We describe a case of a 56-year-old woman with primary hyperparathyroidism. 18F-Choline PET/MRI revealed incidental bilateral axillary lymphadenopathy with mild-moderate increased 18F-choline uptake. The patient had her first and third doses of COVID-19 vaccines from the left arm and second dose of vaccine from the right arm before PET examination.

The practice of anaesthetists relating to the administration of intraoperative oxygen has not been previously quantified in Australia and New Zealand. The optimal regimen of intraoperative oxygen administration to patients undergoing surgery under general anaesthesia is not known, and international recommendations for oxygen therapy are contradictory; the World Health Organization (WHO) recommend administering an intraoperative fraction of inspired oxygen of at least 0.8, while the World Federation of Societies of Anaesthesiologists, British Thoracic Society, and Thoracic Society of Australia and New Zealand recommend a more restrictive approach. We conducted a prospective observational study to describe the pattern of intraoperative oxygen administration among anaesthetists in Australia and New Zealand and, second, to determine the proportion of anaesthetists who administer intraoperative inspired oxygen in accordance with the WHO recommendations. We identified 150 anaesthetists from ten metropolitan hospitals in Australia and New Zealand and observed the patterns of intraoperative oxygen administration to American Society of Anesthesiologists physical status classification (ASA) 3 or 4 patients undergoing prolonged surgery under general anaesthesia. The median (interquartile range) intraoperative time-weighted mean fraction of inspired oxygen (FiO2) for all participants in the study was 0.47 (0.40-0.55). Three out of 150 anaesthetists (2%, 95% confidence interval 0.4 to 5.7) administered an average intraoperative FiO2 of at least 0.8. These findings indicate that most anaesthetists routinely administer an intermediate level of oxygen for ASA 3 or 4 adult patients undergoing prolonged surgery in Australia and New Zealand, rather than down-titrating inspired oxygen to a target pulse oximetry reading (SpO2) or administering liberal perioperative oxygen therapy in line with the current WHO recommendation.

Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In this study, the mechanisms underlying the anti-inflammatory activity of P. emarginatus oleoresin and vouacapanes 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan (V1), 6α-acetoxy-7β,14β-dihydroxyvouacapan (V2), and methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate (V3) were investigated in HaCaT cells. Results: Oleoresin, V2, and V3 inhibited phospholipase A2 (30.78%, 24.96%, and 77.64%, respectively). Both vouacapanes also inhibited the expression of COX-2 (28.3% and 33.17%, respectively). The production of interleukin 6 (IL-6) was inhibited by oleoresin by 35.47%. However, oleoresin did not interfere with Nrf-2 expression or IL-8 production. Conclusion: The results support the ethnomedicinal use of P. emarginatus oleoresin as an anti-inflammatory herbal medicine, and also highlight P. emarginatus oleoresin and isolated vouacapanes as an attractive therapeutic approach for COVID-19 through the reduction or chronological control of the inflammatory mediators IL-6, cyclooxygenase-2 (COX-2), phospholipase A2, and INF-y (indirectly) during the SARS-CoV-2 infection process.

Introduction Invasive blood pressure monitoring is essential in liver transplant surgery due to expected major hemodynamic shifts. The use of central versus peripheral arterial access, however, is institution-dependent, which can affect clinical decisions regarding vasopressor therapy. Although there are studies that demonstrate inconsistencies based on arterial cannulation sites, few studies have compared femoral and radial artery blood pressures in patients undergoing liver transplant surgery. To our knowledge, there are no studies investigating the differences between continuous minute-to-minute femoral and radial artery measurements during all three phases of liver transplant surgery. Objective The main objective of this study was to evaluate for any differences between central and peripheral blood pressure measurements in liver transplant surgery and to assess for any correlation between vasopressor infusion dose and femoral-arterial pressure differences. Methods In this retrospective study, we reviewed and studied the data of 61 patients with American Society of Anesthesiologists (ASA) grade 4 who underwent liver transplant surgery at Loma Linda University Medical Center between January and December of 2019. All patients had both femoral and radial arterial lines placed for liver transplant surgery. Femoral and radial arterial blood pressure values were obtained continuously over 60 minutes in the pre-anhepatic phase, 45 minutes during the anhepatic phase, and 60 minutes into the neo-hepatic phase. Vasopressor infusion doses were also recorded for each patient during these time frames. Results This pilot study found statistically significant differences between the mean femoral and radial systolic blood pressure (SBP; p < 0.0001), diastolic blood pressure (DBP; p < 0.0001), and mean arterial pressure (MAP; p < 0.0001) during all phases of liver transplantation. The meanSBP and MAP differences between femoral and radial arteries were highest (femoral blood pressure reading higher than radial blood pressure measurements) in the late anhepatic and early neo-hepatic phases with SBP differences of 20.8 ± 0.8 mmHg and 22.8 ± 0.8 mmHg, respectively, and MAP differences of 10.0 ± 0.4 mmHg and 9.8 ± 0.4 mmHg, respectively. Higher vasopressor infusion doses were strongly associated with greater differences in femoral-radial SBP and MAP measurements (r = 0.69 for vasopressin, 0.68 for norepinephrine, and 0.68 for epinephrine; p < 0.0001) during the anhepatic phase. Conclusions Peripheral invasive blood pressure monitoring may result in underestimation of the central blood pressure, as was seen in all phases of liver transplantation. This may lead to excessive vasopressor use with potentially adverse effects. Although the cause for the difference between femoral and radial artery measurements is unclear, increasing vasopressor infusion dosages appears to contribute. Femoral artery blood pressure monitoring allows clinicians to interpret hemodynamic status and administer appropriate vasopressors more accurately.

