IDH1 and IDH2 are hotspot mutations commonly identified in WHO-grade 4 astrocytomas. Their association with TAMs has never been investigated. We aim to explore the crosstalk between the IDH1/2 ...mutation metabolic effect and TAMs in tumour microenvironment and how this relationship affects the tumour recurrence.
The study included 20 samples of patients with WHO-grade 4 astrocytoma. The alteration hotspot in codon IDH1
and IDH2
was examined using direct sequencing. The protein expression of CD204 on TAM was detected through immunohistochemistry.
IDH1
and IDH2
were symmetrically identified as wildtype in 18/20 tumours (90%) and the remaining 2 tumours (10%) showed synonymous mutations on both codons. Tumours with IDH1/2-wildtype showed high expression of CD204
TAMs in 10 cases and low expression in 8 cases. Typical expression was seen equally in IDH1/2 mutant tumours. There was no significant association between IDH1/2 and CD204
TAM expression (p= 0.999). The association between the two groups was significantly observed among IDH-wildtype tumours (p=0.027). Highly expressed CD204 in IDH-wildtype tumours showed a median recurrence at 10 months compared to low CD204 expression, showed a median recurrence interval at 24 months.
IDH1
or IDH
has the same impact on the classification and prognosis of WHO-grade 4 astrocytoma. There was no crosstalk between IDH1/2 metabolic effect and CD204
TAM. However, IDH-wildtype glioblastomas with dense CD204
TAM are associated with early recurrence. Because the sample size is small, a larger study is recommended to determine the impact of IDH1/2 on TAMs.
The purpose of this study is to evaluate Iraq’s health facility preparedness for the surge of hospitalised cases associated with the ongoing COVID-19 pandemic. In this article, we review pandemic ...preparedness at both general and tertiary hospitals throughout all districts of Iraq. COVID-19 pandemic preparedness, for the purpose of this review, is defined as: (1) staff to patient ratio, (2) personal protective equipment (PPE) to staff ratio, (3) infection control measures training and compliance and (4) laboratory and surveillance capacity. Despite the designation of facilities as COVID-19 referral hospitals, we did not find any increased preparedness with regard to staffing and PPE allocation. COVID-19 designated hospital reported an increased mean number of respiratory therapists as well as sufficient intensive care unit staff, but this did not reach significant levels. Non-COVID-19 facilities tended to have higher mean numbers of registered nurses, cleaning staff and laboratory staff, whereas the COVID-19 facilities were allocated additional N-95 masks (554.54 vs 147.76), gowns (226.72 vs 104.14) and boot coverings (170.48 vs 86.8) per 10 staff, but none of these differences were statistically significant. Though COVID-19 facilities were able to make increased requisitions for PPE supplies, all facility types reported unfulfilled requisitions, which is more likely a reflection of global storage rather than Iraq’s preparedness for the pandemic. Incorporating future pandemic preparedness into health system strengthening efforts across facilities, including supplies, staffing and training acquisition, retention and training, are critical to Iraq’s future success in mitigating the ongoing impact of the ongoing COVID-19 pandemic.
Undoped and cerium (Ce) doped nanocrystalline copper ferrite (CuFe2O4) materials were synthesized via the molten-salt (M-S) method. Effects of Ce doping on the structural, morphological and gas ...sensing properties of the CuFe2O4 ferrite have been investigated. X-ray diffraction (XRD) analysis revealed the formation of spinel CuFe2O4. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigations showed that the synthesized ferrite is made up of very fine spherical nanoparticles. Moreover, the gas sensing properties of sintered samples were studied towards different reducing gases such as liquefied petroleum gas (LPG), acetone, ethanol and ammonia. The sample with 4% cerium doped CuFe2O4 (Ce4) showed the maximum gas sensitivity (86%) towards LPG with fast response time of 5s and good recovery time of 68s.
