A robust classification of acute lymphocytic leukemia-based microscopic images with supervised Hilbert-Huang transform.

Acute lymphocytic leukemia (ALL) is a malignant condition characterized by the development of blast cells in the bone marrow and their quick dissemination into the bloodstream. It primarily affects children and individuals over the age of 60. Manual blood testing, which has been around for a long time, may be slow. The likelihood of recognizing ALL in its early stages was increased by automating the diagnosis. This research developed an improved criterion for classifying ALL microscopic images into two categories: normal images and blast images. First, to save processing time, innovative image preprocessing techniques were employed to gather data for data augmentation, enhancement, and conversion. The K-means clustering technique was also utilized to effectively segment the relevant nuclei from the background. Furthermore, the most salient features were extracted using an empirical mode decomposition (EMD) based on the Hilbert-Huang transform. MATLAB functions such as principal component analysis, gray level co-occurrence matrix, local binary pattern, shape features, discrete cosine transform, discrete Fourier transform, discrete wavelet transform, and independent component analysis have been used and compared with EMD. The Bayesian regularization (BR) method has been implemented in the neural networks (NNs) classifier. Along with NNs, other classifiers such as support vector machine, K-nearest neighbors, random forest, naive Bayes, logistic regression, and decision tree have been used, evaluated, and contrasted with NNs. According to experimental findings, the ALL-IDB2 (Image Database 2) dataset's NNs-based-EMD model classified objects with an accuracy of 98.7%, sensitivity of 99.3%, and specificity of 98.1%. RESEARCH HIGHLIGHTS: Implement a robust method for classifying normal and blast ALL images in the state of the art using the combination of the BR algorithm and the neural networks classifier. Perform robust data processing via data augmentation and conversion from RGB (Red, Green, and Blue) image LAB (Luminosity, A: color space, B: color space) image. Extract the nuclei correctly from the background image using k-means clustering. Extract the most salient features from the segmented images using EMD in the state of the art of HHT.

Qualitative analysis of a Filippov wild-sterile mosquito population model with immigration.

Effectively combating mosquito-borne diseases necessitates innovative strategies beyond traditional methods like insecticide spraying and bed nets. Among these strategies, the sterile insect technique (SIT) emerges as a promising approach. Previous studies have utilized ordinary differential equations to simulate the release of sterile mosquitoes, aiming to reduce or eradicate wild mosquito populations. However, these models assume immediate release, leading to escalated costs. Inspired by this, we propose a non-smooth Filippov model that examines the interaction between wild and sterile mosquitoes. In our model, the release of sterile mosquitoes occurs when the population density of wild mosquitoes surpasses a specified threshold. We incorporate a density-dependent birth rate for wild mosquitoes and consider the impact of immigration. This paper unveils the complex dynamics exhibited by the proposed model, encompassing local sliding bifurcation and the presence of bistability, which entails the coexistence of regular equilibria and pseudo-equilibria, as crucial model parameters, including the threshold value, are varied. Moreover, the system exhibits hysteresis phenomena when manipulating the rate of sterile mosquito release. The existence of three types of limit cycles in the Filippov system is ruled out. Our main findings indicate that reducing the threshold value to an appropriate level can enhance the effectiveness of controlling wild insects. This highlights the economic benefits of employing SIT with a threshold policy control to impede the spread of disease-carrying insects while bolstering economic outcomes.

Fractional modeling of drug diffusion from cylindrical tablets based on Fickian and relaxed approaches with in vivo validation.

Mathematical simulation of drug diffusion is a significant tool for predicting the bio-transport process. Moreover, the reported models in the literature are based on Fick's approach, which leads to an infinite propagation speed. Consequently, it is essential to construct a mathematical model to represent the diffusion processes for estimating drug concentrations at different sites and throughout the circulation. Thus, in this article, the diffusion process is employed to propose three models for estimating the drug release from multi-layer cylindrical tablets. A fractional model is presented based on Fick's approach, while classical and fractional Cattaneo models are presented using the relaxed principle. Various numerical methods are used to solve the specified problem. The numerical scheme's stability and convergence are demonstrated. Drug concentration and mass profiles are presented for the tablet and the external medium and compared with the in vivo plasma profiles. The results show the efficiency and precision of the proposed fractional models based on the fourth-order weighted-shifted Grünwald-Letnikov difference operator approximation. These models are compatible with the in vivo data compared with the classical Fick's one.