Poorly immunogenic small molecules pose challenges for the production of clinically efficacious vaccines and antibodies. To address this, we generate an immunization platform derived from the immunogenic surface coat of the African trypanosome. Through sortase-based conjugation of the target molecules to the variant surface glycoprotein (VSG) of the trypanosome surface coat, we develop VSG-immunogen array by sortase tagging (VAST). VAST elicits antigen-specific memory B cells and antibodies in a murine model after deploying the poorly immunogenic molecule fentanyl as a proof of concept. We also develop a single-cell RNA sequencing (RNA-seq)-based computational method that synergizes with VAST to specifically identify memory B cell-encoded antibodies. All computationally selected antibodies bind to fentanyl with picomolar affinity. Moreover, these antibodies protect mice from fentanyl effects after passive immunization, demonstrating the ability of these two coupled technologies to elicit therapeutic antibodies to challenging immunogens.

GDP-L-galactose phosphorylase (VTC2) catalyzes the conversion of GDP-L-galactose to L-galactose-1-P, a vital step of ascorbic acid (AsA) biosynthesis in plants. AsA is well known for its function in the amelioration of oxidative stress caused by most pathogen infection, but its function against viral infection remains unclear. Here, we have identified a VTC2 gene in wheat named as TaVTC2 and investigated its function in association with the wheat yellow mosaic virus (WYMV) infection. Our results showed that overexpression of TaVTC2 significantly increased viral accumulation, whereas knocking down TaVTC2 inhibited the viral infection in wheat, suggesting a positive regulation on viral infection by TaVTC2. Moreover, less AsA was produced in TaVTC2 knocking down plants (TaVTC2-RNAi) which due to the reduction in TaVTC2 expression and subsequently in TaVTC2 activity, resulting in a reactive oxygen species (ROS) burst in leaves. Furthermore, the enhanced WYMV resistance in TaVTC2-RNAi plants was diminished by exogenously applied AsA. We further demonstrated that WYMV NIb directly bound to TaVTC2 and inhibited TaVTC2 enzymatic activity in vitro. The effect of TaVTC2 on ROS scavenge was suppressed by NIb in a dosage-dependent manner, indicating the ROS scavenging was highly regulated by the interaction of TaVTC2 with NIb. Furthermore, TaVTC2 RNAi plants conferred broad-spectrum disease resistance. Therefore, the data indicate that TaVTC2 recruits WYMV NIb to downregulate its own enzymatic activity, reducing AsA accumulation to elicit a burst of ROS which confers the resistance to WYMV infection. Thus, a new mechanism of the formation of plant innate immunity was proposed.

Pepper is one of the most vitamin C enriched vegetables worldwide. Although applying nitrogen (N) fertilizer is an important practice for high fruit yield in pepper production, it is still unclear how N application regulates pepper fruit vitamin C anabolism at different maturity stage. To further the understanding, we combined physiological and metabolomic analysis to investigate the fruit vitamin C content (including ascorbic acid (AsA) and dehydroascorbic acid (DHA)), related enzyme activity and non-targeted metabolites of field-grown chili pepper produced under different N levels at mature green and red stages. The results showed that increasing N application reduced AsA content in pepper fruit at both maturity stages, but highly elevated DHA content only at mature green stage. Regardless of N application level, AsA content displayed an increasing trend while DHA content was reduced as pepper fruit maturity advanced, resulting in a higher content of total vitamin C at the mature green stage. The L-galactose pathway, D-galacturonate pathway, and myo-inositol pathway were identified for AsA biosynthesis. The involved precursor metabolites were mainly negatively regulated by increasing N application, and their accumulation increased when pepper fruit developed from green to red stage. Meanwhile, the activities of key enzymes and metabolites in relation to degradation and recycling processes of AsA and DHA were increased or did not change with increasing N application, and they were differently influenced as fruit maturing. As a result, the recommended N application level (250 kg N ha-1) could maintain relatively high total vitamin C content in pepper fruits without yield loss at both maturity stages. These findings highlight the importance of optimizing N application level to maximize vitamin C content in pepper fruits, and provide a better understanding of the maturity stage-dependent N regulation on vitamin C anabolism.

