Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Influence of iron redox state on black ripe olive processing.

BACKGROUND: The oxidation and polymerization of the phenolic compounds present in black ripe olives give rise to their black shiny colour, which is fixed by the addition of ferrous salts such as ferrous gluconate. Among the many variables that can affect the success of this fixation step, the influence of pH on this process was assessed on fruits of the Hojiblanca cultivar processed at pilot plant scale. Hence the aim of this work was to gain knowledge on the development of this fixation step, in particular on olives that were oxidized with a single alkaline treatment. RESULTS: It was found that the penetration of the ferric cation into the olive flesh was an extremely slow process and it led to less-dark olives. Besides, at a pH higher than 6 the oxidation of the ferrous to the ferric cation was a very rapid reaction, and olives that were processed with initial pH adjusted to 4 units had a darker colour than those without pH correction. Ultrafiltration/nanofiltration of oxidized olive solutions spiked with ferric ions or even pure oxidized ferric solutions through membranes of 10, 3 and 1 kDa revealed that ferric ions formed high-molecular structures that inhibited the penetration of the ion into the olive flesh and therefore the fixation of the black colour. CONCLUSION: The results presented in this study suggest that the formation of ferric ions during the colour fixation step of black ripe olives must be avoided to obtain darker olives. Consequently, the initial pH of the ferrous gluconate solution must be corrected to avoid oxidation of the ferrous to ferric cations during the fixation step. This study will contribute to the improvement of the colour fixation step of black ripe olive processing. © 2018 Society of Chemical Industry.

New by-products rich in bioactive substances from the olive oil mill processing.

BACKGROUND: Olive oil extraction generates a large amount of residue consisting mainly of the pomace and leaves when using a two-phase centrifugation system. The aim of this study was to assess the content of phenolic and triterpene compounds in the by-products produced in Spanish olive oil mills. RESULTS: Olive pomace had concentrations of phenolic and triterpene substances lower than 2 and 3 g kg-1 , respectively. The leaves contained a high concentration of these substances, although those collected from ground-picked olives had lost most of their phenolic compounds. Moreover, the sediment from the bottom of the olive oil storage tanks did not have a significant amount of these substances. By contrast, a new by-product called olive pomace skin has been revealed as a very rich source of triterpenic acids, the content of which can reach up to 120 g kg-1 in this waste product, maslinic acid comprising around 70% of total triterpenics. CONCLUSION: Among the by-products generated during extraction of olive oil, olive pomace skin has been discovered to be a very rich source of triterpenic acids, which can reach up to 120 g kg-1 of the waste. These results will contribute to the valorization of olive oil by-products. © 2017 Society of Chemical Industry.

Quantification of bioactive compounds in Picual and Arbequina olive leaves and fruit.

BACKGROUND: Olive leaves and fruit possess bioactive substances such as phenolic compounds and triterpenic acids that can be obtained from olive by-products generated during olive oil extraction. The aim of the present study was the characterization and quantification of these compounds in Picual and Arbequina cultivars from different locations and throughout two seasons in both olive leaves and fruit. RESULTS: The major phenolic compound identified in the leaves was oleuropein, and the total content of phenolic compounds in this material reached 70 g kg-1 fresh weight. The leaves were also rich in triterpenic acids (20 g kg-1 fresh weight), with oleanolic acid being the most concentrated among them. With regard to olives, oleuropein and demethyloleuropein were the main phenolic compounds in the pulp of Picual and Arbequina cultivars, and the total concentration of these phenolic compounds reached 3.5% fresh weight. Olives can also be an important source of triterpenic acids, although this is mainly the skin part, where the maslinic and oleanolic acids are concentrated. CONCLUSION: Olive leaves can contain up to 70 g kg-1 phenolic compounds and 20 g kg-1 triterpenic acids, and olive fruit can contain up to 35 g kg-1 of the former and 3 g kg-1 of the latter. It must also be noted that this level was constant both between seasons and orchard locations. © 2016 Society of Chemical Industry.

Assays to control the development of the green staining alteration in Spanish-style green olives of the Gordal variety.

