A Comparative Study of Narrow/Ultra-Wideband Microwave Sensors for the Continuous Monitoring of Vital Signs and Lung Water Level.

This article presents an in-depth investigation of wearable microwave antenna sensors (MASs) used for vital sign detection (VSD) and lung water level (LWL) monitoring. The study looked at two different types of MASs, narrowband (NB) and ultra-wideband (UWB), to decide which one was better. Unlike recent wearable respiratory sensors, these antennas are simple in design, low-profile, and affordable. The narrowband sensor employs an offset-feed microstrip transmission line, which has a bandwidth of 240 MHz at -10 dB reflection coefficient for the textile substrate. The UWB microwave sensor uses a CPW-fed line to excite an unbalanced U-shaped radiator, offering an extended simulated operating bandwidth from 1.5 to 10 GHz with impedance matching ≤-10 dB. Both types of microwave sensors are designed on a flexible RO 3003 substrate and textile conductive fabric attached to a cotton substrate. The specific absorption rate (SAR) of the sensors is measured at different resonant frequencies on 1 g and 10 g of tissue, according to the IEEE C95.3 standard, and both sensors meet the standard limit of 1.6 W/kg and 2 W/kg, respectively. A simple peak-detection algorithm is used to demonstrate high accuracy in the detection of respiration, heartbeat, and lung water content. Based on the experimental results on a child and an adult volunteer, it can be concluded that UWB MASs offer superior performance when compared to NB sensors.

Therapeutic enhancing potential of piracetam with diethylstilbestrol in prevention of grand-mal seizures in rats: inhibition of PI3K/Akt/mTOR signaling pathway and IL-1ß, IL-6, TNF-α cytokines levels.

OBJECTIVE: Epilepsy, a neurodegenerative disorder, continues to throw challenges in the therapeutic management. The current study sought to ascertain if the therapeutic interactions between piracetam and diethylstilbestrol may prevent grand-mal seizures in rats. MATERIALS AND METHODS: Piracetam (PIR; 10 and 20 mg/kg) and diethylstilbestrol (DES; 10 and 20 mg/kg) alone as a low-dose combination were administered to rats for 14 days. The electroshock (MES; 180 mA, 220 V for 0.20 s) was delivered via auricular electrodes on the last day of treatment and rats were monitored for convulsive behavior. To elucidate the mechanism, hippocampal mechanistic target of rapamycin (mTOR) and interleukin (IL)-1ß, IL-6 and tumor necrotic factor-alpha (TNF-α) levels were quantified. Hippocampal histopathology was conducted to study the neuroprotective effect of drug/s. In vitro studies and in silico studies were conducted in parallel. RESULTS: To our surprise, the low dose of the combination regimen of PIR (10 mg/kg) and DES (10 mg/kg) unfolded synergistic anti-seizure potential, with brimming neuroprotective properties. The mechanism could be related to a significant reduction in the levels of hippocampal mTOR and proinflammatory cytokines. The docking scores revealed higher affinities for phosphatidylinositol 3-kinase (PI3K) in co-bound complex, and when docking DES first, while better affinities for protein kinase B (Akt) were revealed when docking PIR first (both drugs bind cooperatively as well). This indicated that the entire PI3K/Akt/mTOR signaling pathway is intercepted by the said combination. In addition, the % of cell viability of HEK-293 cells [pre-exposed to pentylenetetrazol (PTZ)] was increased by 327.29% compared to PTZ-treated cells (toxic control; 85.16%). CONCLUSIONS: We are the first to report the promising efficacy of the combination (PIR 10 mg/kg + DES 10 mg/kg) to restrain seizures and epileptogenic changes induced by electroshock by a novel mechanism involving inhibiting the PI3K/Akt/mTOR signaling.

Insights into targeting SARS-CoV-2: design, synthesis, in silico studies and antiviral evaluation of new dimethylxanthine derivatives.