Impact of constant light exposure during pregnancy on skin of neonatal New Zealand rabbits: structural and ultrastructural study.

Continuous industrial productivity and modern societies have resulted in excess artificial light. The altered circadian rhythm causes many diseases. During intrauterine life, the mother's maternal melatonin rhythm has a major role in influencing organ development. The aim of this study was to investigate the effect of maternal exposure to constant light on the structure and ultrastructure of neonatal skin. Twenty pregnant New Zealand rabbits were divided into two groups (n=10 each): control group (12-h light/dark) and constant light group (24-h light). Plasma maternal melatonin and corticosterone during pregnancy were determined. At the end of the experiment, the dorsal skin of the neonates of both groups was collected and prepared for histological, morphometric, and transmission electron microscopic study. Histological and morphometric results of skin of neonates from the constant light group revealed statistically significantly reduced epidermal thickness, decreased number of hair follicle, increased surface area of collagen, and decreased proliferating cell nuclear antigen (PCNA) positive cells. Ultrastructural examination showed wide intercellular spaces and disrupted desmosomal junctions in the epidermis. Earlier stages of hair follicles were also observed with indented shrunken nuclei, vacuolization, and swollen mitochondria. Dermal fibroblasts with dilated cisternae of rough endoplasmic reticulum containing electron-dense material were detected. Maternal melatonin was significantly reduced in the constant light group while maternal corticosterone showed no significant difference between groups. Therefore, normal maternal circadian rhythm is a key factor for the integrity of neonatal skin structure.

Impact of constant light exposure during pregnancy on skin of neonatal New Zealand rabbits: structural and ultrastructural study

Continuous industrial productivity and modern societies have resulted in excess artificial light. The altered circadian rhythm causes many diseases. During intrauterine life, the mother's maternal melatonin rhythm has a major role in influencing organ development. The aim of this study was to investigate the effect of maternal exposure to constant light on the structure and ultrastructure of neonatal skin. Twenty pregnant New Zealand rabbits were divided into two groups (n=10 each): control group (12-h light/dark) and constant light group (24-h light). Plasma maternal melatonin and corticosterone during pregnancy were determined. At the end of the experiment, the dorsal skin of the neonates of both groups was collected and prepared for histological, morphometric, and transmission electron microscopic study. Histological and morphometric results of skin of neonates from the constant light group revealed statistically significantly reduced epidermal thickness, decreased number of hair follicle, increased surface area of collagen, and decreased proliferating cell nuclear antigen (PCNA) positive cells. Ultrastructural examination showed wide intercellular spaces and disrupted desmosomal junctions in the epidermis. Earlier stages of hair follicles were also observed with indented shrunken nuclei, vacuolization, and swollen mitochondria. Dermal fibroblasts with dilated cisternae of rough endoplasmic reticulum containing electron-dense material were detected. Maternal melatonin was significantly reduced in the constant light group while maternal corticosterone showed no significant difference between groups. Therefore, normal maternal circadian rhythm is a key factor for the integrity of neonatal skin structure.

