RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

RhIII-promoted directed C-H N-heteroarylation of 2-pyridones.

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

Intervention effect of encouraging mental and programmed nursing of patients in interventional operating room on their compliance and bad moods.

BACKGROUND: Patients' lack of correct understanding of cardiovascular disease and interventional therapy is often accompanied by varying degrees of fear, depression and anxiety. Negative emotion will affect the hemodynamic fluctuation of patients undergoing interventional surgery, which is not conducive to the smooth and safe operation of interventional surgery. Therefore, it is very important to implement effective nursing intervention in the operating room. AIM: To explore the intervention effect of motivational psychological nursing combined with programmed nursing on compliance and bad mood of patients in interventional operating room. METHODS: A total of 98 patients in the interventional operating room of our hospital from October 2019 to March 2021 were randomly divided into study group (n = 49) and control group (n = 49). The control group took routine nursing. However, the study group took motivational psychological nursing combined with procedural nursing on the basis of the control group. Statistics were made on rehabilitation compliance, Positive and Negative Affect Schedule of bad mood, Simplified Coping Styles Questionnaire score of coping style and satisfaction of intervention between the two groups before and after intervention. RESULTS: The rehabilitation compliance of the study group (95.92%) was higher than that of the control group (81.63%) (P < 0.05). After intervention, the scores of upset, fear, irritability, tension and fear in the study group were respectively, which were lower than those in the control group (P < 0.05). After intervention, the score of positive coping in the study group was higher than that in the control group. However, the score of negative coping in the study group was lower than that in the control group (P < 0.05). The intervention satisfaction of the study group (93.88%) was higher than that of the control group (79.59%) (P < 0.05). CONCLUSION: The intervention of motivational psychological nursing combined with procedural nursing can improve the rehabilitation compliance, and alleviate the bad mood. In addition, it can change their coping style to the disease, and the patients are more satisfied with the nursing work.

Applications of triplex DNA nanostructures in sensor development.

Triplex DNA nanostructures are one of the most emerging and fascinating self-assembled nanostructures due to their unique nanoparticle-like organization and inherit characteristics. They have attracted numerous interests recently because of their versatile and powerful utility in diverse areas of science and technology, such as clinical or disease diagnosis and stimuli-based drug delivery. This review addresses particularly the utilization of DNA triplexes in the development of biosensors for detecting nucleic acid; strategies in sensing pH, protein activity, ions, or molecules. Finally, an outlook for potential applications of triplex DNA nanoswitches is provided.

Comparison of two treatments on a covariate variable.

In clinical trials, the efficacy of treatment might be dependent on the value of a covariate variable. Therefore, it might be possible to detect the region over the covariate variable where the two treatments under investigation do not have significantly different efficacy or the region of superiority of one treatment. The non-significant region can be verified to be a confidence interval for the abscissa of the intersection point of two regression lines, and each of the complementary regions of the confidence interval corresponds to a region of superiority. In this study, we develop a method of constructing the confidence interval based on the concept of a generalized pivotal quantity, so as to perform the task of detecting the possible three regions for a clinical trial. Two real-world examples are given to illustrate the application of our proposed method, and a simulation study is conducted to evaluate its performance.

Relationship Between Metabolic Syndrome Severity and Kidney Function as Related to Gender: A Population-Based Longitudinal Study.

The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males (p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate (p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male (p = .005) and female (p = .023) models.

Effects of Heart Rate Variability Biofeedback in Patients With Acute Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND: Autonomic dysfunction, cognitive impairment, and psychological distress are associated with poorer prognosis in patients with acute ischemic stroke (AIS). Heart rate variability (HRV) biofeedback (BF) improves autonomic dysfunction, cognitive impairment, and psychological distress in other patient populations, but its effect in patients with AIS is still unclear. OBJECTIVE: This study investigated the effects of an HRVBF intervention on autonomic function, cognitive impairment, and psychological distress in patients with AIS. METHOD: In this randomized, controlled, single-blind trial, patients with AIS were randomly assigned to the experimental or control group. The experimental group received four HRVBF training sessions. The control group received usual care. Repeated measures of HRV, mini-mental status examination (MMSE), and Hospital Anxiety and Depression Scales (HADS) were collected prior to and at 1 and 3 months postintervention. RESULTS: A total of 35 patients completed the study (19 experimental, 16 control). HRV and HADS significantly improved in the experimental group (p < .001) but not in the control group. Likewise, only the experimental group showed significant improvements in HRV, MMSE, and HADS over time (p < .05). CONCLUSION: HRVBF is a promising intervention for improving autonomic function, cognitive impairment, and psychological distress in patients with AIS. More studies of HRVBF interventions are needed to further optimize the effects of HRVBF on autonomic, cognitive, and psychological function in patients with AIS.