Aiming to achieve efficient activity against severe acute respiratory syndrome coronavirus (SARS-CoV-2), the expansion of the structure- and ligand-based drug design approaches was adopted, which has been recently reported by our research group. Purine ring is a corner stone in the development of SARS-CoV-2 main protease (Mpro) inhibitors. The privileged purine scaffold was elaborated to achieve additional affinity based on hybridization and fragment-based approaches. Thus, the characteristic pharmacophoric features that are required for the inhibition of Mpro and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 were utilized along with the crystal structure information of both targets. The designed pathways involved rationalized hybridization with large sulfonamide moieties and a carboxamide fragment for the synthesis of ten new dimethylxanthine derivatives. The synthesis was performed under diverse conditions to afford N-alkylated xanthine derivatives, and cyclization afforded tricyclic compounds. Molecular modeling simulations were used to confirm and gain insights into the binding interactions at both targets' active sites. The merit of designed compounds and the in silico studies resulted in the selection of three compounds that were evaluated in vitro to estimate their antiviral activity against SARS-CoV-2 (compounds 5, 9a and 19 with IC50 values of 38.39, 8.86 and 16.01 µM, respectively). Furthermore, oral toxicity of the selected antiviral candidates was predicted, in addition to cytotoxicity investigations. Compound 9a showed IC50 values of 8.06 and 3.22 µM against Mpro and RdRp of SARS-CoV-2, respectively, in addition to promising molecular dynamics stability in both target active sites. The current findings encourage further specificity evaluations of the promising compounds for confirming their specific protein targeting.

Successful Management of Severe Hyperhaemolysis with Combined Tocilizumab and Rituximab in Non-Transfusion-Dependent Thalassaemia: A Case Report.

Introduction: This is the fourth case reporting the administration of tocilizumab to control hyperhaemolysis. It was administered with rituximab to stop hyperhaemolysis refractory to frontline therapy. Hyperhaemolysis is a rare life-threatening subtype of delayed haemolytic transfusion reaction. Refractory cases pose a clinical challenge with no standard of care to date. Case Presentation: A 29-year-old lady with non-transfusion-dependent thalassaemia presented with refractory hyperhaemolysis necessitating the administration of rituximab. This was complicated with anaemic heart failure and altered sensorium exacerbated with further transfusions. A nadir haemoglobin of 2.1 g/dL was reached after the initiation of rituximab, and her condition was too critical to wait for the slow expected improvement. Hence, tocilizumab was given as a bridging therapy to block haemolysis till the delayed onset of radical treatment. Conclusion: Tocilizumab can be effectively combined with rituximab to stop hyperhaemolytic episode refractory to first-line treatment when a prompt response is needed.

Rapid Detection of Coronavirus (COVID-19) Using Microwave Immunosensor Cavity Resonator.

This paper presents a rapid diagnostic device for the detection of the pandemic coronavirus (COVID-19) using a micro-immunosensor cavity resonator. Coronavirus has been declared an international public health crisis, so it is important to design quick diagnostic methods for the detection of infected cases, especially in rural areas, to limit the spread of the virus. Herein, a proof-of-concept is presented for a portable laboratory device for the detection of the SARS-CoV-2 virus using electromagnetic biosensors. This device is a microwave cavity resonator (MCR) composed of a sensor operating at industrial, scientific and medical (ISM) 2.45 GHz inserted in 3D housing. The changes of electrical properties of measured serum samples after passing the sensor surface are presented. The three change parameters of the sensor are resonating frequency value, amplitude and phase of the reflection coefficient |S11|. This immune-sensor offers a portable, rapid and accurate diagnostic method for the SARS-CoV-2 virus, which can enable on-site diagnosis of infection. Medical validation for the device is performed through biostatistical analysis using the ROC (Receiver Operating Characteristic) method. The predictive accuracy of the device is 63.3% and 60.6% for reflection and phase, respectively. The device has advantages of low cost, low size and weight and rapid response. It does need a trained technician to operate it since a software program operates automatically. The device can be used at ports' quarantine units, hospitals, etc.

Applying of SP, DC-Resistivity, DC-TDIP and TDEM soundings in high saline coastal aquifer.

