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José Barberán,1 Lorenzo Aguilar,2 María-José Giménez21Infectious Diseases Department, Hospital Central de la Defensa Gomez Ulla, 2Microbiology Department, School of Medicine, Universidad Complutense de Madrid, Madrid, SpainAbstract: This article reviews and updates published data on cefditoren. The in vitro activity of cefditoren and its potential pharmacokinetic/pharmacodynamic adequacy to cover emerging resistance phenotypes in the present decade is reviewed. Cefditoren's in vitro activity against most prevalent bacterial respiratory pathogens in the community and its pharmacokinetic/pharmacodynamic profile suggests a significant role for cefditoren in the treatment of respiratory tract infections. Clinical trials (in acute exacerbations of chronic bronchitis, community-acquired pneumonia, pharyngotonsillitis, and sinusitis) performed during clinical development outside Japan, mainly in adults, are reviewed, together with new clinical studies in the treatment of pharyngotonsillitis, sinusitis, and otitis media in children, mainly in Japan, for efficacy and safety assessment. The results of these studies support the adequacy of cefditoren for the treatment of community-acquired respiratory tract infections with a safety profile similar to previous oral antibiotics. From the data reviewed, it is concluded that cefditoren is an adequate option for the treatment of mild-to-moderate community-acquired respiratory infections, especially in geographical areas with a reported prevalence of phenotypes exhibiting nonsusceptibility to common oral antibiotics.Keywords: acute exacerbations of chronic bronchitis, community-acquired pneumonia, pharyngotonsillitis, sinusitis, otitis media

BACKGROUND:: Community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis (AECB) are frequently caused by Streptococcus pneumoniae, Haemopbilus influenzae, and Moraxella catarrbalis; thus, these are the target pathogens for antibiotic treatment. OBJECTIVES:: This pooled analysis was performed to evaluate the efficacy of cefditoren pivoxil (CDN) in patients with lower respiratory tract infections (CAP or AECB). A particular focus was the per-pathogen bacteriologic response rate among the most common causative pathogens, S pneumoniae, H influenzae, and M catarrbalis. METHODS:: The final reports of all clinical trials of CDN in the treatment of community-acquired lower respiratory tract infection were reviewed. Microbiologic outcome data for CDN 200 and 400 mg and comparator treatments were pooled from 4 CAP studies (3 randomized and 1 noncomparative) and 3 AECB studies. The comparators were the standard oral treatments clarithromycin 500 mg BID, cefuroxime 250 mg BID, cefpodoxime 200 mg BID, and amoxicillin/clavulanate 500/125 mg TID or 875/125 mg BID.Microbiologic response was defined as eradication of the initial pathogen or presumed eradication (absence of sputum for culture in a patient with a clinical response). RESULTS:: The bacteriologically evaluable population contained 654 patients in the CDN 200-mg group, 592 in the CDN 400-mg group, and 664 in the comparator group. A total of 1223 target pathogens were isolated before treatment: 406 isolates of S pneumoniae (including 56 penicillin-nonsusceptible [intermediate + resistant] strains), 595 isolates of H influenzae, and 222 isolates of M catarrbalis. The microbiologic response ranged from 84.1% to 88.8% in the CAP studies and from 75.1% to 77.1% in the AECB studies, with no differences between the CDN 200-mg, CDN 400-mg, and comparator groups. In the analysis of per-pathogen bacteriologic response, similar response rates were found for S pneumoniae (range, 88.5%-92.0%), H influenzae (range, 82.7%-86.6%), and M catarrbalis (range, 84.1%-95.2%), with no significant differences between groups. Focusing on penicillin-nonsusceptible (MIC >/=0.12 mug/mL) strains of S pneumoniae, CDN (both doses pooled) was associated with a response rate of 92.3% (36/39 isolates); all nonresponders were in the CDN 200-mg group. When only penicillin-resistant (MIC >/=2 mug/mL) strains were considered, there was only 1 nonresponder, again in the CDN 200-mg group. Thus, the overall response rate to CDN (both doses pooled) was 94.4% (17/18 isolates). CONCLUSIONS:: In this pooled analysis, CDN was associated with high rates of per-pathogen bacteriologic response among the main causative pathogens in lower respiratory tract infection. The rates of response were approximately 85% against H influenzae and approximately 90% against S pneumoniae, including penicillin-intermediate and penicillin-resistant strains. [ABSTRACT FROM AUTHOR]

A gerbil mode of otitis media induced by a β-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (±106 cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses. [ABSTRACT FROM PUBLISHER]

Primary dysmenorrhea (PD), a prevalent menstrual condition characterized by pelvic pain during the menstrual cycle, significantly impacts the quality of life of women and produces increased pain sensitivity that can persist throughout the menstrual cycle. However, scientific literature has not studied whether there are implications for alterations in muscle function and endurance in the abdominopelvic region during the non-painful phases of the menstrual cycle. The aim of this study was to compare muscle function and endurance capacity in the abdominopelvic region in women with PD versus women without this condition. An observational, cross-sectional study was designed to analyze muscle activation and endurance capacity using electromyography (EMG) during McGill exercises. Forty-four women were included, 22 with PD and 22 without dysmenorrhea. The results did not indicate significant differences in muscle activation and endurance of the abdominopelvic musculature between the two groups (p > 0.05). However, the analysis suggests that women with primary dysmenorrhea might develop compensatory strategies that allow them to maintain physical function despite their condition. These results suggest that the approach to PD could focus more on pain management rather than physical functionality, and more studies are needed from a comprehensive approach to more accurately evaluate the relationship between PD and muscle function., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Commission of Universidad Europea de Madrid (protocol code CIPI/23.146; date of approval: April 20, 2023). Informed consent: Informed consent was obtained from all participants involved in the study., (© 2024. The Author(s).)

