Host genetic variants associated with susceptibility and severity of pneumococcal pneumonia in adult patients.

BACKGROUND: Pneumococcal community-acquired pneumonia (P-CAP) is a major cause of morbidity and hospitalization. Several host genetics factors influencing risk of pneumococcal disease have been identified, with less information about its association with P-CAP. The aim of the study was to assess the influence of single nucleotide polymorphisms (SNP) within key genes involved in the innate immune response on the susceptibility to P-CAP and to study whether these polymorphic variants were associated with the severity and outcome of the episodes in a cohort of adult Caucasian patients. METHODS: Seventeen SNPs from 7 genes (IL-R1, IL-4, IL-10, IL-12B, NFKBIA, NFKBIE, NFKBIZ) were analyzed. For susceptibility, a case-control study including a cohort of 57 adult with P-CAP, and 280 ethnically matched controls was performed. Genetic influence on clinical severity and outcome was evaluated in a prospective observational study including all consecutive adult P-CAP patients from November 2015 to May 2017. RESULTS: The NFKBIA polymorphism rs696 and a haplotype combination were associated with susceptibility to P-CAP (OR = 0.62, p = 0.005 and OR = 0.63, p = 0.008, respectively). The SNP IL4 rs2227284 was associated with severe P-CAP (OR = 2.17, p = 0.04). IL-R1 (rs3917267) and IL-10 (rs3024509) variants were related with respiratory failure (OR = 3.31, p = 0.001 and OR = 0.18, p = 0.003, respectively) as well as several haplotype combinations in NFKBIA, NFKBIZ, IL-R1 and IL-10 (p = 0,02, p = 0,01, p = 0,001, p = 0,03, respectively). CURB-65 values were associated with the IL-10 rs3024509 variant (beta = - 0.4, p = 0.04), and with haplotype combinations of NFKBIZ and IL-10 (p = 0.05, p = 0.04, respectively). Genetic variants in IL-10 (rs3024509) and in IL-12B (rs730691) were associated with PSI values (beta = - 0.54, p = 0.01, and beta = - 0.28, p = 0.04, respectively), as were allelic combinations in IL-R1 (p = 0.02) and IL-10 (p = 0.01). Finally, several polymorphisms in the IL-R1 gene (rs13020778, rs2160227, & rs3917267) were associated with the time elapsed until clinical stability (beta = - 0.83, p = 0.03; beta = - 1, p = 0.02 and beta = 1.07, p = 0.008, respectively). CONCLUSIONS: A genetic variant in NFKBIA was associated with susceptibility to P-CAP in adult Caucasian patients and genetic variants from key cytokines of the innate immune response (Il-4, IL-10, IL-R1 and IL-12B) and NF-κB inhibitors were associated with different phenotypes of severe P-CAP. If validated, these SNPs may help to identify people at risk of P-CAP or severe P-CAP on which preventive measures could be applied.

Unreliable networks with random parameter matrices and time-correlated noises: distributed estimation under deception attacks.

This paper examines the distributed filtering and fixed-point smoothing problems for networked systems, considering random parameter matrices, time-correlated additive noises and random deception attacks. The proposed distributed estimation algorithms consist of two stages: the first stage creates intermediate estimators based on local and adjacent node measurements, while the second stage combines the intermediate estimators from neighboring sensors using least-squares matrix-weighted linear combinations. The major contributions and challenges lie in simultaneously considering various network-induced phenomena and providing a unified framework for systems with incomplete information. The algorithms are designed without specific structure assumptions and use a covariance-based estimation technique, which does not require knowledge of the evolution model of the signal being estimated. A numerical experiment demonstrates the applicability and effectiveness of the proposed algorithms, highlighting the impact of observation uncertainties and deception attacks on estimation accuracy.

Evaluation of Plasma Lipocalin-2 as a Predictor of Etiology and Severity in Adult Patients with Community-Acquired Pneumonia.