The differential distributions of ASPM isoforms and their roles in Wnt signaling, cell cycle progression, and pancreatic cancer prognosis.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and treatment-resistant malignancy. The lack of pathway-informed biomarkers hampers the development of rational diagnostics or therapies. Recently, the protein abnormal spindle-like microcephaly-associated (ASPM) was identified as a novel Wnt and stemness regulator in PDAC, while the pathogenic roles of its protein isoforms remain unclarified. We developed novel isoform-specific antibodies and genetic knockdown (KD) of putative ASPM isoforms, whereby we uncovered that the levels of ASPM isoform 1 (iI) and ASPM-iII are variably upregulated in PDAC cells. ASPM isoforms show remarkably different subcellular locations; specifically, ASPM-iI is exclusively localized to the cortical cytoplasm of PDAC cells, while ASPM-iII is predominantly expressed in cell nuclei. Mechanistically, ASPM-iI co-localizes with disheveled-2 and active ß-catenin as well as the stemness marker aldehyde dehydrogenase-1 (ALDH-1), and its expression is indispensable for the Wnt activity, stemness, and the tumorigenicity of PDAC cells. By contrast, ASPM-iII selectively regulates the expression level of cyclin E and cell cycle progression in PDAC cells. The expression of ASPM-iI and ASPM-iII displays considerable intratumoral heterogeneity in PDAC tissues and only that of ASPM-iI was prognostically significant; it outperformed ALDH-1 staining and clinico-pathological variables in a multivariant analysis. Collectively, the distinct expression patterns and biological functions of ASPM isoforms may illuminate novel molecular mechanisms and prognosticators in PDAC and may pave the way for the development of therapies targeting this novel oncoprotein. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-ß-catenin signaling.

Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify novel diagnostic and/or therapeutic targets to improve the outcome of patients. Recent evidence suggests that activation of Wnt signaling in cancer stem cells (CSCs) contributes to cancer progression in malignant tumors. Here, we report that a novel Wnt co-activator ASPM (abnormal spindle-like microcephaly associated) maintains the prostate CSC subpopulation by augmenting the Wnt-ß-catenin signaling in PCA. ASPM expression is incrementally upregulated in primary and metastatic PCA, implicating its potential role in PCA progression. Consistently, downregulation of ASPM expression pronouncedly attenuated the proliferation, colony formation, and the invasive behavior of PCA cells, and dramatically reduced the number of ALDH+ CSCs and inhibited cancer stemness and tumorigenicity. Mechanistically, ASPM interacts with disheveled-3 (Dvl-3), a cardinal upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing its protein stability and enabling the Wnt-induced ß-catenin transcriptional activity in PCA cells. In keeping with the role of ASPM as a CSC-regulator, ASPM co-localizes with ALDH in PCA tissues and its expression exhibits high intra-tumoral heterogeneity. The proportion of high-ASPM-expressing cells in the tumor inversely correlates with the relapse-free survival of PCA patients. Collectively, our data points to ASPM as a novel oncoprotein and an essential regulator of Wnt signaling and cancer stemness in PCA, which has important clinical and therapeutic significance.

Correction: ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3-ß-catenin signaling.

In the published version of this paper the author Shu-Pin Huang's surname was incorrectly given as Hwang instead of Huang. This has now been corrected in the HTML and PDF versions of the paper.

Isolation of C-phycocyanin from Spirulina platensis microalga using Ionic liquid based aqueous two-phase system.

