The SMAC mimetic GDC-0152 is a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells.

Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the molecular mechanism of action of GDC-0152 in cancer cells is still incompletely understood. In this study, we found that the potency of GDC-0152 is unaffected by the expression of ABCB1 in cancer cells. Interestingly, through in silico and in vitro analysis, we discovered that GDC-0152 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multidrug efflux activity at sub-cytotoxic concentrations (i.e., 0.25×IC50 or less). Further investigation revealed that GDC-0152 also decreases BIRC5 expression, induces mitophagy, and lowers intracellular ATP levels in cancer cells at low cytotoxic concentrations (i.e., 0.5×IC50). Co-treatment with GDC-0152 restored the sensitivity to the known ABCB1 substrates, including paclitaxel, vincristine, and YM155 in ABCB1-expressing multidrug-resistant cancer cells, and it also restored the sensitivity to tamoxifen in BIRC5-overexpressing tamoxifen-resistant breast cancer cells in vitro. Moreover, co-treatment with GDC-0152 restored and potentiated the anticancer effects of paclitaxel in ABCB1 and BIRC5 co-expressing xenograft tumors in vivo. In conclusion, GDC-0152 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide essential information to physicians for designing a more patient-specific GDC-0152 clinical trial program in the future.

DC-SIGN and Galectin-3 individually and collaboratively regulate H5N1 and H7N9 avian influenza A virus infection via interaction with viral envelope hemagglutinin protein.

DC-SIGN and Galectin-3 are two different lectins and have been reported to participate in regulation of several virus infections. WHO has pointed that H5N1 and H7N9 avian influenza viruses (AIVs) play continuous threats to global health. AIV hemagglutinin (HA) protein-a highly glycosylated protein-mediates influenza infection and was proposed to have DC-SIGN and Gal3 interactive domains. This study aims to address the individual and collaborative roles of DC-SIGN and Gal3 toward AIVs infection. Firstly, A549 cells with DC-SIGN expression or Gal3-knockdown, via lentiviral vector-mediated CD209 gene expression or LGALS-3 gene knockdown, respectively were generated. Quantitative reverse transcription PCR (qRT-PCR) results indicated that DC-SIGN expression and Gal3 knockdown in A549 cells significantly promoted and ameliorated HA or NP gene expression, respectively after H5N1 and H7N9-reverse genetics (RG) virus postinfections (P < 0.05). Similar results observed in immunoblotting, indicating that DC-SIGN expression significantly facilitated H5N1-RG and H7N9-RG infections (P < 0.05), whereas Gal3 knockdown significantly reduced both viral infections (P < 0.05). Furthermore, we found that DC-SIGN and Gal3 co-expression significantly enhanced infectivity of both H5N1-RG and H7N9-RG viruses (P < 0.01) and higher regulatory capabilities by DC-SIGN and Gal3 in H5N1-RG than H7N9-RG were noted. The promoting effect mainly relied on exogenous Gal3 and DC-SIGN directly interacting with the HA protein of H5N1 or H7N9 AIVs, subsequently enhancing virus infection. This study sheds light on two different lectins individually and collaboratively regulating H5N1 and H7N9 AIVs infection and suggests that inhibitors against DC-SIGN and Gal3 interacting with HA could be utilized as alternative antiviral strategies.

Loss of oxytocin receptors in hilar mossy cells impairs social discrimination.

Hippocampal oxytocin receptor (OXTR) signaling is crucial for discrimination of social stimuli to guide social recognition, but circuit mechanisms and cell types involved remain incompletely understood. Here, we report a role for OXTR-expressing hilar mossy cells (MCs) of the dentate gyrus in social stimulus discrimination by regulating granule cell (GC) activity. Using a Cre-loxP recombination approach, we found that ablation of Oxtr from MCs impairs discrimination of social, but not object, stimuli in adult male mice. Ablation of MC Oxtr increases spontaneous firing rate of GCs, synaptic excitation to inhibition ratio of MC-to-GC circuit, and GC firing when temporally associated with the lateral perforant path inputs. Using mouse hippocampal slices, we found that bath application of OXTR agonist [Thr4,Gly7]-oxytocin causes membrane depolarization and increases MC firing activity. Optogenetic activation of MC-to-GC circuit ameliorates social discrimination deficit in MC OXTR deficient mice. Together, our results uncover a previously unknown role of MC OXTR signaling for discrimination of social stimuli and delineate a MC-to-GC circuit responsible for social information processing.

