Actinopolyspora algeriensis sp. nov., a novel halophilic actinomycete isolated from a Saharan soil

A halophilic actinomycete strain designated H19T, was isolated from a Saharan soil in the Bamendil region (Ouargla province, South Algeria) and was characterized taxonomically by using a polyphasic approach. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus Actinopolyspora, and 16S rRNA gene sequence analysis confirmed that strain H19T was a novel species of the genus Actinopolyspora. DNA–DNA hybridization value between strain H19T and the nearest Actinopolyspora species, A. halophila, was clearly below the 70 % threshold. The genotypic and phenotypic data showed that the organism represents a novel species of the genus Actinopolyspora for which the name Actinopolyspora algeriensis sp. nov. is proposed, with the type strain H19T (= DSM 45476T = CCUG 62415T)

Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

Mini-open anterior spine surgery for anterior lumbar diseases

Minimally invasive surgeries including endoscopic surgery and mini-open surgery are current trend of spine surgery, and its main advantages are shorter recovery time and cosmetic benefits, etc. However, mini-open surgery is easier and less technique demanding than endoscopic surgery. Besides, anterior spinal fusion is better than posterior spinal fusion while considering the physiological loading, back muscle function, etc. Therefore, we aimed to introduce the modified “mini-open anterior spine surgery” (MOASS) and to evaluate the feasibility, effectiveness and safety in the treatment of various anterior lumbar diseases with this technique. A total of 61 consecutive patients (46 female, 15 male; mean age 58.2 years) from 1997 to 2004 were included in this study, with an average follow-up of 24–52 (mean 43) months. The disease entities included vertebral fracture (20), failed back surgery (13), segmental instability or spondylolisthesis (10), infection (8), herniated disc (5), undetermined lesion for biopsy (4), and hemivertebra (1). Lesions involved 13 cases at T12–L1, 18 at L1–L2, 18 at L2–L3, 22 at L3–L4 and 11 at L4–L5 levels. All patients received a single stage anterior-only procedure for their anterior lumbar disease. We used the subjective clinical results, Oswestry disability index, fusion rate, and complications to evaluate our clinical outcome. Most patients (91.8%) were subjectively satisfied with the surgery and had good-to-excellent outcomes. Mean operation time was 85 (62–124) minutes, and mean blood loss was 136 (minimal-250) ml in the past 6 years. Hospital stay ranged from 4–26 (mean 10.6) days. Nearly all cases had improved back pain (87%), physical function (90%) and life quality (85%). Most cases (95%) achieved solid or probable solid bony fusion. There were no major complications. Therefore, MOASS is feasible, effective and safe for patients with various anterior lumbar diseases

Agent-Based Model of Therapeutic Adipose-Derived Stromal Cell Trafficking during Ischemia Predicts Ability To Roll on P-Selectin

Intravenous delivery of human adipose-derived stromal cells (hASCs) is a promising option for the treatment of ischemia. After delivery, hASCs that reside and persist in the injured extravascular space have been shown to aid recovery of tissue perfusion and function, although low rates of incorporation currently limit the safety and efficacy of these therapies. We submit that a better understanding of the trafficking of therapeutic hASCs through the microcirculation is needed to address this and that selective control over their homing (organ- and injury-specific) may be possible by targeting bottlenecks in the homing process. This process, however, is incredibly complex, which merited the use of computational techniques to speed the rate of discovery. We developed a multicell agent-based model (ABM) of hASC trafficking during acute skeletal muscle ischemia, based on over 150 literature-based rules instituted in Netlogo and MatLab software programs. In silico, trafficking phenomena within cell populations emerged as a result of the dynamic interactions between adhesion molecule expression, chemokine secretion, integrin affinity states, hemodynamics and microvascular network architectures. As verification, the model reasonably reproduced key aspects of ischemia and trafficking behavior including increases in wall shear stress, upregulation of key cellular adhesion molecules expressed on injured endothelium, increased secretion of inflammatory chemokines and cytokines, quantified levels of monocyte extravasation in selectin knockouts, and circulating monocyte rolling distances. Successful ABM verification prompted us to conduct a series of systematic knockouts in silico aimed at identifying the most critical parameters mediating hASC trafficking. Simulations predicted the necessity of an unknown selectin-binding molecule to achieve hASC extravasation, in addition to any rolling behavior mediated by hASC surface expression of CD15s, CD34, CD62e, CD62p, or CD65. In vitro experiments confirmed this prediction; a subpopulation of hASCs slowly rolled on immobilized P-selectin at speeds as low as 2 µm/s. Thus, our work led to a fundamentally new understanding of hASC biology, which may have important therapeutic implications

Trypanosome Lytic Factor, an Antimicrobial High-Density Lipoprotein, Ameliorates Leishmania Infection

Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system

Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge

A novel actinomycete, designated PA3T, was isolated from an oil refinery wastewater treatment plant, located in Palos de la frontera, Huelva, Spain, and characterized taxonomically by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate formed a distinct subclade in the Pseudonocardia tree together with Pseudonocardia asaccharolytica DSM 44247T. The chemotaxonomic properties of the isolate, for example, the presence of MK-8 (H4) as the predominant menaquinone and iso-C16:0 as the major fatty acid are consistent with its classification in the genus Pseudonocardia. DNA:DNA pairing experiments between the isolate and the type strain of P. asaccharolytica DSM 44247T showed that they belonged to separate genomic species. The two strains were readily distinguished using a combination of phenotypic properties. Consequently, it is proposed that isolate PA3T represents a novel species for which the name Pseudonocardia hispaniensis sp. nov. is proposed. The type strain is PA3T (= CCM 8391T = CECT 8030T).Cuesta Amat, G.; Soler Hernández, A.; Alonso Molina, JL.; Ruvira, M.; Lucena, T.; Arahal, D.; Goodfellow, M. (2013). Pseudonocardia hispaniensis sp. nov., a novel actinomycete isolated from industrial wastewater activated sludge. Antonie van Leeuwenhoek. 103(1):135-142. doi:10.1007/s10482-012-9792-1S1351421031Alonso JL, Cuesta G, Ramírez GW, Morenilla JJ, Bernácer I, Lloret RM (2009) Manual de técnicas avanzadas para la identificación y control de bacterias filamentosas. Epsar-Generalitat Valenciana, España, p 21–36Ara I, Tsetseg B, Daram D, Suto M, Ando K (2011) Pseudonocardia mongoliensis sp. nov. and Pseudonocardia khuvsgulensis sp. nov., isolated from soil. 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Sensitivity of MRI Tumor Biomarkers to VEGFR Inhibitor Therapy in an Orthotopic Mouse Glioma Model

MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI) and a slight decrease in the water apparent diffusion coefficient (ADC) were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV), relative microvascular blood volume (rMBV), transverse relaxation time (T2), blood vessel permeability (Ktrans), and extravascular-extracellular space (νe). The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology

Comparative Coastal Risk Index (CCRI): A multidisciplinary risk index for Latin America and the Caribbean

As the world's population grows to a projected 11.2 billion by 2100, the number of people living in low-lying areas exposed to coastal hazards is projected to increase. Critical infrastructure and valuable assets continue to be placed in vulnerable areas, and in recent years, millions of people have been displaced by natural hazards. Impacts from coastal hazards depend on the number of people, value of assets, and presence of critical resources in harm's way. Risks related to natural hazards are determined by a complex interaction between physical hazards, the vulnerability of a society or social-ecological system and its exposure to such hazards. Moreover, these risks are amplified by challenging socioeconomic dynamics, including poorly planned urban development, income inequality, and poverty. This study employs a combination of machine learning clustering techniques (Self Organizing Maps and K-Means) and a spatial index, to assess coastal risks in Latin America and the Caribbean (LAC) on a comparative scale. The proposed method meets multiple objectives, including the identification of hotspots and key drivers of coastal risk, and the ability to process large-volume multidimensional and multivariate datasets, effectively reducing sixteen variables related to coastal hazards, geographic exposure, and socioeconomic vulnerability, into a single index. Our results demonstrate that in LAC, more than 500,000 people live in areas where coastal hazards, exposure (of people, assets and ecosystems) and poverty converge, creating the ideal conditions for a perfect storm. Hotspot locations of coastal risk, identified by the proposed Comparative Coastal Risk Index (CCRI), contain more than 300,00 people and include: El Oro, Ecuador; Sinaloa, Mexico; Usulutan, El Salvador; and Chiapas, Mexico. Our results provide important insights into potential adaptation alternatives that could reduce the impacts of future hazards. Effective adaptation options must not only focus on developing coastal defenses, but also on improving practices and policies related to urban development, agricultural land use, and conservation, as well as ameliorating socioeconomic conditions

Using indirect methods to constrain symbiotic nitrogen fixation rates : a case study from an Amazonian rain forest

© The Authors 2009. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License. The definitive version was published in Biogeochemistry 99 (2010): 1-13, doi:10.1007/s10533-009-9392-y.Human activities have profoundly altered the global nitrogen (N) cycle. Increases in anthropogenic N have had multiple effects on the atmosphere, on terrestrial, freshwater and marine ecosystems, and even on human health. Unfortunately, methodological limitations challenge our ability to directly measure natural N inputs via biological N fixation (BNF)—the largest natural source of new N to ecosystems. This confounds efforts to quantify the extent of anthropogenic perturbation to the N cycle. To address this gap, we used a pair of indirect methods—analytical modeling and N balance—to generate independent estimates of BNF in a presumed hotspot of N fixation, a tropical rain forest site in central Rondônia in the Brazilian Amazon Basin. Our objectives were to attempt to constrain symbiotic N fixation rates in this site using indirect methods, and to assess strengths and weaknesses of this approach by looking for areas of convergence and disagreement between the estimates. This approach yielded two remarkably similar estimates of N fixation. However, when compared to a previously published bottom-up estimate, our analysis indicated much lower N inputs via symbiotic BNF in the Rondônia site than has been suggested for the tropics as a whole. This discrepancy may reflect errors associated with extrapolating bottom-up fluxes from plot-scale measures, those resulting from the indirect analyses, and/or the relatively low abundance of legumes at the Rondônia site. While indirect methods have some limitations, we suggest that until the technological challenges of directly measuring N fixation are overcome, integrated approaches that employ a combination of model-generated and empirically-derived data offer a promising way of constraining N inputs via BNF in natural ecosystems.We acknowledge and are grateful for financial support from the Andrew W. Mellon Foundation (C.C. and B.H.), the National Science Foundation (NSF DEB-0515744 to C.C. and A.T. and DEB-0315656 to C.N.), and the NASA LBA Program (NCC5-285 to C.N.)