Assessing the Impact of COVID-19 on Amateur Runners' Performance: An Analysis through Monitoring Devices.

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.

Effects of Minimalist vs. Traditional Running Shoes on Abdominal Lumbopelvic Muscle Activity in Women Running at Different Speeds: A Randomized Cross-Over Clinical Trial.

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/m2) 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.

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis.

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.

Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients.

BACKGROUND: Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0-24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population. METHODS: Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100-150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0-24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%. RESULTS: Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg. CONCLUSION: The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.

Development of Aspergillosis in a cohort of non-neutropenic, non-transplant patients colonised by Aspergillus spp.

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.

Risk factors for colonization by carbapenemase-producing enterobacteria at admission to a Surgical ICU: A retrospective study.

INTRODUCTION: In 2011, a hospital-wide outbreak of OXA-48 producing Klebsiella pneumoniae occurred in our hospital, an epidemiological setting of high ESBL-producing K. pneumoniae rates. This study identifies risk factors for colonization with carbapenemase-producing enterobacteria (CPE) at Surgical Intensive Care Unit (SICU) admission. METHODS: A 2-year retrospective study was performed in all patients admitted to the SICU that following routine had a rectal swab collected upon admission. RESULTS: Of 254 patients admitted, 41 (16.1%) harbored CPE (five showing two carbapenemase-producing isolates). Most frequent carbapenemase-producing isolates and carbapenemases were K. pneumoniae (39/46, 84.8%) and OXA-48 (31/46; 76.1%), respectively. Carriers significantly had higher rates of chronic renal disease, previous digestive/biliary endoscopy, hospitalization, ICU/SICU admission, intraabdominal surgery, and antibiotic intake, as well as higher median values of clinical scores (SOFA, SAPS II and APACHE II). In the multivariate analysis (R2=0.309, p<0.001), CPE carriage was associated with prior administration of 3rd-4th generation cephalosporins (OR=27.96, 95%CI=6.88, 113.58, p<0.001), ß-lactam/ß-lactamase inhibitor (OR=11.71, 95%CI=4.51, 30.43, p<0.001), abdominal surgery (OR=6.33, 95%CI=2.12, 18.89, p=0.001), and prior digestive/biliary endoscopy (OR=3.88, 95%CI=1.56, 9.67, p=0.004). CONCLUSIONS: A strong association between production of ESBLs and carriage of CPE (mainly OXA-48 producing K. pneumoniae) was found. According to the model, the co-selection of ß-lactamases by previous exposure to broad-spectrum cephalosporins and ß-lactam/ß-lactamase inhibitors (with lower relative risk), abdominal surgery and prior digestive/biliary endoscopy were factors associated with CPE carriage.

Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration.

OBJECTIVES: To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH). PATIENTS AND METHODS: Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions. RESULTS: Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ±â€Š15.87 versus 71.31 ±â€Š14.24; P = 0.008) and Day 2 (119.01 ±â€Š27.20 versus 104.54 ±â€Š21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis. CONCLUSIONS: There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.

Influence of the MBC/MIC ratio on the antibacterial activity of vancomycin versus linezolid against methicillin-resistant Staphylococcus aureus isolates in a pharmacodynamic model simulating serum and soft tissue interstitial fluid concentrations reported in diabetic patients.

OBJECTIVES: To explore serum and tissue pharmacodynamics of linezolid versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates with different MBC/MIC ratios. METHODS: Five strains (vancomycin MIC/MBCs, mg/L) were used: TOL-1 (2/≥64), TOL-2 (1/16), LT-1 and LT-2 (1/8) and NT (1/2). The linezolid MIC/MBC for all strains was 2/≥64 mg/L. A two-compartment dynamic computerized device was used (inocula 10(7) cfu/mL). Free concentrations obtained in serum and interstitial fluid with twice-daily regimens of 1 g of vancomycin or 600 mg of linezolid were simulated over 48 h. ABBCs (differences between control growth curves and killing curves of bacteria exposed to antibiotics; log10 cfu × h/mL) and log10 reductions in initial inocula were calculated. RESULTS: In serum simulations, vancomycin (AUC0-24/MIC = 251.8 for TOL-1 and 503.6 for the remaining strains) was bacteriostatic against strains with MBC/MIC ≥8, but bactericidal against NT. In interstitial fluid simulations (AUC0-24/MIC = 54.6 for TOL-1 and 109.2 for the remaining strains), initial inocula grew in all cases. Linezolid, both in serum (AUC0-24/MIC = 87.0) and in interstitial fluid (AUC0-24/MIC = 130.6) simulations, reduced initial inocula ≥2.2 log10 for all strains (apart from LT-1 in serum simulations that showed a bacteriostatic profile). ABBCs were similar in serum and interstitial fluid with linezolid, but significantly lower in interstitial fluid simulations with vancomycin. CONCLUSIONS: From the pharmacodynamic perspective (serum concentrations), vancomycin tolerance should include MBC/MIC ≥8 since strains exhibiting this ratio showed bacteriostatic profiles similar to those obtained with isolates with MBC/MIC ratios of 16 or 32. Insufficient concentrations of vancomycin at the simulated infected site were linked to bacteriological failure. Free concentrations of linezolid at the infection site pharmacodynamically covered MRSA.

