The importance of prevalence and pre-test probability on the microbiological diagnosis of SARS-CoV-2: the case of Spain in 2020.

OBJECTIVE: The aim of this work was to estimate the conditioned probability for the diagnosis of SARS-CoV-2 infection with reverse transcription polymerase chain reaction (RT-PCR), viral antigen rapid diagnostic tests (Ag-RDT), and antibody detection tests depending on the prevalence in the specific healthcare settings in Spain in 2020, and on the pre-test probability (PTP) according to the clinical situation, age and unknown or close contacts of the patient. METHODS: Performance parameters of tests were obtained from literature. Prevalence data and PTP were obtained from Spanish sources and a survey, respectively. The post-test probability is the positive predictive value (PPV) when test is positive. For negative result, we also calculated the probability of having the infection (false negatives). RESULTS: For both RT-PCR and viral Ag-RDT, the lowest PPV values were for the population screenings. This strategy proved to be useful in ruling out infection but generates a high number of false positives. At individual level, both tools provided high PPV (≥ 97%) when the PTP values are over 35%. In seroprevalence studies, though the specificity of IgG alone tests is high, under low seroprevalence, false positives cannot be avoided. Total antibodies tests are useful for diagnosis of COVID-19 in those doubtful cases with RT-PCR or Ag-RDT tests being repeatedly negative. CONCLUSIONS: The interpretating of results depends not only on the accuracy of the test, but also on the prevalence of the infection in different settings, and the PTP associated to the patient before performing the test.

Sensitization to Vitis vinifera Pollen in a Wine Production Area: Identification of the Allergens Involved.

BACKGROUND: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. MATERIALS AND METHODS: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. RESULTS: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. CONCLUSIONS: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen-positive patients. Five new vine pollen allergens were identified.

Antimicrobial resistance in Gram-negative bacilli in Spain: an experts' view.

BACKGROUND: Antibiotic resistance in Gram-negative bacilli poses a serious problem for public health. In hospitals, in addition to high mortality rates, the emergence and spread of resistance to practically all antibiotics restricts therapeutic options against serious and frequent infections. OBJECTIVE: The aim of this work is to present the views of a group of experts on the following aspects regarding resistance to antimicrobial agents in Gram-negative bacilli: 1) the current epidemiology in Spain, 2) how it is related to local clinical practice and 3) new therapies in this area, based on currently available evidence. METHODS: After reviewing the most noteworthy evidence, the most relevant data on these three aspects were presented at a national meeting to 99 experts in infectious diseases, clinical microbiology, internal medicine, intensive care medicine, anaesthesiology and hospital pharmacy. RESULTS AND CONCLUSIONS: Subsequent local debates among these experts led to conclusions in this matter, including the opinion that the approval of new antibiotics makes it necessary to train the specialists involved in order to optimise how they use them and improve health outcomes; microbiology laboratories in hospitals must be available throughout a continuous timetable; all antibiotics must be available when needed and it is necessary to learn to use them correctly; and the Antimicrobial Stewardship Programs (ASP) play a key role in quickly allocating the new antibiotics within the guidelines and ensure appropriate use of them.

Sensitization to Vitis vinifera Pollen in a Wine Production Area: Identification of the Allergens Involved

Background: Vine cultivation is widely distributed in La Rioja, Spain (37% of all crops) and is associated with exposure of the general population to vine pollen. The aims of this study were to investigate the prevalence of sensitization to Vitis vinifera pollen in persons with respiratory allergy in the general population and to identify the allergens involved. Materials and Methods: The study population comprised patients who came to the hospital between September 2019 and January 2020 with suspected respiratory allergy. All patients underwent skin prick testing with a panel of standardized aeroallergens, profilin, lipid transfer protein (LTP), and V vinifera pollen extract and prick-prick testing with fresh grapes. The in vitro study included specific IgE by ImmunoCap and ELISA, allergenic profile by immunoblot with individual sera from patients positive to V vinifera pollen extract, and 2D immunoblot with a pool of sera. The spots recognized by IgE were identified using mass spectrometry. Results: A total of 151 patients were included. Of these, 124 were positive to some of the allergens tested. Thirty-four (27.4%) were positive to vine pollen in the skin prick tests. The serology study revealed positive results in 20 patients. Five vine pollen allergens were identified, and profilin was the most prevalent (30%). The other 4 allergens could be considered specific to this pollen. Conclusions: Sensitization to vine pollen was frequent in the general population in a vine growing area. The clinical relevance of this finding is unknown owing to sensitization to other pollens in the vine pollen–positive patients. Five new vine pollen allergens were identified (AU)

