The phosphatidylinositol 3'-kinase (PI3K) pathway is frequently activated in thyroid carcinomas through the constitutive activation of stimulatory molecules (e.g., Ras) and/or the loss of expression ...and/or function of the inhibitory PTEN protein that results in Akt activation. Recently, it has been reported that somatic mutations within the PI3K catalytic subunit, PIK3CA, are common (25-40%) among colorectal, gastric, breast, ovarian cancers, and high-grade brain tumors. Moreover, PIK3CA mutations have a tendency to cluster within the helical (exon 9) and the kinase (exon 20) domains. In this study, 13 thyroid cancer cell lines, 80 well-differentiated thyroid carcinomas of follicular (WDFC) and papillary (WDPC) type, and 70 anaplastic thyroid carcinomas (ATC) were investigated, by PCR-direct sequencing, for activating PIK3CA mutations at exons 9 and 20. Nonsynonymous somatic mutations were found in 16 ATC (23%), two WDFC (8%), and one WDPC (2%). In 18 of the 20 ATC cases showing coexisting differentiated carcinoma, mutations, when present, were restricted to the ATC component and located primarily within the kinase domain. Three cell lines of papillary and follicular lineage (K1, K2, and K5) were also found mutated. In addition, activation of Akt was observed in most of the ATC harboring PIK3CA mutations. These findings indicate that mutant PIK3CA is likely to function as an oncogene among ATC and less frequently well-differentiated thyroid carcinomas. The data also argue for a role of PIK3CA targeting in the treatment of ATC patients.
Summary
We describe 36 patients with splenic marginal zone lymphoma (SMZL) with transformation (SMZL‐T), including 15 from a series of 84 patients with SMZL diagnosed at the Hospital Clinic of ...Barcelona (HCB) and 21 diagnosed with SMZL‐T in other centres. In the HCB cohort, the cumulative incidence of transformation at 5 years was 15%. Predictors for transformation were cytopenias, hypoalbuminaemia, complex karyotype (CK) and both the Intergruppo Italiano Linfomi (ILL) and simplified Haemoglobin, Platelet count, lactate dehydrogenase (LDH) and extrahilar Lymphadenopathy (HPLL)/ABC scores (P < 0·05). The only independent predictor for transformation in multivariate analysis was CK hazard ratio (HR) 4·025, P = 0·05. Patients with SMZL‐T had a significantly higher risk of death than the remainder (HR 3·89, P < 0·001). Of the 36 patients with SMZL‐T, one developed Hodgkin lymphoma and 35 a diffuse large B‐cell lymphoma, 71% with a non‐germinal centre phenotype. The main features were B symptoms, lymphadenopathy, and high serum LDH. CK was observed in 12/22 (55%) SMZL‐T and fluorescence in situ hybridisation detected abnormalities of MYC proto‐oncogene, basic helix‐loop‐helix transcription factor (MYC), B‐cell leukaemia/lymphoma 2 (BCL2) and/or BCL6 in six of 14 (43%). In all, 21 patients received immunochemotherapy, six chemotherapy, one radiotherapy and three splenectomy. The complete response (CR) rate was 61% and the median survival from transformation was 4·92 years. Predictors for a worse survival in multivariate analysis were high‐risk International Prognostic Index (HR 5·294, P = 0·016) and lack of CR (HR 2·67, P < 0·001).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•The northern, northwest and Ribeira river valley are endemic areas for CL in Paraná state.•The pioneer mesoregions north and central-north of Paraná have a high climate and suitability for Mg. ...migonei, Ny. neivai and Ny. whitmani.•Temperature and precipitation variables influence in the distribution of Mg. migonei, Ny. neivai and Ny. whitmani.•Migonemyia migonei, Ny. neivai and Ny. whitmani require different climatic conditions.•High suitability de Mg. migonei, Ny. neivai and Ny. whitmani is indicative of LC expansion in Paraná state.
