Structural and Cellular Insights into the l,d-Transpeptidase YcbB as a Therapeutic Target in Citrobacter rodentium, Salmonella Typhimurium, and Salmonella Typhi Infections.

The bacterial cell wall plays a key role in viability and is an important drug target. The cell wall is made of elongated polymers that are cross-linked to one another to form a load-bearing mesh. An alternative cell wall cross-linking mechanism used by the l,d-transpeptidase YcbB has been implicated in the stress-regulated roles of ß-lactam resistance, outer membrane defect rescue, and typhoid toxin release. The role for this stress-linked cross-linking in the context of a host infection was unclear. Here, we resolve the crystallographic structures of both Salmonella Typhi YcbB and Citrobacter rodentium YcbB acylated with ertapenem that delineate the conserved structural characteristics of YcbB. In parallel, we show that the general involvement of YcbB in peptidoglycan reinforcement under conditions of bacterial outer envelope stress does not play a significant role in acute infections of mice by C. rodentium and S Typhimurium. Cumulatively, in this work we provide a foundation for the development of novel YcbB-specific antibacterial therapeutics to assist in treatment of increasingly drug-resistant S Typhi infections.

Hexachlorocyclohexane phytoremediation using Eucalyptus dunnii of a contaminated site in Argentina.

In 1996, a diagnostic study performed in a 16-ha field located in Buenos Aires Province (Argentina), where a chemical industry produced 1,2,3,4,5,6-hexachlorocyclohexane (HCH) from 1960 to 1978, showed contamination with HCH ranging from 10 to 20,000 mg kg-1 dry soil (706.4 mg kg-1 average). For remediation purposes, a forestation plan was put into practice in 1997 employing approximately 12,300 Eucalyptus dunnii seedlings which by 2016 where fully grown into trees that formed a forest where local fauna can be found. Midterm analysis done in 2005, when E. dunnii trees had developed into 8-10 m high trees, indicated that HCH was incorporated into leaves and logs and soil phytoremediation was progressing. Final quantitation analysis of HCH in soil performed in 2016 demonstrated that the 97.2% of the field area was effectively decontaminated with 98.1% overall average efficiency. Thus, this work is the first global example of a successful employment of E. dunnii trees for HCH phytoremediation purposes at field scale. These results may encourage other researchers to test the ability of E. dunnii to phytoremediate soils contaminated with other chlorinated compounds like polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs).

Design and development of low cost polyurethane biopolymer based on castor oil and glycerol for biomedical applications.

In the current study, we present the synthesis of novel low cost bio-polyurethane compositions with variable mechanical properties based on castor oil and glycerol for biomedical applications. A detailed investigation of the physicochemical properties of the polymer was carried out by using mechanical testing, ATR-FTIR, and X-ray photoelectron spectroscopy (XPS). Polymers were also tested in short term in-vitro cell culture with human mesenchymal stem cells to evaluate their biocompatibility for potential applications as biomaterial. FTIR analysis confirmed the synthesis of castor oil and glycerol based PU polymers. FTIR also showed that the addition of glycerol as co-polyol increases crosslinking within the polymer backbone hence enhancing the bulk mechanical properties of the polymer. XPS data showed that glycerol incorporation leads to an enrichment of oxidized organic species on the surface of the polymers. Preliminary investigation into in vitro biocompatibility showed that serum protein adsorption can be controlled by varying the glycerol content with polymer backbone. An alamar blue assay looking at the metabolic activity of the cells indicated that castor oil based PU and its variants containing glycerol are non-toxic to the cells. This study opens an avenue for using low cost bio-polyurethane based on castor oil and glycerol for biomedical applications.

Migraine education brochures and patient-perceived satisfaction.