Background: The modulation of the autonomic nervous system's activity, particularly increasing its parasympathetic tone, is of significant interest in clinical physiotherapy due to its potential benefits for stress-related conditions and recovery processes. This study evaluated the effectiveness of the addition of neurodynamics in enhancing parasympathetic activation in subjects with chronic stress., Methods: A clinical trial randomly assigned participants to a group with neurodynamics (6 bpm breathing protocol + manual therapy + neurodynamic technique) or a group without neurodynamics (6 bpm breathing protocol + manual therapy only). Metrics of heart rate variability (HRV), including the Mean Heart Rate (Mean HR), standard deviation of intervals between consecutive heartbeats (SDNN), Heart Rate Difference (Diff. HR), Root Mean Square of Successive Differences (RMSSD), number of intervals differing by more than 50 ms (NN50), percentage of consecutive NN intervals that differed by more than 50 ms (pNN50), and the high-frequency component measured in standardized units (HF), were assessed before, during, and after the intervention., Results: During the intervention, the group with neurodynamics showed significant changes in all variables except in the pNN50 and HF while the group without neurodynamics only showed improvements in the Mean HR, SDNN, and RMSSD. In the post-intervention phase, the group with neurodynamics maintained an increase in HRV while the group without neurodynamics experienced a decrease, suggesting an increase in sympathetic activity., Conclusions: Vagal nerve neurodynamics appear to represent an effective method for enhancing parasympathetic activation in patients with chronic stress. The results highlight the importance of a more comprehensive analysis of HRV variables in order to obtain a correct picture of the impact of interventions on the complex and multifaceted functioning of the autonomic nervous system.

Background : This cross-sectional observational study aimed to investigate differences in abdominal musculature thickness, pelvic tilt, and trunk mobility between women with primary dysmenorrhea (PD) and a control group (CG). Methods : Participants included 44 women (22 with PD and 22 controls) aged over 18, nulliparous, and of reproductive age. Ultrasound imaging was used to measure the thickness of the transverse abdominis (TrA), internal oblique (IO), external oblique (EO), and rectus abdominis (RA) muscles at rest and during contraction. Additionally, anterior pelvic tilt was assessed using the Palpation Meter (PALM), and trunk flexion and extension were measured using an accelerometer (activForce2). Results : Significant differences ( p < 0.05) were found in RA and EO muscle thickness, with lower values in the PD group compared to CG. However, there were no significant differences ( p > 0.05) in TrA and IO muscle thickness, anterior pelvic tilt, or trunk mobility between groups. Conclusions : These findings contribute to understanding the musculoskeletal factors potentially involved in dysmenorrhea. Further research is needed to explore associations between PD and structural and alignment parameters.

This retrospective study aimed to analyze the return to running of non-professional runners after experiencing asymptomatic or mild COVID-19. Participants aged 18-55 years who maintained a training load of ≥10 km/week for at least three months prior to diagnosis and utilized Garmin/Polar apps were included. From these devices, parameters such as pace, distance, total running time, cadence, and heart rate were collected at three intervals: pre-COVID, immediately post-COVID, and three months after diagnosis. The Wilcoxon signed rank test was used for analysis (significance was set at ≤0.05). Twenty-one participants (57.1% male; mean age 35.0 ± 9.8 years) were included. The results revealed a significant decrease in running duration and distance two weeks after diagnosis, without significant changes in other parameters. Three months after infection, no differences were observed compared to pre-infection data, indicating a return to the pre-disease training load. These findings underscore the transient impact of COVID-19 on training performance among non-professional runners with mild or asymptomatic symptoms, highlighting the importance of tailored strategies for resuming running after infection.

This study aimed to investigate if the characteristics of different running shoes could influence intra-abdominal pressure during running. A single-centre, randomized, prospective cross-over clinical trial was performed measuring activity patterns of internal oblique (IO), lumbar erector (LE), and gluteus maximus (GM) muscles in healthy women when running with minimalist shoes (MS). Participants were randomly allocated into two-sequence (MS/TS or TS/MS) treadmill running at six, nine, and eleven km/h. The surface electromyographic activity of IO, LE, and GM muscles were recorded while running. A repeated measures ANOVA explored the interaction effects of three-muscle x three speeds x two shoes. Significance was set at p ≤ 0.05. Fifty-one healthy nulliparous women (mean age: 26.55 ± 5.11 years; body mass index: 21.29 ± 2.07 Kg/m 2 ) were included. Our findings revealed lower activations of the LE compared to the internal oblique IO and GM, irrespective of running speed and footwear used. Electromyographic activation significantly increased with higher running speeds ( p < 0.001) for all muscles, regardless of the type of footwear. Although electromyographic records with MS consistently showed higher values than those with TS, the differences were not statistically significant for all muscles at all speeds. Our results indicate that electromyographic activation patterns vary according to the muscle group, exhibiting higher values with increased running speed. No significant differences were observed between MS and TS.

The commercialisation of fresh-cut artichokes with optimal quality and appearance and a maximum shelf-life is a great challenge for the artichoke market. The use of different anti-browning agents has been previously studied; however, their effect is still limited. Therefore, the objective of this study is the evaluation of the effect of L-cysteine and, in combination with a mixture of essential oils components (eugenol, thymol and carvacrol) on browning, quality and bioactive compounds of fresh-cut artichokes stored for 9 days at 2 °C. Four different treatments were applied to 'Blanca de Tudela' fresh-cut artichokes: cysteine and cysteine with 75, 150 and 300 µL of the essential oils components (EOs) mixture. After 2, 4 and 9 days of storage, physicochemical parameters (weight loss, colour, respiration rate) and functional (total phenolic content, antioxidant activity) were studied. A descriptive sensorial analysis was also carried out to evaluate sensory attributes. Results showed that the application of cysteine and 150 µL of EOs displayed the lowest browning and highest antioxidant properties, as well as the best quality and sensory parameters. The use of this post-harvest treatment on fresh-cut artichokes would result in a natural and eco-friendly solution to improve artichoke quality and shelf-life.

In the northern hemisphere countries, artichoke harvest occurs in winter months; consequently, they are exposed to cold temperatures. This can lead to frost injury, such as triggering the blistering of the cuticle and detachment of outer bracts, which eventually could display brown or black discolouration. This can cause major economic and production losses. As far as we know, no literature is available about this problem in artichokes. Thus, the main aim of this study was to evaluate the effect of total phenolic content and the antioxidant potential of 'Blanca de Tudela' artichokes in their capacity to tolerate frost injury when they are exposed to low temperatures. Several factors were analysed, including floral head order, weight and size of artichokes, total phenolic content, phenolic profile and total antioxidant activity. Results showed that tertiary heads, which are the smallest in size, exhibited a greater amount of total phenolic content and antioxidant activity. As a result, these characteristics offered enhanced protection to the artichoke against frosting temperatures. In contrast, the largest artichokes, especially the primary heads, were more susceptible to suffer frostbite. Therefore, artichokes with robust antioxidant systems, characterized by elevated phenolic content, are crucial to reduce their susceptibility to frost injury.

