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BACKGROUND: There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability. METHODS: Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds. RESULTS: The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM. CONCLUSION: Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.

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Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

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INTRODUCTION: Thrombosis is one of the leading causes of morbidity and mortality worldwide. Venous thromboembolic disease (VTD) is considered a new epidemic. FXII deficiency is supposed to be a cause of thrombosis. To search for unknown causes of thrombosis in our population, our aim was to determine if FXII deficiency can be considered a risk factor for VTD. METHODS: Young adult Mexican patients with at least one VTD episode and healthy controls were included in this prospective, observational, controlled study. Liver and renal function tests, blood cytometry, and blood coagulation assays were performed. Plasma FXII activity and its concentration were evaluated. RESULTS: Over a two-year period, 250 patients and 250 controls were included. FXII activity was significantly lower in the control group compared to patients with VTD (p = 0.005). However, percentage of patients and controls with FXII deficiency was 8.8 and 9.2%, respectively (p = 1.000). No significant association was found between FXII deficiency and VTD (p = 1.0). FXII plasma concentration was lower in controls vs. patients with VTD: 4.05 vs. 6.19 ng/mL (p <0.001). Percentage of patients with low FXII plasma concentration was 1.6% and 6.0% in patients and controls, respectively (p = 0.010). CONCLUSIONS: FXII deficiency is a frequent finding in patients with VTD and controls in Mexico. Some patients with FXII deficiency had normal APTT result, an effect not described above. FXII plasma concentration was lower in patients with low activity.

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Knowledge of the 10B microdistribution is of great relevance in BNCT studies. Since 10B concentration assesment through neutron autoradiography depends on the correct quantification of tracks in a nuclear track detector, image acquisition and processing conditions should be controlled and verified, in order to obtain accurate results to be applied in the frame of BNCT. With this aim, an image verification process was proposed, based on parameters extracted from the quantified nuclear tracks. Track characterization was performed by selecting a set of morphological and pixel-intensity uniformity parameters from the quantified objects (area, diameter, roundness, aspect ratio, heterogeneity and clumpiness). Their distributions were studied, leading to the observation of varying behaviours in images generated by different samples and acquisition conditions. The distributions corresponding to samples coming from the BNC reaction showed similar attributes in each analyzed parameter, proving to be robust to the experimental process, but sensitive to light and focus conditions. Considering those observations, a manual feature extraction was performed as a pre-processing step. A Support Vector Machine (SVM) and a fully dense Neural Network (NN) were optimized, trained, and tested. The final performance metrics were similar for both models: 93%-93% for the SVM, vs 94%-95% for the NN in accuracy and precision respectively. Based on the distribution of the predicted class probabilities, the latter had a better capacity to reject inadequate images, so the NN was selected to perform the image verification step prior to quantification. The trained NN was able to correctly classify the images regardless of their track density. The exhaustive characterization of the nuclear tracks provided new knowledge related to the autoradiographic images generation. The inclusion of machine learning in the analysis workflow proves to optimize the boron determination process and paves the way for further applications in the field of boron imaging.

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BACKGROUND: The prevalence and consequences of traumatic dental injuries (TDI) make them a public health problem. Trustworthy TDI clinical practice guidelines (CPGs) assist clinicians in determining a diagnosis and guide them to the most appropriate therapy. The aim of this systematic survey was to identify and evaluate the quality of CPGs for the diagnosis, emergency management, and follow-up of TDIs. MATERIALS AND METHODS: A systematic search was carried out in MEDLINE, EMBASE, Epistemonikos, Trip database, CPG websites, and dental societies to identify documents providing recommendations for the emergency and sequelae management of TDIs. Reviewers assessed the included guidelines independently and in duplicate, using the AGREE II instrument. ANOVA or Student's t-tests were used to determine the attributes of CPGs associated with the total score in AGREE II. RESULTS: Ten CPGs published between 2010 and 2020 were included, mostly from Europe (n = 6). The overall agreement between reviewers was very good (0.94; 95%CI 0.91-0.97). The mean scores (the higher the score, the better the domain assessment) per domain were as follows: Scope and purpose 78.0 ± 18.9%; stakeholder involvement 46.9 ± 29.6%; rigour of development 41.8 ± 26.7%; clarity of presentation 75.8 ± 17.6%; applicability 15.3 ± 18.8%; and editorial independence 41.7 ± 41.7%. The overall mean rate was 4 ± 1.3 out of a maximum score of 7. Two guidelines were recommended by the reviewers for use in practice and rated as high quality. CPGs developed by government organizations showed a significantly higher overall score. CONCLUSIONS: The overall quality of CPGs on TDI was suboptimal. CPG developers should synthesize the evidence and formulate recommendations using high-quality methodologies and standards in a structured, transparent, and explicit way.