INTRODUCTION: Brochures are commonly used as educational tools in daily neurological practice. They are provided to increase the general population's knowledge of a specific disease and also to combat sources of erroneous information. Surveys are the most commonly used method of ascertaining user satisfaction with services received. OBJECTIVES: This study will assess patient-perceived satisfaction and provide feedback to measure the comprehensibility and overall utility of an educational brochure on migraine. MATERIAL AND METHODS: Open prospective multicentre study of a group of patients diagnosed with migraine in neurology clinics in Alicante province. During the initial visit, each patient received a migraine brochure prepared by the Valencian Society of Neurology's study group for headaches (CEFALIC). During a follow-up visit, they were then asked to fill out a personal survey on the overall quality of the information in the brochure. RESULTS: We included a total of 257 patients diagnosed with migraine (83% episodic migraine; 17% chronic migraine); mean age was 37.6 years. Two hundred seven patients confirmed having read the brochure (80.5%); 50 patients (19.5%) either forgot to read it or had no interest in doing so. The brochure seemed interesting and easy to understand according to 90% of the patients. Seventy-six per cent of the respondents stated that reading the brochure increased their overall knowledge of migraine, while 50% of the patients found the brochure useful for improving migraine control. CONCLUSIONS: Patients found the migraine educational brochure to be comprehensible, a means of increasing overall knowledge of the disease, and useful for increasing control over migraines. Evaluations of the educational brochures that we provide to our patients with migraine should be studied to discover the causes of dissatisfaction, determine the level of quality of service, and investigate potential areas for improvement.

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

Retrospective analysis of levetiracetam compared to phenytoin for seizure prophylaxis in adults with traumatic brain injury.

BACKGROUND: Phenytoin is standard of care for seizure prophylaxis following traumatic brain injury (TBI). Levetiracetam, an alternative antiepileptic drug, is utilized for seizure prophylaxis despite limited data supporting its use. OBJECTIVE: Our primary outcome was post-TBI seizure activity measured by electroencephalogram (EEG) for levetiracetam versus phenytoin. Secondary outcomes were length of intensive care unit (ICU) stay, requirement for additional antiepileptic drugs (AED), and drug and monitoring costs. METHODS: A retrospective review was performed of patients admitted to neurosurgical or surgical trauma ICU. Adult patients with at least 1 day of EEG monitoring were included. Patients were excluded if they had history of epilepsy, prior TBI, less than 48 hours of AED therapy, or additional AED prior to EEG monitoring. RESULTS: A total 90 patients met inclusion criteria, with 18 receiving levetiracetam and 72 receiving phenytoin. Prevalence of EEG-confirmed seizure activity was similar between the levetiracetam and phenytoin groups (28% vs 29%; P = .99). ICU length of stay (13 vs 18 days; P = .28), time to EEG-confirmed seizure activity (4 vs 6 days; P = .24), and duration of seizure prophylaxis (9 vs 14 days; P = .18) were also similar. The median daily cost of levetiracetam therapy was $43 compared to $55 for phenytoin therapy and monitoring (P = .08). When all anticonvulsant therapy and monitoring were included, costs were lower for the levetiracetam group ($45 vs $83; P = .02). CONCLUSION: Levetiracetam may provide an alternative treatment option for seizure prevention in TBI patients in the ICU. Total antiepileptic drug and monitoring costs were lower for levetiracetam patients.

Hexachlorocyclohexane chemical remediation of a contaminated site in Argentina.

This work describes the complete decontamination of three parcels of a dump site located in Lomas de Zamora county, Buenos Aires province (Argentina) heavily polluted with hexachorocyclohexane (HCH), where phytoremediation, successful in the surrounding areas, was ineffective. HCH contained in contaminated soil (10 g/kg average) was oxidized with sodium persulfate activated with citric acid chelated Fe(II). This chemical remediation process required treatment in situ in each parcel of approximately 10900 tons total of soil that were mechanically removed and initially mixed with 1750 tons of sodium persulfate. The mixture was then transferred to the excavation site, and 105 tons of ferrous sulfate and 35 tons of citric acid were finally added. The process, started in January 2011 and completed in February 2016, was very effective since chemical remediation average efficiency in the three parcels was higher than 99.99%. To the best of our knowledge this work is the first demonstration that persulfate oxidation activated with citric acid chelated Fe(II) can be successfully applied for field remediation of a relatively large area.