Antecedentes: El cultivo de la vid está ampliamente distribuido en La Rioja (37% de los cultivos), lo que supone una exposición de la población general al polen de esta planta. El objetivo de este estudio fue investigar la prevalencia de sensibilización al polen de Vitis vinifera en la población general con alergia respiratoria e identificar los alérgenos implicados. Materiales y métodos: Se incluyeron en el estudio pacientes que acudieron al hospital entre septiembre de 2019 y enero de 2020 con sospecha de alergia respiratoria. A todos ellos se les realizó una prueba cutánea con el panel de aeroalérgenos estandarizados, profilina, LTP, extracto de polen de V. vinifera y Prick prick con uva. El estudio in vitro incluyó IgE específica mediante ImmunoCap y ELISA, perfil alergénico por inmunoblot con sueros individuales de pacientes positivos al extracto de polen de V. vinifera e inmunoblot 2D con un pool de sueros. Las proteínas reconocidas por la IgE fueron identificadas por espectrometría de masas. Resultados: Se incluyeron un total de 151 pacientes. De ellos, 124 fueron positivos a algunos de los alérgenos analizados. 34 (27,4%) fueron positivos a polen de vid por prueba cutánea. 20 fueron positivos tras el estudio serológico. Se identificaron 5 alérgenos del polen de la vid, siendo la profilina el más prevalente (30%). Los otros 4 alérgenos podrían considerarse específicos de este polen. Conclusión: Se detectó una alta sensibilización al polen de vid en la población general en una zona de viñedos. Se desconoce la relevancia clínica debido a la sensibilización a otros pólenes en los pacientes positivos a polen de vid. Se identificaron 5 nuevos alérgenos del polen de la vid (AU)

Subconjunctival human dirofilariasis by Dirofilaria repens in the Mediterranean Basin.

Purpose: Human dirofilariasis cases have increased in Europe for the last few decades. We document an autochthonous case of dirofilariasis infection in the subconjunctival space of a 60-year-old Spanish man. Observations: The patient presented with pain in his right eye, which was diagnosed as epi-scleritis. In spite of the treatment administered, no improvement was reported. An external exam showed conjunctival congestion on the temporal part of the right eye bulbar conjunctiva. The anterior chamber showed no flare or cells in both eyes and dilated fundus exam was normal. Nevertheless, a long whitish vermiform mobile mass was detected under the conjunctiva in the temporal part of the right eye. The worm was surgically removed and diagnosed morphologically and also molecularly as Dirofilaria repens. This species uses dogs and wild canids as definitive hosts and principal reservoirs, while mosquito species are transmitters. Humans act as accidental hosts, and clinical manifestations depend on the location of the worm in the organs and tissues. Conclusions and importance: The correct diagnosis and control of subcutaneous/ocular dirofilariasis by D. repens require several professionals under the One Health approach to deal with this zoonotic disease, which poses a serious public health problem, at least in the Mediterranean Basin.

Value of syndromic panels in the management of severe community-acquired pneumonia.

Community-acquired pneumonia requiring hospital admission is a prevalent and potentially serious infection, especially in high-risk patients (e.g., those requiring ICU admission or immunocompromised). International guidelines recommend early aetiological diagnosis to improve prognosis and reduce mortality. Syndromic panels that detect causative pathogens by molecular methods are here to stay. They are highly sensitive and specific for detecting the targets included in the test. A growing number of studies measuring their clinical impact have observed increased treatment appropriateness and decreased turnaround time to aetiological diagnosis, need for admission, length of hospital stay, days of isolation, adverse effects of medication and hospital costs. Its use is recommended a) per a pre-established protocol on making the diagnosis and managing the patient, b) together with an antimicrobial stewardship programme involving both the Microbiology Service and the clinicians responsible for the patient, and c) the final evaluation of the whole process. However, we recall that microbiological diagnosis with traditional methods remains mandatory due to the possibility that the aetiological agent is not included among the molecular targets and to determine the antimicrobial susceptibility of the pathogens detected.

