract. RGLE reduced acne and improved the skin quality in females compared to placebo as early as 28 days of supplementation. Conclusion: RGLE supplementation at a dose of 100 mg/day has provided a clinically relevant decrease in acne severity and improved the skin hydration and quality of life of the participants with acne after 56 days of dose administration.

The utility of the surprise question by nurses to identify hospitalised older patients nearing the end-of-life and promotion of advance care planning: An interventional study.

AIMS AND OBJECTIVES: To assess the prognostic accuracy of the surprise question (SQ) when used by nurses working in hospital wards to determine 1-year mortality in acutely hospitalised older patients. BACKGROUND: The predictive accuracy of the SQ, when used by general nurses caring for older hospitalised patients, has not been comprehensively studied. DESIGN: A prospective cohort study. METHODS: This cohort study recruited consecutive 10,139 older patients (aged ≥65 years) who were admitted to Taipei City Hospital and were evaluated for the needs of palliative care in 2015. All patients were followed up for 12 months or until their death. The c-statistic value was calculated to indicate the predictive accuracy of the SQ and Palliative Care Screening Tool (PCST). RESULTS: Of all participants, 18.8% and 18.6% had a SQ response of 'no' and a PCST score ≥4, respectively. After controlling for other covariates, an SQ response of 'no' (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.83-2.31) and a PCST score ≥4 (AHR = 1.50; 95% CI: 1.29-1.75) were found to be the independent predictors for patients' 12-month mortality. The C-statistic values of the SQ and the PCST at recognising patients in their last year of life were .663 and .670, respectively. Moreover, there was moderate concordance (k = .44) between the SQ and the PCST in predicting 12-month mortality. CONCLUSIONS: SQ response of 'no' and a PCST score ≥4 were independent predictors of 12-month mortality in older patients. RELEVANCE TO CLINICAL PRACTICE: The SQ, when used by nurses working in hospital wards, is effective in identifying older patients nearing the end of life, as well as in providing advance care planning for patients. PATIENT OR PUBLIC CONTRIBUTION: Patients' palliative care needs at admission were assessed by general nurses using the SQ and PCST.

Cross-Sectional Analysis of Taiwanese Pharmacy Students' Experiences and Perceptions of Transitioning from In-Hospital Internships to Distance Learning Due to COVID-19.

The introductory pharmacy practice experiences (IPPE) in Taiwan, which are traditionally conducted in physical hospital settings, incorporated up to 30% distance learning from May 2021 due to Coronavirus Disease 2019 (COVID-19). A web-based cross-sectional survey was adopted to investigate pharmacy students' experiences and perceptions of transitioning from in-hospital internships to distance learning due to COVID-19 in the pharmacy department of a university in Southern Taiwan. We analyzed the results to discover factors that significantly affected students' perceptions of transitioning from in-hospital internships to distance learning. In total, 81 interns from the university's pharmacy department responded to the questionnaire. Approximately half of the participants felt happy when they learned, before the internship began, that the internship would be partially replaced with distance learning. The overall satisfaction rate was 67.9%, and no significant differences was observed in students' satisfaction between hospital size or distance-learning time. However, more students in the medical center felt they had insufficient time to finish assignments compared to those in the regional hospitals, and the students who had 11-15 days of distance learning felt that they interacted more smoothly with their peers compared to those who had other durations. Program designers should make distance internship courses more student-centered, with a focus on increasing interactions between students, teachers, and peers to compensate for the lack of physical presence.

Isoorientin Decreases Cell Migration via Decreasing Functional Activity and Molecular Expression of Proton-Linked Monocarboxylate Transporters in Human Lung Cancer Cells.

