Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

Morphometric analysis of transsphenoidal surgery in Peruvian population.

Background: Transsphenoidal surgery has become a key element in the approach to skull base pathologies. The objective of the study was to explore the morphometry of the sphenoidal region in the Peruvian population, with an emphasis on understanding its specific anatomical characteristics and providing quantitative data for the planning of transsphenoidal surgery. Methods: A cross-sectional study included a random sample of 81 cases of healthy individuals who presented to the Radiology Department of a Private Hospital Center in Peru over 1 year. Skull computed tomography scans without contrast were performed, and a detailed morphometric analysis was conducted by an expert neurosurgeon, including measurements of four parameters to evaluate the anatomy of the craniofacial region. Results: Most participants exhibited complete sellar pneumatization, followed by incomplete sellar pneumatization, while conchal pneumatization was rare. Significant differences were found between men and women in the distance from the nasal opening to the dorsum of the sella turcica. No significant gender differences were observed in other anatomical measurements or significant changes with age in anatomical measurements. Conclusion: Morphometric analysis provides crucial data for the precise customization of surgical interventions in the Peruvian population, especially in transsphenoidal surgery. The results highlight the importance of considering individual anatomical differences and gender variability during surgical planning. Morphometry emerges as a valuable tool to enhance the quality and safety of transsphenoidal surgery by adapting surgical strategies to the specific anatomical dimensions of each patient.

Morphometric analysis of the foramen magnum in the Peruvian population.

Background: The foramen magnum, as an anatomical structure, holds clinical and functional significance due to its strategic location in the craniovertebral transition. A detailed understanding of its dimensions and shapes is crucial for better comprehension of related pathologies and for enhancing neurosurgical techniques within a specific population. The objective is to measure precise morphometric reference points of the foramen magnum in individuals of Peruvian ancestry, aiming to establish specific anatomical patterns and potential variations within this population. Methods: The study was conducted on 17 unidentified skulls donated to the NeuroZone3D Research Center, utilizing an inelastic and soft measuring tape as the tool. Our report considered direct anthropometric measurement techniques with data collection performed by a single researcher. Results: Distinct morphometric characteristics were observed in the foramen magnum of the Peruvian population compared to other studies. The average measurements of the skull base revealed a foramen magnum with a mean length of 33.80 mm and a width of 28.70 mm, along with right condyles measuring 25 mm in length and 14.10 mm in width, and left condyles measuring 23.80 mm in length and 13.90 mm in width. Conclusion: The morphometric analysis of the foramen magnum in the Peruvian population provides valuable insights into specific anatomical features within this ethnic group. These findings could have significant implications across various medical and surgical disciplines, from interpreting diagnostic images to designing more precise therapeutic interventions tailored to this population.

Catalytic Selective Oxidation of ß-O-4 Bond in Phenethoxybenzene as a Lignin Model Using (TBA)5[PMo10V2O40] Nanocatalyst: Optimization of Operational Conditions.

The catalytic oxidation of phenethoxybenzene as a lignin model compound with a ß-O-4 bond was conducted using the Keggin-type polyoxometalate nanocatalyst (TBA)5[PMo10V2O40]. The optimization of the process's operational conditions was carried out using response surface methodology. The statistically significant variables in the process were determined using a fractional factorial design. Based on this selection, a central circumscribed composite experimental design was used to maximize the phenethoxybenzene conversion, varying temperature, reaction time, and catalyst load. The optimal conditions that maximized the phenethoxybenzene conversion were 137 °C, 3.5 h, and 200 mg of catalyst. In addition, under the optimized conditions, the Kraft lignin catalytic depolymerization was carried out to validate the effectiveness of the process. The depolymerization degree was assessed by gel permeation chromatography from which a significant decrease in the molar mass distribution Mw from 7.34 kDa to 1.97 kDa and a reduction in the polydispersity index PDI from 6 to 3 were observed. Furthermore, the successful cleavage of the ß-O-4 bond in the Kraft lignin was verified by gas chromatography-mass spectrometry analysis of the reaction products. These results offer a sustainable alternative to efficiently converting lignin into valuable products.