Southern Brazil concentrates a considerable number of cases of cutaneous leishmaniasis reported since 1980, and Paraná is the state that most records CL cases in the region. The main sand fly species incriminated as vectors of Leishmania (Viannia) braziliensis (Vianna,1911) are Migonemyia (Migonemyia) migonei (França, 1920), Nyssomyia (Nyssomyia) neivai (Pinto, 1926) and Nyssomyia (Nyssomyia) whitmani (Antunes & Coutinho, 1936). In this study, we evaluated areas with climatic suitability for the distribution of these vectors and correlated these data with CL incidence in the state. The occurrence points of Mg. migonei, Ny. neivai, and Ny. whitmani were extracted from a literature review and field data. For CL analysis in the state of Paraná, data were obtained from the Informatics Department of the Unified Health System of Brazil (DATASUS), covering the period from 2001 to 2019. The layers of bioclimatic variables from the WorldClim database were used
in the study. Species distribution modeling was developed using the MaxEnt Software version 3.4.4. ArcGIS software version 10.5 was used to develop suitability maps and the graphical representation of disease incidence. The AUC values were acceptable for all models (> 0,8). Bioclimatic variables BIO13 and BIO14 were the most influential in the distribution of Mg. migonei, while BIO19 and BIO6 were the variables that most influenced the distribution of Ny. neivai, and Ny. whitmani was most influenced by variables BIO5 and BIO9. During 19 years, 4992 cases of CL were reported in the state by 286 municipalities (71,6%). Northern Paraná showed the highest number of areas with very high and high climatic suitability for the occurrence of these species, coinciding with the highest number of CL cases. The modeling tools allowed analyzing the association between climatic variables and the geographical distribution of CL in the state. Moreover, they provided a better understanding of the climatic conditions related to the distribution of different species, favoring the monitoring of risk areas, the implementation of preventive measures, risk awareness, early and accurate diagnosis, and consequent timely treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important.
Our objective was to assess the prevalence of ...MTBS and the role of both clinical/socio-behavioral risk factors for MTBS in a cohort of PLWH.
All PLWH, over 18 years of age, attending all Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019-January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis was performed to assess factors significantly associated with the main outcome (MTBS).
We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation: 12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and a history of AIDS.
Identifying and addressing risk factors, including those that are socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH, especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in clinical practice.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sources of contamination of carcasses during slaughter include infected pigs as well as environmentally related sources. There are many microbial indicators that can be used in the processing of food ...to assess food hygiene and the safety of food processing. The presence of some microbial indicators can be viewed as a result of direct or indirect contamination of a food with fecal material. The presence of Enterobacteriaceae is often used as a hygiene indicator, as they are found both in the environment and in the intestine of warm-blooded animals. An association between Salmonella isolation and Enterobacteriaceae count (EC) on pre-chill carcasses has been described, however the impact of slaughterhouse and the day of sampling on the occurrence of Salmonella has not been previously investigated. To this end, mixed logistic regressions (MLRs) with random effects and fixed slopes were performed to assess the change in EC and its correlation with Salmonella occurrence using two data sets. The first describes the EC and Salmonella isolation in 60 pork carcasses in one slaughterhouse sampled at 11 different slaughter steps, including the carcass as a random effect. The second describes the EC and Salmonella isolation on 1150 pre-chill carcasses sampled in 13 slaughterhouses over 230 sampling days, and the model combined two random intercepts, slaughterhouse and date of sampling nested with slaughterhouse (day/slaughterhouse). Statistically significant associations (p<0.0001) between the log of the EC and Salmonella occurrence were found in all models. Nevertheless, although a strong association was found between Enterobacteriaceae and Salmonella contamination in pork carcasses, this association was not constant, given that there was a high variation in the probability of a carcass being positive for Salmonella according to the EC mainly between days of samples. The effect of the day of sampling on Salmonella prevalence was so large that the predictive value of the EC count for Salmonella isolation on a daily basis was compromised. It is possible that on some days batches with a high prevalence of Salmonella carriers shedding a high number of Salmonella were slaughtered. On these days, the potential for contamination/cross-contamination of carcasses will be so large that even hygienic slaughter, confirmed by the low EC on carcasses, will not be able to prevent the presence of Salmonella on some carcasses. The results of this study demonstrate that, despite the statistically significant association found, it may be difficult to predict when hygiene failure measured via EC actually indicates Salmonella contamination, and neither the inverse.
