Deep learning algorithms applied to computational chemistry.

Recently, there has been a significant increase in the use of deep learning techniques in the molecular sciences, which have shown high performance on datasets and the ability to generalize across data. However, no model has achieved perfect performance in solving all problems, and the pros and cons of each approach remain unclear to those new to the field. Therefore, this paper aims to review deep learning algorithms that have been applied to solve molecular challenges in computational chemistry. We proposed a comprehensive categorization that encompasses two primary approaches; conventional deep learning and geometric deep learning models. This classification takes into account the distinct techniques employed by the algorithms within each approach. We present an up-to-date analysis of these algorithms, emphasizing their key features and open issues. This includes details of input descriptors, datasets used, open-source code availability, task solutions, and actual research applications, focusing on general applications rather than specific ones such as drug discovery. Furthermore, our report discusses trends and future directions in molecular algorithm design, including the input descriptors used for each deep learning model, GPU usage, training and forward processing time, model parameters, the most commonly used datasets, libraries, and optimization schemes. This information aids in identifying the most suitable algorithms for a given task. It also serves as a reference for the datasets and input data frequently used for each algorithm technique. In addition, it provides insights into the benefits and open issues of each technique, and supports the development of novel computational chemistry systems.

An Equilibrium State Diagram for Storage Stability and Conservation of Active Ingredients in a Functional Food Based on Polysaccharides Blends.

A functional food as a matrix based on a blend of carbohydrate polymers (25% maltodextrin and 75% inulin) with quercetin and Bacillus claussi to supply antioxidant and probiotic properties was prepared by spray drying. The powders were characterized physiochemically, including by moisture adsorption isotherms, X-ray diffraction (XRD), scanning electron microscopy (SEM), and modulated differential scanning calorimetry (MDSC). The type III adsorption isotherm developed at 35 °C presented a monolayer content of 2.79 g of water for every 100 g of dry sample. The microstructure determined by XRD presented three regions identified as amorphous, semicrystalline, and crystalline-rubbery states. SEM micrographs showed variations in the morphology according to the microstructural regions as (i) spherical particles with smooth surfaces, (ii) a mixture of spherical particles and irregular particles with heterogeneous surfaces, and (iii) agglomerated irregular-shape particles. The blend's functional performance demonstrated antioxidant activities of approximately 50% of DPPH scavenging capacity and viability values of 6.5 Log10 CFU/g. These results demonstrated that the blend displayed functional food behavior over the complete interval of water activities. The equilibrium state diagram was significant for identifying the storage conditions that promote the preservation of functional food properties and those where the collapse of the microstructure occurs.

The influence of schooling on performance in chess and at the Olympics.

At the macro-level, it is hard to test the hypothesis that increased schooling in a country will raise labour productivity but sectoral analyses may be tractable. In sports, output is homogenous in that countries' achievements are measurable in the same way. We examine country performances at the Chess Olympiad and the Olympic Games, contrasting tournaments where players in the first use only their minds but most in the second supply substantial physical effort or work with costly physical capital. Modelling success in either leads to a set of results familiar from sports literature: country performance depends on economic resources, represented by population size and per capita income. Supplementary variables capture over-performance by communist/ former communist countries. We then introduce a measure of average years of schooling. This significantly reduces the role of income, especially in chess. It also takes power away from the 'communist' variables, especially at the Olympics. These results suggest that much of any effect from income is mediated through schooling: investment in education is associated with elevated productivity. Increased productivity is observed in both settings, one a knowledge-intensive sub-sector and the other dependent to a significant extent on either raw physical strength or expensive capital input. Supplementary Information: The online version contains supplementary material available at 10.1007/s00181-022-02259-9.

Epidemiological Profile and Social Welfare Index as Factors Associated with COVID-19 Hospitalization and Severity in Mexico City: A Retrospective Analysis.

