Intravenous amoxicillin/clavulanate for the prevention of bacteraemia following dental procedures: a randomized clinical trial.

OBJECTIVES: Although controversy exists regarding the efficacy of antibiotic prophylaxis for patients at risk of infective endocarditis, expert committees continue to publish recommendations for antibiotic prophylaxis regimens. This study aimed to evaluate the efficacy of four antimicrobial regimens for the prevention of bacteraemia following dental extractions. METHODS: The study population included 266 adults requiring dental extractions who were randomly assigned to the following five groups: control (no prophylaxis); 1000/200 mg of amoxicillin/clavulanate intravenously; 2 g of amoxicillin by mouth; 600 mg of clindamycin by mouth; and 600 mg of azithromycin by mouth. Venous blood samples were collected from each patient at baseline and at 30 s, 15 min and 1 h after dental extractions. Samples were inoculated into BACTEC Plus culture bottles and processed in the BACTEC 9240. Conventional microbiological techniques were used for subcultures and further identification of the isolated bacteria. The trial was registered at ClinicalTrials.gov with ID number NCT02115776. RESULTS: The incidence of bacteraemia in the control, amoxicillin/clavulanate, amoxicillin, clindamycin and azithromycin groups was: 96%, 0%, 50%, 87% and 81%, respectively, at 30 s; 65%, 0%, 10%, 65% and 49% at 15 min; and 18%, 0%, 4%, 19% and 18% at 1 h. Streptococci were the most frequently identified bacteria. The percentage of positive blood cultures at 30 s post-extraction was lower in the amoxicillin/clavulanate group than in the amoxicillin group (P < 0.001). The incidence of bacteraemia in the clindamycin group was similar to that in the control group. CONCLUSIONS: Bacteraemia following dental extractions was undetectable with amoxicillin/clavulanate prophylaxis. Alternative antimicrobial regimens should be sought for patients allergic to the ß-lactams.

Multicenter study of epidemiological cutoff values and detection of resistance in Candida spp. to anidulafungin, caspofungin, and micafungin using the Sensititre YeastOne colorimetric method.

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.

Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence.

FoxM1 is a member of the Forkhead family of transcription factors and is implicated in inducing cell proliferation and some forms of tumorigenesis. It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence. The affinity of the isolated FoxM1 DNA-binding domain for this site is in the micromolar range, lower than observed for other Forkhead proteins. To explain these FoxM1 features, we determined the crystal structure of its DNA-binding domain in complex with a tandem recognition sequence. FoxM1 adopts the winged-helix fold, typical of the Forkhead family. Neither 'wing' of the fold however, makes significant contacts with the DNA, while the second, C-terminal, wing adopts an unusual ordered conformation across the back of the molecule. The lack of standard DNA-'wing' interactions may be a reason for FoxM1's relatively low affinity. The role of the 'wings' is possibly undertaken by other FoxM1 regions outside the DBD, that could interact with the target DNA directly or mediate interactions with other binding partners. Finally, we were unable to show a clear preference for tandem consensus site recognition in DNA-binding, transcription activation or bioinformatics analysis; FoxM1's moniker, 'Trident', is not supported by our data.

A variant Nishida's technique for surgical correction of monocular elevation deficiency syndrome.

Monocular elevation deficiency (MED) is characterized by unilateral limitation of supraductions, similar in adduction and abduction, in addition to hypotropia and ptosis. We describe a case of a 62-year-old woman with long-standing left ptosis who was initially operated with a frontal suspension technique. On subsequent examinations, a MED of that eye was found. The passive duction test was positive, so the inferior rectus was recessed. In addition, a modified Nishida technique was performed, consisting of the scleral anchorage of the superior edges of the rectus, medial and lateral, 12mm from the corneal limbus in the superonasal and superotemporal quadrants, respectively. Postoperatively, the left eye presented a minimal hypotropia of 3 PD. This modified technnique used here on the horizontal rectus muscles, turned out to be effective and safe for the correction of MED.

