Memory-like NK cells armed with a neoepitope-specific CAR exhibit potent activity against NPM1 mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) remains a therapeutic challenge, and a paucity of tumor-specific targets has significantly hampered the development of effective immune-based therapies. Recent paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 and IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML NK cells have enhanced antitumor activity and have shown promising results in early phase clinical trials in patients with relapsed/refractory AML. Here, we show that arming CIML NK cells with a neoepitope-specific chimeric antigen receptor (CAR) significantly enhances their antitumor responses to nucleophosphmin-1 (NPM1)-mutated AML while avoiding off-target toxicity. CIML NK cells differentiated from peripheral blood NK cells were efficiently transduced to express a TCR-like CAR that specifically recognizes a neoepitope derived from the cytosolic oncogenic NPM1-mutated protein presented by HLA-A2. These CAR CIML NK cells displayed enhanced activity against NPM1-mutated AML cell lines and patient-derived leukemic blast cells. CAR CIML NK cells persisted in vivo and significantly improved AML outcomes in xenograft models. Single-cell RNA sequencing and mass cytometry analyses identified up-regulation of cell proliferation, protein folding, immune responses, and major metabolic pathways in CAR-transduced CIML NK cells, resulting in tumor-specific, CAR-dependent activation and function in response to AML target cells. Thus, efficient arming of CIML NK cells with an NPM1-mutation-specific TCR-like CAR substantially improves their innate antitumor responses against an otherwise intracellular mutant protein. These preclinical findings justify evaluating this approach in clinical trials in HLA-A2+ AML patients with NPM1c mutations.

CAR T-cell therapy in highly aggressive B-cell lymphoma: emerging biological and clinical insights.

Recently, significant progress has been made in identifying novel therapies, beyond conventional immunochemotherapy strategies, with efficacy in B-cell lymphomas. One such approach involves targeting the CD19 antigen on B cells with autologous-derived chimeric antigen receptor (CAR) cells. This strategy is highly effective in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), as evidenced by recent regulatory approvals. Recent reports suggest that this is an effective strategy for high-grade B-cell lymphoma. The biological underpinnings of these entities and how they overlap with each other and DLBCL continue to be areas of intense investigation. Therefore, as more experience with CAR T-cell approaches is examined, it is interesting to consider how both tumor cell-specific and microenvironmental factors that define these highly aggressive subsets influence susceptibility to this approach.

Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

Predicting concrete strength early age using a combination of machine learning and electromechanical impedance with nano-enhanced sensors.

To ensure the structural integrity of concrete and prevent unanticipated fracturing, real-time monitoring of early-age concrete's strength development is essential, mainly through advanced techniques such as nano-enhanced sensors. The piezoelectric-based electro-mechanical impedance (EMI) method with nano-enhanced sensors is emerging as a practical solution for such monitoring requirements. This study presents a strength estimation method based on Non-Destructive Testing (NDT) Techniques and Long Short-Term Memory (LSTM) and artificial neural networks (ANNs) as hybrid (NDT-LSTMs-ANN), including several types of concrete strength-related agents. Input data includes water-to-cement rate, temperature, curing time, and maturity based on interior temperature, allowing experimentally monitoring the development of concrete strength from the early steps of hydration and casting to the last stages of hardening 28 days after the casting. The study investigated the impact of various factors on concrete strength development, utilizing a cutting-edge approach that combines traditional models with nano-enhanced piezoelectric sensors and NDT-LSTMs-ANN enhanced with nanotechnology. The results demonstrate that the hybrid provides highly accurate concrete strength estimation for construction safety and efficiency. Adopting the piezoelectric-based EMI technique with these advanced sensors offers a viable and effective monitoring solution, presenting a significant leap forward for the construction industry's structural health monitoring practices.

Experimental observation of cavity-free ice-free isochoric vitrification via combined pressure measurements and photon counting x-ray computed tomography.

