Entire hemithorax irradiation for Masaoka stage IVa thymomas

Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions.In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma.Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival.     

Phosphorylation of Yeast Hexokinase 2 Regulates Its Nucleocytoplasmic Shuttling

Nucleocytoplasmic shuttling of Hxk2 induced by glucose levels has been reported recently. Here we present evidence that indicates that Hxk2 nucleocytoplasmic traffic is regulated by phosphorylation and dephosphorylation at serine 14. Moreover, we identified the protein kinase Snf1 and the protein phosphatase Glc7-Reg1 as novel regulatory partners for the nucleocytoplasmic shuttling of Hxk2. Functional studies revealed that, in contrast to the wild-type protein, the dephosphorylation-mimicking mutant of Hxk2 retains its nuclear localization in low glucose conditions, and the phosphomimetic mutant of Hxk2 retains its cytoplasmic localization in high glucose conditions. Interaction experiments of Hxk2 with Kap60 and Xpo1 indicated that nuclear import of the S14D mutant of Hxk2 is severely decreased but that the export is significantly enhanced. Conversely, nuclear import of the S14A mutant of Hxk2 was significantly enhanced, although the export was severely decreased. The interaction of Hxk2 with Kap60 and Xpo1 was found to occur in the dephosphorylated and phosphorylated states of the protein, respectively. In addition, we found that Hxk2 is a substrate for Snf1. Mutational analysis indicated that serine 14 is a major in vitro and in vivo phosphorylation site for Snf1. We also provide evidence that dephosphorylation of Hxk2 at serine 14 is a protein phosphatase Glc7-Reg1-dependent process. Taken together, this study establishes a functional link between Hxk2, Reg1, and Snf1 signaling, which involves the regulation of Hxk2 nucleocytoplasmic shuttling by phosphorylation-dephosphorylation of serine 14.     

The effects of beta acids from hops (Humulus lupulus) on mortality of Varroa destructor (Acari: Varroidae)

Hop (Humulus lupulus L.) beta acids (HBA) were tested for miticidal effects on varroa destructor Anderson and Trueman, a parasitic mite of the honey bee (Apis mellifera L.). When varroa were placed on bees that had topical applications of 1?% HBA, there was 100?% mite mortality. Bee mortality was unaffected. Cardboard strips saturated with HBA and placed in colonies resulted in mite drop that was significantly greater than in untreated hives. HBA was detected on about 60?% of the bees in colonies during the first 48?h after application. Mite drop in colonies lasted for about 7?days with the highest drop occurring in the first 2–3?days after treatment. There was a reduction in the percentages of bees with HBA and in the amounts on their bodies after 7?days. Bee and queen mortality in the colonies were not affected by HBA treatments. When cardboard strips saturated with HBA were put in packages of bees, more than 90?% of the mites were killed without an increase in bee mortality. HBA might have potential to control varroa when establishing colonies from packages or during broodless periods.     

Detection of quantitative trait loci for resistance to gastrointestinal nematode infections in Creole goats

This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome‐wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half‐sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti‐Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti‐L3, and IgE anti‐ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants.     

Influence of liposomal local anesthetics on platelet aggregation in vitro

We assessed the effect of local anesthetics (LA) from different families such as esters (benzocaine), linear aminoamides (lidocaine) and cyclic aminoamides (bupivacaine) on the platelet aggregation induced by ADP. Liposomal formulations of the three LA, prepared with egg phosphatidylcholine:cholesterol alpha-tocopherol, were also tested. The three LA were able to inhibit platelet aggregation induced by ADP, in the following order: bupivacaine > lidocaine > benzocaine. After encapsulation into liposomes the inhibitory effect increased for all anesthetics studied, showing that aggregation tests could be used to assess the toxicity of new drug formulations.     

Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future.     

Reserve selection and persistence: complementing the existing Atlantic Forest reserve system

This study is an exercise to check the efficiency of the existing reserve system, and to show how systematic conservation planning—using information available and the complementarity concept—can improve the basis for decisions and minimize costs. We verified the performance, in number of cells and primate species representation, of the existing Atlantic Forest (Brazil) reserve network with a quarter-degree resolution grid, with 1,884 cells. We used occurrence data of 20 endemic primate species, and the maps of 237 existing reserves. Reserve networks were selected to represent primate species first considering no pre-existing reserves in Atlantic Forest, and then, considering the existing reserve system, taking into account the minimum area for viable population of the larger species (Northern muriqui Brachyteles hypoxanthus). Reserve selection was carried out using the complementarity concept implemented by a simulated annealing algorithm. Primate species representation (at least one occurrence in the network) could be achieved with 8% of the existing reserve system (nine cells in relation to the 120 in the existing reserve system). We found that today’s reserve system represents 89% of endemic primate species, excluding the species Coimbra Filho’s titi monkey (Callicebus coimbrai) and Marcgraf’s capuchin (Cebus flavius). The networks selected without considering existing reserves contained nine cells. The networks selected considering existing reserves (120 cells), had two new cells necessary to represent all the primates. This does not mean that a viable alternative is to start from zero (i.e., nonexistent reserves). Identifying critical supplementary areas using biodiversity information to fill the gaps and then starting “conservation in practice” in these areas should be priorities.