Influence of Neoadjuvant Immunotherapy-Chemotherapy on Perioperative Outcomes in Locally Advanced Esophageal Adenocarcinoma.

BACKGROUND: This study evaluated the perioperative outcomes for patients who had locally advanced esophageal adenocarcinoma (EAC) treated with neoadjuvant immunotherapy (IO) and chemotherapy versus a matched cohort of patients who received neoadjuvant chemotherapy (NAC) alone. METHODS: A single-center non-randomized phase 2 trial was undertaken with locally advanced (cT3-4 and/or N+) EAC, and 49 patients completed neoadjuvant avelumab + docetaxel, cisplatin, 5FU (DCF) and esophagectomy between February 2018 and February 2020. These patients were matched with contemporary patients (January 2018 to June 2020) who met the inclusion criteria but received neoadjuvant chemotherapy alone (NAC) with a comparable docetaxel-based therapy. The postoperative outcomes then were compared between the two groups. RESULTS: For this study, 99 patients with locally advanced EAC underwent esophagectomy and met the enrolment criteria. Of these patients, 50 received NAC alone and 49 received IO + NAC. Baseline characteristics such as age, gender, and clinical stage were comparable between the two groups. Operative approach and rate of minimally invasive esophagectomy (~ 60%) were similar in the two groups. For the NAC-alone and IO + NAC groups, the respective overall and major complication rates were similar between the two groups (50% vs. 51% [p = 0.91] and 20% vs. 26% [p = 0.44], respectively), with concordant rates for anastomotic leak (6 [12%] vs. 6 [12%]; p = 0.86) and respiratory complications (13 [26%] vs. 11 [22%]; p = 0.68). The two groups did not differ significantly in terms of hospital length of stay or 30- and 90-day mortality rates. CONCLUSION: The addition of immunotherapy to neoadjuvant chemotherapy for locally advanced esophageal adenocarcinoma does not appear to alter perioperative short-term outcomes significantly after esophagectomy.

Quantification of pyrrolizidine alkaloids in Senecio brasiliensis, beehive pollen, and honey by LC-MS/MS.

This article presents the determination of eight pyrrolizidine alkaloids (PAs) by LC-MS/MS in honeys, pollen, and Senecio brasiliensis (Asteraceae) samples, all from Santa Catarina state, Brazil. In addition, the Box-Behnken design was used to perform an optimized sample preparation on pollens and S. brasiliensis parts. Senecionine and its N-oxide, besides retrorsine N-oxide, were determined in six of the seven honeys samples. Pollen from species of the Asteraceae, Fabaceae, and Boraginaceae families were found with greater predominance in three of the seven honeys samples. In these three honeys samples were also found the highest PAs levels. In beehive pollen, flower, and leaf of S. brasiliensis, the total levels of PAs and their N-oxides reached 221, 14.1 × 104, and 14.8 × 104 mg kg-1, respectively. In honeys, these compounds are chemical contaminants and therefore undesirable when the sum exceeds 71 µg kg-1, according to EFSA. On the other hand, although PAs are naturally present in plant and pollen of some species (Senecio, Crotalaria, Bacharis, Ecchium, Mimosa scabrella, Vernonia), it is important to monitor their levels in plants but also in honeys, and other beehive products since these compounds are transferred to the final product.

Investigation of cell wall polysaccharides from flour made with waste peel from unripe banana (Musa sapientum) biomass.

BACKGROUND: The peel from unripe banana biomass is an agroindustrial waste. The present study aimed: (i) to extract pectin from enzymatically-treated waste peel from unripe banana biomass (WPUBB) using a Box-Behnken design to optimize the extraction conditions (temperature, pH and extraction time) and obtain a maximum yield and (ii) to fractionate the polysaccharides from WPUBB employing sequential extractions using different solvents. RESULTS: The optimized product was obtained at 86 °C, pH 2.00, for 6 h and it presented a yield of 11.63%. The optimized product had low galacturonic acid content and a high amount of glucose (82.3%), suggesting the presence of starch (as confirmed by the bi-dimensional heteronuclear single quantum coherence NMR spectrum). All of the fractionated polysaccharides had a high glucose content. Low amounts of pectin were found in the water, chelating and diluted alkali-soluble fractions. The fractions extracted using NaOH indicated the presence of glucuronoarabinoxylans. CONCLUSION: Glucose was the main monosaccharide found in all the fractions extracted from the WPUBB. Although the present study suggests that WPUBB is still not suitable for pectin extraction using current technologies, other compounds, such as resistant starch and glucuronoarabinoxylans, were found, suggesting that WPUBB could be used in the development of food formulations. © 2019 Society of Chemical Industry.

