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.

Single-row or Double-row Rotator Cuff Repair.

Rotator cuff tears are potentially a career-ending injury for athletes. The surgeon must identify which patients will benefit from surgical repair. The factors to consider are age, type of sport, time since injury, athlete's level, and the patient's expectations. An essential and independent fact determining the surgical treatment is whether the damage is due to overuse or from a traumatic/collision injury. Some sports are more demanding than others resulting in different return-to-participation (RTP) rates. This RTP return rate can present a real challenge and more so by a desire to reach the pre-injury level of play. The incidence of rotator cuff tearing varies from one sport to another. In football players this can be 12% whereas for tennis players this incidence is 4% to 17%. The RTP rate must be considered when making treatment decisions and is influenced by the level of the athlete: for professional athletes, the rate is 61%, and for recreational 73%. When the surgeon and the patient decide on the surgical treatment, the surgeon must consider whether to perform a double-row or a single-row rotator cuff tendon repair. The decision-making and the surgical technique will be addressed.

Interscalene block in the context of enhanced recovery for shoulder: A case series. / Bloqueo interescalénico en el contexto de la recuperación acelerada para artroscopía de hombro: serie de casos.

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.

Bloqueo interescalénico en el contexto de la recuperación acelerada para artroscopía de hombro: serie de casos / Interscalene block in the context of enhanced recovery for shoulder: A case series

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.

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.

Control Theory and Systems Biology: Potential Applications in Neurodegeneration and Search for Therapeutic Targets.

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.

[Complication related factors in patients undergoing open simple prostatectomy due to Benign Prostate Hyperplasia in a Colombian hospital.] / Factores asociados a complicaciones en los pacientes llevados a prostatectomía abierta retropúbica por Hiperplasia Prostática Benigna en un hospital Colombiano.

INTRODUCTION: Open prostatectomy is an efficacious treatment for Benign Prostatic Hyperplasia (BPH), but its complication rates and risk factors for these might vary due to the characteristics of populations and health systems. OBJECTIVE: To determine the frequency of complications and the risk factors for these, in the first three months after open prostatectomy in a hospital in Medellín (Colombia). METHODS: This is a cohort study in which patients undergoing retropubic open prostatectomy were taken. Medical records were reviewed to obtain demographic, preoperative, and intraoperative data. The main outcome was the incidence of complications in the first three postoperative months and this was divided into early (day 1 to 7 post-surgery) and late (day 8 to 90 post-surgery) complications. Risk factors were determined by estimating Relative Risks (RR). RESULTS: 191 patients with a median age of 70 years were included. The frequency of complications was 34.5%,14.6% occurred early and 19.9% late. Risk factors were dyslipidemia (RR: 2.37, 95% CI: 1.25 to 4.47), irrigation time (RR: 1.31, 95% CI: 1.02 to 1.67) and duration of the postsurgical catheter (RR: 1.07, 95% CI: 1.03 to 1.12); general anesthesia was a protective risk factor compared to spinal (RR: 0.47, 95% CI: 0.24 to 0.91). CONCLUSION: The frequency of complications of open prostatectomy with a retropubic approach was within the figures reported in the literature. The risk factors found could be modifiable and considered for the prevention of adverse outcomes. This study provides an updated basis for future comparisons with alternative treatments for BPH.

INTRODUCCIÓN: La prostatectomía abierta es un tratamiento eficaz para la Hiperplasia Prostática Benigna (HPB) pero sus tasas de complicaciones y los factores de riesgo para estas pueden variar por particularidades de las poblaciones y los sistemas de salud. OBJETIVO: Determinar la frecuencia de complicacione sy factores de riesgo en los primeros tres meses postquirúrgicos de la prostatectomía abierta en un hospital de alta complejidad de Medellín (Colombia). MATERIALES Y MÉTODOS: Este es un estudio de cohortes en el cual se tomaron pacientes llevados a prostatectomía abierta retropúbica. Se revisaron las historias clínicas para obtener datos demográficos, prequirúrgicos e intraquirúrgicos. El desenlace principal fue la presentación de complicaciones en los primeros tres meses postquirúrgicos y éste se dividió en complicaciones tempranas (entre el día 1 y 7) y tardías (entre el día 8 y 90). Se determinaron los factores de riesgo mediante la estimación de Riesgos Relativos (RR). RESULTADOS: Se incluyeron 191 pacientes con una mediana de edad de 70 años. La frecuencia de complicaciones fue de 34,5%, 14,6% tempranas y 19,9% tardías. Los factores de riesgo fueron dislipidemia (RR: 2,37, IC95%: 1,25 a 4,47), tiempo de irrigación (RR: 1,31, IC95%: 1,02 a 1,67) y duración de sonda postquirúrgica (RR: 1,07, IC95%: 1,03 a 1,12); la anestesia general fue un factor de riesgo protector en comparación con la raquídea (RR: 0,47, IC95%: 0,24 a 0,91). CONCLUSIONES: La frecuencia de complicaciones de la prostatectomía abierta bajo enfoque retropúbico estuvo dentro de las cifras reportadas en la literatura. Los factores de riesgo encontrados podrían ser modificables  y tenerse en cuenta para la prevención de desenlaces adversos. Con este estudio se sienta una base actualizada para futuras comparaciones con tratamientos alternativos para HPB.

