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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.

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Introduction: The application of enhanced recovery in shoulder surgery has not had such a favorable acceptance, therefore, the objective of this study was to present and describe the use of interscalene block to promote enhanced recovery in a series of patients undergoing shoulder arthroscopic surgery. Methods: Thirty-five patients undergoing arthroscopic shoulder surgery were included, in whom interscalene blockade and sedation were administered. Subsequently, pain intensity, nausea, vomiting, dyspnea, presence of Horner's syndrome, blurred vision, hoarseness, time elapsed to discharge, unplanned readmissions, patient satisfaction, and compliance with hospital discharge criteria in the first 12 weeks were evaluated, hours following the criteria of an enhanced recovery. Results: 27 patients (77,1%) had ASA I and 8 patients (22,8%) ASA II, 97,1% were rotator cuff repairs. Before discharge, two patients (5.7%) had nausea. At discharge, no patient had dyspnea or blurred vision, two patients (5.7%) developed hoarseness, and the median pain intensity was 1.0 (0.0-7.0). Between 24 and 48 hours only one patient (2.8%) presented nausea and the median pain intensity was 1.0 (0.0-8.0). All the patients were satisfied with their willingness to repeat the experience, 100% of the patients met the criteria for medical discharge after 12 hours, 30 patients (85.7%) were discharged the same day, the stay was 12 (11.5 to 12.5) hours, and no patient was readmitted. Conclusion: In selected patients with a committed, trained and experienced surgical-anesthetic team, there is a high possibility that the interscalene block will favor the performance of enhanced recovery programs in shoulder arthroscopic surgery.

Introducción: La aplicación de la recuperación acelerada en cirugía de hombro no ha tenido una aceptación tan favorable. Por ello, el objetivo de este estudio fue presentar y describir el uso de bloqueo interescalénico para favorecer la recuperación acelerada en una serie de pacientes sometidos a cirugía artroscopica de hombro. Métodos: Se incluyeron 35 pacientes sometidos a cirugía artroscópica de hombro, en quienes se administró bloqueo interescalénico y sedación. Posteriormente se evaluó la intensidad del dolor, náuseas, vómito, disnea, presencia de síndrome de Horner, visión borrosa, ronquera, tiempo transcurrido hasta el alta, reingresos no planeados, satisfacción del paciente y cumplimiento de los criterios de alta hospitalaria en las primeras 12 horas siguiendo los criterios de una recuperación acelerada. Resultados: En total, 27 pacientes (77,1%) tuvieron clasificación de la (ASA) I y 8 pacientes (22,9%) ASA II. Además, 97,1% fueron reparaciones de manguito rotador. Previo al alta, dos pacientes (5,7%) presentaron náuseas. Al momento del alta ningún paciente presentó disnea o visión borrosa, dos pacientes (5,7%) presentaron ronquera y la mediana de intensidad del dolor fue de 1,0 (0,0 a 7,0). Entre las 24 y 48 horas solo un (2,8%) paciente presentó náuseas y la mediana de intensidad del dolor fue de 1,0 (0,0 a 8,0). Todos los pacientes se mostraron satisfechos con disposición a repetir la experiencia. El 100% de pacientes cumplió los criterios médicos de alta a las 12 horas y 30 pacientes (85,7%) se dieron de alta el mismo día. La estancia fue de 12 (11,5 a 12,5) horas y ningún paciente reingresó. Conclusión: En pacientes seleccionados, con un equipo quirúrgico-anestésico comprometido, capacitado y con experiencia, hay una alta posibilidad de que el bloqueo interescalénico favorezca la realización de programas de recuperación acelerada en cirugía artroscópica de hombro.