Background: Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians., Main Body: This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed., Conclusion: There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The effect of oxalic acid (OA) in determining poorly coloured table grape quality remains relatively unknown. Some red cultivars, such as seedless table grape 'Magenta' are characterised by a poor berry colour, an attribute highly demanded by the consumer. The aim of this research was to elucidate the effect of a preharvest OA treatment (5 mM) on berry colour and quality of table grape by investigating its role in berry development, on-vine ripening, and postharvest senescence. We found that OA significantly increased abscisic acid (ABA) and ABA glucose ester (ABA-GE) content in treated berries. This increase was mediated by changes in the ABA biosynthetic pathway, specifically by the upregulation of the 9- cis -epoxycarotenoid dioxygenase ( Vv NCED1) gene. The accumulation of ABA in treated berries resulted in colour improvement and a higher individual and total anthocyanins content at harvest compared with control; whereas at harvest, OA-treated table grapes showed a significantly lower glucose and fructose content and a higher content of tartaric, ascorbic, and succinic acids. Furthermore, antioxidant enzyme activity was increased during berry development in OA-treated berries. On the other hand, those berries treated with OA showed a delay in loss of firmness and colour during cold storage, as well as less susceptibility to postharvest decay incidence. This effect of OA delaying the senescence process was also related to enzymatic antioxidant system stimulation. For the first time, the role of OA on increasing quality, mainly colour, in table grapes was elucidated, highlighting that this treatment upregulated ABA metabolism, relative Vv NCED1 gene expression and antioxidant system, delaying postharvest berry senescence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 García-Pastor, Giménez, Serna-Escolano, Guillén, Valero, Serrano, García-Martínez, Terry, Alamar and Zapata.)

Flower head orders and the use of GA 3 (gibberellic acid) treatment could be two influencing factors determining the bioactive compound levels in artichoke, but little to no information is available about their effects. In this study, we have therefore evaluated the influence of these factors on the hydroxycinnamic acid and luteolin derivative levels in three categories of artichoke: Seed-propagated open-pollinated cultivars; vegetatively propagated cultivars; and seed-propagated hybrids. The hydroxycinnamic acids and luteolin derivatives were quantified by RP-HPLC-DAD. The average flower head weight was the lowest in tertiary heads and GA 3 -treated artichokes, followed by secondary and main heads. Moreover, the hydroxycinnamic acid and luteolin derivatives levels were significantly higher in tertiary heads than in secondary or main heads. In addition, the GA 3 treatment significantly reduced the hydroxycinnamic acid content and, in contrast, improved luteolin derivatives levels. These effects depended on the flower head order and cultivar. Knowledge of the effects of flower head order and GA 3 treatment is therefore key in order to achieve the greatest health-benefits from artichoke consumption.

Lemon trees ( Citrus limon (L.) Burm. F) were treated monthly with oxalic acid (OA) at 0.1, 0.5, and 1 mM from initial fruit growth on the tree until harvest in2019. The experiment was repeated in 2020, with the application of OA 1 mM (according to the best results of 2019). In both years, fruit from OA-treated trees and the controls were stored for 35 days at 10 °C. Results showed that all treatments reduced weight loss (WL) and maintained higher firmness, total soluble solids (TSS), and total acidity (TA) than in the controls. Meanwhile, colour (hue angle) did not show significant differences. The activity of antioxidant enzymes, catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD) in the flavedo of the fruit from the OA-treated trees was higher than in the controls at harvest and after 35 days of storage. Similarly, the total phenolic content (TPC) in the flavedo and juice of the fruit from the OA-treated trees were higher than in the controls. The increase in the activity of the antioxidant enzymes and TPC started with the first preharvest OA treatment and were maintained during fruit development on the tree until harvest. Preharvest OA treatments enhanced the antioxidant system of the lemon fruits, reducing the postharvest incidence of decay. Thus, OA could be a useful tool to increase the quality and functional properties of lemon fruits.

Green pepper fruit is often consumed before it is completely ripe. However, the influence of the phenological stage in which the green pepper is consumed as a potential influencing factor in its bioactive compounds content and antioxidant capacity remains unknown. In addition, no literature is available concerning the bioactive compounds changes in 'Lamuyo' green peppers along its developmental and growth cycle. For this, two different approaches have been carried out, one using twelve different phenological stages (S1 to S12), and in the other, seven different harvest dates (from 27 February to 20 April). Moreover, bioactive compounds changes during 21 days of postharvest storage at 8 °C were investigated. In this study, bioactive compounds (ascorbic acid, dehydroascorbic acid, and total phenolic content) and the total hydrophilic and lipophilic (TAA-H and TAA-L) antioxidant activity were analysed. In addition, total soluble solids, total acidity, individual sugars, and organic acids were determined. Vitamin C levels increased along the phenological stages and harvest dates due to significant increases in ascorbic and dehydroascorbic acid levels. Our results show that the total phenol content decreases as vegetables develop and subsequently increases both as ripening begins and by the last harvest date. Furthermore, TAA-H was also greater by the phenological stage S12 and the 20 April harvest date. In conclusion, the phenological stage and harvest date are key factors that significantly influence the bioactive compounds of green peppers, and those that appear by S12 and 20 April could be more beneficial to health.

Celiac Disease (CD) is an autoimmune disorder that affects approximately 1% of the worldwide population. The α-gliadins of wheat contain the 33-mer peptide, the most active peptide in CD both in adults and pediatric patients. In this study, we have characterized the variants and expression profile of an α-gliadins amplicon, harboring the 33-mer peptide, in two low-gliadin RNAi wheat lines, under two different Nitrogen (N) treatments. We estimated that the amplicon expands 45 different α-gliadin variants with high variability due to length, randomly distributed SNPs, and the presence of encoded CD epitopes. Expression of this amplicon is reduced in both RNAi lines in comparison to the wild type. High N treatment significantly increases transcripts of the amplicon in the wild type, but not in the transgenic lines. Classification of α-gliadin variants, considering the number of epitopes, revealed that amplicon variants containing the full complement of 33-mer peptide were affected by N treatment, increasing their expression when N was increased. Line D793 provided higher and more stable silencing through different N fertilization regimes, expressing fewer CD epitopes than D783. Results of this study are important for better understanding of RNAi α-gliadin silencing in response to N treatments, and for undertaking new strategies by RNAi or CRISPR/Cas toward obtaining new varieties suitable for people suffering gluten intolerances., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sánchez-León, Giménez and Barro.)

