Translation, adaptation, and validation of a Chinese version of the Hypertension Self-Care Activity Level effects (H-SCALE) for patients with hypertension.

BACKGROUND: Lifestyle modification is an essential component of prevention and management of hypertension. Existing instruments in Taiwan focus on assessing lifestyle modifications by evaluating medication adherence or confidence in controlling blood pressure. However, other self-care activities, such as diet, physical activity, weight management, smoking, and alcohol consumption are also important. The Hypertension Self-Care Activity Level Effects (H-SCALE) is one such instrument, but there are no similar tools available in Taiwan. AIM: This study aimed to translate the H-SCALE into Chinese and test its validity, and reliability in a sample of adults with hypertension. METHODS: The English version of the 31-item H-SCALE was translated into Chinese using the forward-backward method. The content validity index (CVI) of the translated scale was determined by five experts in hypertension. Item analysis was conducted with a pilot sample of 20 patients with hypertension. Cronbach's α was used to establish the internal consistency reliability for the Chinese version of the H-SCALE (H-SCALE-C). Exploratory factor analysis (EFA) explored the structure of the H-SCALE-C. Additionally, construct validity was examined with confirmatory factor analysis (CFA). Patients with hypertension were recruited by convenience sampling from a cardiovascular outpatient clinic of a medical center in northern Taiwan. A total of 318 patients met the inclusion criteria and participated in factor analysis in the study. RESULTS: Pilot testing of the scale items indicated most patients could not accurately estimate the number of days of alcohol consumption for the previous week. Therefore, three alcohol-related items were removed. The adaptation resulted in a 28-item H-SCALE-C. EFA revealed a 4-factor solution with 13 items that explained 63.93% of the total variance. CFA indicated a good fit for a 4-factor model and construct validity was acceptable. Internal consistency reliability was acceptable (Cronbach's alpha for the four subscales ranged from 0.65 to 0.94). Convergent validity was acceptable, and discriminant validity was significant. CONCLUSIONS: The H-SCALE-C is a valid, reliable tool for promptly assessing life-style activities for patients with hypertension in Taiwan. The instrument is suitable for assisting healthcare providers in evaluating self-care activities, which could be used to facilitate lifestyle modifications for patients with hypertension.

Exploring morphological similarity and randomness in Alzheimer's disease using adjacent grey matter voxel-based structural analysis.

BACKGROUND: Alzheimer's disease is characterized by large-scale structural changes in a specific pattern. Recent studies developed morphological similarity networks constructed by brain regions similar in structural features to represent brain structural organization. However, few studies have used local morphological properties to explore inter-regional structural similarity in Alzheimer's disease. METHODS: Here, we sourced T1-weighted MRI images of 342 cognitively normal participants and 276 individuals with Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative database. The relationships of grey matter intensity between adjacent voxels were defined and converted to the structural pattern indices. We conducted the information-based similarity method to evaluate the structural similarity of structural pattern organization between brain regions. Besides, we examined the structural randomness on brain regions. Finally, the relationship between the structural randomness and cognitive performance of individuals with Alzheimer's disease was assessed by stepwise regression. RESULTS: Compared to cognitively normal participants, individuals with Alzheimer's disease showed significant structural pattern changes in the bilateral posterior cingulate gyrus, hippocampus, and olfactory cortex. Additionally, individuals with Alzheimer's disease showed that the bilateral insula had decreased inter-regional structural similarity with frontal regions, while the bilateral hippocampus had increased inter-regional structural similarity with temporal and subcortical regions. For the structural randomness, we found significant decreases in the temporal and subcortical areas and significant increases in the occipital and frontal regions. The regression analysis showed that the structural randomness of five brain regions was correlated with the Mini-Mental State Examination scores of individuals with Alzheimer's disease. CONCLUSIONS: Our study suggested that individuals with Alzheimer's disease alter micro-structural patterns and morphological similarity with the insula and hippocampus. Structural randomness of individuals with Alzheimer's disease changed in temporal, frontal, and occipital brain regions. Morphological similarity and randomness provide valuable insight into brain structural organization in Alzheimer's disease.

