Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer.

INTRODUCTION: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). MATERIALS AND METHODS: 100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60-90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. RESULTS: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). CONCLUSION: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Progreso y utilidad actual de la radiómica dentro del estudio PET/TC en cáncer de mama no metastásico: una revisión sistemática / Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review

Objetivo Sintetizar la evidencia actual sobre la utilidad de la radiómica en el análisis de la imagen PET/TC en cáncer de mama local o localmente avanzado y evaluar la calidad metodológica de los estudios radiómicos publicados al respecto. Material y métodos Revisión sistemática de artículos en distintas bases de datos hasta 2021 utilizando los términos «PET», «radiomics», «texture», «breast». Se seleccionaron solo artículos con datos humanos y que incluyeran una imagen de PET en su análisis. Se excluyeron estudios con datos de pruebas y menos de 20 pacientes. De cada artículo se extrajo el tamaño muestral, el radiotrazador utilizado, la técnica de imagen y las características de imagen extraídas. Se determinó la calidad metodológica de los estudios mediante el instrumento QUADAS-2. Resultados Se seleccionaron 18 artículos. El diseño retrospectivo fue el más utilizado. La característica radiómica más estudiada fue el SUVmax. Diversos parámetros radiómicos se correlacionaron con la caracterización tumoral, y la heterogeneidad tumoral demostró utilidad para predecir el curso de la enfermedad y la respuesta al tratamiento. La mayoría de los artículos mostraron un alto riesgo de sesgo, derivado principalmente de la selección de pacientes. Conclusiones Se observó una alta probabilidad de sesgo en los artículos publicados. La radiómica es un campo aún en desarrollo y son necesarios más estudios para demostrar su utilidad en la práctica clínica habitual. La herramienta QUADAS-2 permite la valoración crítica de la calidad metodológica de la evidencia disponible. Pese a las limitaciones, la radiómica se muestra como una herramienta que puede ayudar a conseguir un manejo oncológico personalizado en el cáncer de mama (AU)

Aim To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. Methods Systematic review of articles in different databases until 2021 using the terms «PET», «radiomics», «texture», «breast». Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. The sample size, radiotracer used, imaging technique, and radiomics characteristics were extracted from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. Results Eighteen articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. Conclusions A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer (AU)

Progress and current utility of radiomics in PET/CT study of non-metastatic breast cancer: A systematic review.

AIM: To synthesize the current evidence of the usefulness of radiomics in PET/CT image analysis in local and locally advanced breast cancer. Also, to evaluate the methodological quality of the radiomic studies published. METHODS: Systematic review of articles in different databases until 2021 using the terms "PET", "radiomics", "texture", "breast". Only articles with human data and that included a PET image were included. Studies with simulated data and with less than 20 patients were excluded. Were extracted sample size, radiotracer used, imaging technique, and radiomics characteristics from each article. The methodological quality of the studies was determined using the QUADAS-2 tool. RESULTS: 18 articles were selected. The retrospective design was the most used. The most studied radiomic characteristic was SUVmax. Several radiomic parameters were correlated with tumor characterization, and tumor heterogeneity proved useful for predicting disease course and response to treatment. Most articles showed a high risk of bias, mainly from the patient selection. CONCLUSIONS: A high probability of bias was observed in most of the published articles. Radiomics is a developing field and more studies are needed to demonstrate its usefulness in routine clinical practice. The QUADAS-2 tool allows critical assessment of the methodological quality of the available evidence. Despite its limitations, radiomics is shown to be an instrument that can help to achieve personalized oncologic management of breast cancer.

Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules.

OBJECTIVE: Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action. MATERIALS AND METHODS: 10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed. RESULTS: In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine. CONCLUSIONS: At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.

Development of a new method for the quantitation of metabolites in the absence of chemically synthetized authentic standards.

A new method for the quantification of metabolites in the absence of a chemically synthetized authentic standard is described herein. Metabolites to be used as reference standards were obtained biologically from microsomes incubation. The method is a stepwise process in which, only the radiolabeled (14C) and non-radiolabeled parent compound are required. Briefly, the separation and principles of equimolar detection of LC-radioactivity were applied and, a calibration curve of the 14C-parent compound was used to quantify the formation of its 14C-metabolite. In turn, serial dilutions of this 14C-metabolite were the base for the calibration curve that allowed the quantification of the non-radiolabeled metabolite. This method was applied in plasma samples obtained from a dog pharmacokinetic study in which, a PharmaMar compound (lurbinectedin) and its N-desmethylated metabolite were quantified and, the results compared to those obtained by the classical approach (with the chemically synthetized N-desmethylated metabolite). Plasma concentrations obtained with the two methods were very similar, with standard relative errors between -11% to -4%. Similar, main pharmacokinetic parameters were calculated with the concentrations obtained either thru this method or by using a chemically synthetized authentic standard.

Biological parameters of interbreeding subspecies of Meccus phyllosomus (Hemiptera: Reduviidae: Triatominae) in western Mexico.