Real-Time Immunosensor for Small-Molecule Monitoring in Industrial Food Processes.

Industrial food processes are monitored to ensure that food is being produced with good quality, yield, and productivity. For developing innovative real-time monitoring and control strategies, real-time sensors are needed that can continuously report chemical and biochemical data of the manufacturing process. Here, we describe a generalizable methodology to develop affinity-based biosensors for the continuous monitoring of small molecules in industrial food processes. Phage-display antibody fragments were developed for the measurement of small molecules, as exemplified with the measurement of glycoalkaloids (GAs) in potato fruit juice. The recombinant antibodies were selected for use in a competition-based biosensor with single-molecule resolution, called biosensing by particle motion, using assay architectures with free particles as well as tethered particles. The resulting sensor measures GAs in the micromolar range, is reversible, has a measurement response time below 5 min, and enables continuous monitoring of GAs in protein-rich solutions for more than 20 h with concentration measurement errors below 15%. The demonstrated biosensor gives the perspective to enable a variety of monitoring and control strategies based on continuous measurement of small molecules in industrial food processes.

pH- and temperature-responsive supramolecular assemblies with highly adjustable viscoelasticity: a multi-stimuli binary system.

Stimuli-responsive materials are increasingly needed for the development of smart electronic, mechanical, and biological devices and systems relying on switchable, tunable, and adaptable properties. Herein, we report a novel pH- and temperature-responsive binary supramolecular assembly involving a long-chain hydroxyamino amide (HAA) and an inorganic hydrotrope, boric acid, with highly tunable viscous and viscoelastic properties. The system under investigation demonstrates a high degree of control over its viscosity, with the capacity to achieve over four orders of magnitude of control through the concomitant manipulation of pH and temperature. In addition, the transformation from non-Maxwellian to Maxwellian fluid behavior could also be induced by changing the pH and temperature. Switchable rheological properties were ascribed to the morphological transformation between spherical vesicles, aggregated/fused spherical vesicles, and bicontinuous gyroid structures revealed by cryo-TEM studies. The observed transitions are attributed to the modulation of the head group spacing between HAA molecules under different pH conditions. Specifically, acidic conditions induce electrostatic repulsion between the protonated amino head groups, leading to an increased spacing. Conversely, under basic conditions, the HAA head group spacing is reduced due to the intercalation of tetrahydroxyborate, facilitated by hydrogen bonding.

Maternal exposure to fine particulate matter and congenital heart defects during preconception and pregnancy period: A cohort-based case-control study in the Taiwan maternal and child health database.

BACKGROUND: Few studies have explored the association between maternal exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and congenital heart defects occurring before and during pregnancy. We aimed to investigate the association and the critical time windows between the maternal exposure to PM2.5 and congenital heart defects. METHOD: We conducted a cohort-based case-control study of 507,960 participants obtained from the Taiwan Maternal and Child Health Database between 2004 and 2015. We applied satellite-based spatiotemporal models with 1-km resolution to calculate the average PM2.5 concentration during preconception and the specific periods of pregnancy. We also performed conditional logistic regression with distributed lag non-linear models (DLNMs) to assess the effects of weekly average PM2.5 on both congenital heart defects and their isolated subtypes, as well as the concentration-response relationships. RESULTS: In DLNMs, exposure to PM2.5 (per 10 µg/m3) during weeks 7-12 before conception and weeks 3-9 after conception was associated with congenital heart defects. The strongest association at 12 weeks before conception (odds ratio [OR] = 1.026, 95% confidence intervals [CI]: 1.012-1.040) and 7 weeks after conception (OR = 1.024, 95% CI: 1.012-1.036) for every 10 µg/m3 increase in PM2.5 concentration. In modification analysis, strongest associations were observed for low SES. CONCLUSIONS: Our study revealed that exposure to ambient PM2.5 raises the risk of congenital heart defects, particularly among individuals with lower socioeconomic status. Moreover, our findings suggest that preconception exposure to PM2.5 may be a crucial period for the development of congenital heart defects.

