The recovery of diaphragmatic function is vital for successful extubation from mechanical ventilation. Recent studies have detected diaphragm atrophy in ventilated adults by using ultrasound, but no ...similar report has been conducted in children. In the current study, we hypothesized that mechanically ventilated children may also develop diaphragm atrophy and diaphragmatic dysfunction.
Children who were admitted to the pediatric intensive care unit and were newly intubated for mechanical ventilation were enrolled into this prospective case-control study. Diaphragm ultrasound assessments were performed daily to evaluate diaphragmatic function in the enrolled children until their discharge from the pediatric intensive care unit. Diaphragm thickness and the diaphragmatic thickening fraction (DTF) were measured through these assessments.
A total of 31 patients were enrolled, and overall, 1389 ultrasound assessments were performed. Immediately after intubation, the initial diaphragm thickness and DTF were measured to be 1.94 ± 0.44 mm and 25.85% ± 3.29%, respectively. In the first 24 hours of mechanical ventilation, diaphragm thickness and the DTF decreased substantially and decreased gradually thereafter. After extubation, the DTF was significantly different between the successful and failed extubation groups (P < 0.001), and a DTF value of <17% was associated with extubation failure.
Diaphragm ultrasound is a noninvasive method for measuring diaphragmatic function in mechanically ventilated children. In this study, significant diaphragm atrophy and a decreased DTF were observed within 24 hours of mechanical ventilation. The recovery of diaphragm thickness and the DTF may be a potential predictor of successful extubation from mechanical ventilation.
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to chemotherapy, and tumor recurrence is common. Neuronal precursor cell-expressed ...developmentally downregulated 4-1 (NEDD4-1) is an E3 ligase that controls embryonic development and animal growth. NEDD4-1 regulates the tumor suppressor phosphatase and tensin homolog (PTEN), one of the major regulators of the PI3K/AKT/mTOR signaling axis, as well as the response to oxidative stress.
The expression levels of NEDD4-1 in GBM tissues and different cell lines were determined by quantitative real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo assays were performed to explore the biological effects of NEDD4-1 on GBM cells. Temozolomide (TMZ)-resistant U87MG and U251 cell lines were specifically established to determine NEDD4-1 upregulation and its effects on the tumorigenicity of GBM cells. Subsequently, miRNA expression in TMZ-resistant cell lines was investigated to determine the dysregulated miRNA underlying the overexpression of NEDD4-1. Indole-3-carbinol (I3C) was used to inhibit NEDD4-1 activity, and its effect on chemoresistance to TMZ was verified.
NEDD4-1 was significantly overexpressed in the GBM and TMZ-resistant cells and clinical samples. NEDD4-1 was demonstrated to be a key oncoprotein associated with TMZ resistance, inducing oncogenicity and tumorigenesis of TMZ-resistant GBM cells compared with TMZ-responsive cells. Mechanistically, TMZ-resistant cells exhibited dysregulated expression of miR-3129-5p and miR-199b-3p, resulting in the induced NEDD4-1 mRNA-expression level. The upregulation of NEDD4-1 attenuated PTEN expression and promoted the AKT/NRF2/HO-1 oxidative stress signaling axis, which in turn conferred amplified defense against reactive oxygen species (ROS) and eventually higher resistance against TMZ treatment. The combination treatment of I3C, a known inhibitor of NEDD4-1, with TMZ resulted in a synergistic effect and re-sensitized TMZ-resistant tumor cells both in vitro and in vivo.
These findings demonstrate the critical role of NEDD4-1 in regulating the redox imbalance in TMZ-resistant GBM cells via the degradation of PTEN and the upregulation of the AKT/NRF2/HO-1 signaling pathway. Targeting this regulatory axis may help eliminate TMZ-resistant glioblastoma.
In this study, we developed a range of motion sensing system (ROMSS) to simulate the function of the elbow joint, with errors less than 0.76 degrees and 0.87 degrees in static and dynamic ...verification by the swinging and angle recognition modules, respectively. In the simulation process, the ɣ correlation coefficient of the Pearson difference between the ROMSS and the universal goniometer was 0.90, the standard deviations of the general goniometer measurements were between ±2 degrees and ±2.6 degrees, and the standard deviations between the ROMSS measurements were between ±0.5 degrees and ±1.6 degrees. With the ROMSS, a cloud database was also established; the data measured by the sensor could be uploaded to the cloud database in real-time to provide timely patient information for healthcare professionals. We also developed a mobile app for smartphones to enable patients and healthcare providers to easily trace the data in real-time. Historical data sets with joint activity angles could be retrieved to observe the progress or effectiveness of disease recovery so the quality of care could be properly assessed and maintained.