Prolonged length of stay (LOS) in osteoporotic femoral neck fracture patients increased the hospital care cost and demonstrated in-hospital complications. This study aimed to develop an ease-of use predictive model of prolonged LOS in osteoporotic femoral neck fracture patients. In this 5-year retrospective study, the medical charts of 255 patients admitted to hospital with an osteoporotic femoral neck fracture resulting from a simple fall from January 2014 to December 2018 were reviewed. Multivariable fractional polynomials (MFP) algorithms was applied to develop the predictive model from candidate predictors of prolonged LOS. The discrimination performance of predictive model was evaluated using the receiver operating characteristic curve (ROC). Internal validity was assessed using bootstrapping. From 289 patients who were hospitalized with an osteoporotic fracture of femoral neck throughout this study, 255 (88%) fulfilled the inclusion criteria. There was 54.90% (140 of 255 patients) of patients who had prolonged LOS. The predictors of the predictive model were age, BMI, ASA score class 3 or 4, arthroplasty and time from injury to surgery. The area under ROC curve of the model was 0.83 (95% confidence interval 0.77-0.88). Internal validation with bootstrap re-sampling revealed an optimism of -0.002 (range -0.300-0.296) with an estimated shrinkage factor of 0.907 for the predictive model. The current predictive model developed from preoperative predictors which had a good discriminative ability to differentiate between length of hospitalization less than 14 days and prolonged LOS in osteoporotic femoral neck patients. This model can be applied as ease-of use calculator application to help patients, their families and clinicians make appropriate decisions in terms of treatment planning, postoperative care program, and cost-effectiveness before patients receiving the definitive treatments.

MEK inhibitors are among the most successful molecularly targeted agents used as cancer therapeutics. However, to treat cancer more efficiently, resistance to MEK inhibitor-induced cell death must be overcome. Although previous genetic approaches based on comprehensive gene expression analysis or RNAi libraries led to the discovery of factors involved in intrinsic resistance to MEK inhibitors, a feasible combined treatment with the MEK inhibitor has not yet been developed. Here, we show that a chemoproteoinformatics approach identifies ligands overcoming the resistance to cell death induced by MEK inhibition as well as the target molecule conferring this resistance. First, we used natural products, perillyl alcohol and sesaminol, which induced cell death in combination with the MEK inhibitor trametinib, as chemical probes, and identified ribosomal protein S5 (RPS5) as their common target protein. Consistently, trametinib induced cell death in RPS5-depleted cancer cells via upregulation of the apoptotic proteins BIM and PUMA. Using molecular docking and molecular dynamics (MD) simulations, we then screened FDA- and EMA-approved drugs for RPS5-binding ligands and found that acetylsalicylic acid (ASA, also known as aspirin) directly bound to RPS5, resulting in upregulation of BIM and PUMA and induction of cell death in combination with trametinib. Our chemoproteoinformatics approach demonstrates that RPS5 confers resistance to MEK inhibitor-induced cell death, and that aspirin could be repurposed to sensitize cells to MEK inhibition by binding to RPS5.

The effect of reaction conditions, which comprised the reaction temperature (150-190°C), processing time (0.50, 0.75, 1.00, 1.25, 1.50, 2.00, and 2.50 h), pH (5.0, 7.0, and 9.5), and concentration (0.03-0.07 mol/L) of L-ascorbic acid (ASA), on the degradation of ASA was investigated in hot-compressed water (HCW). The degradation kinetics of ASA and generation kinetics of browning products (BPs) were studied. The results showed that ASA degradation conformed to the pseudo-first-order kinetics, and the formation of BPs was closely related to the concentration of H3O+ in HCW. The acidic condition (pH = 5.0) and lower concentration of ASA (0.03 mol/L) were more favorable for ASA degradation. In HCW, the average apparent activation energy (Ea) of ASA was 15.77, 31.70, and 47.53 kJ/mol at pH 5.0, 7.0, and 9.5, respectively. The possible degradation mechanisms of ASA and the generation of BPs in HCW were proposed based on the experimental results.