Influence of Artichoke Antioxidant Activity in Their Susceptibility to Suffer Frost Injury.

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.

Macrolides and ß-lactam antibiotics enhance C3b deposition on the surface of multidrug-resistant Streptococcus pneumoniae strains by a LytA autolysin-dependent mechanism.

The emergence of Streptococcus pneumoniae strains displaying high levels of multidrug resistance is of great concern worldwide and a serious threat for the outcome of the infection. Modifications of the bacterial envelope by antibiotics may assist the recognition and clearance of the pathogen by the host immune system. Recognition of S. pneumoniae resistant strains by the complement component C3b was increased in the presence of specific anti-pneumococcal antibodies and subinhibitory concentrations of different macrolides and ß-lactam antibiotics for all the strains investigated. However, C3b levels were unchanged in the presence of serum containing specific antibodies and sub-MICs of levofloxacin. To investigate whether LytA, the main cell wall hydrolase of S. pneumoniae, might be involved in this process, lytA-deficient mutants were constructed. In the presence of antibiotics, loss of LytA was not associated with enhanced C3b deposition on the pneumococcal surface, which confirms the importance of LytA in this interaction. The results of this study offer new insights into the development of novel therapeutic strategies using certain antibiotics by increasing the efficacy of the host immune response to efficiently recognize pneumococcal resistant strains.

In vitro interference of tigecycline at subinhibitory concentrations on biofilm development by Enterococcus faecalis.

OBJECTIVES: Since biofilm formation is the hallmark of Enterococcus faecalis isolates, the aim of this study was to quantify biofilm formation in the presence of subinhibitory concentrations of tigecycline. METHODS: Interference of tigecycline on biofilm formation was spectrophotometrically quantified using 20 biofilm-producing E. faecalis isolates with tigecycline MICs of 0.12 (8 strains) or 0.25 mg/L (12 strains). Biofilm production was measured in antibiotic-free tryptic soy broth supplemented with 1% glucose and compared with biofilm production in the same medium with tigecycline at subinhibitory concentrations (0.25× or 0.5× MIC, similar to trough concentrations in serum or concentrations in the colon after a standard dose) by reading the optical density at 450 nm (OD(450)) after staining with Crystal Violet. RESULTS: In the presence of subinhibitory tigecycline concentrations, pooled OD(450) values for the 20 strains [median (IQR)] were significantly lower than those for controls: 0.468 (0.379-0.516) for antibiotic-free controls versus 0.295 (0.200-0.395) for 0.25× MIC tigecycline (P < 0.001) and 0.287 (0.245-0.479) for 0.5× MIC tigecycline (P < 0.001), with significant differences between pooled OD(450) values obtained with each concentration of tigecycline (P = 0.022). In 17 out of 20 (85%) strains the OD(450) obtained with 0.25× MIC tigecycline was significantly (P < 0.05) lower than the basal OD(450), while this occurred in 12 out of 20 (60%) strains with 0.5× MIC. CONCLUSIONS: In vitro tigecycline subinhibitory concentrations were able to interfere with biofilm formation by E. faecalis.

Repeated Aspergillus isolation in respiratory samples from non-immunocompromised patients not selected based on clinical diagnoses: colonisation or infection?

