[Development of clinical practice guidelines for patients with comorbidity and multiple diseases]. / Desarrollo de guías de práctica clínica en pacientes con comorbilidad y pluripatología.

The management of patients with comorbidity and polypathology represents a challenge for all healthcare systems. Clinical practice guidelines (CPGs) have limitations when applied to this population. The aim of this study is to propose the terminology and methodology for optimally approach comorbidity and polypathology in the CPGs. Based on a literature review, we suggest a number of proposals for the approach in different phases of CPG preparation, with special attention to the inclusion of clusters of comorbidity in the initial questions the implementation of indirect evidence, the burden of disease management for patients and their environment, when establishing recommendations, as well as the strategies of dissemination and implementation. These proposals should be developed in greater depth with the implication of more agents in order to have valid and useful tools for this population.

Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission.

Introduction: Preterm birth is a growing problem worldwide. Staying at a neonatal intensive care unit (NICU) after birth is critical for the survival of preterm infants whose feeding often requires the use of nasogastric enteral feeding tubes (NEFT). These can be colonized by hospital-associated pathobionts that can access the gut of the preterm infants through this route. Since the gut microbiota is the most impactful factor on maturation of the immune system, any disturbance in this may condition their health. Therefore, the aim of this study is to assess the impact of NEFT-associated microbial communities on the establishment of the gut microbiota in preterm infants. Material and methods: A metataxonomic analysis of fecal and NEFT-related samples obtained during the first 2 weeks of life of preterm infants was performed. The potential sharing of strains isolated from the same set of samples of bacterial species involved in NICU's outbreaks, was assessed by Random Amplification of Polymorphic DNA (RAPD) genotyping. Results: In the samples taken 48 h after birth (NEFT-1 and Me/F1), Staphylococcus spp. was the most abundant genera (62% and 14%, respectively) and it was latter displaced to 5.5% and 0.45%, respectively by Enterobacteriaceae. Significant differences in beta diversity were detected in NEFT and fecal samples taken at day 17 after birth (NEFT-3 and F3) (p = 0.003 and p = 0.024, respectively). Significant positive correlations were found between the most relevant genera detected in NEFT-3 and F3. 28% of the patients shared at least one RAPD-PCR profile in fecal and NEFT samples and 11% of the total profiles were found at least once simultaneously in NEFT and fecal samples from the same patient. Conclusion: The results indicate a parallel bacterial colonization of the gut of preterm neonates and the NEFTs used for feeding, potentially involving strain sharing between these niches. Moreover, the same bacterial RAPD profiles were found in neonates hospitalized in different boxes, suggesting a microbial transference within the NICU environment. This study may assist clinical staff in implementing best practices to mitigate the spread of pathogens that could threaten the health of preterm infants.

Human gut microbiota analysis of cystic fibrosis infants using metaproteomics.

We report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.

Human intestinal microbiome: Role in health and disease.

The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.

Non-diphtheriae Corynebacterium species: an emerging respiratory pathogen.

The purpose of the study was to describe the microbiological and clinical features of ten cases of lower respiratory tract infection due to Corynebacterium striatum, Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum. Respiratory samples were recovered from hospitalised patients who were diagnosed of pneumonia and exacerbations of chronic respiratory infections. The samples were Gram-stained and seeded on conventional bacterial growing media. Bacteria were identified by matrix-assisted linear desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was tested by the disk diffusion method. All patients presented an acute respiratory onset, most of them in the context of an underlying disease and/or immunosuppression. In all patients, the microscopical examination of Gram-stained respiratory samples showed numerous polymorphonuclear cells and Gram-positive bacilli, suggestive of the Corynebacterium morphotype. A pure culture growth of Corynebacterium was obtained in the majority (72 %) of samples. The conclusions are that non-diphtheriae Corynebacterium species are an emerging cause of respiratory infection among patients with chronic respiratory disease and/or immunosuppression, and cannot always be considered as mere colonisers. The microorganism's predominance in Gram-stained purulent respiratory samples together with abundant growth in the culture is the key for the microbiological diagnosis.

How Does Ball Possession Affect the Physical Demands in Spanish LaLiga? A Multilevel Approach.

Purpose: Using a multilevel approach, this study analyzed the relationship between ball possession and distance covered at different speed sections: total distance (TD), distance covered between 14.1-21 km·h-1 (MIRD), 21.1-24 km·h-1 (HIRD), and > 24.1 km·h-1 (VHIRD). Methods: The sample included 1,520 matches played by 80 Spanish professional soccer teams across four consecutive LaLiga seasons (from 2015/2016 to 2018/2019). Two observations were collected per match, one from each team, resulting in a total of 2,950 records (760 per season). Data were collected using Mediacoach®. Results: At match level (i.e., grand-mean centered), ball possession negatively predicted all distances covered. At team level (i.e., group-mean centered), ball possession negatively predicted total distance covered and distance covered between 14.1-21 km·h-1. Furthermore, cross-level interactions (Match X Team) in ball possession negatively predicted all distances covered at speeds above 14.1 km·h-1. Specifically, in high-possession teams, the negative relationship between match ball possession and distances traveled at all speed ranges above 14.1 km·h-1 was stronger than in teams with medium or low possession. Conversely, match ball possession was positively related todistance covered at low intensities, and negatively related at high intensities in low-possession teams. Conclusion: These findings show practitioners and researchers that the distances covered at different speed ranges depend on technical-tactical parameters such as ball possession.