The aim of this study was to evaluate the diagnostic performance of plasma Lipocalin-2 (LCN2) concentration in adult patients with community-acquired pneumonia (CAP) to determine its etiology, severity and prognosis. A prospective observational study involving adults with CAP from November 2015 to May 2017 was conducted. Plasma LCN2 concentration was measured upon admission by a modified enzyme immunoassay coupled with chemiluminescence (Architect, Abbott Laboratories). The diagnostic performance of LCN2, C-reactive protein (CRP) and white blood cell to predict bacterial CAP was assessed. A total of 130 patients with CAP were included: 71 (54.6%) bacterial CAP, 42 (32.3%) unknown origin CAP and 17 (13.1%) viral CAP. LCN2 was higher in bacterial CAP than in non-bacterial CAP (122.0 vs. 89.7 ng/mL, respectively) (p = 0.03) with a limited ability to distinguish bacterial and non-bacterial CAP (AUROC: 0.62 [95% CI 0.52-0.72]). The LCN2 cutoff ≥ 204 ng/mL predicted the presence of pneumococcal bacteremia with an AUROC of 0.74 (sensitivity 70%, specificity 79.1%). Regarding severity, as defined by CURB-65 and PSI scores, there was a significant linear trend in the mean concentration of LCN2, exhibiting a shift from the low-risk to the intermediate-risk and high-risk group (p < 0.001 and 0.001, respectively). LCN2 concentration was associated with severity in adult patients with CAP. However, its utility as a biomarker to discriminate viral and bacterial etiology in CAP is limited.

Risk factors associated with inappropriate empirical antimicrobial treatment in bloodstream infections. A cohort study.

Introduction: Bloodstream infections (BSI) are a major cause of mortality all over the world. Inappropriate empirical antimicrobial treatment (i-EAT) impact on mortality has been largely reported. However, information on related factors for the election of i-EAT in the treatment of BSI in adults is lacking. The aim of the study was the identification of risk-factors associated with the use of i-EAT in BSI. Methods: A retrospective, observational cohort study, from a prospective database was conducted in a 400-bed acute-care teaching hospital including all BSI episodes in adult patients between January and December 2018. The main outcome variable was EAT appropriation. Multivariate analysis using logistic regression was performed. Results: 599 BSI episodes were included, 146 (24%) received i-EAT. Male gender, nosocomial and healthcare-associated acquisition of infection, a high Charlson Comorbidity Index (CCI) score and the isolation of multidrug resistant (MDR) microorganisms were more frequent in the i-EAT group. Adequation to local guidelines' recommendations on EAT resulted in 91% of appropriate empirical antimicrobial treatment (a-EAT). Patients receiving i-EAT presented higher mortality rates at day 14 and 30 when compared to patients with a-EAT (14% vs. 6%, p = 0.002 and 22% vs. 9%, p < 0.001 respectively). In the multivariate analysis, a CCI score ≥3 (OR 1.90 (95% CI 1.16-3.12) p = 0.01) and the isolation of a multidrug resistant (MDR) microorganism (OR 3.79 (95% CI 2.28-6.30), p < 0.001) were found as independent risk factors for i-EAT. In contrast, female gender (OR 0.59 (95% CI 0.35-0.98), p = 0.04), a correct identification of clinical syndrome prior to antibiotics administration (OR 0.26 (95% CI 0.16-0.44), p < 0.001) and adherence to local guidelines (OR 0.22 (95% CI 0.13-0.38), p < 0.001) were identified as protective factors against i-EAT. Conclusion: One quarter of BSI episodes received i-EAT. Some of the i-EAT related factors were unmodifiable (male gender, CCI score ≥3 and isolation of a MDR microorganism) but others (incorrect identification of clinical syndrome before starting EAT or the use of local guidelines for EAT) could be addressed to optimize the use of antimicrobials.

Enhanced NSAIDs Solubility in Drug-Drug Formulations with Ciprofloxacin.

Drug-drug salts are a kind of pharmaceutical multicomponent solid in which the two co-existing components are active pharmaceutical ingredients (APIs) in their ionized forms. This novel approach has attracted great interest in the pharmaceutical industry since it not only allows concomitant formulations but also has proved potential to improve the pharmacokinetics of the involved APIs. This is especially interesting for those APIs that have relevant dose-dependent secondary effects, such as non-steroidal anti-inflammatory drugs (NSAIDs). In this work, six multidrug salts involving six different NSAIDs and the antibiotic ciprofloxacin are reported. The novel solids were synthesized using mechanochemical methods and comprehensively characterized in the solid state. Moreover, solubility and stability studies, as well as bacterial inhibition assays, were performed. Our results suggest that our drug-drug formulations enhanced the solubility of NSAIDs without affecting the antibiotic efficacy.