The effects of preharvest treatments with 0.1 mM methyl jasmonate (MeJA) and 0.5 mM salicylic acid (SA) on quality parameters of lemon fruit and their relationship with antioxidant systems, gene expression and bioactive compounds at harvest and during cold storage were evaluated. Results showed that total antioxidant activity, total phenolic content and the major individual phenolics (hesperidin and eriocitrin) were always higher in treated fruit than in controls. The activity of the antioxidant enzymes catalase, peroxidase and ascorbate peroxidase was also increased at harvest by SA and MeJA treatments, especially the last enzyme, for which the expression of its codifying gene was also enhanced. In addition, treated fruit had lower weight and firmness losses, respiration rate and production of ethylene than controls. Moreover, sugars and organic acids were maintained at higher concentration in flavedo and juice as a consequence of preharvest SA and MeJA treatments, showing an effect on maintaining fruit quality properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The main goal of this study was to describe impact of preharvest application of methyl salicylate (MeSA), acetyl salicylic acid (ASA) and salicylic acid (SA) on the reduction of disease caused by Botrytis cinerea in two table grape cultivars ('Crimson' and 'Magenta'). Based on previous studies, MeSA and SA were applied at 0.1 and 0.01 mM for both cultivars, while ASA was applied at 1 mM in 'Crimson' and 0.1 mM in 'Magenta'. At time of harvest, berry maturity-quality attributes, bioactive compounds and antioxidant enzymes were determined. In addition, grapes were artificially inoculated with B. cinerea spores, and the berries were ranked for visual decay incidence after 5 days of inoculation. Salicylates preharvest treatments led to higher total acidity, content of bioactive compounds and activity of antioxidant enzymes in treated than in control berries. The application of salicylate derivatives induced resistance to B. cinerea spoilage, since higher percentage of berries with no symptoms was observed and on the contrary, the highest percentages of berries were obtained in control grapes. All preharvest treatments with SA, ASA and MeSA alleviated postharvest disease caused by B. cinerea probably due to increasing levels of phenolic compounds and activity of antioxidant enzymes, although the best results were obtained with MeSA at 0.1 mM. Also, for this treatment and dose, higher quality properties, such as higher concentrations of ascorbic, succinic and fumaric acids, were observed compared with no treated-grapes., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Temperature and nitrogen (N) availability are two important environmental factors that may produce important changes in grain composition during grain filling of bread wheat. In this study, four wheat lines with the down-regulation of gliadins by means of RNA interference (RNAi) have been characterized to determine the effect of thermal stress and N availability on grain weight and quality; with focus on gliadin and glutenin protein fractions. Grain weight was reduced with heat stress (HS) in all RNAi lines, whereas gliadin content was increased in the wild-types. With respect to gliadin content, RNAi lines responded to HS and N availability differently from their respective wild-types, except for ω-gliadin content, indicating a very clear stability of silencing under different environmental conditions. In a context of increased temperature and HS events, and in environments with different N availability, the RNAi lines with down-regulated gliadins seem well suited for the production of wheat grain with low gliadin content., (Copyright © 2020 Marín-Sanz, Giménez, Barro and Savin.)

Background: Previous reports have addressed the effectiveness of postharvest methyl jasmonate (MeJA) treatments on maintaining quality properties of pomegranate fruit during storage. However, there is no literature regarding the effects of preharvest MeJA treatments on pomegranate 'Mollar de Elche' crop yield, fruit ripening, quality attributes and bioactive compounds content (at harvest or after long-term storage), which were evaluated in this research., Results: Preharvest MeJA treatments (1, 5, and 10 mmol L -1 ) increased pomegranate crop yield. MeJA at 1 and 5 mmol L -1 accelerated the on-tree ripening process, while it was delayed with 10 mmol L -1 . Losses in fruit weight, firmness and organic acids during storage at 10 °C were delayed in MeJA treated fruit, leading to quality maintenance. In addition, MeJA treatments improved arils colour due to increased concentration of total and individual anthocyanins, at harvest and during storage. Total phenolic and ascorbic acid contents and total antioxidant activity [hydrophilic (H-TAA) and lipophilic (L-TAA) fractions] were also higher in arils from treated pomegranate fruits than in controls., Conclusion: Preharvest treatments with MeJA could be a promising tool to improve pomegranate crop yield, fruit quality and its content in bioactive compounds at harvest and during storage. The higher effects were obtained with MeJA at 5 mmol L -1 dose, which could be the selected treatment for practical application purposes. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-γ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of α- and γ-gliadins, and low or almost devoid of DQ2.5 and p31-43 α-gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation.

Objectives: Bacterial viability and enrichment of resistance resulting from three different amikacin administration schedules with respect to haemodialysis (HD) were assessed against three OXA-48-producing Klebsiella pneumoniae isolated during an outbreak in a Spanish hospital., Methods: A previously described two-compartment dynamic system was used. Three possible amikacin administration schedules were simulated: (i) haemodialysis immediately after amikacin infusion (pre-HD); (ii) infusion immediately after haemodialysis (post-HD); and (iii) infusion at 50% interdialytic period. Amikacin standard dose (SD) and double dose (DD) were simulated for each schedule. Values of C max /MIC, C max /MPC (mutant prevention concentration), AUC 0-48h /MIC, AUC 0-48h /MPC and %T MSW (percentage of time that the concentration was inside the mutant selection window) were determined with experimental data and were correlated with the area under the bacterial killing curve of the total population and the resistant subpopulation., Results: Both with SD and DD, the pre-HD schedule resulted in increases at 48h in bacterial counts of the total population at the expense of enrichment of pre-existing resistant subpopulations from 12h onwards for all strains. The estimated %T MSW that prevented enrichment of resistant mutants was <61.5%. The AUC 0-48h /MPC (with values of ≈40 being associated with countering of increases in resistant subpopulations) was better than the %T MSW as a predictive parameter., Conclusion: This study showed that the longest times concentrations were above the MPC (i.e. highest AUC 0-48h /MPC, lowest %T MSW ), the lowest enrichment of resistant subpopulations. This implies use of the highest possible amikacin dose (limited by toxicity) and post-HD as the best administration schedule., (Copyright © 2019. Published by Elsevier Ltd.)

