Induction Chemotherapy and Chemoradiotherapy Combined to ASA vs. Placebo for High-Risk Rectal Cancer: Results of a Randomized Trial.

INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response. METHODS: Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS. RESULTS: Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%. CONCLUSION: There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.

Has a river dam affected the life-history traits of a freshwater prawn?

In recent years, species richness and diversity in aquatic ecosystems has declined as environments are increasingly impacted by anthropic actions. Freshwater prawns are well adapted to survive in a disturbed and heterogeneous environment. For instance, Amazon river prawn (Macrobrachium amazonicum) populations vary in migratory behavior between rivers and estuaries, depending on factors such as dams. However, there is limited information on the influence of environmental conditions on life-history traits of this species, which we investigate here using two distinct and unconnected aquatic systems, a dammed river and an estuary, in the eastern Brazilian Amazon. The biological characteristics of M. amazonicum populations in the two environments were compared and related to environmental parameters, which differed significant differences between the two environments and between seasons. Dissolved oxygen, precipitation, and temperature varied most significantly with the seasons in both the estuary and river. M. amazonicum prawns in the estuary were larger and heavier than those in the river during rainy periods. The mass-length ratios and condition factor varied significantly between the M. amazonicum populations in the estuary and river, with negative allometric growth (grows faster in length than in weight) predominating in both populations, and condition factor was better in the estuary for males and in the river for females. The relative frequencies of occurrence of the different female maturation stages and the male morphotypes were related to precipitation and turbidity in both environments and also to salinity in the estuary. In these two distinct aquatic systems, the abiotic parameters determined by the seasonal precipitation cycle profoundly influenced the development of this crustacean, despite its ecological plasticity. Overall, the study showed that river damming triggered environmental changes in the freshwater river ecosystem and played a key role in determining the life-history characteristics of M. amazonicum in these contrasting aquatic systems.

Draft genome sequences of five Calonectria species from Eucalyptus plantations in China, Celoporthe dispersa, Sporothrix phasma and Alectoria sarmentosa.

Draft genome sequences of five Calonectria species [including Calonectria aciculata, C. crousiana, C. fujianensis, C. honghensis and C. pseudoturangicola], Celoporthe dispersa, Sporothrix phasma and Alectoria sarmentosa are presented. Species of Calonectria are the causal agents of Eucalyptus leaf blight disease, threatening the growth and sustainability of Eucalyptus plantations in China. Celoporthe dispersa is the causal agent of stem canker in native Syzygium cordatum and exotic Tibouchina granulosa in South Africa. Sporothrix phasma was first discovered in the infructescences of Protea laurifolia and Protea neriifolia in South Africa. Alectoria sarmentosa is fruticose lichen belongs to the alectorioid clade of the family Parmeliaceae. The availability of these genome sequences will facilitate future studies on the systematics, population genetics, and genomics of these fungi.

Reproductive biology of the tiger pleco Panaqolus tankei (Loricariidae) in a lentic system of the Amazon Basin.

This study presents the first information on the reproduction of the recently described tiger pleco Panaqolus tankei, from Lake Bolonha in the north-eastern Amazon Basin. This loricariid has a long reproductive period, fractionated spawning and low fecundity (on average, female gonads contained 37 oocytes), a total length (LT ) at first maturity of 47.4 mm for females and 54.1 mm LT for males. Correlation of the condition factor and gonado-somatic index with environmental variables suggests that turbidity favours P. tankei reproduction in this environment.

Junior doctors' medical specialty and practice location choice: simulating policies to overcome regional inequalities.

There are nowadays over 1 million Portuguese who lack a primary care physician. By applying a discrete choice experiment to a large representative sample of Portuguese junior doctors (N = 503) in 2014, we provide an indication that this shortage may be addressed with a careful policy design that mixes pecuniary and non-pecuniary incentives for these junior physicians. According to our simulations, a policy that includes such incentives may increase uptake of general practitioners (GPs) in rural areas from 18% to 30%. Marginal wages estimated from our model are realistic and close to market prices: an extra hour of work would require an hourly wage of 16.5€; moving to an inland rural setting would involve an increase in monthly income of 1.150€ (almost doubling residents' current income); a shift to a GP career would imply an 849€ increase in monthly income. Additional opportunities to work outside the National Health Service overcome an income reduction of 433€. Our simulation predicts that an income increase of 350€ would lead to a 3 percentage point increase in choice probability, which implies an income elasticity of 3.37, a higher estimation compared to previous studies.

Preliminary Study on the Effect of Fermented Cheese Whey on Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella Goldcoast Populations Inoculated onto Fresh Organic Lettuce.

