Depressive disorder and elevated risk of bell's palsy: a nationwide propensity score-weighting study.

BACKGROUND: Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell's palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell's palsy. METHODS: This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell's palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168-1.481) for Bell's palsy in DD patients compared to comparison subjects. Further independent factors for Bell's palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010-1.013, p < 0.0001), sex (IPTW-HR: 0.909, 95% CI: 0.869-0.952, p < 0.0001), hypertension (IPTW-HR: 1.268, 95% CI: 1.186-1.355, p < 0.0001), hyperlipidemia (IPTW-HR: 1.084, 95% CI: 1.001-1.173, p = 0.047), and diabetes (IPTW-HR: 1.513, 95% CI: 1.398-1.637, p < 0.0001) CONCLUSION: This Study confirmed that individuals with DD face an elevated risk of developing Bell's palsy. These findings hold significant implications for both clinicians and researchers, shedding light on the potential interplay between mental health and the risk of certain physical health outcomes.

Interval aerobic/resistance exercise training depresses adrenergic-induced apoptosis of lymphocytes in sedentary males.

PURPOSE: Adrenergic stimulation affects lymphocyte autophagy and apoptosis by activating ß1-adrenergic receptor (ß1-AR) and G protein-coupled receptor kinase 2 (GRK-2) downstream signaling. This study investigated how combined aerobic and resistance exercise training on the interval or continuous pattern influences aerobic/muscular fitness and ß1-AR/GRK-2 signaling, and corresponding apoptosis/autophagy of lymphocytes in sedentary males. METHODS: Thirty-four sedentary males were randomized into interval training (IT, age = 22.5 ± 0.6 years, fitness level = 47.5 ± 0.9 mL/min/kg, body mass index (BMI) = 22.4 ± 0.4 kg/m2, n = 17) and continuous training (CT, age = 21.6 ± 0.4 years, fitness level = 45.2 ± 1.0 mL/min/kg, BMI = 22.2 ± 0.3 kg/m2, n = 17) groups. These subjects performed IT (bicycle exercise at alternating 40% and 80%VO2 reserve (VO2R) and isokinetic exercise at alternating 60°/s and 180°/s) or CT (bicycle exercise at continuously 60%VO2R and isokinetic exercise at continuously 120°/s) for 30 min/day, 5 days/week for 6 weeks. Aerobic capacity and muscular strength/endurance were determined by the graded exercise test (GXT) and isokinetic strength test, respectively. Blood lymphocyte autophagy/apoptosis and ß1-AR/GRK-2 signaling were analyzed using flow cytometry. RESULTS: Both IT and CT groups increased isokinetic strengths at various angular velocities, whereas only IT significantly enhanced muscle endurance, indicated by lowered fatigue index from 47.0 ± 1.3% to 41.8 ± 1.6% (P < 0.05). Moreover, the IT group (143 ± 7%) revealed a higher improvement in VO2peak than CT group (132 ± 6%) (P < 0.05). Acute GXT augmented (i) GRK-2 and protein kinase A expressions, (ii) LAMP-2 upregulation and acridine orange staining, (iii) mitochondrial transmembrane potential diminishing, caspase-3 activation, and phosphatidylserine (PS) exposure caused by epinephrine in blood lymphocytes. However, the degree of epinephrine-induced lymphocyte PS exposure potentiated by GXT was suppressed from 65.2 ± 5.2% to 47.4 ± 6.5% following 6 weeks of the IT (P < 0.05). CONCLUSION: The IT may be considered more beneficial than CT in terms of improving aerobic/muscular fitness and simultaneously ameliorating apoptosis of blood lymphocyte evoked by intense exercise or adrenergic stimulation in sedentary males.

Role of Water in CaCO3 Biomineralization.

Biomineralization occurs in aqueous environments. Despite the ubiquity and relevance of CaCO3 biomineralization, the role of water in the biomineralization process has remained elusive. Here, we demonstrate that water reorganization accompanies CaCO3 biomineralization for sea urchin spine generation in a model system. Using surface-specific vibrational spectroscopy, we probe the water at the interface of the spine-associated protein during CaCO3 mineralization. Our results show that, while the protein structure remains unchanged, the structure of interfacial water is perturbed differently in the presence of both Ca2+ and CO32- compared to the addition of only Ca2+. This difference is attributed to the condensation of prenucleation mineral species. Our findings are consistent with a nonclassical mineralization pathway for sea urchin spine generation and highlight the importance of protein hydration in biomineralization.

