Investigating causes and risk factors of pre-chemotherapy viremia in acute lymphoblastic leukemia pediatric patients.

BACKGROUND: Leukemia patients are immune-compromised even before starting chemotherapy because the malignant cells invade the bone marrow and destroy WBC precursors. Leukemic patients are more susceptible to infection by a wide range of microorganisms. Viral infections and reactivations are common and may result in severe complications. The aim of this study is to investigate different causes of viremia in ALL pediatric patients as well as the clinical and the laboratory characteristics associated with viral infections. METHODS: Qualitative real-time PCR was used to detect (polyoma BK, parvo B19 and herpes simplex virus) DNA in the blood of ALL patients and routine hospital records were used to provide the data of hepatitis B & C virus infection. RESULTS: Polyoma BK was the most common detected virus (51.2%) followed by herpes simplex (30.2%). Viremia by single virus was found in 16 (37.2%) cases, while viremia by multiple viruses was found in 15 (34.8%) cases. The most frequent co-detected viruses were herpes simplex and polyoma BK (11.6%) followed by herpes simplex, parvo B19 and polyoma BK (9.3%). CONCLUSION: There is a high frequency of viremia by single virus and viremia by multiple viruses at the time of diagnosis of acute lymphoblastic leukemia in pediatric patients admitted to South Egypt Cancer Institute (SECI) compared to studies in other regions. Polyoma BK is the most common detected virus and is mainly associated with lymphopenia. It was also significantly associated with herpes simplex viremia. HCV infection was associated with increased incidence of CNS leukemia.

Endothelial dysfunction in children with newly diagnosed Graves' disease.

The most frequent cause of hyperthyroidism in children is Graves' disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries' intima-media thickness and the brachial artery's FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32-5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45-3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16-2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18-8.23, P = 0.001).  Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible. What is Known: • Graves' disease is the most common cause of hyperthyroidism in children. • vWF is a reliable marker for detection of vascular endothelial dysfunction. What is New: • Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level. • Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.

Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

BACKGROUND/AIMS: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. METHODS: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. RESULTS: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). CONCLUSION: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

On-Channel Integrated Optofluidic Pressure Sensor with Optically Boosted Sensitivity.

A novel optofluidic sensor that measures the local pressure of the fluid inside a microfluidic channel is presented. It can be integrated directly on-channel and requires no additional layers in fabrication. The detection can be accomplished at a single wavelength; and thereby, only a single laser diode and a single photodetector are required. This renders the sensor to be compact, cheap and easy to fabricate. Basically, the sensor consisted of a Fabry⁻Pérot microresonator enclosing the fluidic channel. A novel structure of the Fabry⁻Pérot was employed to achieve high-quality factor, that was essential to facilitate the single wavelength detection. The enhanced performance was attributed to the curved mirrors and cylindrical lenses used to avoid light diffraction loss. The presented sensor was fabricated and tested with deionized water liquid and shown to exhibit a sensitivity up to 12.46 dBm/bar, and a detection limit of 8.2 mbar. Numerical simulations are also presented to evaluate the mechanical⁻fluidic performance of the device.

Analysis of Fabry-Perot optical micro-cavities based on coating-free all-silicon cylindrical Bragg reflectors.

We study the behavior of Fabry-Perot micro-optical resonators based on cylindrical reflectors, optionally combined with cylindrical lenses. The core of the resonator architecture incorporates coating-free, all-silicon, Bragg reflectors of cylindrical shape. The combined effect of high reflectance and light confinement produced by the reflectors curvature allows substantial reduction of the energy loss. The proposed resonator uses curved Bragg reflectors consisting of a stack of silicon-air wall pairs constructed by micromachining. Quality factor Q ~1000 was achieved on rather large cavity length L = 210 microns, which is mainly intended to lab-on-chip analytical experiments, where enough space is required to introduce the analyte inside the resonator. We report on the behavioral analysis of such resonators through analytical modeling along with numerical simulations supported by experimental results. We demonstrate selective excitation of pure longitudinal modes, taking advantage of a proper control of mode matching involved in the process of coupling light from an optical fiber to the resonator. For the sake of comparison, insight on the behavior of Fabry-Perot cavity incorporating a Fiber-Rod-Lens is confirmed by similar numerical simulations.

Design and Modeling of Fiber-Free Optical MEMS Accelerometer Enabling 3D Measurements.