The concept of healthcare-associated infections (as opposed to hospital-acquired infections) in intraabdominal infections (IAIs) is scarcely supported by data in the literature. The aim of the present study was to analyse community-onset IAIs (non-postoperative/non-nosocomial) in patients admitted to intensive care units (ICUs), to investigate differences in resistance patterns linked to healthcare exposure and mortality-associated factors. A one-year prospective observational study (17 Spanish ICUs) was performed distributing cases as healthcare-associated infections (HCAI), community-acquired infections (CAI) and immunocompromised patients (ICP). Bacteria producing extended-spectrum β-lactamases (ESBL) and/or carbapenemase (CPE), high-level aminoglycoside- and/or methicillin- and/or vancomycin- resistance were considered antimicrobial resistant (AMR). Mortality-associated factors were identified by regression multivariate analysis. Of 345 patients included (18.8% HCAI, 6.1% ICP, 75.1% CAI), 51.6% presented generalized peritonitis; 32.5% were >75 years (55.4% among HCAI). Overall, 11.0% cases presented AMR (7.0% ESBL- and/or CPE), being significantly higher in HCAI (35.4%) vs. CAI (5.8%) (p<0.001) vs. ICP (0%) (p = 0.003). Overall 30-day mortality was 14.5%: 23.1% for HCAI and 11.6% for CAI (p = 0.016). Mortality (R2 = 0.262, p = 0.021) was positively associated with age >75 years (OR = 6.67, 95%CI = 2.56-17.36,p<0.001), Candida isolation (OR = 3.05, 95%CI = 1.18-7.87,p = 0.022), and SAPS II (per-point, OR = 1.08, 95%CI = 1.05-1.11, p<0.001) and negatively with biliary infections (OR = 0.06, 95%CI = 0.01-0.48,p = 0.008). In this study, the antimicrobial susceptibility pattern of bacteria isolated from patients with healthcare contact was shifted to resistance, suggesting the need for consideration of the healthcare category (not including hospital-acquired infections) for severe IAIs. 30-day mortality was positively related with age >75 years, severity and Candida isolation but not with AMR., Competing Interests: E.M. has served as speaker for Merck, Sharp & Dohme (MSD), Pfizer and Astellas; and has received educational grants from Astellas. F.R. has served as speaker for MSD. G.A. has served as speaker for MSD, Astellas, Gilead, and Pfizer and received educational grants from Astellas, Pfizer and MSD. M-JG is employee of PRISM-AG and has received an educational grant from Fundación Micellium para el Desarrollo y Difusión del Conocimiento Científico (Valencia, Spain). The remaining authors have disclosed that they do not have any potential conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Plant proteases play a crucial role in many different biological processes along the plant life cycle. One of the most determinant stages in which proteases are key protagonists is the plant germination through the hydrolysis and mobilization of other proteins accumulated in seeds and cereal grains. The most represented proteases in charge of this are the cysteine proteases group, including the C1A family known as papain-like and the C13 family also called legumains. In cereal species such as wheat, oat or rye, gluten is a very complex mixture of grain storage proteins, which may affect the health of sensitive consumers like celiac patients. Since gluten proteins are suitable targets for plant proteases, the knowledge of the proteases involved in storage protein mobilization could be employed to manipulate the amount of gluten in the grain. Some proteases have been previously found to exhibit promising properties for their application in the degradation of known toxic peptides from gluten. To explore the variability in gluten-degrading capacities, we have now analyzed the degradation of gluten from different wheat cultivars using several cysteine proteases from barley. The wide variability showed highlights the possibility to select the protease with the highest potential to alter grain composition reducing the gluten content. Consequently, new avenues could be explored combining genetic manipulation of proteolytic processes with silencing techniques to be used as biotechnological tools against gluten-related disorders.

Gluten proteins, major determinants of the bread-making quality of wheat, are related to several digestive disorders. Advances in plant genetic breeding have allowed the production of wheat lines with very low gliadin content through the use of RNAi and gene editing technologies. In this review, we carried out a comprehensive study of the application of these cutting-edge technologies towards the development of wheat lines devoid of immunogenic gluten, and their genetic, nutritional and clinical characterization. One line, named E82, showed outstanding nutritional properties, with very low immunogenic gluten and a low stimulation capacity of T-cells from celiac patients. Moreover, a clinical trial with non-celiac wheat sensitivity (NCWS) patients showed that the consumption of bread made with this E82 low gliadin line induced positive changes in the gut microbiota composition.

Objective: To evaluate nephrotoxicity development in patients treated with vancomycin (VAN) and daptomycin (DAP) for proven severe Gram-positive infections in daily practice., Methods: A practice-based, observational, retrospective study (eight Spanish hospitals) was performed including patients ≥18 years with a baseline glomerular filtration rate (GFR)>30 mL/min and/or serum creatinine level<2 mg/dL treated with DAP or VAN for >48h. Nephrotoxicity was considered as a decrease in baseline GRF to <50 mL/min or decrease of >10 mL/min from a baseline GRF<50 mL/min. Multivariate analyses were performed to determine factors associated with 1) treatment selection, 2) nephrotoxicity development, and 3) nephrotoxicity development within each antibiotic group., Results: A total of 133 patients (62 treated with DAP, 71 with VAN) were included. Twenty-one (15.8%) developed nephrotoxicity: 4/62 (6.3%) patients with DAP and 17/71 (23.3%) with VAN (p=0.006). No differences in concomitant administration of aminoglycosides or other potential nephrotoxic drugs were found between groups. Factors associated with DAP treatment were diabetes mellitus with organ lesion (OR=7.81, 95%CI:1.39-4.35) and basal creatinine ≥0.9 mg/dL (OR=2.53, 95%CI:1.15-4.35). Factors associated with VAN treatment were stroke (OR=7.22, 95%CI:1.50-34.67), acute myocardial infarction (OR=6.59, 95%CI:1.51-28.69) and primary bacteremia (OR=5.18, 95%CI:1.03-25.99). Factors associated with nephrotoxicity (R2=0.142; p=0.001) were creatinine clearance<80 mL/min (OR=9.22, 95%CI:1.98-30.93) and VAN treatment (OR=6.07, 95%CI:1.86-19.93). Factors associated with nephrotoxicity within patients treated with VAN (R2=0.232; p=0.018) were congestive heart failure (OR=4.35, 95%CI:1.23-15.37), endocarditis (OR=7.63, 95%CI:1.02-57.31) and basal creatinine clearance<80 mL/min (OR=7.73, 95%CI:1.20-49.71)., Conclusions: Nephrotoxicity with VAN was significantly higher than with DAP despite poorer basal renal status in the DAP group., (©The Author 2018. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira , Dorea , Blautia , Bacteroides , Coprococcus , and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.