Tibial tray cementation is not necessary for knee revision with titanium metaphyseal sleeves: a mid-term prospective study in AORI 2B defects.

PURPOSE: Metaphyseal fixation with porous titanium sleeves in revision knee surgery provides mechanical support to the implant, promotes biological fixation, and has shown satisfactory short- and mid-term results. Cement is commonly used to fix the tibial tray to the epiphyseal area. The objective of this study is to determine whether cement should be used to achieve fixation of the tibial tray with the hypothesis that metaphyseal sleeves would provide enough axial and rotational stability making cementation unnecessary. MATERIAL AND METHODS: Prospective study of 60 patients undergoing knee replacement surgery with metaphyseal sleeves in type 2B defects in femur and tibia. Patients were divided into two groups according to the use of cement on the tibial component. Analysis included the American Knee Society Score (KSS) knee and functional scales, the Western Ontario and McMaster Universities (WOMAC) index, the Short Form 12 (SF-12) health survey, and radiographic assessment with a maximum follow-up of 5 years. RESULTS: No statistically significant differences were found between the two groups in any of the parameters assessed. CONCLUSION: Metaphyseal sleeves showed a 100% survivorship at five years of followup. There were no differences in clinical and radiographic outcomes at five years of follow-up depending on whether or not cement was used for tibial platform fixation. Cementation of the tibial tray would therefore not be required to achieve satisfactory mid-term results. LEVEL OF EVIDENCE: Level II: prospective cohort study. Therapeutic.

ZnO-mesoporous glass scaffolds loaded with osteostatin and mesenchymal cells improve bone healing in a rabbit bone defect.

The use of 3D scaffolds based on mesoporous bioactive glasses (MBG) enhanced with therapeutic ions, biomolecules and cells is emerging as a strategy to improve bone healing. In this paper, the osteogenic capability of ZnO-enriched MBG scaffolds loaded or not with osteostatin (OST) and human mesenchymal stem cells (MSC) was evaluated after implantation in New Zealand rabbits. Cylindrical meso-macroporous scaffolds with composition (mol %) 82.2SiO2-10.3CaO-3.3P2O5-4.2ZnO (4ZN) were obtained by rapid prototyping and then, coated with gelatin for easy handling and potentiating the release of inorganic ions and OST. Bone defects (7.5 mm diameter, 12 mm depth) were drilled in the distal femoral epiphysis and filled with 4ZN, 4ZN + MSC, 4ZN + OST or 4ZN + MSC + OST materials to evaluate and compare their osteogenic features. Rabbits were sacrificed at 3 months extracting the distal third of bone specimens for necropsy, histological, and microtomography (µCT) evaluations. Systems investigated exhibited bone regeneration capability. Thus, trabecular bone volume density (BV/TV) values obtained from µCT showed that the good bone healing capability of 4ZN was significantly improved by the scaffolds coated with OST and MSC. Our findings in vivo suggest the interest of these MBG complete systems to improve bone repair in the clinical practice.

The effect of divergent selection for intramuscular fat on the domestic rabbit genome.