Epidemiological data indicate that Mexico holds the 19th place in cumulative cases (5506.53 per 100,000 inhabitants) of COVID-19 and the 5th place in cumulative deaths (256.14 per 100,000 inhabitants) globally and holds the 4th and 3rd place in cumulative cases and deaths in the Americas region, respectively, with Mexico City being the most affected area. Several modifiable and non-modifiable risk factors have been linked to a poor clinical outcome in COVID-19 infection; however, whether socioeconomic and welfare factors are associated with clinical outcome has been scanty addressed. This study tried to investigate the association of Social Welfare Index (SWI) with hospitalization and severity due to COVID-19. A retrospective analysis was conducted at the Centro Médico Nacional "20 de Noviembre"-ISSSTE, based in Mexico City, Mexico. A total of 3963 patients with confirmed or suspected COVID-19, registered from March to July 2020, were included, retrieved information from the Virology Analysis and Reference Unit Database. Demographic, symptoms and clinical data were analyzed, as well as the SWI, a multidimensional parameter based on living and household conditions. An adjusted binary logistic regression model was performed in order to compare the outcomes of hospitalization, mechanical ventilation requirement (MVR) and mortality between SWI categories: Very high (VHi), high (Hi), medium (M) and low (L). The main findings show that lower SWI were independently associated with higher probability for hospital entry: VHi vs. Hi vs. M vs. L-SWI (0 vs. +0.24 [OR = 1.24, CI95% 1.01-1.53] vs. +0.90 [OR = 1.90, CI95% 1.56-2.32] vs. 0.73 [OR = 1.73, CI95% 1.36-2.19], respectively); Mechanical Ventilation Requirement: VHi vs. M vs. L-SWI (0 vs. +0.45 [OR = 1.45, CI95% 1.11-1.87] vs. +0.35 [OR = 1.35, CI95% 1.00-1.82]) and mortality: VHi vs. Hi vs. M (0 vs. +0.54 [OR = 1.54, CI95% 1.22-1.94] vs. +0.41 [OR = 1.41, CI95% 1.13-1.76]). We concluded that SWI was independently associated with the poor clinical outcomes in COVID-19, beyond demographic, epidemiological and clinical characteristics.

Multicenter Evaluation of the Idylla GeneFusion in Non-Small-Cell Lung Cancer.

Targeted therapy in lung cancer requires the assessment of multiple oncogenic driver alterations, including fusion genes. This retrospective study evaluated the Idylla GeneFusion prototype, an automated and ease-of-use (<2 minutes) test, with a short turnaround time (3 hours) to detect fusions involving ALK, ROS1, RET, and NTRK1/2/3 genes and MET exon 14 skipping. This multicenter study (18 centers) included 313 tissue samples from lung cancer patients with 97 ALK, 44 ROS1, 20 RET, and 5 NTRKs fusions, 32 MET exon 14 skipping, and 115 wild-type samples, previously identified with reference methods (RNA-based next-generation sequencing/fluorescence in situ hybridization/quantitative PCR). Valid results were obtained for 306 cases (98%), overall concordance between Idylla and the reference methods was 89% (273/306); overall sensitivity and specificity were 85% (165/193) and 96% (108/113), respectively. Discordances were observed in 28 samples, where Idylla did not detect the alteration identified by the reference methods; and 5 samples where Idylla identified an alteration not detected by the reference methods. All of the ALK-, ROS1-, and RET-specific fusions and MET exon 14 skipping identified by Idylla GeneFusion were confirmed by reference method. To conclude, Idylla GeneFusion is a clinically valuable test that does not require a specific infrastructure, allowing a rapid result. The absence of alteration or the detection of expression imbalance only requires additional testing by orthogonal methods.

NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model.

Restoring the control of food intake is the key to obesity management and prevention. The arcuate nucleus (ARC) of the hypothalamus is extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces food intake by its action in neuropeptide Y (NPY) neurons of the hypothalamic ARC, but the detailed mode of action observed in human neurons is missing, due to the lack of a human-neuron-based model for pharmacology testing. Here, we validated and utilized a human-neural-stem-cell-based (hNSC) model of ARC to test the effects of NPFF on cellular pathways and neuronal activity. We found that in the human neurons, decreased cAMP levels by NPFF resulted in a reduced rate of cytoplasmic calcium oscillations, indicating an inhibition of ARC NPY neurons. This suggests the therapeutic potential of NPFFR2 in obesity. In addition, we demonstrate the use of human-stem-cell-derived neurons in pharmacological applications and the potential of this model to address functional aspects of human hypothalamic neurons.