Understanding the biological parameters of some triatomine subspecies of Meccus phyllosomus (Burmeister) is a crucial first step in estimating the epidemiological importance of this group. Biological parameters related to egg eclosion, egg-to-adult development time, number of blood meals to moult, percentage of females at the end of the cycle, number of laid eggs, and the accumulative mortality for each instar of three M. phyllosomus subspecies [Meccus phyllosomus pallidipennis (Stål), Meccus phyllosomus longipennis (Usinger), and Meccus phyllosomus picturatus (Usinger)] as well as their laboratory hybrids were evaluated and compared. No significant differences (P > 0.05) were recorded among the experimental hybrids (M. p. longipennis × M. p. pallidipennis, M. p. longipennis × M. p. picturatus, M. p. pallidipennis × M. p. picturatus) and reciprocal cohorts. In five of the six studied parameters (egg eclosion, egg-to-adult development time, number of blood meals to moult, number of laid eggs and accumulative mortality), with the exception of the non-significant percentage of females obtained among all the studied cohorts, at least one of the parental cohorts in each set of crosses exhibited better fitness results than by those of their hybrid descendants. The lack of hybrid fitness in our study indicates the maintenance of reproductive isolation of parental genotypes. Moreover, the results lead us to propose that an incipient speciation process by distance is currently developing among the three studied subspecies, increasing the differences between them that modify the transmission efficiency of Trypanosoma cruzi to human beings in Mexico.

Transcriptional regulation of the assT-dsbL-dsbI gene cluster in Salmonella enterica serovar Typhi IMSS-1 depends on LeuO, H-NS, and specific growth conditions.

The assT gene encodes an arylsulfate sulfotransferase, an enzyme that catalyzes sulfuryl transfer from phenolic sulfate to a phenolic acceptor. In Salmonella enterica serovar Typhi IMSS-1, the assT gene is located upstream of the dsbL and dsbI genes, which are involved in a disulfide bond formation required for its activation. The assT-dsbL-dsbI gene cluster forms an operon transcribed by a LeuO-dependent promoter, in rich medium A (MA). Interestingly, in the absence of cloned leuO and in a ΔleuO background, two transcription start sites were detected for assT and two for dsbL-dsbI in minimal medium. The H-NS nucleoid protein repressed the expression of the assT-dsbL-dsbI LeuO-dependent operon, as well as of the assT transcriptional units. Thus, the expression of the assT-dsbL-dsbI gene cluster depends on the global regulatory proteins LeuO and H-NS, as well as on specific growth conditions.

Biocompatibility of alendronate-loaded acrylic cement for vertebroplasty.

This paper reports a biological evaluation of a non-resorbable acrylic cement loaded with alendronate for the treatment of osteoporotic vertebral compression fractures. The cement formulation was based on polymethyl methacrylate and acrylic monomers; one of these had covalently linked vitamin E residues. The same cement in the absence of alendronate was used as a control. The setting of the charged cement presented a maximum polymerization temperature of 44°C, a setting time of 24 min, a residual monomer content lower than 3 wt.%, a compressive strength of 99±10 MPa and an elastic modulus of 1.2±0.2 GPa. Cytotoxicity studies using human osteoblast cultures revealed that the leachable substances of the alendronate loaded cement collected between 1 and 7 days decreased cell viability to values lower than 80%. However, morphological changes and cellular damage in cells produced by the extracts decreased with the leak time. Cell adhesion and growth on charged cement was significantly lower than on the control. Implantation of the cement paste in the intra-femoral cavity of rabbits showed that initially the osteogenic activity was evident for the cement charged with alendronate, and the osteosynthesis process took place mainly in the trabeculae and was manifested by the presence of a non-mineralised osseous spicule. The interface between material and adjacent bone tissue was initially characterized by a variable fibrous response that in many cases it appeared reduced to thin connective tissue after a 24-week-period.

Response of GABAergic cells in the deep mesencephalic nucleus to dopaminergic cell degeneration: an electrophysiological and in situ hybridization study.

The deep mesencephalic nucleus (DMN) is a large midbrain reticular region located between the substantia nigra compacta and the superior colliculus. It contains GABAergic cells that share striatal afferents, thalamic and collicular efferents, as well as neurochemical and electrophysiological similarities, with those of the substantia nigra reticulata. In the present paper we used electrophysiological (firing rate and firing pattern) and morphological (densitometric analysis of in situ hybridization histochemical labeling for glutamic acid decarboxylase (GAD)65 and GAD67 mRNA) techniques, to study the response of DMN GABAergic cells to the degeneration of nigral dopaminergic cells. Our results showed that unilateral dopaminergic cell loss (after injection of 6-hydroxydopamine in the medial forebrain bundle) induces a bilateral and symmetrical increase in both firing rate and GAD67 mRNA levels and a decrease in GAD65 mRNA levels. These findings support the involvement of DMN GABAergic cells in the basal ganglia modifications that follow dopaminergic cell loss, also suggesting its participation in the pathophysiology of Parkinson's disease. The symmetry of effects, together with its recently reported bilateral projections to the thalamus and superior colliculus, suggest that unlike substantia nigra reticulata, DMN is involved in the interhemispheric regulation of basal ganglia, probably keeping their functional symmetry even after asymmetric lesions.