A novel technique with polypropylene endoport for minimally invasive, microscopic evacuation of intracerebral hemorrhage: illustrative case.

BACKGROUND: Spontaneous intracerebral hemorrhage is a neurological condition with high rates of morbidity and mortality, which is treated by various surgical techniques that seek minimal parenchymal distortion and maximum evacuation of the hematoma. OBSERVATIONS: The advancement of technology has allowed the development of minimally invasive techniques, but the high cost of its equipment is a limitation for its practice in developing countries or third world countries. A new technique called MEP-BA by its acronym in Spanish (microscope, polypropylene endoport and Foley catheter, bipolar forceps and aspiration) is presented, which seeks optimal results with low-cost materials through a polypropylene endoport with a sterile disposable syringe and Foley catheter, allowing the creation of transcortical or transsulcal corridors for the total evacuation of the hematoma. LESSONS: The neurosurgeon must be a creator and innovator of neurosurgical techniques and equipment that allow procedures to be reproducible worldwide. The MEP-BA technique provides low-cost access through which it allows the use of aspiration and coagulation devices, minimizing brain damage and maximizing the safety and efficacy of intracerebral hematoma evacuation.

Lesión difusa de médula espinal, ¿cirugía o tratamiento paliativo?: a propósito de un caso

Las lesiones difusas de médula son raras y un reto diagnóstico. Los gliomas de bajo grado son los de mayor prevalencia y los astrocitomas primarios, el subtipo más frecuente. Presentamos el caso de un varón de 36 años, con tiempo de enfermedad de 13 años de dolor cervical insidioso, progresa con hemiparesia derecha y, posteriormente, paraparesia severa con pérdida de control de esfínteres. Mediante una RMN total de columna se evidenciaron lesiones neoproliferativas difusas abarcando todos los segmentos medulares. Se realizó una biopsia a cielo abierto en segmento T1-T2, la patología diagnosticó glioma de bajo grado. El tratamiento es controversial y se descartó la cirugía por la alta morbilidad. Se optó por radioterapia y quimioterapia por su rol importante en el control de la enfermedad.

Diffuse spinal cord injuries are rare and pose a diagnostic challenge. Low-grade gliomas are the most prevalent type, with primary astrocytomas being the most frequent subtype. We present the case of a 36-year-old man with a 13-year history of squeezing neck pain, which progressed with right hemiparesis and later with severe paraparesis and loss of sphincter control. A whole spine MRI scan showed diffuse neoproliferative lesions that spread throughout all the spinal cord segments. An open biopsy of the lesion in the T1-T2 segment was performed. The pathology report stated low-grade glioma. Treatment is controversial, so surgery was ruled out due to high morbidity. Radiotherapy and chemotherapy were chosen because they play an important role in controlling the disease.

Técnica de clonación 3D aplicada en planificación quirúrgica para craneosinostosis sagital en Latinoamérica-Perú: reporte de caso

La craneosinostosis sagital es el cierre prematuro de la sutura sagital, ocasionando alteraciones funcionales y estructurales. El tratamiento es quirúrgico, y actualmente se cuenta con diversas técnicas, las cuales requieren de una planificación y entrenamiento para lograr óptimos resultados. Se presenta el caso de un varón de 1 año presenta crecimiento anteroposterior anormal del cráneo, indicándose tomografía cerebral sin contraste evidenciando una sinostosis sagital. Se realiza la planificación quirúrgica de la técnica a desarrollar mediante modelo 3D personalizado a escala real. Paciente cursa con buena evolución y es dado de alta. Finalmente, la tecnología de clonación 3D esencial para la educación y desarrollo neuroquirúrgico permitiendo acceder a modelos táctiles de alta precisión y bajo costo que mejoran la calidad del manejo de craneosinostosis.