Factores asociados a complicaciones en los pacientes llevados a prostatectomía abierta retropúbica por Hiperplasia Prostática Benigna en un hospital Colombiano / Complication related factors in patients undergoing open simple prostatectomy due to Benign Prostate Hyperplasia in a Colombian hospital

INTRODUCCIÓN: La prostatectomía abierta es un tratamiento eficaz para la Hiperplasia Prostática Benigna (HPB) pero sus tasas de complicaciones y los factores de riesgo para estas pueden variar por particularidades de las poblaciones y los sistemas de salud. OBJETIVO: Determinar la frecuencia de complicacione sy factores de riesgo en los primeros tres meses postquirúrgicos de la prostatectomía abierta en un hospital de alta complejidad de Medellín (Colombia). MATERIALES Y MÉTODOS: Este es un estudio de cohortes en el cual se tomaron pacientes llevados a prostatectomía abierta retropúbica. Se revisaron las historias clínicas para obtener datos demográficos, prequirúrgicos e intraquirúrgicos. El desenlace principal fue la presentación de complicaciones en los primeros tres meses postquirúrgicos y éste se dividió en complicaciones tempranas (entre el día 1 y 7) y tardías (entre el día 8 y 90). Se determinaron los factores de riesgo mediante la estimación de Riesgos Relativos (RR). RESULTADOS: Se incluyeron 191 pacientes con una mediana de edad de 70 años. La frecuencia de complicaciones fue de 34,5%, 14,6% tempranas y 19,9% tardías. Los factores de riesgo fueron dislipidemia (RR: 2,37, IC95%: 1,25 a 4,47), tiempo de irrigación (RR: 1,31, IC95%: 1,02 a 1,67) y duración de sonda postquirúrgica (RR: 1,07, IC95%: 1,03 a 1,12); la anestesia general fue un factor de riesgo protector en comparación con la raquídea (RR: 0,47, IC95%: 0,24 a 0,91). CONCLUSIONES: La frecuencia de complicaciones de la prostatectomía abierta bajo enfoque retropúbico estuvo dentro de las cifras reportadas en la literatura. Los factores de riesgo encontrados podrían ser modificables y tenerse en cuenta para la prevención de desenlaces adversos. Con este estudio se sienta una base actualizada para futuras comparaciones con tratamientos alternativos para HPB

INTRODUCTION: Open prostatectomy is an efficacious treatment for Benign Prostatic Hyperplasia (BPH), but its complication rates and risk factors for these might vary due to the characteristics of populations and health systems. OBJECTIVE: To determine the frequency of complications and the risk factors for these, in the first three months after open prostatectomy in a hospital in Medellín (Colombia). METHODS: This is a cohort study in which patients undergoing retropubic open prostatectomy were taken. Medical records were reviewed to obtain demographic, preoperative, and intraoperative data. The main outcome was the incidence of complications in the first three postoperative months and this was divided into early (day 1 to 7 post-surgery) and late (day 8 to 90 post-surgery) complications. Risk factors were determined by estimating Relative Risks (RR). RESULTS: 191 patients with a median age of 70 years were included. The frequency of complications was 34.5%, 14.6% occurred early and 19.9% late. Risk factors were dyslipidemia (RR: 2.37, 95% CI: 1.25 to 4.47), irrigation time (RR: 1.31, 95% CI: 1.02 to 1.67) and duration of the postsurgical catheter (RR: 1.07, 95% CI: 1.03 to 1.12); general anesthesia was a protective risk factor compared to spinal (RR: 0.47, 95% CI: 0.24 to 0.91). CONCLUSION: The frequency of complications of open prostatectomy with a retropubic approach was within the figures reported in the literature. The risk factors found could be modifiable and considered for the prevention of adverse outcomes. This study provides an updated basis for future comparisons with alternative treatments for BPH

Advances in Astrocyte Computational Models: From Metabolic Reconstructions to Multi-omic Approaches.

