Exploring the functionality and conservation of Alba proteins in Trypanosoma cruzi: A focus on biological diversity and RNA binding ability.

Trypanosoma cruzi is the causative agent of Chagas disease, as well as a trypanosomatid parasite with a complex biological cycle that requires precise mechanisms for regulating gene expression. In Trypanosomatidae, gene regulation occurs mainly at the mRNA level through the recognition of cis elements by RNA-binding proteins (RBPs). Alba family members are ubiquitous DNA/RNA-binding proteins with representatives in trypanosomatid parasites functionally related to gene expression regulation. Although T. cruzi possesses two groups of Alba proteins (Alba1/2 and Alba30/40), their functional role remains poorly understood. Thus, herein, a characterization of T. cruzi Alba (TcAlba) proteins was undertaken. Physicochemical, structural, and phylogenetic analysis of TcAlba showed features compatible with RBPs, such as hydrophilicity, RBP domains/motifs, and evolutionary conservation of the Alba-domain, mainly regarding other trypanosomatid Alba. However, in silico RNA interaction analysis of T. cruzi Alba proteins showed that TcAlba30/40 proteins, but not TcAlba1/2, would directly interact with the assayed RNA molecules, suggesting that these two groups of TcAlba proteins have different targets. Given the marked differences existing between both T. cruzi Alba groups (TcAlba1/2 and TcAlba30/40), regarding sequence divergence, RNA binding potential, and life-cycle expression patterns, we suggest that they would be involved in different biological processes.

Enzymatic Metabolic Switches of Astrocyte Response to Lipotoxicity as Potential Therapeutic Targets for Nervous System Diseases.

Astrocytes play a pivotal role in maintaining brain homeostasis. Recent research has highlighted the significance of palmitic acid (PA) in triggering pro-inflammatory pathways contributing to neurotoxicity. Furthermore, Genomic-scale metabolic models and control theory have revealed that metabolic switches (MSs) are metabolic pathway regulators by potentially exacerbating neurotoxicity, thereby offering promising therapeutic targets. Herein, we characterized these enzymatic MSs in silico as potential therapeutic targets, employing protein-protein and drug-protein interaction networks alongside structural characterization techniques. Our findings indicate that five MSs (P00558, P04406, Q08426, P09110, and O76062) were functionally linked to nervous system drug targets and may be indirectly regulated by specific neurological drugs, some of which exhibit polypharmacological potential (e.g., Trifluperidol, Trifluoperazine, Disulfiram, and Haloperidol). Furthermore, four MSs (P00558, P04406, Q08426, and P09110) feature ligand-binding or allosteric cavities with druggable potential. Our results advocate for a focused exploration of P00558 (phosphoglycerate kinase 1), P04406 (glyceraldehyde-3-phosphate dehydrogenase), Q08426 (peroxisomal bifunctional enzyme, enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase), P09110 (peroxisomal 3-ketoacyl-CoA thiolase), and O76062 (Delta(14)-sterol reductase) as promising targets for the development or repurposing of pharmacological compounds, which could have the potential to modulate lipotoxic-altered metabolic pathways, offering new avenues for the treatment of related human diseases such as neurological diseases.

Genetic diversity of P1/pathogenic Leptospira species hosted by bats worldwide.

INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.

Molecular detection of tick-borne rickettsial pathogens in ticks collected from domestic animals from Cauca, Colombia.

Some hard ticks' species can act as vectors of a wide variety of pathogens of human and animal importance such as Anaplasma, Ehrlichia and Rickettsia spp. In Colombia, a total of forty-six tick species have been described, and some of them have been implicated as vectors of some infectious agents. The department of Cauca is one of the thirty-two departments of Colombia. Most of its population lives in rural areas and depends on agriculture as the main economic activity, favoring exposure to ticks and tick-borne pathogens. Thus, the present study aimed to determine the tick species and tick-borne pathogens circulating in this region. From August to November 2017, ticks were collected from dogs, horses and cattle from eight rural areas of four municipalities in the department of Cauca. All collected ticks were classified according to taxonomic keys and organized in pools. DNA was extracted from all tick pools for molecular confirmation of tick species and detection of Anaplasma, Ehrlichia and Rickettsia spp. A total of 2809 ticks were collected which were grouped in 602 pools. Ticks were morphologically identified as Amblyomma cajennense sensu lato, Dermacentor nitens, Rhipicephalus microplus and Rhipicephalus sanguineus sensu lato. The molecular identity of A. cajennense s.l. was confirmed as Amblyomma patinoi. A total of 95% of the pools scored positive for members of the Anaplasmataceae family, of which, 7.8% and 7.3% were positive to Anaplasma and Ehrlichia spp., respectively, being identified as Anaplasma marginale, Ehrlichia minasensis and Ehrlichia canis; and 16.1% were positive for Rickettsia spp. with high identity for Rickettsia asembonensis, Rickettsia felis and Candidatus Rickettsia senegalensis. This is the first report describing the natural infection of ticks with rickettsial pathogens and the occurrence of A. patinoi ticks in Cauca department, Colombia.