Isochoric (constant-volume or volumetrically confined) vitrification has shown potential as an alternative cryopreservation-by-vitrification technique, but the complex processes at play within the chamber are yet poorly characterized, and recent investigations have prompted significant debate around whether a truly isochoric vitrification process (in which the liquid remains completely confined by solid boundaries) is indeed feasible. Based on a recent thermomechanical simulation of a high-concentration Me2SO solution, Solanki and Rabin (Cryobiology, 2023, 111, 9-15.) argue that isochoric vitrification is not feasible, because differential thermal contraction of the solution and container will necessarily drive generation of a cavity, corrupting the rigid confinement of the liquid. Here, we provide direct experimental evidence to the contrary, demonstrating cavity-free isochoric vitrification of a ∼3.5M vitrification solution by combined isochoric pressure measurement (IPM) and photon-counting x-ray computed tomography (PC-CT). We hypothesize that the absence of a cavity is due to the minimal thermal contraction of the solution, which we support with additional volumetric analysis of the PC-CT reconstructions. In total, this study provides experimental evidence both demonstrating the feasibility of isochoric vitrification and highlighting the potential of designing vitrification solutions that exhibit minimal thermal contraction.

Exploration of antiproliferative potential of modified triazole-benzohydrazone scaffold: Multitarget approach.

A novel series of triazole-benzohydrazone hybrids was efficiently designed and synthesized as antiproliferative agents, targeting different kinases. All compounds were screened via the National Cancer Institute (NCI) against 60 cancer cell lines, where compounds 16, 17, and 18 exhibited growth inhibition percent (GI%) of various leukemia subpanels with values of 70.33%, 64.13%, and 76.03%, respectively. Compound 18 showed broad-spectrum antiproliferative efficacy toward most cancer cells, with outstanding potency regarding melanoma (MALME-3M GI% = 101.82%) and breast cancer cell lines (MCF7 GI% = 85.87%), while proving safe toward the WI-38 normal cell line, compared to doxorubicin. Multikinase investigation including vascular endothelial growth factor receptor 2 (VEGFR-2), mesenchymal epithelial transition factor (c-Met), proto-oncogene B-Raf, mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, and phosphoinositide 3-kinase was accomplished to reveal its plausible mechanism of action, giving the ultimate potency against both VEGFR-2 and c-Met with IC50 values of 0.055 and 0.042 µM, respectively, while displaying moderate to good inhibition concerning the remaining kinases. DNA binding capability was excluded using the methyl green colorimetric assay. Further, it exhibited both early and late apoptotic induction by about 16- and 9.4-fold over the control, respectively, triggering cell cycle arrest in the G2/M phase. Physicochemical properties and bioavailability radar plot inferred drug-likeness characteristics for compound 18. The molecular docking study assessed the binding pattern with the active sites of c-Met and VEGFR-2.

Allicin and Cancer Hallmarks.

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.

The influence of self-inflating soft tissue expander on the outcomes of horizontal alveolar ridge augmentation: A randomized controlled clinical and histological study.

OBJECTIVE: The present study was conducted to evaluate the effect of soft tissue augmentation using a self-inflating soft tissue expander when performed before horizontal alveolar ridge augmentation on the outcomes of the bone augmentation procedure. The primary outcome is the bucco-palatal radiographical changes in alveolar ridge width, while the secondary outcome is the quality of the augmented bone assessed histomorphometrically. MATERIALS AND METHODS: Sixteen patients underwent horizontal alveolar ridge augmentation using autogenous bone. For the test group, soft tissue expanders were used in a separate surgery before bone grafting surgery. For the control group, patients received treatment including single surgery of bone grafting associated with periosteal releasing incision. Implants were placed in both groups 6 months after bone augmentation. Bucco-palatal changes in alveolar ridge width were evaluated via cone-beam computed tomography. Augmented bone quality was assessed histomorphometrically. RESULTS: After 6 months, regarding radiographic bone width, there was no statistically significant difference between the two groups, as mean bone width in group I and group II were 8.57 mm and 8.75 mm, respectively. Regarding histomorphometric analysis, Group I showed significantly higher mean bone surface area fraction, higher median mature collagen area fraction, and higher median blood vessel count than Group II (p-value = .012), (p-value = .004), and (p-value = .014), respectively. CONCLUSION: Within the limitations of the present study, soft tissue expander has no influence on bone width gain after horizontal alveolar ridge augmentation with an autogenous bone block but may have a positive effect on the quality of augmented bone.