Antibacterial activity of wine phenolic compounds and oenological extracts against potential respiratory pathogens.

AIMS: To investigate the effect of seven wine phenolic compounds and six oenological phenolic extracts on the growth of pathogenic bacteria associated with respiratory diseases (Pseudomonas aeruginosa, Staphylococcus aureus, Moraxella catarrhalis, Enterococcus faecalis, Streptococcus sp Group F, Streptococcus agalactiae and Streptococcus pneumoniae). METHODS AND RESULTS: Antimicrobial activity was determined using a microdilution method and quantified as IC(50) . Mor. catarrhalis was the most susceptible specie to phenolic compounds and extracts. Gallic acid and ethyl gallate were the compounds that showed the greatest antimicrobial activity. Regarding phenolic extracts, GSE (grape seed extract) and GSE-O (oligomeric-rich fraction from GSE) were the ones that displayed the strongest antimicrobial effects. CONCLUSIONS: Results highlight the antimicrobial properties of wine phenolic compounds and oenological extracts against potential respiratory pathogens. The antimicrobial activity of wine phenolic compounds was influenced by the type of phenolic compounds. Gram-negative bacteria were more susceptible than Gram-positive bacteria to the action of phenolic compounds and extracts; however, the effect was species-dependent. SIGNIFICANCE AND IMPACT OF STUDY: The ability to inhibit the growth of respiratory pathogenic bacteria as shown by several wine phenolic compounds and oenological extracts warrants further investigations to explore the use of grape and wine preparations in oral hygiene.

The relationship between running distance and coaches' perception of team performance in professional soccer player during multiple seasons.

This study analyzed how the physical movement profile of soccer matches evolved throughout a season by assessing the variability of different metrics depending on the season phase. In addition, the evolution of running distances was investigated in the relation to the team performance based on the coaches' perception. Games from four consecutives Spanish LaLiga seasons (n = 1520) were recorded using an optical tracking system (i.e., ChyronHego). Total distance (TD), distance covered between 14 and 21 km h-1 (MIRD), 21-24 km h-1 (HIRD), and > 24 km h-1 (VHIRD) were analyzed, as well as the number of efforts between 21 and 24 km h-1 (Sp21) and > 24 km h-1 (Sp24). Seasons were divided into four phases (P): P1 (matches 1-10), P2 (11-19), P3 (20-29), and P4 (30-38). Linear mixed models revealed that soccer players covered significantly greater distances and completed a higher number of sprints in P2 and P3. Also, team performance evaluated by soccer coaches was positively related to TD, HIRD, VHIRD and Sp21 in P1. A negative relationship was observed between team performance and distance covered at speeds below 21 km h-1 in P2 and P3. Team performance was negatively related to TD, MIRD, and HIRD, and Sp21 in P4. As conclusion, the team performance perceived by coaches is related to the movement profile throughout a season, and it significantly influences the evolution of soccer players' movement profiles. Specifically, it seems that the players of the best teams have the best physical performance at the beginning of the season with respect to the rest of the phases.

Consistency and identifiability of football teams: a network science perspective.

We investigated the ability of football teams to develop a particular playing style by looking at their passing patterns. Using the information contained in the pass sequences during matches, we constructed the pitch passing networks of teams, whose nodes are the divisions of the pitch for a given spatial scale and links account for the number of passes from region to region. We translated football passings networks into their corresponding adjacency matrices. We calculated the correlations between matrices of the same team to quantify how consistent the passing patterns of a given team are. Next, we quantified the differences with other teams' matrices and obtained an identifiability parameter that indicates how unique are the passing patterns of a given team. Consistency and identifiability rankings were calculated during a whole season, allowing to detect those teams of a league whose passing patterns are different from the rest. Furthermore, we found differences between teams playing at home or away. Finally, we used the identifiability parameter to investigate what teams imposed their passing patterns over the rivals during a given match.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus from different population groups in Argentina.

