Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods.

Purpose: Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (64Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations. Methods: A mammalian cell nucleus model with a diameter of 9.3 µm available in TOPAS-nBio was used. The cellular nucleus consisted of double-helix DNA geometrical model of 2.3 nm diameter surrounded by a hydration shell with a thickness of 0.16 nm, organized in 46 chromosomes giving a total of 6.08 giga base-pairs (DNA density of 14.4 Mbp/µm3). The cellular nucleus was irradiated with monoenergetic electrons and radiation emissions from several radionuclides including 111In, 125I, 123I, and 99mTc in addition to 64Cu. For monoenergetic electrons, isotropic point sources randomly distributed within the nucleus were modeled. The radionuclides were incorporated in randomly chosen DNA base pairs at two positions near to the central axis of the double-helix DNA model at (1) 0.25 nm off the central axis and (2) at the periphery of the DNA (1.15 nm off the central axis). For all the radionuclides except for 99mTc, the complete physical decay process was explicitly simulated. For 99mTc only total electron spectrum from published data was used. The DNA Double Strand Breaks (DSB) yield per decay from direct and indirect actions were quantified. Results obtained for monoenergetic electrons and radionuclides 111In, 125I, 123I, and 99mTc were compared with measured and calculated data from the literature for verification purposes. The DSB yields per decay incorporated in DNA for 64Cu are first reported in this work. The therapeutic effect of 64Cu (activity that led 37% cell survival after two cell divisions) was determined in terms of the number of atoms incorporated into the nucleus that would lead to the same DSBs that 100 decays of 125I. Simulations were run until a 2% statistical uncertainty (1 standard deviation) was achieved. Results: The behavior of DSBs as a function of the energy for monoenergetic electrons was consistent with published data, the DSBs increased with the energy until it reached a maximum value near 500 eV followed by a continuous decrement. For 64Cu, when incorporated in the genome at evaluated positions (1) and (2), the DSB were 0.171 ± 0.003 and 0.190 ± 0.003 DSB/decay, respectively. The number of initial atoms incorporated into the genome (per cell) for 64Cu that would cause a therapeutic effect was estimated as 3,107 ± 28, that corresponds to an initial activity of 47.1 ± 0.4 × 10-3 Bq. Conclusion: Our results showed that TRT with 64Cu has comparable therapeutic effects in cells as that of TRT with radionuclides currently used in clinical practice.

Componentes de fragilidad, sarcopenia y su asociación con insuficiencia de vitamina D. Estudio transversal analítico / Components of frailty, sarcopenia and their association with vitamin D deficiency. Cross-sectional, analytical study

Resumen Introducción: En adultos mayores, la asociación de fragilidad y sarcopenia con deficiencia de vitamina D es conocida, pero poco se ha estudiado la asociación de los componentes del síndrome de fragilidad. Objetivo: Determinar la asociación entre los componentes de fragilidad, sarcopenia e insuficiencia de vitamina D en adultos mayores. Métodos: Se estudiaron adultos de quienes se registró edad, escolaridad, estado civil, antecedentes de fracturas, hospitalizaciones, indicadores antropométricos, sarcopenia, índice de Charlson, polifarmacia, fenotipo de fragilidad de Fried y vitamina D plasmática; cifras < 30 ng/mL se consideraron indicativas de insuficiencia de vitamina D. Para el análisis estadístico se utilizó estadística descriptiva e inferencial. La asociación fue determinada mediante regresión logística binaria. Resultados: Se estudiaron 175 adultos con un promedio de edad de 71.7 ± 6.7 años (IC 95 % = 60-90 años). La regresión logística binaria demostró que las variables asociadas a insuficiencia de vitamina D fueron agotamiento (RM = 2.6, IC 95 % = 1.0-6.5, p = 0.03), fragilidad (RM = 9.2, IC 95 % = 2.5-34.1, p = 0.001) y prefragilidad (RM = 4.6, IC 95 % = 2.1-10.0, p < 0.001). Conclusión: Los fenotipos frágil, prefrágil y agotamiento se asocian a insuficiencia de vitamina D.