Sagittal craniosynostosis is the premature closure of the sagittal suture, causing functional and structural alterations. The treatment is surgical, and there are currently various techniques, which require planning and training to achieve optimal results. We present the case of a 1-year-old male with abnormal anteroposterior growth of the skull, indicating brain tomography without contrast, showing sagittal synostosis. Surgical planning of the technique to be developed is carried out using a real-scale personalized 3D model. The patient progresses well and is discharged. Finally, essential 3D cloning technology for neurosurgical education and development allows access to high-precision, low-cost tactile models that improve the quality of craniosynostosis management.

Urgencia odontopediátrica asociada a Bola Adiposa de Bichat: informe de un caso / Pediatric dental emergency associated with Bichat ́s fat pad: a case report

Objetivo: Presentar la resolución quirúrgica de un caso clínico poco frecuente en un paciente pediátrico luego de ha- ber sufrido la herniación traumática de la Bola Adiposa de Bichat. Caso clínico: Un paciente de 3 años concurre a la guar- dia del Hospital Interzonal Especializado Materno Infantil "Don Victorio Tetamanti" de Mar del Plata, luego de haber sufrido un traumatismo que le provocó el desplazamiento par- cial de la Bola Adiposa de Bichat. Si bien este tipo de urgencias es poco frecuente, es impor- tante tener los conocimientos para un correcto diagnóstico y tratamiento (AU))

Aim: To present the surgical resolution of an infrequent clinical case in a pediatric patient who suffered traumatic herniation of Bichat's fat pad. Clinical case: A 3-year-old patient who visited the Emergency Service at the "Don Victorio Tetamanti" Hospital in Mar del Plata after suffering a trauma which caused the partial displacement of Bichat's fat pad. Although this type of emergency is quite rare, it is important to know how to per- form proper diagnosis and treatment (AU)

El baile Tejida de cintas del pueblo Kichua Panzaleo. Origen y simbología

Los orígenes de los bailes para los pueblos tienen un alto valor, tanto por el bien que produce esta actividad física como por el significado cultural que provee. La tejida de cintas puede ser considerada como una danza ancestral o un baile producto del mestizaje e igualmente considerada como un legado que anima tanto a la Cultura Física, como a las tradiciones culturales de sus practicantes. Posiblemente es originario del pueblo Panzaleo o de otros pueblos de la sierra ecuatoriana. Sobre la base de un estudio etnográfico y la utilización de fuentes orales, fotográficas y videos, se analizaron su origen, la simbología, los cambios y persistencias de esta tradición. En tal sentido, el objetivo de la investigación es: promover el vínculo que guarda esta manifestación con la actividad física, su origen, la simbología y la vigencia de esta tradición en la parroquia de Pastocalle. El estudio es etnográfico, utilizando la técnica de la observación científica con un registro anecdótico y la entrevista con una guía de preguntas semiestructurada y el portafolio de fotos y videos. Los entrevistados no pueden precisar con exactitud la época de vigencia de la tejida de cintas, ni tampoco si este baile es originario de la parroquia, ya que también se realiza en otros pueblos cercanos. Se concluye que el vestuario original descrito es propio de la parroquia Pastocalle, que la tejida de cintas es originario del pueblo kichua Panzaleo y que actualmente está en proceso de consolidarse como referente simbólico parroquial.