Two Compensation Strategies for Optimal Estimation in Sensor Networks with Random Matrices, Time-Correlated Noises, Deception Attacks and Packet Losses.

Due to its great importance in several applied and theoretical fields, the signal estimation problem in multisensor systems has grown into a significant research area. Networked systems are known to suffer random flaws, which, if not appropriately addressed, can deteriorate the performance of the estimators substantially. Thus, the development of estimation algorithms accounting for these random phenomena has received a lot of research attention. In this paper, the centralized fusion linear estimation problem is discussed under the assumption that the sensor measurements are affected by random parameter matrices, perturbed by time-correlated additive noises, exposed to random deception attacks and subject to random packet dropouts during transmission. A covariance-based methodology and two compensation strategies based on measurement prediction are used to design recursive filtering and fixed-point smoothing algorithms. The measurement differencing method-typically used to deal with the measurement noise time-correlation-is unsuccessful for these kinds of systems with packet losses because some sensor measurements are randomly lost and, consequently, cannot be processed. Therefore, we adopt an alternative approach based on the direct estimation of the measurement noises and the innovation technique. The two proposed compensation scenarios are contrasted through a simulation example, in which the effect of the different uncertainties on the estimation accuracy is also evaluated.

Improvement of pneumococcal pneumonia diagnosis using quantitative real-time PCR targeting lytA in adult patients: a prospective cohort study.

OBJECTIVES: The aim of the study was to assess the performance of real-time PCR targeting the lytA gene (rtPCR-lytA) in plasma, urine and nasopharyngeal (NP) samples for the diagnosis of pneumococcal community-acquired pneumonia (P-CAP). METHODS: Prospective observational study including all consecutive adults with CAP from November 2015 to May 2017. P-CAP was defined if pneumococcus was identified using conventional methods (CM) and/or a positive rtPCR-lytA was detected in blood, urine or NP samples (NP cut-off ≥8000 copies/mL). Diagnostic performance of each test was calculated. RESULTS: A total of 133 individuals with CAP were included. Of these, P-CAP was diagnosed in 62 (46.6%). The proportion of P-CAP diagnosed by rtPCR-lytA methods was significantly higher than that diagnosed by CM (87.1% versus 59.7%, p 0.005). The rtPCR-lytA identified Streptococcus pneumoniae in 25 patients (40.3% of all individuals with P-CAP) whose diagnosis would have been missed by CM. NP-rtPCR-lytA allowed diagnosis of 62.3% of P-CAP. A nasopharyngeal colonization density ≥2351 copies/mL predicted P-CAP diagnosis (area under the curve = 0.82, sensitivity 83.3%, specificity 80.9%). There was a positive correlation between increasing bacterial load in blood and CURB-65 score (Spearman correlation coefficient r = 0.4, p 0.001), pneumonia severity index (r = 0.3, p 0.02) and time to clinical stability (r = 0.33, p 0.01). Median bacterial load in blood was higher in P-CAP patients with bacteraemia (0.65 × 103 versus 0 × 103 copies/mL, p 0.002), intensive care unit admission (0.68 × 103 versus 0 × 103 copies/mL, p 0.04) or mechanical ventilation (7.45 × 103 versus 0 × 103 copies/mL, p 0.04). CONCLUSIONS: The use of rtPCR-lytA methods significantly increased the diagnosis of P-CAP compared with CM. Nasopharyngeal swabs rtPCR-lytA detection, with an accurate cut-off value, was the most promising among molecular methods for the diagnosis of P-CAP.

Molecular Characterization of Imported and Autochthonous Dengue in Northeastern Spain.

Dengue is the most significant arbovirus worldwide and a public health threat to non-endemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global circulation of dengue in endemic areas. The primary travel-related case of the 2018 autochthonous transmission was not identified, but the molecular analysis revealed dengue serotype 1, genotype I of Asian origin. Our results highlight the diversity of imported dengue virus strains and the role of molecular epidemiology in supporting arbovirus surveillance programs.

Deciphering the H-Bonding Preference on Nucleoside Molecular Recognition through Model Copper(II) Compounds.

