A challenging case of fenofibrate induced neutropenia

Fenofibrate induced neutropenia is a rare condition. We reported 59-year-old male who developed neutropenia after taking fenofibrate for 20 days. He presented with complaints of fever, upper respiratory tract infection (URTI) symptoms. At presentation his total counts were 800. He was evaluated thoroughly for other causes of neutropenia and was treated with antibiotics, steroids, G-CSF. Once the fenofibrate was stopped, patient counts improved and his symptoms subsided. Hence, it is very important to always keep in mind the possibility of side effects of drugs, however remotely rare they are.

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.Fil: Mishra, Sneha. No especifíca;Fil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Tamta, Ankit Kumar. No especifíca;Fil: Khan, Danish. No especifíca;Fil: Srinivasan, Shalini. No especifíca;Fil: Ravi, Venkatraman. No especifíca;Fil: Abbotto, Elena. Università degli Studi di Genova; ItaliaFil: Arathi, Bangalore Prabhashankar. No especifíca;Fil: Kumar, Shweta. No especifíca;Fil: Jain, Aditi. No especifíca;Fil: Ramaian, Anand S.. No especifíca;Fil: Kizkekra, Shruti M.. No especifíca;Fil: Rajagopal, Raksha. No especifíca;Fil: Rao, Swathi. No especifíca;Fil: Krishna, Swati. No especifíca;Fil: Asirvatham Jeyaraj, Ninitha. Indian Institute of Technology; IndiaFil: Haggerty, Elizabeth R.. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Kurland, Irwin J.. No especifíca;Fil: Veeranna, Ravindra P.. No especifíca;Fil: Jayavelu, Tamilselvan. No especifíca;Fil: Bruzzone, Santina. Università degli Studi di Genova; ItaliaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Sundaresan, Nagalingam R.. No especifíca

Persistencia de malezas gramíneas en cultivos de trigo del sudeste bonaerense

En la presente tesis se estudió la persistencia de especies poáceas en cultivos de trigo del sudeste de Buenos Aires. En dicha región, Avena fatua L. y Lolium multiflorum Lam. son las malezas poáceas más importantes, tanto por la dificultad de control como por sus efectos competitivos sobre el cultivo. A los efectos de cuantificar la persistencia de dichas especies, se estudió la composición de la comunidad de malezas en dos momentos del ciclo: preaplicación de herbicidas y precosecha. Individuos de ambas malezas fueron registrados en ambos momentos como consecuencia de “escapes” al control realizado con herbicidas, siendo A. fatua más constante que L. mutiflorum. Posteriormente, se estudiaron los procesos que definen la persistencia de ambas malezas. Los resultados obtenidos indican que el ajuste del momento de emergencia es jerárquicamente el factor más importante para explicar la persistencia de A. fatua. Se demostró que los modelos de germinación son diferentes según las semillas provengan de un lote agrícola o de una condición de no cultivo, siendo estas diferencias de naturaleza genética. Por otro lado, la variabilidad en la supervivencia a los herbicidas es el factor que mejor explica la persistencia de L. multiflorum, habiéndose documentado resistencia cruzada a los herbicidas inhibidores de la ALS, pyroxsulam, imazamox y flucarbazone, sin antecedentes previos en la región. Los índices de resistencia encontrados presentan variación con la temperatura ambiente en post-aplicación del herbicida, habiéndose registrado mayor resistencia con mayor temperatura. Además, se comprobó que los individuos resistentes presentan menor tiempo a floración que los susceptibles. Tal atributo puede significar una ventaja demográfica para dichas poblaciones. Queda así demostrada la persistencia de A. fatua y L. multiflorum durante el ciclo del cultivo más allá de las prácticas de control realizadas y la participación de dos procesos demográficos distintos (establecimiento y supervivencia) en dicha persistencia

Constrained Static/Dynamic Economic Emission Load Dispatch Using Elephant Herd Optimization