An aqueous two-phase system (ATPS) with ionic liquids (ILs) was used for the isolate of C-phycocyanin (CPC) from Spirulina platensis microalga. Various imidazolium ILs and potassium salts were studied. The effect of ILs-ATPS on the extraction efficiency of CPC was also studied. The experimental parameters like pH, loading volume, algae concentration, temperature, and alkyl chain length of IL were well-covered in this report. The experimental results showed that the extraction efficiency, the partition coefficient, and the separation factor for CPC were 99%, 36.6, and 5.8, respectively, for an optimal pH value of 7 and a temperature of 308 K. The order of extraction efficiency for CPC using IL-ATPS was: 1-octyl-3-methylimidazolium bromide (C8MIM-Br) > 1-hexyl-3-methylimidazolium bromide (C6MIM-Br) > 1-butyl-3-methylimidazolium bromide (C4MIM-Br). The isolation process followed the pseudo second-order kinetic model and the thermodynamic results were obviously spontaneous.

Effect of oil gauze silver dressings on diabetic foot ulcers in the elderly.

OBJECTIVE: To compare the clinical efficacy and safety of oil gauze silver dressing and silver ions dressing on diabetic ulcers in elderly outpatients. METHODS: Twenty-two patients with Type-2 diabetic foot ulcers were included in the study conducted at Yantai Yuhuangding Hospital between April 2013 and April 2014. At the time of enrolment they were divided into the silver ions and oil gauze silver groups based on the order of admission. Dressings were changed twice weekly until the ulcer had healed. Clinical efficacy measures were healing outcomes and speed of healing. Adverse events were recorded. RESULTS: The silver ions and oil gauze silver groups were comparable at baseline (P>0.05). Before treatment, the fasting blood glucose (FBG) and two hour postprandial blood glucose (2h PBG) levels were 6.88±0.50 mmol /L and 15.55±2.47 mmol/L in the oil gauze silver group, and 6.93±0.41 mmol/L and 15.23±2.58 mmol/L in the silver ions group, respectively. After treatment, the FBG and 2h PBG levels were 6.82±0.32 mmol/L and 8.67±0.86 mmol/L in the oil gauze silver group, and 6.85±0.27 mmol/L and 8.83 ± 0.61 mmol/L in the silver ions group, respectively. The healing time of foot ulcers was 23.8±2.7 days in the silver ions group and 15.8±2.5 days in the oil gauze silver group (P<0.05). CONCLUSION: Oil gauze silver dressings for diabetic foot ulcers were associated with favorable clinical outcomes compared with silver ion dressings, especially with respect to ulcer healing speed.

Vagal withdrawal and psychological distress during ventilator weaning and the related outcomes.

OBJECTIVE: This study investigated the associations between changes in autonomic nervous system (ANS) function, psychological status during the mechanical ventilation (MV) weaning process, and weaning outcomes. METHODS: In this prospective study, we recruited 67 patients receiving MV for >24h at a medical center in northern Taiwan. Patients' ANS function, represented by heart rate variability (HRV), the rapid shallow breathing index (RSBI), anxiety, fear, and dyspnea, was repeatedly measured 10min before and 30min after undergoing a weaning trial. Forty-nine patients capable of sustaining a 2-h weaning trial were successfully weaned. RESULTS: Compared with the failed group, the success group showed significantly smaller decreases in high-frequency HRV (HRV-HF) and smaller increases in RSBI (per 10 breaths/min/L), fear, dyspnea, and anxiety in response to the weaning trial (odds ratio [OR]=2.19, 0.81, 0.69, 0.66, and 0.77, respectively; p<0.05). Multivariate analyses revealed that low-frequency HRV before weaning (OR=2.32; 95% confidence interval [CI]=1.13-4.78, p=0.02), changes in HRV-HF (OR=3.33; 95% CI=1.18-9.44, p=0.02), and psychological fear during the weaning process (OR=0.50; 95% CI=0.27-0.92, p=0.03) were three independent factors associated with 2-h T-piece weaning success. CONCLUSIONS: ANS responses and psychological distress during weaning were associated with T-piece weaning outcomes and may reflect the need for future studies to utilize these factors to guide weaning processes and examine their impact on outcomes.

Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells.

Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif-positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy.