Modulating Wine Aromatic Amino Acid Catabolites by Using Torulaspora delbrueckii in Sequentially Inoculated Fermentations or Saccharomyces cerevisiae Alone.

Yeasts are the key microorganisms that transform grape juice into wine, and nitrogen is an essential nutrient able to affect yeast cell growth, fermentation kinetics and wine quality. In this work, we focused on the intra- and extracellular metabolomic changes of three aromatic amino acids (tryptophan, tyrosine, and phenylalanine) during alcoholic fermentation of two grape musts by two Saccharomyces cerevisiae strains and the sequential inoculation of Torulaspora delbrueckii with Saccharomyces cerevisiae. An UPLC-MS/MS method was used to monitor 33 metabolites, and 26 of them were detected in the extracellular samples and 8 were detected in the intracellular ones. The results indicate that the most intensive metabolomic changes occurred during the logarithm cellular growth phase and that pure S. cerevisiae fermentations produced higher amounts of N-acetyl derivatives of tryptophan and tyrosine and the off-odour molecule 2-aminoacetophenone. The sequentially inoculated fermentations showed a slower evolution and a higher production of metabolites linked to the well-known plant hormone indole acetic acid (auxin). Finally, the production of sulfonated tryptophol during must fermentation was confirmed, which also may explain the bitter taste of wines produced by Torulaspora delbrueckii co-fermentations, while sulfonated indole carboxylic acid was detected for the first time in such an experimental design.

A variant Nishida's technique for surgical correction of monocular elevation deficiency syndrome. / Variante de la técnica de Nishida para la corrección quirúrgica del síndrome de déficit monocular de la elevación.

Monocular elevation deficiency (MED) is characterized by unilateral limitation of supraductions, similar in adduction and abduction, in addition to hypotropia and ptosis. We describe a case of a 62-year-old woman with long-standing left ptosis who was initially operated with a frontal suspension technique. On subsequent examinations, a MED of that eye was found. The passive duction test was positive, so the inferior rectus was recessed. In addition, a modified Nishida technique was performed, consisting of the scleral anchorage of the superior edges of the rectus, medial and lateral, 12mm from the corneal limbus in the superonasal and superotemporal quadrants, respectively. Postoperatively, the left eye presented a minimal hypotropia of 3 PD. This modified technnique used here on the horizontal rectus muscles, turned out to be effective and safe for the correction of MED.

Saccharomyces cerevisiae and Torulaspora delbrueckii Intra- and Extra-Cellular Aromatic Amino Acids Metabolism.

Tryptophan, phenylalanine, and tyrosine play an important role as nitrogen sources in yeast metabolism. They regulate biomass production and fermentation rate, and their catabolites contribute to wine health benefits and sensorial character through the yeast biotransformation of grape juice constitutes into biologically active and flavor-impacting components. A UHPLC-MS/MS method was applied to monitor 37 tryptophan/phenylalanine/tyrosine yeast metabolites both in extra- and intracellular extracts produced by the fermentation of two Saccharomyces cerevisiae strains and one Torulaspora delbrueckii. The results shed light on the intra- and extra-cellular metabolomic dynamics, by combining metabolic needs, stimuli, and signals. Among others, the results indicated (a) the production of 2-aminoacetophenone by yeasts, mainly by the two Saccharomyces cerevisiae; (b) the deactivation and/or detoxification of tryptophol via sulfonation reaction; and (c) the deacetylation of N-acetyl tryptophan ethyl ester and N-acetyl tyrosine ethyl ester by producing the corresponding ethyl esters.

Efficiency of three intracellular extraction methods in the determination of metabolites related to tryptophan and tyrosine in winemaking yeast's metabolism by LC-HRMS.

