A three-dimensional principal component analysis approach for exploratory analysis of hyperspectral data: identification of ovarian cancer samples based on Raman microspectroscopy imaging of blood plasma

Hyperspectral imaging is a powerful tool to obtain both chemical and spatial information of biological systems. However, few algorithms are capable of working with full three-dimensional images, in which reshaping or averaging procedures are often performed to reduce the data complexity. Herein, we propose a new algorithm of three-dimensional principal component analysis (3D-PCA) for exploratory analysis of complete 3D spectrochemical images obtained through Raman microspectroscopy. Blood plasma samples of ten patients (5 healthy controls, 5 diagnosed with ovarian cancer) were analysed by acquiring hyperspectral imaging in the fingerprint region (∼780–1858 cm−1). Results show that 3D-PCA can clearly differentiate both groups based on its scores plot, where higher loadings coefficients were observed in amino acids, lipids and DNA regions. 3D-PCA is a new methodology for exploratory analysis of hyperspectral imaging, providing fast information for class differentiation

Vibrational spectroscopy: a promising approach to discriminate neurodegenerative disorders

Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been attributed to their late diagnosis, after brain damage has already become widespread. An earlier and improved diagnosis is necessary for the enrolment of patients into clinical trials and can pave the way for the development of therapeutic tactics. Novel analytical techniques, such as mass spectrometry and vibrational spectroscopy, have been able to successfully detect and characterise neurodegenerative disorders. It is critical to globally support and make use of innovative basic research and techniques, which could ultimately lead to the creation of a cost-effective diagnostic test. Minimally invasive samples, such as biological fluids, have also been shown to reveal information for these diseases; utilising them could simplify sample collection/analysis and be more preferable to patients

Interventions targeted at women to encourage the uptake of cervical screening

BACKGROUND World-wide, cervical cancer is the second most common cancer in women. Increasing the uptake of screening, alongside increasing informed choice is of great importance in controlling this disease through prevention and early detection. OBJECTIVES To assess the effectiveness of interventions aimed at women, to increase the uptake, including informed uptake, of cervical cancer screening. SEARCH STRATEGY We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Issue 1, 2009. MEDLINE, EMBASE and LILACS databases up to March 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA Randomised controlled trials (RCTs) of interventions to increase uptake/informed uptake of cervical cancer screening. DATA COLLECTION AND ANALYSIS Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. MAIN RESULTS Thirty-eight trials met our inclusion criteria. These trials assessed the effectiveness of invitational and educational interventions, counselling, risk factor assessment and procedural interventions. Heterogeneity between trials limited statistical pooling of data. Overall, however, invitations appear to be effective methods of increasing uptake. In addition, there is limited evidence to support the use of educational materials. Secondary outcomes including cost data were incompletely documented so evidence was limited. Most trials were at moderate risk of bias. Informed uptake of cervical screening was not reported in any trials. AUTHORS' CONCLUSIONS There is evidence to support the use of invitation letters to increase the uptake of cervical screening. There is limited evidence to support educational interventions but it is unclear what format is most effective. The majority of the studies are from developed countries and so the relevance to developing countries is unclear.Output Type: Revie

Underlying role of mitochondrial mutagenesis in the pathogenesis of a disease and current approaches for translational research

Mitochondrial diseases have been extensively investigated over the last three decades but many questions regarding their underlying aetiologies remain unanswered. Mitochondrial dysfunction is not only responsible for a range of neurological and myopathy diseases, but is also considered pivotal in a broader spectrum of common diseases such as epilepsy, autism and bipolar disorder. These disorders are a challenge to diagnose and treat as their aetiology might be multifactorial. In this review, the focus is placed on potential mechanisms capable of introducing defects in mitochondria resulting in disease. Special attention is given to the influence of xenobiotics on mitochondria; environmental factors inducing mutations or epigenetic changes in the mitochondrial genome can alter its expression and impair the whole cell’s functionality. Specifically, we suggest that environmental agents can cause damage by generating abasic sites in mitochondrial DNA, which consequently lead to mutagenesis. Abasic sites are observed in DNA after spontaneous loss of a nucleic base (e.g., “apurinic sites” after loss of purines, adenine or guanine) or through base excision repair; if left unrepaired, they can produce mutagenic DNA lesions. Moreover, we describe current approaches for handling mitochondrial diseases, as well as available prenatal diagnostic tests towards eliminating these maternally-inherited diseases. Undoubtedly, more research is required, as current therapeutic approaches mostly employ palliative therapies rather than targeting primary mechanisms or prophylactic approaches. More effort is needed into further unravelling the relationship between xenobiotics and mitochondria as the extent of influence in mitochondrial pathogenesis is increasingly recognised