Abstract Introduction: In older adults, the association of frailty and sarcopenia with vitamin D deficiency is well known, but the association of the components of frailty syndrome has been poorly studied Objective: To determine the association of the components of frailty and sarcopenia with vitamin D insufficiency in older adults. Methods: Adults were studied, in whom age, education, marital status, history of fractures, hospitalizations, anthropometric indicators, sarcopenia, Charlson index, polypharmacy, Fried's frailty phenotype, and plasma vitamin D were recorded; figures < 30 ng/mL were considered indicative of vitamin D insufficiency. Descriptive and inferential statistics were used for statistical analysis. The association was determined by binary logistic regression. Results: One-hundred and seventy-five adults with a mean age of 71.7 ± 6.7 years (95% CI = 60-90 years) were studied. Binary logistic regression showed that the variables associated with vitamin D deficiency were exhaustion (OR = 2.6, 95% CI = 1.0-6.5, p = 0.03), frailty (OR = 9.2, 95% CI = 2.5-34.1, p = 0.001) and pre-frailty (OR = 4.6, 95% CI = 2.1-10.0, p < 0.001). Conclusion: The frail and pre-frail phenotypes, as well as exhaustion, are associated with vitamin D insufficiency.

Novel 7-Chloro-(4-thioalkylquinoline) Derivatives: Synthesis and Antiproliferative Activity through Inducing Apoptosis and DNA/RNA Damage.

A series of 78 synthetic 7-chloro-(4-thioalkylquinoline) derivatives were investigated for cytotoxic activity against eight human cancer as well as 4 non-tumor cell lines. The results showed, with some exceptions, that sulfanyl 5-40 and sulfinyl 41-62 derivatives exhibited lower cytotoxicity for cancer cell lines than those of well-described sulfonyl N-oxide derivatives 63-82. As for compound 81, the most pronounced selectivity (compared against BJ and MRC-5 cells) was observed for human cancer cells from HCT116 (human colorectal cancer with wild-type p53) and HCT116p53-/- (human colorectal cancer with deleted p53), as well as leukemia cell lines (CCRF-CEM, CEM-DNR, K562, and K562-TAX), lung (A549), and osteosarcoma cells (U2OS). A good selectivity was also detected for compounds 73 and 74 for leukemic and colorectal (with and without p53 deletion) cancer cells (compared to MRC-5). At higher concentrations (5 × IC50) against the CCRF-CEM cancer cell line, we observe the accumulation of the cells in the G0/G1 cell phase, inhibition of DNA and RNA synthesis, and induction of apoptosis. In addition, X-ray data for compound 15 is being reported. These results provide useful scientific data for the development of 4-thioalkylquinoline derivatives as a new class of anticancer candidates.

Intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma: A case report.

Giant chorioangiomas are a potentially life-threatening condition that may require intrauterine therapy. We describe a case of a large chorioangioma (>4cm) diagnosed at 30 weeks of gestation causing severe fetal anemia and hydrops. An intrauterine blood transfusion was performed at 31 weeks with reversal of the anemia and hydrops. The neonate was born at 37 weeks showing respiratory distress syndrome that required neonatal intensive care unit admission but was discharged at 30 days of life. Further evaluation at two months of age showed no signs of abnormal neurodevelopment. When timely indicated, intrauterine transfusion of a hydropic fetus with anemia due to a giant chorioangioma is a potentially life-saving therapy that shows good neurodevelopment of the surviving fetus.

Factors associated with the perception of inadequate sanitary control in 12 Latin American countries during the COVID-19 pandemic.