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit.

BACKGROUND AND OBJECTIVE: Patients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40-49%, HF-mrEF) left ventricular ejection fraction. METHODS: An analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. RESULTS: A total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03-1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03-1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. CONCLUSIONS: This study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.

The invader Carpobrotus edulis promotes a specific rhizosphere microbiome across globally distributed coastal ecosystems.

The importance of plant-microbe interactions to the success of invasive plants has rarely been studied at a global scale. Carpobrotus edulis (L.) N. E. Br is an aggressive invader in many areas around the world, forming dense mats in coastal environments. In an approach at a large geographical scale, over a wide latitudinal and climatic range, we tested the ability of C. edulis to alter the local bacterial and fungal community structure and microbial activity in eight invaded coastal locations. The factors invasiveness and geographical location had a significant effect on the soil microbiota, the microbial community composition and structure from the rhizosphere of native and C. edulis plants being distinct in every location. The effect of the invader on all the chemical, physico-chemical, and microbiological properties studied depended on the invaded location. The soil bacterial and fungal community composition and structure were related to the soil available nutrients and mean annual rainfall, and those of the soil bacterial community were also linked to the soil respiration and latitude. Overall, our results reveal that the ability of the invader C. edulis to alter soil microbial community structure harboring a specific microbiome was widespread across a large invaded range - leading to concurring changes in the rhizosphere microbial functioning, such as nutrient cycling.

Stable interference of EWS-FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target.

BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS-FLI1 target genes still remain unknown and many have been identified in heterologous model systems. METHODS: We have developed a stable RNA interference model knocking down EWS-FLI1 in the Ewing sarcoma cell line TC71. Gene expression analyses were performed to study the effect of RNA interference on the genetic signature of EWS-FLI1 and to identify genes that could contribute to tumourigenesis. RESULTS: EWS-FLI1 inhibition induced apoptosis, reduced cell migratory and tumourigenic capacities, and caused reduction in tumour growth. IGF-1 was downregulated and the IGF-1/IGF-1R signalling pathway was impaired. PBK/TOPK (T-LAK cell-originated protein kinase) expression was decreased because of EWS-FLI1 inhibition. We showed that TOPK is a new target gene of EWS-FLI1. TOPK inhibition prompted a decrease in the proliferation rate and a dramatic change in the cell's ability to grow in coalescence. CONCLUSION: This is the first report of TOPK activity in Ewing sarcoma and suggests a significant role of this MAPKK-like protein kinase in the Ewing sarcoma biology.

Comparison of single-reflection near-infrared and attenuated total reflection mid-infrared spectroscopies to identify and monitor hydrocarbons spilled in the marine environment.

The capability of single-reflection near-IR (NIR) spectroscopy to differentiate, characterize and monitor the fate of a set of hydrocarbons spilled in the marine environment was compared with that of multiple-reflection horizontal attenuated total reflection mid-IR (ATR-MIR) spectroscopy. Multivariate pattern recognition techniques [principal component analysis (PCA), multivariate polynomial regression, cluster analysis and potential curves] were applied to unravel the major trends of the weathering processes of four generic types of crude oils and two heavy fuel oils spilled under controlled conditions for almost 4 months. A chemical interpretation of the NIR spectra related the weathering processes and the PCA loadings, which had not already been done in the literature. Weathering for both light and heavy products was characterized by a contrast among the linear aliphatic structures (more volatile and easy to degrade) and the branched and aromatic structures (more recalcitrant). Potential curves were applied to model each product and determine objectively whether unknown samples could be classified correctly. Polynomial regression on the PCA scores was employed to evaluate the time elapsed from the oil spillage to its sampling; this represents a new approach to assess the age of a hydrocarbon lump. In general, NIR spectroscopy yielded good results when light crude oils were studied, whereas ATR-MIR spectroscopy led to satisfactory results for both light and heavy products.