Four surface geophysical techniques were utilized to study the geological and hydrogeological settings of highly saline a coastal aquifer system to the north-east of River Nile Delta, Egypt. These techniques include SP, DC-Resistivity, TDIP and TDEM methods. The first target was to determine the geological stratification as a differentiation among clay, clayey, sand and sandy layers of high saline water. These techniques reflect that there is a complicated lateral and vertical difference in sediments along study area. The surface layers with depth down to ~120 m have low to medium content of clay that change with depth. Then, the second target was the differentiation laterally and vertically for salinity with depth down to ~250m as an interesting hydrogeological setting. These techniques reported that the sediments consist of thin and thick clay and silts, clayey sand, and sandy clay strata. Investigation depth was up to ~210m due to high salinity and clay content effect. At shallow depths, soil texture (down to ~100m and sometimes down to ~160m) consists of clay and silt with sand intercalation. The TEM data indicate a zone of less saline water and low clay content starting from ~40 to ~100m. There may be an evidence for a significant high to medium clay content after these depths down to ~250m. All four methods were calibrated with each other. Accordingly, good matching between the inversion model of TEMSs and composite logs of new drilled well was found, especially in lithological layers identifications. Also, this calibration confirmed that the area was complicated regarding the geological and hydrogeological conditions and the TDIP and TEM are the best methods in studying the environmental, geological and hydrogeological settings as primary important engineering implications for studying coastal highly saline aquifers.

Increase maize productivity and water use efficiency through application of potassium silicate under water stress.

In Egypt, water shortage has become a key limiting factor for agriculture. Water-deficit stress causes different morphological, physiological, and biochemical impacts on plants. Two field experiments were carried out at Etay El-Baroud Station, El-Beheira Governorate, Agriculture Research Center (ARC), Egypt, to evaluate the effect of potassium silicate (K-silicate) of maize productivity and water use efficiency (WUE). A split-plot system in the four replications was used under three irrigation intervals during the 2017 and 2018 seasons. Whereas 10, 15, and 20 days irrigation intervals were allocated in main plots, while the three foliar application treatments of K-silicate (one spray at 40 days after sowing; two sprays at 40 and 60 days; and three sprays at 40, 60, and 80 days, and a control (water spray) were distributed in the subplots. All the treatments were distributed in 4 replicates. The results indicated that irrigation every 15 days gave the highest yield in both components and quality. The highly significant of (WUE) under irrigation every 20 days. Foliar spraying of K-silicate three times resulted in the highest yield. Even under water-deficit stress, irrigation every fifteen days combined with foliar application of K-silicate three times achieved the highest values of grain yield and its components. These results show that K-silicate treatment can increase WUE and produce high grain yield requiring less irrigation.

Targeted next generation sequencing identifies somatic mutations in a cohort of Egyptian breast cancer patients.

Breast cancer (BC) incidence is progressively increasing in Egypt. However, there is insufficient knowledge of the acquired somatic mutations in Egyptian BC patients which limit our understanding of its progression. To the best of our knowledge, this is the first Egyptian cohort to sequence a multiple-gene panel of cancer related genes on BC patients. Four hundred and nine cancer related genes were sequenced in 46 fresh breast tumors of Egyptian BC patients to identify somatic mutations and their frequencies. TP53 and PIK3CA were the most top two frequently mutated genes. We detected 15 different somatic mutations in TP53 and 8 different ones in PIK3CA, each in 27 samples (58.7%). According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in Tp53, 5 in PIK3CA, and single variants of VHL, STK11, AKT1, KRAS, IDH2, PTEN and ERBB2. We also identified 5 variants with uncertain significance (4 in TP53 and 1 in CEBPA) and 4 variants with conflicting interpretations of pathogenicity (2 in TP53 and 1 in each of APC and JAK3). Moreover, one drug response variant (p.P72R) in TP53 was detected in 8 samples. Furthermore, four novel variants were identified in JAK2, MTOR, KIT and EPHB. Further analysis, by Ingenuity Variant Analysis software (IVA), showed that PI3K/AKT signaling is altered in greater than 50% of Egyptian BC patients which implicates PI3K/AKT signaling as a therapeutic target. In this cohort, we shed the light on the most frequently detected somatic mutations and the most altered pathway in Egyptian BC patients.

Encephalitozoon intestinalis: A new target for auranofin in a mice model.