Yeast nitrogen metabolism produces metabolites, whose origin in wines has scarcely been studied, with an important biological and organoleptic role. The present work focuses on comparing three intracellular extraction methods in order to elucidate efficiency of extraction while measuring the effect of temperature upon the integrity of the compounds related to the metabolism of tryptophan and tyrosine by yeast. Two UHPLC/HRMS methods to measure 16 metabolites were developed and validated. The validation provided optimum values of LOD (7.4·10-6 to 0.1 µg L-1), of LOQ (2·10-5 to 0.02 µg L-1) of precision (11-0.5% RSD) and repeatability (12-0.5% RSD). The removal of interfering molecules enabled matrix effects to be kept at low levels. The results pointed out that the low-temperature methods were more effective, providing better precision for 16 metabolites. The high-temperature extraction method may yield false enhanced compounds concentrations since they originate in cell wall macromolecules degradation.

Perioperative management of a female diagnosed with heterozygous X-linked adrenoleukodystrophy scheduled for shoulder arthroscopy. / Manejo perioperatorio de una mujer portadora del gen de la adrenoleucodistrofia ligada al X para artroscopia de hombro.

X-linked adrenoleukodystrophy (X-ALD) belongs to a family of rare diseases due to inborn errors of metabolism. It has a wide spectrum of clinical manifestations that anaesthesiologists should recognise during the perioperative period (respiratory centre dysfunction, hypotonia, adrenal or hepatic failure, gastroesophageal reflux disease, osteopenia, seizures).The case is presented of a 42-year-old X-linked adrenoleukodystrophy female carrier, who underwent combined general and an ultrasound-guided interscalene brachial plexus block anaesthesia for shoulder arthroscopy. Induction was performed with thiopentone and fentanyl, and sevoflurane was used as inhaled maintenance agent. No events were recorded during the procedure. Her post-operative recovery was satisfactory and she was later discharged home.

Determination of hydroxytyrosol produced by winemaking yeasts during alcoholic fermentation using a validated UHPLC-HRMS method.

Hydroxytyrosol (HT) is a phenolic compound of recognized bioactivity that has been described in wines but little is known about its origin. This work demonstrates that yeast involved in wine making, i.e. Saccharomyces cerevisiae strains and the non-Saccharomyces Torulaspora delbrueckii, can synthesise HT, as this compound was identified in the intracellular media of three strains by means of a developed and validated UHPLC-HRMS method with LOQ and LOD of 0.108 and 0.035ngmL-1 respectively. Controlled fermentations were performed with different varieties of grapes (Corredera, Moscatel, Chardonnay, Palomino fino, Sauvignon Blanc, Vijiriega, and Tempranillo) and synthetic must. The Saccharomyces cerevisiae strain QA23 was the most efficient producer of HT from tested yeasts. On the other hand, the grape variety influences HT wine concentrations. Furthermore, the maximum concentration of HT is reached between the fourth and sixth day of fermentation. This work reveals that yeasts have a great potential for the production of HT.

Role of Pneumocystis jirovecii in patients with different pulmonary underlying condition using a nested-PCR.

OBJECTIVE: The prevalence of Pneumocystis jirovecii colonization and its role in pulmonary disease remains unclear. PCR methods have shown an improved sensitivity in the detection of this fungus. It has been suggested that the PCR results be combined with another test such as IFA to create a diagnostic algorithm. METHODS: A multiplex nested-PCR procedure with a 16S rRNA gene as the internal amplification control was evaluated to determine the role of P. jirovecii in pulmonary disease. RESULTS: A 20% of the 199 bronchoalveolar lavage samples were PCR-positive, 13.5% samples were PCR-inhibited, and the rate of Pneumocystis-colonisation was 6.4%. The sensitivity, specificity, positive predictive value and negative predictive value of the nested-PCR were 100%, 93%, 70% and 100%, respectively. The sensitivity of the nested-PCR was higher than the current "gold standard" immunofluorescence assay (IFA) (p< 0.0001). PCR-negative and PCR-positive patients did not show any clinical or radiological differences in the medical variables studied. CONCLUSIONS: PCR could help the diagnosis of Pneumocystis pulmonary disease given the high negative predictive value of the technique. P. jirovecii DNA can frequently be detected in healthy population, so the analysis of the patient medical history is critical to make the correct clinical decision.

Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains.

Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway. This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC-HRMS system (Qexactive). Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation.

Inhibition of VEGF-Induced VEGFR-2 Activation and HUVEC Migration by Melatonin and Other Bioactive Indolic Compounds.

Excessive concentrations of vascular endothelial growth factor (VEGF) trigger angiogenesis, which causes complications such as the destabilization of atherosclerotic plaques and increased growth of tumors. This work focuses on the determination of the inhibitory activity of melatonin and other indolic related compounds on VEGF-induced VEGF receptor-2 (VEGFR-2) activation and an approximation to the molecular mechanism underlying the inhibition. Quantification of phosphorylated VEGFR-2 was measured by ELISA. Migration wound-healing assay was used to determine cell migration of human umbilical vein endothelial cells (HUVECs). This is the first time that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin are proved to significantly inhibit VEGF-induced VEGFR-2 activation in human umbilical vein endothelial cells and subsequent angiogenesis. 3-Indolacetic acid showed the highest inhibitory effect (IC50 value of 0.9704 mM), followed by 5-hydroxytryptophol (35% of inhibition at 0.1 mM), melatonin (30% of inhibition at 1 mM), and serotonin (24% of inhibition at 1 mM). An approximation to the molecular mechanism of the inhibition has been proposed, suggesting that indolic compounds might interact with the cell surface components of the endothelial membrane in a way that prevents VEGF from activating the receptor. Additionally, wound-healing assay revealed that exposure of HUVECs to melatonin and 3-indolacetic acid in the presence of VEGF significantly inhibited cell migration by 87% and 99%, respectively, after 24 h. These data demonstrate that melatonin, 3-indolacetic acid, 5-hydroxytryptophol, and serotonin would be good molecules for future exploitation as anti-VEGF signaling agents.

Influence of Fermentation Process on the Anthocyanin Composition of Wine and Vinegar Elaborated from Strawberry.

Anthocyanins are the major polyphenolic compounds in strawberry fruit responsible for its color. Due to their sensitivity, they are affected by food processing techniques such as fermentation that alters both their chemical composition and organoleptic properties. This work aims to evaluate the impact of different fermentation processes on individual anthocyanins compounds in strawberry wine and vinegar by UHPLC-MS/MS Q Exactive analysis. Nineteen, 18, and 14 anthocyanin compounds were identified in the strawberry initial substrate, strawberry wine, and strawberry vinegar, respectively. Four and 8 anthocyanin compounds were tentatively identified with high accuracy for the 1st time to be present in the beverages obtained by alcoholic fermentation and acetic fermentation of strawberry, respectively. Both, the total and the individual anthocyanin concentrations were decreased by both fermentation processes, affecting the alcoholic fermentation to a lesser extent (19%) than the acetic fermentation (91%). Indeed, several changes in color parameters have been assessed. The color of the wine and the vinegar made from strawberry changed during the fermentation process, varying from red to orange color, this fact is directly correlated with the decrease of anthocyanins compounds.

Determination of Nonanthocyanin Phenolic Compounds Using High-Resolution Mass Spectrometry (UHPLC-Orbitrap-MS/MS) and Impact of Storage Conditions in a Beverage Made from Strawberry by Fermentation.