Tratamiento conservador de ameloblastoma uniquístico. Presentación de un caso / Conservative treatment of unicystic ameloblastoma. Case presentation

El ameloblastoma es la segunda neoplasia odontogénica más común, es benigno, presenta un comportamiento agresivo e infiltrante localmente, y con una alta tasa de recidiva; por lo que su tratamiento es muy controversial. Se presenta el caso de un paciente masculino de 14 años de edad, sin antecedentes médicos de relevancia, con aumento de volumen en la región mandibular posterior lado izquierda, dura, con color similar a piel adyacente y sin dolor a la palpación. Se le realizó punción y una biopsia incisional, obteniendose como resultado histopatológico: ameloblastoma uniquístico mural, el cual es tratado de forma conservadora con curetaje y ostectomía periférica, evolucionando favorablemente y rehabilitado con implantes osteointegrados. Las modalidades de tratamiento se pueden dividir en radical y conservadora. La técnica a elegir depende principalmente del tipo del ameloblastoma, seguido por la histología, su localización, el tamaño y la edad del paciente; por lo que cada tratamiento debe ser estudiado e individualizado.

Ameloblastomas are the second most common odontogenic neoplasms, they are benign, however, they present an aggressive and locally infiltrative behavior, with a high recurrence rate; so its treatment is very controversial. We present the case of a 14-year-old male patient, with no relevant medical history, with increased volume in the posterior mandibular region left side, hard, with a color like the adjacent skin and painless on palpation. A puncture and an incisional biopsy were performed, obtaining as a histopathological result: mural unicystic ameloblastoma, which was treated conservatively with curettage and peripheral ostectomy, evolving favorably and rehabilitated with osseointegrated implants. Treatment modalities can be divided into radical and conservative. The technique to choose depends mainly on the type of ameloblastoma, followed by histology, its location, size and age of the patient; so each treatment must be studied and individualized.

Disinfection mechanism of the photocatalytic activity of SnO2 thin films against Candida albicans, proposed from experimental and simulated perspectives.

Nosocomial infections are an important health problem and cause of complications and death in hospitalized patients. This problem should be solved from the preventive angle, avoiding the spread of infections by designing disinfection methods based on the photocatalytic activity of semiconductor materials such as tin oxide (SnO2). The antimicrobial activity of UV light was tested by using inoculation with Candida albicans ATCC10231 on SnO2 thin films and counting colony forming units (CFU). The interaction of UV light with SnO2 was analyzed by density functional theory (DFT) and the extension to the Hubbard model (DFT+U) schemes to predict the electron behavior at the subatomic level. After exposure to UV light, C. albicans showed a reduction of 36.5% in viable cells, and when SnO2 was included, cell viability was reduced by 60.2%. Measurements of the electronic structure obtained by the first-principle calculations under the DFT and DFT+U schemes showed that the O-p orbitals mediate the oxidation process in the bulk semiconductor. By including the surface effects when cleaving the (1 0 0) plane, the three orbitals O-p, Sn-p, and Sn-s are the mediators. SnO2 films are promising antimicrobial coatings because UV light has a synergic activity with thin films, resulting in faster disinfection.

Comparative characterization of digestive proteases in redhead cichlid (Vieja melanurus) and twoband cichlid (Vieja bifasciata) (Percoidei: Cichlidae)

In the Southeast of Mexico, there are many native cichlids with commercial interest such as redhead cichlid (Vieja melanurus) and twoband cichlid (V. bifasciata), which have a great local demand and excellent meat quality. However, it is necessary to implement their culture based on nutrition studies and digestive biochemistry. This study's objective was to characterize these two cichlids' digestive proteases (pH, temperature, and inhibitors) through biochemistry techniques. Results showed that V. melanurus and V. bifasciata have a digestive capacity analogous to other omnivore fishes, where the optimal pH values of stomach proteases (4 and 2, respectively) and intestinal proteases (6 and 12, respectively), the optimal temperature of acid (35°C and 55°C, respectively) and alkaline proteases (45°C and 55°C, respectively) are quite similar. Both species presented high thermal and pH stabilities. Inhibition showed that V. melanurus is more sensitive to specific inhibitors for alkaline proteases than V. bifasciata. In conclusion, V. bisfasciata and V. melanurus have different digestive protease patterns. Both species can hydrolyze different protein ingredients to formulate a specific diet. Nevertheless, V. bifasciata is more resistant to the presence of inhibitors, which allow it to include vegetable proteins in its diet.(AU)