As origens das danças para o povo são de grande apreço, tanto pelo bem que esta prática física produz como pelo sentido cultural que ela traz. A tecelagem de fitas pode ser considerada uma dança ancestral ou um produto da dança mestiça e igualmente um legado que anima tanto a cultura física como as tradições culturais dos seus praticantes. Pode eventualmente, vir do povo Panzaleo ou de outros povos das terras altas equatorianas. Com base num estudo etnográfico e na utilização de fontes orais, fotográficas e de vídeo, foi examinada a origem, o simbolismo, as mudanças e a persistência desta tradição. Neste sentido, o objetivo da investigação é: promover a ligação entre este evento e a atividade física, a sua origem, simbolismo e a validade desta tradição na sua Paróquia de Pastocalle. O estudo é etnográfico, utilizando a técnica da observação científica com um registo anedótico e a entrevista com um guia semiestruturado de perguntas e o portfólio de fotografias e vídeos. Os inquiridos não podem dizer exatamente quando se realizou a tecelagem das fitas, nem se esta dança teve origem na Freguesia, como também é realizada em outras aldeias próximas. Conclui-se que o traje original descrito é típico da Paróquia de Pastocalle, que a tecelagem de fitas teve origem no povo Kichua Panzaleo e que está atualmente em processo de consolidação como uma referência simbólica da Paróquia.

The origins of the dances for the people have a high value, both for the good that this physical activity produces and for the cultural significance it provides. La tejida de cintas can be considered as an ancestral dance or a dance product of miscegenation and equally considered as a legacy that animates both the Physical Culture and the cultural traditions of its practitioners. It is possibly originally from the Panzaleo people or from other towns in the Ecuadorian highlands. Based on an ethnographic study and the use of oral, photographic and video sources, its origin, symbolism, changes and persistence of this tradition were analyzed. In this sense, the objective of the research is: to promote the link between this manifestation and physical activity, its origin, symbolism and the validity of this tradition in the parish of Pastocalle. The study is ethnographic, using the technique of scientific observation with an anecdotal record and the interview with a guide of semistructured questions and the portfolio of photos and videos. The interviewees are not able to specify the exact time of validity of La tejida de cintas, nor if this dance is native to the parish, since it is also performed in other nearby towns. It is concluded that the original costume described is typical of the Pastocalle parish, that La tejida de cintas originated in the Kichua Panzaleo people and that it is currently in the process of consolidating itself as a symbolic parochial reference.

Gold nanoparticle-decorated earth-abundant clay nanotubes as catalyst for the degradation of phenothiazine dyes and reduction of 4-(4-nitrophenyl)morpholine.

In the present work, halloysite nanotubes modified with gold nanoparticles (AuNPs-HNT) are successfully prepared by wet chemical method for the catalytic degradation of phenothiazine dyes (azure B (AZB) and toluidine blue O (TBO)) and also cleaner reduction of 4-(4-nitrophenyl)morpholine (4NM) in the sodium borohydride (NaBH4) media. The catalyst is formulated by modifying the HNT support with a 0.964% metal loading using the HNT supports modified with 3-aminopropyl-trimethoxysilane (APTMS) coupling agent to facilitate the anchoring sites to trap the AuNPs and to prevent their agglomeration/aggregation. The AuNPs-HNT catalyst is investigated for structural and morphological characterization to get insights about the formation of the catalyst for the effective catalytic reduction of dyes and 4NM. The microscopic studies demonstrate that AuNPs (2.75 nm) are decorated on the outer surface of HNT. The as-prepared AuNPs-HNT catalyst demonstrates AZB and TBO dye degradation efficiency up to 96% in 10 and 11 min, respectively, and catalytic reduction of 4NM to 4-morpholinoaniline (MAN) is achieved up to 97% in 11 min, in the presence of NaBH4 without the formation of any by-products. The pseudo-first-order rate constant (K1) value of the AuNPs-HNT catalyst for AZB, TBO, and 4NM were calculated to be 0.0078, 0.0055, and 0.0066 s-1, respectively. Moreover, the synthesized catalyst shows an excellent reusability with stable catalytic reduction for 7 successive cycles for both the dyes and 4NM. A plausible mechanism for the catalytic dye degradation and reduction of 4NM by AuNPs-HNT catalyst is proposed as well. The obtained results clearly indicate the potential of AuNPs-HNT as an efficient catalyst for the removal of dye contaminants from the aquatic environments and cleaner reduction of 4NM to MAN, insinuating future pharmaceutical applications.