BACKGROUND: Olives of the Gordal variety processed according to the Spanish style sometimes develop an alteration in color known as green staining (GS), due to the formation of harmless copper-chlorophyll complexes, which makes the product less valuable. The aim of this study was to investigate methods to minimize the impact that this alteration has for the table olive industry. RESULTS: Calcium chloride, sorbic, benzoic and ascorbic acids and SO2 did not inhibit the development of the alteration in olives packed under their own fermentation brine or new fresh brine. It was also discovered that the incubation of olive samples at 45 °C for 20 days accelerates the formation of GS and can be a very useful tool to predict the incidence of the alteration in advance. By applying this test to numerous industrial tanks for four consecutive seasons, it was found that GS was mainly present in olives harvested at the beginning of the season. CONCLUSION: The formation of GS in olives of the Gordal variety is time- and temperature-dependent, and none of the additives tested avoided or retarded the development of the alteration. However, an accelerated test to predict the development of GS formation has been proposed that could contribute to minimize the effects of the alteration. © 2015 Society of Chemical Industry.

Production of 4-ethylphenol in alperujo by Lactobacillus pentosus.

BACKGROUND: Alperujo is the paste generated from the two-phase extraction system of olive oil. This wet pomace must be stored for several months and, during this period, the formation of 4-ethyphenol provokes a strong off-odour. The aim of this work was to identify the microorganisms able to produce this volatile phenol. RESULTS: Yeast and bacterial strains were isolated from stored alperujo and tested for their ability to metabolize p-coumaric acid and form 4-ethylphenol. Among them, Lactobacillus pentosus was the microorganism that both in synthetic medium and alperujo gave rise to 4-ethylphenol formation. This microorganism did not grow in alperujo acidified to pH 2, thereby confirming that acidification as the best method to control odour emissions during alperujo storage. CONCLUSION: Lactic acid bacteria, particularly Lactobacillus pentosus, can be responsible for the formation of the off-odour caused by 4-ethylphenol during the storage of alperujo. This odour can be prevented by acidifying the alperujo.

Health care-associated infections in neonatology.

Health care-associated infections are common in neonatology, but there is no consensus on their definitions. This makes it difficult to compare their incidence or assess the effectiveness of prevention bundles. This is why we think it is very important to achieve a consensus on the definitions and diagnostic criteria for one of the most frequent causes of morbidity in hospitalised neonates. This document aims to standardise the definitions for the most frequent health care-associated infections, such as catheter-associated bloodstream infection, ventilator-associated pneumonia and surgical wound infection, as well as the approach to their diagnosis and treatment.

Together yes, but not coupled: new insights into the roles of RAD51 and DMC1 in plant meiotic recombination.

The eukaryotic recombinases RAD51 and DMC1 are essential for DNA strand-exchange between homologous chromosomes during meiosis. RAD51 is also expressed during mitosis, and mediates homologous recombination (HR) between sister chromatids. It has been suggested that DMC1 might be involved in the switch from intersister chromatid recombination in somatic cells to interhomolog meiotic recombination. At meiosis, the Arabidopsis Atrad51 null mutant fails to synapse and has extensive chromosome fragmentation. The Atdmc1 null mutant is also asynaptic, but in this case chromosome fragmentation is absent. Thus in plants, AtDMC1 appears to be indispensable for interhomolog homologous recombination, whereas AtRAD51 seems to be more involved in intersister recombination. In this work, we have studied a new AtRAD51 knock-down mutant, Atrad51-2, which expresses only a small quantity of RAD51 protein. Atrad51-2 mutant plants are sterile and hypersensitive to DNA double-strand break induction, but their vegetative development is apparently normal. The meiotic phenotype of the mutant consists of partial synapsis, an elevated frequency of univalents, a low incidence of chromosome fragmentation and multivalent chromosome associations. Surprisingly, non-homologous chromosomes are involved in 51% of bivalents. The depletion of AtDMC1 in the Atrad51-2 background results in the loss of bivalents and in an increase of chromosome fragmentation. Our results suggest that a critical level of AtRAD51 is required to ensure the fidelity of HR during interchromosomal exchanges. Assuming the existence of asymmetrical DNA strand invasion during the initial steps of recombination, we have developed a working model in which the initial step of strand invasion is mediated by AtDMC1, with AtRAD51 required to check the fidelity of this process.

Olive Leaf Processing for Infusion Purposes.

Olive leaf is a by-product rich in bioactive compounds, such as polyphenols and triterpenic acids, with numerous biological activities for human health. Nowadays, the existence of dry olive leaves marketed for infusion elaboration is lacking. During the elaboration process, the drying and grinding stages are critical for the conservation of bioactive compounds, and, precisely, the existing research on olive leaf production procedures is quite scarce. This work aimed to study and model the dehydration process using a forced-air oven and infrared with air convection systems. In addition, different grinding grades were studied. The kinetic constant and activation energy during dehydration were obtained. Drying temperatures above 50 °C produced a decrease in the phenolic concentration of olive leaves; however, it has been observed that prior storage of 24 h at room temperature considerably reduced the loss of phenols. Likewise, it was observed that the higher the degree of grinding, the greater the diffusion of both bioactive compounds and colored compounds. Therefore, the drying and grinding stages were closely related to the content of beneficial compounds and the appearance of the infusions, and their optimization was of crucial importance to produce dried olive leaves rich in biocompounds for use as healthy infusions.