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INTRODUCCIÓN: La aplicación de la recuperación acelerada en cirugía de hombro no ha tenido una aceptación tan favorable. Por ello, el objetivo de este estudio fue presentar y describir el uso de bloqueo interescalénico para favorecer la recuperación acelerada en una serie de pacientes sometidos a cirugía artroscópica de hombro. MÉTODOS: Se incluyeron 35 pacientes sometidos a cirugía artroscópica de hombro, en quienes se administró bloqueo interescalénico y sedación. Posteriormente se evaluó la intensidad del dolor, náuseas, vómito, disnea, presencia de síndrome de Horner, visión borrosa, ronquera, tiempo transcurrido hasta el alta, reingresos no planeados, satisfacción del paciente y cumplimiento de los criterios de alta hospitalaria en las primeras 12 horas siguiendo los criterios de una recuperación acelerada. RESULTADOS: En total, 27 pacientes (77,1%) tuvieron clasificación de la (ASA) I y 8 pacientes (22,9%) ASA II. Además, 97,1% fueron reparaciones de manguito rotador. Previo al alta, dos pacientes (5,7%) presentaron náuseas. Al momento del alta ningún paciente presentó disnea o visión borrosa, dos pacientes (5,7%) presentaron ronquera y la mediana de intensidad del dolor fue de 1,0 (0,0 a 7,0). Entre las 24 y 48 horas solo un (2,8%) paciente presentó náuseas y la mediana de intensidad del dolor fue de 1,0 (0,0 a 8,0). Todos los pacientes se mostraron satisfechos con disposición a repetir la experiencia. El 100% de pacientes cumplió los criterios médicos de alta a las 12 horas y 30 pacientes (85,7%) se dieron de alta el mismo día. La estancia fue de 12 (11,5 a 12,5) horas y ningún paciente reingresó. CONCLUSIÓN: En pacientes seleccionados, con un equipo quirúrgico-anestésico comprometido, capacitado y con experiencia, hay una alta posibilidad de que el bloqueo interescalénico favorezca la realización de programas de recuperación acelerada en cirugía artroscópica de hombro.

INTRODUCTION: The application of enhanced recovery in shoulder surgery has not had such a favorable acceptance, therefore, the objective of this study was to present and describe the use of interscalene block to promote enhanced recovery in a series of patients undergoing shoulder arthroscopic surgery. METHODS: Thirty-five patients undergoing arthroscopic shoulder surgery were included, in whom interscalene blockade and sedation were administered. Subsequently, pain intensity, nausea, vomiting, dyspnea, presence of Horner's syndrome, blurred vision, hoarseness, time elapsed to discharge, unplanned readmissions, patient satisfaction, and compliance with hospital discharge criteria in the first 12 weeks were evaluated, hours following the criteria of an enhanced recovery. RESULTS: 27 patients (77,1%) had ASA I and 8 patients (22,8%) ASA II, 97,1% were rotator cuff repairs. Before discharge, two patients (5.7%) had nausea. At discharge, no patient had dyspnea or blurred vision, two patients (5.7%) developed hoarseness, and the median pain intensity was 1.0 (0.0-7.0). Between 24 and 48 hours only one patient (2.8%) presented nausea and the median pain intensity was 1.0 (0.0-8.0). All the patients were satisfied with their willingness to repeat the experience, 100% of the patients met the criteria for medical discharge after 12 hours, 30 patients (85.7%) were discharged the same day, the stay was 12 (11.5 to 12.5) hours, and no patient was readmitted. CONCLUSION: In selected patients with a committed, trained and experienced surgical-anesthetic team, there is a high possibility that the interscalene block will favor the performance of enhanced recovery programs in shoulder arthroscopic surgery.

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An Indigenous agropastoralist population called the Wiwa from the Sierra Nevada de Santa Marta, in North-East Colombia, shows high rates of gastrointestinal infections. Chronic gut inflammatory processes and dysbiosis could be a reason, suggesting an influence or predisposing potential of the gut microbiome composition. The latter was analyzed by 16S rRNA gene amplicon next generation sequencing from stool samples. Results of the Wiwa population microbiomes were associated with available epidemiological and morphometric data and compared to control samples from a local urban population. Indeed, locational-, age-, and gender-specific differences in the Firmicutes/Bacteriodetes ratio, core microbiome, and overall genera-level microbiome composition were shown. Alpha- and ß-diversity separated the urban site from the Indigenous locations. Urban microbiomes were dominated by Bacteriodetes, whereas Indigenous samples revealed a four times higher abundance of Proteobacteria. Even differences among the two Indigenous villages were noted. PICRUSt analysis identified several enriched location-specific bacterial pathways. Moreover, on a general comparative scale and with a high predictive accuracy, we found Sutterella associated with the abundance of enterohemorrhagic Escherichia coli (EHEC), Faecalibacteria associated with enteropathogenic Escherichia coli (EPEC) and helminth species Hymenolepsis nana and Enterobius vermicularis. Parabacteroides, Prevotella, and Butyrivibrio are enriched in cases of salmonellosis, EPEC, and helminth infections. Presence of Dialister was associated with gastrointestinal symptoms, whereas Clostridia were exclusively found in children under the age of 5 years. Odoribacter and Parabacteroides were exclusively identified in the microbiomes of the urban population of Valledupar. In summary, dysbiotic alterations in the gut microbiome in the Indigenous population with frequent episodes of self-reported gastrointestinal infections were confirmed with epidemiological and pathogen-specific associations. Our data provide strong hints of microbiome alterations associated with the clinical conditions of the Indigenous population.