Association between the Physical Activity Behavioral Profile and Sedentary Time with Subjective Well-Being and Mental Health in Chilean University Students during the COVID-19 Pandemic.

OBJECTIVE: To analyze the association between the behavioral profile of physical activity and sedentary time with subjective well-being and mental health in university students during the COVID-19 pandemic in Chile. METHODS: Cross-sectional study in a voluntary sample of 469 university students (22.4 ± 0.19 years; 66% women). According to students' self-reports of physical activity and sedentary time, four behavioral profiles were created to investigate their association with subjective well-being and mental health using one-factor ANOVA that was adjusted to a multifactorial model. RESULTS: The physically inactive and sedentary behavior profile presents the lowest levels of subjective well-being (p < 0.001), positive affective experiences (p < 0.001) and general mental health (p = 0.001). When adjusting for confounding variables, it was observed that the physically active and non-sedentary profile was associated with better general mental health (p < 0.01) in contrast to those who are physically active and sedentary. CONCLUSIONS: Chilean university students with a physically inactive and sedentary profile during the pandemic presented worse well-being and mental health, with a sedentary lifestyle being one of the variables that most affects the mental health of these students. Therefore, measures should be implemented to encourage this population to maintain adequate levels of physical activity and reduce sedentary times.

Dataset from analytical pyrolysis assays for converting waste tires into valuable chemicals in the presence of noble-metal catalysts.

About 25.7 million tons of waste tires (WT) are discarded each year worldwide causing important environmental, and health problems. This waste is difficult to manage and dispose due to its huge rate of generation and its extremely slow biodegradation. Therefore, many efforts are being made to valorise WTs into a series of marketable products under a circular economy framework. In the attempt to convert WT into higher-value products, thermochemical decomposition by pyrolysis has emerged as a promising process [1]. The pyrolysis is a thermochemical transformation (under an oxygen-depleted atmosphere) of the tire´s polymeric constituents: natural rubber (NR), styrene-butadiene rubber (SBR), and butadiene rubber (BR) into three major fractions. These fractions are a gas (10-35%, TPG) which is usually used as a heat source (50 MJ kg-1), a solid consisting mainly of recovered carbon black (12-45%, rCB), and a liquid fraction (35-65%, TPO) containing a complex mixture of organic compounds. Among the high-value compounds that can be found in the TPO are D,L-limonene, isoprene, benzene, toluene, mixed-xylene, ethylbenzene, styrene, p-cymene, and some polycyclic aromatic hydrocarbons. This mixture is commonly used as a diesel substitute and owing to its complex composition it rarely is seen as a source for more valuable products. To overcome such a complexity, and selectively produce specific chemical identities, different types of catalysts have been used [2,3]. Herein, we provide a dataset from a systematic study about catalytic pyrolysis of WT for selectively producing benzene, toluene, and xylenes (BTX) and p-cymene on noble metals (Pd, Pt, Au) supported on titanate nanotubes (NT-Ti). The comprehensive analysis of this data was recently published, thus, the analytical techniques, experimental conditions and dataset are given in the present paper as a complement to that publication [1]. The reaction was evaluated in an analytical pyrolysis unit consisting in a micropyrolizer coupled to a mass spectrometer (Py-GC/MS) operating at temperatures between 400 and 450 °C in a fast pyrolysis regime (12 s). The effectivity of catalysts was measured in terms of selectivity to monoaromatics as BTX and p-cymene, under non-catalytic and for catalytic pyrolysis conditions. Moreover, the reaction was conducted on individual rubbers (Polyisoprene, Polybutadiene, and Styrene-Butadiene) and DL-limonene, to get deep insights into the transformation behaviour and reaction pathways. Therefore, the reader will find a data-in-brief paper containing some characterizations of the WTs used for the investigation, along with a complete dataset of Py-GC/MS results. Finally, the original files for the interpretation of the MS results are also provided, so that the reader can easily use this information to further expand the study to their own interest (industrial or scientific).