•We analyzed the correlation between Salmonella and Enterobacteriaceae.•We fitted three mixed models including source of variation as random effect.•A high variation in the association occurred mainly between days of sampling.•Besides the significant association, EC is not a useful indicator of Salmonella.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In melting flesh peaches, auxin is necessary for system-2 ethylene synthesis and a cross-talk between ethylene and auxin occurs during the ripening process. To elucidate this interaction at the ...transition from maturation to ripening and the accompanying switch from system-1 to system-2 ethylene biosynthesis, fruits of melting flesh and stony hard genotypes, the latter unable to produce system-2 ethylene because of insufficient amount of auxin at ripening, were treated with auxin, ethylene and with 1-methylcyclopropene (1-MCP), known to block ethylene receptors. The effects of the treatments on the different genotypes were monitored by hormone quantifications and transcription profiling.
In melting flesh fruit, 1-MCP responses differed according to the ripening stage. Unexpectedly, 1-MCP induced genes also up-regulated by ripening, ethylene and auxin, as CTG134, similar to GOLVEN (GLV) peptides, and repressed genes also down-regulated by ripening, ethylene and auxin, as CTG85, a calcineurin B-like protein. The nature and transcriptional response of CTG134 led to discover a rise in free auxin in 1-MCP treated fruit. This increase was supported by the induced transcription of CTG475, an IAA-amino acid hydrolase. A melting flesh and a stony hard genotype, differing for their ability to synthetize auxin and ethylene amounts at ripening, were used to study the fine temporal regulation and auxin responsiveness of genes involved in the process. Transcriptional waves showed a tight interdependence between auxin and ethylene actions with the former possibly enhanced by the GLV CTG134. The expression of genes involved in the regulation of ripening, among which are several transcription factors, was similar in the two genotypes or could be rescued by auxin application in the stony hard. Only GLV CTG134 expression could not be rescued by exogenous auxin.
1-MCP treatment of peach fruit is ineffective in delaying ripening because it stimulates an increase in free auxin. As a consequence, a burst in ethylene production speeding up ripening occurs. Based on a network of gene transcriptional regulations, a model in which appropriate level of CTG134 peptide hormone might be necessary to allow the correct balance between auxin and ethylene for peach ripening to occur is proposed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, a comparison between charcoal produced from
Eucalyptus urograndis
modified and unmodified with HNO
3
on the adsorption capacity of metals (Cu(II), Cd(II), and Ni(II)) in aqueous ...solutions was performed. The modification was performed using charcoal from the wood of a hybrid of
Eucalyptus urophylla
x
Eucalyptus grandis
(commonly referred to in Brazil as
Eucalyptus urograndis
). The charcoal was produced at a final temperature of 450 °C. Nitric acid was the oxidizing agent, employed at a concentration of 12.5% (v/v) and a reaction time of 3 h. The materials were characterized and compared using thermogravimetric analysis, thermogravimetric index, specific surface area analysis, scanning electron microscopy, elemental analysis, and point of zero charge. Studies of the process factors (contact time, mass, ideal pH), adsorption isotherms (Langmuir and Freundlich), and the thermodynamics of the process were also carried out. Treatment with nitric acid altered the elemental composition of charcoal, and functional groups, like carbonyl groups, were added to the surface, which caused a significant increase in total adsorption capacity (from 114.27 to 310.53 mg g
−1
in a solution with a mix of metals). The model that best fit the data was Langmuir, and the maximum removal of Cu(II) ions was 96%, and occurred at pH 5, at 318 K, with a dose of biosorbent equal to 0.4 g 50 mL
−1
