Proof of concept: Pull down assay using bovine serum albumin and an immunomodulator small molecule.

In the past decade, there has been increasing interest in use of small molecules for immunomodulation. The affinity-based pull-down purification is an essential tool for target identification of small molecules and drug discovery. This study presents our recent efforts to investigate the cellular target(s) of Compound A, a small molecule with demonstrated immunomodulatory properties in human peripheral blood mononuclear cells (PBMCs). While we have previously observed the immunomodulatory activity of Compound A in PBMCs, the specific molecular targets underlying its effects remains elusive. To address this challenge, we synthesized a trifluoromethyl phenyl diazirine (TPD)-bearing trifunctional Probe 1 based on the chemical structure of Compound A, which could be used in a pull-down assay to efficiently bind to putative cellular targets via photoaffinity labelling. In this report, we utilized bovine serum albumin (BSA) as a model protein to establish a proof-of-concept in order to assess the suitability of Probe 1 for binding to an endogenous target. By the successful synthesis of Probe 1 and demonstrating the efficient binding of Probe 1 to BSA, we propose that this method can be used as a tool for further identification of potential protein targets of small molecules in living cells. Our findings provide a valuable starting point for further investigations into the molecular mechanisms underlying the immunomodulatory effects of Compound A.

Recurrence of pediatric intussusception: A nationwide population-based descriptive study in Taiwan.

Intussusception is frequently observed pediatric emergency that is often followed by recurrent intussusception after initial treatment. This study investigated the risk factors associated with recurrent intussusception in children aged ≤ 3 years. Between January 2007 and December 2015, a cohort study was conducted by linking the Taiwan Maternal and Child Health Database to the Birth Certificate Application database and the National Health Insurance Research Database in Taiwan. Patients aged ≤ 3 years with intussusception diagnosis and related treatment were included in our study. Multivariable logistic regression was used to analyze the risk factors associated with recurrent intussusception. In total, 5341 children with intussusception aged ≤ 3 years were enrolled in our cohort. The adjusted odds ratio (aOR) for recurrent intussusception in children aged 2 to 3 years was 0.62 (95% confidence interval [CI]: 0.47-0.82) compared with children aged < 1 year, and surgery decreased the risk of recurrent intussusception (aOR = 0.64, 95% CI: 0.46-0.88). Male patients had higher risk of recurrent intussusception than female patients had (aOR = 1.41, 95% CI: 1.13-1.75). Higher birth weight may increase the risk of recurrent intussusception, but this association was not statistically significant. Furthermore, gestational age did not seem to affect the risk of recurrent intussusception. Surgical treatment and delayed onset of intussusception are associated with a reduced risk of recurrent intussusception; males are associated with increased risk of recurrent intussusception. In addition, we suggest that in early infancy, patients who received non-surgical treatment as the initial treatment for intussusception should be closely followed up for potential recurrence of intussusception.

Prevalence, Characteristics, and Treatment of Hemorrhoids During Pregnancy: A Nationwide Population-Based Cohort Study in Taiwan.

Background: Hemorrhoids, a gastrointestinal tract disorder, are common during pregnancy. However, large-scale epidemiological studies on hemorrhoids during pregnancy are limited. Therefore, this study used analyzed data from a nationwide population-based database to investigate the prevalence, characteristics, and treatment of hemorrhoids in Taiwan. Materials and Methods: This retrospective population-based study used data from the National Health Insurance Research Database and Taiwan Birth Certificate Application to collect the medical records of women who were pregnant at any time during 2009-2018. Hemorrhoids was defined by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) (455. X) and International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) (K64.X, O22.4X) with related treatment. Results: We enrolled 1,608,804 deliveries in 1,070,708 women. The proportion of hemorrhoids increased with age in both primipara and multipara women. Of the pregnant women, 31% received oral medication, and 93.2% used the topical ointment to treat their hemorrhoids. Few patients (1.8%) required procedure or surgery during pregnancy, and 41.4% of those patients underwent procedure or surgery in their first trimester. The cumulative incidence of hemorrhoids during pregnancy was significantly higher in women with a history of hemorrhoids and those with multifetal pregnancies. No significant difference in the incidence of hemorrhoids was observed between multiparous and primiparous women. Conclusion: Women with a history of hemorrhoids or those carrying multiple fetuses had an increased risk of hemorrhoids during pregnancy. The most commonly used treatment for hemorrhoids during pregnancy was topical ointments, with only a small proportion (1.8%) of patients requiring procedure or surgery.