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Control theory, a well-established discipline in engineering and mathematics, has found novel applications in systems biology. This interdisciplinary approach leverages the principles of feedback control and regulation to gain insights into the complex dynamics of cellular and molecular networks underlying chronic diseases, including neurodegeneration. By modeling and analyzing these intricate systems, control theory provides a framework to understand the pathophysiology and identify potential therapeutic targets. Therefore, this review examines the most widely used control methods in conjunction with genomic-scale metabolic models in the steady state of the multi-omics type. According to our research, this approach involves integrating experimental data, mathematical modeling, and computational analyses to simulate and control complex biological systems. In this review, we find that the most significant application of this methodology is associated with cancer, leaving a lack of knowledge in neurodegenerative models. However, this methodology, mainly associated with the Minimal Dominant Set (MDS), has provided a starting point for identifying therapeutic targets for drug development and personalized treatment strategies, paving the way for more effective therapies.

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The association between neurodegenerative diseases (NDs) and obesity has been well studied in recent years. Obesity is a syndrome of multifactorial etiology characterized by an excessive accumulation and release of fatty acids (FA) in adipose and non-adipose tissue. An excess of FA generates a metabolic condition known as lipotoxicity, which triggers pathological cellular and molecular responses, causing dysregulation of homeostasis and a decrease in cell viability. This condition is a hallmark of NDs, and astrocytes are particularly sensitive to it, given their crucial role in energy production and oxidative stress management in the brain. However, analyzing cellular mechanisms associated with these conditions represents a challenge. In this regard, metabolomics is an approach that allows biochemical analysis from the comprehensive perspective of cell physiology. This technique allows cellular metabolic profiles to be determined in different biological contexts, such as those of NDs and specific metabolic insults, including lipotoxicity. Since data provided by metabolomics can be complex and difficult to interpret, alternative data analysis techniques such as machine learning (ML) have grown exponentially in areas related to omics data. Here, we developed an ML model yielding a 93% area under the receiving operating characteristic (ROC) curve, with sensibility and specificity values of 80% and 93%, respectively. This study aimed to analyze the metabolomic profiles of human astrocytes under lipotoxic conditions to provide powerful insights, such as potential biomarkers for scenarios of lipotoxicity induced by palmitic acid (PA). In this work, we propose that dysregulation in seleno-amino acid metabolism, urea cycle, and glutamate metabolism pathways are major triggers in astrocyte lipotoxic scenarios, while increased metabolites such as alanine, adenosine, and glutamate are suggested as potential biomarkers, which, to our knowledge, have not been identified in human astrocytes and are proposed as candidates for further research and validation.

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Chagas disease (CD) is one of the leading neglected tropical diseases. In the Americas, CD is endemic in about 21 countries, but only less than 1% of the patients have access to medical treatment. Indigenous populations are particularly affected because they live in socio-economic and climate conditions that favor CD infections. In this study, diagnostic strategies and regional prevalence of the Chagas disease were assessed. In nine villages of the indigenous tribe Wiwa, 1134 persons were tested with a Chagas-antibody-specific rapid test (RT), two different Chagas-antibody-specific ELISAs and a Chagas-specific real-time polymerase chain reaction. The overall prevalence of CD in the villages was 35.4%, with a variation from 24.9% to 52.8% for the different communities. Rapid tests and ELISAs showed the same results in all cases. The proportion of replication-active infections, defined by positive PCR results, was 8.7%. In conclusion, the assessed indigenous population in Colombia was shown to be severely affected by CD. For a serological diagnosis, one rapid test was shown to be sufficient. Replacements of ELISAs by RT would decrease costs, increase feasibility and would relevantly help detect positive patients, especially if combined with the applied real-time PCR protocol. Real-time PCR can be considered for the detection of acute cases, outbreaks, chronic cases with re-infection/activation, as well as for therapy management and control.