[Speech perception and cognitive abilities in seniors without subjective hearing loss]. / Sprachverstehen und kognitive Leistungen bei Senioren ohne subjektive Hörminderung.

The aim of this study was to assess the ability of elderly test subjects without self-reported hearing loss to perceive, hear and comprehend speech in quiet and noise. Furthermore, the effects of age and cognitive performance on hearing were also investigated.The study included 40 subjects aged over 60 years (average age: 69.3 ±â€…7.1 years). The subjects were screened for dementia (DemTect test) to test for any signs of cognitive deficiencies. Average hearing loss (PTA_4) and average high-frequency hearing loss (PTA_HT) were determined. Speech perception in quiet was tested by means of the Freiburg monosyllabic speech test and in noise by means of the Oldenburg sentence test with two different types of noise (temporally continuous and amplitude modulated). While the results of the DemTect test were age-appropriate for 65 % of the subjects, the remaining 35 % showed signs of mild cognitive impairments. The parameters of cognitive performance decreased significantly with age. The hearing loss (PTA_4 and PTA_HT) of the subjects correlated significantly with both age and DemTect score. Speech perception in both quiet and noise decreased significantly with age as well as within the parameters to assess cognitive performance.Seniors should undergo routine hearing screenings in order to detect hearing disorders as soon as possible so that hearing aids can be prescribed at an early stage. This would also allow, patients to get accustomed to their hearing aids early on and to achieve better hearing, thereby improving their quality of life.

Comparative proteomic profiling of the choline transporter-like1 (CHER1) mutant provides insights into plasmodesmata composition of fully developed Arabidopsis thaliana leaves.

In plants, intercellular communication and exchange are highly dependent on cell wall bridging structures between adhering cells, so-called plasmodesmata (PD). In our previous genetic screen for PD-deficient Arabidopsis mutants, we described choline transporter-like 1 (CHER1) being important for PD genesis and maturation. Leaves of cher1 mutant plants have up to 10 times less PD, which do not develop to complex structures. Here we utilize the T-DNA insertion mutant cher1-4 and report a deep comparative proteomic workflow for the identification of cell-wall-embedded PD-associated proteins. Analyzing triplicates of cell-wall-enriched fractions in depth by fractionation and quantitative high-resolution mass spectrometry, we compared > 5000 proteins obtained from fully developed leaves. Comparative data analysis and subsequent filtering generated a list of 61 proteins being significantly more abundant in Col-0. This list was enriched for previously described PD-associated proteins. To validate PD association of so far uncharacterized proteins, subcellular localization analyses were carried out by confocal laser-scanning microscopy. This study confirmed the association of PD for three out of four selected candidates, indicating that the comparative approach indeed allowed identification of so far undescribed PD-associated proteins. Performing comparative cell wall proteomics of Nicotiana benthamiana tissue, we observed an increase in abundance of these three selected candidates during sink to source transition. Taken together, our comparative proteomic approach revealed a valuable data set of potential PD-associated proteins, which can be used as a resource to unravel the molecular composition of complex PD and to investigate their function in cell-to-cell communication.

A meta-analysis of cognitive functions in children and adolescents with major depressive disorder.

The cumulative prevalence rates of major depressive disorders (MDD) in children and adolescents averages 9.5 %. The majority of adults with MDD suffer from significant cognitive deficits, but the available neuropsychological data on the cognitive performance of children and adolescents with MDD yielded mixed results. Meta-analytic methods were used to assess the severity of cognitive deficits in children and adolescents with MDD as compared to healthy children and adolescents. We identified 17 studies comparing the intelligence, executive functions, verbal memory and attention of 447 patients with DSM-IV MDD and 1,347 healthy children and adolescents. Children and adolescents with MDD performed 0.194-0.772 (p < 0.001) standard mean differences worse than healthy control subjects in neuropsychological test procedures. The most pronounced deficits of children and adolescents with MDD were seen in inhibition capacity (STD = 0.772; p = 0.002), phonemic verbal fluency (STD = 0.756; p = 0.0001), sustained attention (STD = 0.522; p = 0.000), verbal memory (STD = 0.516; p = 0.0009) and planning (STD = 0.513; p = 0.014). We revealed cognitive deficits of children and adolescents with MDD in various cognitive domains. Long-term studies should investigate how the cognitive deficits of depressed youth affect their academic and social functioning, and whether age, comorbidity and depression severity play a role in this process.