Mediating Effect of Heart Rate Variability on the Relationship Between Anxiety Symptoms and Blood Pressure in Patients with Primary Hypertension.

Patients with hypertension (HTN) are at increased risk of developing cardiovascular disease, which can be reduced with blood pressure (BP) control. Anxiety can contribute to high BP and low heart rate variability (HRV). Although relationships between social support, self-rated health-status (SRHS), anxiety and measures of HRV and BP have been suggested, they have not been clearly established. This cross-sectional correlational study aimed to 1) examine relationships between social support, SRHS, and anxiety; and 2) examine if HRV mediated relationships between anxiety symptoms and BP. Patients with primary HTN were recruited from a cardiovascular outpatient clinic using convenience sampling (N = 300). Data included scale scores for SRHS, social support, and anxiety (Hospital Anxiety and Depression Scale). A handheld limb-lead electrocardiogram monitor measured HRV, using the ratio of low-frequency bands to high-frequency bands; an automatic sphygmomanometer measured systolic and diastolic blood pressure (SBP and DBP, respectively). Path analysis of structural equation models examined relationships between variables; the bootstrap method examined the mediating effects of HRV. Analysis showed scores for SRHS and social support had a direct effect on anxiety scores. Scores for anxiety directly affected HRV and BP. HRV also had a direct effect on BP. Bootstrapping indicated HRV mediated the relationship between anxiety symptoms and BP. The final model indicated SRHS, social support, and anxiety symptoms together explained 80% of SBP and 33% of DBP. These findings suggest HRV could be used to measure the effectiveness of strategies aimed at reducing anxiety and improving control of BP.

Identification and Functional Characterization of an Omega-Class Glutathione S-Transferase Gene PcGSTO1 Associated with Cyetpyrafen Resistance in Panonychus citri (McGregor).

Cyetpyrafen is a recently developed acaricide. The citrus red mite, Panonychus citri (McGregor), has developed significant resistance to cyetpyrafen. However, the molecular mechanism underlying the cyetpyrafen resistance in P. citri remains unclear. Glutathione S-transferases (GSTs) play a critical role in arthropod pesticide resistance. This study showed that GSTs were potentially related to the resistance of P. citri to cyetpyrafen through synergistic experiments and enzyme activity analysis. An omega-family GST gene, PcGSTO1, was significantly up-regulated in the egg, nymph, and adult stages of the cyetpyrafen-resistant strain. Additionally, silencing of PcGSTO1 significantly increased the mortality of P. citri to cyetpyrafen and recombinant PcGSTO1 demonstrated the ability to metabolize cyetpyrafen. Our results indicated that the overexpression of PcGSTO1 is associated with cyetpyrafen resistance in P. citri, and they also provided valuable information for managing resistance in P. citri.

Ultrashort channel MoSe2transistors with selenium atoms replaced at the interface: first-principles quantum-transport study.

Realizing n- and p-type transition metal dichalcogenide (TMD)-based field-effect transistors for nanoscale complementary metal oxide semiconductor (CMOS) applications remains challenging owing to undesirable contact resistance. Quantumtransport calculations were performed by replacing single-sided Se atoms of TMD near the interface with As or Br atoms to further improve the contact resistance. Here, partial selenium replacement produced a novel interface with a segment of metamaterial MoSeX (Pt/MoSeX/MoSe2; X = As, Br). Such stable metamaterials exhibit semi-metallicity, and the contact resistance can be thus lowered. Our findings provide insights into the potential of MoSe2-based nano-CMOS logic devices.

Patient-reported frailty phenotype (PRFP) vs. International Myeloma Working Group frailty index (IMWG FI) proxy: A comparison between two approaches to measuring frailty.