Despite the fact that many approaches have been developed over years to find efficient and well-tolerated therapeutic regimens for microsporidiosis, the effectiveness of current drugs remains doubtful, and effective drugs against specific targets are still scarce. The present study is the first that was designed to evaluate the potency of auranofin, an anti-rheumatoid FDA approved drug, against intestinal Encephalitozoon intestinalis. Evaluation of the drug was achieved through counting of fecal and intestinal spores, studying the intestinal histopathological changes, measuring of intestinal hydrogen peroxide level, and post therapy follow-up of mice for 2 weeks for detection of relapse. Results showed that auranofin has promising anti-microsporidia potential. It showed a promising efficacy in mice experimentally infected with E. intestinalis. It has revealed an obvious reduction in fecal spore shedding and intestinal tissue spore load, amelioration of intestinal tissue pathological changes, and improvement of the local inflammatory infiltration without significant changes in hydrogen peroxide level. Interestingly, auranofin prevented the relapse of infection. Thus, considering the results of the present work, auranofin could be considered a therapeutic alternative for the gold standard drug 'albendazole' against the intestinal E. intestinalis infection especially in relapsing cases.

Prevalence of oro-dental pathology in a working horse population in Egypt and its relation to equine health.

REASONS FOR PERFORMING STUDY: Oro-dental disease can have a significant impact on equine welfare. OBJECTIVES: To determine the prevalence of oro-dental disease and to identify risk factors for oro-dental disorders and poor body condition scores (BCS) in a working horse population in Egypt. STUDY DESIGN: Cross-sectional survey. METHODS: Oro-dental examination was performed on 450 working horses in 2 Egyptian provinces. Horse and management historical data were collected and horses were assigned to no/mild, moderate and severe dental disease categories based on findings on examination. Multivariable logistic regression and generalised additive models were used to identify risk factors for oral mucosal injuries and very poor/poor BCS, and to explore the relationship between age and different oro-dental disorders. RESULTS: Oro-dental disease was common, with 45.3% and 8.4% of horses considered to have moderate and severe oro-dental disease, respectively. None of these horses had previously undergone any form of proper dental examination and treatment by trained personnel. Oral mucosal injuries (64.2%) and sharp enamel points (79.8%) were most common. Oral mucosal injuries were significantly associated with increasing age (odds ratio (OR) 1.1, 95% confidence interval (CI) 1.01-1.1, P = 0.03), focal dental overgrowths (OR 2.4, 95% CI 1.4-4.0, P = 0.002) and sharp enamel points (OR 6.3, 95% CI 3.5-11.0, P<0.001). Very poor and poor BCS were significantly associated with severe dental disease (OR 2.6, 95% CI 1.2-5.8, P = 0.02), horses aged 16-30 years (OR 3.5, 95% CI 1.7-7.0, P = 0.001), height (OR 0.9, 95% CI 0.9-0.97, P = 0.001) and packed cell volume (OR 0.9, 95% CI 0.85-0.95, P<0.001). CONCLUSIONS: There is a need for education of working horse-owners in Egypt about the importance of oro-dental disease and for greater availability of veterinarians with suitable training and equipment to perform dental prophylaxis and treatment. Even simple dental prophylaxis could have a significant impact on the health and welfare of this population of working horses.

Metabolic engineering of Cyanobacteria and microalgae for enhanced production of biofuels and high-value products.

A lot of research has been performed on Cyanobacteria and microalgae with the aim to produce numerous biotechnological products. However, native strains have a few shortcomings, like limitations in cultivation, harvesting and product extraction, which prevents reaching optimal production value at lowest costs. Such limitations require the intervention of genetic engineering to produce strains with superior properties. Promising advancements in the cultivation of Cyanobacteria and microalgae have been achieved by improving photosynthetic efficiency through increasing RuBisCO activity and truncation of light-harvesting antennae. Genetic engineering has also contributed to final product extraction by inducing autolysis and product secretory systems, to enable direct product recovery without going through costly extraction steps. In this review, we summarize the different enzymes and pathways that have been targeted thus far for improving cultivation aspects, harvesting and product extraction in Cyanobacteria and microalgae. With synthetic biology advancements, genetically engineered strains can be generated to resolve demanding process issues and achieve economic practicality. This comprehensive overview of gene modifications will be useful to researchers in the field to employ on their strains to increase their yields and improve the economic feasibility of the production process.

Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013.