Fifteen years after its licensure, this revision assesses the role of cefditoren facing the current pharmacoepidemiology of resistances in respiratory human-adapted pathogens ( Streptococcus pneumoniae , Streptococcus pyogenes , Haemophilus influenzae and Moraxella catarrhalis ). In the era of post- pneumococcal conjugate vaccines and in an environment of increasing diffusion of the fts I gene among H. influenzae isolates, published studies on the cefditoren in vitro microbiological activity, pharmacokinetic/pharmcodynamic (PK/PD) activity and clinical efficacy are reviewed. Based on published data, an overall analysis is performed for PK/PD susceptibility interpretation. Further translation of PK/PD data into clinical/microbiological outcomes obtained in clinical trials carried out in the respiratory indications approved for cefditoren in adults (tonsillitis, sinusitis, acute exacerbation of chronic bronchitis and community-acquired pneumonia) is commented. Finally, the role of cefditoren within the current antibiotic armamentarium for the treatment of community respiratory tract infections in adults is discussed based on the revised information on its intrinsic activity, pharmacodynamic adequacy and clinical/bacteriological efficacy. Cefditoren remains an option to be taken into account when selecting an oral antibiotic for the empirical treatment of respiratory infections in the community caused by human-adapted pathogens, even when considering changes in the pharmacoepidemiology of resistances over the last two decades., Competing Interests: Not applicable.Not applicable. All data included in the review is published and referenced.PRISM-AG SL have received grants from Tedec-Meiji Pharma S.A. (Madrid, Spain) for the performance of pharmacodynamic studies with cefditoren. MJG and LA are members of the Research Department of PRISM-AG.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Coeliac disease is an autoimmune disorder triggered in genetically predisposed individuals by the ingestion of gluten proteins from wheat, barley and rye. The α-gliadin gene family of wheat contains four highly stimulatory peptides, of which the 33-mer is the main immunodominant peptide in patients with coeliac. We designed two sgRNAs to target a conserved region adjacent to the coding sequence for the 33-mer in the α-gliadin genes. Twenty-one mutant lines were generated, all showing strong reduction in α-gliadins. Up to 35 different genes were mutated in one of the lines of the 45 different genes identified in the wild type, while immunoreactivity was reduced by 85%. Transgene-free lines were identified, and no off-target mutations have been detected in any of the potential targets. The low-gluten, transgene-free wheat lines described here could be used to produce low-gluten foodstuff and serve as source material to introgress this trait into elite wheat varieties., (© 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Tritordeum is a novel cereal obtained from the hybridization between durum wheat and a wild barley. This study evaluates acceptance, digestibility and immunotoxic properties of tritordeum, a novel cereal for food processing. Nineteen healthy volunteers participated in a study with different diets to compare tritordeum bread with wheat and gluten-free breads., Results: Tritordeum breads had a similar acceptance to the wheat bread usually consumed, and the acceptance was significantly higher than the gluten-free bread and standardized wheat bread supplied in the study. There was no evidence for gastrointestinal symptoms among volunteers during the study. The reductions in the numbers of immunogenic epitopes in tritordeum in comparison with wheat were 78% for α-gliadins, 57% for γ-gliadins and 93% for ω-gliadins. The analysis of gluten immunogenic peptides (GIP) in stool samples showed a significantly lower excretion in the tritordeum ingestion phase than in the wheat ingestion phase., Conclusions: These results suggest that tritordeum may be an option of interest for general food processing, and especially for those who want to reduce their intake of gluten. However, it is not suitable for celiac disease sufferers as it contains gluten. © 2017 Society of Chemical Industry., (© 2017 Society of Chemical Industry.)

The effects of methyl jasmonate (MeJa) treatment as an elicitor of artichoke plants [Cynara cardunculus var. scolymus (L.) Fiori] on the yield and quality attributes of artichokes, especially those related to individual phenolic content and antioxidant activity, at two harvest dates and along storage were analyzed in this research. Plants treated gave a higher yield of artichokes in comparison to control plants, with 0.55 kg more per plant. MeJa treatment also increased artichoke quality and phenolic content in the edible fraction at harvest and during storage at 2 °C for 28 days as a result of the accumulation of hydroxycinnamic acids and luteolin derivatives. In addition, antioxidant activity was enhanced by MeJa treatment and correlated with the total phenolic content. Results suggest that MeJa foliar application could be a simple and practical tool to improve the yield and phytochemical content on artichokes, with elicitation being a cheap and environmentally friendly procedure to improve the health-beneficial effects of artichoke consumption.

Background: Sweet cherries are much appreciated by consumers as a result of their organoleptic quality attributes and antioxidant properties, although they deteriorate rapidly after harvest. Different preharvest strategies have been carried out to increase their quality at the time of harvest. We present data regarding the effect of preharvest salicylic acid (SA) and acetyl salicylic acid (ASA) treatments on sweet cherry quality during postharvest storage., Results: At harvest and during postharvest storage, sweet cherry fruits ('Sweet Heart', 'Sweet Late' and 'Lapins') from SA (0.5 mmol L -1 ) and ASA (1 mmol L -1 ) treated trees had a higher colour (lower chroma index), firmness, total soluble solids, total phenolics, total anthocyanins and hydrophilic total antioxidant activity. In addition, the activity of the antioxidant enzymes catalase, peroxidase, superoxide dismutase and ascorbate peroxidase was also enhanced in SA- and ASA-treated cherries., Conclusion: Both SA and ASA preharvest treatments could be promising tools for improving sweet cherry quality at harvest and after storage, with an additional effect on delaying the postharvest ripening process by increasing the levels of antioxidant compounds and the activity of the antioxidant enzymes. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients.

