Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with 'aggressive' multiple sclerosis.

BACKGROUND: Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standard disease-modifying therapies (DMTs). However, the optimal time for offering AHSCT to patients with 'aggressive' MS is yet to be established. OBJECTIVES: The objective was to explore the safety and efficacy of AHSCT as a first-line DMT in patients with 'aggressive' MS. METHODS: All patients with 'aggressive' MS who received AHSCT as a first-line DMT in five European and North American centres were retrospectively evaluated. RESULTS: Twenty patients were identified. The median interval between diagnosis and AHSCT was 5 (1-20) months. All had multiple poor prognostic markers with a median pre-transplant Expanded Disability Status Scale (EDSS) score of 5.0 (1.5-9.5). After a median follow-up of 30 (12-118) months, the median EDSS score improved to 2.0 (0-6.5, p < 0.0001). No patient had further relapses. Three had residual magnetic resonance imaging (MRI) disease activities in the first 6 months post-transplant, but no further new or enhancing lesions were observed in subsequent scans. CONCLUSION: AHSCT is safe and effective as a first-line DMT in inducing rapid and sustained remission in patients with 'aggressive' MS.

Imaging following thermal ablation of early lung cancers: expected post-treatment findings and tumour recurrence.

Thermal ablation is a minimally invasive technique that is growing in acceptance and popularity in the management of early lung cancers. Although curative resection remains the optimal treatment strategy for stage I pulmonary malignancies, percutaneous ablative treatments may also be considered for selected patients. These techniques can additionally be used in the treatment of oligometastatic disease. Thermal ablation of early lung tumours can be achieved using several different techniques. For example, microwave ablation (MWA) and radiofrequency ablation (RFA) utilise extreme heat, whereas cryoablation uses extremely cold temperatures to cause necrosis and ultimately cell death. Typically, post-ablation imaging studies are performed within the first 1-3 months with subsequent imaging performed at regular intervals to ensure treatment response and to evaluate for signs of recurrent disease. Surveillance imaging is usually undertaken with computed tomography (CT) and integrated positron-emission tomography (PET)/CT. Typical imaging findings are usually seen on CT and PET/CT following thermal ablation of lung tumours, and it is vital that radiologists are familiar with these appearances. In addition, radiologists should be aware of the imaging findings that indicate local recurrence following ablation. The objective of this review is to provide an overview of the expected post-treatment findings on CT and PET/CT following thermal ablation of early primary lung malignancies, as well as describing the imaging appearances of local recurrence.

Detection of exon location in eukaryotic DNA using a fuzzy adaptive Gabor wavelet transform.

The existing model-independent methods for the detection of exons in DNA could not prove to be ideal as commonly employed fixed window length strategy produces spectral leakage causing signal noise The Modified-Gabor-wavelet-transform exploits a multiscale strategy to deal with the issue to some extent. Yet, no rule regarding the occurrence of small and large exons has been specified. To overcome this randomness, scaling-factor of GWT has been adapted based on a fuzzy rule. Due to the nucleotides' genetic code and fuzzy behaviors in DNA configuration, this work could adopt the fuzzy approach. Two fuzzy membership functions (large and small) take care of the variation in the coding regions. The fuzzy-based learning parameter adaptively tunes the scale factor for fast and precise prediction of exons. The proposed approach has an immense plus point of being capable of isolating detailed sub-regions in each exon efficiently proving its efficacy comparing with existing techniques.

An integrated approach for identification of exon locations using recursive Gauss Newton tuned adaptive Kaiser window.

Identification of exon location in a DNA sequence has been considered as the most demanding and challenging research topic in the field of Bioinformatics. This work proposes a robust approach combining the Trigonometric mapping with Adaptive tuned Kaiser Windowing approach for locating the protein coding regions (EXONS) in a genetic sequence. For better convergence as well as improved accurateness, the side lobe height control parameter (ß) of Kaiser Window in the proposed algorithm is made adaptive to track the changing dynamics of the genetic sequence. This yields better tracking potential of the anticipated Adaptive Kaiser algorithm as it uses the recursive Gauss Newton tuning which in turn utilizes the covariance of the error signal to tune the ß factor which has been shown through numerous simulation results under a variety of practical test conditions. A detailed comparative analysis with the existing mapping schemes, windowing techniques, and other signal processing methods like SVD, AN, DFT, STDFT, WT, and ST has also been included in the paper to focus on the strength and efficiency of the proposed approach. Moreover, some critical performance parameters have been computed using the proposed approach to investigate the effectiveness and robustness of the algorithm. In addition to this, the proposed approach has also been successfully applied on a number of benchmark gene sets like Musmusculus, Homosapiens, and C. elegans, etc., where the proposed approach revealed efficient prediction of exon location in contrast to the other existing mapping methods.