We describe a novel spike pseudoparticle neutralisation assay (ppNT) for seroepidemiological studies on Middle East respiratory syndrome coronavirus (MERSCoV) and apply this assay together with conventional microneutralisation (MN) tests to investigate 1,343 human and 625 animal sera. The sera were collected in Egypt as a region adjacent to areas where MERS has been described, and in Hong Kong, China as a control region. Sera from dromedary camels had a high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and 10,240 and higher in ppNT assays. No other investigated species had any antibody reactivity to MERS-CoV. While seropositivity does not exclude the possibility of infection with a closely related virus, our data highlight the need to attempt detection of MERSCoV or related coronaviruses in dromedary camels. The data show excellent correlation between the conventional MN assay and the novel ppNT assay. The newly developed ppNT assay does not require Biosafety Level 3 containment and is thus a relatively high-throughput assay, well suited for large-scale seroepidemiology studies which are needed to better understand the ecology and epidemiology of MERS-CoV.

Do commercial avian influenza H5 vaccines induce cross-reactive antibodies against contemporary H5N1 viruses in Egypt?

After emerging in Egypt in 2006, highly pathogenic avian influenza H5N1 viruses continued to cause outbreaks in Egyptian poultry and sporadic human infections. The strategy used by Egyptian authorities relied on vaccinating poultry, depopulating infected areas, and increasing awareness and biosecurity levels. Despite those efforts, H5N1 became endemic, and vaccine-escape variants are thought to have emerged even though commercial poultry vaccines were protective in laboratory settings. We studied the cross-reactivity of 6 commercially available H5 poultry vaccines against recent H5N1 Egyptian isolates in a field setting in Egypt. Only one vaccine based on an Egyptian H5N1 virus induced high cross-reactive antibody titers. Our results may be explained by the fact that the seed viruses in these vaccines are genetically distinct from H5N1 viruses currently circulating in Egypt. In light of our findings, we recommend that the H5N1 prevention and control strategy in Egypt be updated and reinforced. Special consideration should be given to the vaccination strategy, and the use of vaccines based on currently circulating viruses is advisable.

Infection with a pathogenic turkey coronavirus isolate negatively affects growth performance and intestinal morphology of young turkey poults in Canada.

Turkey coronavirus (TCoV) is an important viral pathogen causing diarrhoea of young turkey poults that is associated with sizeable economic losses for the turkey industry. Using a field isolate that was found to be free from turkey astrovirus and avian reovirus we were able to reproduce the clinical disease associated with TCoV. Clinical signs and weight gain of poults during experimental infections were compared with age-matched, uninfected controls. Poults infected at 2 days of age had 100% morbidity and 10% mortality, and birds infected at 28 days of age showed 75% morbidity and no mortality. Diarrhoea was consistently seen in infected poults at 2 to 3 days post infection (d.p.i.) with a duration of about 3 to 5 days. Mean body weights of birds infected at 2 or 28 days of age were significantly reduced compared with uninfected birds by 7 d.p.i. and remained significantly lower for the duration of the study. At 44 days of age, poults infected at 2 or 28 days of age weighed only 68.1% or 77.7%, respectively, compared with uninfected turkeys of the same age on the same diet, a mean difference in body weights of 683 or 477g, respectively. Infected birds had profound villus atrophy with some compensatory crypt hyperplasia at 5 to 7 d.p.i. Villus heights in the duodenum were significantly reduced at 7 d.p.i. We were able to reproduce enteric disease using only a pathogenic field isolate (MG10) of TCoV that negatively affected growth performance and intestinal morphology of young turkey poults.

Virus shedding and serum antibody responses during experimental turkey coronavirus infections in young turkey poults.