An experiment of divergent selection for intramuscular fat was carried out at Universitat Politècnica de València. The high response of selection in intramuscular fat content, after nine generations of selection, and a multidimensional scaling analysis showed a high degree of genomic differentiation between the two divergent populations. Therefore, local genomic differences could link genomic regions, encompassing selective sweeps, to the trait used as selection criterion. In this sense, the aim of this study was to identify genomic regions related to intramuscular fat through three methods for detection of selection signatures and to generate a list of candidate genes. The methods implemented in this study were Wright's fixation index, cross population composite likelihood ratio and cross population - extended haplotype homozygosity. Genomic data came from the 9th generation of the two populations divergently selected, 237 from Low line and 240 from High line. A high single nucleotide polymorphism (SNP) density array, Affymetrix Axiom OrcunSNP Array (around 200k SNPs), was used for genotyping samples. Several genomic regions distributed along rabbit chromosomes (OCU) were identified as signatures of selection (SNPs having a value above cut-off of 1%) within each method. In contrast, 8 genomic regions, harbouring 80 SNPs (OCU1, OCU3, OCU6, OCU7, OCU16 and OCU17), were identified by at least 2 methods and none by the 3 methods. In general, our results suggest that intramuscular fat selection influenced multiple genomic regions which can be a consequence of either only selection effect or the combined effect of selection and genetic drift. In addition, 73 genes were retrieved from the 8 selection signatures. After functional and enrichment analyses, the main genes into the selection signatures linked to energy, fatty acids, carbohydrates and lipid metabolic processes were ACER2, PLIN2, DENND4C, RPS6, RRAGA (OCU1), ST8SIA6, VIM (OCU16), RORA, GANC and PLA2G4B (OCU17). This genomic scan is the first study using rabbits from a divergent selection experiment. Our results pointed out a large polygenic component of the intramuscular fat content. Besides, promising positional candidate genes would be analysed in further studies in order to bear out their contributions to this trait and their feasible implications for rabbit breeding programmes.

SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019).

Small-cell lung cancer (SCLC) accounts for 15% of lung cancers. Only one-third of patients are diagnosed at limited stage. The median survival remains to be around 15-20 months without significative changes in the strategies of treatment for many years. In stage I and IIA, the standard treatment is the surgery followed by adjuvant therapy with platinum-etoposide. In stage IIB-IIIC, the recommended treatment is early concurrent chemotherapy with platinum-etoposide plus thoracic radiotherapy followed by prophylactic cranial irradiation in patients without progression. However, in the extensive stage, significant advances have been observed adding immunotherapy to platinum-etoposide chemotherapy to obtain a significant increase in overall survival, constituting the new recommended standard of care. In the second-line treatment, topotecan remains as the standard treatment. Reinduction with platinum-etoposide is the recommended regimen in patients with sensitive relapse (≥ 3 months) and new drugs such as lurbinectedin and immunotherapy are new treatment options. New biomarkers and new clinical trials designed according to the new classification of SCLC subtypes defined by distinct gene expression profiles are necessary.

Quantitative bidimentional and Doppler ultrasound assessment of the effect of a GnRH antagonist on canine prostatic hyperplasia.

The objectives of this article were: a) To describe the effect of a single administration of the third generation GnRH antagonist, acyline, on canine benign prostatic hyperplasia (BPH) b)To quantitatively compare parenchyma echogenicity, heterogeneity (SD echogenicity) and blood flow in hyperplastic and treated prostate glands. Seven mixed bred dogs, 11.14 ± 0.8 years of age, weighing 8.5 ± 1.4 (3.8-15.6) kg, with BPH were included in this study and administered acyline 330 mg/kg sc (day 0). Then the dogs were examined by B Mode and Doppler ultrasound on days 15, 30 and 60 after treatment. Parenchymal frozen images were digitally analyzed. On day -7, prostatic volume was 1.60-5.36 fold (volume ratio) enlarged in relation to the expected volume. Prostatic volume decreased up to a mean of -38.44% (P < 0.01; range -32.2 to -70.9%) on day 30 to gradually increase towards pretreatment values. A correlation between volume ratio and nadir treatment volume was also found (r = - 0.87; P < 0.05). Mean parenchyma echogenicity (P < 0.01) and heterogeneity (P < 0.01) diminished in all the post treatment evaluations. Pretreatment intraprostatic cysts disappeared at the time point of peak treatment effect. Prostatic arteries RI increased on day 30, being different from day -7 and also from day 60 values (P < 0.05). It was concluded that a single administration of a third generation GnRH antagonist safely decreased prostatic volume and parenchyma and blood flow abnormities associated with canine BPH during 30 days. Monthly administrations of this treatment could represent a rapid, efficient and safe therapeutic option for BPH.