Uncovering the Role of Bicarbonate in Calcium Carbonate Formation at Near-Neutral pH.

Mechanistic pathways relevant to mineralization are not well-understood fundamentally, let alone in the context of their biological and geological environments. Through quantitative analysis of ion association at near-neutral pH, we identify the involvement of HCO3- ions in CaCO3 nucleation. Incorporation of HCO3- ions into the structure of amorphous intermediates is corroborated by solid-state nuclear magnetic resonance spectroscopy, complemented by quantum mechanical calculations and molecular dynamics simulations. We identify the roles of HCO3- ions as being through (i) competition for ion association during the formation of ion pairs and ion clusters prior to nucleation and (ii) incorporation as a significant structural component of amorphous mineral particles. The roles of HCO3- ions as active soluble species and structural constituents in CaCO3 formation are of fundamental importance and provide a basis for a better understanding of physiological and geological mineralization.

The Repository Chemotion: Infrastructure for Sustainable Research in Chemistry*.

The repository Chemotion provides solutions for current challenges to store research data in a feasible manner. A main advantage of Chemotion is the comprehensive functionality, offering options to collect, prepare, and reuse data with discipline-specific methods and data-processing tools.

Mortality Risk of Atypical Antipsychotics for Behavioral and Psychological Symptoms of Dementia: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis of Randomized Controlled Trials.

BACKGROUND: Evidence suggests that atypical antipsychotics (AAPs) exert a short-term mortality risk in people with dementia. We assessed whether additional randomized clinical trials influence the current evidence and the potential effect modifiers. METHODS: Electronic databases were systematically searched for randomized controlled trials from their inception through March 2018. A random-effects model was used for analysis. Potential effect modifiers were examined through meta-regression. Trial sequential analysis was performed to quantify the statistical reliability of data in the cumulative meta-analysis with adjustment of significance levels for sparse data and repetitive testing on accumulating data. Certainty of evidence and risk of bias were also evaluated. RESULTS: We found that compared with placebos, AAPs may increase the risk of mortality (odds ratio [OR], 1.536; 95% confidence intervals [CIs], 1.028-2.296; P = 0.036, high certainty). In the subgroup analysis, the estimated ORs were the highest for olanzapine (1.919; P = 0.232), followed by those for quetiapine (1.663; P = 0.506), aripiprazole (1.649; P = 0.297), and risperidone (1.354; P = 0.277); however, the mortality risk presented by individual AAPs did not exhibit between-group differences. The meta-regression did not identify any effect modifiers, including the chlorpromazine equivalent dose, trial duration, and cognitive status. The trial sequential analysis revealed that future similar trials are unlikely to alter our findings. CONCLUSIONS: Atypical antipsychotics are associated with increased short-term mortality risk, although a disease-drug interaction may contribute to such risk in people with dementia. Patients with dementia may still benefit by AAPs after appropriate assessment of the disease severity as well as the dosage of AAPs, treatment duration, and monitoring of AAPs.

The influence of laser intensity activated plasmonic gold nanoparticle-generated photothermal effects on cellular morphology and viability: a real-time, long-term tracking and monitoring system.

In this study, a microfluidic apparatus embedded with microstructures was designed and aligned with a laser and dark-field microscope for real-time, long-term observation of photothermal effects on cells. Gold nanorods (AuNRs, 10 ppm) were incubated with MG-63 human osteosarcoma cells for 3 h. Then, the cells were exposed to a continuous-wave laser at a wavelength of 830 nm for 10, 20, and 30 min at 5, 9, 14, 24, and 32 W cm-2. Subsequent changes in morphology were observed. Under different conditions, cell membrane blebbing occurred at different times, indicating that actin filaments were destroyed in large quantities and apoptosis was induced. In suitable conditions, we first induced slight cell injury by causing cytoskeletal fractures with a high-energy laser; then, the cells were irradiated with a low-energy laser at 0.3 W cm-2. We found that among cells treated with the high-energy laser, cells treated additionally with a low-energy laser showed extended viability compared with cells that did not receive the additional treatment.

Selective Synergism Created by Interactive Nacre Framework-Associated Proteins Possessing EGF and vWA Motifs: Implications for Mollusk Shell Formation.

