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Excess oxidative stress and inadequate antioxidant capacities are critical features in the development of hepatocellular carcinoma. This study aimed to determine whether supplementation with glutathione (GSH) and/or selenium (Se), as antioxidants, attenuates diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. C57BL/6J male mice were randomly assigned to control, DEN, DEN + GSH, DEN + Se, and DEN + GSH + Se groups for 20 weeks. Daily supplementation with GSH and/or Se commenced in the first experimental week and continued throughout the study. DEN was administered in weeks 2-9 and 16-19 of the experimental period. DEN administration induced significant pathological alterations of hepatic foci, evidenced by elevated levels of liver function, accompanied by high malondialdehyde (MDA) levels; low GSH levels; and glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S -transferase (GST) activities. Supplementation with GSH and Se significantly ameliorated liver pathological changes, reducing liver function and MDA levels while increasing GSH levels and GPx, GR, and GST activities. Notably, combined supplementation with GSH and Se more effectively increased the GSH/glutathione disulfide ratio and GPx activity than individual supplementation. Supplementation with GSH and Se attenuated liver injury in DEN-induced hepatocarcinogenic mice by enhancing GSH and its related antioxidant capacities, thereby mitigating oxidative damage.

Achieving fluid homeostasis and the management of fluid and electrolyte complications are constants in the treatment of seriously ill children worldwide. Consensus on the most appropriate fluid strategy for unwell children has been difficult to achieve and has evolved over the last two decades, most notably in high-income countries where adverse events relating to poor fluid management were identified more readily, and official robust inquiries were possible. However, this has not been the situation in many low-income settings where fluids that are prohibited from use in high-income countries may be all that are available, local guidelines and processes to recognise adverse events are not developed, and there has been limited training on safe fluid management for front-line healthcare workers. This narrative review outlines the fluid and electrolyte pathophysiology of common febrile illnesses in children, describes the evolution of this field and concludes with implications and principles of a fluid management strategy for seriously ill children. This review was prepared as a physiological background paper to support evidence presented to the WHO Guideline Development Group for Fluid Guidelines in Children, Geneva, March 2024., Competing Interests: Competing interests: TD was co-chair of the WHO Guideline Development Group on Fluid Management in Children, 2022–2024., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The associations of tumor angiogenesis with folate and antioxidant capacities in patients with hepatocellular carcinoma (HCC) and their effects on HCC recurrence have not yet been investigated. We investigated the changes and relationships of VEGF, folate, GSH, and GSH-related antioxidant enzymes in patients with HCC before tumor resection, as well as 1 month, 1 year, and 3 years after tumor resection, and their effects on HCC recurrence. 95 HCC patients who underwent tumor resection were recruited. Patients were followed up before tumor resection (pre-resection), 1 month after tumor resection (post-resection), 1 year, and 3 years of follow-up. The recurrence and survival status of patients were evaluated. Plasma VEGF concentrations decreased slightly during follow-up. Serum folate and GSH concentrations and plasma GPx and GR activities increased significantly from pre-resection to post-resection and remained stable at follow-up. Pre-resection plasma VEGF was positively correlated with GSH, GPx, and GR, but negatively correlated with folate and GST. The high pre-resection plasma VEGF was a significant predictor of a high HCC rate (hazard ratio = 1.05, p = 0.035), remaining significant after adjustments for folate, GSH, GPx, GR, and GST to diminish their interference with VEGF. Pre-tumor-resection plasma VEGF constitutes a potential independent marker for predicting HCC recurrence. However, the associations of plasma VEGF with folate and GSH-related antioxidant capacities in HCC patients cannot be ignored., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder, characterized by fibrosis of the oral mucosa. TGF-β signaling pathways have been implicated in the development of OSMF, with areca nut extract (ANE) contributing to the disease progression. Simvastatin, a statin drug, has demonstrated anti-fibrotic properties in various fibrotic conditions. However, its therapeutic potential in treating OSMF remains unclear. In this study, 8-week-old male BALB/c mice were randomly divided into three groups based on different time points. Each mouse was then treated with four different drug formulations. Post-treatment, specimens were collected for histopathological examination and staining to assess skin thickness, fibrosis, and collagen deposition. ANE treatment alone significantly increased skin thickness and collagen deposition compared to the control group after the 4-week time point. The combined administration of ANE and simvastatin, resulted in a notable reduction in skin thickness and collagen deposition. Western blot analysis revealed that simvastatin effectively suppressed the expression of fibrosis-related proteins, including CTGF, and α-SMA, in ANE-induced subdermal fibrosis. These results suggest that simvastatin has potential therapeutic effects on ANE-induced subdermal fibrosis, providing a foundation for future studies and possible clinical applications.