Composites of thermoplastic starch and nanoclays produced by extrusion and thermopressing.

The aim of this study was to produce thermoplastic starch (TPS) films and to enhance their properties by reinforcing them with hydrophilic and hydrophobic nanoclays. TPS films were prepared by extrusion and thermopressing, and their crystallinity, water vapor permeability (WVP), and mechanical properties were studied. The hydrophilic nanoclay lowered the material WVP due to the formation of an intercalated composite. The hydrophobic nanoclays increased the rigidity of the films but did not alter the tensile strength. The blending of nanoclays with thermoplastic starch modifies the mechanical properties and WVP, and these changes are strongly associated with the dispersion of nanoclay in the polymer matrix. The dispersion, in turn, depends on the compatibility of the matrix and the nanoclay in terms of the hygroscopicity and the concentration in which the nanoclay is used. The addition of nanoclays to starch-based films is a promising way to enhance them for industrial manufacture.

Age Differences in Speech Perception in Noise and Sound Localization in Individuals With Subjective Normal Hearing.

Hearing loss in old age, which often goes untreated, has far-reaching consequences. Furthermore, reduction of cognitive abilities and dementia can also occur, which also affects quality of life. The aim of this study was to investigate the hearing performance of seniors without hearing complaints with respect to speech perception in noise and the ability to localize sounds. Results were tested for correlations with age and cognitive performance. The study included 40 subjects aged between 60 and 90 years (mean age: 69.3 years) with not self-reported hearing problems. The subjects were screened for dementia. Audiological tests included pure-tone audiometry and speech perception in two types of background noise (continuous and amplitude-modulated noise) which was either co-located or spatially separated (multi-source noise field, MSNF) from the target speech. Sound localization ability was assessed and hearing performance was self-evaluated by a questionnaire. Speech in noise and sound localization was compared with young normal hearing adults. Although considering themselves as hearing normal, 17 subjects had at least a mild hearing loss. There was a significant negative correlation between hearing loss and dementia screening (DemTect) score. Speech perception in noise decreased significantly with age. There were significant negative correlations between speech perception in noise and DemTect score for both spatial configurations. Mean SRTs obtained in the co-located noise condition with amplitude-modulated noise were on average 3.1 dB better than with continuous noise. This gap-listening effect was severely diminished compared to a younger normal hearing subject group. In continuous noise, spatial separation of speech and noise led to better SRTs compared to the co-located masker condition. SRTs in MSNF deteriorated in modulated noise compared to continuous noise by 2.6 dB. Highest impact of age was found for speech perception scores using noise stimuli with temporal modulation in binaural test conditions. Mean localization error was in the range of young adults. Mean amount of front/back confusions was 11.5% higher than for young adults. Speech perception tests in the presence of temporally modulated noise can serve as a screening method for early detection of hearing disorders in older adults. This allows for early prescription of hearing aids.

Combined analysis of hypoxia-inducible factor 1 alpha and metallothionein indicates an aggressive subtype of colorectal carcinoma.

PURPOSE: Hypoxia-inducible factor 1 (HIF-1) is a hypoxia-induced transcription factor that regulates gene expression in critical pathways involved in tumour growth and metastasis. Metallothionein (MT) is a group of small molecular weight cysteine-rich proteins with a broad variety of functions. The present study aimed to analyse the prognostic impact of HIF-1alpha and MT expression in colorectal cancer and to evaluate a possible link of combined HIF-1alpha and MT expression with colorectal cancer progression. MATERIALS AND METHODS: We investigated the relationship of HIF-1alpha and MT with each other and clinicopathological parameters including proliferative activity (Ki67) and apoptosis (terminal desoxyribonucleotide transferase-mediated dUTP nick-end labelling) using immunohistochemistry. RESULTS: HIF-1alpha expression was identified as an independent prognostic parameter in multivariate survival analysis and characterised an aggressive cancer phenotype. In addition, HIF-1alpha was significantly linked to an increased expression of MT. CONCLUSIONS: HIF-1alpha expression qualified as an independent prognostic and characterised an aggressive cancer phenotype associated with an increased expression of MT. Our study suggests that MT can be added to the complex biological pathways induced by hypoxia in human cancer tissue.