Physico-chemical pre-treatments of anaerobic digestion liquor for aerobic treatment.

Centrifugation of anaerobically digested sewage sludge gives rise to a solid phase, which could be employed as a fertilizer, and a liquid fraction (ADL), which should be treated before being spilled out. This is not an easy task because this liquor is characterized for presenting high COD (~16000 mg O2/L), high ammonium content (~4000 mg/L) and low biodegradability (BOD5/COD ~0.2). With the objective to pre-treat this aqueous waste before its treatment by means of more traditional aerobic processes, different physico-chemical methods (ultrasound, ozonation, hydrolysis and wet air oxidation) were assessed in this work. Ultrasound and thermal hydrolysis gave solubilizations around 47% and 68% respectively. The best results in terms of total COD removal were obtained when wet air oxidation (8 h, 160 C-200 °C and 6.0 MPa) and ozonation (8 h, 25 °C, 12 g/h O3) techniques were employed achieving COD degradations of 71% and 38%, respectively. The pre-treatment of ADL with the four assayed techniques improved considerably the biodegradability (BOD5/COD) of the effluent, with values around 0.3-0.4, depending on the treatment. The experimental data were successfully fitted by kinetic models and the kinetic constants for the solubilization and degradation steps were obtained. Application of the proposed models can be of interest for the optimization and selection of the most suitable techniques and operational conditions, in each particular case.

Impacto pronóstico de la especialidad en el paciente ambulatorio con insuficiencia cardiaca: un análisis emparejado de los registros REDINSCOR y RICA / Prognostic impact of physician specialty on the prognosis of outpatients with heart failure: propensity matched analysis of the REDINSCOR and RICA registries

Introducción y objetivos: La especialidad responsable del paciente hospitalizado por insuficiencia cardiaca (IC) tiene impacto pronóstico, pero esta cuestión no está clara en el medio ambulatorio. Nuestro objetivo es comparar el perfil clínico y pronóstico de pacientes ambulatorios con IC tratados por cardiólogos o internistas. Métodos: Estudio retrospectivo en el que se analizan los datos de 2 registros multicéntricos nacionales, REDINSCOR (n = 2.150, cardiología) y RICA (n = 1.396, medicina interna). Para medir el efecto del especialista, se realizó un emparejamiento por puntuación de propensión que incluyó sus principales diferencias clínicas. Resultados: Los pacientes a cargo de cardiología fueron frecuentemente varones, jóvenes, con IC isquémica y fracción de eyección del ventrículo izquierdo (FEVI) reducida. Entre los seguidos por medicina interna predominó el sexo femenino, la edad avanzada, un mayor porcentaje con FEVI preservada y comorbilidades. La mortalidad a los 9 meses fue menor entre los pacientes del REDINSCOR (el 11,6 frente al 16,9%; p < 0,001), con una tasa de reingreso por IC similar (el 15,7 frente al 16,9%; p = 0,349). La puntuación de propensión seleccionó a 558 parejas comparables y continuó mostrando una mortalidad significativamente menor entre los pacientes tratados por cardiología (el 12,0 frente al 18,8%; riesgo relativo = 0,64; intervalo de confianza del 95%, 0,48-0,85; p = 0,002), sin diferencias en el reingreso (el 18,1 frente al 17,2%; riesgo relativo = 0,95; intervalo de confianza del 95%, 0,74-1,22; p = 0,695). Conclusiones: Edad, sexo, FEVI y comorbilidades contribuyen al distinto perfil de los pacientes con IC según especialidad. Después del emparejamiento por puntuación de propensión, la mortalidad a los 9 meses fue menor entre los pacientes a cargo de cardiología (AU)