The prevalence of familial vesicoureteric reflux in infants with normal antenatal scans.

AIM: To determine the prevalence of familial vesicoureteric reflux (VUR) by studying the outcomes of screening in a contemporary cohort of newborns with normal antenatal kidney scans. METHODS: A review of screening outcomes in newborns with a first degree relative with VUR, normal antenatal scans and no prior urine infections between 2014-2019 at three maternity units in the North East of England was conducted. Imaging consisted of micturating cystourethrogram (MCUG) in all and renal tract ultrasound scan (RUS) routinely in two units and by clinician preference in one unit. RESULTS: At a median age of 59 days, 265 infants underwent MCUG. High-grade VUR (Grades 3-5) was detected in 13 (4.9%) and low-grade VUR (Grades 1-2) in 24 (9.1%). In the 152 infants who had a RUS, abnormalities were detected in 21 (13.8%). An abnormal postnatal RUS has a low positive predictive value (14.3%) for high-grade VUR, but a normal RUS has a high negative predictive value (95.4%). CONCLUSION: Compared to historical cohorts from two decades ago, the yield from familial VUR screening is low and unjustifiable in the setting of normal antenatal anomaly scans.

The causes and frequency of kidney allograft failure in a low-resource setting: observational data from Iraqi Kurdistan.

BACKGROUND: In the developing world, transplantation is the most common long-term treatment for patients with end-stage renal disease, but rates and causes of graft failure are uncertain. METHODS: This was a retrospective outcomes study of renal transplant patients seen in Iraqi Kurdistan nephrology clinics in the year 2019. In 2019, 871 renal transplant patients were registered and outcomes followed through 12/31/2020. Indicated renal biopsies were obtained on 431 patients at 1 day to 18 years post-transplantation. Outcomes were compared with United States Renal Data System (USRDS) living donor reports. RESULTS: All donors were living. The recipient age was 38.5 ± 13.3 years, 98.2% were < 65 years old, 3.7% had previous transplants, and 2.8% had pretransplant donor-specific antibodies (DSA). Gehan-Breslow estimated failure rates for all-cause, return to HD, and death with functional graft were 6.0, 4.2, and 1.9% at 1 year and 18.1, 13.7, and 5.1% at 5 years post-engraftment (USRDS 2000; 1 year: 7.0, 5.0, 2.6%; 5 year: 22.3, 15.2, 10.6%. USRDS 2010; 1 year: 3.7, 2.4, 1.4%; 5 year: 15.3, 9.6, 7.3%). The median graft survival was 15 years. Acute tubular injury (ATI), infarction, and acute T cell-mediated rejection accounted for 22.2% of graft loss, with > 75% of these failures taking place in the first year. Most graft failures occurred late, at a median post-transplant time of 1125 (interquartile range, 365-2555) days, and consisted of interstitial fibrosis and tubular atrophy (IF/TA) (23.8%), transplant glomerulopathy (13.7%), and acquired active antibody-mediated rejection (12.0%). The significant predictors of graft loss were C4d + biopsies (P < 0.01) and advanced IF/TA (P < 0.001). CONCLUSIONS: Kurdistan transplant patients had graft failure rates similar to living donors reported by the USRDS for the year 2000 but higher than reported for 2010. Compared to USRDS 2010, Kurdistan patients had a moderate excess of HD failures at one and 5 years post-engraftment. Nevertheless, prolonged survival is the norm, with chronic disorders and acquired DSA being the leading causes of graft loss.