Background: A previous study explored factors discriminating colonization and true infection among non-transplant, non-neutropenic patients with repeated Aspergillus spp. isolation from lower respiratory samples. The present study explored the evolution of patients with Aspergillus colonization in that study to determine the percentage of cases progressing to aspergillosis and time to development., Methods: Clinical records were retrospectively reviewed (for each patient from his end date in the past study) and data from all respiratory processes suffered by patients up to April 2015 were recorded. Comparisons of variables were performed between colonized patients that developed aspergillosis and those that did not. A Kaplan-Meier curve was used to describe time to development of aspergillosis in chronic obstructive pulmonary disease (COPD) patients for II-IV stages of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification., Results: Sixty seven colonized patients were followed, 12 of them (17.9%) developed aspergillosis. Diagnoses included six tracheobronchitis (4 invasive, 2 simple tracheobronchitis), four pulmonary disease (2 invasive pulmonary aspergillosis, 2 chronic pulmonary aspergillosis), one allergic bronchopulmonary aspergillosis and one pulmonary aspergilloma. Up to 47 (70.4%) of the study patients presented COPD. Among patients developing aspergillosis COPD was more frequent (100%) than among those that did not develop aspergillosis (35 out of 55; 63.6%) (p = 0.012), as well as GOLD IV patients were more frequent among COPD patients developing aspergillosis than among COPD patients that did not (50.0 vs. 26.1%, p = 0.046). Mean time to development of aspergillosis was 18.4 months (median: 8.5) with a wide range (1-58). Overtime, the percentage of patients developing aspergillosis was significantly higher among GOLD IV patients than among GOLD II-III patients (p = 0.032)., Conclusions: The high percentage of cases progressing to aspergillosis among colonized patients, especially among those with COPD (25.5%), stresses the importance of colonization as risk factor, and creates awareness of the possible change from colonization to invasive disease in GOLD IV patients.

Leptochloa virgata (L.) P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14, and R15) collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S). Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha -1 (field dose) were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14 C-glyphosate than resistant ones, and translocated up to 32.2% of 14 C-glyphosate to the roots at 96 h after treatment (HAT). The R8, R14, and R15 populations translocated only 24.5, 26.5, and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14 C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico.

Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite.

Gluten proteins are responsible for the viscoelastic properties of wheat flour but also for triggering pathologies in susceptible individuals, of which coeliac disease (CD) and noncoeliac gluten sensitivity may affect up to 8% of the population. The only effective treatment for affected persons is a strict gluten-free diet. Here, we report the effectiveness of seven plasmid combinations, encompassing RNAi fragments from α-, γ-, ω-gliadins, and LMW glutenin subunits, for silencing the expression of different prolamin fractions. Silencing patterns of transgenic lines were analysed by gel electrophoresis, RP-HPLC and mass spectrometry (LC-MS/MS), whereas gluten immunogenicity was assayed by an anti-gliadin 33-mer monoclonal antibody (moAb). Plasmid combinations 1 and 2 downregulated only γ- and α-gliadins, respectively. Four plasmid combinations were highly effective in the silencing of ω-gliadins and γ-gliadins, and three of these also silenced α-gliadins. HMW glutenins were upregulated in all but one plasmid combination, while LMW glutenins were downregulated in three plasmid combinations. Total protein and starch contents were unaffected regardless of the plasmid combination used. Six plasmid combinations provided strong reduction in the gluten content as measured by moAb and for two combinations, this reduction was higher than 90% in comparison with the wild type. CD epitope analysis in peptides identified in LC-MS/MS showed that lines from three plasmid combinations were totally devoid of CD epitopes from the highly immunogenic α- and ω-gliadins. Our findings raise the prospect of breeding wheat species with low levels of harmful gluten, and of achieving the important goal of developing nontoxic wheat cultivars., (© 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.)

Objective: Patients with recent intraabdominal events are at uniquely risk for intraabdominal candidiasis (IAC). Candida peritonitis is a frequent and life-threatening complication in surgically ill patients. International guidelines do not specifically address IAC. This study describes clinical features of IAC in critical patients treated with anidulafungin in Surgical ICUs (SICUs)., Methods: A practice-based retrospective study was performed including all adults with IAC admitted to 19 SICUs for ≥24h treated with anidulafungin. IAC was documented (Candida isolation from blood/peritoneal fluid/abscess fluid and/or histopathological confirmation) or presumptive (host factors plus clinical criteria without mycological support). Total population and the subgroup of septic shock patients were analyzed., Results: One hundred and thirty nine patients were included, 94 (67.6%) with septic shock, 112 (86.2%) after urgent surgery. Of them, 77.7% presented peritonitis and 21.6% only intraabdominal abscesses. Among 56.8% cases with documented IAC, C. albicans (52.8%) followed by C. glabrata (27.8%) were the most frequent species. Anidulafungin was primarily used as empirical therapy (59.7%), microbiologically directed (20.9%) and anticipated therapy (15.8%). Favourable response was 79.1% (76.6% among patients with septic shock). Intra-SICU mortality was 25.9% (28.7% among patients with septic shock)., Conclusions: Among IACs managed at SICUs, peritonitis was the main presentation, with high percentage of patients presenting septic shock. C. albicans followed by C. glabrata were the main responsible species. Anidulafungin treatment was mostly empirical followed by microbiologically directed therapy, with a favourable safety profile, even among patients with septic shock.