En el sureste de México, existen muchas especies de cíclidos nativos de interés comercial como el cíclido rojo (Vieja melanurus) y el cíclido de dos bandas (V. bifasciata), los cuales tienen una gran demanda local y tienen una excelente calidad de carne; sin embargo, es necesario implementar su cultivo con base en estudios de nutrición y bioquímica digestiva. El objetivo de este estudio fue caracterizar las proteasas digestivas (pH, temperatura e inhibidores) de estos dos cíclidos nativos mediante técnicas bioquímicas. Los resultados mostraron que V. melanurus y V. bifasciata tienen una capacidad digestiva similar a otros peces omnívoros, donde los valores óptimos de pH de proteasas estomacales (4 y 2, respectivamente) e intestinales (6 y 12, respectivamente), la temperatura óptima de proteasas ácidas (35°C y 55°C, respectivamente) y alcalinas (45°C y 55°C, respectivamente) son muy parecidas. Ambas especies presentaron alta estabilidad térmica y de pH. La inhibición mostró que V. melanurus es más sensible a inhibidores específicos de proteasas alcalinas que V. bifasciata. En conclusión, V. bisfasciata y V. melanurus tienen diferentes patrones de proteasas digestivas, pero ambas especies pueden hidrolizar diversos ingredientes proteicos para formular dietas específicas; sin embargo, V. bifasciata es más resistente a la presencia de inhibidores, lo que permitiría incluir proteínas vegetales en su dieta.(AU)

Melatonin Induces Melanogenesis in Human SK-MEL-1 Melanoma Cells Involving Glycogen Synthase Kinase-3 and Reactive Oxygen Species.

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3ß seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3ß. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.

Partial characterization of digestive proteases in juveniles of Microphis brachyurus (short-tailed pipefish) (Syngnathiformes: Syngnathidae)

Short-tailed pipe fish (Microphis brachyurus) is a freshwater organism with high economic potential for the aquarium hobby, so it is necessary to implement methods to promote its culture through studies of digestive physiology. General activities of acid and alkaline proteases were evaluated, as well as the effect of pH, temperature and inhibitors. The optimal pH of stomach proteases was 2, while the optimal pH of intestinal proteases was 10. Optimal temperature for the acidic proteases was 35 ºC, while for alkaline proteases it was 45 ºC. Thermal stability showed high resistance at 35 ºC for both acid and alkaline proteases (above 100% residual activity). Acid proteases are resistant at pH 2 (50% of residual activity), meanwhile alkaline proteases were highly resistant at pH 10 (90% of residual activity). Acid proteases were inhibited by 80% with pepstatin A and alkaline proteases were inhibited with TLCK and TPCK for trypsin (75%) and chymotrypsin (80%), respectively. Finally, metallo-proteases were 75% partially inhibited some serine proteases by 75% with EDTA. In conclusion, M. brachyurus has a good digestive capacity, since they can degrade a wide variety of proteins due to their greater proteolytic activity.(AU)

El pez pipa (Microphis brachyurus) es un organismo dulceacuícola con alto potencial económico para la acuarofilia; sin embargo, es necesario implementar su cultivo a través de estudios de fisiología digestiva. Se evaluó el efecto del pH, temperatura e inhibidores sobre las actividades enzimáticas de proteasas ácidas y alcalinas. El pH óptimo de proteasas estomacales es de 2, mientras que el de proteases intestinales es de 10. La temperatura óptima de proteasas ácidas es de 35 ºC y las alcalinas de 45 ºC. La estabilidad térmica para proteasas ácidas y alcalinas es a los 35 ºC (más de 100% de actividad residual). La estabilidad a los diferentes pH de las proteasas ácidas es en 2 (50 % de la actividad residual), mientras que para las proteasas alcalinas es en 10 (90 % de la actividad residual). Las proteasas ácidas fueron inhibidas en 80% con pepstatina A y las proteasas alcalinas fueron altamente inhibidas con TLCK para tripsina (75%) y TPCK quimitripsina (80%). Finalmente, las metaloproteasas fueron inactivadas con EDTA en 70%. En conclusión, M. brachyurus tiene una buena capacidad digestiva al degradar una amplia variedad de proteinas debido a su alta actividad proteolítica.(AU)

Modification of HIF-1α, NF-aκB, IGFBP-3, VEGF and adiponectin in diabetic foot ulcers treated with hyperbaric oxygen.