INTRODUCTION: Frailty assessments may help to identify patients at highest risk for treatment-related toxicity, early treatment discontinuation due to toxicity, and death in Multiple Myeloma. We aimed to compare the patient-reported frailty phenotype (PRFP) and a modified version of the International Myeloma Working Group frailty index (IMWG FI) in terms of their strengths, limitations, and classification of frailty in a cohort of patients with relapsed/refractory multiple myeloma (RRMM). MATERIALS AND METHODS: Data were pooled from six RRMM Phase 3 randomized clinical trials submitted to the Food and Drug Administration for regulatory review between 2010 and 2021. Patients were classified as fit, intermediate fit/pre-frail, or frail using both PRFP and the IMWG FI proxy. Agreement between the two approaches in classification of patient frailty was assessed using weighted Cohen's kappa. A contingency table and Venn diagram were generated to analyze overlap in categorization of patient frailty across the different severity groups. Descriptive statistics were used to summarize and compare the clinical and demographic characteristics of patients categorized as frail by PRFP vs. IMWG FI proxy. RESULTS: Of the 2,750 patients included in this analysis, IMWG FI proxy classified 16.4% (452) patients as frail, 28.1% (772) as intermediate fit/pre-frail, and 55.5% (1,526) as fit. Meanwhile, PRFP classified 21.7% (597) of patients as frail, 24.5% (675) as intermediate fit/pre-frail, and 53.8% (1478) as fit. Fair agreement was observed between PRFP and IMWG FI proxy (weighted Cohen's Kappa = 0.34 [0.31-0.37]). On average, patients who were categorized as frail by IMWG FI proxy were older and had higher Charlson Comorbidity Index scores than patients classified as frail by PRFP. In contrast, patients who were classified as frail by PRFP had worse EORTC QLQ-C30 Physical Functioning subscale summary scores as compared to patients in the IMWG FI proxy frail group (median score of 40 vs. 47 out of 100). DISCUSSION: Our analysis found fair concordance between IMWG FI proxy and PRFP. This demonstrates that while both frailty models measure the same underlying construct, the variables that constitute each approach may result in differing frailty categorizations for the same patient. Further prospective studies are needed to establish and compare the predictive and prognostic abilities of the different frailty indices in MM.

Multiple criteria decision analytic methods in management with T-spherical fuzzy information.

With a focus on T-spherical fuzzy (T-SF) sets, the aim of this paper is to create a split-new appraisal mechanism and an innovative decision analytic method for use with multiple-criteria assessment and selection in uncertain situations. The T-SF frame is the latest recent advancement in fuzzy settings and uses four facets (consisting of membership grades of positivity, neutrality, negativity, and refusal) to elucidate complex uncertainties, thereby evidently reducing information loss, in anticipation of fully manifesting indistinct and equivocal information. This paper adds to the body of knowledge regarding multiple criteria choice modeling by raising T-SF correlation-oriented measurements connected to the fixed and displaced ideal/anti-ideal benchmarks and by creating an approachable appraisal mechanism for advancing a T-SF decision analytic methodology. Consider, in particular, the performance ratings of available options in terms of judging criteria under the T-SF type of uncertainties. This research gives correlation-oriented measurements focusing on two varieties of maximum and square root functions in T-SF situations, which serve as a solid foundation for an efficacious appraisal mechanism from two views of anchored judgments corresponding to the fixed and displaced benchmarks. The T-SF Minkowski distance index is generated to integrate the outranking and outranked identifiers relying on correlation-oriented measurements for figuring out the local outranking and outranked indices. The T-SF decision analytic procedures are constructed using a new appraisal significance index that is founded on certain valuable insights of correlation-oriented maximizing and minimizing indices as well as global outranking and outranked indices. Additionally, a concrete location selection dilemma is dealt with in this research to showcase the applicability and efficiency of the suggested T-SF decision analytic methodology. Sensitivity analyses and comparative studies are carried out to investigate substantial modifications in pertinent parameters and to confirm the robustness of the predominance relationships among the available options. The suggested approaches are adaptable, flexible, and reliable, according to the application outcomes and comparison findings. This research provides four scientific contributions: (1) the utilization of T-SF correlation coefficients as the basis for prioritization analysis involving multiple criteria assessments, (2) the evolution of the T-SF Minkowski distance index to model outranking decision-making processes, (3) the creation of a reliable appraisal mechanism based on T-SF correlation-oriented measurements for intelligent decision support, and (4) the advancement of computational tools and procedures (e.g., correlation-oriented maximizing and minimizing indices, global outranking and outranked indices, and appraisal significance indices) to perform the decision analytic procedure in T-SF settings. In terms of managerial implications, the solution findings support the employment of the fixed ideal/anti-ideal benchmarking mechanism, as its measurements and indices are easy to operate and suitably sensitive. Next, in practical implementations of the T-SF decision analytic procedure, it is advised to utilize the T-SF Manhattan distance index for calculating convenience. Finally, the T-SF decision analytic techniques offer fundamental ideas and measurements appropriate for manipulating T-SF information in complex decision situations, thereby increasing the application potential in the area of decision-making with information uncertainty.