Cheese whey fermented by an industrial starter consortium of lactic acid bacteria was evaluated for its antibacterial capacity to control a selection of pathogenic bacteria. For their relevance on outbreak reports related to vegetable consumption, this selection included Listeria monocytogenes, serotype 4b, Escherichia coli O157:H7, and Salmonella Goldcoast. Organically grown lettuce was inoculated with an inoculum level of ∼10(7) colony-forming unit (CFU)/mL and was left for about 1 h in a safety cabinet before washing with a perceptual solution of 75:25 (v/v) fermented whey in water, for 1 and 10 min. Cells of pathogens recovered were then counted and their number compared with that obtained for a similar treatment, but using a chlorine solution at 110 ppm. Results show that both treatments, either with chlorine or fermented whey, were able to significantly reduce (p < 0.05) the number of bacteria, in a range of 1.15-2.00 and 1.59-2.34 CFU/g, respectively, regarding the bacteria tested. Results suggest that the use of fermented whey may be as effective as the solution of chlorine used in industrial processes in reducing the pathogens under study (best efficacy shown for Salmonella), with the advantage of avoiding health risks arising from the formation of carcinogenic toxic chlorine derivates.

Species or Genotypes? Reassessment of Four Recently Described Species of the Ceratocystis Wilt Pathogen, Ceratocystis fimbriata, on Mangifera indica.

Ceratocystis wilt is among the most important diseases on mango (Mangifera indica) in Brazil, Oman, and Pakistan. The causal agent was originally identified in Brazil as Ceratocystis fimbriata, which is considered by some as a complex of many cryptic species, and four new species on mango trees were distinguished from C. fimbriata based on variation in internal transcribed spacer sequences. In the present study, phylogenetic analyses using DNA sequences of mating type genes, TEF-1α, and ß-tubulin failed to identify lineages corresponding to the four new species names. Further, mating experiments found that the mango isolates representing the new species were interfertile with each other and a tester strain from sweet potato (Ipomoea batatas), on which the name C. fimbriata is based, and there was little morphological variation among the mango isolates. Microsatellite markers found substantial differentiation among mango isolates at the regional and population levels, but certain microsatellite genotypes were commonly found in multiple populations, suggesting that these genotypes had been disseminated in infected nursery stock. The most common microsatellite genotypes corresponded to the four recently named species (C. manginecans, C. acaciivora, C. mangicola, and C. mangivora), which are considered synonyms of C. fimbriata. This study points to the potential problems of naming new species based on introduced genotypes of a pathogen, the value of an understanding of natural variation within and among populations, and the importance of phenotype in delimiting species.

Genetic Analyses Trace the Yunnan, China Population of Ceratocystis fimbriata on Pomegranate and Taro to Populations on Eucalyptus in Brazil.

Genotypes of the Latin American wilt pathogen Ceratocystis fimbriata have been moved around the world in vegetatively propagated material of various crop plants, including Ipomoea batatas (sweet potato), Colocasia esculenta (taro), and Eucalyptus spp. When compared to a worldwide collection of isolates of C. fimbriata, isolates from taro, Punica granatum (pomegranate), and Eriobotrya japonica (loquat) from Yunnan Province, China were found to have sequences of internal transcribed spacer (ITS) rDNA and mating type genes that were identical to isolates from Eucalyptus in Brazil. Analyses of 35 isolates with 14 microsatellite markers revealed that the Yunnan population was nearly uniform, consisting of only 19 alleles and seven closely related genotypes, suggesting that the population is not natural and is the result of an introduction. As in comparisons of sequences of ITS rDNA and mating type genes, the microsatellite alleles of the Yunnan isolates were most similar to those of Eucalyptus isolates from Minas Gerais and Bahia, Brazil, where C. fimbriata is native, soilborne, and commonly infects cuttings of Eucalyptus spp. used for rooting in nurseries. Thus, the Yunnan population, which is causing severe losses on pomegranate, may have been indirectly derived from introductions of C. fimbriata in contaminated Eucalyptus cuttings from Brazil.

Attitudes and anxiety levels of medical students towards the acquisition of competencies in communication skills.

OBJECTIVE: Results of third year medical students' attitudes and stress levels towards the acquisition of communication skills before and after a Communication and Clinical Skills Course (CCSC) at the Faculty of Medicine of the University of Porto (FMUP), Portugal, are presented. METHODS: 115 students attending third-year CCSC completed a demographic questionnaire, State-Trait Anxiety Inventory, Communication Skills Attitudes Scale and Interpersonal Behavior Survey. RESULTS: Significant negative correlation was found between anxiety levels and attitudes towards learning communication skills in general as well as the teaching and learning process. At the end of the Course students reported that when compared to the start, their communication skills are less sufficient. CONCLUSION: At the end of this CCSC at FMUP, students recognized its major importance and how they need to invest and improve communication skills. However, it seems important to monitor the attitudes and anxiety levels of students towards patient care and communication during the medical course and to identify ways of overcoming barriers towards learning communication skills. PRACTICE IMPLICATIONS: It is recommended that there should be a complete (transversal and vertical) integration of communication skills, including effective teaching methods, assessments, and examinations in order to be valued by the students. This would necessitate curricular changes.

Movement of genotypes of Ceratocystis fimbriata within and among Eucalyptus plantations in Brazil.