Intracellular calcium mishandling leads to cardiac dysfunction and ventricular arrhythmias in a mouse model of propionic acidemia.

Propionic acidemia (PA) is a rare metabolic disease associated with mutations in genes encoding the α and ß subunits of the enzyme propionyl-CoA carboxylase. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species production and oxidative damage, which have been associated with the disease pathophysiology. Clinical symptoms are heterogeneous and include cardiac complications, mainly cardiac dysfunction and arrhythmias, which are recognized as one of the major life-threatening manifestations in patients. We aimed to investigate the molecular mechanisms underlying the cardiac phenotype using a hypomorphic mouse model (Pcca-/-(A138T)) that recapitulates some biochemical and clinical characteristics of PA. We demonstrate that Pcca-/-(A138T) mice present with depressed cardiac function along with impaired cell contractility when compared to the wild-type mice. Cardiac dysfunction in Pcca-/-(A138T) mice was associated with lower systolic Ca2+ release ([Ca2+]i transients), impairment in the sarcoplasmic reticulum (SR) Ca2+ load and decreased Ca2+ re-uptake by SR-Ca2+ ATPase (SERCA2a). These functional changes correlated well with the depressed activity of SERCA2a, the elevated ROS levels and SERCA2a oxidation rate in cardiomyocytes isolated from Pcca-/-(A138T) mice. In addition, decreased SR-Ca2+ load in Pcca-/-(A138T) cardiomyocytes was associated with increased diastolic Ca2+ release. The increase in Ca2+ sparks, Ca2+ waves and spontaneous [Ca2+]i transients in Pcca-/-(A138T) cardiomyocytes could be responsible for the induction of ventricular arrhythmias detected in these mice. Overall, our results uncover the role of impaired Ca2+ handling in arrhythmias and cardiac dysfunction in PA, and identify new targets for the development of therapeutic approaches for this devastating metabolic disease.

Correlated responses on growth traits after two-stage selection for ovulation rate and litter size in rabbits.

Rabbit commercial maternal lines are usually selected for litter size (LS) and paternal lines for growth rate (GR). Line OR_LS was selected by ovulation rate (OR) and LS to improve LS more efficiently. In this study, growth traits of line OR_LS were evaluated by estimating the correlated response on weaning weight (WW), slaughter weight (SW) and GR during fattening period as well as their variability (DWW, DSW and DGR, respectively). Data were analyzed using Bayesian inference methods. Heritability estimates were low for growth traits (0.09, 0.13 and 0.14 for WW, SW and GR, respectively) and negligible for growth traits variability (0.01, 0.004 and 0.01 for DWW, DSW and DGR, respectively). Moderate common litter effect ratio (c2; 0.35, 0.28 and 0.27) and low maternal effect ratio (m2; 0.11, 0.05 and 0.01) were obtained for WW, SW and GR, respectively. Both c2 and m2 were lower at slaughter than at weaning. In addition, low common litter effect and negligible maternal effect were observed for growth traits variability. Genetic correlations between LS and both growth traits and their variability were close to zero. Positive genetic correlations were observed between OR and growth traits (0.19, 0.38 and 0.36 for WW, SW and GR, respectively) as well as between OR and growth traits variability (0.35, 0.62 and 0.20 for DWW, DSW and DGR, respectively). Positive correlated responses in both periods were obtained for growth traits, WW, SW and GR (0.037, 0.156 and 0.110 kg, respectively). The correlated response found in growth traits might be due to the positive genetic correlations between OR and these traits. However, selection for OR and LS using independent culling levels did not modify the growth traits variability. Therefore, no negative consequences on growth traits can be expected in current commercial maternal lines.

Deciphering pharmacokinetics and pharmacodynamics of fosfomycin.