Ultrasonographic imaging findings of the shoulder in patients with Parkinson disease.

BACKGROUND: Shoulder disorders, including frozen shoulder, bursitis, and rotator cuff lesions, are common musculoskeletal problems in patients with Parkinson disease (PD). Because musculoskeletal ultrasound (US) can clearly image shoulder joints, we aimed to evaluate shoulder joints using US in patients with PD and healthy participants and correlation between US and PD severity. METHODS: This is a prospective case-control study. 50 patients with PD and 50 healthy subjects from the outpatient department were administered US for bilateral shoulders. For data analysis, we chose the more severely affected side in the PD group for matching with the corresponding shoulder in the control group according to age, sex, and body mass index. Pain and disability were measured using the Visual Analogue Scale (VAS) for pain, Shoulder Pain and Disability Index (SPADI), and the Shoulder Disability Questionnaire (SDQ). RESULTS: The PD group had higher VAS pain scores during activity (p = 0.003) and rest (p < 0.001), as well as the SPADI and SDQ scores (p < 0.001). In US findings, biceps long head tendon sheath effusion (p = 0.001), humeral head cortical irregularity (p = 0.012), and abnormality in the supraspinatus tendon (p = 0.003) were significantly greater in the PD group. Intra-group analysis in the PD group demonstrated a significant difference in passive flexion (p = 0.019) and supraspinatus tendinopathy (p = 0.033) on US examination during different disease stages. CONCLUSIONS: Patients with PD had more supraspinatus tendinopathy on US findings than control subjects. The lesion was significantly associated with disease severity. CLINICAL TRIAL NUMBER: NCT02702232.

Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Sustained Release of Antifungal and Antibacterial Agents from Novel Hybrid Degradable Nanofibers for the Treatment of Polymicrobial Osteomyelitis.

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis.

Influence of the Door-to-ECG Time on the Prognosis of Patients with Acute Coronary Syndrome.

Background: The rapid acquisition of an electrocardiogram (ECG) plays a crucial role in the diagnosis and management decisions in patients with acute coronary syndrome (ACS). Objectives: We determined the time-to-ECG acquisition, identified factors associated with timely acquisition, and evaluated the influence of time-to-ECG on in-hospital mortality. Methods: We measured the door-to-ECG time for 903 of 2140 patients in the emergency department of Far Eastern Memorial Hospital with a diagnosis of ACS from January 1, 2016 to December 31, 2018, via a retrospective chart review. The primary outcome was in-hospital mortality. Outcome analysis of mortality was conducted using multivariable logistic regression. The secondary outcome was to determine which factors influenced whether or not a patient received an ECG within 10 min. The analysis was conducted using multiple logistic regression. Results: The median time-to-ECG was 5 min (interquartile range: 4-11 min) in all patients. In multivariable logistic regression analysis, we found that older age and more severe heart-broken index were significantly related to timely ECG acquisition. In-hospital mortality was higher in those in whom ECG was performed after more than 10 min. However, in the multivariable logistic regression analysis, it did not have a significant positive correlation with ECG acquisition time. Conclusions: Timely ECG acquisition owing to the triage protocol at our institution, the heart-broken index, led to early PCI and thus better outcomes for the ACS patients in this study. The implementation of a protocol-driven timely evaluation of patients with ACS and prompt PCI are important.

Glucose and Ethanol Detection with an Affinity-Switchable Lateral Flow Assay.

The lateral flow assay (LFA) is one of the most successful analytical platforms for rapid on-site detection of target substances. This type of assay has been used in many rapid diagnoses, for example, pregnancy tests and infectious disease prevention. However, applications of LFAs for very small molecules remain a demanding challenge due to the problem of obtaining the corresponding binding partners to form sandwich complexes. In this paper, we report an affinity-switchable (AS) LFA (ASLFA) for the rapid and selective detection of hydrogen peroxide (H2O2), glucose, and ethanol in blood serum and urine samples. Unlike classical LFAs, which rely on the "always on" interaction between the antigen and the antibody, the working principle of ASLFA is based on the gold nanoparticle-conjugated AS biotin probe Au@H2O2-ASB, which can be activated by H2O2 for binding with the streptavidin (SA) protein. In the presence of glucose and ethanol, glucose oxidase and alcohol oxidase can react with the substrate to generate H2O2 and thereby activate Au@H2O2-ASB for binding with SA. Therefore, this ASLFA approach can be an alternative for classical glucose and ethanol detection methods in a wide variety of samples, where simple and rapid on-site detection is essential.