Introduction: Sanitary control mechanisms differ greatly from country to country. Therefore, it is important to know citizens' perception of different realities. We aimed to determine the factors associated with the perception of inadequate sanitary control in 12 Latin American countries during the COVID-19 pandemic. Methods: This is an analytical cross-sectional study. We asked about six perceptions in regard to different situations experienced by inhabitants of 12 Latin American countries during the pandemic. Frequencies according to country were described and associations vs. other important variables were obtained. Results: Out of 8,489 participants, 68% stated that there were moments of collective hysteria. Honduras was the country that most perceived inadequate control mechanisms established by the government. Multivariate analysis showed that there were statistically significant differences among many of the countries according to the six evaluated items. The higher the level of education, the greater the perception of poor control in five of the aspects. Additionally, men had a lower perception of inadequate control. The older the age, the lower the perception of inadequate control regarding whether there was collective hysteria and shortages of basic essentials. Those with COVID-19 had a lower perception of medicine shortages. Conclusion: The population of multiple realities in Latin America have perceived a bad management of the pandemic. Citizens' perception is an important indicator of the performance of each government during the COVID-19 pandemic. This study may provide valuable information on the relationship between the effectiveness of government sanitary control and people's mental health, which ultimately helps to create objective prevention programs against post-traumatic stress disorder, depression, fear of contagion, and collective hysteria. In addition, governments could use this information to design effective mitigation plans for future unavoidable pandemic events based on the six criteria discussed here.

Comparative analysis of striatal [18 F]FDOPA uptake in a partial lesion model of Parkinson's disease in rats: Ratio method versus graphical model.

Animal models of Parkinson's disease are useful to evaluate new treatments and to elucidate the etiology of the disease. Hence, it is necessary to have methods that allow quantification of their effectiveness. [18 F]FDOPA-PET (FDOPA-PET) imaging is outstanding for this purpose because of its capacity to measure changes in the dopaminergic pathway noninvasively and in vivo. Nevertheless, PET acquisition and quantification is time-consuming making it necessary to find faster ways to quantify FDOPA-PET data. This study evaluated Male Wistar rats by FDOPA, before and after being partially injured with 6-OHDA unilaterally. MicroPET scans with a duration of 120 min were acquired and Patlak reference plots were created to estimate the influx constant Kc in the striatum using the full dynamic scan data. Additionally, simple striatal-to-cerebral ratios (SCR) of short static acquisitions were computed and compared with the Kc values. Good correlation (r > 0.70) was obtained between Kc and SCR, acquired between 80-120 min after FDOPA administration with frames of 10 or 20 min and both methods were able to separate the FDOPA-uptake of healthy controls from that of the PD model (SCR -28%, Kc -71%). The present study concludes that Kc and SCR can be trustfully used to discriminate partially lesioned rats from healthy controls.

Components of frailty, sarcopenia and their association with vitamin D deficiency. Cross-sectional, analytical study.

INTRODUCTION: In older adults, the association of frailty and sarcopenia with vitamin D deficiency is well known, but the association of the components of frailty syndrome has been poorly studied. OBJECTIVE: To determine the association of the components of frailty and sarcopenia with vitamin D insufficiency in older adults. METHODS: Adults were studied, in whom age, education, marital status, history of fractures, hospitalizations, anthropometric indicators, sarcopenia, Charlson index, polypharmacy, Fried's frailty phenotype, and plasma vitamin D were recorded; figures < 30 ng/mL were considered indicative of vitamin D insufficiency. Descriptive and inferential statistics were used for statistical analysis. The association was determined by binary logistic regression. RESULTS: One-hundred and seventy-five adults with a mean age of 71.7 ± 6.7 years (95% CI = 60-90 years) were studied. Binary logistic regression showed that the variables associated with vitamin D deficiency were exhaustion (OR = 2.6, 95% CI = 1.0-6.5, p = 0.03), frailty (OR = 9.2, 95% CI = 2.5-34.1, p = 0.001) and pre-frailty (OR = 4.6, 95% CI = 2.1-10.0, p < 0.001). CONCLUSION: The frail and pre-frail phenotypes, as well as exhaustion, are associated with vitamin D insufficiency.

