Transplant ineligible multiple myeloma patients presenting as paraplegia/paraparesis a prospective single institution study

Background: Multiple myeloma a plasma cell neoplasm characterized by heterogeneous myriad of presentation with paraparesis or paraplegia in 20% cases due to spinal cord compression by vertebral collapse, compression or fracture.Methods: This is a prospective observational study of thirty transplant ineligible multiple myeloma patients with paraplegia/paraparesis. Pretreatment evaluation done as per standard protocol including MRI whole spine. Involved spine XRT 8Gy single fraction followed by BLD (Bortezomib 1.3mg/m2 weekly once, Lenalidomide 10mg/m2 for 21 days, oral dexamethasone 40 mg weekly once). Neurological parameters, time to neurological and tumor response at 6 months assessed. Patients in very good partial response or complete response were maintained on Lenalidomide and bisphosphonate therapy for a period of two years. The duration of symptoms and time to response were analyzed with Mann Whitney Cox test.Results: 15 patients were grade 0 power and others grade 1 or 2. Median time to any neurological response was 2.97 weeks. 63.3% of patients achieved power of grade 5, 30% grade 4 and 6.7% grade 3 powers. 23.3% patients received complete response while 63.3% patient’s very good partial response.Conclusions: Bedridden myeloma patients had an excellent improvement in quality of life and tumor control with this treatment schedule.

A Bayesian Analysis of the Correlations Among Sunspot Cycles

Sunspot numbers form a comprehensive, long-duration proxy of solar activity and have been used numerous times to empirically investigate the properties of the solar cycle. A number of correlations have been discovered over the 24 cycles for which observational records are available. Here we carry out a sophisticated statistical analysis of the sunspot record that reaffirms these correlations, and sets up an empirical predictive framework for future cycles. An advantage of our approach is that it allows for rigorous assessment of both the statistical significance of various cycle features and the uncertainty associated with predictions. We summarize the data into three sequential relations that estimate the amplitude, duration, and time of rise to maximum for any cycle, given the values from the previous cycle. We find that there is no indication of a persistence in predictive power beyond one cycle, and conclude that the dynamo does not retain memory beyond one cycle. Based on sunspot records up to October 2011, we obtain, for Cycle 24, an estimated maximum smoothed monthly sunspot number of 97 +- 15, to occur in January--February 2014 +- 6 months.Comment: Accepted for publication in Solar Physic

AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture

The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require datamanagement plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices

Transplant ineligible multiple myeloma patients presenting as paraplegia/paraparesis a prospective single institution study

oai:ojs.msjonline.org:article/1Background: Multiple myeloma a plasma cell neoplasm characterized by heterogeneous myriad of presentation with paraparesis or paraplegia in 20% cases due to spinal cord compression by vertebral collapse, compression or fracture.Methods: This is a prospective observational study of thirty transplant ineligible multiple myeloma patients with paraplegia/paraparesis. Pretreatment evaluation done as per standard protocol including MRI whole spine. Involved spine XRT 8Gy single fraction followed by BLD (Bortezomib 1.3mg/m2 weekly once, Lenalidomide 10mg/m2 for 21 days, oral dexamethasone 40 mg weekly once). Neurological parameters, time to neurological and tumor response at 6 months assessed. Patients in very good partial response or complete response were maintained on Lenalidomide and bisphosphonate therapy for a period of two years. The duration of symptoms and time to response were analyzed with Mann Whitney Cox test.Results: 15 patients were grade 0 power and others grade 1 or 2. Median time to any neurological response was 2.97 weeks. 63.3% of patients achieved power of grade 5, 30% grade 4 and 6.7% grade 3 powers. 23.3% patients received complete response while 63.3% patient’s very good partial response.Conclusions: Bedridden myeloma patients had an excellent improvement in quality of life and tumor control with this treatment schedule.

