A multicentre cross-sectional descriptive study evaluating the cardiovascular risk profile of preoperatively identified patients with hypertension.

BACKGROUND: The prevalence of hypertension in adults in South Africa (SA) is 35%. Hypertension is the most important modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD) in sub-Saharan Africa. However, 49% of people are unaware of their blood pressure status. Screening for hypertension prior to surgery provides a unique opportunity to diagnose and treat affected individuals. Furthermore, assessing overall CV risk identifies patients at highest risk for complications, and improves the utilisation of scarce resources. OBJECTIVES: To evaluate the CV risk profile of hypertensive patients in the adult population of the Western Cape Province presenting for elective non-cardiac, non-obstetric surgery. METHODS: This report documents the CV risk profile of patients recruited to the HASS-2 study (Hypertension and Surgery Study 2), which was undertaken in seven Western Cape hospitals. Patients were screened for hypertension and pharmacological treatment was initiated or adjusted in patients with stages 1 and 2 disease. Stage 3 patients were referred to a physician. In the present substudy, patients with stages 1 and 2 hypertension were assessed for associated CV risk factors, the presence of target organ damage, and documented CV or kidney disease; they received an overall risk stratification according to the 2018 European Society of Cardiology and the European Society of Hypertension Guidelines. RESULTS: Sixty-one patients with stage 1 and 12 with stage 2 hypertension were analysed. Established CV disease was present in 13.7% of the study population, and CKD (eGFR <60 mL/min) in 10.8%. Seventy-one percent of the study group had a raised body mass index, and 55.9% underlying metabolic syndrome. Prediabetes and diabetes were present in 16.1% and 14.5%, respectively. According to the 2018 European guidelines, 34.7% were at moderate, 33.3% at high and 16.7% at very high risk for a CV event in the following 10 years. CONCLUSIONS: The perioperative period is a critical time during which surgeons, nurses and anaesthetists can influence patients' CV risk of adverse events. This involves appropriate screening, education and treatment. In this study population, nearly 9 out of 10 elective surgical patients with stage 1 or 2 hypertension had CV risk factors placing them at moderate to very high risk. The simultaneous assessment of these additional CV risk parameters, in addition to diagnosis and management of hypertension, may further decrease the health and financial burden in resource-limited facilities in SA, and improve CV outcomes.

A novel test for determination of wild felid-domestic cat hybridization.

In October 2018, Colorado Parks and Wildlife seized an animal believed to be an illegally possessed bobcat. The owner claimed the animal was a bobcat/domestic cat hybrid, exempted from license requirements. Burden of proof lay with CPW to determine the lineage of the animal. Commercial microsatellite arrays and DNA barcoding have not been developed for identification of bobcat/domestic cat hybrids, and limited time and resources prevented development of such tests for this application. Instead, we targeted endogenous feline leukemia virus (enFeLV) to quickly and inexpensively demonstrate the absence of domestic cat DNA in the contested animal. Using this assay, we were able to confirm that the contested animal lacked enFeLV, and therefore was not a domestic cat hybrid.

Osteoarthritis and stem cell therapy in humans: a systematic review.

OBJECTIVE: Osteoarthritis (OA) is a leading cause of disability in the world. Mesenchymal stem cells (MSCs) have been studied to treat OA. This review was performed to systematically assess the quality of literature and compare the procedural specifics surrounding MSC therapy for osteoarthritis. DESIGN: PubMed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials were searched for studies using MSCs for OA treatment (final search December 2017). Outcomes of interest included study evidence level, patient demographics, MSC protocol, treatment results and adverse events. Level I and II evidence articles were further analyzed. RESULTS: Sixty-one of 3,172 articles were identified. These studies treated 2,390 patients with osteoarthritis. Most used adipose-derived stem cells (ADSCs) (n = 29) or bone marrow-derived stem cells (BMSCs) (n = 30) though the preparation varied within group. 57% of the sixty-one studies were level IV evidence, leaving five level I and nine level II studies containing 288 patients to be further analyzed. Eight studies used BMSCs, five ADSCs and one peripheral blood stem cells (PBSCs). The risk of bias in these studies showed five level I studies at low risk with seven level II at moderate and two at high risk. CONCLUSION: While studies support the notion that MSC therapy has a positive effect on OA patients, there is limited high quality evidence and long-term follow-up. The present study summarizes the specifics of high level evidence studies and identifies a lack of consistency, including a diversity of MSC preparations, and thus a lack of reproducibility amongst these articles' methods.