Clinical T4b Squamous Cell Carcinoma Resection With Hemimandibulectomy and Temporomandibular Joint Reconstruction With Bridging Plate and Modified Dautrey Procedure.

ABSTRACT: Clinical T4b oral squamous cell carcinoma is traditionally considered nonoperable. We present a case of right mandibular squamous cell carcinoma (PT4bN0M0, stage IVB). The tumor had extended to the right mandibular condylar head and masticatory space. The patient received right modified radical neck dissection and radical operation with hemimandibulectomy to remove the right mandibular condyle. Then, we reconstructed the resected portion with an anterior lateral thigh free flap and bridging plate, which was bent to form an artificial condyle and fixed using the modified Dautrey procedure. The patient had stable postoperative occlusion and normal hinge movement of the temporomandibular joint. After postoperative concurrent chemotherapy and radiotherapy, the patient is under regular out patient department follow-up with satisfactory jaw function and oral intake.

Cross-Correlations between Scientific Physical Fitness, Body Mass Index Distribution, and Overweight/Obesity Risks among Adults in Taiwan.

Background and Objectives: Health-related physical fitness reduces the risk of chronic disease, promotes quality of life, and has enormous economic benefits considering the global health care costs resulting from obesity. However, relatively limited information is available regarding the dose-response relationship between scientific physical fitness and obesity risk. This study aimed to determine the associations of scientific physical fitness with body mass index (BMI) distribution and overweight/obesity risk among adults aged 23-64 years in Taiwan. Materials and Methods: We conducted a cross-sectional study and reviewed data derived from the Scientific Physical Fitness Testing Program, Sports Administration, Ministry of Education, Taiwan. Responses from 16,939 participants from the database (7761 men and 9178 women, aged 23-64 years) were collected in this study. Each participant completed a series of scientific physical fitness measurements, including cardiorespiratory fitness (3 min progressive knee-up and step [3MPKS] test), muscular fitness (hand grip strength), and flexibility (sit-and-reach test). Anthropometric measurements included body height, weight, and BMI. The quartiles of scientific physical fitness results were identified as the dependent variable in the multiple linear and multiple logistic regression analysis to determine the associations of the scientific physical fitness measurements with BMI distribution and overweight/obesity risk, as well as the dose-response relationship. Results: The 3MPKS test was significantly associated with BMI (quartile 1 (Q1): ß = 1.900; quartile 2 (Q2): ß = 1.594; quartile 3 (Q3): ß = 1.079 for men, and Q1: ß = 1.454; Q2: ß = 0.882; Q3: ß = 0.555 for women), overweight (Q1: odds ratio (OR) = 2.117; Q2: OR = 2.056; Q3: OR = 2.063 for men, and Q1: OR = 3.036; Q2: OR = 2.542; Q3: OR = 1.959 for women), and obesity (Q1: OR = 6.530; Q2: OR = 5.747; Q3: OR = 3.557 for men, and Q1: OR = 3.238; Q2: OR = 1.431 for women) risk compared with quartile 4 (Q4) as the reference group with a dose-response relationship. In addition, relative hand grip strength was significantly associated with BMI (Q2: ß = -0.922; Q3: ß = -1.865; Q4: ß = -3.108 for men, and Q2: ß = -1.309; Q3: ß = -2.161; Q4: ß = -2.759 for women), overweight (Q2: OR = 0.806; Q3: OR = 0.697; Q4: OR = 0.278 for men, and Q2: OR = 0.667; Q3: OR = 0.398; Q4: OR = 0.228 for women), and obesity (Q1: OR = 0.528; Q2: OR = 0.206; Q3: OR = 0.049 for men, and Q1: OR = 0.351; Q2: OR = 0.129; Q3: OR = 0.051 for women) risk compared with Q1 as the reference group with a dose-response relationship. Conclusions: Higher levels of performance of the 3MPKS and relative grip strength tests were associated with lower BMI and overweight/obesity risk in both sexes. However, the sit-and-reach test was only partially related to BMI and overweight/obesity risk in both sexes. Cardiorespiratory fitness and muscular fitness were effective predictors of BMI distribution and overweight/obesity risk in Taiwanese adults.