Prohexadione calcium (Pro-Ca), as a growth retardant, can effectively alleviate the damage of salt stress to plants. In order to explore the effects of NaCl stress on the physiological characteristics and panicle traits of rice plants as well as the alleviating effect of Pro-Ca at the booting stage, we performed pot experiments on two rice cultivars: conventional rice 'Huanghuazhan' and hybrid rice 'Xiangliangyou900'. Rice plants were treated with 0.3% NaCl 48 hours after Pro-Ca (100 mg L-1) treatment to study the effects of Pro-Ca on the physiological characteristics of the leaves and panicles, as well as the panicle and yield traits of rice under salt stress. Our analysis indicated that NaCl treatment inhibited the morphological growth parameters and photosynthetic efficiency, destroyed the antioxidant defense systems of leaves and panicles, increased soluble protein and proline in both rice cultivars. Foliar application of Pro-Ca significantly increased the leaf area, uppermost internode length, panicle length, panicle weight, number of primary branches, number of grains per panicle, seed setting rate and yield under salt stress. Pro-Ca application significantly affected chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), and apparent mesophyll conductance (AMC) in NaCl-treated rice cultivars compared with NaCl treatment alone. Moreover, Pro-Ca also increased ascorbic acid (AsA) content, enhanced superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) activity, and further increased the accumulation of soluble protein and proline in leaves and panicles. These results illustrated that foliar application of Pro-Ca at the booting stage could alleviate the damage caused by NaCl stress by regulating the physiological and metabolic processes of rice plants, thereby enhancing the stress resistance of the plants, increasing total rice yield in salt stress conditions.

The efficacy and safety of self-expanding metallic stent (SEMS) placement as a bridge to elective surgery versus emergency surgery to treat malignant colonic obstruction is debated. This study aimed to evaluate the outcomes of patients with malignant colonic obstruction treated using different procedure. Subjects admitted to the authors' department with colonic obstruction (n = 87) were studied. They underwent colonic stenting as a bridge to elective surgery (SEMS group: n = 14) or emergency surgery (ES group: n = 22).Their demographic characteristics, stoma rate, laparoscopy rate and postoperative complications were analyzed, and the potential risk factors of postoperative complications and the optimal time interval from SEMS implantation to elective surgery were explored. The stoma rate was 15.4% in the SEMS group versus 60.0% in the ES group (P = 0.015), and the postoperative complication rate was 7.7% in the SEMS group versus 40.0% in the ES group (P = 0.042). The proportion of patients undergoing laparoscopy in SEMS group was significantly higher than that in ES group (69.2% vs. 15.0%; P = 0.003).The effect of ASA grade on postoperative complications was statistically significant (OR = 24.565; P = 0.008). The Receiving operating characteristic (ROC) curve could not determine the optimal time interval between SEMS implantation and elective surgery (AUC = 0.466). SEMS implantation has the advantages of lower temporary stoma rate, less postoperative complications and higher laparoscopy rate compared with ES in the treatment of left malignant intestinal obstruction. ASA grade is a risk factor for postoperative complications. However, larger sample size prospective randomized controlled trials (RCT) are still needed to confirm long-term oncological outcomes.

Pear ring rot, a fungal disease caused by Botryosphaeria dothidea (B. dothidea), is one of the most damaging diseases in pear production, affecting fruit yield and causing economic losses. It is not clear whether dopamine, one of the catecholamines, has any role in pear ring rot resistance. In this study, we found that dopamine treatment of B. dothidea resulted in a significant upregulation of PbrTYDC expression compared to H2O treatment (control) and reduced the levels of Hydrogen Peroxide (H2O2) and Superoxide Anion (O2-), increased Peroxidase (POD), Catalase (CAT), Superoxide Dismutase (SOD) and Phenylalanine Ammonia-Lyase (PAL) activities, and induced a significant upregulation of related gene expression. Dopamine treatment promoted the oxidationreduction capacity of the AsA-GSH cycle to scavenge Reactive Oxygen Species (ROS), increased the expression of autophagy-related genes and the accumulation of autophagic structures, and enhanced autophagic activity. Silencing PbrTYDC and PbrATG8 in pear increased H2O2 and ·O2-, decreased POD, CAT and SOD activities and reduced resistance to B. dothidea, which was restored by dopamine treatment. In conclusion, exogenous dopamine enhances resistance to B. dothidea by increasing the antioxidant capacity and autophagic activity of pears, and this study provides new insights for subsequent studies on B. dothidea as well as autophagy.