Fosfomycin, a low molecular weight and hydrophilic drug with negligible protein binding, is eliminated almost exclusively by glomerular filtration, whose clearance is subject to patient renal function. The volume of distribution approximates to the extracellular body water (about 0.3 L/Kg) in healthy volunteers, but it is increased in critically ill patients with bacterial infections. Fosfomycin presents a high ability to distribute into many tissues, including inflamed tissues and abscess fluids. Based on PK/PD analysis and Monte Carlo simulations, we have evaluated different fosfomycin dosing regimen to optimize the treatment of septic patients due to Enterobacterales and Pseudomonas aeruginosa. As PK/PD targets, we selected %T>MIC > 70% for all pathogens, and AUC24/MIC > 24 and AUC24/MIC > 15 for net stasis of Enterobacterales and P. aeruginosa, respectively. Pharmacokinetic parameters in critically ill patients were obtained from the literature. Several dosing regimens were studied in patients with normal renal function: fosfomycin 2-8 g given every 6-12 hours, infused over 30 minutes- 24 hours. At the susceptibility EUCAST breakpoint for Enterobacterales and Staphylococcus spp. (MIC ≤ 32 mg/L), fosfomycin 4 g/8h or higher infused over 30 minutes achieved a probability of target attainment (PTA) > 90%, based in both %T>MIC and AUC24/MIC. For MIC of 64 mg/L, fosfomycin 6 g/6h in 30-minute infusion and 8 g/ 8h in 30-minute and 6 hours infusions also achieved PTA values higher than 90%. No fosfomycin monotherapy regimen was able to achieve PK/PD targets related to antimicrobial efficacy for P. aeruginosa with MICs of 256-512 mg/L.

Results measured by means of a motion capture system in proximal humerus fractures treated by osteosynthesis with locking plate. / Resultados medidos con captura de movimiento en las fracturas de húmero proximal tratadas mediante osteosíntesis con placa bloqueada.

OBJECTIVE: To evaluate the results after locking plate internal fixation of proximal humerus fractures by means of a motion capture system, and functional scales. MATERIAL AND METHOD: Retrospective study of a cohort of 47 elderly patients undergoing surgery from January 2010 to December 2014. After a minimum follow-up of two years, two functional scales (Constant-Murley and Quick DASH), and a quality of life scale (EQ-5D) were used for clinical evaluation. For objective evaluation of the range of motion a kinematic marker-free analysis with cameras was performed. RESULTS: The average age was 74.85 years. Average functional scores were: Constant-Murley 70.06 points, Quick DASH 35.74 points and EQ-5D 6.79 points. The average range of motion was: flexion, 111.49°; extension: 24.13°; abduction: 109.40°; adduction: 15.13°; external rotation: 38.96°, and internal rotation: 49.28°. Correlation was found between the two functional scales, between them and the EQ-5D, and between range of motion and functional scales (except for external rotation) as well as between range of motion and EQ-5D (except for flexion and external rotation). CONCLUSION: Locking plate osteosynthesis in proximal humerus fragility fractures achieved good functional and quality of life scores. Motion capture systems can be a useful tool for the functional assessment of shoulder pathology allowing an objective evaluation of range of motion.

Correlated response to selection for litter size environmental variability in rabbits' resilience.

Resilience is the ability of an animal to return soon to its initial productivity after facing diverse environmental challenges. This trait is directly related to animal welfare and it plays a key role in fluctuations of livestock productivity. A divergent selection experiment for environmental variance of litter size has been performed successfully in rabbits over ten generations. The objective of this study was to analyse resilience indicators of stress and disease in the divergent lines of this experiment. The high line showed a lower survival rate at birth than the low line (-4.1%). After correcting by litter size, the difference was -3.2%. Involuntary culling rate was higher in the high than in the low line (+12.4%). Before vaccination against viral haemorrhagic disease or myxomatosis, concentration of lymphocytes, C-reactive protein (CRP), complement C3, serum bilirubin, triglycerides and cholesterol were higher in the high line than in the low line (difference between lines +4.5%, +5.6 µg/ml, +4.6 mg/ml, +7.9 mmol/l, +0.3 mmol/l and +0.4 mmol/l). Immunological and biochemical responses to the two vaccines were similar. After vaccination, the percentage of lymphocytes and CRP concentration were higher in the low line than in the high one (difference between lines +4.0% and +13.1 µg/ml). The low line also showed a higher increment in bilirubin and triglycerides than the high line (+14.2 v. +8.7 mmol/l for bilirubin and +0.11 v. +0.01 mmol/l for triglycerides); these results would agree with the protective role of bilirubin and triglycerides against the larger inflammatory response found in this line. In relation to stress, the high line had higher basal concentration of cortisol than the low line (+0.2ng/ml); the difference between lines increased more than threefold after the injection of ACTH 1 to 24, the increase being greater in the high line (+0.9 ng/ml) than in the low line (+0.4 ng/ml). Selection for divergent environmental variability of litter size leads to dams with different culling rate for reproductive causes and different kits' neonatal survival. These associations suggest that the observed fitness differences are related to differences in the inflammatory response and the corticotrope response to stress, which are two important components of physiological adaptation to environmental aggressions.