Soluble and insoluble phenolic compounds and antioxidant activity of immature calamondin affected by solvents and heat treatment.

Hot water extract of immature calamondin peel contains high total phenolic content, which shows significant correlation to DPPH scavenging potency. By heat treatment, the extraction yields of naringin, tangeretin, ferulic acid, p-coumaric acid and gallic acid increased, but the amount of 3',5'-di-C-ß-glucopyranosylphloretin (DGPP) decreased drastically. The major soluble phenolic compounds in the nonpolar extract are nobiletin and tangeretin, while DGPP and hesperidin are in the hot water extract. For insoluble phenolic compounds, ferulic acid, p-coumaric acid and sinapic acid are mainly in ester linkage form. After heat treatment, gallic acid and p-coumaric acid are the major increased soluble and insoluble phenolic acids, respectively. This indicates that high temperature heating (150°C) probably produces two major effects: (1) degradation of flavonoids, such as DGPP and hesperidin; (2) destruction of the cell wall structure, leading to an increase in soluble nobiletin, tangeretin and gallic acid, as well as insoluble ferulic and p-coumaric acids.

Genome-wide analysis of DNA copy number alterations and loss of heterozygosity in intracranial germ cell tumors.

BACKGROUNDS: Intracranial germ cell tumors (GCTs) are rare and heterogeneous with very little is known about their pathogenesis and underlying genetic abnormalities. PROCEDURES: In order to identify candidate genes and pathways which are involved in the pathogenesis of these tumors, we have profiled 62 intracranial GCTs for DNA copy number alterations (CNAs) and loss of heterozygosity (LOH) by using single nucleotide polymorphism (SNP) array and quantitative real time PCR (qPCR). RESULTS: Initially 27 cases of tumor tissues with matched blood samples were fully analyzed by SNP microarray and qPCR. Statistical analysis using the genomic identification of significant targets in cancer (GISTIC) tool identified 10 regions of significant copy number gain and 11 regions of significant copy number loss. While overall pattern of genomic aberration was similar between germinoma and nongerminomatous germ cell tumors (NGGCTs), a few subtype-specific peak regions were identified. Analysis by SNP array and qPCR was replicated using an independent cohort of 35 cases. CONCLUSIONS: Frequent aberrations of CCND2 (12p13) and RB1 (13q14) suggest that Cyclin/CDK-RB-E2F pathway might play a critical role in the pathogenesis of intracranial GCTs. Frequent gain of PRDM14 (8q13) implies that transcriptional regulation of primordial germ cell specification might be an important factor in the development of this tumor.

Immunodepletion plasma proteomics by tripleTOF 5600 and Orbitrap elite/LTQ-Orbitrap Velos/Q exactive mass spectrometers.

Plasma proteomic experiments performed rapidly and economically using several of the latest high-resolution mass spectrometers were compared. Four quantitative hyperfractionated plasma proteomics experiments were analyzed in replicates by two AB SCIEX TripleTOF 5600 and three Thermo Scientific Orbitrap (Elite/LTQ-Orbitrap Velos/Q Exactive) instruments. Each experiment compared two iTRAQ isobaric-labeled immunodepleted plasma proteomes, provided as 30 labeled peptide fractions, and 480 LC-MS/MS runs delivered >250 GB of data in 2 months. Several analysis algorithms were compared. At 1% false discovery rate, the relative comparative findings concluded that the Thermo Scientific Q Exactive Mass Spectrometer resulted in the highest number of identified proteins and unique sequences with iTRAQ quantitation. The confidence of iTRAQ fold-change for each protein is dependent on the overall ion statistics (Mascot Protein Score) attainable by each instrument. The benchmarking also suggested how to further improve the mass spectrometry parameters and HPLC conditions. Our findings highlight the special challenges presented by the low abundance peptide ions of iTRAQ plasma proteome because the dynamic range of plasma protein abundance is uniquely high compared with cell lysates, necessitating high instrument sensitivity.

Histone induced platelet aggregation is inhibited by normal albumin.