Maternal alpha-1-antitrypsin as a noval marker for growth restriction in pre-eclampsia.

AIM: To verify the role of maternal serum levels of alpha-1-antitrypsin (AAT), an acute-phase inflammatory protein, as a marker for distinguishing between fetal growth restriction (FGR) and normal birth weight in pre-eclamptic women. We correlate serum AAT levels to the essential feto-maternal parameters for an earlier and cost-benefit diagnostic method, thus distinguishing between FGR and normal birth weight in pre-eclamptic women. METHODS: An observational study conducted at the University hospital recruited 100 pregnant women in 32/34 weeks of a singleton single tone pregnancy; all were pre-eclampsia cases. All were tested by laboratory and ultrasound examination. Two sets of data were collected; one is maternal parameters such as blood pressure (BP), maternal serum AAT mean platelet volume (MPV), platelet distribution width (PDW), and serum uric acid levels, and the other is fetal parameters such as amniotic fluid index (AFI), fetal weight centile and estimated fetal weight. RESULTS: A strong negative correlation proved between serum levels of AAT and all study variables except fetal weight (systolic BP, diastolic BP, MPV, PDW, serum uric acid, fetal weight percentile, and AFI) with a correlation coefficient of; -0.95, -0.95, -0.85, -0.93, -0.91, -0.94, and -0.93 respectively. The cut-off value for AAT 0.013 mg/ml showed the highest sensitivity and specificity as a diagnostic marker for FGR. Area under the curve was 0.99. CONCLUSIONS: Negative correlations between maternal serum AAT and fetal parameters used to assess FGR were confirmed, suggesting that AAT is closely related to the pathophysiology of FGR among pre-eclamptic patients and may serve as a helpful tool in distinguishing between FGR and normal birth weight babies, pending further validation in feto-maternal outcomes.

Nasogastric versus Orogastric Bolus Tube Feeding in Preterm Infants: Pilot Randomized Clinical Trial.

OBJECTIVE: According to the most recent metanalysis, the best way to establish safe enteral feeding in preterm babies using nasogastric or orogastric tubes is still not well understood. This study aimed to determine the effects of bolus nasal tubes versus bolus orogastric tubes on the time required to reach full enteral feeding in preterm infants, as well as to compare the incidence rates of adverse events including nonintentional removal or displacement of the feeding tube, aspiration pneumonia/pneumonitis, apnea, necrotizing enterocolitis, gastric residual, and growth parameters between the studied cohort of preterm infants. STUDY DESIGN: We conducted an unblinded pilot randomized clinical trial on hemodynamically stable preterm infants (>28 weeks) recruited from level 2 neonatal intensive care unit at Mansoura University Children's Hospital from June 2015 to May 2017. RESULTS: Our study included 98 stable preterm infants with mean gestational age (orogastric group: 33.27 ± 1.08, nasogastric group: 33.32 ± 1.57) and mean birthweight (orogastric group: 1,753.3 ± 414.51, nasogastric group: 1,859.6 ± 307.05). Preterm infants who were fed via bolus nasogastric tube achieved full enteral feeding in a significantly shorter duration compared with the infants fed via bolus orogastric tube. The incidence rates of aspiration and feeding tube displacement were significantly higher in the bolus orogastric tube group compared with the bolus nasogastric tube group. There was no difference in the incidence rates of apnea, necrotizing enterocolitis, bradycardia, oxygen desaturation, and gastric residual in both groups. CONCLUSION: Preterm infants without any respiratory support receiving bolus nasogastric tube feeding achieved full enteral feeding significantly sooner than those receiving bolus orogastric tube feeding. Additionally, bolus nasogastric tube feeding had a lower incidence of aspiration, tube displacement, and the infants regained birthweight more quickly than those receiving orogastric tube feeding. KEY POINTS: · Preterm babies achieve full entral feeds sooner by nasogastric tubes than orogastric tubes.. · Incidence of nasogastric tube displacement and aspiration is less than orogastric tube.. · Infants on nasogastric tubes feeding regain birth weight quicker than those fed by orogastric tubes..