Early Life Exposure to C16-Ceramide Improves Learning and Short-Term Memory Behavior during Adulthood in Mice.

Ceramides, structural components of the cell, are known to play a range of roles in glucose metabolism and apoptosis. C16-ceramide, an abundant molecular species of endogenous ceramide, has not had its influence on learning and memory explored. We administered C16-ceramide to mice immediately after weaning and examined the learning and memory behavior of these mice during adulthood. Mice given C16-ceramide early in life showed improved adult learning/short-term memory behavior without affecting their glucose metabolism. Looking for a plausible mechanism for this, we found that calcium influx, CaMKII/CREB, and the Erk-relevant signaling transduction are increased after C16-ceramide stimulation in primary neurons in vitro. Possible downstream epigenetic molecular events, such as H3K4 methylation and Egr-1 abundance, were also found to be upregulated. Utilizing J20 mice, an Alzheimer disease mice model in which mice were injected after weaning with C16-ceramide, we found that these mice also show improved learning and short-term memory behavior when assessed by the Morris water maze test. Taken together, giving C16-ceramide early in life would seem to benefit learning and short-term memory behavior during adulthood.

Paclitaxel exerts antiplatelet and antithrombotic activities: Additional benefit from use of paclitaxel-coated balloons and -eluting stents in coronary revascularization and prevention of in-stent restenosis.

INTRODUCTION: Paclitaxel is a microtubule-stabilizing drug used to treat several types of cancer, including ovarian and breast cancer. Because of its antiproliferative effect on vascular smooth muscle cells, balloons and stents are coated with paclitaxel for use in coronary revascularization and prevention of in-stent restenosis (ISR). However, mechanisms underlying ISR are complicated. Platelet activation is one of the major causes of ISR after percutaneous coronary intervention. Although the antiplatelet activity of paclitaxel was noted in rabbit platelets, the effect of paclitaxel on platelets remains unclear. This study investigated whether paclitaxel exhibits antiplatelet activity in human platelets. METHODS AND RESULTS: Paclitaxel inhibited platelet aggregation induced by collagen but not that induced by thrombin, arachidonic acid, or U46619, suggesting that paclitaxel is more sensitive to the inhibition of collagen-induced platelet activation. Moreover, paclitaxel blocked collagen receptor glycoprotein (GP) VI downstream signaling molecules, including Lyn, Fyn, PLCγ2, PKC, Akt, and MAPKs. However, paclitaxel did not directly bind to GPVI and cause GPVI shedding, as detected by surface plasmon resonance and flow cytometry, respectively, indicating that paclitaxel may interfere with GPVI downstream signaling molecules, such as Lyn and Fyn. Paclitaxel also prevented granule release and GPIIbIIIa activation induced by collagen and low convulxin doses. Moreover, paclitaxel attenuated pulmonary thrombosis and delayed platelet thrombus formation in mesenteric microvessels without significantly affecting hemostasis. CONCLUSION: Paclitaxel exerts antiplatelet and antithrombotic effects. Thus, paclitaxel may provide additional benefits beyond its antiproliferative effect when used in drug-coated balloons and drug-eluting stents for coronary revascularization and prevention of ISR.

Using in vivo cerebellar electroporation to study neuronal cell proliferation and differentiation in a Joubert syndrome mouse model.

