Chronic rhinosinusitis is associated with prolonged SARS-CoV-2 RNA shedding in upper respiratory tract samples: A case-control study.

BACKGROUND: SARS-CoV-2, the COVID-19 causative agent, has infected millions of people and killed over 1.6 million worldwide. A small percentage of cases persist with prolonged positive RT-PCR on nasopharyngeal swabs. The aim of this study was to determine risk factors for prolonged viral shedding amongst patient's basal clinical conditions. METHODS: We have evaluated all 513 patients attended in our hospital between 1 March and 1 July. We have selected all 18 patients with prolonged viral shedding and compared them with 36 sex-matched randomly selected controls. Demographic, treatment and clinical data were systematically collected. RESULTS: Global median duration of viral clearance was 25.5 days (n = 54; IQR, 22-39.3 days), 48.5 days in cases (IQR 38.7-54.9 days) and 23 days in controls (IQR 20.2-25.7), respectively. There were not observed differences in demographic, symptoms or treatment data between groups. Chronic rhinosinusitis and atopy were more common in patients with prolonged viral shedding (67%) compared with controls (11% and 25% respectively) (P < 0.001 and P = 0.003). The use of inhaled corticosteroids was also more frequent in case group (P = 0.007). Multivariate analysis indicated that CRS (odds ratio [OR], 18.78; 95% confidence interval [95%CI], 3.89-90.59; P < 0.001) was independently associated with prolonged SARS-CoV-2 RNA shedding in URT samples, after adjusting for initial PCR Ct values. CONCLUSION: We found that chronic rhinosinusitis and atopy might be associated with increased risk of prolonged viral shedding. If confirmed in prospective trials, this finding might have clinical implications for quarantine duration due to increased risk of pandemic spread.

Biomarkers of post-match recovery in semi-professional and professional football (soccer).

High-level football (soccer) players face intense physical demands that result in acute and residual fatigue, impairing their physical performance in subsequent matches. Further, top-class players are frequently exposed to match-congested periods where sufficient recovery times are not achievable. To evaluate training and recovery strategies, the monitoring of players' recovery profiles is crucial. Along with performance and neuro-mechanical impairments, match-induced fatigue causes metabolic disturbances denoted by changes in chemical analytes that can be quantified in different body fluids such as blood, saliva, and urine, thus acting as biomarkers. The monitoring of these molecules might supplement performance, neuromuscular and cognitive measurements to guide coaches and trainers during the recovery period. The present narrative review aims to comprehensively review the scientific literature on biomarkers of post-match recovery in semi-professional and professional football players as well as provide an outlook on the role that metabolomic studies might play in this field of research. Overall, no single gold-standard biomarker of match-induced fatigue exists, and a range of metabolites are available to assess different aspects of post-match recovery. The use of biomarker panels might be suitable to simultaneously monitoring these broad physiological processes, yet further research on fluctuations of different analytes throughout post-match recovery is warranted. Although important efforts have been made to address the high interindividual heterogeneity of available markers, limitations inherent to these markers might compromise the information they provide to guide recovery protocols. Further research on metabolomics might benefit from evaluating the long-term recovery period from a high-level football match to shed light upon new biomarkers of post-match recovery.

Compositional Aspects of Beverages Designed to Promote Hydration Before, During, and After Exercise: Concepts Revisited.

Hypohydration can impair aerobic performance and deteriorate cognitive function during exercise. To minimize hypohydration, athletes are recommended to commence exercise at least euhydrated, ingest fluids containing sodium during long-duration and/or high-intensity exercise to prevent body mass loss over 2% and maintain elevated plasma osmolality, and rapidly restore and retain fluid and electrolyte homeostasis before a second exercise session. To achieve these goals, the compositions of the fluids consumed are key; however, it remains unclear what can be considered an optimal formulation for a hydration beverage in different settings. While carbohydrate-electrolyte solutions such as sports drinks have been extensively explored as a source of carbohydrates to meet fuel demands during intense and long-duration exercise, these formulas might not be ideal in situations where fluid and electrolyte balance is impaired, such as practicing exercise in the heat. Alternately, hypotonic compositions consisting of moderate to high levels of electrolytes (i.e., ≥45 mmol/L), mainly sodium, combined with low amounts of carbohydrates (i.e., <6%) might be useful to accelerate intestinal water absorption, maintain plasma volume and osmolality during exercise, and improve fluid retention during recovery. Future studies should compare hypotonic formulas and sports drinks in different exercise settings, evaluating different levels of sodium and/or other electrolytes, blends of carbohydrates, and novel ingredients for addressing hydration and rehydration before, during, and after exercise.