INTRODUCTION: Histones are small, nuclear proteins that serve to package DNA. Recent reports suggest that extracellular histones, including histone H4, may contribute to the pathogenesis of sepsis; they promote platelet aggregation and thrombosis when released into the circulation during inflammation or cell death. The mechanisms by which the body minimizes the deleterious effects of circulating histones are unclear. Because histones can bind to plasma proteins, including albumin, we hypothesized that normal albumin can prevent histones from activating platelets. MATERIALS AND METHODS: Platelets and platelet-free plasma were obtained from healthy, adult subjects. The dose-dependent effects of histone H4 on platelet aggregation were studied by optical aggregometry. The effects of native and albumin-depleted plasma (prepared by affinity chromatography) on histone-induced platelet aggregation were also assessed. The effects of normal and surface-neutralized albumin (through modification of carboxyl groups) on histone-induced platelet activation and aggregation were evaluated using flow cytometry and aggregometry. RESULTS: Histone H4 induced platelet aggregation in a dose-dependent manner. This histone-induced platelet aggregation was inhibited by both plasma and human serum albumin in a dose-dependent fashion. Furthermore, depletion of albumin from plasma reduced its ability to inhibit aggregation. Finally, surface neutralization of albumin decreased its ability to inhibit histone-induced activation and aggregation. DISCUSSION: These data suggest that normal albumin serves a role in preventing histone-induced platelet aggregation in a charge-dependent manner.

Curcumin modulates DNA methylation in colorectal cancer cells.

AIM: Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. MATERIALS AND METHODS: To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. RESULTS: As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean ß-values of 0.12), however, non-significant changes in mean ß-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. CONCLUSIONS: Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical.

NO donor KMUP-1 improves hepatic ischemia-reperfusion and hypoxic cell injury by inhibiting oxidative stress and pro-inflammatory signaling.

This study investigates whether KMUP-1 improves hepatic ischemia-reperfusion (I/R) and hypoxic cell injury via inhibiting Nox2- and reactive oxygen species (ROS)-mediated pro-inflammation. Rats underwent ischemia by occlusion of the portal vein and hepatic artery for 45 minutes. Reperfusion was allowed for 4 h. Serum was used for analysis of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). DNA extracted from liver homogenate was analyzed by electrophoresis to observe the fragmentation. Lipid peroxidation (LPO) was evaluated by measuring thiobarbituric acid-reactive substances (TBARS). NO and ROS contents were measured using Griess reagent and 2'-7'-dichlorofluorescein, respectively. Proteins levels were visualized by Western blotting. Liver damage was observed under a microscope. Intravenous KMUP-1 (0.25, 0.5 and 1 mg/kg) reduced I/R-induced ALT and AST levels, DNA fragmentation, ROS and malondialdehyde (MDA) and restored the NO levels of I/R rats. KMUP-1 protected the liver architecture from worsening of damage and focal sinusoid congestion, increased endothelium NO synthase (eNOS), guanosine 3', 5'cyclic monophosphate (cGMP), protein kinase G (PKG) and the B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, attenuated phosphodiesterase 5A (PDE-5A) and cleaved caspase-3 expression in I/R-liver. In hypoxic HepG2 cells, KMUP-1 increased cGMP/PKG, restored peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and decreased matrix metalloproteinases-9 (MMP-9), Rho kinase II (ROCK II), hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelium growth factor (VEGF). KMUP-1 protects liver from I/R-injury and hypoxic hepatocytes from apoptosis-associated free radical generation and pro-inflammation by restoring/increasing NO/cGMP/PPAR-gamma, reducing ROS/Nox2 and inhibiting ROCKII/MMP-9.

Antioxidant activity and effective compounds of immature calamondin peel.

The antioxidant activity and the flavonoids of mature and immature calamondin (Citrus mitis Blanco) peel were investigated. The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity (ORAC), reducing power, and superoxide scavenging effect. 3',5'-Di-C-ß-glucopyranosylphloretin, naringin, hesperidin, nobiletin, and tangeretin are the five major flavonoids found in hot water extract with the levels of 6888±522, 2333±157, 1350±94, 165±13, and 8±4 mg/100 g dry basis, respectively. The contents of nobiletin and tangeretin increased after ripening. The hot water extract of immature calamondin peel was fractionated using a semi-preparative HPLC. Fraction VI showed the highest ORAC value (28.02±2.73 mmol Trolox equivalents (TE)/g fraction) and two compounds, naringin and hesperidin, were identified as the major active components attributed to the antioxidant activity. Fraction V contained 3',5'-di-C-ß-glucopyranosylphloretin, which revealed low ORAC value with 7.43 mmol TE/g fraction. However, it might also contribute to antioxidant activity in immature calamondin peel due to its greatest quantity.

Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells.