Atmospheric Ar and Ne returned from mantle depths to the Earth's surface by forearc recycling.

In subduction zones, sediments, hydrothermally altered lithosphere, fluids, and atmospheric gases are transported into the mantle, where ultrahigh-pressure (UHP) metamorphism takes place. However, the extent to which atmospheric noble gases are trapped in minerals crystallized during UHP metamorphism is unknown. We measured Ar and Ne trapped in phengite and omphacite from the youngest known UHP terrane on Earth to determine the composition of Ar and Ne returned from mantle depths to the surface by forearc recycling. An (40)Ar/(39)Ar age [7.93 ± 0.10 My (1σ)] for phengite is interpreted as the timing of crystallization at mantle depths and indicates that (40)Ar/(39)Ar phengite ages reliably record the timing of UHP metamorphism. Both phengite and omphacite yielded atmospheric (38)Ar/(36)Ar and (20)Ne/(22)Ne. Our study provides the first documentation, to our knowledge, of entrapment of atmospheric Ar and Ne in phengite and omphacite. Results indicate that a subduction barrier for atmospheric-derived noble gases does not exist at mantle depths associated with UHP metamorphism. We show that the crystallization age together with the isotopic composition of nonradiogenic noble gases trapped in minerals formed during subsolidus crystallization at mantle depths can be used to unambiguously assess forearc recycling of atmospheric noble gases. The flux of atmospheric noble gas entering the deep Earth through subduction and returning to the surface cannot be fully realized until the abundances of atmospheric noble gases trapped in exhumed UHP rocks are known.

Innate and humoral recognition of the products of cell death: differential antigenicity and immunogenicity in lupus.

While apoptotic debris is believed to constitute the original antigenic insult in lupus (which is characterized by a time-dependent diversification of autoreactivity), whether such debris and autoantibodies specifically recognizing its constituents mediate differential effects on innate and humoral responses in lupus-prone mice is currently unknown. Apoptotic blebs (as opposed to cellular lysate) enhanced preferentially the maturation of dendritic cells (DCs) from bone marrow precursors drawn from lupus-prone mice. Murine, somatically mutated, apoptotic cell-reactive immunoglobulin (Ig)G monoclonal antibodies demonstrated enhanced recognition of DCs and also displayed a prominent lupus strain-specific bias in mediating DC maturation. Further, immunization of such antibodies specifically in lupus-prone mice resulted in widespread humoral autoreactivity; hypergammaglobulinaemia (a hallmark of systemic autoimmunity) was observed, accompanied by enhanced antibody titres to cellular moieties. Induced antibodies recognized antigens distinct from those recognized by the antibodies employed for immunization; in particular, nephritis-associated anti-double stranded (ds) DNA antibodies and neonatal lupus-associated anti-Ro60 antibodies were elicited by a non-dsDNA, non-Ro60 reactive antibody, and Sm was a favoured target. Further, only in lupus-prone mice did such immunization enhance the kinetics of humoral anti-self responses, resulting in the advanced onset of glomerulosclerosis. These studies reveal that preferential innate and humoral recognition of the products of cell death in a lupus milieu influence the indices associated with autoimmune pathology.

Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells.

BACKGROUND: 17ß-Oestradiol (E2)-induced reactive oxygen species (ROS) have been implicated in regulating the growth of breast cancer cells. However, the underlying mechanism of this is not clear. Here we show how ROS through a novel redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27 contribute to E2-induced growth of MCF-7 breast cancer cells. METHODS: Chromatin immunoprecipitation, qPCR, mass spectrometry, redox western blot, colony formation, cell proliferation, ROS assay, and immunofluorescence microscopy were used to study the role of NRF-1. RESULTS: The major novel finding of this study is the demonstration of oxidative modification of phosphatases PTEN and CDC25A by E2-generated ROS along with the subsequent activation of AKT and ERK pathways that culminated in the activation of NRF-1 leading to the upregulation of cell cycle genes. 17ß-Oestradiol-induced ROS by influencing nuclear proteins p27 and Jab1 also contributed to the growth of MCF-7 cells. CONCLUSIONS: Taken together, our results present evidence in the support of E2-induced ROS-mediated AKT signalling leading to the activation of NRF-1-regulated cell cycle genes as well as the impairment of p27 activity, which is presumably necessary for the growth of MCF-7 cells. These observations are important because they provide a new paradigm by which oestrogen may contribute to the growth of breast cancer.