Aggressive tumor cells mainly rely on glycolysis, and further release vast amounts of lactate and protons by monocarboxylate transporter (MCT), which causes a higher intracellular pH (pHi) and acidic extracellular pH. Isoorientin, a principle flavonoid compound extracted from several plant species, shows various pharmacological activities. However, effects of isoorientin on anticancer and MCT await to explore in human lung cancer cells. Human lung cancer tissues were obtained from cancer patients undergoing surgery, while the human lung adenocarcinoma cells (A549) were bought commercially. Change of pHi was detected by microspectrofluorometry method with a pH-sensitive fluorescent dye, BCECF. MTT and wound-healing assay were used to detect the cell viability and migration, respectively. Western blot techniques and immunocytochemistry staining were used to detect the protein expression. Our results indicated that the expression of MCTs1/4 and CD147 were upregulated significantly in human lung tissues. In experiments of A549 cells, under HEPES-buffer, the resting pHi was 7.47, and isoorientin (1-300µM) inhibited functional activity of MCT concentration-dependently (up to -42%). Pretreatment with isoorientin (3-100µM) for 24h, MCT activity and cell migration were significantly inhibited (-25% and -40%, respectively), while the cell viability was not affected. Moreover, the expression of MCTs1/4, CD147, and matrix metalloproteinase (MMP) 2/9 were significantly down regulated. In summary, MCTs1/4 and CD147 are significantly upregulated in human lung adenocarcinoma tissues, and isoorientin inhibits cells-migration by inhibiting activity/expression of MCTs1/4 and MMPs2/9 in human lung cancer cells. These novel findings suggest that isoorientin could be a promising pharmacological agent for lung cancer.

An interprofessional training program for intrahospital transport of critically ill patients: model build-up and assessment.

Intrahospital transport of critically ill patients for diagnostic or therapeutic procedures can be compromised by patient instability, equipment problems or inexperienced teamworking. This quasi-experimental study aimed to assess the effectiveness of an in-situ interprofessional simulation-based training (IIST) model for junior member transport teams. Newly registered postgraduate physicians, nurses and respiratory therapists underwent the IIST. The technical skills (TS) of each participant and non-technical skills (NTS) of each interprofessional team were assessed using well-validated checklists. Thirty-six participants enrolled and were randomly assigned to six experimental and six control teams. Most participants achieved a significantly higher level of both TS and NTS. Both the control and experimental teams overvalued their NTS in the pretest, while the posttest self-assessment scores among the experimental groups more closely matched the expert assessments. Despite challenges in scheduling and the setting, the IIST was successfully conducted in a crowded hospital, which enabled trainees to optimize their learning in a real-life environment. In conclusion, the IIST model can facilitate the development of both TS and NTS for transport team members. Transport teams made up of newly registered staff from different disciplines may lack insight into their NTS in critical patient transfer management, but simulation training may cause improvements.

Astragaloside VI and cycloastragenol-6-O-beta-D-glucoside promote wound healing in vitro and in vivo.

BACKGROUND: Astragalus genus includes most of the common, historical herbal medicines that have various applications in Asian countries. However, clinical data and mechanistic insights into their actions are still lacking. PURPOSE: In this study, we aimed to examine the effects of astragalosides on wound healing in vitro and in vivo, as well as the underlying mechanisms of these actions. METHODS: The wound healing activity of astragalosides was investigated in human HaCaT keratinocytes, human dermal fibroblast (HDF) cells, and murine models of wound healing. RESULTS: All eight astragalosides studied enhanced epidermal growth factor receptor (EGFR) activity in HaCaT cells. Among them, astragaloside VI (AS-VI) showed the strongest EGFR activation. Consistently, AS-VI and cycloastragenol-6-O-beta-D-glucoside (CMG), which is the major metabolite of astragalosides, enhanced extracellular signal-regulated kinase (ERK) activity in a concentration-dependent manner. In agreement, both compounds induced EGFR-dependent cell proliferation and migration in HaCaT and HDF cells. In addition, we showed that AS-VI and CMG accelerated the healing of both sterile and infected wounds in vivo. These effects were associated with increased angiogenesis in the scar tissue. CONCLUSION: AS-VI and CMG increased the proliferation and migration of skin cells via activation of the EGFR/ERK signalling pathway, resulting in the improvement of wound healing in vitro and in vivo. These findings indicate the therapeutic potential of AS-VI and CMG to accelerate wound healing; additionally, they suggest the mechanistic basis of this activity.

