PET-adapted therapy after three cycles of ABVD for all stages of Hodgkin lymphoma: results of the GATLA LH-05 trial.

The role of Ann Arbor staging in determining treatment intensity after achieving a negative positron emission tomography (PET) has not been established in classical Hodgkin lymphoma (cHL). Patients with stage I-IV cHL, received three cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and an interim PET scan (PET3). PET3-negative patients received no further therapy. PET3-positive patients received three additional cycles of ABVD plus involved-field radiation therapy or salvage chemotherapy, if refractory to ABVD, and were re-evaluated by PET scan (PET6). Study endpoints were 3-year progression-free survival (PFS) and overall survival (OS) rates. Two hundred and thirty-nine patients with early-stage and 138 with advanced-stage were evaluable. Overall, 260 patients (70%) were PET3-negative and had higher 3-year PFS (90% vs. 65%; P < 0·0001) and OS (98% vs. 92%; P = 0·007) rates than PET3-positive patients. All PET3-negative patients, regardless of disease stage at diagnosis, achieved similarly good PFS (90-91%; P = 0·76) and OS (97-99%). The only independent prognostic factor for PFS was PET3-negativity (Hazard ratio 3·8; 95% confidence interval 2·4-6·3; P < 0·0001). This study suggests that cHL patients who achieve a negative PET3 following ABVD have an excellent outcome, regardless of stage at diagnosis. An appropriately powered, phase III trial will be necessary to confirm these findings.

Abscisic acid enhances cold tolerance in honeybee larvae.

The natural composition of nutrients present in food is a key factor determining the immune function and stress responses in the honeybee (Apis mellifera). We previously demonstrated that a supplement of abscisic acid (ABA), a natural component of nectar, pollen, and honey, increases honeybee colony survival overwinter. Here we further explored the role of ABA in in vitro-reared larvae exposed to low temperatures. Four-day-old larvae (L4) exposed to 25°C for 3 days showed lower survival rates and delayed development compared to individuals growing at a standard temperature (34°C). Cold-stressed larvae maintained higher levels of ABA for longer than do larvae reared at 34°C, suggesting a biological significance for ABA. Larvae fed with an ABA-supplemented diet completely prevent the low survival rate due to cold stress and accelerate adult emergence. ABA modulates the expression of genes involved in metabolic adjustments and stress responses: Hexamerin 70b, Insulin Receptor Substrate, Vitellogenin, and Heat Shock Proteins 70. AmLANCL2, the honeybee ABA receptor, is also regulated by cold stress and ABA. These results support a role for ABA increasing the tolerance of honeybee larvae to low temperatures through priming effects.

Resistance phenomena to amitraz from populations of the ectoparasitic mite Varroa destructor of Argentina.

In Argentina, Varroa destructor resistance to coumaphos has been previously reported. However, the status of mite susceptibility to other hard acaricides is still unknown. At present, high infestation levels of V. destructor are being detected in colonies of Apis mellifera after treatment with amitraz. The aim of the present study was to determine the LC(50) of amitraz in V. destructor from three apiaries with high mite density after treatment with the acaricide. The LC(50) values were 3.9, 3.5, and 3.7 µg/Petri dish for mites from three different apiaries. Significant LC(50) differences were detected between resistant and susceptible mites. LC(50) increased 35-39-fold when compared to the corresponding baseline, suggesting the development of resistance. These results are the first report of resistance to amitraz in V. destructor in Argentina and extend the knowledge according to the status of acaricides resistance in the country.

Bees increase crop yield in an alleged pollinator-independent almond variety.

Wild pollinators are declining and the number of managed honey bee colonies is growing slower than agricultural demands for pollination. Because of these contrasting trends in pollinator demand and availability, breeding programs for many pollinator-dependent crops have focused on reducing the need for pollinators. Although numerous crop varieties are now available in the market with the label of pollinator-independent, the real dependence of these varieties on pollinators is mostly unknown. We evaluated the hypothesis of pollinator independence in the Independence almond variety, the fastest growing variety in California that is the main almond production region in the world. In this presumed pollinator-independent variety, we measured the effect of honey bees on fruit set, yield, and kernel nutritional quality at tree level. Fruit set was 60% higher in bee-pollinated than bee-isolated trees, which translated into a 20% increase in kernel yield. Despite its effect on almond production, there was no evidence that bee visitation affected almond nutritional quality. Based on these results, we recommend the use of bees, whether they are wild or managed, to maximize yield even in self-fertile almond varieties.