Associations among integrated psychoneuroimmunological factors and metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) has been reported to cause considerable psychoneuroimmunology (PNI) disturbances such as, psychological distress, autonomic nervous imbalance, and impaired immune function. Associations among these psychoneuroimmunology (PNI) factors and their integrated effects with MetS and risk components of MetS necessitate further exploration. OBJECTIVE: This study investigated associations among psychoneuroimmunological factors, their integrated effects with MetS and risk components of MetS. METHODS: This was a cross-sectional study. Participants were recruited from two health management centers at a medical center in Northern Taiwan. Demographics and data on psychological distress (e.g., perceived stress and depression) were collected using self-reported questionnaires. Heart rate variability (HRV) and C-reactive protein values (CRP) were measured to evaluate participants' autonomic nervous function and immune reaction. The risk components of MetS (e.g., elevated blood pressure, impaired fasting glucose, dyslipidemia, and abdominal obesity) were identified according to the Taiwan-specific definition of MetS and were determined based on participants' health examination profiles. RESULTS: A total of 345 participants with complete data were included for data analysis. Compared with healthy controls, participants with MetS exhibited higher depression scores (11.2±8.5 vs. 8.7±7.0), higher CRP values (2.1±2.5 vs. 0.7±1.0), and lower HRV (total power: 758.7±774.9 vs. 1064.4±1075.0). However, perceived stress in participants with MetS did not significantly differ from that of their healthy counterparts (p>0.05). Univariate analyses indicated that associations among psychoneuroimmunological factors and MetS risk components were statistically heterogeneous: a) perceived stress and depression were significantly associated only with high blood glucose (p<0.05); b) CRP was significantly associated with all MetS risk components (p<0.05); and c) HRV was significantly associated with high triglycerides and high fasting blood glucose (p<0.05). Multivariate analysis indicated that the integrated effects of depression, CRP, and HRV were significantly associated with MetS (p<0.01) after controlling for age and education level. CONCLUSIONS: Higher depression scores, higher CRP values, and lower HRV are independently and additively associated with MetS and risk components of MetS. Accordingly, a multidisciplinary approach to alleviating psychological distress, immune dysfunction, and autonomic nervous imbalance is recommended for promoting well-being in people with subclinical metabolic abnormalities or MetS to minimize downstream health consequences.

The growth and development of children born to adolescent mothers in Taiwan.

BACKGROUND: Adolescent pregnancy carries a higher risk of adverse birth outcomes. Currently, there are very few longitudinal studies that have investigated the growth of children born to adolescents. This study explores the birth outcomes and determinants in adolescent pregnancies with subjects enrolled from the Taiwan Birth Cohort Study (TBCS). METHODS: Using the data of Wave I (6 months old), II (18 months old), and III (36 months old) of TBCS, a national sample of 19,381 pairs of mothers and their children were included for analysis. Out of these subjects, therewere560 pairs of adolescent mothers and children. Through completed field interviews with structured questionnaires, surveys with mothers or other family members, and with references to each child's birth certificate and Passport of Well-baby Care, the differences in birth outcomes, personal, pregnancy, and social profiles of the mothers were analyzed. RESULTS: A total of 560 adolescent mothers (<20 years old) and 18,821 adult mothers (20-34 years old) were included in this study. There was no significant difference between the two groups in terms of parameters of children growth and development. The numbers (proportions) of failure in milestones at 3 years old in gross motor functions, fine motor function, language, and social/personal development of children born to adolescent mothers are 13(2.32), 34(6.07), 10(1.79), and 24(4.29 %), respectively; while there are 392(2.08), 1015(5.39), 308(1.64) and 512(2.72 %) for those born to adult mothers, respectively. The risk factors of failure in children development were identified as "the mother isn't the night-time caregiver" and "family dysfunction". CONCLUSION: There was no significant difference in development at 3 years old among children born to adolescent and adult mothers.

Late-career unemployment and all-cause mortality, functional disability and depression among the older adults in Taiwan: A 12-year population-based cohort study.