Protective effect and mechanism of lycopene on endothelial progenitor cells (EPCs) from type 2 diabetes mellitus rats.

Endothelial progenitor cells (EPCs), widely existing in bone marrow and peripheral blood, are involved in the repair of injured vascular endothelium and angiogenesis which are important to diabetic mellitus (DM) patients with vascular complications. The number and the function of EPCs are related to the advanced glycation end products (AGEs) generated in DM patients. Lycopene (Lyc) is an identified natural antioxidant that protects EPCs under the microenvironment of AGEs from damage. However, the underlying mechanism remains unclear. To investigate the effect of Lyc on EPCs, we isolated EPCs from DM rat bone marrow and determined cell proliferation, cell cycle,apoptosis and autophagy of EPCs. The present study showed that 10µg/mL Lyc improved cell proliferation and had low cytotoxicity in the presence of AGEs. In addition, Lyc rescued S phase of the cell cycle arrest, reduced apoptosis rate and decreased autophagic reaction including ROS and mitochondrial membrane potential (MMP) of EPCs. Moreover, Lyc combined use of autophagy inhibitors, 3-MA, had better protective effects. Taken together, our data suggests that Lyc promotes EPCs survival and protect EPCs from apoptosis and oxidative autophagy induced by AGEs, further remaining the number and function of EPCs. This study provides new insights into Lyc protective mechanism of AGEs-induced oxidative autophagy in EPCs from DM patients and offers a new therapy for DM vascular complications.

Sensitivity and specificity of executive function tests for Alzheimer's disease.

Decline in executive function (EF) occurs early in Alzheimer's disease (AD) and can interfere with daily functioning. Unfortunately, little is known about the relative ability of traditional EF tests to detect these cognitive changes. Given that timely diagnosis and intervention are essential to improving functional outcome in this population, our aim was to identify the specific EF measures that best differentiated mild dementia from normal aging. Thirty-one patients with mild AD and 31 controls were administered 7 EF tests. Findings indicated significant between-group differences on all measures except Wisconsin Card Sorting Test. The remaining 6 tests displayed fair to good accuracy discriminating between AD cases and controls. Only category fluency and Tower of London test remained in the final regression model that yielded the highest AUC of 0.90, which was not statistically different from that of either test alone. Overall, most of the tests employed were valid for assessing mild EF disturbances. Specifically, the two measures can be used in isolation for quick screening or in combination to facilitate a more in-depth evaluation of EF performance. This study contributes to clinical field by testifying to the validity of various EF tests to identify AD-related compromises in this cognitive domain.

An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression.

The Na(+)/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. It has been shown that the intestinal SGLT1 level is significantly increased in diabetic individuals and positively correlated with the pathogenesis of diabetes. The development of targeted therapeutics that can reduce the intestinal SGLT1 expression level is, therefore, important. In this study, we showed that ginsenoside Rg1 effectively decreased intestinal glucose uptake through inhibition of SGLT1 gene expression in vivo and in vitro. Transient transfection analysis of the SGLT1 promoter revealed an essential cAMP response element (CRE) that confers the Rg1-mediated inhibition of SGLT1 gene expression. Chromatin immunoprecipitation assay and targeted CRE-binding protein (CREB) silencing demonstrated that Rg1 reduced the promoter binding of CREB and CREB binding protein associated with an inactivated chromatin status. In addition, further studies showed that the epidermal growth factor receptor (EGFR) signaling pathway also plays an essential role in the inhibitory effect of Rg1; taken together, our study demonstrates the involvement of the EGFR-CREB signaling pathway in the Rg1-mediated downregulation of SGLT1 expression, which offers a potential strategy in the development of antihyperglycemic and antidiabetic treatments.

An essential role of cAMP response element-binding protein in epidermal growth factor-mediated induction of sodium/glucose cotransporter 1 gene expression and intestinal glucose uptake.