The synthetic nucleoside acyclovir is considered an outstanding model of the natural nucleoside guanosine. With the purpose of deepening on the influence and nature of non-covalent interactions regarding molecular recognition patterns, three novel Cu(II) complexes, involving acyclovir (acv) and the ligand receptor N-(2-hydroxyethyl)ethylenediamine (hen), have been synthesized and thoroughly characterized. The three novel compounds introduce none, one or two acyclovir molecules, respectively. Molecular recognition has been evaluated using single crystal X-ray diffraction. Furthermore, theoretical calculations and other physical methods such as thermogravimetric analysis, infrared and UV-Vis spectroscopy, electron paramagnetic resonance and magnetic measurements have been used. Theoretical calculations are in line with experimental results, supporting the relevance of the [metal-N7(acv) + H-bond] molecular recognition pattern. It was also shown that (hen)O-H group is used as preferred H-donor when it is found within the basal coordination plane, since the higher polarity of the terminal (hen)O-H versus the N-H group favours its implication. Otherwise, when (hen)O-H occupies the distal coordination site, (hen)N-H groups can take over.

A Two-Phase Distributed Filtering Algorithm for Networked Uncertain Systems with Fading Measurements under Deception Attacks.

In this paper, the distributed filtering problem is addressed for a class of discrete-time stochastic systems over a sensor network with a given topology, susceptible to suffering deception attacks, launched by potential adversaries, which can randomly succeed or not with a known success probability, which is not necessarily the same for the different sensors. The system model integrates some random imperfections and features that are frequently found in real networked environments, namely: (1) fading measurements; (2) multiplicative noises in both the state and measurement equations; and (3) sensor additive noises cross-correlated with each other and with the process noise. According to the network communication scheme, besides its own local measurements, each sensor receives the measured outputs from its adjacent nodes. Based on such measurements, a recursive algorithm is designed to obtain the least-squares linear filter of the state. Thereafter, each sensor receives the filtering estimators previously obtained by its adjacent nodes, and these estimators are all fused to obtain the desired distributed filter as the minimum mean squared error matrix-weighted linear combination of them. The theoretical results are illustrated by a simulation example, where the efficiency of the developed distributed estimation strategy is discussed in terms of the error variances.

Higher accuracy of genotypic identification compared to phenotyping in the diagnosis of coagulase-negative staphylococcus infection in orthopedic surgery.

PURPOSE: To determine whether Repetitive Extragenic Palindromic PCR (rep-PCR) genotyping can improve the diagnosis of coagulase-negative staphylococcal (CoNS) orthopaedic infections in comparison to phenotyping. METHODS: Prospective study comparing the results of phenotypic/genotypic (rep-PCR) testing in patients with suspected CoNS infection. Each strain was analysed using both methods. Strains identified as identical in ≥2 samples were considered as pathogenic. RESULTS: 255 CoNS strains from 52 surgical episodes were included. Infection was diagnosed by phenotyping in 38(73%) cases and by genotyping in 40(77%). The Kappa index was 0.59. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for phenotyping (vs. rep-PCR) were: 88%, 75%, 92%, and 64%. 5/14(36%) of cases not considered as true infections by phenotyping were diagnosed as infections with genotyping. In a subgroup of 203 strains from 41 surgical procedures with orthopaedic implants, the kappa index was 0.68. Sensitivity, Specificity, PPV, and NPV for phenotyping were: 93%, 73%, 90% and 80%. Again, 2/10 episodes in which CoNS were considered non-infective by phenotyping were diagnosed as infected by genotyping. CONCLUSIONS: Rep-PCR genotyping can identify identical CoNS strains that differ in their phenotype and should be used as a complementary technique. One-third of infected cases may be misdiagnosed without genotypic analysis.

Relationship between skin and urine colonization and surgical site infection in the proximal femur fracture: a prospective study.

PURPOSE: Antibiotic prophylaxis is routinely used in the surgical management of proximal femur fractures. The role of bacterial colonization of the skin and urine in the development of deep surgical site infections (SSI) is yet to be elucidated. This study aimed to evaluate the role of previous skin and urine colonization in the development of deep SSI after a proximal femoral fracture surgery. METHODS: We conducted a prospective observational study in 326 patients > 64 years old, who were scheduled to surgery. Cultures from skin samples of the surgical site and from urine were performed prior to the procedure, and cefazoline was administered as prophylaxis. RESULTS: Skin microbiota was isolated in 233 (71.5%) cases; 8 (2.5%) samples were positive for other bacteria, and 85 (26%) were negative. Of 236 urine samples, 168 were negative or contaminated (71.2%), and 68 (28.8%) were positive, being 58/236 for Enterobacterales (24.6%). Acute deep SSI were diagnosed in nine out of 326 patients (2.7%), and two (22%) were infected by Gram-negative bacilli. Of the 9 cases, normal skin microbiota was isolated in 7 (78%), and the remaining two were negative. Seven cases had negative or contaminated urine cultures, and the one with E. coli did not correlate with SSI bacteria. CONCLUSION: In our elderly hip fracture population, most patients harbored normal skin microbiota, and Enterobacterales urine cultures were positive in one-quarter of cases. There was no relationship between skin colonization, urine culture, and deep SSI. We therefore do not believe that our patients would benefit from modifying the current antibiotic prophylaxis.