Effect of exposure to fine particulate matter during pregnancy and infancy on paediatric allergic rhinitis.

BACKGROUND: The effect of prenatal and postnatal exposure to fine particulate matter (PM2.5) on the development of allergic rhinitis (AR) is poorly understood. We further identified the vulnerable period for AR development to determine methods to decrease adverse effects. METHODS: We used a large population-based birth cohort of 140 911 singleton live infants in Taichung, Taiwan with a highly temporal-resolution satellite-based hybrid model to evaluate the effects of prenatal and early postnatal exposure on the onset of AR. RESULTS: Among 140 911 children, 47 276 (33.55%) were cases of incident AR. The mean age of the children with AR at initial diagnosis was 2.97±1.78 years. We identified a significant association of AR with an interquartile range (IQR 17.98 µg/m3) increase in PM2.5 from 30 gestational weeks to 52 weeks after birth. The exposure-response relationship revealed that AR had a significant positive association between PM2.5 of 26-76 µg/m3 (adjusted hazard ratios ranged from 1.00 to 1.05). CONCLUSION: Our study provides evidence that both prenatal and postnatal exposures to PM2.5 are associated with later development of AR. The vulnerable time window may be within late gestation and the first year of life. Further study is required to confirm the vulnerable time period of PM2.5 on AR.

Self-Assembly of Elastin-like Polypeptide Brushes on Silica Surfaces and Nanoparticles.

Control over the placement and activity of biomolecules on solid surfaces is a key challenge in bionanotechnology. While covalent approaches excel in performance, physical attachment approaches excel in ease of processing, which is equally important in many applications. We show how the precision of recombinant protein engineering can be harnessed to design and produce protein-based diblock polymers with a silica-binding and highly hydrophilic elastin-like domain that self-assembles on silica surfaces and nanoparticles to form stable polypeptide brushes that can be used as a scaffold for later biofunctionalization. From atomic force microscopy-based single-molecule force spectroscopy, we find that individual silica-binding peptides have high unbinding rates. Nevertheless, from quartz crystal microbalance measurements, we find that the self-assembled polypeptide brushes cannot easily be rinsed off. From atomic force microscopy imaging and bulk dynamic light scattering, we find that the binding to silica induces fibrillar self-assembly of the peptides. Hence, we conclude that the unexpected stability of these self-assembled polypeptide brushes is at least in part due to peptide-peptide interactions of the silica-binding blocks at the silica surface.

Combined Experimental and Computational Study on the Reaction Dynamics of the D1-Silylidyne(SiD) - Silane (SiH4) System.

Small silicon hydrides have attracted extensive interest because of their role in the chemical evolution of circumstellar envelopes of evolved carbon stars and applications in surface growth processes and as transients in semiconductor manufacturing. Combined with electronic structure calculations, we demonstrate that monobridged silylidynesilylenes [(Si(µ-D)SiH2, Si(µ-H)SiHD, Si(µ-H)SiH2] and silylsilylidyne [H3SiSi, H2DSiSi], which are nearly isoenergetic, can be prepared via molecular hydrogen loss channels in the crossed molecular beam study of the reaction of D1-silylidyne (SiD; X2Π) with silane (SiH4; X1A1) in a crossed molecular beams machine. Compared to the dynamics of the isovalent methylidyne (CH) - methane (CH4) system, our study delivers a unique view at the intriguing isomerization processes and reaction dynamics of dinuclear silicon hydride transients, thus contributing to our knowledge on the chemical bonding of silicon hydrides at the molecular level.

Near-IR Charge-Transfer Emission at 77 K and Density Functional Theory Modeling of Ruthenium(II)-Dipyrrinato Chromophores: High Phosphorescence Efficiency of the Emitting State Related to Spin-Orbit Coupling Mediation of Intensity from Numerous Low-Energy Singlet Excited States.