Deciphering Root Architectural Traits Involved to Cope With Water Deficit in Oat.

Drought tolerance is a complex phenomenon comprising many physiological, biochemical and morphological changes at both aerial and below ground levels. We aim to reveal changes on root morphology that promote drought tolerance in oat in both seedling and adult plants. To this aim, we employed two oat genotypes, previously characterized as susceptible and tolerant to drought. Root phenotyping was carried out on young plants grown either in pots or in rhizotrons under controlled environments, and on adult plants grown in big containers under field conditions. Overall, the tolerant genotype showed an increased root length, branching rate, root surface, and length of fine roots, while coarse to fine ratio decreased as compared with the susceptible genotype. We also observed a high and significant correlation between various morphological root traits within and between experiments, identifying several of them as appropriate markers to identify drought tolerant oat genotypes. Stimulation of fine root growth was one of the most prominent responses to cope with gradual soil water depletion, in both seedlings and adult plants. Although seedling experiments did not exactly match the response of adult plants, they were similarly informative for discriminating between tolerant and susceptible genotypes. This might contribute to easier and faster phenotyping of large amount of plants.

Release of simvastatin from scaffolds of poly(lactic-co-glycolic) acid and biphasic ceramic designed for bone tissue regeneration.

The aim of this study was to evaluate the release of simvastatin from scaffolds composed of poly(lactic-co-glycolic) acid (PLGA) and biphasic ceramic designed for bone engineering and to assess the physico-chemical and mechanical properties of the scaffolds. Samples with 30% and 70% porosity were obtained with 0, 2, 5, and 8 wt %. of simvastatin through the solvent evaporation technique and leaching of sucrose particles. Scaffold degradation and simvastatin release were evaluated in phosphate-buffered saline. Scaffolds were analyzed by scanning electron microscopy and microtomography for two-dimensional and three-dimensional morphological characterization of the porosity, connectivity, and intrinsic permeability. The mechanical characterization was conducted based on the compressive strength and the chemical characterization by differential scanning calorimetry and energy dispersive X-ray spectroscopy. Gradual and prolonged simvastatin release from the scaffolds was observed. The release followed the Korsmeyer kinetics model with the predominance of case II transport for 30% porosity scaffolds, and anomalous behavior for the 70% porosity samples. Simvastatin release was also influenced by the slow scaffold degradation due to the strong chemical interaction between simvastatin and PLGA, as observed by differential scanning calorimetry. The scaffolds presented spherical and sucrose crystal-shaped pores that resulted in a homogenous porosity, with a predominance of open pores, ensuring interconnectivity. Simvastatin incorporation into the scaffolds and increased porosity did not influence the mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties. The scaffolds presented gradual and prolonged simvastatin release, with satisfactory physico-chemical and mechanical properties, a promise for applications in bone regeneration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2152-2164, 2019.

Synthesis and characterization of cassava starch with maleic acid derivatives by etherification reaction.

Cassava starch was grafted with three different esters by the etherification reaction and its modification was characterized by 1H NMR, FTIR, DSC, SEM, XDR, contact angle and SLS. The samples grafted with diethyl maleate, dipropyl maleate, and dibutyl maleate showed DS values of 2.3, 1.0 and 2.0, respectively, determined from 1H NMR analysis and confirmed by FTIR analysis, with the appearance of bands at 1721, 1550 and 1126cm-1. The FTIR, XRD, SEM and DSC results indicated a change in the intra and intermolecular hydrogen interactions in the grafted starch when compared to native starch. Based on the contact angles, it was observed that the macromolecular starch chain acquired hydrophobic characteristics through the substitution of the hydrogens with di maleate esters. The characteristics acquired by grafted starch allow it to be used for the encapsulation of bioactive molecules for the production of bioactive packages and the production of biodegradable packages.