The enhancing effects of Biobran/MGN-3, an arabinoxylan rice bran, on healthy old adults' health-related quality of life: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: The world's older population is growing rapidly and the need to find measures to combat age-associated decline of physical, mental, and cognitive functions and improve their health-related quality of life (HRQOL) is escalating. Biobran/MGN-3, an arabinoxylan rice bran, has been previously reported to improve the quality of life in cancer patients. The objective of the current study was to examine the effect of a low dose of Biobran/MGN-3 supplementation on the HRQOL in a healthy older adult population. METHODS: Sixty apparently healthy subjects, 40 males and 20 females, over 56 years old were recruited and blindly randomized into two group receiving either placebo or Biobran/MGN-3 (250 mg/day for 3 months). Participants did not take any vitamins or medications during the study and their health was closely monitored. HRQOL was assessed at the initiation and termination of the study using the previously validated Arabic version of SF-12v2 questionnaire. RESULTS: For all measured HRQOL domains, there was no statistically significant difference in baseline scores between the two groups. Compared to baseline values and placebo-treated subjects, Biobran/MGN-3 supplementation significantly enhanced the levels of physical and mental component summary scores as well as role-physical, bodily pain, vitality, and social functioning subdomain scores. CONCLUSION: These results show that Biobran/MGN-3 is a promising psychoneuroimmune modulatory agent that could improve the HRQOL in healthy old adults.

Angiotensin II type 2 receptor gene polymorphisms and serum angiotensin-converting enzyme level in Egyptian children with systemic lupus erythematosus.

BACKGROUND: There are no reports about the association of angiotensin II type 2 receptor ( AT2R) gene polymorphisms and susceptibility to systemic lupus erythematosus (SLE) in children. OBJECTIVE: The objective of this research is to study AT2R gene polymorphisms in exon 3 (C1593A) and intron 1 (A1675G) in Egyptian children with SLE and its correlation with disease manifestations and serum angiotensin-converting enzyme (ACE) level. METHODS: Typing of AT2R gene polymorphisms was conducted in 123 children with SLE in comparison with 100 healthy controls using the restriction fragment length polymorphism method. RESULTS: Significant differences were found between SLE patients and controls for A-containing genotypes (CA + AA) and A-allele frequencies of AT2R in exon 3 (C1593A) ( p = 0.01, odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.3-5.05; p = 0.01, OR = 2.2, 95% CI = 1.2-4.1, respectively). G-containing genotypes (AG + GG) and G allele of AT2R in intron 1 (A1675G) were more frequent in SLE patients compared to controls ( p = 0.01, OR = 2.3, 95% CI = 1.2-4.5; p = 0.02, OR = 2.1, 95% CI = 1.2-3.7, respectively). Serum ACE level was significantly higher in SLE patients than in controls ( p < 0.001). There was no association between AT2R gene polymorphisms and ACE level in serum. Moreover, there was no association between AT2R gene polymorphisms and SLE clinical manifestations. CONCLUSION: AT2R gene polymorphisms can be considered risk factors for SLE development in Egyptian children.

Distribution and health risk assessment of organochlorine pesticides (OCPs) residue in edible cattle tissues from northeastern part of Egypt: High accumulation level of OCPs in tongue.

Food consumption is an important route of human exposure to organochlorine pesticides (OCPs). In order to assess the potential human health risks associated with OCPs, edible cattle tissues (liver, kidney and tongue) were collected from three slaughter houses in Mansoura, Zagazig and Ismailia cities, Egypt. Levels of 22 OCPs such as hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), aldrin, dieldrin and endrin (Drins), chlordanes (CHLs), heptachlors (HPTs) and hexachlorobenzene (HCB) residues were investigated. Among the investigated OCPs, HCHs represented the most dominant group with high proportions of γ-HCH isomer (53-91% of total HCHs). Mansoura city had the highest OCPs contamination load ranged from 0.1 to 2827 ng g(-1) lw (lipid weight). Surprisingly, tongue samples collected from Mansoura showed the highest concentration of HCHs (448 ng g(-1) lw) in comparison to liver (152 ng g(-1) lw) and kidney (266 ng g(-1) lw). Generally, contamination pattern of OCPs was in the order of HCHs > Drins > CHLs > DDTs ≅ HCB and HPTs. Estimated daily intakes (EDIs) through dietary consumption of cattle tissues were lower than the recommended acceptable daily intakes (ADIs) established by FAO/WHO. However, the hazard ratios (HRs) based on cancer risk were greater than 1.0 for HCHs based on the average and 95th centile concentrations, indicating carcinogenic effects to consumers through cattle tissues consumption.