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients' recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post-pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence.

Vitamin B-6 and glutathione (GSH) are antioxidant nutrients, and inadequate vitamin B-6 may indirectly limit glutathione synthesis and further affect the antioxidant capacities. Since liver cirrhosis is often associated with increased oxidative stress and decreased antioxidant capacities, we conducted a double-blind randomized controlled trial to assess the antioxidative effect of vitamin B-6, GSH, or vitamin B-6/GSH combined supplementation in cirrhotic patients. We followed patients after the end of supplementation to evaluate the association of vitamin B-6 and GSH with disease severity. In total, 61 liver cirrhosis patients were randomly assigned to placebo, vitamin B-6 (50 mg pyridoxine/d), GSH (500 mg/d), or B-6 + GSH groups for 12 weeks. After the end of supplementation, the condition of patient's disease severity was followed until the end of the study. Neither vitamin B-6 nor GSH supplementation had significant effects on indicators of oxidative stress and antioxidant capacities. The median follow-up time was 984 d, and 21 patients were lost to follow-up. High levels of GSH, a high GSH/oxidized GSH ratio, and high GSH-St activity at baseline (Week 0) had a significant effect on low Child-Turcotte-Pugh scores at Week 0, the end of supplementation (Week 12), and the end of follow-up in all patients after adjusting for potential confounders. Although the decreased GSH and its related enzyme activity were associated with the severity of liver cirrhosis, vitamin B-6 and GSH supplementation had no significant effect on reducing oxidative stress and increasing antioxidant capacities.

Aim: The study intended to determine the specific ultrasonographic features of acute arthritis with periarticular bone erosions caused by acute osteomyelitis (OM), rheumatoid arthritis (RA) and gouty arthritis (GA)., Method: We included 33 patients (seven with acute OM, 18 with RA flares, and eight with GA attacks) having acute monoarthritis or oligoarthritis, and receiving ultrasound (US) examinations in the acute stage. The US images were rated by three rheumatologists blinded to the diagnosis. The median scores of their evaluation of the subcutaneous tissue, periosteum, and synovium were compared. Interrater reliability was calculated using Cronbach's alpha., Results: The highest mean grade of subcutaneous edema appeared in patients with acute OM, and grade 2 edema was more frequent than patients with RA and GA (P = .003 and P = .026, respectively; α = .869). The prevalence of subcutaneous power Doppler signal was also higher in patients with acute OM than in those with RA and GA (P < .001 and P = .041, respectively; α = .756). Periosteal vascularity presented more frequently in acute OM (P = .003 compared with RA; P = .041 compared with GA), but the interrater reliability was poor (α = .518). The tophaceous material in GA was distinctive from OM and RA (P = .010 and P < .001, respectively; α = .774)., Conclusion: The most discriminative US features in this study were the subcutaneous tissue changes in addition to the periosteal findings. US could contribute to the differential diagnosis of acute erosive arthritis., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: The high prevalence of diabetes is associated with body mass index (BMI), and diabetes can cause many complications, such as hip fractures. This study investigated the effects of BMI and diabetes on the risk of hip fractures and related factors., Methods: We retrospectively reviewed data from 22,048 subjects aged ≧ 40 years from the National Health Interview Survey in Taiwan (NHIST) in 2001, 2005, and 2009. We linked the NHIST data for individual participants with the National Health Insurance Research Database (NHIRD), which includes the incidence of hip fracture from 2000 to 2013. We defined five categories for BMI: low BMI (BMI < 18.5), normal BMI (18.5 ≦ BMI < 24), overweight (24 ≦ BMI < 27), mild obesity (27 ≦ BMI < 30), and moderate obesity (BMI ≧ 30). The Cox proportional hazards model was used to analyze the effects of BMI and diabetes on risk of hip fracture., Results: The Cox proportional hazards model shows that hip fracture risk in participants with diabetes was 1.64 times that of non-diabetes patients (95% confidence interval [CI]:1.30-2.15). Participants with low BMIs showed a higher hip fracture risk (HR: 1.75) than those with normal BMI. Among the five BMI groups, compared with non-diabetes patients, only diabetes patients with a normal BMI showed a significantly higher risk on hip fracture (HR: 2.13, 95% CI: 1.48-3.06). In participants with diabetes, compared with those with normal BMI, those with overweight or obesity showed significantly lower hip fracture risks (HR: 0.49 or 0.42). The hip fracture risk in participants who expend ≧ 500 kcal/week in exercise was 0.67 times lower than in those who did not exercise., Conclusions: Diabetes and low BMI separately are important risk factors for hip fracture. There was an interaction between diabetes and BMI in the relationship with hip fracture (p = 0.001). The addition of energy expenditure through exercise could effectively decrease hip fracture risk, regardless of whether the participants have diabetes or not. The results of this study could be used as a reference for health promotion measures for people with diabetes.