New and Rapid Analytical Method Using HPLC-MS Detection for Acrylamide Determination in Black Ripe Olives.

The presence of acrylamide, a known human carcinogen, in various heated foods raises significant concerns among consumers. Therefore, the development of a good analytical method is of paramount interest to the scientific community. Keeping this in view, a rapid, simple, reliable, and low-cost analytical method was developed and validated for acrylamide quantification in black ripe olives. The method consisted of the water extraction of the compounds from crushed olives with the addition of (13C3)acrylamide as an internal standard. The quantification was performed using high-pressure liquid chromatography and mass detection with positive electrospray ionization. The limits of detection and quantification were determined to be 4 and 11 µg/kg, respectively. The developed method exhibited excellent results in terms of accuracy (98.4-104.8%) and intra- and inter-day precision limits, both less than 20%. This new method was carried out by analyzing 15 samples of Spanish commercial black ripe olives, revealing a wide range of values, from 79 to 1068 µg/kg of fruit. The new protocol reduces the analysis time to just one hour per sample versus the minimum 24 h required by gas chromatography and mass detection, meaning that it could be a good option for the routine analysis of acrylamide in black ripe olives, and may be extendable to the analysis of this compound in other foods.

Short-course empiric antibiotic therapy for possible early-onset sepsis in the NICU.

OBJECTIVE: On 2/2019, the Neonatal Antimicrobial Stewardship Program at Nationwide Children's Hospital recommended reducing empirical antibiotic therapy for early-onset sepsis (EOS) from 48 to 24 hours with a TIME-OUT. We describe our experience with this guideline and assess its safety. METHODS: Retrospective review of newborns evaluated for possible EOS at 6 NICUs from 12/2018-7/2019. Safety endpoints were re-initiation of antibiotics within 7 days after discontinuation of the initial course, positive bacterial blood or cerebrospinal fluid culture in the 7 days after antibiotic discontinuation, and overall and sepsis-related mortality. RESULT: Among 414 newborns evaluated for EOS, 196 (47%) received a 24 hour rule-out sepsis antibiotic course while 218 (53%) were managed with a 48 hour course. The 24-hour rule-out group were less likely to have antibiotics re-initiated and did not differ in the other predefined safety endpoints. CONCLUSION: Antibiotic therapy for suspected EOS may be discontinued safely within 24 hours.

Short-course antibiotic therapy for pneumonia in the neonatal intensive care unit.

OBJECTIVE: To determine the adherence and safety outcomes of a 5-day antibiotic course with a "time-out" for treatment of "blood culture-negative" pneumonia in the NICU. STUDY DESIGN: Prospective surveillance of all infants diagnosed with pneumonia at 7 NICUs from 8/2020-12/2021. Safety outcomes were defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation and overall and sepsis-related mortality. RESULTS: 128 infants were diagnosed with 136 episodes of pneumonia; 88% (n = 119) were treated with 5 days of definitive antibiotic therapy. Antibiotics were restarted within 14 days in 22 (16%) of the 136 pneumonia episodes. However, only 3 (3%) of the 119 episodes of pneumonia treated for 5 days had antibiotics restarted for pneumonia. Mortality was 5% (7/128); 5 of the 7 deaths were assessed as sepsis-related. CONCLUSION: Adherence to the 5-day definitive antibiotic treatment for "culture-negative" pneumonia was high and the intervention seemed safe.

Assessment of Helicobacter pylori eradication by virgin olive oil.