Non-truncating LIFR mutation: causal for prominent congenital pain insensitivity phenotype with progressive vertebral destruction?

We present a Qatari family with two children who displayed a characteristic phenotype of congenital marked pain insensitivity with hypohidrosis and progressive aseptic destruction of joints and vertebrae resembling that of hereditary sensory and autonomic neuropathies (HSANs). The patients, aged 10 and 14, remained of uncertain genetic diagnosis until whole genome sequencing was pursued. Genome sequencing identified a novel homozygous C65S mutation in the LIFR gene that is predicted to markedly destabilize and alter the structure of a particular domain and consequently to affect the functionality of the whole multi-domain LIFR protein. The C65S mutant LIFR showed altered glycosylation and an elevated expression level that might be attributed to a slow turnover of the mutant form. LIFR mutations have been reported in Stüve-Wiedemann syndrome (SWS), a severe autosomal recessive skeletal dysplasia often resulting in early death. Our patients share some clinical features of rare cases of SWS long-term survivors; however, they also phenocopy HSAN due to the marked pain insensitivity phenotype and progressive bone destruction. Screening for LIFR mutations might be warranted in genetically unresolved HSAN phenotypes.

Hematological effect of benzene exposure with emphasis of muconic acid as a biomarker.

Human exposure to benzene in work environment is a global occupational health problem. It is established that benzene requires to be metabolized to induce its effects. Benzene has been associated with various hematotoxins and carcinogens. The aim of this study was to investigate the effect of benzene on complete blood picture, with emphasis of trans, trans-muconic acid (t,t-MA) as a biomarker of benzene in urine, considering the influence of cigarette smoke. A total of 81 workers (61 males and 20 females) have been occupationally exposed to benzene. In addition, 83 workers (55males and 28 females) were also recruited as a control group. Complete blood picture was analyzed and urinary t,t-MA was determined by liquid chromatography. In addition, creatinine in the urine samples was determined. Levels of blood elements (white blood cells, red blood cells and platelets) were decreased among exposed workers compared with the controls. The urinary level of t,t-MA/creatinine of the exposed workers was elevated especially in the smoking group compared to the controls. This study recommends that complete blood picture and t,t-MA are helpful biomarker tests that should be done to detect the early effects of benzene exposure.

Antibiotic residues in food: the African scenario.

Antibiotics are substances either produced naturally by living organisms or synthetically in the laboratory, and they are able to kill or inhibit the growth of microorganisms. Antibiotics are also used as feed additives for the purpose of livestock health maintenance. Antibiotic residues in feedstuffs are currently a problem of some magnitude in different parts of the world, particularly due to associated public health concerns that include hypersensitivity reactions, antibiotic resistance, toxicity, teratogenicity, and carcinogenicity. In Africa, as in other parts of the world, antibiotic residues in animal-derived foods have been extensively recorded in many African countries; these residues have exceeded the WHO maximum residue levels in many cases. It has been reported that tetracyclines are the most predominantly prescribed antibiotics in Africa, and of all antibiotic-associated residues they represent 41% of cases, followed by beta-lactams at 18%. Great care should be taken to monitor antibiotic cessation periods before the release of animal-derived foods for human consumption. In addition, strict legislation should be implemented in order to minimize the abuse of antibiotics.

Determination of organochlorine pesticides (OCPs) in the edible offal of Egyptian buffalo.

Environmental contamination by OCPs has a great concern, since most of these pesticide compounds are very toxic and harmful to human and ecosystems. This study was conducted to determine the concentrations of OCPs residues in the edible offal (livers, kidneys and tongues) of Egyptian buffalo collected from three locations (Zagazig, Ismailia and Mansoura) in Egypt. Examined samples from Mansura city had the highest OCPs contamination load. Tongues had the highest concentration of these toxic residues in a comparison to livers and kidneys in the examined samples. The overall results showed that OCPs residues did not exceed the Egyptian maximum permissible limits in all of the samples analyzed from the three different locations.