Aetiologies of diarrhoea in adults from urban and rural treatment facilities in Bangladesh.

The objective of our analysis was to describe the aetiology, clinical features, and socio-demographic background of adults with diarrhoea attending different urban and rural diarrhoeal disease hospitals in Bangladesh. Between January 2010 and December 2011, a total of 5054 adult diarrhoeal patients aged ⩾20 years were enrolled into the Diarrhoeal Disease Surveillance Systems at four different hospitals (two rural and two urban) of Bangladesh. Middle-aged [adjusted odds ratio (aOR) 0·28, 95% confidence interval (CI) 0·23-0·35, P < 0·001] and elderly (aOR 0·15, 95% CI 0·11-0·20, P < 0·001) patients were more likely to present to rural diarrhoeal disease facilities than urban ones. Vibrio cholerae was the most commonly isolated pathogen (16%) of the four pathogens tested followed by rotavirus (5%), enterotoxigenic Escherichia coli (ETEC) (4%), and Shigella (4%). Of these pathogens, V. cholerae (19% vs. 11%, P < 0·001), ETEC (9% vs. 4%, P < 0·001), and rotavirus (5% vs. 3%, P = 0·013) were more commonly detected from patients presenting to urban hospitals than rural hospitals, but Shigella was more frequently isolated from patients presenting to rural hospitals than urban hospitals (7% vs. 2%, P < 0·001). The isolation rate of Shigella was higher in the elderly than in younger adults (8% vs. 3%, P < 0·001). Some or severe dehydration was higher in urban adults than rural adults (P < 0·001). Our findings indicate that despite economic and other progress made, conditions facilitating transmission of V. cholerae and Shigella prevail in adults with diarrhoea in Bangladesh and further efforts are needed to control these infections.

Determinants of percent expenditure of household income due to childhood diarrhoea in rural Bangladesh.

There is limited information on percent expenditure of household income due to childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged <5 years with acute diarrhoea were studied. Percent expenditure was calculated as total expenditure for the diarrhoeal episode divided by monthly family income, multiplied by 100. Overall median percent expenditure was 3·04 (range 0·01-94·35). For Vibrio cholerae it was 6·42 (range 0·52-82·85), for enterotoxigenic Escherichia coli 3·10 (range 0·22-91·87), for Shigella 3·17 (range 0·06-77·80), and for rotavirus 3·08 (range 0·06-48·00). In a multinomial logistic regression model, for the upper tertile of percent expenditure, significant higher odds were found for male sex, travelling a longer distance to reach hospital (⩾median of 4 miles), seeking care elsewhere before attending hospital, vomiting, higher frequency of purging (⩾10 times/day), some or severe dehydration and stunting. V. cholerae was the highest and rotavirus was the least responsible pathogen for percent expenditure of household income due to childhood diarrhoea.

Antimicrobial activity of metal based nanoparticles against microbes associated with diseases in aquaculture.

The emergence of diseases and mortalities in aquaculture and development of antibiotics resistance in aquatic microbes, has renewed a great interest towards alternative methods of prevention and control of diseases. Nanoparticles have enormous potential in controlling human and animal pathogens and have scope of application in aquaculture. The present investigation was carried out to find out suitable nanoparticles having antimicrobial effect against aquatic microbes. Different commercial as well as laboratory synthesized metal and metal oxide nanoparticles were screened for their antimicrobial activities against a wide range of bacterial and fungal agents including certain freshwater cyanobacteria. Among different nanoparticles, synthesized copper oxide (CuO), zinc oxide (ZnO), silver (Ag) and silver doped titanium dioxide (Ag-TiO2) showed broad spectrum antibacterial activity. On the contrary, nanoparticles like Zn and ZnO showed antifungal activity against fungi like Penicillium and Mucor species. Since CuO, ZnO and Ag nanoparticles showed higher antimicrobial activity, they may be explored for aquaculture use.

Electroencephalogram (EEG) in the management of epilepsy in children.