OBJECTIVES: In Latin America, methicillin-resistantStaphylococcus aureus (MRSA) is a leading cause of nosocomial infections. Limited studies have addressed the molecular epidemiology of MRSA clones in Argentina, characterised by continuous human migratory movements. The aim of this study was to describe the MRSA epidemiology, including distinct patient populations from different regions of the country. METHODS: MRSA strains were collected in epidemiological studies conducted from 2009 to 2015 in three cities (Formosa, Córdoba and Tucumán) and involving four population groups: community adult patients; hospitalised adults; hospitalised children; and healthy children (nasal colonisation). Antimicrobial susceptibility testing, SCCmec and Panton-Valentine leukocidin (PVL) typing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed. RESULTS: A total of 120 MRSA isolates were recovered with an important population diversity in the groups studied; in community adult patients, MRSA isolates corresponded to ST5, ST267 and ST1619; from hospitalised adults they were ST97, ST5, ST72, ST125, ST200, ST647, ST747, ST935 and ST2941; from hospitalised children they were ST5, ST30, ST34, ST1163 and ST1619; and from colonised children they were ST5, ST125, ST34, ST100, ST1619, ST207 and ST1163. Results of SCCmec typing showed SCCmec I, SCCmec IIIA, SCCmec IV and SCCmec ND associated or not with PVL genes. CONCLUSIONS: MRSA genetic lineages have differing distribution in the three regions. The most prevalent was ST5 in colonisation, community and invasive settings. Here we describe ST34-SCCmec IV clone for the first time in the hospitalised paediatric population. These findings contribute to the understanding of epidemiological changes in recent years.

Global CO2 emissions from dry inland waters share common drivers across ecosystems.

Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y-1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle.

Systematic review of kidney transplantation functional predictors. / Revisión sistemática de los métodos predictores de la funcionalidad del trasplante renal.

CONTEXT: Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. OBJECTIVE: The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. ACQUISITION OF EVIDENCE: We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. SUMMARY OF THE EVIDENCE: The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. DISCUSSION: None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. CONCLUSIONS: We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney.

Cytocompatibility, biofilm assembly and corrosion behavior of Mg-HAP composites processed by extrusion.

In this work the cytocompatibility of pure magnesium and Mg-xHAP composites (x=5, 10 and 15wt%) fabricated by powder metallurgy routes has been investigated. The materials were produced from raw HAP powders with particle mean sizes of 6µm (S-xHAP) or 25µm (L-xHAP). The biocompatibility study has been performed for MC3T3 cells (osteoblasts/osteoclasts) and L929 fibroblasts. The results indicate that S-Mg (pure magnesium), S-10HAP and L-10HAP composites are the materials with the best biocompatibility. The ability of S. aureus bacteria to assemble biofilms was also evaluated. Biofilm formation assays showed that these materials are not particular prone to colonization and biofilm assembly is strain dependent. The corrosion resistance of S-Mg, S-10HAP and L-10HAP materials immersed in the media used for the cells culture has also been analyzed. Different trends in the corrosion resistance have been found: S-Mg and S-10HAP show a very high resistance to corrosion whereas the corrosion of L-10HAP steadily increases with time.

Processing and mechanical characteristics of magnesium-hydroxyapatite metal matrix biocomposites.

Magnesium/hydroxyapatite composites were produced by conventional extrusion and their mechanical behavior studied under uniaxial compression at room temperature. The results evidence the capability of the HA for strengthening the Mg material, lowering its microstructural anisotropy and inhibiting deformation twinning. They also reveal that the ECAP processing is effective for improving the grain structure and reducing the crystallographic texture of these composites, giving rise to a significant enhancement of their yield strength and microhardness although the ultimate compressive stress worsens. The analysis of the strain hardening rate of the flow curves demonstrates that the HA addition and the ECAP processing are also effective in inhibiting non-basal dislocation slip.

Gut dysbiosis and neuroimmune responses to brain infection with Theiler's murine encephalomyelitis virus.

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice.

Genetic relatedness and antimicrobial resistance determinants among clinical isolates of enterococci from Cuba.

This study describes the genetic relationships and antimicrobial resistance determinants found among 99 clinical isolates of enterococci from 15 different hospitals in Cuba. Pulsed-field gel electrophoresis SmaI analysis demonstrated a high degree of genetic diversity. A limited number of multiresistant Enterococcus faecalis clones, showing resistance to three or more families of antimicrobial agents, were detected simultaneously in different institutions, suggesting inter-hospital circulation of selected clones, and/or selection of particular clones following their introduction into the hospital environment. Antimicrobial resistance determinants, including erm(B), aac(6')-aph(2'), aph(3'), ant(6), vanB (E. faecalis) and vanA (Enterococcus faecium) were detected by PCR in various isolates.

Genetic and phenotypic differences among Enterococcus faecalis clones from intestinal colonisation and invasive disease.

