Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles.

Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs.

Impaired nerve conduction velocity in MPTP-treated mouse model of Parkinson's disease.

Electrophysiological examination can provide valuable information on functional abnormalities in patients with Parkinson's disease (PD). Although there are numerous reports on biochemical and molecular alterations in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental parkinsonism in mice, the mode of electrophysiology in this animal model of PD is not clear. This study provides a comparative evaluation of corticomotor evoked potential (CMEP), compound muscle action potential (CMAP) and motor nerve conduction velocity (NCV) in mice treated with MPTP (30 mg/kg, ip, daily for 4 days) or saline (control group). Although the CMEP latencies were similar in both the groups, the CMEP amplitude was non-significantly decreased in MPTP-treated mice. There was a significant increase in the CMAP latency (1.37 ± 0.03 versus 1.20 ± 0.02 ms) and decrease in CMAP amplitude (4.50 ± 0.89 versus 8.31 ± 0.86 mV) in MPTP-treated mice as compared with control group. This prolonged conduction time resulted in a significant decrease in NCV in MPTP-treated mice (21.98 ± 0.54 m/s) as compared with control mice (24.47 ± 0.33 m/s). There was a significant depletion of striatal dopamine in MPTP-treated animals. These findings demonstrate that systemic administration of MPTP significantly impairs both the central and peripheral nervous systems in mice. However, the resemblance of this neurophysiological status with idiopathic PD or other animal models of PD is not clear and requires additional studies.

Evaluation of HbA1c criteria for diagnosis of diabetes mellitus: a retrospective study of 12 785 type 2 Saudi male patients.

Recently, American Diabetic Association has recommended glycated hemoglobin (HbA1c ≥6.5%) as an alternate to fasting plasma glucose (FPG ≥7.0 mmol/L) for diagnosis of diabetes. However, studies from different groups showed inconsistent results with the use of HbA1c criteria. We examined the validity of HbA1c cut-point of 6.5% for diagnosis of diabetes. A total of 12 785 male diabetic patients (FGP ≥7.0 mmol/L), aged 56.27 ± 13.32 years were included. The average values of FPG and HbA1c of all the 12 785 patients were 10.127 ± 0.026 mmol/L and 8.729 ± 0.013%, respectively. Sub-grouping of patients into different age categories showed significantly high levels of FPG (10.934 ± 0.123 mmol/L) in the youngest group (age, ≥20-35 years) as compared to FPG (ranged from 10.021 ± 0.052 to 10.190 ± 0.050 mmol/L) in patients with other age categories. The level of HbA1c was highest in the youngest group (8.809 ± 0.056%) and lowest in the oldest group (8.653 ± 0.082%). There was a significant correlation between FPG and HbA1c (R = 0.571, p < 0.001). There were 484 patients below the diagnostic threshold (HbA1c <6.5%), resulting in 3.78% false negative predictions. Majority of the false negative patients were in the age group of 40-75 years and had borderline FPG (7.0-8.0 mmol/L) and HbA1c (6.0-6.5%). These findings suggest that Saudi individuals with HbA1c between 6.0% and 6.5% may be considered as "probable diabetic" and their status should be verified by combined FPG and HbA1c criteria.

A systematic review of the clinical characteristics and course of atrioventricular blocks in hyperthyroidism.

BACKGROUND: Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH. METHODS: We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598. RESULTS: A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% (n = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB (N = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing. CONCLUSION: Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

BACKGROUND: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. METHODS: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. RESULTS: The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. CONCLUSION: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Assessing the reliability and degradation of 10-35 years field-aged PV modules.

The objective of this study was to conduct a reliability analysis on photovoltaic (PV) modules from the oldest PV installation site in Pakistan. Four sets of modules; Type A & B (30 years old), Type C (10 years old), and Type D (35 years old) were identified for this analysis. It has been observed that modules have shown degradation after working for a good number of years in the field. Comparing with nameplate data (available for Type B & C only), a drop of 28.68% and 2.99 percentage points (pp) was observed in the output power (Pmax) and efficiency (Eff.) respectively for Type B, while a drop of 22.21% and 4.05 pp was observed in Pmax and Eff. respectively for Type C. A greater drop in ISC and Pmax was observed in Type B, which is attributed to severe browning of EVA in them. While the greater drop in Pmax, in case of Type C, is attributed to the poor quality of materials used. Amongst the different defects observed, the junction box defects which include cracking and embrittlement, etc., and backsheet defects which include discoloration, delamination and cracking, etc. were found in all four types of modules. Other defects include browning of EVA, observed in Type B and D, and corrosion of frame and electrical wires, found in Type A, B, and D. This first-ever study will provide valuable information in understanding the degradation mechanism and henceforth, improving the long term reliability of PV modules in the humid-subtropical conditions of Pakistan.