Efficient charge-transfer (CT) phosphorescence in the near-IR (NIR) spectral region is reported for four substituted Ru-(R-dipyrrinato) complexes, [Ru(bpy)2(R-dipy)](PF6), where bpy is 2,2'-bipyridine and the substituent R is phenyl (ph), 2,4,6-trimethylphenyl, 4-carboxyphenyl (HOOC-ph), or 4-pyridinyl. The experimentally determined phosphorescence efficiency, ιem(p) = kRAD(p)/(νem(p))3 (where kRAD(p) and νem(p) are the phosphorescence rate constant and the phosphorescence frequency, respectively), of the [Ru(bpy)2(R-dipy)]+ complexes was approximately double that of [Ru(bpy)(Am)4]2+ complexes (Am = ammine ligand) in the NIR region. Density functional theory (DFT) modeling indicated two strikingly different electronic configurations of the triplet emitting state (Te) in the two types of complexes. The Te of [Ru(bpy)2(R-dipy)]+ complexes shows a CT-type corresponding to the metal-to-ligand charge transfer (MLCT)-(Ru-(R-dipy)) and the ππ*-(R-dipy) moiety configurations, and the Te state in the [Ru(bpy)(Am)4]2+ complexes corresponds to an approximately MLCT excited state consisting of mostly MLCT-(Ru-bpy) with a minimal ππ*(bpy) contribution. DFT modeling also indicated that the low-energy singlet excited states in the Te geometry (Sn(T)) of the [Ru(bpy)2(ph-dipy)]+ complex consist of numerous CT-Sn(T)-type states of the Ru-dipy and Ru-bpy moieties, whereas the [Ru(bpy)(Am)4]2+ ions show quite simple MLCT-Sn(T)-type states of the Ru-bpy moiety. Based on experimental observations, DFT modeling, and the plain spin-orbit coupling (SOC) principle, we conclude that the remarkably high ιem(p) amplitudes of the [Ru(bpy)2(R-dipy)]+ complexes relative to those of [Ru(bpy)(Am)4]2+ complexes can be attributed to the relatively substantial contribution of intrinsic SOC-mediated intensity stealing from the numerous low-energy CT-type Sn(T) states.

Long-term exposure to fine particulate matter and osteoporotic fracture: A case-control study in Taiwan.

Few studies have explored the relationship between long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and osteoporotic fracture, particularly in high PM2.5 level areas. The aim of this study was to assess the association between long-term exposure to PM2.5 and osteoporotic fracture. We performed a matched case-control study of 16,175 participants obtained from a hospital registry during 2005-2014 in Taiwan. A major osteoporotic fracture was defined as a fracture of the spine, hip, proximal humerus, and forearm. We applied satellite-based spatiotemporal models with 1-km resolution to individually calculate the 1-year average PM2.5 concentration before the index date which was defined as the first visit date for the osteoporotic fracture. Logistic regression models with and without potential confounding factors were used to estimate odds ratios (OR) and 95% confidence intervals (CI) between PM2.5 and osteoporotic fracture, whereas a restricted cubic spline model was used to estimate the dose-response relationship. The sample's median age was 44.7 years (interquartile range: 30.7, 63.1 years). We observed that long-term PM2.5 exposure was associated with osteoporotic fracture, the OR was 1.12 (95% CI: 1.03, 1.22) per 10-µg/m3 increase in PM2.5 in women. In the dose-response association, the OR of osteoporotic fracture was significantly increased for PM2.5 exposures more than 41 µg/m3. We did not find a significant association between PM2.5 (per 10-µg/m3 increase) and osteoporotic fracture among overall population (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) and men (adjusted OR, 0.94 [95% CI, 0.86 to 1.02]). The results of the stratified analysis showed that women were more sensitive to the adverse impact of PM2.5 that were men, and evidence was obtained of sex-based effect modification (P for interaction = 0.002). Our findings suggest that long-term exposure to PM2.5 is associated with osteoporotic fracture, particularly among women.

Use of ICD-10-CM T codes in hospital claims data to identify adverse drug events in Taiwan.