Abstract
The rotation of a C = C bond in an alkene can be efficiently accelerated by creating the high-strain ground state and stabilizing the transition state of the process. Herein, the synthesis, ...structures, and properties of several highly twisted alkenes are comprehensively explored. A facile and practical synthetic approach to target molecules is developed. The twist angles and lengths of the central C = C bonds in these molecules are 36–58° and 1.40–1.43 Å, respectively, and confirmed by X-ray crystallography and DFT calculations. A quasi-planar molecular half with the π-extended substituents delivers a shallow rotational barrier (down to 2.35 kcal/mol), indicating that the rotation of the C = C bond is as facile as that of the aryl-aryl bond in 2-flourobiphenyl. Other versatile and unique properties of the studied compounds include a broad photoabsorption range (from 250 up to 1100 nm), a reduced HOMO-LUMO gap (1.26–1.68 eV), and a small singlet-triplet energy gap (3.65–5.68 kcal/mol).
The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study ...examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension.
A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio HR, 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 95% CI, 0.87-1.59). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all
values for interaction >0.05).
In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.
To systematically quantify the production, consumption, and migration of methane, 210 sediment cores were collected from offshore southwestern Taiwan and analyzed for their gas and aqueous ...geochemistry. These data, combined with published results, were used to calculate the diffusive methane fluxes across different geochemical transitions and to develop scenarios of mass balance and constrain deep microbial and thermogenic methane production rates within the accretionary prism. The results showed that methane diffusive fluxes ranged from 2.71 × 10−3 to 2.78 × 10−1 and from –1.88 × 10−1 to 3.97 mmol m−2 d−1 at the sulfate‐methane‐transition‐zone (SMTZ) and sediment‐seawater interfaces, respectively. High methane fluxes tend to be associated with structural features, suggesting a strong structural control on the methane transport. A significant portion of ascending methane (>50%) is consumed by anaerobic oxidation of methane at the SMTZ at most sites, indicating effective biological filtration. Gas compositions and isotopes revealed a transition from the predominance of microbial methane in the passive margin to thermogenic methane at the upper slope of the active margin and onshore mud volcanoes. Methane production and consumption at shallow depths were nearly offset with a small fraction of residual methane discharged into seawater. The flux imbalance arose primarily due to the larger production of methane through deep microbial and thermogenic processes at a magnitude of 1512–43,096 Tg Myr−1 and could be likely accounted for by the sequestration of methane into hydrate forms, and clay absorption.
Key Points
We apply a systematic approach to quantify the rates of methane sources and sinks in different compartments in Taiwan accretionary prism
CH4 production and consumption rates at shallow depth were nearly offset by each other, leaving total effluxes less than production at depth
The potential flux imbalance could be likely accounted for by the sequestration of methane into hydrate forms and the clay absorption
The use of livestock waste for the production of biogas and the application of biogas slurry to agricultural soil can resolve livestock waste problems and reduce synthetic fertiliser use. However, ...the migration of veterinary drugs to land and crops resulting from biogas slurry irrigation is a potential food safety concern. This study employed an ultra-performance liquid chromatography coupled with quadrupole-time of flight high-resolution mass spectrometry system for wide-scope suspect screening of pharmaceutically active substances on crop cultivated under biogas slurry irrigation. Briefly, a total of 22 pak choi samples were obtained from a greenhouse farmed in tropical south Taiwan between March 2019 and March 2020. Molecular spectra and fragmented ions (between m/z 70 and 1100) were acquired. Ion features were searched and matched with a library consisting of 1068 compounds. The matrixes in the crop production environment including soil, livestock wastewater, biogas slurry, and groundwater were included in this study to elucidate potential sources of the pharmaceutically active substances. Results demonstrated 23 suspects were matched with high mass accuracy (mass error within ±5.0 ppm) in pak choi. The detection of both bufexamac and nandrolone were confirmed using standards, where a new system of identification points was applied. Nandrolone was detected throughout the pak choi samples as well as livestock wastewater. Tetracycline, macrolide, and sulfonamide antibiotics were presented in biogas slurry and soil but not pak choi. This is the first study to reveal the presence of multiclass pharmaceutically active substances in a crop supplied as food. Such findings suggest that anabolics and antibiotics should be closely monitored in the corps irrigated by biogas slurry in future.
