JNK Activation in Alzheimer's Disease Is Driven by Amyloid ß and Is Associated with Tau Pathology.

c-Jun N-terminal kinase 3 (JNK3) is suggested to play a key role in neurodegenerative disorders, especially in Alzheimer's disease (AD). However, it remains unclear whether JNK or amyloid ß (Aß) appears first in the disease onset. Postmortem brain tissues from four dementia subtypes of patients (frontotemporal dementia, Lewy body dementia, vascular dementia, and AD) were used to measure activated JNK (pJNK) and Aß levels. pJNK expression is significantly increased in AD; however, similar pJNK expression was found in other dementias. Furthermore, there was a significant correlation, co-localization, and direct interaction between pJNK expression and Aß levels in AD. Significant increased levels of pJNK were also found in Tg2576 mice, a model of AD. In this line, Aß42 intracerebroventricular injection in wild-type mice was able to induce a significant elevation of pJNK levels. JNK3 overexpression, achieved by intrahippocampal injection of an adeno-associated viral vector expressing this protein, was enough to induce cognitive deficiencies and precipitate Tau aberrant misfolding in Tg2576 mice without accelerating amyloid pathology. JNK3 overexpression may therefore be triggered by increased Aß. The latter, together with subsequent involvement of Tau pathology, may be underlying cognitive alterations in early stages of AD.

Hypopigmentation in mantled howler monkeys Alouatta palliata (gray 1849): First documented cases of whole-body leucism in South America.

The existence of hypopigmentation like leucism is the result of genetic anomalies that might be enhanced by external factors such as pollution. This anomaly may reduce survival rates. Leucism has been recorded in wildlife, but overall, it is considered very rare. There have been few records of mantled howler monkeys with leucism in Mexico and Costa Rica, but whole-body leucism in howler monkeys from South America was unknown. In this article, we report for the first-time documented cases of whole-body leucism in young individuals of mantled howler monkeys Alouatta palliata in an isolated remanent of tropical dry forest in southwestern Ecuador known as Cerro Blanco Protective Forest. In total, we found two juvenile individuals with leucism in October 2021. The report of howler monkeys with whole-body leucism may be caused by two processes: inbreeding because of isolated populations, environmental pressure caused by pollution, or the interaction of both. Our findings also reveal that hypopigmentation is becoming more frequent in howler monkey populations along its distributional range. Therefore, it is important to promote research in this field to disentangle the causes of hypopigmentation and to consider a regional management strategy for the species.

La existencia de afecciones que causan hipopigmentación, como el leucismo, son el resultado de anomalías genéticas que pueden verse potenciadas por factores externos como la contaminación. Estas anomalías puedes reducir las tasas de supervivencia. Se ha registrado leucismo en la vida silvestre, pero en general, se considera muy raro. En México y Costa Rica se ha reportado la existencia de casos aislados de monos aulladores de manto con leucismo, pero se desconocía el leucismo de cuerpo completo en monos aulladores para América del Sur. En este artículo, reportamos por primera vez casos documentados de leucismo en todo el cuerpo en individuos juveniles de monos aulladores de manto Alouatta palliata en un remanente aislado de bosque seco tropical en el suroeste de Ecuador conocido como Bosque Protector Cerro Blanco. En total, encontramos dos individuos juveniles con leucismo en octubre de 2021. Este reporte de monos aulladores con leucismo en todo el cuerpo puede ser causado por dos procesos: apareamiento dentro de individuos de la misma población causado por el aislamiento, la presión ambiental causada por la contaminación o la interacción de ambos. Nuestros hallazgos también revelan que la hipopigmentación es cada vez más frecuente en las poblaciones de monos aulladores a lo largo de su rango de distribución. Por lo tanto, es importante promover la investigación en este campo para determinar las causas de la hipopigmentación y considerar una estrategia de manejo regional para la especie. Palabras clave: aberraciones cromáticas, pérdida de conectividad, anomalías genéticas, endogamia, cambio de pigmentación en primates por contaminación, Bosque Seco del Pacífico Ecuatorial.

[The efficacy of caloric intake in critically ill patients with traumatic pathology]. / Eficacia del aporte calórico en pacientes con patología traumática.