Treatment of infections caused by carbapenemase-producing Enterobacterales.

Antibiotic resistance is one of the main menaces to public and individual health worldwide. In the last two decades, an increase in the detection of carbapenem-resistant Enterobacterales has been reported. The treatment of infections caused by these strains is a therapeutic challenge. The use of carbapenems may be beneficial depending on MIC value and source of infection. New drugs, with different activity against the different classes of carbapenemases, are developed showing significant benefits.

Dietary Complex and Slow Digestive Carbohydrates Promote Bone Mass and Improve Bone Microarchitecture during Catch-Up Growth in Rats.

Catch-up growth is a process that promotes weight and height gains to recover normal growth patterns after a transient period of growth inhibition. Accelerated infant growth is associated with reduced bone mass and quality characterized by poor bone mineral density (BMD), content (BMC), and impaired microarchitecture. The present study evaluated the effects of a diet containing slow (SDC) or rapid (RDC) digestible carbohydrates on bone quality parameters during the catch-up growth period in a model of diet-induced stunted rats. The food restriction period negatively impacted BMD, BMC, and microarchitecture of appendicular and axial bones. The SDC diet was shown to improve BMD and BMC of appendicular and axial bones after a four-week refeeding period in comparison with the RDC diet. In the same line, the micro-CT analysis revealed that the trabecular microarchitecture of tibiae and vertebrae was positively impacted by the dietary intervention with SDC compared to RDC. Furthermore, features of the cortical microstructure of vertebra bones were also improved in the SDC group animals. Similarly, animals allocated to the SDC diet displayed modest improvements in growth plate thickness, surface, and volume compared to the RDC group. Diets containing the described SDC blend might contribute to an adequate bone formation during catch-up growth thus increasing peak bone mass, which could be linked to reduced fracture risk later in life in individuals undergoing transient undernutrition during early life.

Beneficial Effects of Bovine Milk Exosomes in Metabolic Interorgan Cross-Talk.

Extracellular vesicles are membrane-enclosed secreted vesicles involved in cell-to-cell communication processes, identified in virtually all body fluids. Among extracellular vesicles, exosomes have gained increasing attention in recent years as they have unique biological origins and deliver different cargos, such as nucleic acids, proteins, and lipids, which might mediate various health processes. In particular, milk-derived exosomes are proposed as bioactive compounds of breast milk, which have been reported to resist gastric digestion and reach systemic circulation, thus being bioavailable after oral intake. In the present manuscript, we critically discuss the available evidence on the health benefits attributed to milk exosomes, and we provide an outlook for the potential future uses of these compounds. The use of milk exosomes as bioactive ingredients represents a novel avenue to explore in the context of human nutrition, and they might exert important beneficial effects at multiple levels, including but not limited to intestinal health, bone and muscle metabolism, immunity, modulation of the microbiota, growth, and development.

Neural crest regionalisation for enteric nervous system formation: implications for Hirschsprung's disease and stem cell therapy.

Midbrain, hindbrain and vagal neural crest (NC) produced abundant enteric nervous system (ENS) in co-grafted aneural hindgut and midgut, using chick-quail chorio-allantoic membrane grafts, forming complete myenteric and submucosal plexuses. This ability dropped suddenly in cervical and thoracic NC levels, furnishing an incomplete ENS in one or both plexuses. Typically, one plexus was favoured over the other. This deficiency was not caused by lower initial trunk NC number, yet overloading the initial number decreased the deficiency. No qualitative difference in neuronal and glial differentiation between cranial and trunk levels was observed. All levels formed HuC/D+ve, NOS+ve, ChAT+ve, and TH-ve enteric neurons with SoxE+ve, GFAP+ve, and BFABP+ve glial cells. We mathematically modelled a proliferative difference between NC populations, with a plexus preference hierarchy, in the context of intestinal growth. High proliferation achieved an outcome similar to cranial NC, while low proliferation described the trunk NC outcome of incomplete primary plexus and even more deficient secondary plexus. We conclude that cranial NC, relative to trunk NC, has a positionally-determined proliferation advantage favouring ENS formation. This has important implications for proposed NC stem cell therapy for Hirschsprung's disease, since such cells may need to be optimised for positional identity.

In vitro activity of imipenem/relebactam against Gram-negative clinical isolates in two Spanish tertiary hospitals.