An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia

Introduction: High-risk HPV (HR-HPV) related invasive cervical cancer (ICC) causes >270,000 deaths per annum world-wide with over 85% of these occurring in low-resource countries. Ablative and excisional treatment modalities are restricted for use with high-grade pre-cancerous cervical disease with HPV infection and low-grade dysplasia mostly managed by a watch-and-wait policy.Areas Covered: Various pharmacological approaches have been investigated as non-destructive alternatives for the treatment of HR-HPV infection and associated dysplasia. These are discussed dealing with efficacy, ease-of-use (physician or self-applied), systemic or locally applied, side-effects, cost and risks. The main focus is the perceived impact on current clinical practice of a self-applied, effective and safe pharmacological anti-HPV treatment.Expert opinion: Current prophylactic HPV vaccines are expensive, HPV type restricted and have little effect in already infected women. Therapeutic vaccines are under development but are also HPV type-restricted. At present, the developed nations use national cytology screening and surgical procedures to treat only women identified with HPV-related high-grade dysplastic disease. However, since HPV testing is rapidly replacing cytology as the test-of-choice, a suitable topically-applied and low-cost antiviral treatment could be an ideal solution for treatment of HPV infection per se with test-of-cure carried out by repeat HPV testing. Cytology would only then be necessary for women who remained HPV positive. Although of significant benefit in the developed countries, combining such a treatment with self-sampled HPV testing could revolutionise the management of this disease in the developing world which lack both the infrastructure and resources to establish national cytology screening programs

Detection of ovarian cancer (± neo-adjuvant chemotherapy effects) via ATR-FTIR spectroscopy: comparative analysis of blood and urine biofluids in a large patient cohort

Ovarian cancer remains the most lethal gynaecological malignancy, as its timely detection at early stages remains elusive. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy of biofluids has been previously applied in pilot studies for ovarian cancer diagnosis, with promising results. Herein, these initial findings were further investigated by application of ATR-FTIR spectroscopy in a large patient cohort. Spectra were obtained by measurements of blood plasma and serum, as well as urine, from 116 patients with ovarian cancer and 307 patients with benign gynaecological conditions. A preliminary chemometric analysis revealed significant spectral differences in ovarian cancer patients without previous chemotherapy (n=71) and those who had received neo-adjuvant chemotherapy - NACT (n=45), so these groups were compared separately with benign controls. Classification algorithms with blind predictive model validation demonstrated that serum was the best biofluid, achieving 76% sensitivity and 98% specificity for ovarian cancer detection, whereas urine exhibited poor performance. A drop in sensitivities for the NACT ovarian cancer group in plasma and serum indicates the potential of ATR-FTIR spectroscopy to identify chemotherapy-related spectral changes. Comparisons of regression coefficients plots for identification of biomarkers suggest that glycoproteins (such as CA125) are the main classifiers for ovarian cancer detection and responsible for smaller differences in spectra between NACT patients and benign controls. This study confirms the capacity of biofluids’ ATR-FTIR spectroscopy (mainly blood serum) to diagnose ovarian cancer with high accuracy and demonstrates its potential in monitoring response to chemotherapy, which is reported for the first time

Immediate referral to colposcopy versus cytological surveillance for minor cervical cytological abnormalities in the absence of HPV test

A C K N O W L E D G E M E N T S The authors wish to acknowledge Jo Morrison for her clinical and editorial advice, Jane Hayes f or designing the search strategy and Gail Quinn, Clare Jess and Tracey Bishop for their contribution to the editorial process.This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Group. The views and opinions expressed therein are those of the authors andd o not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.Peer reviewedPublisher PD

Aluminium foil as a potential substrate for ATR-FTIR, transflection FTIR or Raman spectrochemical analysis of biological specimens

The substantial cost of substrates is an enormous obstacle in the successful translation of biospectroscopy (IR or Raman) into routine clinical/laboratory practice (screening or diagnosis). As a cheap and versatile substrate, we compared the performance of readily available aluminium (Al) foil with low-E, Au-coated and glass slides for cytological and histological specimen analysis by attenuated total reflection Fourier-transform infrared (ATR-FTIR), transflection FTIR or Raman spectroscopy. The low and almost featureless background signal of Al foil enables the acquisition of IR or Raman spectra without substrate interference or sacrificing important fingerprint biochemical information of the specimen, even for very thin samples with thicknesses down to 2 \ensuremathμm. Al foil is shown to perform as well as, if not better than, low-E or Au-coated slide, irrespective of its relatively rough surface. Although transmission FTIR is not possible on Al foil, this work demonstrates Al foil is an inexpensive, readily available and versatile substrate suitable for ATR-FTIR, transflection FTIR or Raman spectrochemical measurements of diverse biological specimens. The features of Al foil demonstrated here could promote a transition towards accessible substrates that can be readily implemented in either research or clinical settings