BACKGROUND: A recent study conducted by Medina et al. disclosed that virgin olive oil has a bactericidal effect in vitro against Helicobacter pylori because of its contents of certain phenolic compounds with dialdehydic structures. We carried out two clinical trials to evaluate the effect of virgin olive oil on H. pylori-infected individuals. MATERIALS AND METHODS: Two different pilot studies were performed with 60 H. pylori-infected adults. In the first study, thirty subjects who tested positive for H. pylori received 30 g of washed virgin olive oil for 14 days, and after 1 month, the patients took 30 g of unwashed virgin olive oil for another 14 days. In a second study, a group of 30 subjects received 30 g of a different virgin olive oil for 14 days. Helicobacter pylori-infection status was checked by the urea breath test. RESULTS: Helicobacter pylori was eradicated in 8 of 30 individuals when microorganism status was checked after 4-6 weeks from the first clinical intervention although 12 of 30 individuals did not show H. pylori infection at 24-72 hour of the last oil dose. Eradication rates were 27 and 40% by intention to treat and per protocol, respectively. Moreover, only 3 of 30 individuals were H. pylori negative after 4-6 weeks from the second clinical intervention but 5 of 30 were negative at 24-72 hour of the last oil dose. Eradication rates were 10 and 11% by intention to treat and per protocol, respectively. It must also be noted that 13 subjects withdrew from the studies because of taste and nausea drawbacks. CONCLUSIONS: The administration of virgin olive oil showed moderate effectiveness in eradicating H. pylori. Further studies are needed to confirm these findings, especially with longer periods, different administration conditions, and several types of olive oils.

Chemical and Enzymatic Characterization of Leaves from Spanish Table Olive Cultivars.

Olive leaves are generated as by-products in the olive industry and contain substances with biological properties that provide health benefits. Although these compounds have been characterized in many leaves from olive cultivars devoted to olive oil extraction, few data are available on leaves from the processing of table olives. In this study, the concentration of polyphenols, triterpenic acids, sugars and enzymatic activities (polyphenol oxidase, peroxidase, ß-glucosidase and esterase) were determined in the leaves of the olive tree (Olea europaea L.) of cvs. Aloreña, Cacereña, Empeltre, Hojiblanca, Manzanilla, Verdial, Gordal and Morona. The mean total phenolic content in olive leaves reached 75.58 g/kg fresh weight, and oleuropein was the main polyphenol identified (89.7-96.5%). The main triterpenic acid identified was oleanolic acid, and the main sugar was mannitol, with mean values of 15.83 and 22.31 g/kg, respectively. However, the content of these biocompounds was influenced by the type of cultivar and the orchards of origin. The highest oleuropein content was found in the Manzanilla variety, while the Gordal had the highest triterpene and mannitol content. In particular, the phenolic content could also be affected by endogenous enzymatic activities. High polyphenol oxidase, peroxidase and ß-glucosidase activity and low esterase activity were detected, compared to the fruit. Similar to the phenolic compounds, enzymatic activities varied with the harvesting season. The lowest phenolic content corresponded to the highest polyphenol oxidase activity detected during spring. The rest of the enzymatic activities also varied throughout the year, but no common trend was observed.

Reuse of KOH Solutions during Black Ripe Olive Processing, Effect on the Quality of the Final Product and Valorization of Wastewaters as Possible Fertilizer Product.

A high volume of water is needed to produce black ripe olives, which also entails a significant volume of wastewater with a high organic and inorganic contaminant charge. To reduce this problem, the reuse of KOH solutions (lyes) in a new process was studied. Once the lyes were removed from the tanks, KOH was then added for a new darkening process. Reusing the lyes up to four times gave rise to a product with similar physico-chemical and organoleptic characteristics as obtained with fresh solutions. The application of this process reduced coadjutant consumption by 32% and water by 20%, while global wastewater presented a high K content whose concentration could be valorized as a fertilizer by replacing commercial potassium nitrate.

Determining Time to Positivity of Blood Cultures in a Neonatal Unit.

Blood cultures are the gold standard for detecting bacteremia. We have studied the time to positivity of blood cultures in our neonatal unit to reduce antibiotic doses in patients with a negative blood culture. Empirical antibiotic treatment of neonatal sepsis could be withdrawn 24 hours after obtaining blood cultures.

Packing black ripe olives in acid conditions.

The type of container (airtight and pouches with different O2 permeability) and packing conditions (cover brine, air or N2 atmosphere) has been studied to preserve black ripe olives in acid medium for a year. Unlike the traditional sterilized product, these acidified olives only needed pasteurization to assure its microbial safety, the absence of acrylamide being an additional advantage. Surprisingly, an increase in the oxygen diffusion through the films (i) faded the black color of the olives, (ii) softened the fruit that lost around 33% of its initial firmness in only 6 months, and (iii) produced the lipid́s oxidation forming volatile compounds that transmitted an abnormal flavor which tasters identified as rancid. Therefore, ripe olives in acid medium must be packed in airtight containers such as glass jars, cans o metallic pouches with cover brine or N2 atmosphere. The addition of calcium is recommended to avoid olive softening.

Industrial Processing of Algerian Table Olive Cultivars Elaborated as Spanish Style.