This study investigated the differences among Enterococcus faecalis isolates from the intestinal compartment of healthy volunteers (n = 36), intensive care unit (ICU) patients (n = 29) and blood isolates (n = 31) from the same institution, in comparison with seven epidemic clones from other institutions. In general, isolates from colonised ICU patients and from bacteraemic patients showed higher rates of antimicrobial resistance than isolates from colonised healthy volunteers, particularly for erythromycin and aminoglycosides. The proportion of isolates/clone was 1.05 in the community, 2.63 in the ICU, and 1.47 among bacteraemic cases, suggesting low clonal variation in ICUs. Two clones, RENC1 and RENC2, were frequently found as intestinal colonisers of ICU patients, and RENC1 was also found to colonise healthy volunteers. These two clones were a cause of bacteraemia in the institution studied, and RENC2 was also detected in various other Spanish hospitals. Both RENC1 and RENC2 were esp+, bacteriocin producers, and were resistant to all antibiotics tested except vancomycin and ampicillin. RENC1 produced haemolysin whereas RENC2 produced protease. The ace, agg, cylA, esp and gelE genes were more common among colonising strains from ICU patients than among isolates from individuals in the community. In both colonised groups (ICUs and the community), 40-50% of isolates harbouring the gelE and cylA genes did not express the corresponding phenotypes. Thus, the study indicated that particular E. faecalis clones might be well-adapted to hospital environments, and that surveillance should be directed specifically towards rapid detection of these disseminating clones in order to prevent infections and clonal spread.

Comparison of different methods for identification of species of the genus Raoultella: report of 11 cases of Raoultella causing bacteraemia and literature review.

The genus Raoultella was excised from Klebsiella in 2001, but difficulties in its identification may have led to an underestimation of its incidence and uncertainty on its pathogenic role. Recently, clinical reports involving Raoultella have increased, probably through the introduction of mass-spectrometry in clinical microbiology laboratories and the development of accurate molecular techniques. We performed a retrospective analysis using our blood culture collection (2011-14) to identify Raoultella isolates that could have been erroneously reported as Klebsiella. PCR and gene sequencing of highly specific chromosomal class A ß-lactamase genes was established as the reference method, and compared with 16S rRNA and rpoß sequencing, as well as matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS), MicroScan Walkaway system and API20E biochemical identification. MALDI-TOF and rpoß correctly identified all Raoultella isolates, whereas 16S rRNA provided inconclusive results, and MicroScan and API20E failed to detect this genus. The analysis of the clinical characteristics of all Raoultella bacteraemia cases reported in the literature supports the role of Raoultella as an opportunistic pathogen that causes biliary tract infections in elderly patients who suffer from some kind of malignancy or have undergone an invasive procedure. Two salient conclusions are that Raoultella shows tropism for the biliary tract and so its identification could help clinicians to suspect underlying biliary tract disease when bacteraemia occurs. Concomitantly, as most phenotypic identification systems are not optimized for the identification of Raoultella, the use of MALDI-TOF or additional phenotypic tests is recommended for the reliable identification of this genus.

The rise of ampicillin-resistant Enterococcus faecium high-risk clones as a frequent intestinal colonizer in oncohaematological neutropenic patients on levofloxacin prophylaxis: a risk for bacteraemia?

Levofloxacin extended prophylaxis (LEP), recommended in oncohaematological neutropenic patients to reduce infections, might select resistant bacteria in the intestine acting as a source of endogenous infection. In a prospective observational study we evaluated intestinal emergence and persistence of ampicillin-resistant Enterococcus faecium (AREfm), a marker of hospital adapted high-risk clones. AREfm was recovered from the faeces of 52 patients with prolonged neutropenia after chemotherapy, at admission (Basal), during LEP, and twice weekly until discharge (Pos-LEP). Antibiotic susceptibility, virulence traits and population structure (pulsed-field gel electrophoresis and multilocus sequence typing) were determined and compared with bacteraemic isolates. Gut enterococcal population was monitored using a quantitative PCR quantification approach. AREfm colonized 61.4% of patients (194/482 faecal samples). Sequential AREfm acquisition (25% Basal, 36.5% LEP, 50% Pos-LEP) and high persistent colonization rates (76.9-89.5%) associated with a decrease in clonal diversity were demonstrated. Isolates were clustered into 24 PFGE-patterns within 13 sequence types, 95.8% of them belonging to hospital-associated Bayesian analysis of population structure subgroups 2.1a and 3.3a. Levofloxacin resistance and high-level streptomycin resistance were a common trait of these high-risk clones. AREfm-ST117, the most persistent clone, was dominant (60.0% isolates, 32.6% patients). It presented esp gene and caused 18.2% of all bacteraemia episodes in 21% of patients previously colonized by this clone. In AREfm-colonized patients, intestinal enrichment in the E. faecium population with a decline in total bacterial load was observed. AREfm intestinal colonization increases during hospital stay and coincides with enterococci population enrichment in the gut. Dominance and intestinal persistence of the ST117 clone might increase the risk of bacteraemia.