A review of the logistic role of L-carnitine in the management of radiation toxicity and radiotherapy side effects.

Radiation therapy is a key modality in the treatment of different cancer types. Fatigue is the most common side effect of radiotherapy, while others include nausea, hair loss, skin irritation, anemia, infertility, cardiovascular disease, cognitive impairment and even the development of second cancers. Studies in experimental animals have shown protective effects of carnitine against exposure of various organs to ionizing radiation, whereas carnitine deficiency is known to enhance radiation-induced toxicity. This report summarizes the recent literature on the adverse effects of radiotherapy and the impact of radiation on carnitine homeostasis. Although some studies have demonstrated the prophylactic benefits of carnitine against the toxic effects of chemotherapy, the role of carnitine in the prognosis and management of cancer patients receiving radiotherapy is not clear and needs to be explored.

Novel perovskite solar cell with Distributed Bragg Reflector.

This paper reports numerical modeling of perovskite solar cell which has been knotted with Distributed Bragg Reflector pairs to extract high energy efficiency. The geometry of the proposed cells is simulated with three different kinds of perovskite materials including CH3NH3PbI3, CH3NH3PbBr3, and CH3NH3SnI3. The toxic perovskite material based on Lead iodide and lead bromide appears to be more efficient as compared to non-toxic perovskite material. The executed simulated photovoltaic parameters with the highest efficient structure are open circuit voltage = 1.409 (V), short circuit current density = 24.09 mA/cm2, fill factor = 86.18%, and efficiency = 24.38%. Moreover, a comparison of the current study with different kinds of structures has been made and surprisingly our novel geometry holds enhanced performance parameters that are featured with back reflector pairs (Si/SiO2). The applied numerical approach and presented designing effort of geometry are beneficial to obtain results that have the potential to address problems with less efficient thin-film solar cells.

Recent Trends of Metabolic Syndrome and Its Components in Military Recruits from Saudi Arabia.

Metabolic syndrome (Met-S) constitutes the risk factors and abnormalities that markedly increase the probability of developing diabetes and coronary heart disease. An early detection of Met-S, its components and risk factors can be of great help in preventing or controlling its adverse consequences. The aim of the study was to determine the prevalence of cardio-metabolic risk factors in young army recruits from Saudi Arabia. A total of 2010 Saudis aged 18-30 years were randomly selected from groups who had applied to military colleges. In addition to designed questionnaire, anthropometric measurements and blood samples were collected to measure Met-S components according to the International Diabetes Federation (IDF) criteria. Met-S prevalence was 24.3% and it was higher in older subjects than the younger ones. There were significant associations between Met-S and age, education level and marital status. The most common Met-S components were high fasting blood sugar (63.6%) followed by high blood pressure (systolic and diastolic, 63.3% and 37.3% respectively) and high body mass index (57.5%). The prevalence of pre-diabetes and diabetes were found to be 55.2% and 8.4%, respectively. Hypertriglyceridemia was found in 19.3% and low levels of high-density lipoproteins (HDL) in 11.7% of subjects. In conclusion, there is a high prevalence of Met-S in young adults of Saudi Arabia. There is a need for regular monitoring of Met-S in young populations to keep them healthy and fit for nation building. It is also important to design and launch community-based programs for educating people about the importance of physical activity, cessation of smoking and eating healthy diet in prevention of chronic diseases.

In-Vitro and In-Vivo Evaluation of Velpatasvir- Loaded Mesoporous Silica Scaffolds. A Prospective Carrier for Drug Bioavailability Enhancement.