The rapid growth in greenhouse gases (GHGs), the lack of electricity production, and an ever-increasing demand for electrical energy requires an optimal reduction in coal-fired thermal generating units (CFTGU) with the aim of minimizing fuel costs and emissions. Previous approaches have been unable to deal with such problems due to the non-convexity of realistic scenarios and confined optimum convergence. Instead, meta-heuristic techniques have gained more attention in order to deal with such constrained static/dynamic economic emission load dispatch (ELD/DEELD) problems, due to their flexibility and derivative-free structures. Hence, in this work, the elephant herd optimization (EHO) technique is proposed in order to solve constrained non-convex static and dynamic ELD problems in the power system. The proposed EHO algorithm is a nature-inspired technique that utilizes a new separation method and elitism strategy in order to retain the diversity of the population and to ensure that the fittest individuals are retained in the next generation. The current approach can be implemented to minimize both the fuel and emission cost functions of the CFTGUs subject to power balance constraints, active power generation limits, and ramp rate limits in the system. Three test systems involving 6, 10, and 40 units were utilized to demonstrate the effectiveness and practical feasibility of the proposed algorithm. Numerical results indicate that the proposed EHO algorithm exhibits better performance in most of the test cases as compared to recent existing algorithms when applied to the static and dynamic ELD issue, demonstrating its superiority and practicability

Forecasting the heavy rainfall during Himalayan flooding—June 2013

On 17th June 2013 the state of Uttarakhand in India (Latitude 28.72°N to 31.45°N and Longitude 77.57°E–81.03°E) received more than 340 mm of rainfall, which is 375% more than the daily normal (65.9 mm) rainfall during monsoon. This caused heavy floods in Uttarakhand as well as unprecedented damage to life and property. In this study we aim at assessing the performance of two deterministic forecast models, Global Forecast System (GFS/T574) and Unified Model (NCUM), run at NCMRWF, in predicting the heavy rainfall observed over Uttarakhand region of India during 17–18th June, 2013. Verification of the synoptic features in forecasts of the two models suggests that NCUM accurately captures the circulation features as compared to T574. Further verification of this event is carried out based on the contiguous rain area (CRA) technique. CRA verification is used in computing the total mean square error (MSE) which is based on displacement, volume and pattern errors. This verification technique also, confirms the better skill of NCUM over T574 in terms of forecast peak rainfall amounts, volume and average rain rate, lower MSE and root mean square error (RMSE) as well as having higher hit rates and lower misses and false alarm rates for different rainfall thresholds from Day 1 to Day 5 forecasts

Supression of Perforin-like Protein pores inhibit Plasmodium multistage-growth, transmission and erythrocyte senescence

status: Published onlin

Comparative Metagenomic Analysis of Soil Microbial Communities across Three Hexachlorocyclohexane Contamination Levels

This paper presents the characterization of the microbial community responsible for the in-situ bioremediation of hexachlorocyclohexane (HCH). Microbial community structure and function was analyzed using 16S rRNA amplicon and shotgun metagenomic sequencing methods for three sets of soil samples. The three samples were collected from a HCH-dumpsite (450 mg HCH/g soil) and comprised of a HCH/soil ratio of 0.45, 0.0007, and 0.00003, respectively. Certain bacterial; (Chromohalobacter, Marinimicrobium, Idiomarina, Salinosphaera, Halomonas, Sphingopyxis, Novosphingobium, Sphingomonas and Pseudomonas), archaeal; (Halobacterium, Haloarcula and Halorhabdus) and fungal (Fusarium) genera were found to be more abundant in the soil sample from the HCH-dumpsite. Consistent with the phylogenetic shift, the dumpsite also exhibited a relatively higher abundance of genes coding for chemotaxis/motility, chloroaromatic and HCH degradation (lin genes). Reassembly of a draft pangenome of Chromohalobacter salaxigenes sp. (~8X coverage) and 3 plasmids (pISP3, pISP4 and pLB1; 13X coverage) containing lin genes/clusters also provides an evidence for the horizontal transfer of HCH catabolism genes