Electroencephalogram (EEG) has an important role in the management of seizure disorder in children. It helps in diagnosis and classification of epilepsy, choosing of antiepileptic medication and prediction of prognosis. When history of epilepsy is unclear, EEG can help to distinguish epileptiform discharges from its counterpart. But EEG has limitations. In epilepsy, EEG has variable range of sensitivity and specificity. Hereby, during interpretation of EEG, clinical situation should not be ignored. Interictal EEG has important diagnostic and prognostic value in epilepsy. But caution is needed during evaluation of significance of interictal epileptiform discharge (IED). Methods like recording of EEG in awake and sleep state, hyperventilation and photic stimulation enhances the yield of interictal EEG. Long term EEG recording has an important role in the assessment of patients who present diagnostic or management difficulties following clinical evaluation and routine EEG.

Field tuning Kitaev systems for spin fractionalization and topological order.

The honeycomb Kitaev model describes aZ2spin liquid with topological order and fractionalized excitations consisting of gappedπ-fluxes and free Majorana fermions. Competing interactions, even when not very strong, are known to destabilize the Kitaev spin liquid. Magnetic fields are a convenient parameter for tuning between different phases of the Kitaev systems, and have even been investigated for potentially counteracting the effects of other destabilizing interactions leading to a revival of the topological phase. Here we review the progress in understanding the effects of magnetic fields on some of the perturbed Kitaev systems, particularly on fractionalization and topological order.

Effect of concentration and addition method of glycerol on the quality of cryopreserved mithun (Bos frontalis) spermatozoa.

The effect of concentration and addition method of glycerol on the quality of cryopreserved mithun (Bos frontalis) spermatozoa was investigated. Semen samples were collected from five healthy mithun bulls through rectal massage method and cryopreserved in liquid nitrogen. The samples were diluted in Tris-egg yolk-glycerol extender, equilibrated for 4 h at 4 °C and loaded into 0.50-ml straws. The straws were then frozen in liquid nitrogen vapour for 10 min and finally plunged into liquid nitrogen for storage. The required amount of glycerol was added into the diluted samples either in a single dose (3%, 4%, 5%, 6% or 7%; added at 37 °C immediately before equilibration) or in split doses (5%, 6% or 7%; the total amount was divided into four equal parts, and a part was added at 37 °C immediately before equilibration, and the remaining parts were added subsequently at 1, 2 and 3 h of equilibration at 4 °C). In the single-dose addition method, following freeze-thawing, greater (p < 0.05) motility (%) and proportion of live spermatozoa with intact acrosome (LSIA, %) in 5% glycerol (40.6 ± 1.7 and 43.4 ± 1.8 respectively) and lesser (p < 0.05) total morphological abnormalities (%) in 5% (14.1 ± 0.8) and 6% (13.7 ± 1.0) glycerol were observed compared to the other glycerol concentrations. In the split-dose addition method, following freeze-thawing, greater (p < 0.05) motility (%) and LSIA proportion (%) were found in 5% (50.2 ± 1.9 and 53.3 ± 1.8 respectively) compared to 6% or 7% glycerol, but the total morphological abnormalities were not different among the glycerol concentrations. In addition, in all the glycerol concentrations, better (p < 0.05) post-freeze-thaw motility and LSIA proportions were observed when glycerol was added in split doses compared to a single dose. In conclusion, Tris-egg yolk extender with 5% glycerol added in split doses was found most suitable for cryopreserving mithun sperm.

Correlation of phase values with CT Hounsfield and R2* values in calcified neurocysticercosis.

PURPOSE: To correlate phase and R2* derived from susceptibility-weighted magnetic resonance imaging (MRI) with computed tomography-Hounsfield (CT-HU) values in calcified neurocysticercosis and to evaluate phase imaging in the assessment of calcified neurocysticercosis. MATERIALS AND METHODS: Thirty-five patients with 52 calcified lesions underwent both CT and MRI. Phase and R2* were calculated from multi-echo 3D-T2-star-weighted-angiography data. MRI and CT data were coregistered using mutual information. Spearman's correlation was performed between quantitative phase and CT-HU and R2* values. The Mann-Whitney U-test was used to see differences between CT-HU and R2* values from corresponding positive and negative phase regions. RESULTS: The median values of CT-HU and R2* from regions with positive and negative phase were found to be 142.10 (range: 41.89-491.75) and 68.5/sec (range: 20-110/sec) and 137.30 (range: 30.83-458.88) and 69/sec (range: 0-110/sec), respectively. There was a significant correlation of positive phase values with corresponding CT-HU and R2* values. In addition, there was a significant correlation of R2* and CT-HU with negative phase values. CONCLUSION: We conclude that there is a significant correlation between negative and positive phase with CT-HU and R2* values, suggesting that the CT hyperdense lesion may have both calcium and other minerals, which can be differentiated using phase imaging. Conventional MRI should include phase imaging to detect calcified neurocysticercosis.

Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism.

Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR=0.45, 95% CI: 0.30-0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30-0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40-0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis.

Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure.

Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.

Integrated multiplex network based approach for hub gene identification in oral cancer.

Background: The incidence of Oral Cancer (OC) is high in Asian countries, which goes undetected at its early stage. The study of genetics, especially genetic networks holds great promise in this endeavor. Hub genes in a genetic network are prominent in regulating the whole network structure of genes. Thus identification of such genes related to specific cancer types can help in reducing the gap in OC prognosis. Methods: Traditional study of network biology is unable to decipher the inter-dependencies within and across diverse biological networks. Multiplex network provides a powerful representation of such systems and encodes much richer information than isolated networks. In this work, we focused on the entire multiplex structure of the genetic network integrating the gene expression profile and DNA methylation profile for OC. Further, hub genes were identified by considering their connectivity in the multiplex structure and the respective protein-protein interaction (PPI) network as well. Results: 46 hub genes were inferred in our approach with a high prediction accuracy (96%), outstanding Matthews coefficient correlation value (93%) and significant biological implications. Among them, genes PIK3CG, PIK3R5, MYH7, CDC20 and CCL4 were differentially expressed and predominantly enriched in molecular cascades specific to OC. Conclusions: The identified hub genes in this work carry ontological signatures specific to cancer, which may further facilitate improved understanding of the tumorigenesis process and the underlying molecular events. Result indicates the effectiveness of our integrated multiplex network approach for hub gene identification. This work puts an innovative research route for multi-omics biological data analysis.

DNA numerical encoding schemes for exon prediction: a recent history.

Bioinformatics in the present day has been firmly established as a regulator in genomics. In recent times, applications of Signal processing in exon prediction have gained a lot of attention. The exons carry protein information. Proteins are composed of connected constituents known as amino acids that characterize the specific function. Conversion of the nucleotide character string into a numerical sequence is the gateway before analyzing it through signal processing methods. This numeric encoding is the mathematical descriptor of nucleotides and is based on some statistical properties of the structure of nucleic acids. Since the type of encoding extremely affects the exon detection accuracy, this paper is devised for the review of existing encoding (mapping) schemes. The comparative analysis is formulated to emphasize the importance of the genetic code setting of amino acids considered for application related to computational elucidation for exon detection. This work covers much helpful information for future applications.

Assessment of cosmesis and quality of life and their correlation using novel, validated methods in breast cancer patients who had undergone breast conservation therapy.

PURPOSE: To assess cosmesis [Breast Cancer Conservation Treatment. Cosmetic Results (BCCT.CORE) software] & QOL [EORTC QLQ (Quality of Life Questionnaire)-C30, BR23 questionnaires] using objective methods &to correlate effect of cosmesis on QOL (Quality of life) in breast cancer patients post BCT (Breast conservation therapy) using a cross-sectional observational study from a tertiary hospital. MATERIALS & METHODS: Cosmesis & QOL had been assessed in all biopsy-proven adult patients of unilateral breast cancer, who had undergone BCT with minimum three months post-BCT & three months post last adjuvant chemotherapy cycle, whichever is delivered last (with just hormonal therapy or followup remaining based on hormone receptor status). Pearson chi-square & Kendall correlation Tau-b tests had been used for testing association between Cosmesis & QOL. Variation of QOL scores between Cosmetic groups had been assessed using Mann-Whitney U-test. RESULTS: Cosmesis was Excellent/Good in 60.4 % of patients. 58.4 % of patients had Excellent/Good Quality of Life. Cosmesis & QOL had a positive correlation (intermediate strength) [Kendall correlation factor-0.484]. QOL-Global scale had better median scores in Excellent/ Good cosmetic group when compared to Fair/Poor group, while for functional & symptomatic scales, contrary had been true. Difference of median-scores between the two groups hadn't been statistically significant in five aspects - being upset over hair loss (p-0.09), sexual-enjoyment (p-0.33), nausea-vomiting (p-0.29), constipation (p0.32) & diarrhea (p-0.72). CONCLUSION: About 2/3rds of patients post-BCT had Excellent/Good Cosmesis & Excellent/Good QOL. Every measure taken before, during & post-BCT to improve Cosmesis might result in better QOL. Future studies must use more accurate three-dimensional methods to assess Cosmesis & its effect on QOL.