Rhizosphere effects on microbial community structure and dissipation and toxicity of polycyclic aromatic hydrocarbons (PAHs) in spiked soil.

Phytoremediation of soils polluted with polycyclic aromatic hydrocarbons (PAHs) has so far neglected the possible role of the ubiquitous symbiotic associations between plant roots and fungi known as arbuscular mycorrhizas. A time course laboratory experiment with clover and ryegrass grown on spiked [500 + 500 + 50 mg kg-1 of anthracene, chrysene and dibenz(a,h)anthracene] soil demonstrated for the first time that dissipation of condensed PAHs may be enhanced in the presence of arbuscular mycorrhiza [66 and 42% reductions in chrysene and dibenz(a,h)anthracene, respectively, versus 56 and 20% reductions in nonmycorrhizal controls]. Addition of a surfactant accelerated initial PAH dissipation but did not attain final PAH concentrations below those obtained with nonmycorrhizal plants. Toxicity tests (earthworm survival and bioluminescence inhibition in Vibrio fischeri) indicated that mycorrhiza reduced the toxicity of PAHs and/or their metabolites and counteracted a temporally enhanced toxicity mediated by surfactant addition. Phospholipid fatty acid profiles demonstrated that the imposed treatments altered the microbial community structure and indicated that the mycorrhiza-associated microflora was responsible for the observed reductions in PAH concentrations in the presence of mycorrhiza.

Effects of anticonvulsant lactams on in vitro seizures in the hippocampal slice preparation.

Some 3,3-disubstituted 2-pyrrolidinones and 2-piperidinones (five- and six-membered ring lactams, respectively) possess potent in vivo anticonvulsant activity. In vitro these lactams potentiate GABA(A) receptor-mediated chloride currents, which is thought to be the mechanism by which they exert their therapeutic effects. However, the apparent affinity for these GABA(A) interactions is low: EC50s range from hundreds of micromolar to low millimolar values. In order to more completely characterize the activities of these compounds, it was necessary to know the concentrations required to curtail epileptiform activity in an intact neural network, and the mechanism by which this occurs. To address these questions, we used two methods of inducing ictal activity in hippocampal-entorhinal cortical slices: 4-aminopyridine (4-AP) and low Mg2+. We found that 3,3-diethyl-2-pyrrolidinone (diethyl-lactam) prevents seizure-like discharges with IC50s of 1.1 and 2.1 mM in the two models, respectively. These values are nearly identical to the EC50 value obtained in whole-cell studies of diethyl-lactam's GABA(A) receptor modulation. The addition of the GABA(A) antagonist picrotoxin to the low Mg2+ ACSF produced seizures which persisted during diethyl-lactam application. Neither 3-benzyl-3-ethyl-2-piperidinone (3-BEP) nor alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone (alpha-EMTBL), two compounds which are similar to diethyl-lactam, but demonstrate picrotoxin-insensitive inhibition of voltage-dependent currents, diminished low Mg2+/picrotoxin seizure activity. Our results support the hypothesis that diethyllactam and related compounds exert their anticonvulsant activity primarily, if not exclusively, by modulating the GABA(A) receptor.

Histochemical and immunohistochemical detection of neurons that produce nitric oxide: effect of different fixative parameters and immunoreactivity against non-neuronal NOS antisera.

This study focused on two points concerning the histochemical and immunohistochemical detection of neurons that produce nitric oxide (NO): (a) the effect of fixation and other methodological parameters on the staining pattern of both NADPH-diaphorase (NADPH-d) histochemistry and nitric oxide synthase (NOS) immunohistochemistry, and (b) the possibility that neurons display immunoreactivity against NOS antisera obtained from non-neuronal sources. Frontal sections of rat brains, fixed with 4% paraformaldehyde according to different protocols, were processed for single and double labeling using NADPH-d histochemistry and neuronal (nNOS), macrophagic (macNOS), and endothelial (eNOS) NOS immunohistochemistry. Our results show that variations in the fixative schedule, even within standard parameters, produce qualitative and quantitative changes in NADPH-d labeling. The effect of fixative on weakly stained neurons is different from that on heavily stained neurons. In subfixed brains, a large number of NOS-positive neurons lose their NADPH-d activity, whereas NOS immunolabeling remains unaltered. This finding may be particularly interesting in morphological studies that compare NADPH-d activity under experimental conditions that can affect brain perfusion. On the other hand, many cortical and subcortical neurons show macNOS immunoreactivity, most of it colocalized with nNOS.