OBJECTIVE: To evaluate whether late-career unemployment is associated with increased all-cause mortality, functional disability, and depression among older adults in Taiwan. METHOD: In this long-term prospective cohort study, data were retrieved from the Taiwan Longitudinal Study on Aging. This study was conducted from 1996 to 2007. The complete data from 716 men and 327 women aged 50-64 years were retrieved. Participants were categorized as normally employed or unemployed depending on their employment status in 1996. The cumulative number of unemployment after age 50 was also calculated. Logistic regression analysis was used to examine the effect of the association between late-career unemployment and cumulative number of late-career unemployment on all-cause mortality, functional disability, and depression in 2007. RESULTS: The average age of the participants in 1996 was 56.3 years [interquartile range (IQR)=7.0]. A total of 871 participants were in the normally employed group, and 172 participants were in the unemployed group. After adjustment of gender, age, level of education, income, self-rated health and major comorbidities, late-career unemployment was associated with increased all-cause mortality [Odds ratio (OR)=2.79; 95% confidence interval (CI)=1.74-4.47] and functional disability [OR=2.33; 95% CI=1.54-3.55]. The cumulative number of late-career unemployment was also associated with increased all-cause mortality [OR=1.91; 95% CI=1.35-2.70] and functional disability [OR=2.35; 95% CI=1.55-3.55]. CONCLUSION: Late-career unemployment and cumulative number of late-career unemployment are associated with increased all-cause mortality and functional disability. Older adults should be encouraged to maintain normal employment during the later stage of their career before retirement. Employers should routinely examine the fitness for work of older employees to prevent future unemployment.

Comparison of Pregnancy Stress Between In Vitro Fertilization/Embryo Transfer and Spontaneous Pregnancy in Women During Early Pregnancy.

BACKGROUND: Women who undergo in vitro fertilization/embryo transfer (IVF/ET) face complicated psychological stress and negative emotions, which may affect health during pregnancy and the development of the fetus. The current literature does not address the question of whether women who become pregnant spontaneously and women who undergo IVF face similar levels of pregnancy stress. PURPOSE: This study investigates the differences in pregnancy stress between women with spontaneous pregnancy and women with IVF/ET pregnancy living in central Taiwan during their first 20 weeks of pregnancy. METHODS: A prospective, longitudinal design with repeated measures, generalized estimated equations model, Wilks' λ, and Bonferroni test was used. Purposive samples of 163 women who had undergone IVF/ET and of 94 women who had undergone spontaneous pregnancy were enrolled as participants. Pregnancy stress was measured using the Chinese version of the self-administered Pregnancy Stress Scale at the 9th, 12th, and 20th weeks of pregnancy. RESULTS: The psychological stress experienced by IVF participants significantly increased with gestational week during the first 20 weeks of pregnancy (p < .01) but did not significantly increase in spontaneous-pregnancy participants. Gestational week was the main factor found to influence stress ratings for "identifying maternal role." "Altering body structure and body function" was the main factor found to influence pregnancy stress (p < .00). The method of becoming pregnant had no significant influence on pregnancy stress during the first 20 weeks of pregnancy (p > .05). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this study provide clinical evidence that IVF/ET does not cause more stress for women than spontaneous pregnancy. However, the intensity and trend of stresses differed between these two groups. These findings suggest that nurses should consider method of pregnancy when assessing the risk of stress in expectant mothers for each gestational week and when providing appropriate care and support.

Social support and mortality among the aged people with major diseases or ADL disabilities in Taiwan: a national study.

OBJECTIVE: To determine the effects of social support on mortality among the aged people with major diseases or ADL disabilities. METHOD: In this prospective cohort study, data were retrieved from the Taiwan Longitudinal Study on Aging from 1996 to 2007. Data for 1297 males and 1666 females aged ≥65 years were collected. The participants were divided into having major diseases or ADL disability or none. Subjects received financial, instrumental, and emotional support, and they actively provided instrumental and emotional support to others. The effect of the association between providing and receiving social support on mortality was examined using Cox regression analysis after adjusting several covariates. RESULTS: Results showed a significant finding that providing instrumental support can lower mortality rates in the aged people [Hazard ratio (HR)=0.77; 95% confidence interval (CI)=0.66-0.90; p=0.0009] and those with major diseases or impairment of activities of daily living [Hazard ratio (HR)=0.62; 95% confidence interval (CI)=0.50-0.78; p≤0.0001] after adjusting for several covariates. Providing instrumental social support to others may prolong life expectancy in the aged people and even those with major diseases or those facing difficulties performing ADL. CONCLUSION: Based on the finding, we should encourage older adults who have major diseases or ADL disabilities to be supporting providers especially in providing instrumental social support.