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•Farm samples were screened for 1068 pharmaceutically active substances using HRMS.•Pak choi, intended for human consumption, was irrigated with biogas slurry.•23 substances were tentatively identified and 2 were further confirmed in pak choi.•Nandrolone was prevalent in pak choi and found in livestock wastewater.•Antibiotics rarely occurred in pak choi but could be an environmental soil concern.
Phloretin, a dihydrochalcone flavonoid, possesses anti-inflammatory activity and inhibits the growth of various cancers. However, the flavonoid's effect on cervical cancer metastasis and angiogenesis ...remains unknown.
In this study, we provide molecular evidence associated with the antimetastatic and antiangiogenic effects of phloretin.
In this study, the anti-invasive effect of phloretin (0–60 μM) in cervical cancer cells was evaluated using the Matrigel invasion assay, gelatin zymography, cell-matrix adhesion assay, wound healing assay, and Western blotting. Antiangiogenic potential of phloretin (0–100 μM) was assessed by the Matrigel tube formation assay. The in vivo antitumor effect of phloretin (10 or 20 mg/kg) was fed by oral gavage and determined using subcutaneous inoculation and tail vein injection in immunodeficient nude mice.
Phloretin (60 μM) showed marked suppression of invasion and migration through downregulation of matrix metalloproteinase (MMP)-2, MMP-3, and cathepsin S in human SiHa cervical cancer cells. Phloretin (60 μM) reversed the epithelial-mesenchymal transition induced by transforming growth factor-β1 and downregulated mesenchymal markers, such as fibronectin, vimentin, and RhoA. Phloretin (100 μM) treatment significantly inhibited the aldehyde dehydrogenase 1 activity of SiHa cells, reduced the self-renewal properties and stemness signatures of CD44 and Sox-2 in sphere-forming cervical cancer-derived tumor-initiating cells, and inhibited the invasion, MMP-2 activity, and tube formation capacity of human umbilical vein endothelial cells. The ability of phloretin (20 mg/kg) to suppress lung metastasis and tumor growth in SiHa cells was evidenced by tail vein injection and subcutaneous inoculation in a tumor xenograft model.
In summary, the findings indicate that phloretin inhibits the metastatic and angiogenic abilities and cancer stemness of SiHa cells, thereby suggesting that this flavonoid is a promising therapeutic agent for the treatment of human cervical cancer cells.
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Supermicrosurgical lymphaticovenous anastomosis (LVA) is a minimally invasive surgical technique that creates bypasses between lymphatic vessels and veins, thereby improving lymphatic drainage and ...reducing lymphedema. This retrospective single-center study included 137 patients who underwent non-intubated LVA in southern Taiwan. A total of 119 patients were enrolled and assigned to two study groups: the geriatric (age ≥ 75 years,
= 23) and non-geriatric groups (age < 75 years,
= 96). The primary outcome was to investigate and compare the arousal and maintenance of the propofol effect-site concentration (Ce) using an electroencephalographic density spectral array (EEG DSA) in both groups. The results showed that the geriatric group required less propofol (4.05 3.73-4.77 mg/kg/h vs. 5.01 4.34-5.92 mg/kg/h,
= 0.001) and alfentanil (4.67 2.53-5.82 μg/kg/h vs. 6.68 3.85-8.77 μg/kg/h,
= 0.047). The median arousal Ce of propofol among the geriatric group (0.6 0.5-0.7 μg/mL) was significantly lower than that in patients aged ≤ 54 years (1.3 1.2-1.4 μg/mL,
< 0.001), 55-64 years (0.9 0.8-1.0 μg/mL,
< 0.001), and <75 years (0.9 0.8-1.2 μg/mL,
< 0.001). In summary, the combined use of EEG DSA provides the objective and depth of adequate sedation for extensive non-intubated anesthesia in late-elderly patients who undergo LVA without perioperative complications.
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