OBJECTIVE: The aim of this study was to analyze the activity of the imipenem-relebactam combination (IMI/REL) against a collection of multidrug-resist Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii clinical isolates. METHODS: The study was conducted in two tertiary hospitals in Spain and included 192 clinical isolates of these 3 genera (139 resistant and 53 susceptible to IMI). The MICs for IMI with and without REL (at a fixed concentration of 4 mg/L) were determined by a standard broth microdilution method according to international recommendations. RESULTS: All IMI-susceptible E. coli strains were also susceptible to IMI/REL. Enterobacterales resistant to IMI due to the production of carbapenemases, the MIC50 and MIC90 decreased from 64/256 with IMI to 8/64 mg/L with IMI/REL. This high activity was principally detected among isolates with KPC enzymes. Enterobacterales with class B carbapenemases, P. aeruginosa carrying VIM carbapenemase and A. baumannii strains showed no changes on IMI MIC50 or MIC90 after adding REL. Among P. aeruginosa strains without carbapenemase the MIC for IMI/REL was reduced between 1 to 5 dilutions. CONCLUSIONS: IMI/REL showed high activity against the strains that carry Klebsiella pneumoniae carbapenemase (KPC) and against carbapenem-resistant P. aeruginosa unrelated to the VIM enzyme, mainly AmpC beta lactamase associated with impermeability. Against strains carrying oxacillinase 48 (OXA-48) associated with extended-spectrum beta-lactamase (ESBL), IMI/REL presented activity only slightly better than IMI and had no beneficial effect superior to IMI against A. baumannii.

Role of Dlx genes in craniofacial morphogenesis: Dlx2 influences skeletal patterning by inducing ectomesenchymal aggregation in ovo.

Dlx homeodomain transcription factors are expressed in neural crest-derived mesenchyme of the pharyngeal arches and are required for patterning of the craniofacial skeleton. However, the cellular and molecular mechanisms by which Dlx factors control skeletogenesis in the facial primordia are unclear. We have investigated the function of Dlx2 and Dlx5 by sustained misexpression in ovo. We find that RCAS-Dlx2- and RCAS-Dlx5-infected avian embryos exhibit very similar patterns of local, stereotypical changes in skeletal development in the upper jaw. The changes include ectopic dermal bone along the jugal arch, and ectopic cartilages that develop between the quadrate and the trabecula. The ectopic cartilage associated with the trabecula is reminiscent of a normally occurring element in this region in some bird taxa. Analysis of the distribution of RCAS-Dlx2-infected cells suggests that Dlx2 induces aggregation of undifferentiated mesenchyme, which subsequently develops into the ectopic skeletal elements. Comparison of infected embryos with restricted or widespread misexpression, and of embryos in which Dlx genes were delivered to migratory or postmigratory neural crest, indicate that there are limited regions of competence in which the ectopic elements can arise. The site-specific differentiation program that the aggregates undergo may be dependent on local environmental signals. Our results suggest that Dlx factors mediate localization of ectomesenchymal subpopulations within the pharyngeal arches and in doing so define where skeletogenic condensations will arise. Consequently, variation in Dlx expression or activity may have influenced the morphology of jaw elements during vertebrate evolution.

Application of fluorescence in situ hybridization technique to detect simazine-degrading bacteria in soil samples.

We propose a new approach to evaluate the natural attenuation capacity of soil by using fluorescence in situ hybridization (FISH). A specific oligonucleotide probe AtzB1 was designed based on the sequence data of the atzB gene involved in the hydrolytic deamination of s-triazines; this gene, located in a multiple copy plasmid was detected by the optimized FISH protocol. Two agricultural soils (Lodi and Henares) with a history of simazine treatments, and two natural soils (Soto and Monza), without previous exposure to simazine, were studied. AtzB1 probe-target cells were found only in the agricultural soils and, in a greater percentage, in the Lodi soil, compared to the Henares one. Moreover, the greatest percentage of AtzB1 probe-target cells in Lodi was accompanied by a greater mineralization rate, compared to the Henares soil. The FISH method used in this study was suitable for the detection of simazine-degrading bacteria and could be a useful indicator of the potential of soil bioremediation.

[Comparative study of refractive errors in simple congenital myogenic ptosis and control children]. / Estudio comparativo de los defectos de refracción en niños con ptosis miogénica congénita simple y niños control.