Introduction: Diabetic foot ulcers are a frequent complication of diabetes and the first cause of non-traumatic lower limb amputation. They affect quality of life, restrict social productivity and generate a high economic burden for health care systems. Hyperbaric oxygen (HBO2) therapy is an adjunctive treatment option because it improves wound healing in the short term. However, its ability to modulate the pro- and anti-inflammatory balance and the hypoxic cell response in the clinical setting has not been fully described. Objective: To determine modifications in HIF-1α, NF-κB, IGFBP-3, and VEGF expression in wounds as well as circulating inflammatory cytokines in patients with diabetic foot ulcers subjected to HBO2. Materials and methods: We studied 17 ambulatory patients and one hospitalized patient with diabetic foot ulcers classified as Grade 3 or 4 according to the Wagner scale. All underwent HBO2 therapy. Tissue expression of HIF-1α, NF-κB, IGFBP-3, and VEGF was determined by immunohistochemistry. Plasma levels of adiponectin, IL-6, IFN-γ, IL-10 and IL-4 were measured by ELISA and chemiluminescence. Fibrosis and angiogenesis were determined by Masson's trichrome staining. Results: Ulcers in all patients healed after one month of HBO2, and none presented relapses at the one-year follow-up. At the beginning of treatment, HIF-1α and NF-κB expression was observed mainly in the nucleus, whereas these proteins were localized in the cytoplasm at the end of HBO2. There were significant modifications in VEGF expression after therapy, an increase in the plasma level of proinflammatory IL-6, and a decrease in that of IFN-γ. IGFBP-3 expression and plasma levels of adiponectin were increased at the end of HBO2. Increases in fibrosis and angiogenesis were also observed. Conclusion: These results suggest that adjuvant HBO2 modifies the proinflammatory balance related to the cellular response to hypoxia.

Changes in digestive enzymes activities during the initial ontogeny of wolf cichlid, Parachromis dovii (Perciformes: Cichlidae)

Wolf cichlid, Parachromis dovii, is a species with a high potential for aquaculture in Central America; however, the knowledge of the digestive physiology in larvae period is limited. For these reason, this study evaluated the changes on digestive enzymes (alkaline and acid proteases, trypsin, chymotrypsin, aminopeptidase, carboxypeptidase, lipases, amylases, and phosphatases) during early ontogeny by biochemical analysis. All digestive enzymes were detected at first feeding (6 days after hatching, DAH, 9.49 mm, 168 degree-days DD). Afterwards all enzymes reached two main peaks in activity at 14 or 22 DAH (15.10 mm, 364 DD and 20.83 mm, 550 DD, respectively). Later, there was a gradual decrease in activity for trypsin and acid and alkaline phosphatases until reach the lowest values at 41 DAH. In the case of acid proteases, chymotrypsin, aminopeptidase, carboxypeptidase, lipase and amylase, all activities reached their maximum values at the end of the larval period, except for alkaline proteases, which showed the maximum value at 14 DAH (15.10 mm, 364 DD). Parachromis dovii larvae have an early capability to hydrolyze exogenous food, agreeing with other carnivorous neotropical cichlid species, for this reason we proposed that the weaning process could begin at 14 DAH.(AU)

El guapote lagunero (Parachromis dovii) es una especie con un alto potencial para la acuicultura en la región de América Central; sin embargo, existe un conocimiento limitado sobre la capacidad digestiva en el periodo larval. Por este motivo, este estudio evaluó los cambios de las enzimas digestivas (proteasas alcalinas y ácidas, tripsina, quimotripsina, aminopeptidasa, carboxipeptidasa, lipasas, amilasas y fosfatasas) durante la ontogenia temprana mediante análisis bioquímico. Todas las enzimas digestivas analizadas se detectaron en la primera alimentación (6 días después de la eclosión, DAH, 9.49 mm, 168 día-grados DD). Después, todas las enzimas alcanzaron dos picos máximos a los 14 o 22 DAH (15.10 mm, 364 DD and 20.83 mm, 550 DD, respectivamente). Después las actividades tripsina, fosfatasas ácidas y alcalina disminuyeron a sus valores más bajos a los 41 DAH. En el caso de las proteasas ácidas y alcalinas, quimotripsina, aminopeptidasa, carboxipeptidasa, lipasa y amilasa, los niveles de actividad aumentaron y alcanzaron su máximo valor al final del período larvario, excepto las proteasas alcalinas, que mostraron su máximo valor a los 14 DAH (15.10 mm, 364 DD). Las larvas de P. dovii tienen una capacidad temprana para hidrolizar alimentos exógenos, lo que concuerda con otras especies de cíclidos neotropicales carnívoros, por lo que proponemos que el proceso de destete inicie a los 14 DAH.(AU)