The sodium/glucose cotransporter 1 (SGLT1) is responsible for glucose uptake in intestinal epithelial cells. Its expression is decreased in individuals with intestinal inflammatory disorders and is correlated with the pathogenesis of disease. The aim of this study was to understand the regulatory mechanism of the SGLT1 gene. Using the trinitrobenzene sulfonic acid-induced mouse models of intestinal inflammation, we observed decreased SGLT1 expression in the inflamed intestine was positively correlated with the mucosal level of epidermal growth factor (EGF) and activated CREB. Overexpression of EGF demonstrated that the effect of EGF on intestinal glucose uptake was primarily due to the increased level of SGLT1. We identified an essential cAMP binding element (CRE) confers EGF inducibility in the human SGLT1 gene promoter. ChIP assay further demonstrated the increased binding of CREB and CBP to the SGLT1 gene promoter in EGF-treated cells. In addition, the EGFR- and PI3K-dependent CREB phosphorylations are involved in the EGF-mediated SGLT1 expression. This is the first report to demonstrate that CREB is involved in EGF-mediated transcription regulation of SGLT1 gene in the normal and inflamed intestine, which can provide potential therapeutic applications for intestinal inflammatory disorders.

A gut microbial metabolite of ginsenosides, compound K, induces intestinal glucose absorption and Na(+) /glucose cotransporter 1 gene expression through activation of cAMP response element binding protein.

SCOPE: The Na(+) /glucose cotransporter 1 (SGLT1) plays a crucial role in glucose uptake in intestinal epithelial cells (IECs), which has been shown essential in ameliorating intestinal inflammation. Ginseng has historically been used to treat inflammatory disorders. Understanding the regulatory mechanism of ginseng-mediated induction of SGLT1 gene expression in human intestinal cells is therefore important. METHODS AND RESULTS: We demonstrate that ginsenoside compound K (CK) enhances SGLT1-mediated glucose uptake in mice and human intestinal Caco-2 cells. Transient transfection analysis using SGLT1 promoter-luciferase reporters demonstrated that the presence of an essential cAMP response element (CRE) is required for CK-mediated induction of SGLT1 gene expression. The ChIP assays indicated that increased CRE-binding protein (CREB) and CREB-binding protein (CBP) binding to the SGLT1 promoter in CK-treated cells is associated with an activated chromatin state. Our result showed that the increased CREB phosphorylation is directly correlated with SGLT1 expression in IECs. Further studies indicated that the epidermal growth factor receptor (EGFR) signaling pathway is involved in the CK-mediated effect. CONCLUSION: These findings provide a novel mechanism for the CK-mediated upregulation of SGLT1 expression through EGFR-CREB signaling activation, which could contribute to reducing gut inflammation.

Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose.

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 µg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 µg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

Maximally efficient two-stage screening: Determining intellectual disability in Taiwanese military conscripts.

OBJECTIVE: The purpose of this study was to apply a two-stage screening method for the large-scale intelligence screening of military conscripts. METHODS: We collected 99 conscripted soldiers whose educational levels were senior high school level or lower to be the participants. Every participant was required to take the Wisconsin Card Sorting Test (WCST) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) assessments. RESULTS: Logistic regression analysis showed the conceptual level responses (CLR) index of the WCST was the most significant index for determining intellectual disability (ID; FIQ ≤ 84). We used the receiver operating characteristic curve to determine the optimum cut-off point of CLR. The optimum one cut-off point of CLR was 66; the two cut-off points were 49 and 66. Comparing the two-stage window screening with the two-stage positive screening, the area under the curve and the positive predictive value increased. Moreover, the cost of the two-stage window screening decreased by 59%. CONCLUSION: The two-stage window screening is more accurate and economical than the two-stage positive screening. Our results provide an example for the use of two-stage screening and the possibility of the WCST to replace WAIS-R in large-scale screenings for ID in the future.

Effect of ginsenosides on glucose uptake in human Caco-2 cells is mediated through altered Na+/glucose cotransporter 1 expression.