The unspecificity of the relationships between the invasive Pennisetum setaceum and mycorrhizal fungi may provide advantages during its establishment at semiarid Mediterranean sites.

The involvement of mutualistic plant-fungal interactions in invasion processes, especially in some climatic regions including semiarid areas, has not been sufficiently investigated. We compared the arbuscular mycorrhizal fungi (AMF) communities hosted by the invasive plant Pennisetum setaceum with those from the co-occurring native Hyparrhenia hirta at five Mediterranean semiarid locations with different edaphic characteristics. Illumina technology was used to investigate the AMF communities in the roots. The subsequent multivariate analysis showed that native and non-native host plants shared a similar AMF community, whereas the invaded locations differed in AMF communities harbored in the plant roots. The indicator species analysis revealed the absence of indicator virtual taxa for the fungal communities of the roots of native or invasive plants. In contrast, different numbers of indicator species were recorded in different sampling locations. According to the canonical correspondence analysis, the variability in the AMF communities between sampling sites was related to changes in soil total carbon, electrical conductivity, respiration, and protease and urease activities. These findings reveal the unspecificity of P. setaceum in relation to its association with the AMF community encountered in the invaded locations, which could have facilitated its successful establishment and spread.

Arbuscular mycorrhizal fungi inoculation mediated changes in rhizosphere bacterial community structure while promoting revegetation in a semiarid ecosystem.

The main goal of this study was to assess the effect of the inoculation of four autochthonous shrub species with the arbuscular mycorrhizal (AM) fungus Rhizophagus intraradices on the rhizosphere bacterial community and to ascertain whether such an effect is dependent on the host plant species. Additionally, analysis of rhizosphere soil chemical and biochemical properties was performed to find relationships between them and the rhizosphere bacterial communities. Non-metric multidimensional scaling analysis and subsequent permutational multivariate analysis of variance revealed differences in bacterial community composition and structure between non-inoculated and inoculated rhizospheres. Moreover, an influence of the plant species was observed. Different bacterial groups were found to be indicator taxonomic groups of non-inoculated and inoculated rhizospheres, Gemmatimonadetes and Anaerolineaceae, respectively, being the most notable indicators. As shown by distance based redundancy analysis, the shifts in bacterial community composition and structure mediated by the inoculation with the AM fungus were mainly related to changes in plant nutrients and growth parameters, such as the shoot phosphorus content. Our findings suggest that the AM fungal inoculum was able to modify the rhizosphere bacterial community assemblage while improving the host plant performance.

Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults?

BACKGROUND: Regular physical activity is a promising strategy to treat and prevent cognitive decline. The mechanisms that mediate these benefits are not fully clear but physical activity is thought to attenuate the harmful effects of chronic psychological stress and hypercortisolism on cognition. However, the circadian pattern of cortisol secretion is complex and it is not known which aspects are most closely associated with increased cognitive function and better physical performance. This is the first study to simultaneously measure cognitive function, the diurnal cycle of salivary cortisol and physical performance in older adults, without cognitive impairment (n = 30) and with amnestic Mild Cognitive Impairment (aMCI) (n = 30). RESULTS: Regression analysis showed that better cognitive function was associated with better physical performance. A greater variance in cortisol levels across the day from morning to evening was associated with better cognitive function and physical performance. CONCLUSIONS: The results support the idea that a more dynamic cortisol secretion pattern is associated with better cognitive function and physical performance even in the presence of cognitive impairment, but our results could not confirm a mediating role in this relationship.

Arbuscular mycorrhizal fungal assemblages in biological crusts from a Neotropical savanna are not related to the dominant perennial Trachypogon.