Accumulating evidence suggests that chemopreventive effects of some dietary polyphenols may in part be mediated by their ability to influence epigenetic mechanisms in cancer cells. Boswellic acids, derived from the plant Boswellia serrata, have long been used for the treatment of various inflammatory diseases due to their potent anti-inflammatory activities. Recent preclinical studies have also suggested that this compound has anti-cancer potential against various malignancies. However, the precise molecular mechanisms underlying their anti-cancer effects remain elusive. Herein, we report that boswellic acids modulate DNA methylation status of several tumor suppressor genes in colorectal cancer (CRC) cells. We treated RKO, SW48 and SW480 CRC cell lines with the active principle present in boswellic acids, acetyl-keto-ß-boswellic acid (AKBA). Using genome-wide DNA methylation and gene expression microarray analyses, we discovered that AKBA induced a modest genome-wide demethylation that permitted simultaneous re-activation of the corresponding tumor suppressor genes. The quantitative methylation-specific PCR and RT-PCR validated the gene demethylation and re-expression in several putative tumor suppressor genes including SAMD14 and SMPD3. Furthermore, AKBA inhibited DNMT activity in CRC cells. Taken together, these results lend further support to the growing notion that anti-cancer effect of boswellic acids may in part be due to its ability to demethylate and reactivate methylation-silenced tumor suppressor genes. These results suggest that not only boswellic acid might be a promising epigenetic modulator in the chemoprevention and treatment of CRC, but also provide a rationale for future investigations on the usefulness of such botanicals for epigenetic therapy in other human malignancies.

De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one.

Lynch syndrome is an autosomal dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2. Constitutional epimutations of the MLH1 gene, characterized by soma-wide methylation of a single allele of the promoter and allelic transcriptional silencing, have been identified in a subset of Lynch syndrome cases lacking a sequence mutation in MLH1. We report two individuals with no family history of colorectal cancer who developed that disease at age 18 and 20 years. In both cases, cancer had arisen because of the de novo occurrence of a constitutional MLH1 epimutation and somatic loss-of-heterozygosity of the functional allele in the tumors. We show for the first time that the epimutation in one case arose on the paternally inherited allele. Analysis of 13 tumors from seven individuals with constitutional MLH1 epimutations showed eight tumors had lost the second MLH1 allele, two tumors had a novel pathogenic missense mutation and three had retained heterozygosity. Only 1 of 12 tumors demonstrated the BRAF V600E mutation and 3 of 11 tumors harbored a mutation in KRAS. The finding that epimutations can originate on the paternal allele provides important new insights into the mechanism of origin of epimutations. It is clear that the second hit in MLH1 epimutation-associated tumors typically has a genetic not epigenetic basis. Individuals with mismatch repair-deficient cancers without the BRAF V600E mutation are candidates for germline screening for sequence or methylation changes in MLH1.

Cholecystectomy prevalence and treatment cost: an 8-year study in Taiwan.

BACKGROUND: This study characterized the prevalence and treatment costs of laparoscopic cholecystectomy (LC) and open cholecystectomy (OC) procedures performed for a population-based patient cohort. METHODS: This study analyzed 32,535 OC and 80,335 LC procedures performed in Taiwan from 1996 to 2004. The odds ratio (OR) and effect size were calculated to assess the relative change rate. Bootstrap estimation was used to derive 95% confidence intervals (CIs) for differences in effect sizes of LC and OC. Multiple regression models were used to predict total treatment cost. RESULTS: The prevalences of OC and LC were respectively 18.19 and 25.44 per 100,000 persons in 1996. In 2004, OC gradually decreased to 13.21, but LC dramatically increased to 48.35, which represented change rates of -27.38% and 90.06%, respectively. The patient characteristics associated with an increased likelihood of undergoing LC were age, female gender, and lack of current comorbidities. The total treatment cost for the OC patients increased during the study period, whereas that for the LC patients declined. The LC patients were more responsive than the OC patients with respect to average length of hospital stay (ALOS) (-0.23; 95% CI, -0.33 to -0.13) and total treatment cost (-0.43; 95% CI, -0.63 to -0.23). Considerably increased total treatment cost was associated with advanced age, female gender, one or more co-morbidities, current treatment at a medical center, and long ALOS. CONCLUSIONS: Decreases in ALOS and total treatment cost were greater for the LC patients than for the OC patients. Government officials and health care providers should understand that total treatment cost depends on both patient and hospital attributes. These results can be generalized to patient populations elsewhere in Taiwan as well as to other countries with similar patient profiles.

World psychiatric association section of old age psychiatry consensus statement on ethics and capacity in older people with mental disorders.