PURPOSE: To study refractive errors in children with relatively serious congenital myogenic ptosis and to carry out a comparative study in relation to control children in our population. METHODS: We included 35 children with simple congenital myogenic ptosis, 27 of them had minor ptosis, 3 moderate ptosis and 5 serious ptosis. Thirty-five children were also in the control group. One eye of every subject was included, the worst eye in subjects of the ptosis group and an eye selected at random in control group subjects. A comparative study of refractive data in every group was carried out, using the Student's t-test, ANOVA and Chi square or Yates correction tests. RESULTS: We obtained significant differences between children with ptosis and controls in average spherical equivalent (3.08/1.49), in average absolute sphere (2.80/1.42) and in average absolute cylinder (0.81/0.31) (p<0.05). We also observed a relation between the presence of astigmatism and the seriousness of ptosis (chi2=6.88>5.99), and between the need for optical correction and the presence of ptosis (chi2=15.92>3.84). CONCLUSIONS: Children with simple congenital myogenic ptosis in our enviroment have greater refractive errors than control children. Ptosis children require optical correction more frequently than control. The more serious the ptosis, the more likelihood there is of having astigmatism.

Fungal biofilms: From bench to bedside.

Biofilms cause recurrent invasive infections that are difficult to eradicate because of their high resistance to antimicrobials and host defence mechanisms. Fungal biofilm-related infections are associated with high mortality rates. Although current guidelines recommend catheter removal for catheter-related bloodstream infections due to Candida species, several studies have shown that the efficacy of the antifungal lock technique. The use of combinations of antifungal agents may improve the management of biofilm-related fungal infections and prevent the emergence of resistance associated with monotherapy. Since the presence of mixed bacterial-fungal biofilm infections is very prevalent, a combination of antibacterial and antifungal agents should be considered.

Construction of a BAC library and its application to the identification of simple sequence repeats in peach [ Prunus persica (L.) Batsch].

The Rosaceae contains many economically important crop species, but their genomes are not well characterized, and comparative genetic mapping lags well behind that of other families. To facilitate genome comparisons and gene discovery in the Rosaceae, we have begun the development of genomic resources for peach as the model genome for this family. First, we developed a simplified, cost-effective method for constructing BAC libraries, particularly appropriate for plant species of relatively minor economic importance. Second, we used the library to investigate the abundance and local distribution of simple sequence repeats (SSRs) in peach. Our results indicate that microsatellite loci are locally much more highly abundant than previously estimated, and BAC sequencing results suggest that microsatellite repeats are not randomly distributed within gene-containing regions of the peach genome. This makes it relatively easy to identify SSRs in peach by hybridization to BAC clones, and even by random sequencing of BAC clones, not known a priori to contain SSRs.

Time course of fungal removal of lipophilic extractives from Eucalyptus globulus wood.

Free and esterified sitosterol, the main lipophilic constituents of eucalypt wood extractives, have been associated with the formation of pitch deposits during manufacturing of environmentally-sound paper pulp from Eucalyptus globulus wood. These, and other lipophilic compounds, were analyzed by gas chromatography-mass spectrometry in the course of wood treatments (up to 7 weeks) with four extractive-degrading fungi in order to optimize biotechnological control of pitch deposition in eucalypt pulp (with moderate loss of wood weight). In contrast to commercialized fungi used in pitch control, which are not able to degrade sitosterol, the fungi investigated in this paper produced a rapid decline of both free and esterified sterols in wood. The degradation rate of steroid hydrocarbons and squalene was moderate, and the amount of steroid ketones (probably formed during oxidative degradation of steroids) and triglycerides increased at different stages of wood treatment. Up to 95% removal of total steroids (including free and esterified sterols, steroid ketones and steroid hydrocarbons) by fungi was obtained at the end of wood treatment under the solid-state fermentation conditions used. The most promising results from the point of view of industrial applicability, however, were obtained after 1-2 weeks of treatment with either Phlebia radiata or Poria subvermispora, which enabled 70% steroid removal with a moderate wood weight loss of 1-4%.

Immobilized native bacteria as a tool for bioremediation of soils and waters: implementation and modeling.

Based on 3,4-dihydroxyphenylacetate (3,4-DHPA) dioxygenase amino acid sequence and DNA sequence data for homologous genes, two different oligonucleotides were designed. These were assayed to detect 3,4-DHPA related aromatic compound-degrading bacteria in soil samples by using the FISH method. Also, amplification by PCR using a set of ERIC primers was assayed for the detection of Pseudomonas GCH1 strain, which used in the soil bioremediation process. A model was developed to understand and predict the behavior of bacteria and pollutants in a bioremediation system, taking into account fluid dynamics, molecular/cellular scale processes, and biofilm formation.

[Chronic obstructive lung disease in the general population. An epidemiologic study performed in Guipúzcoa]. / Enfermedad pulmonar obstructiva crónica en la población general. Estudio epidemiológico realizado en Guipúzcoa.