In the nacre layer of the Pinctada fucata oyster shell there exists a multimember proteome, known as the framework family, which regulates the formation of the aragonite mesoscale tablets and participates in the creation of an organic coating around each tablet. Several approaches have been developed to understand protein-associated mechanisms of nacre formation, yet we still lack insight into how protein ensembles or proteomes manage nucleation and crystal growth. To provide additional insights we have created a proportionally defined combinatorial model consisting of two recombinant framework proteins, r-Pif97 (containing a von Willebrand Factor Type A domain (vWA)) and r-n16.3 (containing an EGF-like domain), whose individual in vitro mineralization functionalities are distinct from one another. We find that at 1:1 molar ratios r-Pif97 and r-n16.3 exhibit little or no synergistic activity regarding modifying existing calcite crystals. However, during the early stages of nucleation in solution, we note synergistic effects on nucleation kinetics and ACC formation/stability (via dehydration) that are not observed for the individual proteins. This selective synergism is generated by Ca2+-mediated protein-protein interactions (∼4 molecules of r-n16.3 per 1 molecule of r-Pif97) which lead to the formation of nucleation-responsive hybrid hydrogel particles in solution. Interestingly, in the absence of Ca2+ there are no significant interactions occurring between the two proteins. This unique behavior of the framework-associated n16.3 and Pif97 proteins suggests that the Asp/Glu-containing regions of the vWA and EGF-like domains may play a role in both nacre matrix formation and mineralization.

Addition of dithi(ol)anylium tetrafluoroborates to α,ß-unsaturated ketones.

In the presented study, dithi(ol)anylium tetrafluoroborates are added to α,ß-unsaturated ketones in a Michael-type reaction yielding diverse substituted ketene diothi(ol)anes. The reactions proceed at room temperature in 1 or 13 h without the need of further additives. The presented procedure is in particular useful for dithi(ol)anylium tetrafluoroborates without electron-withdrawing groups in α-position. This is advantageous with respect to previous approaches, which were limited to the use of ketene dithioacetals substituted with electron-withdrawing groups. Aiming for the systematic investigation of possible steric and electronic influences on the outcome of the reaction, various combinations of electrophiles and nucleophiles were used and the results of the reactions were compared based on the type of the used dithioacetal. The scope of the presented procedure is shown with four additional transformations including the use of additional electrophiles and nucleophiles, the use of a chiral auxiliary and subsequent reduction of selected products. Additionally, we extended the reaction to the synthesis of diene dithiolanes by addition of an ynone to α-alkyl or aryl-substitued dithiolanylium TFBs.

A Model Sea Urchin Spicule Matrix Protein, rSpSM50, Is a Hydrogelator That Modifies and Organizes the Mineralization Process.

In the purple sea urchin Strongylocentrotus purpuratus, the formation and mineralization of fracture-resistant skeletal elements such as the embryonic spicule require the combinatorial participation of numerous spicule matrix proteins such as SpSM50. However, because of its limited abundance and solubility issues, it has been difficult to pursue extensive in vitro biochemical studies of SpSM50 protein and deduce its role in spicule formation and mineralization. To circumvent these problems, we expressed a tag-free bacterial model recombinant spicule matrix protein, rSpSM50. Bioinformatics and biophysical experiments confirm that rSpSM50 is an intrinsically disordered, aggregation-prone C-type lectin-like domain-containing protein that forms dimensionally and internally heterogeneous protein hydrogels that control the in vitro mineralization process in three ways. The hydrogels (1) kinetically stabilize the aqueous calcium carbonate system against nucleation and thermodynamically destabilize the initially formed ACC in bulk solution, (2) promote and organize faceted single-crystal calcite and polycrystalline vaterite nanoparticles, and (3) promote surface texturing of calcite crystals and induce subsurface nanoporosities and channels within both calcite and vaterite crystals. Many of these features are also common to mollusk shell nacre proteins and the sea urchin spicule matrix glycoprotein, SpSM30B/C, and we conclude that rSpSM50 is a spiculogenesis hydrogelator protein that exhibits traits found in other calcium carbonate mineral-modification proteins.

Functional Prioritization and Hydrogel Regulation Phenomena Created by a Combinatorial Pearl-Associated Two-Protein Biomineralization Model System.