Descriptive Study of Mastitis in Postpartum Women in Taiwan: Incidence and Related Factors.

Background: Mastitis is a common disorder among postpartum women. The discomfort and pain caused by mastitis may lead to the discontinuation of breastfeeding. Large-scale epidemiological studies examining mastitis are limited. Accordingly, the present study used a nationwide population-based database to collect information about all postpartum women in Taiwan to determine the incidence of and related factors for mastitis. Materials and Methods: This retrospective population-based study used the National Health Insurance Research Database to collect records of patients with mastitis during 2008-2017 and then linked the collected data to the Taiwan Birth Registry. We included women diagnosed as having lactational mastitis within 6 months of delivery. A multivariable logistic regression model was used to compare the risk of mastitis between parity in multiparous women. Results: We identified 1,686,167 deliveries in 1,204,544 women. 19,794 women with 20,163 deliveries had a medical claim for mastitis. The incidence proportion of mastitis for 6 months postpartum was ∼1.19% and highest during the first month after delivery. Multivariable logistic regression revealed that multiparous women with a history of mastitis were likely to experience mastitis again after subsequent deliveries (adjusted odds ratio = 5.86; 95% confidence interval = 5.21-6.58). The Kaplan-Meier curve indicated that primiparous women had a higher risk of mastitis than did multiparous women (log-rank test, p < 0.001). Conclusion: Mastitis generally occurred during the first month postpartum, and primiparous women had a higher risk of mastitis than did multiparous women. Furthermore, multiparous women with a history of mastitis had a 5.86-fold increased risk of recurrence during subsequent deliveries.

Integrating Resonator to Enhance Magnetometer Microelectromechanical System Implementation with ASIC Compatible CMOS 0.18 µm Process.

In this study, a multi-function microelectromechanical system (MEMS) was integrated with a MEMS oscillator, using the resonant frequency oscillation characteristics of the oscillator to provide the Lorentz current of the magnetometer to enhance a large dynamic range of reading, which eliminates the off-chip clock and current generator. The resonant frequency can be adjusted by adjusting the bias voltage of the oscillator to further adjust the sensitivity of the magnetometer. With the mechanical Q value characteristic, a great dynamic range can be achieved. In addition, using the readout circuit of the nested chopper and correlated double-sampling (CDS) to reduce the noise and achieve a smaller resolution, the calibration circuit compensates for errors caused by the manufacturing process. The frequency of the tuning range of the proposed structure is 17,720-19,924 Hz, and the tuning range of the measurement result is 110,620.36 ppm. The sensitivities of the x-, y-, and z-axes of the magnetometer with driving current of 2 mA are 218.3, 74.33, and 7.5 µV/µT for ambient pressure of 760 torr. The resolutions of the x-, y-, and z-axes of the magnetometer with driving current of 2 mA are 3.302, 9.69, and 96 nT/√Hz for ambient pressure of 760 torr.

Multi-Function Microelectromechanical Systems Implementation with an ASIC Compatible CMOS 0.18 µm Process.

A multi-function microelectromechanical system (MEMS) with a three-axis magnetometer (MAG) and three-axis accelerometer (ACC) function was implemented with an application-specific integrated circuit (ASIC)-compatible complementary metal-oxide-semiconductor (CMOS) 0.18 µm process. The readout circuit used the nested chopper, correlated double-sampling (CDS), noise reduction method; the frequency division multiplexing method; the time-division multiplexing method; and the calibration method. Sensing was performed by exciting the MEMS three-axis magnetometer at X/Y/Z axes mechanical resonant frequencies of 3.77/7.05/7.47 kHz, respectively. A modest die-level vacuum packaging resulted in in-plane and out-of-plane mechanical quality factors of 471-500 and 971-1000, respectively. The sensitivities of both the three-axis magnetometer with 2 mA driving current and the three-axis accelerometer were 7.1-10.7 uV/uT and 58.37-88.87 uV/ug. The resolutions of both the three-axis magnetometer with 2 mA driving current and three-axis accelerometer resolution were 44.06-87.46 nT/√Hz and 5.043-7.5 ng/√Hz. The resolution was limited by circuit noise equivalent acceleration (CNEM) and Brownian noise equivalent magnetic field (BNEM).