The upsurge in the Internet of Things (IoT) has led towards an increasing interest in simplifying the control mechanism in the wireless network. The control mechanism is a challenge as it involves ...data acquisition and analysis, decision making, and actuation/control in IoT networks. This has led towards combining Software Defined Networks (SDN) and IoT for easy of controlling the network devices. The mobile application available at the tip of hands to control the connected devices to the internet has led to exponential growth in data. The management and handling the data intensive applications is a challenge to the network operators.
SDN is a paradigm shift that enables network programmability, control, and management of diverse networking devices. This paper describes the data transmission in SDN and integration of SDN and IoT. The light weight protocol Message Queue Telemetry Transport (MQTT) is used for data transmission between the IoT devices. The result analysis shows that the light weight protocol MQTT is 30% efficient for data transmission in SDN IoT architecture. The testbed for integrating virtual network in SDN and real-time network for IoT applications using lightweight protocol is described.
Clonidine is a useful analgesic-sedative agent; however, few data exist regarding its use in infants after congenital heart disease surgery. We thus aimed to assess the absorption and safety of ...enterally administered clonidine in this setting.
Sixteen infants (median age 6.7 months) received a single nasogastric dose of 3 μg kg−1 clonidine 2–6 h after surgery. Blood samples were obtained at seven time intervals (up to 480 min). Plasma concentration profiles were obtained, and then pooled with a previous study (137 samples, 30 infants) for estimation of population pharmacokinetic parameters (NONMEM version 7.2).
Enteral absorption showed considerable inter-individual variability, with clonidine Cmax ranging from 0.15 to 1.55 ng ml−1 (median 0.73), and Tmax from 12 to 478 min (median 190). Although therapeutic sedative plasma concentrations were achieved in 94% of patients, only half had attained this by 70 min post-dose. Patients who did not receive inotropes exhibited a positive association between cumulative morphine dose and Tmax (interaction effect P=0.03); this was not seen among those receiving inotropes. The haemodynamic profile was favourable; few patients required fluid boluses, and this bore no relationship to plasma clonidine concentration. Population pharmacokinetic parameter estimation yielded results similar to previous paediatric studies: clearance 13.7 litre h−1 70 kg−1 and Vd 181 litre 70 kg−1.
Early postoperative enteral clonidine produces favourable haemodynamic profiles and therapeutic plasma concentrations in the majority of cardiac surgical infants; however, the time to achieve this can be erratic. Thus, parenteral administration may be preferable if rapid analgo-sedative effects are needed.
Pro-inflammatory polarization of adipose tissue macrophages (ATMs) plays a critical role in the pathogenesis of obesity-associated chronic inflammation. However, little is known about the role of ...lipids in the regulation of ATMs polarity and inflammation in response to metabolic stress. Deletion of α/β-hydrolase domain-containing 6 (ABHD6), a monoacylglycerol (MAG) hydrolase, has been shown to protect against diet-induced obesity and insulin resistance.
Here we investigated the immunometabolic role of macrophage ABHD6 in response to nutrient excess using whole-body ABHD6-KO mice and human and murine macrophage cell-lines treated with KT203, a selective and potent pharmacological ABHD6 inhibitor.
KO mice on high-fat diet showed lower susceptibility to systemic diet-induced inflammation. Moreover, in the setting of overnutrition, stromal vascular cells from gonadal fat of KO vs. control mice contained lower number of M1 macrophages and exhibited enhanced levels of metabolically activated macrophages (MMe) and M2 markers, oxygen consumption, and interleukin-6 (IL-6) release. Likewise, under in vitro nutri-stress condition, inhibition of ABHD6 in MMe-polarized macrophages attenuated the expression and release of pro-inflammatory cytokines and M1 markers and induced the upregulation of lipid metabolism genes. ABHD6-inhibited MMe macrophages showed elevated levels of peroxisome proliferator-activated receptors (PPARs) and 2-MAG species. Notably, among different MAG species, only 2-MAG treatment led to increased levels of PPAR target genes in MMe macrophages.