The limited aqueous solubility of many active pharmaceutical ingredients (APIs) is responsible for their poor performance and low drug levels in blood and at target sites. Various approaches have been adopted to tackle this issue. Most recently, mesoporous silica nanoparticles (MSN) have gained attention of pharmaceutical scientists for bio-imaging, bio-sensing, gene delivery, drug solubility enhancement, and controlled and targeted drug release. Here, we have successfully incorporated the poorly water soluble antiviral drug velpatasvir (VLP) in MSN. These spherical particles were 186 nm in diameter with polydispersity index of 0.244. Blank MSN have specific surface area and pore diameter of 602.5 ± 0.7 m2/g and 5.9 nm, respectively, which reduced after successful incorporation of drug. Drug was in amorphous form in synthesized VLP-loaded silica particles (VLP-MSN) with no significant interaction with carrier. Pure VLP showed poor dissolution with progressive increment in pH of dissolution media which could limit its availability in systemic circulation after oral administration. After VLP loading in silica carriers, drug released rapidly over a wide range of pH values, i.e., 1.2 to 6.8, thus indicating an improvement in the solubility profile of VLP. These particles were biocompatible, with an LD50 of 448 µg/mL, and in-vivo pharmacokinetic results demonstrated that VLP-MSN significantly enhanced the bioavailability as compared to pure drug. The above results clearly demonstrate satisfactory in-vitro performance, biocompatibility, non-toxicity and in-vivo bioavailability enhancement with VLP-MSN.

Pentoxifylline attenuates iminodipropionitrile-induced behavioral abnormalities in rats.

This investigation was undertaken to study the effect of pentoxifylline (PTX) on iminodipropionitrile (IDPN)-induced behavioral abnormalities [excitation with choreiform and circling movements (ECC) syndrome] in rats. The animals were intraperitoneally injected with IDPN (100 mg/kg) daily for 7 days. PTX was administered daily 30 min before IDPN in the doses of 25, 50, and 100 mg/kg for 9 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex, and contact inhibition of the righting reflex. The onset of ECC syndrome was observed on day 8 in the group treated with IDPN alone; all animals in this group became dyskinetic on day 10. Co-treatment with PTX dose dependently delayed the onset time and significantly reduced the incidence and severity of IDPN-induced ECC syndrome; high dose of PTX completely inhibited the abnormal behavioral signs in IDPN-treated rats. Administration of IDPN caused significant depletions in cerebral glutathione and vitamin E levels. Treatment with PTX dose dependently attenuated IDPN-induced oxidative stress in rats. The beneficial effects of PTX against IDPN toxicity may be attributed to its antioxidant and anti-inflammatory properties.

A priming dose protects against gold nanoparticles-induced proinflammatory cytokines mRNA expression in mice.

AIM: To study the effect of priming doses of gold nanoparticles (GNPs) on proinflammatory cytokines in different organs of mice. MATERIALS & METHODS: Mice were injected with a single or two doses (priming group) of GNPs (5, 20 and 50 nm) and sacrificed after 1 or 7 days. The mRNA expressions of IL-1ß, IL-6 and TNF-α were determined in liver, kidney and spleen. RESULTS: A single injection of 5 nm GNPs significantly increased the mRNA expressions of IL-1ß and IL-6 in liver, which were normalized on day 7. In spleen, the GNPs of all sizes significantly increased IL-1ß and IL-6 mRNA expressions on day 1 that persisted on day 7. The priming dose of GNPs protected the animals against the acute phase induction of IL-1ß and IL-6 expressions in liver and spleen. CONCLUSION: Primed animals showed protection against GNP-induced acute immune activation suggesting the importance of the priming dose in nanomedicine.

CalcNTCP: a simple tool for computation of normal tissue complication probability (NTCP) associated with cancer radiotherapy.

PURPOSE: This study was aimed to develop a simple and user-friendly software for fast and accurate computation of normal tissue complication probability (NTCP) in accordance with the Lyman model. MATERIALS AND METHODS: The software CalcNTCP has been developed in Visual Basic and is equipped with two functional modes. Mode 1 is based on pre-stored values of various parameters for 27 different organ systems and the user has only to input the values of volume fraction (v) and radiation dose (D), whereas Mode 2 is designed for the customized entries. RESULTS: The results of software validation have demonstrated that CalcNTCP is more efficient and time-saving as compared to manual or semi-manual procedures. The shapes and locations of representative survival curves generated by CalcNTCP-based computations for various radiation doses (10 - 100 Gy) and reference volumes (0.33 - 1.00) absolutely matched with optimal curves. CONCLUSION: CalcNTCP is a simple, fast and accurate tool for the computation of NTCP with a direct implication in the evaluation or optimization of radiotherapy treatment plans.