Not Available

Not AvailableLeptospirosis is a common but largely underreported zoonotic disease in India. It has been recognized as a re-emerging infectious disease causing deaths in dogs as well as humans. Leptospires have been isolated from both clinically ill and apparently healthy animals from different geographical regions but there is no information on the presence of leptospires in various clinical conditions of animals in the northern state of Himachal Pradesh, India. Here, using dark field microscopy, culture isolation and molecular biology-based tests, we confirm leptospirosis in three clinically affected dogs with chronic renal involvement. The study reports the first isolation and molecular confirmation of leptospires from clinically affected dogs in Himachal Pradesh, India.Not Availabl

Complete nucleotide sequence analysis of a vaccine strain and a field isolate of foot-and-mouth disease virus serotype Asia1 with an insertion in VP1 genomic region

Complete nucleotide sequences except the poly (C) tract and poly (A) tail of a vaccine strain (IND 491/97) and an atypical field isolate (IND 321/01) of Foot-and-mouth disease virus (FMDV) serotype Asia1 are described. Amino acid (aa) sequence analysis of the VP1 protein of the field isolate revealed that the latter has 212 instead of 210 or 211 aa found in the so far available sequences of other FMDV isolates of Asia1 serotype. The insertion was localized in the hypervariable region of aa 130-160 of VP1 protein. Nucleotide sequencing of the entire genome was therefore carried out to detect changes in other parts of the genome, if any, besides VP1, which could contribute to its fitness. An 8.16 kb sequence of IND 491/97 and an 8.162 kb sequence of IND 321/01 were compared with each other and also with the known sequence of IND 63/72, another vaccine strain of serotype Asia1. Comparison of the entire polyprotein coding (L to 3D) region of IND 321/01 with those of the two Asia1 vaccine strains (IND 63/72 and IND 491/97) revealed no significant differences. A similar comparison of IND 491/97 with IND 63/72 revealed variability across the entire length of the genome. In addition to the capsid-coding region, sequence variability was also observed in non-structural proteins albeit to different extent. This study shows that in the gene pool of serotype Asia1 at least three groups of isolates/strains are present with respect to the length of VP1 protein

Sequence analysis of Vpg protein of Asia-1 field isolates of Foot and Mouth Disease Virus in India

Foot-and-Mouth Disease (FMD), the most economically important disease of cloven-hoofed animals is endemic in India. A total of twenty field isolates belonging to serotype Asia1, collected from different states in India during 1986-2002 were taken as BHK-21 cell culture adapted virus from the National Repository of FMDV at the Project Directorate on Foot-and-Mouth Disease (PD FMD). RT-PCR products of the revived viruses were confirmed by agarose gel electrophoresis and the gel-purified products were subjected to cycle sequencing in an automated sequencer. Vpg protein, which on uridylation serves as a primer during FMDV replication is found conserved across serotypes O, A and C. The sequences generated in the present work were compared with respect to other serotypes with the objective of investigating the amino acid variability of the three redundant copies of VPg proteins in a diverse group field isolates of type Asia1

Mycobacterium tuberculosis requires SufT for Fe-S cluster maturation, metabolism, and survival in vivo.

Iron-sulfur (Fe-S) cluster proteins carry out essential cellular functions in diverse organisms, including the human pathogen Mycobacterium tuberculosis (Mtb). The mechanisms underlying Fe-S cluster biogenesis are poorly defined in Mtb. Here, we show that Mtb SufT (Rv1466), a DUF59 domain-containing essential protein, is required for the Fe-S cluster maturation. Mtb SufT homodimerizes and interacts with Fe-S cluster biogenesis proteins; SufS and SufU. SufT also interacts with the 4Fe-4S cluster containing proteins; aconitase and SufR. Importantly, a hyperactive cysteine in the DUF59 domain mediates interaction of SufT with SufS, SufU, aconitase, and SufR. We efficiently repressed the expression of SufT to generate a SufT knock-down strain in Mtb (SufT-KD) using CRISPR interference. Depleting SufT reduces aconitase's enzymatic activity under standard growth conditions and in response to oxidative stress and iron limitation. The SufT-KD strain exhibited defective growth and an altered pool of tricarboxylic acid cycle intermediates, amino acids, and sulfur metabolites. Using Seahorse Extracellular Flux analyzer, we demonstrated that SufT depletion diminishes glycolytic rate and oxidative phosphorylation in Mtb. The SufT-KD strain showed defective survival upon exposure to oxidative stress and nitric oxide. Lastly, SufT depletion reduced the survival of Mtb in macrophages and attenuated the ability of Mtb to persist in mice. Altogether, SufT assists in Fe-S cluster maturation and couples this process to bioenergetics of Mtb for survival under low and high demand for Fe-S clusters