Optical accelerometers are popular in some applications because of their better immunity to electromagnetic interference, and they are often more sensitive than other accelerometer types. Optical fibers were employed in most previous generations, making micro-fabrication problematic. The optical accelerometers that are suitable for mass manufacture and previously mentioned in the literature have various problems and are only sensitive in one direction (1D). This study presents a novel optical accelerometer that provides 3D measurements while maintaining simple hybrid fabrication compatible with mass production. The operating concept is based on a power change method that allows for measurements without the need for complex digital signal processing (DSP). Springs hold the proof mass between a light-emitting diode and a quadrant photo-detector, allowing the proof mass to move along three axes. Depending on the magnitude and direction of the acceleration affecting the system, the proof mass moves by a certain amount in the corresponding axis, causing some quadrants of the quadrant detector to receive more light than other quadrants. This article covers the design, implementation, mechanical simulation, and optical modeling of the accelerometer. Several designs have been presented and compared. The best simulated mechanical sensitivity reaches 3.7 µm/G, while the calculated overall sensitivity and resolution of the chosen accelerometer is up to 156 µA/G and 56.2 µG, respectively.

Electrostatically Tuned Optical Filters Based on Hybrid Plasmonic-Dielectric Thin Films for Hyperspectral Imaging.

Hyperspectral imaging has a wide range of uses, from medical diagnostics to crop monitoring; however, conventional hyperspectral imaging systems are relatively slow, bulky, and rather costly. In this paper, we present an inexpensive, compact tunable optical filter for hyperspectral applications. The filter is based on a Fabry-Pérot interferometer utilizing hybrid metallic-dielectric mirrors and actuated using a MEMS electrostatic actuator. The optical filter is designed using the transfer matrix method; then, the results were verified by an electromagnetic wave simulator. The actuator is based on a ring-shaped parallel plate capacitor and is designed using COMSOL Multiphysics. An actuation displacement of 170 nm was used, which is the required distance to tune the filter over the whole visible range (400-700 nm). There are two designs proposed for the optical filter: the first was optimized to provide maximum transmission and the other is optimized to have minimum full-width-half-maximum (FWHM) value. The first design has a maximum transmission percentage of 94.45% and a minimum transmission of 86.34%; while the minimum FWHM design had an average FWHM value of 7.267 nm. The results showed improvements over the current commercial filters both in transmission and in bandwidth.

Apolipoprotein M Gene Polymorphism Rs805297 (C-1065A): Association With Type 2 Diabetes Mellitus and Related Microvascular Complications in South Egypt.

BACKGROUND: Apolipoprotein M (ApoM) may have a role in the susceptibility of type 2 diabetes mellitus (T2DM). Polymorphisms in the promoter region of the ApoM gene were found to be significantly associated with diabetes. The aim of this study was to investigate the association of ApoM SNP rs805297 (C-1065A) with the susceptibility of T2DM and related microvascular complications in South Egypt. METHODS: We conducted a case-control study of 60 T2DM patients and 60 healthy control subjects. Lipid profile, fasting, and 2 hours postprandial glucose and creatinine levels were estimated. Patients were subjected to general and Fundus examinations, and screening for nephropathy by urinary albumin levels. ApoM level was assayed by ELISA. Genotyping of the human ApoM gene polymorphism SNP rs805297 (C-1065A) was done by PCR-restriction fragment length polymorphism followed by sequencing to confirm the polymorphism results. RESULTS: ApoM was not different between T2DM and the control group (p=0.075) and was negatively correlated with LDL-c (p=0.029). There were significant differences in ApoM genotypes (p=0.001) and allele frequencies (p=0.019) between T2DM and the control group. A significant reduction in FBG, 2hPPG, and HbA1c levels in the heterozygous than the wild genotype in the group with diabetes with no difference in other lab parameters and microvascular complications. The C-allele is associated with lower blood glucose levels and retinopathy. The wild (CC) genotype is considered as a risk factor for developing T2DM in South Egyptians but not CA+AA genotypes. CONCLUSIONS: In South Egyptians the ApoM polymorphism rs805297 (C-1065A) wild type (CC) was associated with T2DM susceptibility and may have a role in controlling hyperglycemia in these patients. The A-allele is associated with hyperglycemia and diabetic retinopathy.

Efficacy of adipose-derived stromal vascular fraction cells in the management of chronic ulcers: a randomized clinical trial.