High clonal diversity of ESBL-producing Klebsiella pneumoniae isolates from clinical samples in a non-outbreak situation. A cohort study.

Background: Klebsiella pneumoniae has been responsible for a large number of clonal hospital outbreaks. However, some epidemiological changes have been observed since the emergence of CTX-M enzymes in K. pneumoniae. Aim: To analyse the transmission dynamics of Extended Spectrum ß-Lactamase-producing Klebsiella pneumoniae (ESBL-Kp) in an acute care hospital. Methods: In 2015 a prospective cohort study was conducted. All new consecutive adult patients with ESBL-Kp isolates in all clinical samples were included. Patients with a previous known infection/colonization by ESBL-Kp and patients in high risk areas (e.g., intensive care units) were excluded. Cross-transmission was defined as the carriage of a clonally-related ESBL-Kp between newly diagnosed patients who shared the same ward for ≥48 h with another case, within a maximum time window of 4 weeks. ESBL-production was confirmed using the double-disk diffusion method and PCR. Clonal relationships were investigated by rep-PCR and multilocus sequence typing (MLST). Results: Sixty ESBL-Kp isolates from 60 patients were included and analysed. Infections and colonizations were classified as hospital-acquired (52%), healthcare-related (40%) or community-acquired (8%).High genetic diversity was detected. When epidemiological clinical data were combined with the rep-PCR, the patterns identified did not show any cases of cross-transmission. ESBL-Kp were detected in 12.5% of environmental samples. No clonal relationship could be established between environmental reservoirs and patients. The genetic mechanism detected in all strains was associated with blaCTX-M genes, and 97% were CTX-M-15. Conclusions: The dynamics of ESBL-K. pneumoniae isolated in our setting could not be explained by clonal transmission from an index patient. A polyclonal spread of ESBL-Kp was identified.

Molecular and supramolecular recognition patterns in ternary copper(II) or zinc(II) complexes with selected rigid-planar chelators and a synthetic adenine-nucleoside.

Four ternary metal-complexes with Cu(II) or Zn(II), 2,6-pyridine-dicarboxylate (pdc) or glycyl-glycinate (GG) and the synthetic nucleoside 9-(2-hydroxyethyl)adenine (9heade) have been synthesized and studied by single-crystal X-ray diffraction and other physical methods. Relevant supramolecular assemblies found in the solid state structures have been further studied using density functional theory (DFT) calculations. In addition, the energetic features of the non-covalent interactions as well as the cooperativity effects have been calculated and characterized using the non-covalent interaction plot computational tool. Compounds trans-[Cu(pdc)(9heade)(H2O)2]·3H2O (1a) and [Cu(pdc)(9heade)(H2O)]·H2O (1b), trans-[Zn(pdc)(9heade)(H2O)2] (2), share the same molecular recognition pattern consisting in the cooperation of the metal-N7(9heade) bond and an interligand (9heade)N6-H···O(pdc) interaction, regardless of the nature of the metal, the coordination environment and the water content. At a supramolecular level, these compounds exhibit pairs of complex molecules linked by H-bonds and interesting anion-π/π-π/π-anion assemblies (in 1a and 1b) or the unprecedented π-π interactions (in 2), involving the purine moieties or the exocyclic -6NH2 purine groups, respectively. Compound 3, {[Cu(GG)(9heade)(H2O)·Cu(GG)(µ2-9heade)]·8H2O}n, consists in asymmetric dinuclear complex units (Cu···Cu 7.83 Å) that connect with adjacent ones by pairs of very weak Cu-O(carboxylate) bonds (Cu···Cu 3.81 Å) building a polymeric chain. The supramolecular transition from a single molecule to dinuclear units and finally a polymeric chain is also observed in the electron paramagnetic resonance spectra and discussed from a structural point of view as well as by DFT calculations. The unprecedented N7 and µ-N7,O(ol) metal binding patterns of 9heade differs from that recently reported (µ-N1,N7) in a Cd(II) polymer.