Protective effect of hydrocortisone on iminodipropionitrile-induced neurotoxicity in rats.

Occupational and environmental exposure of synthetic nitriles is of potential relevance to human health. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to hydrocortisone and IDPN on behavioural abnormalities namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats were given hydrocortisone (0, 10, 30 and 60 mg/kg, gavage, for 10 days) 30 min. before IDPN (100 mg/kg, intraperitoneally for 8 days). Two additional groups of rats were treated with either saline (control group) or 60 mg/kg of hydrocortisone (drug alone group). The animals were observed for neurobehavioural abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. After behavioural studies, the animals were killed, and the discrete brain regions and temporal bones were collected for biochemistry and inner ear histopathology, respectively. Hydrocortisone significantly and dose dependently attenuated the incidence and severity of IDPN-induced behavioural syndrome. Administration of hydrocortisone (60 mg/kg) alone significantly increased glutathione (GSH) levels in olfactory bulb and striatum, whereas IDPN alone significantly reduced GSH levels in olfactory bulb, striatum and hippocampus. Hydrocortisone (60 mg/kg) significantly compensated IDPN-induced depletions of GSH in different brain regions. Hydrocortisone also protected the animals against IDPN-induced vestibular hair cell degeneration. The protective effect of hydrocortisone may be attributed to its anti-inflammatory and antioxidant properties.

Paired values of serum fructosamine and blood glucose for the screening of gestational diabetes mellitus: A retrospective study of 165 Saudi pregnant women.

This study reports the utilization of serum fructosamine and blood glucose for the screening of gestational diabetes mellitus (GDM). Blood samples from 165 pregnant women were analyzed for fasting blood glucose (FBG), random blood glucose (RBG) and serum fructosamine. The actual fructosamine levels were corrected for serum protein (c-Fruct) for more precise presentation. Two cut-off values of FBG (>5.3 mmol/L and >7.0 mmol/L) and RBG (>7.8 mmol/L and >11.0 mmol/L) were used to classify hyperglycemic subjects for subsequent evaluation. The average values±standard deviations for FBG, RBG and cFruct were 5.865±1.95, 7.767±3.21 and 2.387±0.47 mmol/L, respectively. FBG levels were significantly correlated with RBG (Pearson correlation=0.597, P<0.001). Significant correlations were also observed between cFruct and FBG (Pearson correlation=0.673, P<0.001) or RBG (Pearson correlation=0.641, P<0.001). Out of 165 subjects, 24 (14.5%) cases were classified as hyperglycemic on the basis of FBG>7.0 mmol/L or RBG>11.0 mmol/L; use of lower cut-off values resulted higher frequencies of hyperglycemia. Whereas, a combined criteria of FBG>5.3 mmol/L and cFruct >2.5 mmol/L predicted 35 patients as the most probable hyperglycemic as compared to 32 patients identified using the criteria of RBG >7.8 mmol/L and cFruct >2.5 mmol/L. These criteria were associated with 4.8% and 3.6% false-positivity at the expense of 3.6% and 3.0% false-negative outcomes, respectively. The levels of FBG, RBG and cFruct were significantly higher in hyperglycemic groups (irrespective of grouping criteria) as compared to the respective normal groups. In conclusion, these findings clearly indicate that the paired values of cFruct with FBG or RBG could help in filtering high-risk individuals for OGTT and therefore avoiding a unnecessary OGTT.

Current trends for customized biomedical software tools.

In the past, biomedical scientists were solely dependent on expensive commercial software packages for various applications. However, the advent of user-friendly programming languages and open source platforms has revolutionized the development of simple and efficient customized software tools for solving specific biomedical problems. Many of these tools are designed and developed by biomedical scientists independently or with the support of computer experts and often made freely available for the benefit of scientific community. The current trends for customized biomedical software tools are highlighted in this short review.

Potential of lipoproteins as biomarkers in acute myocardial infarction.