Towards Precision Nutrition: A Novel Concept Linking Phytochemicals, Immune Response and Honey Bee Health.

The high annual losses of managed honey bees (Apis mellifera) has attracted intensive attention, and scientists have dedicated much effort trying to identify the stresses affecting bees. There are, however, no simple answers; rather, research suggests multifactorial effects. Several works have been reported highlighting the relationship between bees' immunosuppression and the effects of malnutrition, parasites, pathogens, agrochemical and beekeeping pesticides exposure, forage dearth and cold stress. Here we analyze a possible connection between immunity-related signaling pathways that could be involved in the response to the stress resulted from Varroa-virus association and cold stress during winter. The analysis was made understanding the honey bee as a superorganism, where individuals are integrated and interacting within the colony, going from social to individual immune responses. We propose the term "Precision Nutrition" as a way to think and study bees' nutrition in the search for key molecules which would be able to strengthen colonies' responses to any or all of those stresses combined.

Effect of Abscisic Acid (ABA) Combined with Two Different Beekeeping Nutritional Strategies to Confront Overwintering: Studies on Honey Bees' Population Dynamics and Nosemosis.

In temperate climates, beekeeping operations suffer colony losses and colony depopulation of Apis mellifera during overwintering, which are associated with biotic and abiotic stressors that impact bees' health. In this work, we evaluate the impacts of abscisic acid (ABA) dietary supplementation on honey bee colonies kept in Langstroth hives. The effects of ABA were evaluated in combination with two different beekeeping nutritional strategies to confront overwintering: "honey management" and "syrup management". Specifically, we evaluated strength parameters of honey bee colonies (adult bee and brood population) and the population dynamics of Nosema (prevalence and intensity) associated with both nutritional systems and ABA supplementation during the whole study (late autumn-winter-early spring). The entire experiment was designed and performed with a local group of beekeepers, "Azahares del sudeste", who showed interest in answering problems associated with the management of honey bee colonies during the winter. The results indicated that the ABA supplementation had positive effects on the population dynamics of the A. mellifera colonies during overwintering and on the nosemosis at colony level (prevalence) in both nutritional strategies evaluated.

Dietary Supplementation of Honey Bee Larvae with Arginine and Abscisic Acid Enhances Nitric Oxide and Granulocyte Immune Responses after Trauma.

Many biotic and abiotic stressors impact bees' health, acting as immunosupressors and contribute to colony losses. Thus, the importance of studying the immune response of honey bees is central to develop new strategies aiming to enhance bees' fitness to confront the threats affecting them. If a pathogen breaches the physical and chemical barriers, honey bees can protect themselves from infection with cellular and humoral immune responses which represent a second line of defense. Through a series of correlative studies we have previously reported that abscisic acid (ABA) and nitric oxide (NO) share roles in the same immune defenses of Apis mellifera (A. mellifera). Here we show results supporting that the supplementation of bee larvae's diet reared in vitro with l-Arginine (precursor of NO) or ABA enhanced the immune activation of the granulocytes in response to wounding and lipopolysaccharide (LPS) injection.

Inversions of chromosomes 2 and 6 in mantle cell lymphoma. Cytogenetic, FISH, and molecular studies.

Inversions are infrequent events in hematological malignancies. We here report the cytogenetic, fluorescence in situ hybridization (FISH), and molecular studies of 2 patients diagnosed with mantle cell lymphoma (MCL) that showed inversions of chromosomes 2 and 6 as part of complex karyotypes. Both patients showed a cytogenetically identical inv(6)(p23q11) detected as a secondary aberration. In addition, both patients had a derivative chromosome 2 which originated by partial deletion of the short arm and a pericentric inversion with different breakpoints on the long arm: der(2)del(2)(p21)inv(2)(p21q11) and der(2)del(2)(p21)inv(2)(p21q13), respectively. The presence of t(11;14)(q13;q32) was confirmed by interphase FISH and by molecular study. Residual normal cells were found in both cases. The patients showed a different clinical evolution with a poor outcome for one case and a favorable course of the disease for the other one. The review of the literature in MCL showed a total of 9 inversions affecting different chromosomes. Considering that inversions are very infrequent events in MCL, our findings could be important for detecting genes potentially involved in development and/or progression of this aggressive non-Hodgkin lymphoma subtype.