Middle and late holocene micromammal pathologies from Cueva Tixi (Tandilia Range, Buenos Aires Province, Argentina).

Paleopathology in bones of very small mammals has rarely been studied. Different types of osseous lesions of mammals weighing under 0.2kg, recovered from the Holocene strata of Cueva Tixi archaeological and paleontological site (Tandilia range, province of Buenos Aires, Argentina), are described and discussed in this report. Several types of trauma, entheseal changes, degenerative joint diseases, and probable osteomyelitis were identified. The lesions were chronic, indicating that the animals were able to survive a period of convalescence, although in many cases the decreased capacity for locomotion likely was significant. These pathological findings open research avenues for very small mammals that usually are not considered in archaeological disease studies.

Uterine Extramedullary Plasmacytoma as a Primary Manifestation of Multiple Myeloma / Plasmocitoma extramedular uterino comomanifestação primária de mieloma múltiplo

Abstract The association between plasmacytomas and multiple myeloma (MM) is well-described, and in about one third of the cases of plasmacytoma the additional study will lead to the diagnosis of MM. The finding of plasmacytomas in the genital tract is extremely rare, with sparse cases described in the literature, and these cases pose a challenge regarding the optimal guidance and treatment. This paper describes a case of uterine extramedullary plasmacytoma in a 79-year-old woman with complaints of postmenopausal abnormal uterine bleeding. The complementary study led to the diagnosis of uterine plasmacytoma and, subsequently, of MM. Despite the unfavorable outcome of this case, we consider pertinent to report it because it constitutes a differential diagnosis to be taken into account in the approach of pelvic masses.

Resumo A associação entre plasmocitomas e mieloma múltiplo (MM) encontra-se bem demonstrada, e em cerca de um terço dos casos de plasmocitoma o estudo adicional conduzirá ao diagnóstico de MM. O achado de plasmocitomas no trato genital é extremamente raro, havendo um número muito limitado de casos descritos na literatura, o que dificulta concluir sobre a melhor forma de orientação e tratamento destes casos. O presente trabalho descreve um caso de plasmocitoma extramedular uterino em mulher de 79 anos estudada por queixas de hemorragia uterina anômala pós-menopáusica. O estudo complementar levou ao diagnóstico de plasmocitoma uterino e, posteriormente, de MM. Apesar do desfecho desfavorável do caso, consideramos pertinente o seu relato por se tratar de um diagnóstico diferencial a levar em consideração na abordagem de massas pélvicas.

Uterine Extramedullary Plasmacytoma as a Primary Manifestation of Multiple Myeloma.

The association between plasmacytomas and multiple myeloma (MM) is well-described, and in about one third of the cases of plasmacytoma the additional study will lead to the diagnosis of MM. The finding of plasmacytomas in the genital tract is extremely rare, with sparse cases described in the literature, and these cases pose a challenge regarding the optimal guidance and treatment. This paper describes a case of uterine extramedullary plasmacytoma in a 79-year-old woman with complaints of postmenopausal abnormal uterine bleeding. The complementary study led to the diagnosis of uterine plasmacytoma and, subsequently, of MM. Despite the unfavorable outcome of this case, we consider pertinent to report it because it constitutes a differential diagnosis to be taken into account in the approach of pelvic masses.