Quantum memory is an important component in the long-distance quantum communication based on the quantum repeater protocol. To outperform the direct transmission of photons with quantum repeaters, it is crucial to develop quantum memories with high fidelity, high efficiency and a long storage time. Here, we achieve a storage efficiency of 92.0 (1.5)% for a coherent optical memory based on the electromagnetically induced transparency scheme in optically dense cold atomic media. We also obtain a useful time-bandwidth product of 1200, considering only storage where the retrieval efficiency remains above 50%. Both are the best record to date in all kinds of schemes for the realization of optical memory. Our work significantly advances the pursuit of a high-performance optical memory and should have important applications in quantum information science.

We have determined the fundamental frequency of the cesium atom 6S 1/2 -6D 3/2 two-photon transition, for the first time, to our knowledge. Moreover, our high-resolution scheme made it possible to address the influence of the nuclear magnetic octupole on the hyperfine structure. We found that the octupole-interaction hyperfine constant deduced from the cesium 6D-level has a value nearly eight times larger than what has been deduced from the 6P-level.

Background/purpose: Matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs) have been shown to play an important role in the pathogenesis of tissue destruction in periodontitis. The associations between single nucleotide polymorphisms (SNPs) in the promoter regions of MMP-2, MMP-9, and TIMP-2 genes and the risk of aggressive periodontitis (AgP) and chronic periodontitis (CP) were investigated in a Taiwanese population., Materials and Methods: MMP-2 C-1306T, C-735T, T-790G, and MMP-9 C-1562T and TIMP-2 G-418C SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 69 patients and 129 patients with AgP and CP, respectively, and 117 periodontal healthy individuals who served as healthy controls (HC). Chi-square test and logistic regression analysis were used to investigate the possible association of genotypes with periodontitis., Results: No significant differences in the distributions of the C-1306T and C-735T variants between periodontitis and HC were detected. Patients with genotype of MMP-2 -790 TT or T allele of MMP-2-790T/G as compared to genotypes of GT + GG genotypes or G allele, were less susceptible to CP [odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.25-1.00 and OR = 0.52, 95% CI = 0.28-0.96, respectively]. The frequencies of TIMP-2 G-418C gene polymorphisms in nonsmokers were statistically significantly different among AgP, CP, and HC groups (P = 0.024). The nonalcohol drinking participants with C allele of MMP-9 C-1562T as compared to T allele, were less susceptible to AgP (adjusted OR = 0.4; 95% CI, 0.18-0.90)., Conclusion: It is suggested that MMP-2 T-790G, MMP-9 C-1562T, and TIMP-2 G-418C gene polymorphisms might be associated with periodontitis in the Taiwanese Han population.

The electronic structure and magnetic properties of SrMn0.5Fe0.5O3 powder and films grown on (1 0 0)-SrTiO3 (STO) and (1 0 0)-LaAlO3 (LAO) substrates by pulsed laser deposition (PLD) were investigated by temperature dependent magnetization and soft x-ray absorption. The results exhibit characteristics of 3d (5) Fe(3+), [Formula: see text], and 3d (3)  +  3d (4) [Formula: see text] Mn(4+) at room temperature in all samples. However, the features of 3d (5) Fe(3+) and 3d (3) Mn(4+) increased significantly for SMFO/LAO at 35 K, which also displayed substantial competition between antiferromagnetic and ferromagnetic order well-above the Néel temperature of SrFeO3 (T N ~ 134 K). We attributed this to being caused by charge disproportionation resulting from ligand-hole localization, which is more favorable to take place when the sample is under compressive strain.