Knowledge of the arbuscular mycorrhizal fungal assemblages in the Trachypogon savanna ecosystems is very important to a better understanding of the ecological processes mediated by this soil microbial group that affects multiple ecosystem functions. Considering the hypothesis that the biocrusts can be linked to vegetation through the arbuscular fungi mycelial network, the objectives proposed in this study were to determine (i) whether there are arbuscular mycorrhizal fungi (AMF) in the biocrusts (ii) whether arbuscular mycorrhizal fungal assemblages are linked to the Trachypogon patches, and (iii) whether the composition of the assemblages is related to soil properties affected by microbiological activity. The community structure of the AMF was investigated in three habitats: rhizospheric soil and roots of Trachypogon vestitus, biological soil crusts, and bare soil. The canonical correspondence analysis showed that two soil properties related to enzymatic activity (protease and ß-glucosidase) significantly affected the community composition of the AMF. The biocrusts in the Venezuelan savanna are colonized by an AM fungal community linked to that of the bare soil and significantly different from that hosted by the roots of the surrounding T. vestitus, suggesting that assemblages of AMF in biocrusts might be related more closely to those of annual plant species appearing in favorable conditions.

[An analysis of avoidable admissions to a neurology service]. / Análisis de los ingresos evitables en un servicio de neurología.

INTRODUCTION: Inappropriate admissions to a hospital service generate unnecessary costs for our health care service. Most admissions to a hospital service come from the emergency department. The presence of a neurologist to attend hospital emergencies would be an important factor allowing admission criteria to be streamlined. AIMS: To determine the number of avoidable admissions (AA) in a neurology service, and to define their characteristics. PATIENTS AND METHODS: We conducted a prospective, descriptive study of the admissions that took place in the Neurology Service of the Hospital General Universitario de Elche (Alicante) over a period of three months. The neurologist determines whether admission is indicated or not. We collected demographic data concerning the patient, the admission diagnosis, neurological diagnosis, the reason for appropriateness and the reason for AA. RESULTS: A total of 250 admissions were attended; 65 were considered to be AA (26%). The most frequent diagnoses in the cases of AA were non-neurological (32.3%), clinical findings (15.4%), neuropathies (10.8%) and epilepsy (10.8%). The reasons leading to AA were non-neurological and transfer to another service (30.8%), follow-up by neurology outpatient department (NOD) (29.2%), NOD study (21.5%), non-neurological and discharge (16.9%) and not specified (1.5%). The mean length of stay in the case of AA was 4.3 days. CONCLUSIONS: The number of AA in our service is higher than that found in other studies. On-duty neurologists, streamlining outpatient diagnostic testing and the design of flexible schedules for outpatient care would reduce the amount of resources that are used, while at the same time increasing the quality of the health service.

Osteoma de oído medio asintomático

Resumen El osteoma de oído medio es un tumor poco común, de crecimiento lento y características benignas. Frecuentemente cursa de forma asintomática y su diagnóstico suele ser casual como en el caso que exponemos. Se presenta el caso de un varón de 26 años, que consultó por odinofagia y otalgia derecha en el contexto de una infección de vía aérea alta. Al explorarlo mediante otoscopia se visualizó en el oído izquierdo una lesión blanquecina y redondeada retrotimpánica compatible con osteoma de oído medio. El tratamiento de elección en pacientes con osteomas de oído medio sintomáticos es la cirugía. Sin embargo, en pacientes asintomáticos el seguimiento es la opción más recomendada.

Abstract The middle ear osteoma is a benign, infrequent, slow-growing tumor. This lesion is frequently asymptomatic and its diagnosis is usually accidental, as the case presented here. We present a case of a 26-year-old man who consulted for odynophagia and right ear pain in the context of an upper airway infection. By otoscopy in the left ear, we observed a whitish retrotympanic lesion that was compatible with a middle ear osteoma. To manage symptomatic patients with middle ear osteomas, surgery is the treatment of first choice. Nevertheless, for asymptomatic patients, follow up is recommended.