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine.

OBJECTIVE: To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM). METHODS: PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful. RESULTS: When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study. CONCLUSIONS: We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Accuracy of the BD MAX™ vaginal panel in the diagnosis of infectious vaginitis.

The aim of this study was to evaluate the BD MAX™ vaginal panel in the diagnosis of bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis by comparing it with conventional methods: (i) combination of Hay criteria and presence of clue cells with predominant growth of Gardnerella vaginalis, (ii) yeast culture, and (iii) combination of culture, wet mount microscopic examination, and an alternative molecular assay. One thousand vaginal samples of women ≥ 14 years were analyzed; 5% of the samples belonged to pregnant women. 19.3% were classified as BV, in 33.6% yeasts were recovered and in 1.5% TV was detected. For BV, sensitivity and specificity were of 89.8% and 96.5%, respectively; for VVC, sensitivity and specificity were of 97.4% and 96.8%, respectively, and for T. vaginalis, the sensitivity and specificity were of 100%. The BD MAX™ vaginal panel is highly sensitive and specific and simplifies the identification of infectious vaginitis.

Correlated response in body condition and energy mobilisation in rabbits selected for litter size variability.

A divergent selection experiment on litter size variability (high and low lines) was performed in rabbits over seven generations. The aim of this study was to evaluate the correlated responses to selection in body condition and fat reserves mobilisation. Litter size variability was estimated as phenotypic variance of litter size within female after correcting for the year-season and the parity-lactation status effects. A total of 226 females were used in this study, of which 158 females were used to measure body condition and energy mobilisation. Body condition was measured as BW and perirenal fat thickness. Females were stimulated with the adrenergic isoproterenol. Mobilisation capacity of fat reserves was measured by the lipolytic potential, defined as the increment in non-esterified fatty acids (NEFA) levels from basal concentration until adrenergic stimulation at mating, delivery and 10 days after delivery of the second reproductive cycle. Females were classified as survivor or non-survivor when they were culled for sanitary reasons or died before the third kindling. Data were analysed using Bayesian methodology. Survivor females presented higher BW than the non-survivor females at delivery (238 g, P=1.00) and 10 days after delivery (276 g, P=1.00). They also showed higher perirenal fat thickness at 10 days after delivery (0.62 mm, P=1.00). At delivery, basal NEFA levels was lower in survivor than non-survivor females (-0.18 mmol/l, P=1.00), but their lipolytic potential (∆NEFA) was higher (0.08 mmol/l, P=0.94). Body weight was similar between lines in survivor females. Perirenal fat thickness was lower in the high line than in the low line at delivery (-0.23 mm, P=0.90) and 10 days after delivery (-0.28 mm, P=0.92). The high line exhibited higher NEFA (0.10 mmol/l, P=0.93) and lower ∆NEFA (-0.08 mmol/l, P=0.92) than the low line at delivery. The low line showed a favourable correlated response to selection on body condition and fat reserves mobilisation. In conclusion, the low line selected for litter size variability seems to adapt better to adverse conditions, as it has a greater capacity to mobilise energy reserves at delivery than the high line. Females that adequately manage their body reserves and perform energy mobilisation correctly have a lower risk of dying or being culled.