of solution and equilibrium contact time of 30 min. Thermodynamic parameters suggested that adsorption occurred spontaneously and occurred through the ion exchange and electrostatic interaction mechanisms. In systems with the presence of more than one metal ion, the total adsorption capacity increased.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Perinatal asphyxia (PA) is responsible for a large proportion of neonatal deaths and numerous neurological sequelae, including visual dysfunction and blindness. In PA, the retina is exposed to ...ischemia/reoxygenation, which results in nitric oxide overproduction and neurotoxicity. We hypothesized that methylene blue (MB), a guanylyl cyclase inhibitor and free-radical scavenger currently used in the clinic, may block this pathway and prevent PA-induced retinal degeneration. Male rat pups were subjected to an experimental model of PA. Four groups were studied: normally delivered (CTL), normally delivered treated with 2 mg Kg-1 MB (MB), exposed to PA for 20 min at 37ºC (PA), and exposed to PA and, then, treated with MB (PA-MB). Scotopic electroretinography performed 45 days after birth showed that PA animals had significant defects in the a- and b-waves and oscillatory potentials. The same animals presented a significant increase in the thickness of the inner retina and a large number of TUNEL-positive cells. All these physiological and morphological parameters were significantly prevented by the treatment with MB. Gene expression analysis demonstrated significant increases in iNOS, MMP9, and VEGF in the eyes of PA animals, which were prevented by MB treatment. In conclusion, MB regulates key players of inflammation, matrix remodeling, gliosis, and angiogenesis in the eye and could be used as a treatment to prevent the deleterious visual consequences of PA. Given its safety profile and low cost, MB may be used clinically in places where alternative treatments may be unavailable.
A one-step synthesis of near infrared fluorescent platinum nanoclusters (PtNCs) in aqueous medium is described. The proposed optimized procedure for PtNC synthesis is rather simple, fast and it is ...based on the direct metal reduction with NaBH4. Bidentated thiol ligands (lipoic acid) were selected as nanoclusters stabilizers in water media. The structural characterization revealed attractive features of the PtNCs, including small size, high water solubility, near-infrared luminescence centered at 680 nm, long-term stability and the highest quantum yield in water reported so far (47%) for PtNCs. Moreover, their stability in different pH media and an ionic strength of 0.2 M NaCl was studied and no significant changes in fluorescence emission were detected. In brief, they offer a new type of fluorescent noble metal nanoprobe with a great potential to be applied in several fields, including biolabeling and imaging experiments.
The aim of the present study was to investigate the potential allelopathic effects of isolated or intercropped aqueous forage extracts on the physiological performance of soybean Glycine max (L.) ...Merr. and corn (Zea mays L.) seeds, as well as their phytotoxicity to the weed species Bidens pilosa L. Aqueous extracts were prepared at a concentration of 5%, and the tests with soy and corn were conducted by wetting the germination papers with different treatments and performing procedures within the standards of the Brazilian Rules of Seed Analysis. Tests with the cover plant extracts on the seeds of B. pilosa used BOD-type repetitions. Fifty weed seeds were placed in a gerbox with filter paper moistened with the different treatments with five repetitions. Distilled water was used as the control in all tests. Extracts of Avena strigosa Schreb and Raphanus sativus L. (radish), cultivated individually and in combination, increased the seed germination percentage (%G) and the length of soybean seedlings. Similarly, extracts of Pennisetum glaucum (L.) R.Br and Crotalaria spectabilis Roth, in individual and combined cultivation, provided gains in corn %G. Furthermore, all tested extracts suppressed germination and decreased the speed of the germination index of the hairy beggarticks when compared to the control, with the radish extract showing the greater reduction effect on the %G of the weed plant B. pilosa.
Highlights:
The use of Crotalaria as a cover crop has a positive effect on the initial growth of corn.
The use of black oat and forage radish intercropped had the potential to increase soybean yield.
The use of cover crops contributes to the integrated management of weeds.
The choice of cover plant is important for the success of crop rotation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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