Child with prolonged leg pain and bruising.

A 12-year-old boy was admitted to the paediatric ward with a 4-month history of worsening pain and bruising to his legs, which had resulted in a progressive reduction in his mobility. He initially had had difficulty weight bearing, which had then progressed further making him wheelchair bound. On examination, there was extensive bruising (figure 1) to his oedematous legs, worse on his right leg compared with his left. His background of autism and 15q13.3 deletion, along with maternal learning difficulties, made deciphering a clear history difficult. However, there was no account of trauma, and he had been afebrile throughout his illness. He had though lost 6 kg in weight but remained clinically stable. He was admitted to the ward for further assessment.

Vitamin C and IL-6 in women with preterm premature rupture of membranes compared to normal pregnant women - a case-control study.

OBJECTIVE: The study assessed the relationship of plasma ascorbic acid (vitamin C) level and IL-6 with preterm premature rupture of membranes (PPROM) in pregnant women. METHODS: A case-control study was carried out in University Hospital, Baghdad from July 2019 to July 2020. Two groups of pregnant women with a gestational age between 28-36+6 weeks were included. There were 50 PPROM cases, and 50 healthy controls showing uncomplicated pregnancy and intact amniotic membrane. Both groups matched with their body mass index and gestational age. Plasma vitamin C and interleukin-6 (IL-6) were assessed at the time of admission and 48 hours later in the study group while it was measured at the onset of labour in healthy controls. In addition, the culture and sensitivity of the placental membranes after delivery were assessed in both groups. RESULTS: The mean serum vitamin C value was 2.016±0.15 mg/dl in the PPROM group while it was 5.04±0.22 mg/dl for controls at the time of enrollment. Therefore, women with low vitamin C levels were at a higher risk to have PPROM. The plasma IL-6 mean values were higher in the PPROM group versus healthy controls (18.88±0.31pg/ml vs 5.99±0.12 pg/ml ), P <0.0001. CONCLUSIONS: This study highlighted the ability of vitamin C deficiency with the elevated level of IL-6 in pregnant women in the third trimester to predict preterm premature rupture of the membrane.

Hyperemesis gravidarum and risks of placental dysfunction disorders.

OBJECTIVE: To investigate the association between hospitalisation of cases affected during the first and second trimester of pregnancy with the increased intrapartum complication attributed to placental dysfunction disorders. Additionally to highlight the distinct maternal factors and foetal morbidity patterns for improving the obstetrical outcome. METHODS: An observational study was carried out in Al-Yarmouk Hospital, Baghdad, Iraq from the 1st December 2019 to end December, 2020, recruiting 250 singleton pregnancy of gestational age >10 to >21 completed weeks until delivery. Patients were grouped into two; taking gestational age on admission as a divider; group1 < 10 weeks and group 2 > 12 weeks till completed 21weeks. Participants had at least one hospitalisation for this diagnosis. After a detailed history and examination and recording associated maternal morbidities, including hypertension, hyperthyroidism and diabetes; furthermore, we excluded intrapartum complications as Prematurity, abnormality in foetal weight including stillbirth and preeclampsia risk. RESULTS: None of the demographic criteria nor maternal morbidity factors were significant on analyses. Conversely, all intrapartum complications were significantly higher in both recruited groups. CONCLUSIONS: The strong relationship between hyperemesis gravidarum and placental dysfunction related complications highlight admitted HG cases as a higher risk group; being liable for severe foetomaternal morbidities, demanding more surveillance for a better outcome.

Increased serum amyloid A and C- Reactive Protein in preterm labour women: A case control study.