Screening for asymptomatic cardiovascular disease in Arab patients with diabetes.

AIM: Diabetes mellitus is a major risk factor for atherosclerosis and accordingly increased morbidity and mortality. This study aimed at screening high risk diabetic patients for atherosclerosis in different arterial territories. METHODS: All high risk asymptomatic patients attending the diabetic clinic, King Fahd Hospital of the University, Saudi Arabia were invited to be screened for peripheral arterial disease (PAD), extra-cranial cerebrovascular disease (CVD) and coronary artery disease (CAD) over one year. All participants underwent measurement of ankle brachial pressure index, carotid Duplex scan and exercise electrocardiography (ECG). All patients underwent evaluation of conventional risk factors for atherosclerosis RESULTS: One hundred and sixty nine patients were invited to be screened. Of these 138 (82%) completed all the screening tests. The mean age was 53.5±7.18 years. Seventy-five (55%) had evidence of subclinical atherosclerosis. In the atherosclerotic group, 24 patients had PAD, 47 had CVD and 30 had CAD. There were significant differences between the atherosclerotic and non-atherosclerotic groups with regard to most risk factors. In age, sex adjusted, the risk of developing atherosclerosis was significantly increased with all risk factors. Dyslipidemia had the highest association (OR 9.7, 95% CI 8.1-10.2) CONCLUSION: Participation and diagnostic yield of screening for atherosclerosis had satisfactory validity and reliability. Routine screening in high-risk diabetic patients can serve as an effective tool for diagnosis of sub clinical cardiovascular disease and provide strategies to optimize risk reduction.

Carotenoids as regulators for inter-species difference in cytochrome P450 1A expression and activity in ungulates and rats.

Ungulates (deer, cattle and horses) are reported as animal species which show extreme-accelerated metabolism of CYP1A substrates, such as ethoxyresorufin compared to rats. This study was undertaken to investigate whether accumulation of carotenoids is a possible cause for inter-species difference in CYP1A-dependent activity in this group of animals. The relationship between inter-species differences in CYP1A-dependent activity and the accumulated carotenoids and retinoids as candidates of dietary CYP1A inducers in ungulate species was clarified. Interestingly, there were positive correlations between the accumulated carotenoids, such as ß-carotene, with both EROD activity and CYP1A protein expression. These correlations were negative with the accumulated retinoids, such as retinol. The ß-carotene was major component of carotenoids in ungulates, and known as an inducer of CYP1A. On the other hand, the retinol is reported as the inhibitor of CYP1A. Other factors which affect CYP1A1 expression, such as polycyclic aromatic hydrocarbons, were also analyzed. To cancel the effects of inter-species difference in CYP1A induction signal cascade among these animals, the rat cell line (H4-II-cells) was treated with the extracted carotenoids from the examined animals. In conclusion, carotenoids and retinoids may have direct effects on the inter-species differences in CYP1A-dependent activity and protein expression.

Glutathione peroxidase activity in patients with renal disorders.