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Antecedentes: Los dispositivos de asistencia ventricular (VAD, sigla en inglés) se utilizan cada vez más para el manejo de la insuficiencia cardíaca descompensada en unidades de cuidados intensivos. El manejo nutricional es fundamental para la evolución clínica de estos pacientes. Objetivos: El objetivo fue evaluar en cuánto tiempo se puede alcanzar las necesidades nutricionales, utilizando distintas modalidades de apoyo nutricional, en pacientes que requirieron asistencia con VAD por insuficiencia cardíaca aguda en una clínica privada del país. Métodos: En una clínica privada se efectuó un estudio observacional retrospectivo analizando los datos clínicos relacionados al aporte nutricional de 12 pacientes que requirieron asistencia con VAD. Las vías de aporte nutricional evaluadas fueron la nutrición enteral (NE) y/o nutrición parenteral (NP). Se midió el tiempo de implementación del apoyo nutricional y su efecto se estimó por una valoración nutricional subjetiva y por la medición de indicadores de laboratorio. Además, se vigilaron las complicaciones asociadas al aporte nutricional. Resultados: El estudio incluyó a 12 pacientes. Los objetivos nutricionales se alcanzaron por completo en el 91% de los pacientes (n=11) en 3,7 ± 1 días después de iniciado el apoyo nutricional. En ese momento, 5 pacientes recibían NE exclusiva, 4 pacientes NP complementaria a la NE, 1 paciente NE complementaria a la alimentación oral y 1 paciente con vía oral. Al momento de alcanzar los requerimientos nutricionales ningún paciente tenía NP exclusiva. Conclusión: Concluimos que el apoyo nutricional precoz es factible y seguro en pacientes con VAD. Alcanzar los objetivos nutricionales es posible sin efectos adversos graves. Se necesitan estudios futuros para determinar el beneficio a largo plazo del apoyo nutricional agresivo para pacientes en estado crítico que requieren apoyo hemodinámico.

Background: Ventricular assist devices (VAD) are being used more frequently in patients with severe heart failure. Nutritional support is a critical factor for the outcome in these patients. Aim: to evaluate the time required and mode of nutritional support in patients with severe cardiac dysfunction being treated with VAD. Methods: 12 patients with VAD being treated in an intensive care unit were evaluated to determine the time and mode of support required to achieve adequate nutrition. Enteral and / or parenteral modes of nutritional support were used. The outcomes were evaluated by subjective appreciation, weight measurement and serum levels of albumin, pre-albumin and vitamin D. Results: Adequate nutritional support was achieved in 91% of patients a mean of 3 days after beginning of treatment (SD 1 day). At that time 5 patients were receiving only enteral nutrition, 4 patients enteral and parenteral nutrition, 1 patient enteral nutrition in addition to oral nutrition and 1 patients was receiving only oral nutrition. No patient was receiving only parenteral nutrition. Conclusion: early nutritional support is posible and safe in patients with an VAD. Further studies are needed to evaluate long term benefits of this strategy of nutritional support.

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Introduction: Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus (SLE). Methods: We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers. Results: Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere. Conclusions: According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples.

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The potential effects of climate change on plant reproductive phenology include asynchronies with pollinators and reductions in plant fitness, leading to extinction and loss of ecosystem function. In particular, plant phenology is sensitive to extreme weather events, which are occurring with increasing severity and frequency in recent decades and are linked to anthropogenic climate change and shifts in atmospheric circulation. For 15 plant species in a Venezuelan cloud forest, we documented dramatic changes in monthly flower and fruit community composition over a 35-year time series, from 1983 to 2017, and these changes were linked directly to higher temperatures, lower precipitation, and decreased soil water availability. The patterns documented here do not mirror trends in temperate zones but corroborate results from the Asian tropics. More intense droughts are predicted to occur in the region, which will cause dramatic changes in flower and fruit availability.

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