Joubert syndrome (JS) is an autosomal recessive ciliopathy that mainly affects the morphogenesis of the cerebellum and brain stem. To date, mutations in at least 39 genes have been identified in JS; all these gene-encoding proteins are involved in the biogenesis of the primary cilium and centrioles. Recent studies using the mouse model carrying deleted or mutated JS-related genes exhibited cerebellar hypoplasia with a reduction in neurogenesis; however, investigating specific neuronal behaviors during their development in vivo remains challenging. Here, we describe an in vivo cerebellar electroporation technique that can be used to deliver plasmids carrying GFP and/or shRNAs into the major cerebellar cell type, granule neurons, from their progenitor state to their maturation in a spatiotemporal-specific manner. By combining this method with cerebellar immunostaining and EdU incorporation, these approaches enable the investigation of the cell-autonomous effect of JS-related genes in granule neuron progenitors, including the pathogenesis of ectopic neurons and the defects in neuronal differentiation. This approach provides information toward understanding the multifaceted roles of JS-related genes during cerebellar development in vivo.

Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma.

PURPOSE: The objective of this retrospective study was to determine the feasibility of measuring frailty using patient responses to relevant EORTC QLQ-C30 items as proxy criteria for the Fried Frailty Phenotype, in a cohort of patients with Relapsed/Refractory Multiple Myeloma (RRMM). METHODS: Data were pooled from nine Phase III randomized clinical trials submitted to the FDA for regulatory review between 2010 and 2021, for the treatment of RRMM. Baseline EORTC QLQ-C30 responses were used to derive a patient-reported frailty phenotype (PRFP), based on the Fried definition of frailty. PRFP was assessed for internal consistency reliability, structural validity, and known groups validity. RESULTS: This study demonstrated the feasibility of adapting patient responses to relevant EORTC QLQ-C30 items to serve as proxy Fried frailty criteria. Selected items were well correlated with one another and PRFP as a whole demonstrated adequate internal consistency reliability and structural validity. Known groups analysis demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles, with frail patients reporting more difficulty in walking about, washing/dressing, and doing usual activities, as compared to their pre-frail and fit counterparts. Among the 4928 patients included in this study, PRFP classified 2729 (55.4%) patients as fit, 1209 (24.5%) as pre-frail, and 990 (20.1%) as frail. CONCLUSION: Constructing a frailty scale from existing PRO items commonly collected in cancer trials may be a patient-centric and practical approach to measuring frailty. Additional psychometric evaluation and research is warranted to further explore the utility of such an approach.

Factors influencing self-care among patients with primary hypertension: path analysis of mediating roles of self-efficacy and depressive symptoms.

AIMS: Blood pressure control requires medication adherence and lifestyle modifications. Social cognitive theory suggests social support, psychological adaptation, and self-efficacy can reinforce lifestyle modifications. This study investigated if self-efficacy was a mediator between self-rated health status (SRHS), social support, depressive symptoms, anxiety, and self-care among patients with hypertension. METHOD AND RESULTS: This cross-sectional study recruited patients with primary hypertension by convenience sampling (N = 318) from an outpatient cardiology clinic. Data included participant characteristics and self-report scales for social support, SRHS, anxiety, depressive symptoms, Self-efficacy and self-care diet quality and weight management. We used path analysis to test the hypothesized model. The mean age of participants was 63.91 ± 11.80 years. Mean scale scores for social support and depressive symptoms were 54.23 ± 13.26 and 6.14 ± 3.14, respectively; SRHS was 66.91 ± 13.80, self-efficacy was 34.31 ± 11.62, self-care for diet quality and weight management were 36.50 ± 13.19 and 27.38 ± 8.64, respectively. Bootstrapping demonstrated self-efficacy was the mediator between social support and self-care for diet quality and weight management; depressive symptoms mediated the relationship between social support and self-efficacy. In addition, the variable of depressive symptoms was also a mediator between SRHS and self-efficacy. The final model showed SRHS, social support, depressive symptoms, and self-efficacy explained 28% of self-care. CONCLUSION: Our findings suggest developing theory-based interventions for patients with hypertension that provide education and/or psychological support for increasing patients' self-efficacy and reducing depressive symptoms simultaneously to facilitate their long-term self-care behaviours.

Evolved distance measures for circular intuitionistic fuzzy sets and their exploitation in the technique for order preference by similarity to ideal solutions.