In the nacre or aragonitic layer of an oyster pearl, there exists a 12-member proteome that regulates both the early stages of nucleation and nanoscale-to-mesoscale assembly of nacre tablets and calcitic crystals from mineral nanoparticle precursors. Several approaches to understanding protein-associated mechanisms of pearl nacre formation have been developed, yet we still lack insight into how protein ensembles or proteomes manage nucleation and crystal growth. To provide additional insights, we have created a proportionally defined combinatorial model consisting of two pearl nacre-associated proteins, PFMG1 and PFMG2 (shell oyster pearl nacre, Pinctada fucata) whose individual in vitro mineralization functionalities are distinct from one another. Using scanning electron microscopy, atomic force microscopy, Ca(II) potentiometric titrations, and quartz crystal microbalance with dissipation monitoring quantitative analyses, we find that at 1:1 molar ratios, rPFMG2 and rPFMG1 co-aggregate in specific molecular ratios to form hybrid hydrogels that affect both the early and later stages of in vitro calcium carbonate nucleation. Within these hybrid hydrogels, rPFMG2 plays a role in defining protein co-aggregation and hydrogel dimension, whereas rPFMG1 defines participation in nonclassical nucleation processes; both proteins exhibit synergy with regard to surface and subsurface modifications to existing crystals. The interactions between both proteins are enhanced by Ca(II) ions and may involve Ca(II)-induced conformational events within the EF-hand rPFMG1 protein, as well as putative interactions between the EF-hand domain of rPFMG1 and the calponin-like domain of rPFMG2. Thus, the pearl-associated PFMG1 and PFMG2 proteins interact and exhibit mineralization functionalities in specific ways, which may be relevant for pearl formation.

A Wirelessly Powered Smart Contact Lens with Reconfigurable Wide Range and Tunable Sensitivity Sensor Readout Circuitry.

This study presented a wireless smart contact lens system that was composed of a reconfigurable capacitive sensor interface circuitry and wirelessly powered radio-frequency identification (RFID) addressable system for sensor control and data communication. In order to improve compliance and reduce user discomfort, a capacitive sensor was embedded on a soft contact lens of 200 µm thickness using commercially available bio-compatible lens material and a standard manufacturing process. The results indicated that the reconfigurable sensor interface achieved sensitivity and baseline tuning up to 120 pF while consuming only 110 µW power. The range and sensitivity tuning of the readout circuitry ensured a reliable operation with respect to sensor fabrication variations and independent calibration of the sensor baseline for individuals. The on-chip voltage scaling allowed the further extension of the detection range and prevented the implementation of large on-chip elements. The on-lens system enabled the detection of capacitive variation caused by pressure changes in the range of 2.25 to 30 mmHg and hydration level variation from a distance of 1 cm using incident power from an RFID reader at 26.5 dBm.

Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a cross-sectional study in patients hospitalized with acute heart failure.

BACKGROUND: Increased myocardial triglyceride (TG) content has been recognized as a risk factor for cardiovascular disease. However, its relation with cardiac function in patients on recovery from acute heart failure (HF) remains unclear. In this cross-sectional study, we sought to investigate the association between myocardial TG content measured on magnetic resonance spectroscopy ((1)H-MRS) and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. METHODS: A total of 50 patients who were discharged after hospitalization for acute HF and 21 age- and sex-matched controls were included in the study. Myocardial TG content and LV parameters (function and mass) were measured on a 3.0 T MR scanner. Fatty acid (FA) and unsaturated fatty acid (UFA) content was normalized against water (W) using the LC-Model algorithm. The patient population was dichotomized according to the left ventricular ejection fraction (LVEF, <50% or ≥ 50%). RESULTS: H-MRS data were available for 48 patients and 21 controls. Of the 48 patients, 25 had a LVEF <50% (mean, 31.2%), whereas the remaining 23 had a normal LVEF (mean, 60.2%). Myocardial UFA/W ratio was found to differ significantly in patients with low LVEF, normal LVEF, and controls (0.79% vs. 0.21% vs. 0.14%, respectively, p = 0.02). The myocardial UFA/TG ratio was associated with LV mass (r = 0.39, p < 0.001) and modestly related to LV end-diastolic volume (LVEDV; r = 0.24, p = 0.039). We also identified negative correlations of the myocardial FA/TG ratio with both LV mass (r = -0.39, p < 0.001) and LVEDV (r = -0.24, p = 0.039). CONCLUSIONS: As compared with controls, patients who were discharged after hospitalization for acute HF had increased myocardial UFA content; furthermore, UFA was inversely related with LVEF, LV mass and, to a lesser extent, LVEDV. Our study may stimulate further research on the measure of myocardial UFA content by (1)H-MRS for outcome prediction. TRIAL REGISTRATION: ClinicalTrial.gov: NCT02378402 . Registered 27/02/2015.