INTRODUCCIÓN: En adultos mayores, la asociación de fragilidad y sarcopenia con deficiencia de vitamina D es conocida, pero poco se ha estudiado la asociación de los componentes del síndrome de fragilidad. OBJETIVO: Determinar la asociación entre los componentes de fragilidad, sarcopenia e insuficiencia de vitamina D en adultos mayores. MÉTODOS: Se estudiaron adultos de quienes se registró edad, escolaridad, estado civil, antecedentes de fracturas, hospitalizaciones, indicadores antropométricos, sarcopenia, índice de Charlson, polifarmacia, fenotipo de fragilidad de Fried y vitamina D plasmática; cifras < 30 ng/mL se consideraron indicativas de insuficiencia de vitamina D. Para el análisis estadístico se utilizó estadística descriptiva e inferencial. La asociación fue determinada mediante regresión logística binaria. RESULTADOS: Se estudiaron 175 adultos con un promedio de edad de 71.7 ± 6.7 años (IC 95 % = 60-90 años). La regresión logística binaria demostró que las variables asociadas a insuficiencia de vitamina D fueron agotamiento (RM = 2.6, IC 95 % = 1.0-6.5, p = 0.03), fragilidad (RM = 9.2, IC 95 % = 2.5-34.1, p = 0.001) y prefragilidad (RM = 4.6, IC 95 % = 2.1-10.0, p < 0.001). CONCLUSIÓN: Los fenotipos frágil, prefrágil y agotamiento se asocian a insuficiencia de vitamina D.

Bone regeneration using Wollastonite/ß-TCP scaffolds implants in critical bone defect in rat calvaria.

In order to provide favorable conditions for bone regeneration, a lot of biomaterials have been developed and evaluated, worldwide. Composite biomaterials have gained notoriety, as they combine desirable properties of each isolated material. Thus, in this research, bone repair capacity of three developed formulations of ceramic scaffolds were evaluated histomorphometrically, after implantation. Scaffolds were based on wollastonite (W) andß-tricalcium phosphate (ß-TCP) composites in three different ratios (wt.%). ThirtyWistarrats were randomly assigned to three experimental groups: W-20 (20 W/80ß-TCP wt.%), W-60 (60 W/40ß-TCP wt.%), and W-80 (80 W/20ß-TCP wt.%), evaluated by optical microscopy at biological tests after 15 and 45 days of implantation. Throughout the study, the histological results evidenced that the scaffolds remained at the implantation site, were biocompatible and presented osteogenic potential. The percentage of neoformed mineralized tissue was more evident in the W-20 group (51%), at 45 days. The composite of the W-80 group showed more evident biodegradation than the biomaterials of the W-20 and W-60 groups. Thus, it is concluded that the scaffold containing 20 W/80ß-TCP (wt.%) promoted more evident bone formation, but all composites evaluated in this study showed notorious bioactivity and promising characteristics for clinical application.

[68Ga]Ga-iPSMA-Lys3-Bombesin: Biokinetics, dosimetry and first patient PET/CT imaging.