To perform a cross-sectional descriptive study of chronic obstructive pulmonary disease in the general population. We studied 600 men aged between 40 and 60 from a random sample (69.9% of the total, 76.6% eligible subjects). Each subject answered a questionnaire, underwent spirometric testing and measurement of CO in expired air. Smokers accounted for 50.8% of the sample, although only 24.8% of the population had CO levels in expired air greater than 10 ppm. The prevalence of chronic bronchitis was 9.2%. Forty subjects (6.8%), only 25% of whom had previously undergone spirometry, met the criteria for air flow limitation. Air flow limitation was associated with chronic bronchitis and smoking, which were also mutually associated. Our data underline the need to combat smoking, given its relation with chronic bronchitis and airflow limitation, as well as to perform spirometry more routinely, mainly in smokers or patients with symptoms of chronic bronchitis.

[Serum adenosine deaminase in human immunodeficiency virus infection. Its relationship with CD4+ lymphocytes and beta 2-microglobulin]. / Adenosina desaminasa sérica en la infección por el virus de la inmunodeficiencia humana. Su relación con los linfocitos CD4+ y la beta 2-microglobulina.

BACKGROUND: The activity of the deaminase adenosine enzyme (ADA) has principally been related with the functionalism and replication of the T lymphocytes. Its serum behavior and possible clinical use in infection by the human immunodeficiency virus type 1 (HIV-1) was studied. METHODS: A multicenter study in which the serum values of ADA were examined and compared with those of two reference markers (CD4+ lymphocytes and beta 2-microglobulin) in 35 presumably healthy donors used as controls, in 60 intravenous drug users (IVDU) seronegative for HIV-1, in 69 HIV-1 asymptomatic seropositive intravenous drug users (HIV-1+) and in 48 patients with AIDS. RESULTS: The serum values of ADA were as follows: control group 10.9 +/- 4.2 U/I; IVDU group 17.6 +/- 7.4 U/I; asymptomatic HIV-1+ group 32.7 +/- 10.2 U/I, AIDS group 46.2 +/- 18.2 U/I. Differences between the different groups were statistically significant in themselves and in relation to the control group. A negative correlation was observed (r = 0.47, p < 0.01) with the number of CD4+ lymphocytes and a positive correlation was found with respect to beta 2-microglobulin (r = 0.76, p < 0.001). The values of serum ADA activity in patients with AIDS and tuberculosis (47.4 +/- 17.2 U/I) were not significantly higher (p < 0.05) to those of patients with AIDS without this second infection (45.9 +/- 19.3 U/I). CONCLUSIONS: Serum deaminase adenosine may be a useful evolutive marker for human immunodeficiency virus type 1 given that its activity increases significantly in infected patients in agreement with the grade of immunodeficiency and its values correlate well with those of reference markers (CD4+ lymphocytes and beta 2-microglobulin).

High invasiveness of pneumococcal serotypes included in the new generation of conjugate vaccines.

The implementation of the seven-valent pneumococcal conjugate vaccine, PCV7, has resulted in significant changes in the pneumococcal population being carried and causing disease. We aimed to determine the invasive disease potential of serotypes causing invasive paediatric disease in the era of conjugate vaccines in Catalonia, Spain, and their potential coverage by the 13-valent pneumococcal conjugate vaccine, PCV13. As a secondary objective, we evaluated whether implementation of PCV7 had resulted in significant changes in the invasive disease potential of the most frequent serotypes circulating in the area. Two pneumococcal collections obtained from children admitted to the University Hospital Sant Joan de Déu (Barcelona, Spain) between 2007 and 2011 were compared: a first set of 159 invasive disease isolates, and a second set of 209 nasopharyngeal isolates recovered from healthy children admitted for minor surgery. The most common invasive serotypes were 1 (24.5%, n = 39), 19A (21.2%, n = 34), 5 (8.8%, n = 14), 7F (8.8%, n = 14) and 3 (5%, n = 8). The most common serotypes in carriage were 19A (10%, n = 21), 6C (9%, n = 19), 23B (8.1%, n = 17), 6A (7.6%, n = 16) and 19F (6.2%, n = 13). A significantly higher propensity to cause invasive disease was observed for serotypes 1, 3, 5, 7F and 19A, all of which are included in PCV13. After false-discovery-rate correction, the results were robust for serotypes 1, 5, 7F and 19A. Non-PCV13 serotypes had a low invasive disease potential. Our data reinforce the need for continuous surveillance and should encourage efforts to introduce universal vaccination with PCV13 in children in our region.