Paromomycin is superior to metronidazole in Dientamoeba fragilis treatment.

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013-2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem.

Subjective Emotional Well-Being, Emotional Intelligence, and Mood of Gifted vs. Unidentified Students: A Relationship Model.

Subjective well-being (SWB) is a basic component of the health of children and adolescents. Studies of SWB in gifted students are scarce and show contradictory results. Some researchers consider these groups to be vulnerable, and according to some reports they are more often involved in situations of harassment as victims and/or harassers. Emotional intelligence (EI) is related to SWB and can be a protective factor in these situations. However, the underlying mechanism remains relatively unexplored, especially in the affective dimension of SWB. The present study develops and tests a model for the mediating role of mood in the relationship between EI and SWB. The participants were 273 Spanish students aged 8 to 18 years, distributed into two samples: sample 1, gifted students, and sample 2, unidentified students. The results showed that (1) gifted students exhibited lower scores in EI (specifically, in clarity) and SWB (specifically, in positive experiences) and higher scores on the sadness dimension of mood states and that (2) EI was positively related to SWB, and mood was a significant mediator in the relationship between EI and SWB. The mediating role of the positive mood is given in both groups; however, the negative mood only mediates this relationship in gifted students. The results are discussed, theoretical and practical contributions to the literature are proposed, and implications for parents and teachers are suggested.

Covariance-Based Estimation for Clustered Sensor Networks Subject to Random Deception Attacks.

In this paper, a cluster-based approach is used to address the distributed fusion estimation problem (filtering and fixed-point smoothing) for discrete-time stochastic signals in the presence of random deception attacks. At each sampling time, measured outputs of the signal are provided by a networked system, whose sensors are grouped into clusters. Each cluster is connected to a local processor which gathers the measured outputs of its sensors and, in turn, the local processors of all clusters are connected with a global fusion center. The proposed cluster-based fusion estimation structure involves two stages. First, every single sensor in a cluster transmits its observations to the corresponding local processor, where least-squares local estimators are designed by an innovation approach. During this transmission, deception attacks to the sensor measurements may be randomly launched by an adversary, with known probabilities of success that may be different at each sensor. In the second stage, the local estimators are sent to the fusion center, where they are combined to generate the proposed fusion estimators. The covariance-based design of the distributed fusion filtering and fixed-point smoothing algorithms does not require full knowledge of the signal evolution model, but only the first and second order moments of the processes involved in the observation model. Simulations are provided to illustrate the theoretical results and analyze the effect of the attack success probability on the estimation performance.

Mediterranean spotted fever in the elderly: a prospective cohort study.

The objective of this study is to evaluate the characteristics and outcome of elderly patients with Mediterranean spotted fever (MSF). This study was a prospective observational cohort study of all adult cases with confirmed MSF treated in a teaching hospital (1984-2015) to compare the characteristics of elderly patients (> 65 years) with younger adults. We identified 263 adult patients with MSF, and 53 (20.2%) were elderly. Severe MSF was more frequent in the elderly (26.4% vs. 10.5%; p = 0.002). Gastrointestinal symptoms, impaired consciousness, lung infiltrate, oedema, acute hearing loss, raised alanine transaminase, hyponatremia, and thrombocytopenia occurred more frequently in elderly patients, and arthromyalgia occurred less frequently. Most patients were treated with a single-day doxycycline regimen (two oral doses of 200 mg for 1 day). All patients recovered uneventfully. Fever disappeared 2.55 ± 1.16 days after treatment initiation in elderly patients, and the remaining symptoms disappeared after 3.65 ± 1.42 days. These figures were similar to non-elderly patients. Severe MSF was more frequent in elderly patients. Some clinical manifestations occurred with different frequencies in the elderly compared with younger patients. Single-day doxycycline therapy is an effective and well-tolerated treatment for MSF in elderly patients.