BACKGROUND: The prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) are overexpressed in prostate cancer (PCa). In preclinical studies, the iPSMA-Lys3-Bombesin (iPSMA-BN) heterodimeric ligand has shown a suitable affinity for PSMA and GRPR. This research aimed to assess the biokinetics and radiation dosimetry of [68Ga]Ga-iPSMA-BN in four healthy volunteers based on biodistribution data obtained from whole-body PET/CT studies, as well as to visualize the [68Ga]Ga-iPSMA-BN tumor uptake in a patient with PCa. METHODS: PET/CT images acquired at 5 min, 0.5, 1, and 2 h after radiotracer administration (124.5 ± 2.1 MBq) were corrected for attenuation, scattering, dead-time, and decay. The activity in the segmented volumes of interest (VOIs) in each source organ at different times was adjusted to mono- and bi-exponential biokinetic models (A(t)VOI), from which the total disintegrations (N) were calculated to assess the internal radiation doses by using the OLINDA V1.1 code. RESULTS: Images from the patient showed an evident uptake by the metastasis (SUVmax of 4.7) and by the organs expressing GRPR (pancreas) and PSMA (salivary glands). The average effective dose was 2.70 ± 0.05 mSv, which was like those known for most of the 68Ga studies, making [68Ga]Ga-iPSMA-BN a promising dual-target PET imaging radiotracer for PCa. CONCLUSIONS: [68Ga]Ga-iPSMA-BN, capable of detecting both PSMA and GRPR with suitable biokinetics and dosimetric patterns, could be a potential complementary diagnostic tool for the improvement of prostate cancer PET imaging.

Production of Copper Radionuclides in Compact Medical Cyclotrons using Solid Targets.

Over the last several years there has been a growing interest in the use of radiopharmaceuticals labeled with metallic radionuclides, especially isotopes of copper (Cu). Cu has a unique set of radionuclides with a potential application not only for diagnostic imaging but also for applications in targeted radionuclide therapy. To review the methods and routes used for the production of Cu radionuclides in compact medical cyclotrons (Ep<20 MeV) using solid targets. The cyclotron production of Cu radionuclides using solid targets has proven to be very efficient. The large number of compact medical cyclotrons distributed worldwide, and the high target yields in the production of Cu radionuclides achieved at these energies, form a potential network of distribution to satisfy the growing demand for these radionuclides, especially 64Cu.

Synthesis and in vivo evaluation of a scaffold containing wollastonite/ß-TCP for bone repair in a rabbit tibial defect model.

Scaffolds are models designed to aid the interaction between cells and extracellular bone matrix, providing structural support for newly formed bone tissue. In this work, wollastonite with ß-TCP porous ceramic scaffolds was developed by the polymer sponge replication. Their microstructure, cell viability and bioactivity were tested. in vivo was performed to evaluate the use of a calcium silicate-based implant in the repair of rabbit tibias. Holes were made in the both proximal and distal tibial metaphysis of each animal and filled with calcium silicate-based implant, and in the left tibia, no implant were used, serving as control group. Animals underwent euthanasia after 30 and 60 days of study. The animals were submitted to clinical-radiographic evaluations and their histology was analyzed by optical and scanning electron microscope. The studied calcium silicate implant provided biocompatibility and promoted bone formation, stimulating the process of bone repair in rabbits, features observed by gradual radiopacity shown in the radiographic evaluations.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy.

BACKGROUND: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. METHODS: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. RESULTS: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. CONCLUSION: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

In Silico Study of the Resistance to Organophosphorus Pesticides Associated with Point Mutations in Acetylcholinesterase of Lepidoptera: B. mandarina, B. mori, C. auricilius, C. suppressalis, C. pomonella, H. armígera, P. xylostella, S. frugiperda, and S. litura.

An in silico analysis of the interaction between the complex-ligands of nine acetylcholinesterase (AChE) structures of Lepidopteran organisms and 43 organophosphorus (OPs) pesticides with previous resistance reports was carried out. To predict the potential resistance by structural modifications in Lepidoptera insects, due to proposed point mutations in AChE, a broad analysis was performed using computational tools, such as homology modeling and molecular docking. Two relevant findings were revealed: (1) Docking results give a configuration of the most probable spatial orientation of two interacting molecules (AChE enzyme and OP pesticide) and (2) a predicted ΔGb. The mutations evaluated in the form 1 acetylcholinesterase (AChE-1) and form 2 acetylcholinesterase (AChE-2) structures of enzymes do not affect in any way (there is no regularity of change or significant deviations) the values of the binding energy (ΔGb) recorded in the AChE-OPs complexes. However, the mutations analyzed in AChE are associated with a structural modification that causes an inadequate interaction to complete the phosphorylation of the enzyme.