The course of turkey coronavirus (TCoV) infection in young turkey poults was examined using a field isolate (TCoV-MG10) from a diarrhoeal disease outbreak on a commercial turkey farm in Ontario, Canada. Two-day-old and 28-day-old poults were inoculated orally with TCoV-MG10 to examine the effect of age on viral shedding and serum antibody responses to the virus. The presence of coronavirus particles measuring 105.8+/-21.8 nm in the cloacal contents was confirmed using transmission electron microscopy. The pattern of cloacal TCoV shedding was examined by reverse-transcription polymerase chain reaction amplification of the nucleocapsid gene fragment. TCoV serum antibody responses were assessed with two recently developed TCoV enzyme-linked immunosorbent assays that used TCoV nucleocapsid and S1 polypeptides as coating antigens. Poults were found equally susceptible to TCoV infection at 2 days of age and at 4 weeks of age, and turkeys of either age shed virus in their faeces starting as early as 1 day post-inoculation and up to 17 days post-inoculation. Poults infected at 2 days of age were immunologically protected against subsequent challenge at 20 days post-inoculation. The protection was associated with measurable serum antibody responses to both the nucleocapsid and S1 structural proteins of TCoV that were detectable as early as 1 week post-infection.

Complete genomic sequence of turkey coronavirus.

Turkey coronavirus (TCoV), one of the least characterized of all known coronaviruses, was isolated from an outbreak of acute enteritis in young turkeys in Ontario, Canada, and the full-length genomic sequence was determined. The full-length genome was 27,632 nucleotides plus the 3' poly(A) tail. Two open reading frames, ORFs 1a and 1b, resided in the first two thirds of the genome, and nine additional downstream ORFs were identified. A gene for hemagglutinin-esterase was absent in TCoV. The region between the membrane (M) and nucleocapsid (N) protein genes contained three potential small ORFs: ORF-X, a previously uncharacterized ORF with an associated putative TRS within the M gene (apparently shared among all group III coronaviruses), and previously described ORFs 5a and 5b. The TCoV genome is organized as follows: 5' UTR--replicase (ORFs 1a, 1b)--spike (S) protein--ORF3 (ORFs 3a, 3b)--small envelop (E or 3c) protein--membrane (M) protein--ORF5 (ORFs X, 5a, 5b)--nucleocapsid (N) protein--3' UTR--poly(A). TCoV genome structure and sequence was most similar, but distinct from, avian infectious bronchitis virus (IBV). This is the first complete genome sequence for a TCoV and confirms that TCoV belongs to group III coronaviruses.

Tumor grade, microvessel density, and activities of malate dehydrogenase, lactate dehydrogenase, and hexokinase in squamous cell carcinoma.

Squamous cell carcinomas were evaluated with respect to tumor differentiation (through use of hematoxylin and eosin stain), microvessel density (through use of CD-34 immunocytochemical stain), and magnitudes of malate dehydrogenase (MDH), hexokinase, and lactate dehydrogenase (LDH) enzyme activities. Direct correlations were found between tumor grade, MDH activity, and microvessel density. Direct correlations were also found between hexokinase activity and MDH activity and microvessel density. Inverse correlations were found between LDH activity and both tumor grade and MDH activity. These results suggest that the high rate of glucose utilization (indicated by hexokinase activity) found in more poorly differentiated tumors has a higher component of aerobic oxidative metabolism (indicated by MDH activity) and a relatively lower contribution from anaerobic metabolism (indicated by LDH activity) than do the rates found in more differentiated tumors. It is also suggested that as the glycolytic rate increases, more pyruvate goes into the Krebs cycle than into lactate. The availability of glucose-derived pyruvate for oxidative metabolism would mean less of a dependency on glutamine as a carbon source in squamous cell carcinoma.

Effect of high pressure ammoniation procedure on the detoxification of aflatoxins.

Ammoniation represents the best technique to detoxify aflatoxin-contaminated grain and it is considered as economically practicable for commercial applications. In the present studyAspergillus parasiticus was used to contaminate yellow corn to produce the final concentration reached 4000 µg/kg corn total aflatoxin. Two procedures of ammoniation (in aqueous ammonia concentrations, 0.25, 0.5, 1, 1.5 and 2% ) were adopted for aflatoxin destruction. The first procedure was under atmospheric pressure at ambient temperature (AP/AT) for 24 hrs, and the second procedure was under high pressure (2 bar) at high temperature (121°C) (HP/HT ) for 15 min. Aflatoxin concentrations were determined by HPLC using fluorescence detection. The effect of HP/HT procedure was compared with the ammoniation procedure under AP/AT. The detoxification pattern of the two ammoniation procedures as well as the detoxification pattern of the different types of aflatoxins under the two procedures was studied.