Circular intuitionistic fuzzy (C-IF) sets are an up-and-coming tool for enforcing indistinct and imprecise information in variable and convoluted decision-making situations. C-IF sets, as opposed to typical intuitionistic fuzzy sets, are better suited for identifying the evaluation data with uncertainty in intricate realistic decision situations. The architecture of the technique for order preference by similarity to ideal solutions (TOPSIS) provides powerful evaluation tools to aid decision-making in intuitionistic fuzzy conditions. To address appraisal issues associated with decision analysis involving extremely convoluted information, this paper propounds a novel C-IF TOPSIS approach in the context of C-IF uncertainty. This research makes three significant contributions. First, based on the three- and four-term operating rules, this research introduces C-IF Minkowski distance measures, which are new generalized representations of distance metrics applicable to C-IF values and C-IF sets. Such general C-IF distance metrics can alleviate the constraints of established C-IF distance measures, provide usage resiliency through parameter settings, and broaden the applicability of metric analysis. Second, unlike existing C-IF TOPSIS methods, this research fully utilizes C-IF information characteristics and extends the core structure of the classic TOPSIS to C-IF contexts. With the newly developed C-IF Minkowski metrics, this study faithfully demonstrates the trade-off evaluation and compromise decision rules in the TOPSIS framework. Third, this research builds on the core strengths of the pioneered C-IF Minkowski distance measures to create innovative C-IF TOPSIS techniques utilizing four different combinations, including displaced and fixed anchoring frameworks, as well as three- and four-term representations. Such a refined C-IF TOPSIS methodology can assist decision-makers in proactively addressing increasingly sophisticated decision-making problems in practical settings. Finally, this research employs two innovative prioritization algorithms to address a site selection issue of large-scale epidemic hospitals to illustrate the superior capabilities of the C-IF TOPSIS methodology over some current related approaches.

Optimization of acetamide based deep eutectic solvents with dual cations for high performance and low temperature-tolerant aqueous zinc ion batteries via tuning the ratio of co-solvents.

In this work, a novel acetamide-based deep eutectic solvent (DES) with Zn2+/ Li+ dual ions is designed and its physicochemical properties are tuned by adjusting the co-solvents (water and acetonitrile). Furthermore, the interplay between electrolyte components is investigated by spectroscopic analyses and molecular dynamics calculations. The addition of acetonitrile facilitates the formation of solid electrolyte interphase (SEI) with organic/inorganic components on the zinc anode. The presence of SEI coating enhances Coulombic efficiency and cycling stability by inhibiting the parasitic reactions and dendrite formation in the anode. The advantages of using dual cations in DES are demonstrated by assembling Zn ion batteries (ZIB) with the composite of δ-MnO2 and reduced graphene oxide as the cathode. The study of electrode kinetics in hybrid DES electrolytes suggests that Zn2+ and Li+ ions are responsible for battery-like and pseudocapacitive behavior of δ-MnO2 electrodes, respectively. With these merits, ZIB with the cutoff voltage of 2 V delivers a high cell capacity of 208 mAh g-1 at 0.1 Ag-1 and achieves 91% capacity retention after 1500 cycles at 2 Ag-1. More importantly, ZIB with hybrid DES is stably operated at the temperature of -20 °C, which is impossibly achieved by ZIB with conventional aqueous electrolytes.

The relationship between hot flashes and fatty acid binding protein 2 in postmenopausal women.