Anaerobic ammonium oxidation linked to sulfate and ferric iron reduction fuels nitrogen loss in marine sediments.

Availability of fixed nitrogen is a pivotal driver on primary productivity in the oceans, thus the identification of key processes triggering nitrogen losses from these ecosystems is of major importance as they affect ecosystems function and consequently global biogeochemical cycles. Denitrification and anaerobic ammonium oxidation coupled to nitrite reduction (Anammox) are the only identified marine sinks for fixed nitrogen. The present study provides evidence indicating that anaerobic ammonium oxidation coupled to the reduction of sulfate, the most abundant electron acceptor present in the oceans, prevails in marine sediments. Tracer analysis with 15N-ammonium revealed that this microbial process, here introduced as Sulfammox, accounts for up to 5 µg 15N2 produced g-1 day-1 in sediments collected from the eastern tropical North Pacific coast. Raman and X-ray diffraction spectroscopies revealed that elemental sulfur and sphalerite (ZnFeS) were produced, besides free sulfide, during the course of Sulfammox. Anaerobic ammonium oxidation linked to Fe(III) reduction (Feammox) was also observed in the same marine sediments accounting for up to 2 µg 15N2 produced g-1 day-1. Taxonomic characterization, based on 16S rRNA gene sequencing, of marine sediments performing the Sulfammox and Feammox processes revealed the microbial members potentially involved. These novel nitrogen sinks may significantly fuel nitrogen loss in marine environments. These findings suggest that the interconnections among the oceanic biogeochemical cycles of N, S and Fe are much more complex than previously considered.

The sequences of MinE responsible for its subcellular localization analyzed by competitive binding method in Escherichia coli.

The subcellular localization of a protein is important for its proper function. Escherichia coli MinE is a small protein with clear subcellular localization, which provides a good model to study protein localization mechanism. In the present study, a series of recombinant minEs truncated in one end or in the middle regions, fused with egfp, was constructed, and these recombinant proteins could compete to function with the chromosomal MinE. Our results showed that the sequences related to the subcellular localization of MinE span several functional domains, demonstrating that MinE positioning in cells depends on multiple factors. The eGFP fusions with some truncated MinE from N-terminal resulted in different cell phenotypes and localization features, implying that these fusions can interfere chromosomal MinE's function, similar to MinE36-88 phenotype in the previous report. The amino acid in the region (32-48) is sensitive to change MinE conformation and influence its dimerization. Some truncated protein structure could be unstable. Thus, the MinE localization is prerequisite for its proper anti-MinCD function and some new features of MinE were demonstrated. This approach can be extended for subcellular localization research for other essential proteins.

Disruption of behavior and brain metabolism in artificially reared rats.

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.

Development of AlN and TiB2 Composites with Nb2O5, Y2O3 and ZrO2 as Sintering Aids.

The synthesis of AlN and TiB2 by spark plasma sintering (SPS) and the effect of Nb2O5, Y2O3 and ZrO2 additions on the mechanical properties and densification of the produced composites is reported and discussed. After the SPS process, dense AlN and TiB2 composites with Nb2O5, Y2O3 and ZrO2 were successfully prepared. X-ray diffraction analysis showed that in the AlN composites, the addition of Nb2O5 gives rise to Nb4N3 during sintering. The compound Y3Al5O12 (YAG) was observed as precipitate in the sample with Y2O3. X-ray diffraction analysis of the TiB2 composites showed TiB2 as a single phase in these materials. The maximum Vickers and toughness values were 14.19 ± 1.43 GPa and 27.52 ± 1.75 GPa for the AlN and TiB2 composites, respectively.

Targeting Metabolic Remodeling in Triple Negative Breast Cancer in a Murine Model.

Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis. Materials and Methods: Thirty-five female nude mice were transplanted subcutaneously with MDA-MB-231 triple negative human cancer cell line. Once tumors were visible, mice were treated with doxorubicin, metformin, oxamate or all possible pharmacologic combinations. Treatments were administered daily for 15 days and tumors were measured by calipers every day. MicroPET images were taken in three different occasions, basal state, in the middle of the treatment, and at the end of treatment. Western blot analyses, qRT-PCR, flow cytometry, and cytotoxicity assays were performed to elucidate the mechanism of cell death promoted by the drugs in vitro. Results: In this work we assessed the proof of concept of metabolic correction in solid tumors as an effective drug treatment; hence, mice bearing tumors treated with the DoxMetOx therapy showed a complete inhibition of the tumor mass growing in 15 days of treatment depicted by the micro PET images. In vitro studies displayed that the three drugs together act by inhibiting both, mTOR-phosphorylation and expression of LDH-A gene, promoting apoptosis via dependent on the caspase-3 pathway, accompanied by cleavage of PARP. Moreover, induction of autophagy process was observed by the accumulation of LC3-II, a primordial protein implicated in the conformation and elongation of the autophagolysosome. Conclusions: The lack of effective drugs to inhibit TNBC growth is the main cause of therapy failure and tumor relapse. We have showed that targeting crucial molecular pathways in cancer by the combination of Doxorubicin, Metformin, and Oxamate resulted as an efficient and rapid tumor growth inhibitor in a triple negative xenograft model. Our findings are promising for patients diagnosed with TNBC tumors, for which unfortunately there are no reliable drug therapies.

Biodistribution in rats and estimates of doses to humans from (64)CuCl2, a potential theranostic tracer.

The aim of this study was to obtain data on the biodistribution of (64)CuCl2 in rats and to obtain estimates of the radiation doses to humans by extrapolating the animal data. MicroPET imaging and biodistribution studies were carried out with Wistar rats, and the doses were estimated with OLINDA/EXM. The lower large intestine wall was found to be the critical organ with an absorbed dose of 139±34 and 125±32µGy/MBq for females and males, respectively. The corresponding effective doses were estimated as 47±4 and 39±4µSv/MBq.

Reacción sistémica tras la ingesta de una oruga procesionaria del pino: ¿Manejo conservador? / Systemic reaction after pine processionary caterpillar ingestion: Conservative management?

La oruga procesionaria del pino, forma larvaria de la mariposa nocturna Thaumetopoea pityocampa, es una de las principales plagas forestales del sur de Europa. Con frecuencia, estas orugas producen reacciones locales en humanos debidas a los pelillos urticantes microscópicos que las recubren. La mayoría de los síntomas ocasionados son cutáneos, como urticaria aguda, y son mucho más infrecuentes las reacciones sistémicas. Se presenta un caso de reacción sistémica, con edema orofacial, babeo y urticaria tras la ingesta de una oruga procesionaria del pino en un lactante de 11 meses, en el cual el tratamiento farmacológico fue suficiente para la resolución de los síntomas. No tuvo, en ningún momento, compromiso de la vía aérea ni otros datos de anafilaxia, por lo que se desestimaron actuaciones más agresivas, como intubación orotraqueal, endoscopía o laringoscopía.

The larval form of the moth Thaumetopoea pityocampa, known as pine processionary caterpillar, is one of the main forest pests in southern Europe. Often, these caterpillars cause local reactions in humans, due to their microscopic stinging hairs. Most symptoms affect skin, in form of acute urticaria. Systemic reactions are rare. An eleven month old infant with a systemic reaction after ingestion of a pine processionary caterpillar is presented. The boy reached the Emergency Room with orofacial edema, drooling and urticaria. Drug treatment was enough to resolve the symptoms. The patient did not present airway commitment, nor anaphylaxis data at any moment, so more aggressive actions, such as endotracheal intubation, endoscopy or laryngoscopy, were rejected.