Microcirugía mínimamente invasiva para aneurisma de la arteria comunicante anterior: abordaje supraorbitario lateral más angiografía con fluoresceína intraoperatoria / Minimally invasive micro surgery for aneurysm of the anterior communicating artery: supra-orbitary lateral approach with intraoperative Fluorescein Angiography

RESUMEN Los aneurismas de la arteria comunicante anterior son complejos y requieren de tratamiento endovascular o microquirúrgico según sus características. El uso de enfoques mínimamente invasivos en microcirugía continúa evolucionando. Presentamos el caso de un paciente de 34 años con un aneurisma cerebral no roto de AcoA de cuello ancho, con escala de Glasgow de 15 puntos. Se realizó un abordaje supraorbitario lateral más "clipaje" total del aneurisma usando angio fluoresceína intraoperatoria. Se logró el objetivo con seguridad y eficacia; al mismo tiempo se optimizó el tiempo quirúrgico y hospitalario, maximizando la comodidad del paciente, estética y reanudación a sus actividades tempranas. (AU)

SUMMARY Anterior communicating artery aneurisms (ACAA) are complex and require endovascular or microsurgery approaches. The use of minimally invasive microsurgery techniques is evolving. We present the case of a 34-yearold patient with a broad neck, non-broken, ACAA with a Glasgow coma scale of 15 points. A lateral supra-orbitary approach with total clipping of the ACAA using intra-operatory fluorescein angiography was performed. The objective was accomplished successfully and safe, optimizing both intra-operative and hospitalization times, thus,maximizing patient comfort, esthetic and prompt return to normal duties. (AU)

A Simplified Kinetic Model for the Enantioselective Hydrogenation of 1-Phenyl-1,2-Propanedione over Ir/TiO2 in the Presence of a Chiral Additive.

This communication proposes a preliminary simplified kinetic model for the hydrogenation of 1-phenyl-1,2-propanedione that can render up to eight compounds, involving regioselectivity and enantioselectivity. The catalytic system comprises two functionalities; the heterogeneous catalyst (Ir/TiO2) plays the role for the hydrogenation, whereas the adsorption/binding to the active site is played by a chiral molecule (cinchonidine), added to the reaction mixture. The reaction occurs at room temperature and total pressure of 40 bar. The product distribution shows competitive parallel and series pathways with up to 12 possible reactions. Despite the complexity of both reaction and catalyst system, a simplified kinetic model was able to predict the concentrations profiles. The model assumes the reactions to be apparent first order in the concentrations of reactant and intermediate products, while the kinetic constants include all other effects (partial pressure of hydrogen, solvent and catalyst effects, and the concentration of the chiral additive). The concentration profiles were well-modeled with low residual values. The errors in the kinetic constants (k-values) were small for all relevant parameters of the main reaction pathways. Two k-values are nil, which is the lower bound imposed in the model, suggesting that these reaction pathways are likely negligible. The positive outcome from this simplified model suggests that the process can be formally treated as a first-order irreversible homogeneous catalyzed reaction, despite a heterogeneous catalyst was employed (with a modifier). Despite the promising results, the model must be extended for a more general applicability, or conditions where it is applicable.

Anxiety, Low Self-Esteem and a Low Happiness Index Are Associated with Poor School Performance in Chilean Adolescents: A Cross-Sectional Analysis.