This study analyzed temporal trends of non-susceptibility/serotypes in invasive pneumococci from Spanish regions where pneumococcal conjugate vaccines (PCVs) were not included in paediatric immunization programmes. All invasive pneumococcal isolates voluntarily sent to the Spanish Reference Laboratory for Pneumococci (January 1990-December 2013) from hospitals located in target study regions were analyzed by age group. The PCV estimated coverage in children <24 months was correlated with 13-valent PCV (PCV13) serotypes trends. A total of 28,124 invasive isolates were analyzed: 3138 (11.2%) from children <24 months, 2161 (7.7%) from children 24-59 months, 781 (2.8%) from children 5-14 years, and 22,044 (78.4%) from adults. The estimated coverage increased from 17.6% (2002) to around 40% (2010-2013). The percentage of PCV13 serotypes among all isolates over time followed a cubic significant trend (R(2)=0.884), with an increasing trend up to 2001 followed by a decrease (more prominent from 2010 onwards). The estimated PCVs coverage was significantly correlated with the decrease in the percentage of PCV13 isolates in children <24 months (r(2)=0.824) and in adults (r(2)=0.786), mainly due to decreases in serotypes 1 and 7F in adults, and in serogroup 6 and serotypes 7F and 19A in children <24 months. None of the non-PCV13 serotypes stood out with substantial increases in the last period. This study showed that the different serotypes (and its associated non-susceptibility trends) were not equally affected by low PCVs disposition. Lack of impact in certain serotypes as serotype 1 (in children 24-59 months), 6C (in all age groups), and 19A (in adults) suggests the need for increasing vaccine coverage in the target vaccine population to increase direct and indirect protection., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The gluten proteins from wheat, barley and rye are responsible both for celiac disease (CD) and for non-celiac gluten sensitivity, two pathologies affecting up to 6-8% of the human population worldwide. The wheat α-gliadin proteins contain three major CD immunogenic peptides: p31-43, which induces the innate immune response; the 33-mer, formed by six overlapping copies of three highly stimulatory epitopes; and an additional DQ2.5-glia-α3 epitope which partially overlaps with the 33-mer. Next-generation sequencing (NGS) and Sanger sequencing of α-gliadin genes from diploid and polyploid wheat provided six types of α-gliadins (named 1-6) with strong differences in their frequencies in diploid and polyploid wheat, and in the presence and abundance of these CD immunogenic peptides. Immunogenic variants of the p31-43 peptide were found in most of the α-gliadins. Variants of the DQ2.5-glia-α3 epitope were associated with specific types of α-gliadins. Remarkably, only type 1 α-gliadins contained 33-mer epitopes. Moreover, the full immunodominant 33-mer fragment was only present in hexaploid wheat at low abundance, probably as the result of allohexaploidization events from subtype 1.2 α-gliadins found only in Aegilops tauschii, the D-genome donor of hexaploid wheat. Type 3 α-gliadins seem to be the ancestral type as they are found in most of the α-gliadin-expressing Triticeae species. These findings are important for reducing the incidence of CD by the breeding/selection of wheat varieties with low stimulatory capacity of T cells. Moreover, advanced genome-editing techniques (TALENs, CRISPR) will be easier to implement on the small group of α-gliadins containing only immunogenic peptides., (© 2015 Society for Experimental Biology and John Wiley & Sons Ltd.)

Introduction: Based on tigecycline linear pharmacokinetic/pharmacodynamics, dose increases have been advocated to maximise activity especially when severe infections with high bacterial load and/or multidrug resistance are suspected. This practice-based observational study explored factors associated with tigecycline administration (100 mg/12h, 200 mg loading dose) in severely ill patients with complicated intra-abdominal infection (cIAI) admitted to four Surgical Critical Care Units (SCCUs)., Methods: Medical records of all consecutive adult patients with cIAI and controlled infection source requiring surgery and admission for ≥ 48 h to SCCU were reviewed and divided into patients treated with a regimen including tigecycline (tigecycline group) and those that not (control group). A logistic regression model was performed using "tigecycline administration" (dependent variable) and variables showing differences (p ≤ 0.1) in bivariate analyses (independent variables)., Results: One hundred and twenty one patients were included. In the tigecycline group, higher percentage of patients (vs. controls) presented colon as surgical site (66.7% vs. 41.8%, p = 0.006), nosocomial infection (55.6% vs. 26.9%, p = 0.001), mechanical ventilation (48.1% vs. 28.4%, p = 0.025), chronic renal replacement therapy (40.7% vs. 19.4%, p =0.008), septic shock (72.2% vs. 46.3%, p = 0.004), and higher values of SAPS II (48.0 ± 15.0 vs. 39.6 ± 15.5, p = 0.003), SOFA at admission (7.0 ± 3.3 vs. 5.5 ± 3.7, p = 0.020), lactate-24h (2.5 ± 2.8 vs. 1.6 ± 0.9, p = 0.029) and CRP-72 h (207.4 ± 87.9 vs. 163.7 ± 76.8, p = 0.021). In the multivariate analysis (R2 = 0.187, p < 0.001) nosocomial infection (OR = 7.721; 95%CI = 2.193, 27.179; p = 0.001), colon as infection site (OR = 4.338; 95%CI = 1.432, 13.145; p = 0.009) and CRP-72 h (OR = 1.009 per-unit; 95%CI = 1.002, 1.016; p = 0.012) were associated with tigecycline administration., Conclusions: In severely ill patients with cIAI, high-dose tigecycline administration was associated with nosocomial origin of cIAI and colon as source infection site.

Aeromonas infections are rare in Europe and often related to traveller's diarrhoea. A total of 185 Aeromonas isolates from river water, fish and clinical sources, recovered during a 1-year period, were used to investigate the disease spectrum and impact of multidrug-resistant (MDR) strains. They were all identified by biochemical tests and 25% of them were also identified by sequencing of the 16S rRNA gene. The minimum inhibitory concentrations (MICs) of 21 antimicrobials were determined for all isolates by broth microdilution/E-strips methods, and susceptibility was assessed according to the Clinical and Laboratory Standards Institute (CLSI). Strains pathogenicity was determined by using Swiss Webster mice as the animal model. Aeromonas diseases had an incidence of around 20 cases/million inhabitants in the metropolitan area of Valencia (Spain). Acute gastroenteritis in children with no history of travel abroad was the main pathology. These cases were related to A. caviae, A. veronii biovar sobria, A. hydrophila and A. dhakensis. A significant incidence of A. caviae in humans was found, while the other species were equally present in clinical and environmental origins. A. jandaei, A. bestiarum and A. media had mainly an environmental distribution. The prevalence of MDR Aeromonas was maximal in clinical samples, and resistance phenotypes were significantly related to this source. 7.2% of environmental Aeromonas was resistant to at least five drugs; most of them were moderately virulent for mice and, in addition, belonged to clinically significant species. The present study demonstrates a diseases spectrum similar to that reported in tropical countries, and also that pathogenic and heavily MDR Aeromonas are present in environmental reservoirs. MDR Aeromonas from any source analysed were susceptible to aztreonam, netilmicin, cefotaxime, ceftazidime, cefepime and fluoroquinolones.

The effects of salicylic acid (SA) or acetylsalicylic acid (ASA) treatments during on-tree cherry growth and ripening on fruit quality attributes, especially those related with the content on bioactive compounds and antioxidant activity were analysed in this research. For this purpose, two sweet cherry cultivars, 'Sweet Heart' and 'Sweet Late', were used and SA or ASA treatments, at 0.5, 1.0 and 2.0mM concentrations, were applied at three key points of fruit development (pit hardening, initial colour changes and onset of ripening). These treatments increased fruit weight and ameliorated quality attributes at commercial harvest, and led to cherries with higher concentration in total phenolics and in total anthocyanins, as well as higher antioxidant activity, in both hydrophilic and lipophilic fractions. Thus, preharvest treatments with SA or ASA could be promising tools to improve sweet cherry quality and health beneficial effects for consumers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)