Background: Cell therapy is a promising method for improving healing in chronic ulcers through delivery of isolated adipose-derived stromal vascular fraction. Objectives: This study investigates the autologous stem cell yield of adipose tissue and its efficacy in chronic ulcers compared with conventional methods. Methods: This study was a randomized controlled trial. After the study design and protocol were established and ethical committee approval was obtained, we enrolled 100 patients divided into study and control groups. In the study group, we performed debridement and autologous stem cell injection every 3 weeks. The control group was treated with debridement and conventional dressing. Assessments included clinical and histological parameters. Results: The study group showed improved healing. Conclusion: Using autologous adipose-derived stromal vascular fraction cells is an effective treatment method for chronic ulcers. This study was registered on the Pan-African Clinical Trial Registry and the number of the registry was PACTR201709002519185.

Association of lipid peroxidation and interleukin-6 with carotid atherosclerosis in type 2 diabetes.

Enhanced lipid peroxidation and elevated interleukin-6 levels are common in type 2 diabetes mellitus patients. Atherosclerotic vascular complications greatly contribute to morbidity and mortality in diabetes. The aim of this study was to assess the relation of lipid peroxidation and interleukin-6 with carotid atherosclerosis in type 2 diabetes mellitus. METHODS: This cross-sectional study included 90 type 2 diabetes mellitus male patients with age ≥ 40 years and 30 healthy male subjects matched for age. All of them were subjected to measuring of 8-iso prostaglandin F2α as a marker of lipid peroxidation, interleukin-6 and carotid intima media thickness as a marker of carotid atherosclerosis. RESULTS: Both 8-iso prostaglandin F2α and interleukin-6 were found to have significant positive correlation with carotid intima media thickness (P < 0.001) and both were found to be significant predictors of the presence of subclinical carotid atherosclerosis in multiple regression analysis. CONCLUSION: Lipid peroxidation and interleukin-6 may play an important role in atherogenesis in type 2 diabetes mellitus and limiting their effects may reduce atherosclerotic vascular complications in type 2 diabetes mellitus.

Association of fasting glucagon-like peptide-1 with oxidative stress and subclinical atherosclerosis in type 2 diabetes.

AIM: Glucagon-like peptide-1(GLP-1) is a gut hormone that beside its main function in glucose homeostasis may play a role as an anti-oxidant and anti-atherosclerotic factor. The aim of this study was to estimate fasting total GLP-1 level in type 2 diabetes (T2DM) patients and to determine its relation with oxidative stress and atherosclerotic vascular changes. METHODS: The study included 60 T2DM male patients with age ≥40 and 30 healthy male subjects matched for age. All of them were subjected to measuring of fasting total GLP-1, 8-iso prostaglandin F2α (8-iso PGF2α) as a marker of oxidative stress and carotid intima media thickness (CIMT) as a marker of subclinical atherosclerosis. RESULTS: Fasting total GLP-1 was not significantly different in diabetics in comparison with healthy subjects (p = 0.52). Fasting total GLP-1 was found to have significant negative correlations with both 8-iso PGF2α (p < 0.05) and CIMT (p < 0.001). CONCLUSION: Endogenous fasting GLP-1 appears to have anti-oxidant and anti-atherosclerotic effects in T2DM.

Matrix Metalloproteinase-2 Single Nucleotide Polymorphism in Egyptian Non-Hodgkin Lymphoma Patients: Correlation with Clinicopathological Characteristics and Outcome.

Non-Hodgkin's lymphoma (NHL) is an exceedingly diversified group of lymphoproliferative neoplasms emerging from B-, T- or natural killer -lymphocytes. This study was done to detect Matrix metalloproteinase-2 (MMP2)-735C/T gene polymorphism in patients with NHL and its relation to the clinicopathological characteristics of the studied patients in addition to detection the association between it and NHL disease susceptibility and progression. Clinico-hematological profiles were done on 50 NHL patients. The genotypes and allelic frequencies of MMP-2 polymorphisms were recognized utilizing Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). PCR products after adding restriction endonuclease were analyzed using QIAxcel advanced (automated) instrument. The CT + TT genotypes and T allele of MMP2 735C/T were statistically significant in patients having advanced clinical stages III/IV compared to patients with stages I/II. Another significance was observed in patients with intermediate high/high IPI score and BM infiltration. Interestingly, patients with MMP2-735C/T genotype exhibit lower rate of survival. Our results demonstrated that MMP2-735C/T polymorphism may potentially affect the progression of NHL. Further larger scale studies are needed.

High-Q Fabry⁻Pérot Micro-Cavities for High-Sensitivity Volume Refractometry.