BACKGROUND: the effective contribution of enteral nutrition (EN) in intensive care units (ICU) is due to multiple factors. OBJECTIVES: to determine the efficacy of caloric intake in critically ill patients with traumatic pathology receiving enteral nutrition, and to analyze cause and time of interruption of EN. METHOD: prospective observational study (November 2015 - August 2016). INCLUSION CRITERIA: patient with EN ≥ 48 hours and age ≥ 18 years. EXCLUSION CRITERIA: patient with oral and/or parenteral nutrition. VARIABLES: demographic, day of EN, prescribed and administered kilocalories (kcal), caloric difference, caloric objective and variables related to the interruptions of the EN. The handling of EN and interruptions are made according to the unit's internal protocol. Kcal/patient are calculated according to the Harris-Benedict equation and multiplied by a stress factor depending on the type of trauma of the patient. RESULTS: sixty-nine patients were included, 79.71% were men, with a median age of 46 (34-58) years. A total of 1,112 days of EN were monitored. As of the third day of admission to the ICU (979 days monitored), the nutritional efficacy was optimal (caloric intake > 80%): 92.43% (72.8-97.5). The optimal caloric goal was maintained in 67.9% of these days. The most frequent causes of interruption of NE were procedures unrelated to airway, with holding time of three (1-7.25) hours. CONCLUSIONS at the third day, the patients with traumatic pathology received at least 80% of the prescribed caloric intake. Among the most frequent causes of interruption of EN were the procedures unrelated to airway.

INTRODUCCIÓN: el aporte efectivo de la nutrición enteral (NE) en las unidades de cuidados intensivos (UCI) se ve afectado por múltiples factores. OBJETIVOS: determinar la eficacia en el aporte calórico a los pacientes críticos con patología traumática que reciben nutrición enteral. Analizar causa y tiempo de interrupción de NE. MÉTODO: estudio observacional prospectivo (de noviembre de 2015 a agosto de 2016). Criterios de inclusión: paciente con NE ≥ 48 horas y edad ≥ 18 años. Criterios de exclusión: paciente con dieta oral y/o parenteral. Variables: demográficas, día de NE, kilocalorías (kcal) prescritas, administradas, diferencia calórica, objetivo calórico y relacionadas con las interrupciones de la NE. El manejo de NE e interrupciones se realiza según protocolo interno de la unidad. Las kcal/paciente se calculan según la ecuación de Harris-Benedict y multiplicando por un factor de estrés en función del tipo de trauma del paciente. RESULTADOS: se incluyeron 69 pacientes (el 79,71% eran hombres) con una mediana de edad de 46 (34-58) años. Se monitorizaron un total de 1.112 días de NE. A partir del tercer día de ingreso en UCI (979 días monitorizados) la eficacia nutricional fue óptima (aporte calórico > 80%): 92,43% (72,8-97,5). Mantenemos el objetivo calórico óptimo en el 67,9% de estos días. Observamos como causa más frecuente de interrupción de la NE los procedimientos no relacionados con la vía aérea, con un tiempo de parada de tres (1-7,25) horas. CONCLUSIÓN: el aporte calórico del paciente crítico con patología traumática se logra de forma óptima a partir del día 3. Entre las causas de interrupción de la NE más frecuentes se encuentran los procedimientos no relacionados con la vía aérea.

Pain Assessment in Mechanically Ventilated, Noncommunicative Severe Trauma Patients.

The aim of this study was to measure pain levels in noncommunicative patients with severe trauma who required tracheal suctioning and mobilization and to determine the utility of the Behavioral Indicators of Pain Scale (ESCID) in these cases. The pain scores for the procedures were recorded on Days 1, 3, and 6 of the patients' stay in the intensive care unit. These assessments were performed at 3 moments: before, during, and after the application of the procedures. Because of the longitudinal character of the study, data were fitted into a multivariate model using the Generalized Estimating Equations method. The sample of 124 patients comprised 77.4% males and 22.6% females with an average age of 45.93 (SD = 16.43) years. A significant increase (p < .01) in the ESCID score was observed during the application of the procedures that produced similar pain levels. Kappa coefficient value obtained for interobserver agreement of ESCID scale scores during the application of care procedures at the intervals being evaluated was greater than 0.84, which should be interpreted as almost perfect. The ESCID scores increased during 2 care procedures that are frequently carried out in intensive care units and indicated that they produced similar pain levels.

c-Jun N-terminal Kinase (JNK) Signaling as a Therapeutic Target for Alzheimer's Disease.

c-Jun N-terminal kinases (JNKs) are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death, and regulation of cellular senescence. It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or Aß peptides. Altogether, JNKs have become a focus of screening strategies searching for new therapeutic approaches to diabetes, cancer or liver diseases. In addition, activation of JNK has been identified as a key element responsible for the regulation of apoptosis signals and therefore, it is critical for pathological cell death associated with neurodegenerative diseases and, among them, with Alzheimer's disease (AD). In addition, in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with pathogenesis and neuronal death in AD. JNK's, particularly JNK3, not only enhance Aß production, moreover it plays a key role in the maturation and development of neurofibrillary tangles. This review aims to explain the rationale behind testing therapies based on inhibition of JNK signaling for AD in terms of current knowledge about the pathophysiology of the disease. Keeping in mind that JNK3 is specifically expressed in the brain and activated by stress-stimuli, it is possible to hypothesize that inhibition of JNK3 might be considered as a potential target for treating neurodegenerative mechanisms associated with AD.