Serotype, virulence profile, antimicrobial resistance and macrolide-resistance determinants in Streptococcus agalactiae isolates in pregnant women and neonates in Catalonia, Spain / Serotipo, perfil de virulencia, resistencia antimicrobiana y determinantes de la resistencia a macrólidos aislados de Streptococcus agalactiae en mujeres embarazadas y neonatos de Cataluña, España

INTRODUCTION: Streptococcus agalactiae, or group B streptococci (GBS), is the main aetiological agent of early neonatal sepsis in developed countries. This microorganism belongs to the gastrointestinal tract microbiota wherefrom it can colonize the vagina and be vertically transmitted to the child either before or at birth, and subsequently cause infection in the newborn. Approximately, 50% of newborns born to women with GBS become colonized, with 1-2% developing early neonatal infection if no preventive intervention is performed. The aim of this study was to characterize and compare serotypes, virulence factors and antimicrobial resistance of GBS isolates collected from pregnant women and newborns in several hospitals in Catalonia. METHODS: 242 GBS strains were analyzed including 95 colonizers and 68 pathogenic strains isolated from pregnant women, and 79 strains isolated from neonates with sepsis in order to determine serotype, virulence and antimicrobial resistance. RESULTS: Serotype distribution was different among the three groups, with serotypes Ia and II being significantly more frequent among colonizing strains (p = 0.001 and 0.012, respectively). Virulence factors bca and scpB were significantly more frequent among neonatal strains than pathogenic or colonizing strains (p = 0.0001 and 0.002, respectively). Pathogenic strains were significantly more resistant to erythromycin, clindamycin and azithromycin than their non-pathogenic counterparts. CONCLUSIONS: Taking into account that neonatal sepsis represents a significant problem on a global scale, epidemiological surveillance, antimicrobial resistance and GBS virulence at the local level could provide important knowledge about these microorganisms as well as help to improve treatment and prevent invasive infection caused by this microorganism

INTRODUCCIÓN: Streptococcus agalactiae o estreptococos del grupo B (SGB) es el principal agente etiológico de la sepsis neonatal temprana en los países desarrollados. Este microorganismo pertenece a la microbiota del tracto gastrointestinal desde donde puede colonizar la vagina y ser transmitido verticalmente al niño antes o al nacer y posteriormente causar infección en el recién nacido. Aproximadamente el 50% de los recién nacidos de mujeres embarazadas que albergan SGB se colonizan, con 1-2% desarrollando infección neonatal temprana si no se realiza intervención preventiva. El objetivo de este estudio fue caracterizar y comparar serotipos, factores de virulencia y la resistencia a los antimicrobianos de aislamientos de SGB de mujeres embarazadas y neonatos procedentes de varios hospitales de Cataluña. MÉTODOS: Se analizaron 242 cepas de SGB incluyendo 95 colonizadoras y 68 cepas patógenas aisladas de mujeres embarazadas y 79 cepas aisladas de neonatos con sepsis para determinar serotipo, virulencia y resistencia antimicrobiana. RESULTADOS: La distribución de los serotipos fue diferente entre los 3 grupos, siendo los serotipos Ia y II significativamente más frecuentes entre las cepas colonizadoras (p = 0,001 y 0,012, respectivamente). Los factores de virulencia bca y scpB fueron significativamente más frecuentes entre las cepas neonatales que entre las patógenas o colonizadoras (p = 0,0001 y 0,002, respectivamente). Las cepas patógenas fueron significativamente más resistentes a eritromicina, clindamicina y azitromicina que las no patógenas. CONCLUSIONES: Teniendo en cuenta que la sepsis neonatal es un problema importante a nivel mundial, la vigilancia de la epidemiología, la resistencia a los antimicrobianos y la virulencia del SGB a nivel local podría proporcionar un gran conocimiento de estos microorganismos y ayudar a mejorar el tratamiento y la prevención de la infección invasiva causada por este microorganismo

Rifampin Resistance in Staphylococci after Rifaximin Intake for Surgical Prophylaxis in Elective Colorectal Surgery.

The aim of our study was to determine whether rifampin resistance emerges in human skin staphylococci after oral intake of rifaximin for surgical prophylaxis. Rifampin-resistant staphylococci appeared on the skin of 32 out of 74 patients (43.2%) two weeks after prophylactic treatment with rifaximin. In all cases, the resistant strains were coagulase-negative staphylococci. The resistance completely reverted after three months. This study shows the emergence of transient resistance to rifampin after rifaximin intake.