This work reports a novel structure for a Fabry⁻Pérot micro cavity that combines the highest reported quality factor for an on-chip Fabry⁻Pérot resonator that exceeds 9800, and a very high sensitivity for an on-chip volume refractometer based on a Fabry⁻Pérot cavity that is about 1000 nm/refractive index unit (RIU). The structure consists of two cylindrical Bragg micromirrors that achieve confinement of the Gaussian beam in the plan parallel to the chip substrate, while for the perpendicular plan, external fiber rod lenses (FRLs) are placed in the optical path of the input and the output of the cavity. This novel structure overcomes number of the drawbacks presented in previous designs. The analyte is passed between the mirrors, enabling its detection from the resonance peak wavelengths of the transmission spectra. Mixtures of ethanol and deionized (DI)-water with different ratios are used as analytes with different refractive indices to exploit the device as a micro-opto-fluidic refractometer. The design criteria are detailed and the modeling is based on Gaussian-optics equations, which depicts a scenario closer to reality than the usually used ray-optics modeling.

Optofluidic Fabry-Pérot Micro-Cavities Comprising Curved Surfaces for Homogeneous Liquid Refractometry-Design, Simulation, and Experimental Performance Assessment.

In the scope of miniaturized optical sensors for liquid refractometry, this work details the design, numerical simulation, and experimental characterization of a Fabry-Pérot resonator consisting of two deeply-etched silicon cylindrical mirrors with a micro-tube in between holding the liquid analyte under study. The curved surfaces of the tube and the cylindrical mirrors provide three-dimensional light confinement and enable achieving stability for the cavity illuminated by a Gaussian beam input. The resonant optofluidic cavity attains a high-quality factor (Q)-over 2800-which is necessary for a sensitive refractometer, not only by providing a sharp interference spectrum peak that enables accurate tracing of the peak wavelengths shifts, but also by providing steep side peaks, which enables detection of refractive index changes by power level variations when operating at a fixed wavelength. The latter method can achieve refractometry without the need for spectroscopy tools, provided certain criteria explained in the details are met. By experimentally measuring mixtures of acetone-toluene with different ratios, refractive index variations of 0.0005 < Δn < 0.0022 could be detected, with sensitivity as high as 5500 µW/RIU.

p-Stat3 and bcr/abl gene expression in chronic myeloid leukemia and their relation to imatinib therapy.

Flowcytometry analysis was carried out to evaluate the expression of the p-Stat3 in 50 CML patients and 20 age-matched healthy controls. p-Stat3 expression was increased in advanced stages of CML. Imatinib treatment was found to suppress the expression of p-Stat3 in bone marrow cells. The level of p-Stat3 was found to be higher in resistant cases than in responsive cases, which suggest the beneficial use of p-Stat3 as an indicator to follow the clinical course and the treatment response.

Optical trapping and binding of particles in an optofluidic stable Fabry-Pérot resonator with single-sided injection.

In this article, microparticles are manipulated inside an optofluidic Fabry-Pérot cylindrical cavity embedding a fluidic capillary tube, taking advantage of field enhancement and multiple reflections within the optically-resonant cavity. This enables trapping of suspended particles with single-side injection of light and with low optical power. A Hermite-Gaussian standing wave is developed inside the cavity, forming trapping spots at the locations of the electromagnetic field maxima with a strong intensity gradient. The particles get arranged in a pattern related to the mechanism affecting them: either optical trapping or optical binding. This is proven to eventually translate into either an axial one dimensional (1D) particle array or a cluster of particles. Numerical simulations are performed to model the field distributions inside the cavity allowing a behavioral understanding of the phenomena involved in each case.

On the free-space Gaussian beam coupling to droplet optical resonators.

In this paper, light coupling into droplet optical resonators by means of a free-space Gaussian beam (GB) is investigated through numerical simulations and experiments. This method is introduced as an alternative to previously reported methods based on coupling through tapered fibers or prisms. Though applicable to solid-state optical resonators, this method is investigated here in the context of optofluidics for preserving the integrity of the droplet shape and for facilitating the steps of alignment and light coupling. The glycerol droplet under study is supported by a super-hydrophobic surface, which consists of Teflon-coated nanostructured silicon, to provide the advantage of keeping the droplet at a specific location, while maintaining a nearly spherical shape. The effectiveness of this method is tested with millimeter-sized droplets through measurements of their spectral responses. Quality factors Q in excess of 6 × 10(3) have been recorded. An analytical model for the external quality factor associated with this coupling technique has been derived, and the effect of the coupling parameters is demonstrated, allowing discussion about the scaling effects.