Ultrasonic-assisted extraction combined with sample preparation and analysis using LC-ESI-MS/MS allowed the identification of 24 new phenolic compounds in pecan nut shell [Carya illinoinensis (Wangenh) C. Koch] extracts.

Ultrasonic-assisted extraction combined with statistical tools (factorial design, response surface methodology and kinetics) were used to evaluate the effects of the experimental conditions of temperature, solid-to-solvent ratio, ethanol concentration and time for the extraction of the total phenolic content from pecan nut shells. The optimal conditions for the aqueous and hydroalcoholic extract (with 20% v/v of ethanol) were 60 and 80 °C; solid to solvent ratio of 30 mL·g-1 (for both) and extraction time of 35 and 25 min, respectively. Using these optimize extraction conditions, 426 and 582 mg GAE·g-1 of phenolic compounds, from the aqueous and hydroalcoholic phases respectively, were obtained. In addition, the analysis of the phenolic compounds using the LC-ESI-MS/MS system allowed the identification of 29 phenolic compounds, 24 of which had not been reported in literature for this raw material yet.

GrowScreen-PaGe, a non-invasive, high-throughput phenotyping system based on germination paper to quantify crop phenotypic diversity and plasticity of root traits under varying nutrient supply.

New techniques and approaches have been developed for root phenotyping recently; however, rapid and repeatable non-invasive root phenotyping remains challenging. Here, we present GrowScreen-PaGe, a non-invasive, high-throughput phenotyping system (4 plants min-1) based on flat germination paper. GrowScreen-PaGe allows the acquisition of time series of the developing root systems of 500 plants, thereby enabling to quantify short-term variations in root system. The choice of germination paper was found to be crucial and paper☓root interaction should be considered when comparing data from different studies on germination paper. The system is suitable for phenotyping dicot and monocot plant species. The potential of the system for high-throughput phenotyping was shown by investigating phenotypic diversity of root traits in a collection of 180 rapeseed accessions and of 52 barley genotypes grown under control and nutrient-starved conditions. Most traits showed a large variation linked to both genotype and treatment. In general, root length traits contributed more than shape and branching related traits in separating the genotypes. Overall, results showed that GrowScreen-PaGe will be a powerful resource to investigate root systems and root plasticity of large sets of plants and to explore the molecular and genetic root traits of various species including for crop improvement programs.

Thermoplastic starch/polyester films: effects of extrusion process and poly (lactic acid) addition.

Biodegradable films were produced using the blown extrusion method from blends that contained cassava thermoplastic starch (TPS), poly(butylene adipate-co-terephthalate) (PBAT) and poly(lactic acid) (PLA) with two different extrusion processes. The choice of extrusion process did not have a significant effect on the mechanical properties, water vapor permeability (WVP) or viscoelasticity of the films, but the addition of PLA decreased the elongation, blow-up ratio (BUR) and opacity and increased the elastic modulus, tensile strength and viscoelastic parameters of the films. The films with 20% PLA exhibited a lower WVP due to the hydrophobic nature of this polymer. Morphological analyses revealed the incompatibility between the polymers used.

Studies toward the development of new silicon-containing building blocks for the direct (18)F-labeling of peptides.

Silicon-containing prosthetic groups have been conjugated to peptides to allow for a single-step labeling with (18)F radioisotope. The fairly lipophilic di-tert-butylphenylsilane building block contributes unfavorably to the pharmacokinetic profile of bombesin conjugates. In this article, theoretical and experimental studies toward the development of more hydrophilic silicon-based building blocks are presented. Density functional theory calculations were used to predict the hydrolytic stability of di-tert-butylfluorosilanes 2-23 with the aim to improve the in vivo properties of (18)F-labeled silicon-containing biomolecules. As a further step toward improving the pharmacokinetic profile, hydrophilic linkers were introduced between the lipophilic di-tert-butylphenylsilane building block and the bombesin congeners. Increased tumor uptake was shown with two of these peptides in xenograft-bearing mice using positron emission tomography and biodistribution studies. The introduction of a hydrophilic linker is thus a viable approach to improve the tumor uptake of (18)F-labeled silicon-bombesin conjugates.