Background: In mechanically ventilated (MV) cardiac arrest (CA) survivors admitted to the intensive care unit (ICU) avoidance of hypoxia is considered crucial. However, avoidance of hyperoxia may also be important. A conservative approach to oxygen therapy may reduce exposure to both., Methods: We evaluated the introduction of conservative oxygen therapy (target SpO2 88-92% using the lowest FiO2) during MV for resuscitated CA patients admitted to the ICU., Results: We studied 912 arterial blood gas (ABG) datasets: 448 ABGs from 50 'conventional' and 464 ABGs from 50 'conservative' oxygen therapy patients. Compared to the conventional group, conservative group patients had significantly lower PaO2 values and FiO2 exposure (p<0.001, respectively); more received MV in a spontaneous ventilation mode (18% vs 2%; p=0.001) and more were exposed to a FiO2 of 0.21 (19 vs 0 patients, p=0.001). Additionally, according to mean PaO2, more conservative group patients were classified as normoxaemic (36 vs 16 patients, p<0.01) and fewer as hyperoxaemic (14 vs 33 patients, p<0.01). Finally, ICU length of stay was significantly shorter for conservative group patients (p=0.04). There was no difference in the proportion of survivors discharged from hospital with good neurological outcome (14/23 vs 12/22 patients, p=0.67)., Conclusions: Our findings provide preliminary support for the feasibility and physiological safety of conservative oxygen therapy in patients admitted to ICU for MV support after cardiac arrest (Trial registration, NCT01684124)., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Rapid Response Team (RRT) calls can often occur within 24h of hospital admission to a general ward. We seek to determine whether it is possible to identify these patients before there is a significant clinical deterioration., Methods: Retrospective case-controlled study comparing patient characteristics, vital signs, and hospital outcomes in patients triggering RRT activation within 24h of ED admission (cases) with matched ED admissions not receiving a RRT call (controls)., Results: Over 12 months, there were 154 early RRT calls. Compared with controls, cases had a higher heart rate (HR) at triage (92 vs. 84 beats/min; p=0.008); after 3h in the ED (91 vs. 80 beats/min; p=0.0007); and at ED discharge (91 vs. 81 beats/min; p=0.0005). Respiratory rate (RR) was also higher at triage (21.2 vs. 19.2 breaths/min; p=0.001). On multiple variable analysis, RR at triage and HR before ward transfer predicted early RRT activation: OR 1.07 [95% CI 1.02-1.12] for each 1 breath/min increase in RR; and 1.02 [95% CI 1.002-1.030] for each beat/minute increase in HR, respectively. Study patients required transfer to the intensive care in approximately 20% of cases and also had a greater mortality: (21% vs. 6%; OR 4.65 [95% CI 1.86-11.65]; p=0.0003) compared with controls., Conclusions: Patients that trigger RRT calls within 24h of admission have a fourfold increase in risk of in-hospital mortality. Such patients may be identified by greater tachycardia and tachypnoea in the ED., (Copyright © 2015 College of Emergency Nursing Australasia Ltd. Published by Elsevier Ltd. All rights reserved.)

The rotation of the γ subunit of F(1)-ATPase is stochastic, processive, unidirectional, reversible through an external torque, and stepwise with a slow rotation. We propose a mechanism that can explain these properties of the rotary molecular motor, and that can determine the direction of rotation. The asymmetric structures of the γ subunit, both at the tip of the shaft (C and N termini) and at the part (ε subunit) protruding from the α(3)β(3) subunits, are critical. The torque required for stochastic rotation is generated from the impulsive reactive force due to the random collisions between the γ subunit and the quasihexagonal α(3)β(3) subunits. The rotation is the result of the random motion of the confined asymmetric γ subunit. The steps originate from the chemical reactions of the γ subunit and physical interaction between the γ subunit and the flexible protrusions of the α(3)β(3) subunits. An external torque as well as a configurational modification in the γ subunit (the central rotor) can reverse the rotational direction. We demonstrate the applicability of the mechanism to a macroscopic simulation system, which has the essential ingredients of the F(1)-ATPase structure, by reproducing the dynamic properties of the rotation.

We employed a microfluidic device to study the effects of hydraulic pressure on cardiomyoblast H9c2. The 170 mm Hg pressure increased the cellular area and the expression of atrial natriuretic peptide. With the same device, we demonstrated that the effects of hydraulic pressure on the cardiomyoblast could be reduced by the inhibitor of focal adhesion kinase. This mechanical-chemical antagonism could lead to a potential therapeutic strategy of hypertension-induced cardiac hypertrophy.