Histone acetyltransferase p300 mediates the upregulation of CTEN induced by the activation of EGFR signaling in cancer cells.

Upregulation of C-terminal tensin-like (CTEN) is induced by the activation of epidermal growth factor receptor (EGFR) signaling and mainly contributes to cancer cell migration and invasion. CTEN is known as a downstream target of the EGFR-RAF-MEK-ERK pathway but the regulatory mechanism underlying EGFR signaling regulates the increased expression of CTEN is still incompletely understood. In this study, we investigated the epigenetic regulation of CTEN gene transcription upon EGFR activation. Analyses of chromatin accessibility revealed that the structure of CTEN promoter became more loosed and the acetylation state of the histone tails within the core promoter region was increased after EGF treatment. Moreover, activation of EGFR signaling facilitates histone acetyltransferase p300 to be recruited to CTEN promoter through MEK-ERK pathway. MEK-ERK activation also induces the phosphorylation of p300, thereby enhancing the levels of histone acetylation within CTEN promoter, which in turn upregulates CTEN gene expression. Our work provides new insights into the actions of EGFR signaling to upregulate CTEN, which may lead to the rational design of novel therapeutic approaches.

Team Resource Management Perception Under Managerial Coaching Skills and Organizational Climate: Cross-Level Analysis in Taiwan's Hospitals.

There is growing recognition of the importance of teamwork and integration of resources in the health care industry. This article studied the influence of organizational climate and managerial coaching skills on team perception of team resource management (TRM) and coaching techniques in selected hospitals in Taiwan. Structural survey method was used to measure the relationship between organizational climate, managerial coaching skills, and team perception of TRM. The participants of this research were 530 administrative staff from 12 hospitals in Taiwan. Cross-level relationship between organizational climate (group level), managerial coaching skills (individual level), and team perception of TRM (individual level) was examined. The results revealed that organizational climate had a significant influence on team perception of TRM. Second, recognition of managerial coaching skills shaped team perception during TRM implementation. Third, organizational climate had a moderating effect on the relationship between managerial coaching skills and team perception of TRM. The study concluded that positive organizational climate and good managerial coaching skills contribute to effective team management and development. Thus, it is important for health care organizations to understand the importance of coaching and mentoring and create a workplace that makes learning, growth, and adaptation possible across different departments and functional teams.

Supercontinuum generation by noise-like pulses transmitted through normally dispersive standard single-mode fibers.

We report generation of broadband supercontinuum (SC) by noise-like pulses (NLPs) with a central wavelength of 1070 nm propagating through a long piece of standard single-mode fibers (~100 meters) in normal dispersion region far from the zero-dispersion point. Theoretical simulations indicate that the physical mechanism of SC generation is due to nonlinear effects in fibers. The cascaded Raman scattering is responsible for significant spectral broadening in the longer wavelength regions whereas the Kerr effect results in smoothing of SC generated spectrum. The SC exhibits low threshold (43 nJ) and a flat spectrum over 1050-1250 nm.

The effects of an educational training workshop for community leaders on self-efficacy of program planning skills and partnerships.

AIM: This aim of this study was to evaluate the effects of a 6-month educational workshop for community leaders designed to improve their confidence in health promotion programmes and to develop partnerships among the participants. BACKGROUND: It is important for public health nurses to work with community leaders to provide community-orientated services. However, only a few existing studies have reported the content and effects of training programmes aimed at enhancing the capabilities of community leaders. METHODS: A participatory action research design with pre- and post-test methods was applied in this study. Fifteen community leaders completed a 6-month educational workshop that was held in Tamsui, Taipei and Taiwan. It was designed to enable community leaders to improve their confidence in planning health programmes and developing group partnerships. Data were collected from April 2009 to October 2009, and descriptive statistics and Wilcoxon signed-rank test analyses were carried out. RESULTS: Participants demonstrated improvements in their self-efficacies of planning health programmes by completing a structured questionnaire after attending a 6-month educational workshop (Z =-2·90, P = 0·004). Their confidence in data collection, needs assessment and diagnosis, programme planning, and programme evaluation were significantly improved (Z = -3·1, P = 0·002; Z = -2·42, P = 0·016, Z = -2·84, P = 0·004, and Z = -2·68, P = 0·007, respectively). CONCLUSIONS: Providing training workshops for community leaders is a useful strategy for increasing their capabilities and confidence in planning health programmes. Nurses have a responsibility to advocate and provide training programmes for community leaders.