BACKGROUND: Glutathione peroxidase (GPx) protects cells from oxidative damage by catalyzing the reduction of both organic and hydrogen peroxides, using glutathione as a reducing agent. Both plasma GPx (P-GPx) and erythrocyte GPx (E-GPx) have been identified in human blood. Kidney proximal tubular cells are the main source of GPx activity in the plasma. Oxidative damage has been reported to participate in the progression and complications of renal diseases. METHODS: The activities of both E-GPx and P-GPx were determined, using Randox commercial kits, in 12 patients with nephrotic syndrome (NS), 48 patients with renal impairment (RI), and 50 patients with chronic renal failure on maintenance hemodialysis (HD; before as well as immediately after dialysis), and in 50 healthy volunteers who served as controls. RESULTS: Compared to the results in healthy controls, P-GPx activity was reduced in the HD group and the RI group, whereas the NS group showed no significant difference from the control. The HD group showed a higher drop in P-GPx (reduced to 36.6% of the mean control value) than the RI group (reduced to 61.8% of the mean control value). Further analysis of the RI group showed a highly significant negative correlation between P-GPx activity and serum creatinine level (r = -0.691; P < 0.001). Also, a highly significant negative correlation was found between P-GPx and blood urea nitrogen (r = -0.792; P < 0.001). However, E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. E-GPx was reduced to 55.2% and 68.9% of the mean control 1 value in the NS group and the RI group respectively, while the HD group showed no significant change. Further analysis of the RI group found that E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. In HD patients, GPx activity was measured before and immediately after hemodialysis. E-GPx activity was similar before and after dialysis, without a significant difference (pre-dialysis, 37.7 +/- 13.5 U/g hemoglobin [Hb]; post-dialysis, 38.72 +/- 12.31 U/g Hb). However, P-GPx activity was significantly increased (pre-dialysis, 254.4 +/- 62.6 U/ml; post-dialysis, 296.98 +/- 74.04 U/ml; P < 0.001), but it was still significantly lower when compared to that in the healthy controls. CONCLUSIONS: P-GPx activity is an important test to assess the oxidative damage in patients with kidney diseases. The progression of renal disorders is accompanied by a decrease in P-GPx activity, but not by a decrease in E-GPx activity. Thus, we conclude that P-GPx activity largely depends on physiological renal function, whereas E-GPx activity does not.

PGE1 protection against apoptosis induced by D-galactosamine is not related to the modulation of intracellular free radical production in primary culture of rat hepatocytes.

D-galactosamine (D-GalN) toxicity is a useful experimental model of liver failure in human. It has been previously observed that PGE1 treatment reduced necrosis and apoptosis induced by D-GalN in rats. Primary cultured rat hepatocytes were used to evaluate if intracellular oxidative stress was involved during the induction of apoptosis and necrosis by D-GalN (0-40mM). Also, the present study investigated if PGE1 (1 microM) was equally potent reducing both types of cell death. The presence of hypodiploid cells, DNA fragmentation and caspase-3 activation were used as a marker of hepatocyte apoptosis. Necrosis was measured by lactate dehydrogenase (LDH) release. Oxidative stress was evaluated by the intracellular production of hydrogen peroxide (H2O2), the disturbances on the mitochondrial transmembrane potential (MTP), thiobarbituric-reacting substances (TBARS) release and the GSH/GSSG ratio. Data showed that intermediate range of D-GalN concentrations (2.5-10mM) induced apoptosis in association with a moderate oxidative stress. High D-GalN concentration (40 mM) induced a reduction of all parameters associated with apoptosis and enhanced all those related to necrosis and intracellular oxidative stress, including a reduction of GSH/GSSG ratio and MTP in comparison with D-GalN (2.5-10 mM)-treated cells. Although PGE1 reduced apoptosis induced by D-GalN, it was not able to reduce the oxidative stress and cell necrosis induced by the hepatotoxin in spite to its ability to abolish the GSH depletion.

Tissue oxygen distribution in head and neck cancer patients.

BACKGROUND: The importance of hypoxia in limiting the sensitivity of tumor cells to ionizing radiation has long been known. METHODS: We evaluated the tissue oxygenation status with a polarographic needle electrode system in 37 patients with malignancies of the head and neck and correlated the pO2 of 25 patients with treatment outcome. RESULTS: Sixteen tumors contained areas of severe hypoxia, defined by pO2 values below 2.5 mm Hg. Tumor oxygenation parameters were not correlated with hemoglobin, age, and history of tobacco use. There were no subcutaneous PO2 values below 10 mm Hg (ie, no areas of moderate or severe hypoxia), whereas this degree of hypoxia was commonly found in the tumors. Though not statistically significant, hypoxic tumors showed trends for poorer treatment outcome. CONCLUSION: Our data demonstrate a great interindividual variability in the oxygenation of head and neck cancers and appears unassociated with clinical parameters. The method is capable of identifying patients with poorly oxygenated tumors, thereby providing important information for selecting patients who might need customized therapy designed to kill hypoxic tumor cells. Hypoxic tumors show a consistent trend for poor treatment outcome.