Overproduction of strawberry leads to food waste, as it is very perishable. Therefore, strategies to transform it into new products are appreciated. This research focuses on characterization of the nonanthocyanin phenolic content of a beverage obtained from strawberry by gluconic and acetic fermentation and subsequently monitored for 90 days of storage, at two temperatures. Sixty-four nonanthocyanin (poly)phenols were identified by high-resolution mass spectrometry (UHPLC coupled with linear trap quadrupole and Orbitrap mass analyzer) and, for the first time, four compounds were reported in beverages fermented from strawberry: aromadendrin hexoside, phloretin 2'-O-xylosyl glucoside, dihydroferulic acid 4-O-glucuronide, and kaempferol hexosyl hexoside. During the storage time the increase in protocatechuic acid content was 13 times and condensed tannins diminished, especially procyanidin trimer. Statistical analysis showed that the composition remains unchanged until day 15 of storage at room temperature (27-30 °C) and until day 30 under refrigerated conditions (4 °C).

Estudio del impacto de la pandemia por COVID-19 en las Urgencias Pediátricas de un hospital de tercer nivel / Study on the impact of COVID-19 pandemic on pediatric emergencies of a third level hospital

Introducción. En los últimos años, los servicios de urgencias hospitalarias han experimentado un aumento progresivo de la demanda asistencial, a expensas de patología banal. Esta tendencia cambia a partir del 14 de marzo, cuando se decreta el estado de alarma debido a la pandemia por COVID-19, lo que supone el confinamiento obligatorio poblacional. Objetivos. Determinar el impacto que este estado de alarma ha tenido en el volumen de las urgencias pediátricas de un hospital de tercer nivel. Material y métodos. Se ha realizado un estudio retrospectivo de cohortes y se han incluido los menores de 14 años que demandaron asistencia durante los meses del estado de alarma y durante los mismos meses en el año anterior. Se han analizado diferentes datos epidemiológicos y clínicos. Resultados. 3.371 pacientes acudieron a nuestro Servicio de Urgencias en 2019 y 650 lo hicieron en 2020, siendo la media de edad de los pacientes similar. Los grupos diagnósticos al alta más frecuentes en ambos periodos de tiempo fueron las patologías infecciosa y digestiva. En cuanto a los ingresos hospitalarios, en 2019 requirieron ingreso el 7,12%, y en 2020, el 13,69%. Respecto al servicio a cargo del paciente durante el ingreso, destaca que en 2020 el 27,72% lo hizo a cargo de Cirugía Pediátrica. Conclusiones. La actividad en las Urgencias Pediátricas de nuestro hospital ha variado notablemente durante el estado de alarma. Se ha producido una disminución considerable del número de pacientes que han demandado asistencia debido a la percepción de riesgo de contagio por parte de la población. Además, hemos percibido un aumento relativo de los ingresos hospitalarios y, en concreto, en la patología quirúrgica urgente con respecto al año anterior (AU)

Objectives. In recent years, hospital emergency departments have experienced a progressive increase in the demand for care, at the expense of trivial pathology. This trend changes from 14 March 2020, when the state of alarm was declared due to the COVID-19 pandemic, which led to the compulsory confinement of the population. The main objective of this study was to determine the impact that this state of alarm has had on the volume of paediatric emergencies in a third level hospital. Material and methods. A retrospective study of cohorts was carried out and included those under 14 years of age who demanded care during the months of the state of alarm and during the same months in the previous year. Different epidemiological and clinical data have been analysed. Results. 3,371 patients attended our Emergency Department in 2019, and 650 in 2020, with a similar average patient age. The most frequent diagnostic groups at discharge in both time periods were infectious and digestive diseases. In terms of hospital admissions, 7.12% required admission in 2019 and 13.69% in 2020. Regarding the department in charge of the patient during admission, in 2020 27.72% of patients were admitted by Paediatric Surgery. Conclusions. The activity in the paediatric emergency departments of our hospital varied considerably during the state of alarm. There has been a considerable decrease in the number of patients who have requested assistance due to the perceived risk of contagion by the population. In addition, we have perceived a relative increase in hospital admissions and, specifically, in urgent surgical pathology compared to the previous year (AU)