OBJECTIVE: To assess the possible relation between serum Amyloid A and pregnant women presenting with preterm births. METHOD: The retrospective case-control study was conducted at Al-Yarmouk Teaching Hospital, Baghdad, Iraq, and comprised data from December 1, 2019, to December 1, 2020, of patients who presented with preterm labour with gestational age 28-37 weeks. Data of similar women with complication-free pregnancy was taken to raise the control group. Serum samples were taken from the subjects at admission before any intervention for the measurement of serum amyloid A, total white blood cells, C-reactive protein, and neutrophil-leukocytes ratio. Data was analysed using SPSS 25. RESULTS: Of the 100 subjects, 50(50%) were in each of the two groups that had no significant differences regarding age, gravida, parity, smoking, and neutrophil-leukocytes ratio (p>0.05). There were significant inter-group differences regarding serum amyloid A and C-reactive protein levels (p<0.05). The cut-off value for serum amyloid A level was 84.61ng/ml. There was a positive correlation between micro-C-reactive protein and serum amyloid A (p<0.05). CONCLUSIONS: Maternal serum amyloid A level in the 2nd trimester may be a predictive marker for preterm labour.

COMPARISON OF THE EFFECT OF DEXAMETHASONE ON THE BLOOD GLUCOSE LEVEL IN PREGNANT AND NON-PREGNANT WOMEN UNDER GENERAL ANESTHESIA.

OBJECTIVE: The aim: To compared blood glucose concentrations after intravenous injection of dexamethasone in the pregnant and non-pregnant women under general anesthesia. PATIENTS AND METHODS: Materials and methods: Eighty patients aged 18-50 years took part in the study (ASA class 1 and 2). Forty of patients were undergoing elective cesarean section under G/A and the other forty undergoing elective laparoscopic Cholecystectomy under G/A. Anesthesia was induced using IV anesthetic drugs (0.5mg/kg ketamine, sleeping dose of propofol up to 2mg/kg, muscle relaxant was 0.6 mg/kg rocuronium and maintained with isoflurane). All of patients have been injected with 0,1mg/kg dexamethasone intravenously, at induction of anesthesia, Blood glucose concentrations were measured at induction and then in 60min, 180min and in 360 min after injection of dexamethasone and results were compared between the groups; IV fluid added was normal saline (0.9%) during the study. RESULTS: Results: Regarding to blood glucose levels, we noticed that its level significantly increased over time and peaked in 180min after dexamethasone injection in both groups. The difference percentage between the lower reading (pre injection) and the upper reading (in 180min after) was 33.5% in pregnant woman and 46.2%for non-pregnant women, this difference was statistically significant relative to the pre injection, as this difference was lower in the pregnant women. In 360min after blood glucose level began to drop in both groups. After giving 0.1 mg/kg of dexamethasone, blood glucose level increased in both groups, but it was lower in pregnant women.

Interleukin-18 up-regulates amino acid transporters and facilitates amino acid-induced mTORC1 activation in natural killer cells.

Upon inflammation, natural killer (NK) cells undergo metabolic changes to support their high energy demand for effector function and proliferation. The metabolic changes are usually accompanied by an increase in the expression of nutrient transporters, leading to increased nutrient uptake. Among various cytokines inducing NK cell proliferation, the mechanisms underlying the effect of interleukin (IL)-18 in promoting NK cell proliferation are not completely understood. Here, we demonstrate that IL-18 is a potent cytokine that can enhance the expression of the nutrient transporter CD98/LAT1 for amino acids independently of the mTORC1 pathway and thereby induce a dramatic metabolic change associated with increased proliferation of NK cells. Notably, treatment of IL-18-stimulated NK cells with leucine activates the metabolic sensor mTORC1, indicating that the high expression of amino acid transporters induces amino acid-driven mTORC1 activation. Inhibition of the amino acid transporter CD98/LAT1 abrogated the leucine-driven mTORC1 activation and reduced NK cell effector function. Taken together, our study identified a novel role of IL-18 in up-regulating nutrient transporters on NK cells and thereby inducing metabolic changes, including the mTORC1 activation by amino acids.