Acute myocardial infarction (AMI), commonly known as heart attack, is a medical emergency that is potentially fatal if not promptly and properly managed. The early diagnosis of AMI is critically important for the timely institution of pharmacotherapy to prevent myocardial damage and preserve cardiac function. Ischemic insults during AMI cause myocardial tissue damage, releasing the cardiac muscle protein troponin T into the blood stream. Therefore, serum troponin T levels are used as a sensitive and specific indicator of myocardial injury for diagnosing AMI. However, there remains a requirement for developing technologies for more accurate biomarkers or signatures for AMI diagnosis or prognosis. Previous studies have implicated impaired lipid metabolism as a causative factor in AMI development. Lipoproteins are important constituents of lipid metabolism; their levels in the blood stream are a convenient biomarker tool for monitoring lipid metabolism. This review summarizes recent findings (data of studies from 2001 to 2016) regarding the biomarker potentials of various lipoproteins, including low-density lipoprotein, oxidized low-density lipoprotein, high-density lipoprotein, lipoprotein-a, and remnant lipoprotein, for the risk stratification of AMI.

Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential target for the treatment of several disorders. In view of several FDA approved kinase inhibitors, in the current study, we have investigated the interaction of selected kinase inhibitors with PPARγ using computational modeling, docking, and molecular dynamics simulations (MDS). The docked conformations and MDS studies suggest that the selected KIs interact with PPARγ in the ligand binding domain (LBD) with high positive predictive values. Hence, we have for the first time shown the plausible binding of KIs in the PPARγ ligand binding site. The results obtained from these in silico investigations warrant further evaluation of kinase inhibitors as PPARγ ligands in vitro and in vivo.

Saudi medicinal plants for the treatment of scorpion sting envenomation.

Scorpion sting envenoming poses major public health problems. The treatment modalities include antivenoms, chemical antidotes and phytotherapy, with varying degrees of effectiveness and side effects. In this investigation, we reviewed the use of Saudi medicinal plants for the treatment of scorpion sting patients. The relevant literature was collected using the online search engines including Science Direct, Google and PubMed with the help of specific keywords. We also used the printed and online resources at our institutional library to gather the relevant information on the use of medicinal plants for the treatment of scorpion sting patients. A descriptive statistics was used for data compilation and presentation. The results of this survey showed the use of at least 92 medicinal plants with beneficial effects for treating victims of stings of different scorpion species. These commonly used herbs spanned to 37 families whilst different parts of these plants were employed therapeutically for alleviation of envenomation symptoms. The application of leaves (41%) was preferred followed by roots (19%), whole plant (14%) and seeds (9%). The use of latex (4%), stem (3%), flowers (3%) and bark (3%) was also reported. In some cases, tannin (2%), rhizome (1%) and shoot (1%) were also used. In conclusion, herbal medicines are effectively used for the treatment of patients with scorpion envenomation. This type of medication is free from side effects as observed with chemical antidotes or antivenom therapy. It is important to identify the active ingredients of herbal drugs for improving their therapeutic potential in traditional medicine.

ArrayVigil: a methodology for statistical comparison of gene signatures using segregated-one-tailed (SOT) Wilcoxon's signed-rank test.

Due to versatile diagnostic and prognostic fidelity molecular signatures or fingerprints are anticipated as the most powerful tools for cancer management in the near future. Notwithstanding the experimental advancements in microarray technology, methods for analyzing either whole arrays or gene signatures have not been firmly established. Recently, an algorithm, ArraySolver has been reported by Khan for two-group comparison of microarray gene expression data using two-tailed Wilcoxon signed-rank test. Most of the molecular signatures are composed of two sets of genes (hybrid signatures) wherein up-regulation of one set and down-regulation of the other set collectively define the purpose of a gene signature. Since the direction of a selected gene's expression (positive or negative) with respect to a particular disease condition is known, application of one-tailed statistics could be a more relevant choice. A novel method, ArrayVigil, is described for comparing hybrid signatures using segregated-one-tailed (SOT) Wilcoxon signed-rank test and the results compared with integrated-two-tailed (ITT) procedures (SPSS and ArraySolver). ArrayVigil resulted in lower P values than those obtained from ITT statistics while comparing real data from four signatures.