Introduction and objectives: The specialty treating patients with heart failure (HF) has a prognostic impact in the hospital setting but this issue remains under debate in the ambulatory environment. We aimed to compare the clinical profile and outcomes of outpatients with HF treated by cardiologists or internists. Methods: We analyzed the clinical, electrocardiogram, laboratory, and echocardiographic data of 2 prospective multicenter Spanish cohorts of outpatients with HF treated by cardiologists (REDINSCOR, n = 2150) or by internists (RICA, n = 1396). Propensity score matching analysis was used to test the influence of physician specialty on outcome. Results: Cardiologist-treated patients were often men, were younger, and had ischemic etiology and reduced left ventricular ejection fraction (LVEF). Patients followed up by internists were predominantly women, were older, and a higher percentage had preserved LVEF and associated comorbidities. The 9-month mortality was lower in the REDINSCOR cohort (11.6% vs 16.9%; P < .001), but the 9-month HF-readmission rates were similar (15.7% vs 16.9%; P = .349). The propensity matching analysis selected 558 pairs of comparable patients and continued to show significantly lower 9-month mortality in the cardiology cohort (12.0% vs 18.8%; RR, 0.64; 95% confidence interval [95%CI], 0.48-0.85; P = .002), with no relevant differences in the 9-month HF-readmission rate (18.1% vs 17.2%; RR, 0.95; 95%CI, 0.74-1.22; P = .695). Conclusions: Age, sex, LVEF and comorbidities were major determinants of specialty-related referral in HF outpatients. An in-depth propensity matched analysis showed significantly lower 9-month mortality in the cardiologist cohort (AU)

Prognostic Impact of Physician Specialty on the Prognosis of Outpatients With Heart Failure: Propensity Matched Analysis of the REDINSCOR and RICA Registries.

INTRODUCTION AND OBJECTIVES: The specialty treating patients with heart failure (HF) has a prognostic impact in the hospital setting but this issue remains under debate in the ambulatory environment. We aimed to compare the clinical profile and outcomes of outpatients with HF treated by cardiologists or internists. METHODS: We analyzed the clinical, electrocardiogram, laboratory, and echocardiographic data of 2 prospective multicenter Spanish cohorts of outpatients with HF treated by cardiologists (REDINSCOR, n=2150) or by internists (RICA, n=1396). Propensity score matching analysis was used to test the influence of physician specialty on outcome. RESULTS: Cardiologist-treated patients were often men, were younger, and had ischemic etiology and reduced left ventricular ejection fraction (LVEF). Patients followed up by internists were predominantly women, were older, and a higher percentage had preserved LVEF and associated comorbidities. The 9-month mortality was lower in the REDINSCOR cohort (11.6% vs 16.9%; P<.001), but the 9-month HF-readmission rates were similar (15.7% vs 16.9%; P=.349). The propensity matching analysis selected 558 pairs of comparable patients and continued to show significantly lower 9-month mortality in the cardiology cohort (12.0% vs 18.8%; RR, 0.64; 95% confidence interval [95%CI], 0.48-0.85; P=.002), with no relevant differences in the 9-month HF-readmission rate (18.1% vs 17.2%; RR, 0.95; 95%CI, 0.74-1.22; P=.695). CONCLUSIONS: Age, sex, LVEF and comorbidities were major determinants of specialty-related referral in HF outpatients. An in-depth propensity matched analysis showed significantly lower 9-month mortality in the cardiologist cohort.

Optimization of the resources management in fighting wildfires.

Wildfires lead to important economic, social, and environmental losses, especially in areas of Mediterranean climate where they are of a high intensity and frequency. Over the past 30 years there has been a dramatic surge in the development and use of fire spread models. However, given the chaotic nature of environmental systems, it is very difficult to develop real-time fire-extinguishing models. This article proposes a method of optimizing the performance of wildfire fighting resources such that losses are kept to a minimum. The optimization procedure includes discrete simulation algorithms and Bayesian optimization methods for discrete and continuous problems (simulated annealing and Bayesian global optimization). Fast calculus algorithms are applied to provide optimization outcomes in short periods of time such that the predictions of the model and the real behavior of the fire, combat resources, and meteorological conditions are similar. In addition, adaptive algorithms take into account the chaotic behavior of wildfire so that the system can be updated with data corresponding to the real situation to obtain a new optimum solution. The application of this method to the Northwest Forest of Madrid (Spain) is also described. This application allowed us to check that it is a helpful tool in the decision-making process.