The World Psychiatric Association (WPA) Section of Old Age Psychiatry, since 1997, has developed Consensus Statements relevant to the practice of Old Age Psychiatry. Since 2006 the Section has worked to develop a Consensus Statement on Ethics and Capacity in older people with mental disorders, which was completed in Prague, September 2008, prior to the World Congress in Psychiatry. This Consensus meets one of the goals of the WPA Action Plan 2008-2011, "to promote the highest ethical standards in psychiatric practice and advocate the rights of persons with mental disorders in all regions of the world". This Consensus Statement offers to mental health clinicians caring for older people with mental disorders, caregivers, other health professionals and the general public the setting out of and discourse in ethical principles which can often be complex and challenging, supported by practical guidance in meeting such ethical needs and standards, and to encouraged good clinical practice.

Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens.

BACKGROUND: This phase II study evaluated the efficacy and safety of lapatinib in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer that progressed during prior trastuzumab therapy. PATIENTS AND METHODS: Women with stage IIIB/IV HER2-overexpressing breast cancer were treated with single-agent lapatinib 1250 or 1500 mg once daily after protocol amendment. Tumor response according to RECIST was assessed every 8 weeks. HER2 expression was assessed in tumor tissue by immunohistochemistry and FISH. RESULTS: Seventy-eight patients were enrolled in the study. Investigator and independent review response rates [complete response (CR) or partial response (PR)] were 7.7% and 5.1%, and clinical benefit rates (CR, PR, or stable disease for >or=24 weeks) were 14.1% and 9.0%, respectively. Median time to progression was 15.3 weeks by independent review, and median overall survival was 79 weeks. The most common treatment-related adverse events were rash (47%), diarrhea (46%), nausea (31%), and fatigue (18%). CONCLUSIONS: Single-agent lapatinib has clinical activity with manageable toxic effects in HER2-overexpressing breast cancer that progressed on trastuzumab-containing therapy. Studies of lapatinib-based combination regimens with chemotherapy and other targeted therapies in metastatic and earlier stages of breast cancer are warranted.

Recall and recognition of verbal paired associates in early Alzheimer's disease.

The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support.

Recall and recognition measures of paired associate learning in healthy aging.

Associate-recognition has received little attention as a potential clinical tool for detecting early Alzheimer's disease (AD). As an important preliminary stage to investigating the paradigm's diagnostic utility, we designed and administered a verbal associate-recognition task to healthy elderly participants (n = 62) and compared their performance to that on traditional cued-recall PAL. In both test conditions, the stimulus list comprised of a mixture of highly imageable and less imageable word pairs. Overall, performance on the associate-recognition task was superior to that on the cued-recall analogue. This 'recognition advantage' was not attributable to the higher baseline or chance guessing rate in the associate-recognition condition, as the size of the recognition advantage varied across learning trials and stimulus imageability. In comparison to performance on the imageable stimuli, performance on the less imageable stimuli was poor in both associate-recognition and cued-recall conditions. Across the delay, performances were more likely to drop in the cued-recall condition than the associate-recognition condition. These results suggest that verbal associate-recognition may be clinically efficacious and better tolerated in elderly populations than traditional cued-recall paradigms. Although these results are encouraging, further research is required to examine the utility of associate-recognition in clinical populations, particularly early AD.

Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data.

BACKGROUND: Like microarray-based investigations, high-throughput proteomics techniques require machine learning algorithms to identify biomarkers that are informative for biological classification problems. Feature selection and classification algorithms need to be robust to noise and outliers in the data. RESULTS: We developed a recursive support vector machine (R-SVM) algorithm to select important genes/biomarkers for the classification of noisy data. We compared its performance to a similar, state-of-the-art method (SVM recursive feature elimination or SVM-RFE), paying special attention to the ability of recovering the true informative genes/biomarkers and the robustness to outliers in the data. Simulation experiments show that a 5%- approximately 20% improvement over SVM-RFE can be achieved regard to these properties. The SVM-based methods are also compared with a conventional univariate method and their respective strengths and weaknesses are discussed. R-SVM was applied to two sets of SELDI-TOF-MS proteomics data, one from a human breast cancer study and the other from a study on rat liver cirrhosis. Important biomarkers found by the algorithm were validated by follow-up biological experiments. CONCLUSION: The proposed R-SVM method is suitable for analyzing noisy high-throughput proteomics and microarray data and it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features. The multivariate SVM-based method outperforms the univariate method in the classification performance, but univariate methods can reveal more of the differentially expressed features especially when there are correlations between the features.