BACKGROUND: Isolation of Aspergillus from lower respiratory samples is associated with colonisation in high percentage of cases, making it of unclear significance. This study explored factors associated with diagnosis (infection vs. colonisation), treatment (administration or not of antifungals) and prognosis (mortality) in non-transplant/non-neutropenic patients showing repeated isolation of Aspergillus from lower respiratory samples. METHODS: Records of adult patients (29 Spanish hospitals) presenting ≥ 2 respiratory cultures yielding Aspergillus were retrospectively reviewed and categorised as proven (histopathological confirmation) or probable aspergillosis (new respiratory signs/symptoms with suggestive chest imaging) or colonisation (symptoms not attributable to Aspergillus without dyspnoea exacerbation, bronchospasm or new infiltrates). Logistic regression models (step-wise) were performed using Aspergillosis (probable + proven), antifungal treatment and mortality as dependent variables. Significant (p < 0.001) models showing the highest R2 were considered. RESULTS: A total of 245 patients were identified, 139 (56.7%) with Aspergillosis. Aspergillosis was associated (R2 = 0.291) with ICU admission (OR = 2.82), congestive heart failure (OR = 2.39) and steroids pre-admission (OR = 2.19) as well as with cavitations in X-ray/CT scan (OR = 10.68), radiological worsening (OR = 5.22) and COPD exacerbations/need for O2 interaction (OR = 3.52). Antifungals were administered to 79.1% patients with Aspergillosis (100% proven, 76.8% probable) and 29.2% colonised, with 69.5% patients receiving voriconazole alone or in combination. In colonised patients, administration of antifungals was associated with ICU admission at hospitalisation (OR = 12.38). In Aspergillosis patients its administration was positively associated (R(2) = 0.312) with bronchospasm (OR = 9.21) and days in ICU (OR = 1.82) and negatively with Gold III + IV (OR = 0.26), stroke (OR = 0.024) and quinolone treatment (OR = 0.29). Mortality was 78.6% in proven, 41.6% in probable and 12.3% in colonised patients, and was positively associated in Aspergillosis patients (R2 = 0.290) with radiological worsening (OR = 3.04), APACHE-II (OR = 1.09) and number of antibiotics for treatment (OR = 1.51) and negatively with species other than A. fumigatus (OR = 0.14) and aspergillar tracheobronchitis (OR = 0.27). CONCLUSIONS: Administration of antifungals was not always closely linked to the diagnostic categorisation (colonisation vs. Aspergillosis), being negatively associated with severe COPD (GOLD III + IV) and concomitant treatment with quinolones in patients with Aspergillosis, probably due to the similarity of signs/symptoms between this entity and pulmonary bacterial infections.

Correlation between clinical parameters characterising peri-implant and periodontal health: a practice-based research in Spain in a series of patients with implants installed 4-5 years ago.

OBJECTIVES: To explore peri-implant health (and relation with periodontal status) 4-5 years after implant insertion. STUDY DESIGN: A practice-based dental research network multicentre study was performed in 11 Spanish centres. The first patient/month with implant insertion in 2004 was considered. Per patient four teeth (one per quadrant) showing the highest bone loss in the 2004 panoramic X-ray were selected for periodontal status assessment. Bone losses in implants were calculated as the differences between 2004 and 2009 bone levels in radiographs. RESULTS: A total of 117 patients were included. Of the 408 teeth considered, 73 (17.9%) were lost in 2009 (losing risk: >50% for bone losses ≥7 mm). A total of 295 implants were reviewed. Eight of 117 (6.8%) patients had lost implants (13 of 295 implants installed; 4.4%). Implant loss rate (quadrant status) was 1.4% (edentulous), 3.6% (preserved teeth), and 11.1% (lost teeth) (p=0.037). The percentage of implant loss significantly (p<0.001) increased when the medial/distal bone loss was ≥3 mm. The highest (p≤0.001) pocket depths were found in teeth with ≥5 mm and implants with ≥3 mm bone losses, with similar mean values (≥4 mm), associated with higher rates of plaque index and bleeding by probing. CONCLUSIONS: The significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs and pocket depths or bleeding (both in teeth and implants, and between them) together with the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm suggest that the patient's periodontal status is a critical issue in predicting implant health/lesion.

Evolution of clonal and susceptibility profiles of serotype 19A Streptococcus pneumoniae among invasive isolates from children in Spain, 1990 to 2008.