Olives from the Sigoise, Verdale, and Sevillana cultivars were elaborated as Spanish-style table olives by four Algerian factories, and the quality and food safety of the industrial table olives have been studied by the analysis of physicochemical and microbiological parameters. Differences were observed between the treatments carried out by the different factories throughout the manufacturing process, especially during the washing stage, but no significant differences were found between the analyzed samples for the concentration of sugars and polyphenols. The final pH values reached at the end of fermentation ranged between 5.04 and 4.27, and the titratable acidity was above 0.4% for all samples. Lactic and acetic acids were produced in mean concentrations of 0.68% and 0.21% as a result of lactic acid bacteria (LAB) and yeast metabolism, respectively. However, the presence of butyric, isobutyric, and propionic acids was also detected, and was related to the growth of undesirable spoilage microorganisms, responsible for secondary fermentations. The high-throughput sequencing of bacterial DNA suggested the dominance of LAB species belonging to genera Lactiplantibacillus, Leuconostoc, Pediococcus, Oenococcus, or Enterococcus. The Enterobacteriaceae family was detected during the first days of brining and in only one sample after 120 days of fermentation. Other spoilage microorganisms were found, such as Lentilactobacillus buchneri or the Pectinatus and Acetobacter genera, capable of consuming lactic acid and these played an essential role in the onset of spoilage. The Clostridium and Enterobacter genera, producers of butyric and propionic acids, were responsible for the malodorous fermentation present in the industrial samples that were analyzed. The study concluded that the safety of the table olives analyzed was compromised by the presence of undesirable microorganisms and microbial stability was not guaranteed. The elaboration process can be improved by reducing the washing steps and the time should be reduced to avoid the loss of fermentable matter, with the goal of reaching a pH < 4.0 after the fermentation and preventing the possibility of the growth of spoilage microorganisms and foodborne pathogens.

Effect of fertilisation with black table olive wastewater solutions on production and quality of tomatoes cultivated under open field conditions.

This study was aimed at making progress on the valorisation of table olive wastewater that currently represent a big environmental problem for factories. Concentrates from vacuum evaporation of the wastewater generated during processing of black ripe olives treated with KOH were tested as fertilisers of tomato plants in open field assays for three consecutive crops. Fertilisation was performed by drip irrigation every 15 days; the first treatment being 15 days after transplanting, and a total of five fertilisation treatments were carried out. A phytotoxic effect was not observed on plants or fruit in any case but higher yield (fruit/plant and g/plant) was obtained in comparison to irrigation with only tap water. Moreover, the combined use of the olive concentrate with inorganic nitrogen supply (NH4NO3), in order to comply with the nutrient needs of plants, was also tested. The results demonstrated that the olive concentrates could be a good substitute for inorganic potassium (as KNO3) during the cultivation of tomato plants without any negative effect on the tomato quality (pH, °Brix, sugars, organic acids) or content of bioactive substances (phenolic compounds and carotenoids).

Serum Biomarkers in Differential Diagnosis of Idiopathic Pulmonary Fibrosis and Connective Tissue Disease-Associated Interstitial Lung Disease.

INTRODUCTION: The goal of this study is to determine whether Advanced glycosylated end-products (AGE), Advanced oxidation protein products (AOPP) and Matrix metalloproteinase 7 (MMP7) could be used as differential biomarkers for idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). METHOD: Seventy-three patients were enrolled: 29 with IPF, 14 with CTD-ILD, and 30 healthy controls. The study included a single visit by participants. A blood sample was drawn and serum was analysed for AGE using spectrofluorimetry, AOPP by spectrophotometry, and MMP7 using sandwich-type enzyme-linked immunosorbent assay. RESULTS: AGE, AOPP and MMP7 serum levels were significantly higher in both IPF and CTD-ILD patients versus healthy controls; and AGE was also significantly elevated in CTD-ILD compared to the IPF group. AGE plasma levels clearly distinguished CTD-ILD patients from healthy participants (AUC = 0.95; 95% IC 0.86-1), whereas in IPF patients, the distinction was moderate (AUC = 0.78; 95% IC 0.60-0.97). CONCLUSION: In summary, our results provide support for the potential value of serum AGE, AOPP and MMP7 concentrations as diagnostic biomarkers in IPF and CTD-ILD to differentiate between ILD patients and healthy controls. Furthermore, this study provides evidence, for the first time, for the possible use of AGE as a differential diagnostic biomarker to distinguish between IPF and CTD-ILD. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF and CTD-ILD diagnosis needs to be considered and further explored. Multicentre studies are necessary to understand the role of AGE in differential diagnosis.