INTRODUCTION: Hot flashes, the most bothering symptom of menopause, are linked to a metabolic inflammation. Due to estrogen deficiency in menopause, dysbiosis is observed. The intestinal barrier affects the interaction of microbiota in healthy or unhealthy individuals. This study investigates the relationship between hot flashes and gut permeability in postmenopausal women. PARTICIPANTS AND DESIGN: In this cross-sectional study, we divided 289 women, aged 40-65 years, into four groups based on their hot-flash severity: HF0: never experienced hot flashes; HFm: mild hot flashes; HFM: moderate hot flashes; HFS: severe hot flashes. The measured variables included the clinical parameters; hot flashes experience; fasting plasma levels of zonulin, fatty acid binding protein 2 (FABP2), endotoxin, and cytokines/chemokines. We used multiple linear regression analysis to evaluate the relationship between hot flashes and the previously mentioned gut barrier proteins. SETTINGS: The study was performed in a hospital medical center. RESULTS: The hot flashes had a positive tendency toward increased levels of circulating FABP2 (P-trend = 0.001), endotoxin (P-trend = 0.031), high-sensitivity C-reactive protein (hs-CRP) (P-trend = 0.033), tumor necrosis factor alpha (TNF-α) (P-trend = 0.017), and interferon-inducible protein-10 (IP10) (P-trend = 0.021). Spearman's correlation analysis revealed significant correlations of FABP2 with endotoxin, TNF-α, monocyte chemoattractant protein-1, IP10, and hs-CRP in the 289 postmenopausal women included in this study. Linear regression analysis revealed that hot-flash severity had significant assoiciations with FABP2 (P-trend = 0.002), but not with zonulin. After adjusting for body mass index, age, and menopause duration, multivariate linear regression analysis revealed the differences between HFs (% difference (95% confidence interval), 22.36 (8.04, 38.59), P = 0.01) and HF0 groups in terms of FABP2 levels. CONCLUSIONS: This study shows that hot flashes are significantly associated with FABP2 levels in postmenopausal women. It suggests that severe hot flashes are linked to an increase in intestinal barrier permeability and low-grade systemic inflammation.

Fuzzy optimization for identifying anti-cancer targets with few side effects in constraint-based models of head and neck cancer.

Computer-aided methods can be used to screen potential candidate targets and to reduce the time and cost of drug development. In most of these methods, synthetic lethality is used as a therapeutic criterion to identify drug targets. However, these methods do not consider the side effects during the identification stage. This study developed a fuzzy multi-objective optimization for identifying anti-cancer targets that not only evaluated cancer cell mortality, but also minimized side effects due to treatment. We identified potential anti-cancer enzymes and antimetabolites for the treatment of head and neck cancer (HNC). The identified one- and two-target enzymes were primarily involved in six major pathways, namely, purine and pyrimidine metabolism and the pentose phosphate pathway. Most of the identified targets can be regulated by approved drugs; thus, these drugs are potential candidates for drug repurposing as a treatment for HNC. Furthermore, we identified antimetabolites involved in pathways similar to those identified using a gene-centric approach. Moreover, HMGCR knockdown could not block the growth of HNC cells. However, the two-target combinations of (UMPS, HMGCR) and (CAD, HMGCR) could achieve cell mortality and improve metabolic deviation grades over 22% without reducing the cell viability grade.

Artesunate as a glycoprotein VI antagonist for preventing platelet activation and thrombus formation.

Platelets play a crucial role on hemostasis and are also involved in cardiovascular diseases, such as heart attack and stroke. Artesunate has been reported to possess multiple biological activities, including antitumor and anti-inflammatory activities. However, its effect on platelet activation remains unclear. Thus, we explored the detailed mechanisms underlying its antiplatelet effect. For the in vitro study, the data indicated that artesunate inhibited platelet aggregation induced by collagen, but not thrombin or U46619, indicating that artesunate may selectively inhibit collagen-mediated platelet activation Artesunate also blocked glycoprotein VI (GPVI) downstream signaling, including Syk, PLCγ2, PKC, Akt, and MAPKs. Moreover, artesunate could compete with collagen for binding to collagen receptor and bind to human recombinant GPVI with a high affinity (KD = 44 nM), indicating that it may directly interfere with GPVI. Artesunate also reduced collagen-induced granule release, calcium mobilization, and GPIIbIIIa activation. For the in vivo study, artesunate markedly prevented pulmonary thrombosis and delayed platelet thrombus formation in mesenteric veins and arteries but had minimal effects on hemostasis. In conclusion, we for the first time demonstrated that artesunate acts as a GPVI antagonist and effectively prevents platelet activation and thrombus formation with minimal risk of bleeding, highlighting its therapeutic potential in cardiovascular diseases.

A web-based self-care program to promote healthy lifestyles and control blood pressure in patients with primary hypertension: A randomized controlled trial.