OBJECTIVE: To analyze the relationship between anxiety, self-esteem, happiness index and primary school students' academic performance in Chilean adolescents from the Biobío province. METHODOLOGY: 733 (46.1% girls; 12 (1.3 years)) public primary school students that completed the 2018 Health and School Performance Survey carried out in the Biobío province were included in this cross-sectional analysis. The BECK Anxiety Inventory (BAI) was used to measure anxiety while happiness index and self-esteem were measured using the subjective happiness scale and the Rosenberg self-esteem scale, respectively. School performance was measured by grade point average (GPA) of language, math, physical education and cumulative GPA, and behavior associated with cognition in the school context was also considered. The relationship between mental health indicators and school performance was investigated using a one-way ANOVA and Pearson correlation. RESULTS: In comparison to students with low anxiety levels and high self-esteem and happiness levels, students with higher anxiety levels, lower self-esteem and happiness levels perceived themselves as having memory problems. They were also slower to solve math problems, had a shorter attention span in class and presented more difficulties in solving complex tasks, as well as being more nervous during testing. These students also got the lowest grade point average in math, language and physical education. CONCLUSIONS: High anxiety levels, low self-esteem and low happiness levels were associated with lower school performance and weaker behavior associated with cognition in Chilean adolescents. Implementing plans of emotional education and mental health could improve academic achievement.

Rational Design of Novel Glycomimetic Peptides for E-Selectin Targeting.

E-selectin is a cell-adhesion receptor with specific recognition capacity toward sialo-fucosylated Lewis carbohydrates present in leukocytes and tumor cells. E-selectin interactions mediate the progress of inflammatory processes and tumor metastasis, which aroused the interest in using this protein as a biomolecular target to design glycomimetic inhibitors for active targeting or therapeutic purposes. In this work, we report the rational discovery of two novel glycomimetic peptides targeting E-selectin based on mutations of the reference selectin-binding peptide IELLQAR. Sixteen single or double mutants at Ile1, Leu3, Leu4, and Arg7 residues were evaluated as potential candidates for E-selectin targeting using 50 ns molecular dynamics (MD) simulations. Nine peptides showing a stable association with the functional pocket were modified by adding a cysteine residue to the N-terminus to confer versatility for further chemical conjugation. Subsequent 50 ns MD simulations resulted in five cysteine-modified peptides with retained or improved E-selectin binding potential. Then, 300 ns accelerated MD (aMD) simulations were used to examine the binding properties of the best five cysteine-modified peptides. CIEELQAR and CIELFQAR exhibit the most selective association with the functional pocket of E-selectin, as revealed by potential of mean force profiles. Microscale thermophoresis experiments confirmed the E-selectin binding capacity of the selected peptides with KD values in the low micromolar range (CIEELQAR KD = 35.0 ± 1.4 µM; CIELFQAR KD = 16.4 ± 0.7 µM), which are 25-fold lower than the reported value for the native ligand sLex (KD = 878 µM). Our findings support the potential of CIEELQAR and CIELFQAR as novel E-selectin-targeting peptides with high recognition capacity and versatility for chemical conjugation, which are critical for enabling future applications in active targeting.

High extracellular ATP levels released through pannexin-1 channels mediate inflammation and insulin resistance in skeletal muscle fibres of diet-induced obese mice.