Effects of Operating Temperature on Droplet Casting of Flexible Polymer/Multi-Walled Carbon Nanotube Composite Gas Sensors.

This study examined the performance of a flexible polymer/multi-walled carbon nanotube (MWCNT) composite sensor array as a function of operating temperature. The response magnitudes of a cost-effective flexible gas sensor array equipped with a heater were measured with respect to five different operating temperatures (room temperature, 40 °C, 50 °C, 60 °C, and 70 °C) via impedance spectrum measurement and sensing response experiments. The selected polymers that were droplet cast to coat a MWCNT conductive layer to form two-layer polymer/MWCNT composite sensing films included ethyl cellulose (EC), polyethylene oxide (PEO), and polyvinylpyrrolidone (PVP). Electrical characterization of impedance, sensing response magnitude, and scanning electron microscope (SEM) morphology of each type of polymer/MWCNT composite film was performed at different operating temperatures. With respect to ethanol, the response magnitude of the sensor decreased with increasing operating temperatures. The results indicated that the higher operating temperature could reduce the response and influence the sensitivity of the polymer/MWCNT gas sensor array. The morphology of polymer/MWCNT composite films revealed that there were changes in the porous film after volatile organic compound (VOC) testing.

Purification of recombinant nacre-associated mineralization protein AP7 fused with maltose-binding protein.

Formation of biominerals often involves specific proteins that modulate the process of matrix assembly, nucleation, and crystal growth. AP7 is an aragonite-associated protein of 7 kDa and is intrinsically disordered. The structural disorder of AP7 makes it very difficult to express in Escherchiacoli. In this work, we report the first successful expression and purification of recombinant AP7 using the maltose-binding protein (MBP) fusion approach. We obtain a high-yield production of recombinant MBP-AP7 protein inE. coli (∼60 mg/L). We also establish an efficient protocol to remove the MBP fusion protein by Factor Xa, followed by purification using size-exclusion chromatography. Characterization of the recombinant AP7 protein has been carried out using MALDI-TOF, peptide mass fingerprinting, and circular dichroism (CD). The mass data confirm that the purified recombinant protein is AP7. The CD data suggest that the recombinant AP7 protein exists as partially disordered structure at neutral pH. The calcium carbonate precipitation assay shows that both MBP-AP7 and AP7 exhibit morphological modification on calcite crystallites. The co-precipitation of MBP-tagged AP7 derivatives and calcium carbonate generate different types of AP7 composite calcite and vaterite crystals. This system should be helpful to establish a model for understanding the structure/function relationship between the protein and inorganic mineral interaction.

Anti-biofilm activities and antibiotic synergy of naturally occurring compounds against drug-resistant rapidly growing mycobacteria.

Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus, M. fortuitum, and M. chelonae. We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans-cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans-cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases. IMPORTANCE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.

Dielectrophoretically Assembled SWCNTs Networks on SU-8 Substrate for PEG/SWCNTs Composite Gas Sensor.

This study proposed a SU-8 based gas sensor, integrated with heater and sensing electrodes, to develop a multi-channel gas sensor with PEG/SWCNTs composite films. The impedance of single-walled carbon nanotubes (SWCNTs) on each sensing electrode was well controlled via dielectrophoresis technology. To investigate dielectrophoretic mobility characteristics, the concentric circular sensing electrode has three different spacing between the inner and outer electrodes, including 10 µm, 15 µm, and 20 µm. The electrodes were applied with a 5 MHz AC source with a voltage ranging from 1 Vpp to 5 Vpp. Polyethylene glycol (PEG) was deposited on the gas sensor via drop casting. The fabricated gas sensor was operated at different working temperatures, including 25 °C, 40 °C, 50 °C and 60 °C, to examine the sensing response. The response results revealed that the PEG/SWCNTs composites gas sensor with 60 °C working temperature exhibited the ability to detect 80 ppm ethanol vapor.