A associação entre plasmocitomas e mieloma múltiplo (MM) encontra-se bem demonstrada, e em cerca de um terço dos casos de plasmocitoma o estudo adicional conduzirá ao diagnóstico de MM. O achado de plasmocitomas no trato genital é extremamente raro, havendo um número muito limitado de casos descritos na literatura, o que dificulta concluir sobre a melhor forma de orientação e tratamento destes casos. O presente trabalho descreve um caso de plasmocitoma extramedular uterino em mulher de 79 anos estudada por queixas de hemorragia uterina anômala pós-menopáusica. O estudo complementar levou ao diagnóstico de plasmocitoma uterino e, posteriormente, de MM. Apesar do desfecho desfavorável do caso, consideramos pertinente o seu relato por se tratar de um diagnóstico diferencial a levar em consideração na abordagem de massas pélvicas.

Melatonin enhances hyperthermia-induced apoptotic cell death in human leukemia cells.

Melatonin is an endogenous indoleamine with a wide range of biological functions. In addition to modulating circadian rhythms, it plays important roles in the health as an antioxidant. Melatonin has also the ability to induce apoptosis in cancer cells and to enhance the antitumoral activity of chemotherapeutic agents. In this study, the effect of melatonin on hyperthermia-induced apoptosis was explored using human leukemia cells. The results demonstrate that melatonin greatly improved the cytotoxicity of hyperthermia in U937 cells. The potentiation of cell death was achieved with 1 mmol/L concentrations of the indoleamine but not with concentrations close to physiological levels in blood (1 nmol/L). This effect was associated to an enhancement of the apoptotic response, revealed by an increase in cells with hypodiploid DNA content and activation of multiple caspases (caspase-2, caspase-3, caspase-8, and caspase-9). Melatonin also increased hyperthermia-induced Bid activation as well as translocation of Bax from the cytosol to mitochondria and cytochrome c release. Hyperthermia-provoked apoptosis and potentiation by melatonin were abrogated by a broad-spectrum caspase inhibitor (z-VAD-fmk) as well as by specific inhibitors against caspase-8 or caspase-3. In contrast, blocking of the mitochondrial pathway of apoptosis either with a caspase-9 inhibitor or overexpressing the anti-apoptotic protein Bcl-2 (U937/Bcl-2) reduced the number of apoptotic cells in response to hyperthermia but it was unable to suppress melatonin enhancement. Melatonin appears to modulate the apoptotic response triggered by hyperthermia in a cell type-specific manner as similar results were observed in HL-60 but not in K562 or MOLT-3 cells.

Cytotoxicity of protein-carbon nanotubes on J774 macrophages is a functionalization grade-dependent effect.

Carbon nanotubes (CNTs) are used as carriers in medicine due to their ability to be functionalized with chemical substances. However, cytotoxicity analysis is required prior to use for in vivo models. The aim of this study was to evaluate the cytotoxic effect of CNTs functionalized with a 46 kDa surface protein from Entamoeba histolytica (P46-CNTs) on J774A macrophages. With this purpose, CNTs were synthesized by spray pyrolysis and purified (P-CNTs) using sonication for 48 h. A 46 kDa protein, with a 4.6-5.4 pI range, was isolated from E. histolytica HM1:IMSS strain trophozoites using an OFFGEL system. The P-CNTs were functionalized with the purified 46 kDa protein, classified according to their degree of functionalization, and characterized by Raman and Infrared spectroscopy. In vitro cytotoxicity was evaluated by MTT, apoptosis, and morphological assays. The results demonstrated that P46-CNTs exhibited cytotoxicity dependent upon the functionalized grade. Contrary to what was expected, P46-CNTs with a high grade of functionalization were more toxic to J774 macrophages than P46-CNTs with a low grade of functionalization, than P-CNTs, and had a similar level of toxicity as UP-CNT. This suggests that the nature of the functionalized protein plays a key role in the cytotoxicity of these nanoparticles.

[Protein-losing enteropathy due to intestinal lymphangiectasis: a rare disease. Report of two cases]. / Enteropatía perdedora de proteínas por linfangiectasia intestinal: una enfermedad rara. Presentación de 2 casos.

Congenital intestinal lymphangiectasis (LIP) is a protein-losing enteropathy that appears sporadically in children. It begins with edema due to hypoproteinemia and hypoalbuminemia, and in some cases with ascites, immunodeficience and hypocalcemic tetania. The purpose of this report is to present two patients with LIP which appeared during the first year of life. The diagnosis was certificated by upper gastrointestinal videoendoscopy and histological findings. Both patients were treated with a new formula containing mean chain triglycerides with an adequate response, not obtained before with a common semielemental formula.