WHAT IS KNOWN AND OBJECTIVE: Adverse drug events (ADEs) are a major public health concern worldwide and may prolong hospital stays, causing a burden on the healthcare system and increasing the associated costs. Therefore, optimizing medication use and reducing ADEs are priorities for public health. Medication safety can be monitored and improved by identifying ADEs. The utilization of diagnoses coded according to the International Statistical Classification of Diseases and Related Health Problems (ICD) system for the identification of ADEs has been firmly established. In Taiwan, however, the validity of recording ADEs on the basis of inpatient ICD-10-CM T codes has not been evaluated. Therefore, this study investigated the potential usefulness of ICD-10-CM T codes in routine hospital data for the identification of ADEs and for increasing the rate of reporting. METHODS: We use hospital claims data of hospitalized patients from one medical centre in northern Taiwan between 1 July 2016 and 30 June 2018. We defined an ADE to have taken place if an ICD-10-CM T code was present among the primary or secondary diagnosis codes. The inpatients who were discharged with T codes in a primary or secondary diagnosis were identified by the computerized T code information platform, and the retrospective review of the medical charts was performed by pharmacists to confirm the ADEs. RESULTS AND DISCUSSION: 1384 inpatients who were discharged with the relevant T codes in a primary or secondary diagnosis were identified during the study period. Code T36 (poisoning by, adverse effect of or underdosing of systemic antibiotics) was the most common code, accounting for 56.6%, followed by T42 (17.7%; poisoning by, adverse effect of or underdosing of antiepileptic, sedative-hypnotic or antiparkinsonism drug). Overall, 789 clinically significant ADEs were identified after medical chart review. The dermatologic system was the most commonly involved. The overall positive predictive value for a flagged code representing an ADE was 57%. Furthermore, the use of T codes to confirm the number of ADE cases increased the ADE reporting rate by 9.17%. WHAT IS NEW AND CONCLUSION: The PPV of ICD-10-CM T codes analysed in our study was insufficient for identifying ADEs during hospitalization. The sensitivity and specificity of this were inadequate. However, the T code system can be used as an auxiliary resource for pharmacists to identify potential ADEs and report the information as prompts on the physician order entry system. When a physician prescribes a drug that may cause an ADE in a patient, an alert is issued to ensure medication safety. In conclusion, the T codes did not perform well in our study and caution should be exercised in their use to identify ADEs on their own.

Particulate Air Pollution and Progression to Kidney Failure With Replacement Therapy: An Advanced CKD Registry-Based Cohort Study in Taiwan.

RATIONALE & OBJECTIVE: Limited evidence concerns fine particulate matter (with aerodynamic diameter ≤ 2.5µm [PM2.5]) exposure and the risk for kidney failure with replacement therapy (KFRT). This study assessed whether PM2.5 exposure was associated with progression of chronic kidney disease (CKD) to KFRT. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 6,628 adult patients with CKD were recruited from the Advanced CKD Program in Taiwan between 2003 and 2015. EXPOSURE: Satellite-based spatiotemporal models were used to calculate each individual's 1-year PM2.5 exposure before the date of enrollment into the Advanced CKD Program. OUTCOMES: Time to KFRT (defined as initiation of maintenance hemodialysis, peritoneal dialysis, or kidney transplantation) and time to all-cause mortality. ANALYTICAL APPROACH: Multivariable proportional hazard regression analyses were used to estimate the association of PM2.5 with KFRT and all-cause mortality. Restricted cubic splines were used to explore dose-response relationships. RESULTS: The study population included 6,628 adult patients with CKD who were aged 20 to 90 years. 941 KFRT events and 1,653 deaths occurred during follow-up. The adjusted HR for progression to KFRT was 1.19 (95% CI, 1.08-1.31) per 7.8µg/m3 greater PM2.5, an amount spanning the interquartile range. There was evidence of a dose-response relationship (adjusted HRs of 1.16 [95% CI, 0.90-1.51], 1.19 [95% CI, 0.94-1.52], and 1.42 [95% CI, 1.12-1.80] for low, medium, and high PM2.5 levels). There was no significant association between PM2.5 and all-cause mortality (adjusted HR, 1.01 [95% CI, 0.95-1.08]). LIMITATIONS: Misclassification of PM2.5 exposure assessment and the potential for residual confounding. CONCLUSIONS: Our findings suggest that long-term exposure to PM2.5 is associated with increased risk for progression to KFRT in patients with CKD.