Collectively, our findings identify ABHD6 as a key component of pro-inflammatory macrophage activation in response to excess nutrition and implicate an endogenous macrophage lipolysis/ABHD6/2-MAG/PPARs cascade, as a lipid signaling and immunometabolic pathway, which favors the anti-inflammatory polarization of ATMs in obesity.
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•ABHD6 is a determinant of macrophage pro-inflammatory polarization and systemic inflammation during nutri-stress conditions.•ABHD6 contributes to MAG lipolysis in SVF cells from visceral and brown fat depots during obesity.•ABHD6 inhibition promotes a macrophage 2-MAG/PPAR signaling which favors anti-inflammatory polarization of ATMs in obesity.
Raf kinase inhibitory protein (RKIP; also known as PEBP, for phosphatidylethanolamine-binding protein) is an endogenous inhibitor of the Raf- MAPK kinase (MEK)-MAP kinase pathway. It has emerged as a ...significant metastasis suppressor in a variety of human cancers including colorectal cancer (CRC) and was recently shown to regulate the spindle checkpoint in cultured cells. This study aims at correlating RKIP expression with chromosomal instability in colorectal cancer samples and identifies possible mechanisms of RKIP loss.
Chromosomal instability was assessed using metaphase-based comparative genomic hybridisation (CGH) and loss of heterozygosity (LOH) in 65 cases with microsatellite stable CRC and correlated with RKIP expression. Methyl-specific PCR was used on DNA extracted from 82 cases with CRC to determine CpG methylation status at the RKIP promoter and the results correlated with RKIP protein expression.
We demonstrate for the first time that in microsatellite stable (MSS) CRC, the number of chromosomal losses is inversely proportional to RKIP expression levels. We also show that methylation of the RKIP promoter is a major mechanism by which RKIP expression is silenced in CRC.
RKIP loss by hypermethylation of its promoter could have a significant influence on colorectal cancer aneuploidy, which might explain its association with metastatic progression.
Nanocrystalline CoFe2−xCexO4 ferrites (x=0, 0.04, 0.08) were synthesized by using the inexpensive, simple and eco-friendly molten-salt (M-S) method. Effects of Ce doping on the structural, ...morphological and gas sensing properties of the CoFe2O4 ferrite were investigated. X-ray diffraction (XRD) analysis revealed the formation of spinel CoFe2O4. Transmission electron microscopy (TEM) investigations showed that the synthesized ferrite is made up of very fine spherical nanoparticles. Furthermore, the gas response of nanocrystalline ferrite materials was investigated in the temperature range of 200–450°C toward the reducing gases like liquefied petroleum gas (LPG), acetone, ethanol and ammonia. The sensor response was found to be sensitive and selective toward acetone as compared to other reducing gases. It is observed that the addition of Ce (4wt%) strongly influenced the response and the operating temperature of the sensor material and thus can serve as acetone-sensing sensors.
Traffic classification with accuracy is of prime importance in network activities such as security monitoring, traffic engineering, fault detection, accounting of network usage, billing and for ...providing differentiation in Quality of Service (QoS) parameters of the various network services. Network Traffic Classification is significant in recent days due to rapid growth in the number of internet consumers. The different primitive techniques of network traffic classification have failed to provide reliable accuracy because of 1000 fold scaling in the amount of devices as well as flows. To overcome this drawback, the integration of Software Defined Network (SDN) architecture and machine learning technology is proposed in this paper. Three different supervised learning models, namely Support Vector Machine (SVM), nearest centroid and Naïve Bayes (NB), are applied to classify the data traffic based on the applications in a software-defined network platform. The network traffic traces are captured and flows features are generated, which is sent to the classifier for prediction. The accuracy obtained for SVM is 92.3%, NB is 96.79% and the nearest centroid is 91.02%. The challenges faced are in the live network data traffic capture and classification of the applications in the SDN platform.