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Leptospirosis is among the most important zoonotic diseases in (sub-)tropical countries. The research objective was to evaluate the accuracy of the Serion IgM ELISA EST125M against the Microscopic Agglutination Test (MAT = imperfect reference test); to assess its ability to diagnose acute leptospirosis infections and to detect previous exposure to leptospires in an endemic setting. In addition, to estimate the overall Leptospira spp. seroprevalence in the Wiwa indigenous population in North-East Colombia. We analysed serum samples from confirmed leptospirosis patients from the Netherlands (N = 14), blood donor sera from Switzerland (N = 20), and sera from a cross-sectional study in Colombia (N = 321). All leptospirosis ELISA-positive, and a random of negative samples from Colombia were tested by the MAT for confirmation. The ELISA performed with a sensitivity of 100% (95% CI 77% - 100%) and a specificity of 100% (95% CI 83% - 100%) based on MAT confirmed Leptospira spp. positive and negative samples. In the cross-sectional study in Colombia, the ELISA performed with a sensitivity of 100% (95% CI 2-100%) and a specificity of 21% (95% CI 15-28%). Assuming a 5% Leptospira spp. seroprevalence in this population, the positive predictive value was 6% and the negative predictive value 100%. The Leptospira spp. seroprevalence in the Wiwas tested by the ELISA was 39%; however, by MAT only 0.3%. The ELISA is suitable to diagnose leptospirosis in acutely ill patients in Europe several days after onset of disease. For cross-sectional studies it is not recommended due to its low specificity. Despite the evidence of a high leptospirosis prevalence in other study areas and populations in Colombia, the Wiwa do not seem to be highly exposed to Leptospira spp.. Nevertheless, leptospirosis should be considered and tested in patients presenting with febrile illness.

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Enteric pathogens, which are frequently food- and waterborne transmitted, are highly abundant in Indigenous people living in remote rural areas of Colombia. As the frequency of gastroenteritis in the tropics shows seasonal differences, we analyzed variations of pathogen patterns in the stool samples of a Colombian Indigenous tribe called Wiwa during the dry (n = 105) and the rainy (n = 227) season, applying real-time PCR from stool samples and statistical analysis based on a multi-variable model. Focusing on bacterial pathogens, increased detection rates could be confirmed for enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli with a tendency for an increase in Campylobacter jejuni detections during the rainy season, while there was no seasonal effect on the carriage of Tropheryma whipplei. Salmonellae were recorded during the rainy season only. A differentiated pattern was seen for the assessed parasites. Entamoeba histolytica, Necator americanus and Trichuris trichiura were increasingly detected during the rainy season, but not Ascaris lumbricoides, Giardia duodenalis, Hymenolepis nana, Strongyloides stercoralis, and Taenia solium, respectively. Increased detection rates during the dry season were not recorded. Negative associations were found for Campylobacter jejuni and Giardia duodenalis with age and for Tropheryma whipplei with the body mass index, respectively. Positive associations of enteropathogenic Escherichia coli and Taenia solium detections were observed with age. In conclusion, facilitating effects of the tropical rainy season were more pronounced on bacterial enteric pathogens compared to enteropathogenic parasites.

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The life of the indigenous Wiwa tribe in northeast Colombia is characterized by lacking access to clean drinking water and sanitary installations. Furthermore, free-roaming domestic animals and use of yucca and/or manioc as a primary food source favor the transmission of soil-transmitted helminths, e.g., Toxocara canis and Toxocara cati, the roundworms of dogs and cats. Infection may result in the clinical picture of toxocarosis, one of the most common zoonotic helminthoses worldwide. To estimate the Toxocara seroprevalence in four different villages of the Wiwa community, serum samples from 483 inhabitants were analyzed for anti-Toxocara-antibodies. Overall, 79.3% (383/483) of analyzed samples were seropositive. Statistically significant differences were observed between the four villages, as well as age groups (adults > adolescents > children), while sex had no effect. The high seropositivity rate demonstrates the risk of zoonotic roundworm infections and potential clinical disease in vulnerable indigenous inhabitants.