We present an experimental study of the coherence properties of amplified slow light by four-wave mixing (FWM) in a three-level electromagnetically induced transparency (EIT) system driven by one additional pump field. High energy gain (up to 19) is obtained with a weak pump field (a few mW/cm2) using optically dense cold atomic gases. A large fraction of the amplified light is found to be phase incoherent to the input signal field. The dependence of the incoherent fraction on pump field intensity and detuning and the control field intensity is systematically studied. With the classical input pulses, our results support a recent theoretical study by Lauk et al. [Phys. Rev. A88, 013823 (2013)], showing that the noise resulting from the atomic dipole fluctuations associated with spontaneous decay is significant in the high gain regime. This effect has to be taken into consideration in EIT-based applications in the presence of FWM.

Background: In hospital cardiac arrests (CA) treated with cardio-pulmonary resuscitation (CPR) outside of the intensive care unit (ICU) have poor outcomes. Most are preceded by deranged vital signs. There are, however, limited studies assessing antecedents to CAs inside the ICU., Objectives: To study the antecedents to, and characteristics of CAs in ICU., Study Population: We prospectively identified CA cases that occurred inside our ICU between January 2010 and July 2012. Controls were obtained by sequentially matching ICU patients based on APACHE III diagnosis, APACHE III score, age, gender and length of stay in ICU., Results: Thirty-six patients had a CA during the study period (6.28/1000 admissions). In the 12h prior to CA, index patients had higher maximum (22 breaths/min vs. 18 breaths/min, p=0.001) and minimum respiratory rates (16 breaths/min vs. 12 breaths/min, p=0.031), a lower median mean arterial pressure (65 mmHg vs. 70 mmHg, p=0.029) and systolic blood pressure (97 mmHg vs. 106 mmHg, p=0.033), a higher central venous pressure (14 cm H2O vs. 11 cm H2O, p=0.008) and a lower bicarbonate level (20.5 mmol vs. 26 mmol, p=0.018) compared to controls. CA patients also had a higher maximum dose of noradrenaline (norepinephrine) (17.5 mcg/min vs. 8.0 mcg/min, p=0.052) but there was no difference in any other levels of intensive care support. Two-thirds of CA's occurred within the first 48 h of ICU admission. The initial monitored rhythm was non-shock responsive (pulseless electrical activity, bradycardia or asystole) in 26/36 (72%). Return of spontaneous circulation was achieved in 29/36 (80.6%) patients, with 16/36 (44.4%) surviving to hospital discharge., Conclusions: In the period leading up to the CA inside ICU, there were signs of physiological instability and the need for higher doses of noradrenaline. Return of spontaneous circulation was achieved in 80%. However, in-hospital mortality was greater than 50%., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We use a double-passed acousto-optic modulator (AOM), driven by an arbitrary waveform generator to produce multiple frequency components for a laser with arbitrary frequency spacings. A programmed sequence containing various sections of radio-frequency sinusoidal signal at different frequency is applied to drive the AOM. The diffracted light is used to injection-lock a diode laser. The combined techniques allow us to generate the multi-line spectra for the diode laser with arbitrary frequency spacings in the range of 100 MHz at a relatively high output power of 80 mW and a small power variation of 2%. Such a light source can be used in the application for laser cooling of molecules.

This paper investigates the optimal selection of processing parameters for motion table performance. The main objective of the mechanism of a one-axis servo motor table is to avoid vibration, thereby reducing experimental error. This experimental controller uses a grey-based Taguchi method to make a quality evaluation of three table characteristics; displacement, arriving time, and torsion. It is shown that the multiple response performance characteristics are greatly improved through this study., (2009 ISA. Published by Elsevier Ltd. All rights reserved.)

An oviraptosaurian specimen (Dinosauria, Theropoda) from an Upper Cretaceous formation in China retains a pair of shelled eggs in the pelvis, providing direct evidence that oviraptorosaurian dinosaurs laid paired elongatoolithid eggs. The presence of the paired eggs suggests that theropod dinosaurs had two functional oviducts (like crocodiles) but that each oviduct produced only one egg at a time and that an entire egg clutch was laid through multiple ovipositions (like birds). The orientations of the eggs inside the skeleton and in clutches indicate that the mother came to the center of the nest to lay eggs.