The genetic structure and antibiotic nonsusceptibility of all serotype 19A Streptococcus pneumoniae pediatric pneumococcal isolates received at the Spanish Pneumococcal Reference Laboratory (1990 to 2008) were analyzed. Of them, 410 (79.8%) isolates belonged to 14 sequence types (STs) with >10 isolates each, and 104 to 73 STs (with 21 new STs, ST5141 to ST5161, with one isolate each). Time trends in 2000 to 2008 (n=471) were explored by lineal regression. Serotype 19A increased from 5.7% in 2000 to 16.8% in 2008 (R2=0.872; P=0.001). Decreasing trends (P<0.03) were found for ST202 (R2=0.774) and ST81 (R2=0.559), and increasing trends (P<0.03) for ST878 (R2=0.544) and ST320 (R2=0.530), both belonging to the clonal complex (CC) Denmark(14)-32 and first detected in 2003 and 2007, respectively, and ST2013 (R2=0.704) and ST4461 (R2=0.707), both appearing in 2004. Penicillin nonsusceptibility was clustered in ST81, ST276, ST320, ST878, ST2013, and ST4461 (>90% nonsusceptibility), and amoxicillin and cefotaxime nonsusceptibility in ST320: 87% amoxicillin (MIC50/MIC90=8/8 µg/ml) and 43.5% cefotaxime (MIC50/MIC90=1/2 µg/ml) nonsusceptibility. No trends were found for erythromycin nonsusceptibility (ranging from 38.5% to 66.7%) and cefotaxime nonsusceptibility (ranging from 0.0% to 7.8%), but increasing trends (P<0.02) were found for oral penicillin (from 16.7% in 2000 to 56.3% in 2008; R2=0.628) and amoxicillin (from 0.0% before 2007 to 13.8% in 2008; R2=0.628) nonsusceptibility. This study warns about the emergence of serotype 19A STs associated with high-level antibiotic nonsusceptibility, with a role for ST320 and ST878 occupying the niche left by some pneumococcal 7-valent conjugate vaccine (PCV7)-related resistant STs. The rapid expansion of serotype 19A and STs related to antibiotic resistance indicates that vaccines covering serotype 19A present advantages in countering invasive disease.

Efficacy of simulated cefditoren versus amoxicillin-clavulanate free concentrations in countering intrastrain ftsI gene diffusion in Haemophilus influenzae.

This study explores the effects of cefditoren (CDN) versus amoxicillin-clavulanic acid (AMC) on the evolution (within a single strain) of total and recombined populations derived from intrastrain ftsI gene diffusion in ß-lactamase-positive (BL⁺) and ß-lactamase-negative (BL⁻) Haemophilus influenzae. DNA from ß-lactamase-negative, ampicillin-resistant (BLNAR) isolates (DNA(BLNAR)) and from ß-lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) (DNA(BLPACR)) isolates was extracted and added to a 107-CFU/ml suspension of one BL⁺ strain (CDN MIC, 0.007 µg/ml; AMC MIC, 1 µg/ml) or one BL⁻ strain (CDN MIC, 0.015 µg/ml; AMC MIC, 0.5 µg/ml) in Haemophilus Test Medium (HTM). The mixture was incubated for 3 h and was then inoculated into a two-compartment computerized device simulating free concentrations of CDN (400 mg twice a day [b.i.d.]) or AMC (875 and 125 mg three times a day [t.i.d.]) in serum over 24 h. Controls were antibiotic-free simulations. Colony counts were performed; the total population and the recombined population were differentiated; and postsimulation MICs were determined. At time zero, the recombined population was 0.00095% of the total population. In controls, the BL⁻ and BL⁺ total populations and the BL⁻ recombined population increased (from ≈3 log10 to 4.5 to 5 log10), while the BL⁺ recombined population was maintained in simulations with DNA(BLPACR) and was decreased by ≈2 log10 with DNA(BLNAR). CDN was bactericidal (percentage of the dosing interval for which experimental antibiotic concentrations exceeded the MIC [ft>MIC], >88%), and no recombined populations were detected from 4 h on. AMC was bactericidal against BL⁻ strains (ft>MIC, 74.0%) in DNA(BLNAR) and DNA(BLPACR) simulations, with a small final recombined population (MIC, 4 µg/ml; ft>MIC, 30.7%) in DNA(BLPACR) simulations. When AMC was used against the BL⁺ strain (in DNA(BLNAR) or DNA(BLPACR) simulations), the bacterial load was reduced ≈2 log10 (ft>MIC, 44.3%), but 6.3% and 32% of the total population corresponded to a recombined population (MIC, 16 µg/ml; ft>MIC, 0%) in DNA(BLNAR) and DNA(BLPACR) simulations, respectively. AMC, but not CDN, unmasked BL⁺ recombined populations obtained by transformation. ft>MIC values higher than those classically considered for bacteriological response are needed to counter intrastrain ftsI gene diffusion by covering recombined populations.

Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997-2009.

BACKGROUND: Conjugate vaccines, such as the 7-valent conjugate vaccine (PCV7), alter serotype nasopharyngeal carriage, potentially increasing cases of otitis media by non-vaccine serotypes. METHODS: All paediatric middle ear fluid (MEF) isolates received in the Spanish Reference Laboratory for Pneumococci through a passive, laboratory-based surveillance system from January 1997 to June 2009 were analysed. Data from 1997 to 2000 were pooled as pre-vaccination period. Trends over time were explored by linear regression analysis. RESULTS: A total of 2,077 isolates were analysed: 855 belonging to PCV7 serotypes, 466 to serotype 19A, 215 to serotype 3, 89 to serotype 6A and 452 to other serotypes (< 40 isolates each). Over time, there has been a decreasing trend for PCV7 serotypes (R(2) = 0.944; p < 0.001, with significant decreasing trends for serotypes 19F, 14, 23F and 9V), and increasing trends for serotype 19A (R(2) = 0.901; p < 0.001), serotype 3 (R(2) = 0.463; p = 0.030) and other non-PCV7 serotypes (R(2) = 0.877; p < 0.001), but not for serotype 6A (R(2) = 0.311; p = 0.094). Considering all isolates, amoxicillin non-susceptibility showed an increasing trend (R(2) = 0.528; p = 0.017). Regarding serotype 19A, increasing trends in non-susceptibility to penicillin (R(2) = 0.726; p = 0.001), amoxicillin (R(2) = 0.804; p < 0.001), cefotaxime (R(2) = 0.546; p = 0.005) and erythromycin (R(2) = 0.546; p = 0.009) were found, with amoxicillin non-susceptibility firstly detected in 2003 (7.4%) and increasing up to 38.0% in 2009. In PCV7 serotypes (which prevalence decreased from 70.7% during 1997-2000 to 10.6% in 2009) amoxicillin non-susceptibility rates showed an increasing trend (R(2) = 0.702; p = 0.002). However, overall, amoxicillin non-susceptibility (≈25% in 2008-9) could be mainly attributed to serotype 19A (> 35% isolates) since PCV7 strains represented < 11% of total clinical isolates. CONCLUSIONS: In contrast to reports on invasive pneumococcal strains, in MEF isolates the reduction in the prevalence of PCV7 serotypes was not associated with decreases in penicillin/erythromycin non-susceptibility. The high prevalence of serotype 19A among paediatric MEF isolates and the amoxicillin non-susceptibility found in this serotype are worrisome since amoxicillin is the most common antibiotic used in the treatment of acute otitis media. These data suggest that non-PCV7 serotypes (mainly serotype 19A followed by serotypes 3 and 6A) are important etiological agents of acute otitis media and support the added value of the broader coverage of the new 13-valent conjugate vaccine.

The α-Gliadins in Bread Wheat: Effect of Nitrogen Treatment on the Expression of the Major Celiac Disease Immunogenic Complex in Two RNAi Low-Gliadin Lines.

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.

The Influence of Flower Head Order and Gibberellic Acid Treatment on the Hydroxycinnamic Acid and Luteolin Derivatives Content in Globe Artichoke Cultivars.

Flower head orders and the use of GA3 (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 GA3-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 GA3 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 GA3 treatment is therefore key in order to achieve the greatest health-benefits from artichoke consumption.

Preharvest Treatment with Oxalic Acid Improves Postharvest Storage of Lemon Fruit by Stimulation of the Antioxidant System and Phenolic Content.

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.

Susceptibility of recently collected Spanish pneumococci nonsusceptible to oral penicillin from serotypes not included in the 7-valent conjugate vaccine.

The susceptibilities of pneumococci recently collected (up to June 2009) in Spain (500 isolates nonsusceptible to oral penicillin and 150 susceptible isolates) from serotypes not included in the conjugate vaccine were determined. Most nonsusceptible isolates (53.6%) belonged to serotype 19A. Susceptibility rates in serotype 19A penicillin-intermediate (n = 201)/penicillin-resistant (n = 67) isolates were <33%/< or =6.0% (erythromycin and oral cephalosporins with defined breakpoints), 85.1%/11.9% (amoxicillin), and 96.0%/52.2% (cefotaxime), respectively. Low susceptibility to common oral beta-lactams was also found in serotypes 11A (95.5% susceptibility to cefotaxime and erythromycin) and 35B.