In this study, we measured the effect of ginsenosides on glucose uptake using the Caco-2 cell system. At submicromolar concentrations, these compounds exhibited marked effects on the rate of glucose transport across the differentiated Caco-2 cell monolayer. Compound K (CK), the main intestinal bacterial metabolite of the protopanaxadiol ginsenosides, significantly enhanced the steady-state glucose transport rate to about 50% of the control sample rate (from 1.54 +/- 0.09 to 2.25 +/- 0.15 nmol/min). Conversely, the protopanaxatriol ginsenoside Rg1 inhibited glucose transport to about 70% of the original rate (from 1.54 +/- 0.09 to 1.02 +/- 0.05 nmol/min). Consistent with the effect on glucose uptake rate, CK and Rg1 conferred a significant and paralleled alteration on both the protein and mRNA expression levels of the Na+/glucose cotransporter 1 (SGLT1) gene. Unlike SGLT1, there is no significant alteration on the protein or mRNA levels of GLUTs in CK- or Rg1-treated cells. Taken together, our results demonstrate that ginsenosides CK and Rg1 elicited potent enhancing and suppressing effects, respectively, on glucose uptake across human intestinal Caco-2 monolayer through modulation of SGLT1 expression.

Psychosocial characteristics of criminals committing incest and other sex offenses: a survey in a Taiwanese prison.

The purpose of this study was to investigate the psychosocial characteristics of criminals who had committed incest or other sexual offenses. The participants, 240 criminals serving sentences for sex offenses in a Taiwanese prison, were divided into two groups: incest offenders (20.4%) and other sex offenders (79.6%). The psychosocial characteristics taken into consideration included age, parental survival, education, marital status, previous crime records, drug and alcohol abuse, diagnosed mental disorders, and victim abuse at the time of the offense. After an analysis of the data, the authors concluded that even though incest offenders showed fewer mental disorders, they needed psychiatric treatment and that this treatment should be focused not only on their mental disorder and related symptoms but especially to correct their abnormal behavior. Also, attention should be given to their psychosocial characteristics.

Fluorinated aminoalkoxide and ketoiminate indium complexes as MOCVD precursors for In2O3 thin film deposition.

The syntheses of two distinctive types of indium complex derived from trimethylindium (InMe(3)) are reported. The first kind has a generalized structural formula [InMe(2)(amak)](2), where (amak)H is an abbreviation for a series of chelating amino alcohol ligands HOC(CF(3))(2)CH(2)NHR, R = (CH(2))(2)OMe (1), Me (2), and Bu(t) (3), as well as HOC(CF(3))(2)CH(2)NMe(2) (4); while the second type of complex is illustrated by [InMe(2)(keim)] (5), for which (keim)H is a tridentate ketoimine ligand of structural formula O=C(CF(3))CH(2)C(CF(3))=NCH(2)CH(2)NMe(2). The solid-state structures of 2 and 5 were determined using single crystal X-ray diffraction studies. For the aminoalkoxide complexes 2-4, the existence of dimeric In(2)O(2) core structures in the solid state has been established with the amino fragment located trans to the alkoxide ligands, in a molecular arrangement which is in contrast to the distorted, trigonal bipyramidal geometry observed for the ketoiminate complex 5. Moreover, VT NMR studies of 2 revealed a rapid dimer-to-monomer equilibration and simultaneous rupture of the N-->In dative interaction, affording two interconvertible isomers related by having the N-Me substituents in either trans or cis dispositions. For complexes 2 and 5, deposition of In(2)O(3) thin films was successfully conducted at temperatures 400-500 degrees C, using O(2) as the carrier gas to induce indium oxide deposition and to suppress carbon impurity present in the thin film. Scanning electron micrographs (SEMs) revealed the surface morphologies. The atomic composition of these films was examined by both X-ray photoelectron spectroscopy (XPS) and Rutherford backscattering (RBS) methods, while X-ray diffraction studies (XRD) confirmed the formation of a preferred orientation along the (222) planes.