BACKGROUND: Hypertension is a major risk factor for cardiovascular diseases, which contributes to the worldwide mortality rate. Successful blood pressure control requires adherence to medications and lifestyle modifications. However, motivating patients with primary hypertension to change and sustain behaviors long-term is challenging. A web-based self-care program centered on self-efficacy theory could provide feedback for effective control of blood pressure. PURPOSE: To examine the effect of a web-based self-care program for patients with primary hypertension on cardiovascular risk-factors (pulse pressure and lipids), self-efficacy, and self-care behaviors (medication adherence and lifestyle). DESIGN: A two-armed randomized controlled trial with 3-month and 6-month follow-ups. SETTING AND PARTICIPANTS: A total of 222 patients with primary hypertension were recruited between February 2017 and August 2018 at a cardiology clinic of a medical center in Taipei, Taiwan. METHODS: Eligible patients were randomized by permuted block randomization into the intervention group (n = 111) and control group (n = 111). Patients in the intervention group received a 6-month web-based self-care program, based on the theory of self-efficacy, while patients in the control group received usual care. Baseline and outcome measures (3 and 6 months) included self-efficacy, evaluated with the Chinese version of the 6-item Self-Efficacy for Managing Chronic Diseases (SEMC6), self-care, using subscales of the Hypertension Self-Care Activity Level Effects Scale (H-SCALE) for lifestyle and medication adherence, and blood pressure and serum lipid data, collected through web-based self-reports and chart review. Generalized estimating equations evaluated the effects of the intervention. FINDINGS: At baseline, the control group had higher scores on the SEMC6, and lower cholesterol (HDL) compared with the intervention group (t = -2.70, p < 0.05; and t = 1.76, p < 0.05, respectively). Pulse pressure decreased significantly (ß = -20.30, 95% CI -23.76, -16.83), and serum triglycerides and low-density lipoprotein cholesterol levels were significantly lower compared with controls at 6 months (all p < 0.001). At 6 months, the intervention group had significantly higher mean scores for the SEMC6 compared with the control group (ß = 21.84, 95% confidence interval [CI] 19.25, 24.42) and H-SCALE subscale for medication adherence, diet, weight management, and physical activity compared with controls at 6 months (all, p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The greatest benefit of this program was allowing participants to immediately consult with the researchers about self-care issues via the website. Lifestyles vary from person to person; therefore, the individuality of each participant was considered when providing feedback. We provided devising interventions for participants that would increase their confidence in self-care for hypertension and ultimately achieve home blood pressure control. We encourage incorporating this program into standard clinical care for patients with hypertension.

Nomogram for prognosis of patients with esophageal squamous cell cancer after minimally invasive esophagectomy established based on non-textbook outcome.

BACKGROUND: Non-textbook outcome (non-TO) represents a new prognostic evaluation index for surgical oncology. The present study aimed to develop new nomograms based on non-TO to predict the mortality and recurrence rate in patients with esophageal squamous cell cancer (ESCC) after minimally invasive esophagectomy (MIE). METHODS: The study involved a retrospective analysis of 613 ESCC patients, from the prospectively maintained database from January 2011 to December 2018. All the included ESCC patients underwent MIE, and they were randomly (1:1) assigned to the training cohort (307 patients) and the validation cohort (306 patients). Kaplan-Meier survival analysis was used to analyze the differences recorded between overall survival (OS) and disease-free survival (DFS). In the case of the training cohort, the nomograms based on non-TO were developed using Cox regression, and the performance of these nomograms was calibrated and evaluated in the validation cohort. RESULTS: Significant differences were recorded for 5-year OS and DFS between non-TO and TO groups (p < 0.05). Multivariate cox analysis revealed that non-TO, intraoperative bleeding, T stage, and N stage acted as independent risk factors that affected OS and DFS (p < 0.05). The results for multivariate regression were used to build non-TO-based nomograms to predict OS and DFS of patients with ESCC, the t-AUC curve analysis showed that the nomograms predicting OS and DFS were more accurate as compared to TNM staging, during the follow-up period in the training cohort and validation cohort. Further, the nomogram score was used to divide ESCC patients into low-, middle-, and high-risk groups and significant differences were recorded for OS and DFS between these three groups (p < 0.001). CONCLUSIONS: Non-TO was identified as an independent prognostic factor for ESCC patients. The nomograms based on non-TO could availably predict OS and DFS in ESCC patients after MIE.