Severe heat stress can cause human and animal heart failure and sudden death, which is an important issue of public health worldwide. Our previous studies in animals showed that myocardial cells injury was critical in the above process, and Hsp90 induction has a definite anti-myocardial injury effect, especially through aspirin (ASA). But the mechanism has not been fully clarified. In this study, an in vitro heat stress model of chicken primary myocardial cells (CPMCs) most sensitive to heat stress was used to explore the cell injuries and corresponding molecular resistance mechanism. We found that heat stress resulted in serious oxidation stress and calcium overload in mitochondria, which destroyed the mitochondrial structure and function and then triggered the cell death mechanism of CPMCs. Hsp90 was proven to be a central regulator for resisting heat-stress injury in CPMCs mitochondria using its inhibitor and inducer (geldanamycin and ASA), respectively. The mechanism involved that Hsp90 could activate Akt and PKM2 signals to promote Bcl-2 translocation into mitochondria and its phosphorylation, thereby preventing ROS production and subsequent cell apoptosis. In addition, Hsp90 inhibited mitochondrial calcium overload to overcome MPTP opening and MMP suppression through the inhibitory effect of Raf-1-ERK activation on the CREB-IP3R pathway. This study is the first to reveal a pivotal reason for heat-stressed damage in chicken myocardial cells at subcellular level and identify an effective regulator, Hsp90, and its protective mechanism responsible for maintaining mitochondrial homeostasis.

Advanced age, American Society of Anesthesiologists physical status (ASA) classification and the presence of cognitive impairment are associated with an elevated risk of postoperative morbidity and mortality. The visual paired comparison (VPC) task, which relies on recognition of novel images, examines declarative memory. VPC scores have demonstrated the ability to detect mild cognitive impairment and track progression of neurodegenerative disease. Quantitative pupillometry may have similar value. We evaluate for associations between these variables of interest and the feasibility of performing these tests in the preoperative clinic. Prospective data from 199 patients seen in the preoperative clinic at a tertiary academic center were analyzed. A 5 min VPC task (Neurotrack Technologies, Inc, Redwood City, CA) was administered during their scheduled preoperative clinic visit. Pupillary light reflexes were measured at the same visit (PLR-3000™, Neuroptics Corp, Irvine, California).Thirty-four percent of patients were categorized as ASA 2 and 58% as ASA 3. Median age was 57 (IQR: 44-69). Associations were demonstrated between age and ASA physical status (Mann-Whitney U Test, p < 0.0001), maximum pupil size (Spearman Rank Correlation, r = - 0.40, p < 0.0001), and maximum constriction velocity (Spearman Rank Correlation, r = - 0.39, p < 0.0001). Our data also revealed an association between VPC score and age (Spearman Rank Correlation, p = 0.0016, r = - 0.21) but not ASA score (Kruskal-Wallis Test, p = 0.14). When compared to a nonsurgical cohort with no history of memory impairment, our population scored worse on the VPC task (Mann-Whitney U Test, p = 0.0002). A preoperative 5 min VPC task and pupillometry are feasible tests in the preoperative setting and may provide a valuable window into an individual's cognition prior to elective surgery.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are life-threatening multidrug-resistant bacteria. In this study, CR-Kp strains isolated from sewage treatment plants (STPs) (n = 12) were tested for carbapenemase genes (blaKPC, blaNDM, blaIMP, blaVIM and blaOXA-48) and had their sequence types (ST) and clonal complexes (CCs) defined. A collection of clinical CR-Kp strains recovered in local hospitals was added to phylogenetic analyses along with sewage strains in order to infer clonality among CR-Kp strains. A total of 154 CR-Kp strains were isolated from raw sewage [55.8% (86/154)], treated sewage [25.3% (39/154)] and from water body downstream from STPs [18.8% (29/154)]. No CR-Kp strain was isolated from upstream water samples. blaKPC or blaNDM were detected in 143 (92.8%) strains. The occurrence of blaKPC-or-NDM CR-Kp strains was positively associated with the number of hospitalized patients in the areas serviced by STPs. Eleven STs were detected in CR-Kp strains, most of them belonging to the clinically relevant CC11 [ST11 (n = 13-28.2%) and ST340 (n = 7-15.2%)]. CCs 11, 15, 17, 147 and 2703 are shared by clinical and sewage CR-Kp strains. In conclusion, sewage harbors clinically relevant clones of CR-Kp that resist sewage treatments, contaminating water bodies downstream from STPs.