The growing importance of astrocytes in the field of neuroscience has led to a greater number of computational models devoted to the study of astrocytic functions and their metabolic interactions with neurons. The modeling of these interactions demands a combined understanding of brain physiology and the development of computational frameworks based on genomic-scale reconstructions, system biology, and dynamic models. These computational approaches have helped to highlight the neuroprotective mechanisms triggered by astrocytes and other glial cells, both under normal conditions and during neurodegenerative processes. In the present review, we evaluate some of the most relevant models of astrocyte metabolism, including genome-scale reconstructions and astrocyte-neuron interactions developed in the last few years. Additionally, we discuss novel strategies from the multi-omics perspective and computational models of other glial cell types that will increase our knowledge in brain metabolism and its association with neurodegenerative diseases.

Plasmacytoid Urothelial Carcinoma of the Bladder: Case Report and Review of the Literature / Carcinoma urotelial de vejiga, variante plasmocitoide: Reporte de un caso y revisión de la literatura

Introduction Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histological variant, accounting for 1 to 3% of the invasive urothelial carcinomas, and it is typically aggressive. So far, it has not been well characterized, and the literature is based on reports and case series. Case Report A 70-year-old male patient presenting with 4 months of constitutional and urinary symptoms, with an ultrasound finding of bilateral hydronephrosis and diffuse thickening of the bladder walls. In the cystoscopy, trigone of infiltrated appearance, a biopsy wass performed, whose immunohistochemistry revealed a PUC. The abdominopelvic image showed an infiltrative lesion that compromised the muscle of the bladder and extended to the perivesical fat, without adequate plane of cleavage with the prostate and a single hypogastric adenopathy suspected of malignancy. It was classified as cT3b vs cT4aN1M0 (chest computed tomography [CT] negative for malignancy), and the patient was submitted to a radical cystoprostatectomy, extended pelvic lymphadenectomy and non-continent urinary diversion with ileal conduit. The pathology revealed a diffuse PUC with prostatic stromal involvement and 22 of 39 lymph nodes positive for malignancy. Finally, the patient presented a series of postoperative complications and died. Conclusion Plasmacytoid urothelial carcinoma of the bladder is a rare entity, characterized by high aggressiveness, an advanced stage at the time of diagnosis, and a poor prognosis. Currently, an aggressive approach is recommended due to its high invasive potential.

Introducción El carcinoma urotelial plasmocitoide (CUP) de la vejiga es una variante histológica poco frecuente; representa el 1 al 3% de los carcinomas uroteliales invasivos y es típicamente agresiva. Hasta el momento no ha sido bien caracterizada, y la literatura se basa en reportes y series de casos. Reporte de Caso Paciente masculino de 70 años presentando por 4 meses síntomas constitucionales y urinarios, con hallazgo ecográfico de hidronefrosis bilateral y engrosamiento difuso de las paredes vesicales. En la cistoscopia, trígono de apariencia infiltrada, se realizó biopsia cuya inmunohistoquímica reveló un CUP. En imagen abdominopélvica, se evidenció lesión infiltrativa que comprometía la muscular de la vejiga y se extendía a la grasa perivesical, sin adecuado plano de clivaje con la próstata y un único ganglio hipogástrico sospechoso de malignidad. Se clasificó como cT3b vs cT4aN1M0 (TAC tórax negativo para malignidad) y fue llevado a cistoprostatectomía radical, linfadenectomía pélvica extendida y derivación urinaria no continente con conducto ileal. La patología reveló un carcinoma urotelial variante difusa plasmocitoide con compromiso de estroma prostático y 22 de 39 ganglios positivos para malignidad. Finalmente, el paciente presentó una serie de complicaciones posoperatorias y falleció. Conclusión El carcinoma urotelial de vejiga variante plasmocitoide es una entidad poco frecuente, caracterizada por alta agresividad, un estadio avanzado al momento del diagnóstico, y un pobre pronóstico. En la actualidad, se recomienda un enfoque agresivo dado su alto potencial invasivo.