Ceratocystis wilt on eucalyptus, caused by Ceratocystis fimbriata, was first recognized in 1997 in the state of Bahia, Brazil, but is now known in five other states and in four other countries. C. fimbriata is a native, soilborne pathogen in some parts of Brazil but we hypothesized that genotypes of the pathogen have been moved among plantations in rooted cuttings collected from diseased trees and within plantations on cutting tools. We used six microsatellite markers to identify 78 genotypes of C. fimbriata among 177 isolates from individual trees in 20 eucalyptus plantations. The highest gene and genotypic diversity values were found in plantations on formerly wild Cerrado forest in Minas Gerais, suggesting that the fungus was in the soil prior to planting eucalyptus. In contrast, one or only a few genotypes were found in plantations on previous pastureland (with no woody hosts) in Bahia and São Paulo, and most of these genotypes were found in a Bahian nursery or in one of two Bahian plantations that were sources for rooted cuttings. Sources of cuttings tended to be dominated by one or a few genotypes that may have been spread within the plantation on cutting tools.

TP53 mutation profile of esophageal squamous cell carcinomas of patients from Southeastern Brazil.

Esophageal cancer (EC) is among the 10 most common and fatal malignacies in the world, presenting a marked geographic variation in incidence rates between and within different countries. The TP53 tumor suppressor gene is highly mutated in esophageal tumors and its mutation pattern can offer clues to the etiopathology of the tumor. As Brazil presents one of the highest incidence areas in the West, a deeper knowledge of the molecular mechanisms related to EC development in the Brazilian population is needed. We analyzed the mutation profile of 110 esophageal squamous cell carcinomas (ESCC) of patients from Southeastern Brazil (Rio de Janeiro and São Paulo) and collected data regarding alcohol intake and tobacco smoking. We detected 41 mutations in tumor samples from 38 patients. There was no association between mutation frequency and tobacco smoking or alcohol drinking. The most frequently mutated codons were 179, 214, 220 and 248. Codons 179, 220 and 248 are hot-spots for ESCC, but codon 214 presents only 0.7% of the mutations registered in the IARC database. The mutation profile revealed a high percentage of mutations at A:T base pairs (34.1%) followed by deletions (17.1%). We concluded that the mutation profile detected in this study is different from that of patients from Southern Brazil but very similar to that previously seen in French patients, being characterized by a high frequency of mutations at A:T base pairs, which may be associated with acetaldehyde, the metabolic product of ethanol.

Properties of whey protein-based films containing organic acids and nisin to control Listeria monocytogenes.

Whey protein isolate and glycerol were mixed to form a matrix to incorporate antimicrobial agents and produce edible films with antimicrobial activity against Listeria monocytogenes strains isolated from cheeses. Various organic acids were used to decrease pH down to approximately 3. In a preliminary assay without nisin, the effect of each organic acid was evaluated with respect to the rheological properties of the film solutions and the inhibitory and mechanical properties of the films. Lactic, malic, and citric acids (3%, wt/vol), which were used in a subsequent study of their combined inhibitory effect with nisin (50 IU/ml), had significantly higher antilisterial activity (P < 0.05) compared with the control (2 N HCl, 3% [wt/vol], with nisin). The largest mean zone of inhibition was 4.00 +/- 0.92 mm for malic acid with nisin. Under small-amplitude oscillatory stress, the protein-glycerol-acid film solutions exhibited a predominantly viscous behavior or a weak gel behavior, with the storage modulus (G') slightly higher than the loss modulus (G"). The malic acid-based solution was the only one whose viscosity was not influenced by the addition of nisin. The addition of nisin resulted in a nonsignificant (P > 0.05) increase in the percentage of elongation at break. Results from tensile and puncture stress were variable, but in general no significant differences were found after the incorporation of nisin. The overall results support the use of malic acid with nisin to produce effective antimicrobial films to control L. monocytogenes growth.

Association between a case study of asymptomatic ovine listerial mastitis and the contamination of soft cheese and cheese processing environment with Listeria monocytogenes in Portugal.

For 5 months, the udders of milking ewes, raw ewe's milk, cheese, and the plant and environment of a cheese manufacturer in Portugal were investigated using standard methods for the presence of Listeria spp. An association between subclinical mastitis and Listeria monocytogenes in a single lactating sheep was investigated by visual inspection of udders for signs of inflammation, application of somatic cell counts, the California mastitis test, pH measurement to milk, and culture of L. monocytogenes and Staphylococcus spp. To track the routes of contamination by L. monocytogenes, 103 isolates were characterized by molecular serotyping and amplified fragment length polymorphism, and a selection was further tested by pulsed-field gel electrophoresis. This study provides molecular and epidemiological evidence tracking the persistence of a single L. monocytogenes strain causing a subclinical udder infection without obvious inflammation in a single ewe. This infection was the likely source of contamination of raw milk that was subsequently used to produce unpasteurised milk cheese and resulted in a single strain of this bacterium colonizing the processing environment and the final cheese product.