AIMS/HYPOTHESIS: Skeletal muscle is a key target organ for insulin's actions and is the main regulator of blood glucose. In obese individuals and animal models, there is a chronic low-grade inflammatory state affecting highly metabolic organs, leading to insulin resistance. We have described that adult skeletal muscle fibres can release ATP to the extracellular medium through pannexin-1 (PANX1) channels. Besides, it is known that high extracellular ATP concentrations can act as an inflammatory signal. Here, we propose that skeletal muscle fibres from obese mice release high levels of ATP, through PANX1 channels, promoting inflammation and insulin resistance in muscle cells. METHODS: C57BL/6J mice were fed with normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. Muscle fibres were isolated from flexor digitorum brevis (FDB) muscle. PANX1-knockdown FDB fibres were obtained by in vivo electroporation of a short hairpin RNA Panx1 plasmid. We analysed extracellular ATP levels in a luciferin/luciferase assay. Gene expression was studied with quantitative real-time PCR (qPCR). Protein levels were evaluated by immunoblots, ELISA and immunofluorescence. Insulin sensitivity was analysed in a 2-NBDG (fluorescent glucose analogue) uptake assay, immunoblots and IPGTT. RESULTS: HFD-fed mice showed significant weight gain and insulin resistance compared with NCD-fed mice. IL-6, IL-1ß and TNF-α protein levels were increased in FDB muscle from obese mice. We observed high levels of extracellular ATP in muscle fibres from obese mice (197 ± 55 pmol ATP/µg RNA) compared with controls (32 ± 10 pmol ATP/µg RNA). ATP release in obese mice fibres was reduced by application of 100 µmol/l oleamide (OLE) and 5 µmol/l carbenoxolone (CBX), both PANX1 blockers. mRNA levels of genes linked to inflammation were reduced using OLE, CBX or 2 U/ml ATPase apyrase in muscle fibres from HFD-fed mice. In fibres from mice with pannexin-1 knockdown, we observed diminished extracellular ATP levels (78 ± 10 pmol ATP/µg RNA vs 252 ± 37 pmol ATP/µg RNA in control mice) and a lower expression of inflammatory markers. Moreover, a single pulse of 300 µmol/l ATP to fibres from control mice reduced insulin-mediated 2-NBDG uptake and promoted an elevation in mRNA levels of inflammatory markers. PANX-1 protein levels were increased two- to threefold in skeletal muscle from obese mice compared with control mice. Incubation with CBX increased Akt activation and 2-NBDG uptake in HFD fibres after insulin stimulation, rescuing the insulin resistance condition. Finally, in vivo treatment of HFD-fed mice with CBX (i.p. injection of 10 mg/kg each day) for 14 days, compared with PBS, reduced extracellular ATP levels in skeletal muscle fibres (51 ± 10 pmol ATP/µg RNA vs 222 ± 28 pmol ATP/µg RNA in PBS-treated mice), diminished inflammation and improved glycaemic management. CONCLUSIONS/INTERPRETATION: In this work, we propose a novel mechanism for the development of inflammation and insulin resistance in the skeletal muscle of obese mice. We found that high extracellular ATP levels, released by overexpressed PANX1 channels, lead to an inflammatory state and insulin resistance in skeletal muscle fibres of obese mice.

NanoMIPs Design for Fucose and Mannose Recognition: A Molecular Dynamics Approach.

Nanoscale molecularly imprinted polymers (nanoMIPs) are powerful molecular recognition tools with broad applications in the diagnosis, prognosis, and treatment of complex diseases. In this work, fully atomistic molecular dynamics (MD) simulations are used to assist the design of nanoMIPs with recognition capacity toward l-fucose and d-mannose as prototype disease biomarkers. MD simulations were conducted on prepolymerization mixtures containing different molar ratios of the monomers N-isopropylacrylamide (NIPAM), methacrylamide (MAM), and (4-acrylamidophenyl)(amino)methaniminium acetate (AB) and fixed molar ratios of the cross-linker ethylene glycol dimethacrylate (EGDMA) in explicit acetonitrile as the porogenic solvent. Prepolymerization mixtures containing ternary mixtures of NIPAM (50%), MAM (25%), and AB (25%) exhibit the best imprinting potential for both l-fucose and d-mannose, as they maximize (i) the stability of template-monomer plus template-cross-linker interactions, (ii) the number of functional monomers plus cross-linkers organized around the template, and (iii) the number of hydrogen bonds participating in template recognition. The studied prepolymerization mixtures exhibit an overall increased recognition capacity toward d-mannose over l-fucose, which is attributed to the higher hydrogen-bonding capacity of the former template. Our results are valuable to guide the synthesis of efficient nanoMIPs for sugar recognition and provide a computational framework extensible to any other template, monomer, or cross-linker combination, thus constituting a promising strategy for the rational design of molecularly imprinted materials.