Effects of the organic acids produced by a lactic acid bacterium in Apis mellifera colony development, Nosema ceranae control and fumagillin efficiency.

The European honey bee Apis mellifera is known to be affected by many parasites and pathogens that have great impact over the insect development. Among parasites affecting bee health, Nosema ceranae is one of the main biotic factors affecting colony populations. As honey bee populations decline, interest in pathogenic and mutualistic relationships between bees and microorganisms has increased. The main goal of the current study was to assess the effect of the oral administration of the metabolites produced by Lactobacillus johnsonii CRL1647 (mainly organic acids) supplemented in syrup, on: (I) N. ceranae sporulation dynamics before and after fumagillin application, and (II) performance of A. mellifera colonies. Different experiments were conducted to evaluate the effects of these bacterial metabolites on bees: in vitro administration revealed no toxic effects against bees. Colonies fed with the lactic acids incremented their beehive population and also the amount of fat bodies per bee. Finally, the organic acids reduced the intensity of the pathogen after the second application of treatment as well as enhanced the fumagillin efficiency. This study provides important information for the development of new control substances against nosemosis.

Grinvex-Aracê: Desafios para Consolidação do Grupo de Pesquisa de Invéxis / Group of Existential Inversion-Aracê: Challenges for the Consolidation of Existential Invertors Research Group / Grinvex-Aracê: Desafios para consolidación del Grupo de Investigación de Invexis

O presente artigo trata da trajetória de implantação do grupo de pesquisa da técnicade inversão existencial no Campus Aracê. O objetivo é divulgar os primeiros desafiospara implantação do Grinvex-Aracê e a proposição de ações para enfrentá-los visandoservir como ferramenta para auxílio na formação de outros Grinvexes. Foramlistados, com base nas vivências pessoais de cada integrante do Grinvex-Aracêe embasados através da leitura e análise de artigos da ciência Conscienciologia, bemcomo verbetes da Enciclopédia da Conscienciologia, os principais desafios encontradospelo grupo durante os seus seis primeiros meses de existência. A pesquisa foi realizadade Junho a Setembro de 2013. O principal resultado foi a proposição de açõescoletivas com foco na consolidação do Grinvex-Aracê(AU)

The present article has to do with the research group implantation trajectory ofthe existential inversion technique in the Campus Aracê. The objective is to publishthe first challenges for implantation of the Group of existential invertors-Aracê andthe proposition of actions to face them, seeking to serve as tool to aid in the formationof other Groups of existential invertors. They were listed, based in the personal experiencesof each integrant of the Group of Existential Invertors-Aracê and upon the readingand analysis of the science Conscientiology´ articles, as well as entries of theEncyclopedia of Conscientiology, the main challenges found by the group duringtheir first six months of existence. The research was done from June to September of2013. The main result was the proposition of collective actions with focus in the con solidation of the Group of Existential Invertors-Aracê(AU)

El presente artículo trata de la trayectoría de implantación del grupo de investigaciónde la técnica de inversión existencial en el Campus Aracê. El objetivo es divulgarlos primeros desafios para implantación del Grinvex-Aracê y la proposición deacciones para enfrentarlos visando servir como herramienta para auxílio en la formaciónde otros Grinvexes. Fueron listados, con base en las vivencias personales decada integrante del Grinvex-Aracê y basados a través de la lectura y análisis de artí-culos de la ciencia concienciología, bien como verbetes de la Enciclopedia de la Concienciología,los principales desafios encontrados por el grupo durante sus seis primerosmeses de existencia. La investigación fue realizada de Junio a Setiembre de 2013.El principal resultado fue la proposición de acciones colectivas con foco en la consolidacióndel Grinvex-Aracê(AU)