Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review

Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2- negative (HER2-) breast cancer constitutes a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patientpresenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.info:eu-repo/semantics/publishedVersio

The dynamics of apparent horizons in Robinson-Trautman spacetimes

We present an alternative scheme of finding apparent horizons based on spectral methods applied to Robinson-Trautman spacetimes. We have considered distinct initial data such as representing the spheroids of matter and the head-on collision of two non-rotating black holes. The evolution of the apparent horizon is presented. We have obtained in some cases a mass gap between the final Bondi and apparent horizon masses, whose implications were briefly commented in the light of the thermodynamics of black holes.Comment: 9 pages, 7 figure

Understanding the role of growth factors in modulating stem cell tenogenesis

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.Authors thank the Portuguese Foundation for Science and Technology (FCT) for the research project BIBS (PTDC/CVT/102972/2008) and for the post-doc fellowship grant: SFRH/BPD/86775/2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Time sequence of the damage to the acceptor and donor sides of photosystem II by UV-B radiation as evaluated by chlorophyll a fluorescence

The effects of ultraviolet-B (UV-B) radiation on photosystem II (PS II) were studied in leaves of Chenopodium album. After the treatment with UV-B the damage was estimated using chlorophyll a fluorescence techniques. Measurements of modulated fluorescence using a pulse amplitude modulated fluorometer revealed that the efficiency of photosystem II decreased both with increasing time of UV-B radiation and with increasing intensity of the UV-B. Fluorescence induction rise curves were analyzed using a mechanistic model of energy trapping. It appears that the damage by UV-B radiation occurs first at the acceptor side of photosystem II, and only later at the donor side

Effect of bilirubin on cytochrome c oxidase activity of mitochondria from mouse brain and liver

<p>Abstract</p> <p>Background</p> <p>The unbound, free concentration (B_f) of unconjugated bilirubin (UCB), and not the total UCB level, has been shown to correlate with bilirubin cytotoxicity, but the key molecular mechanisms accounting for the toxic effects of UCB are largely unknown.</p> <p>Findings</p> <p>Mouse liver mitochondria increase unbound UCB oxidation, consequently increasing the apparent rate constant for unbound UCB oxidation by HRP (Kp), higher than in control and mouse brain mitochondria, emphasizing the importance of determining Kp in complete systems containing the organelles being studied. The <it>in vitro </it>effects of UCB on cytochrome <it>c </it>oxidase activity in mitochondria isolated from mouse brain and liver were studied at B_franging from 22 to 150 nM. The results show that UCB at B_fup to 60 nM did not alter mitochondrial cytochrome <it>c </it>oxidase activity, while the higher concentrations significantly inhibited the enzyme activity by 20% in both liver and brain mitochondria.</p> <p>Conclusions</p> <p>We conclude that it is essential to include the organelles being studied in the medium used in measuring both Kp and B_f. A moderately elevated, pathophysiologically-relevant B_fimpaired the cytochrome <it>c </it>oxidase activity modestly in mitochondria from mouse brain and liver.</p

On the equivalence between implicit regularization and constrained differential renormalization.

Constrained differential renormalization (CDR) and the constrained version of implicit regularization are two regularization independent techniques that do not rely on dimensional continuation of the space-time. These two methods, which have rather distinct bases, have been successfully applied to several calculations, which show that they can be trusted as practical, symmetry invariant frameworks (gauge and supersymmetry included) in perturbative computations even beyond one-loop order. In this paper, we show the equivalence between these two methods at one-loop order. We show that the configuration space rules of CDR can be mapped into the momentum-space procedures of implicit regularization, the major principle behind this equivalence being the extension of the properties of regular distributions to regularized ones

PEEP-ZEEP technique: cardiorespiratory repercussions in mechanically ventilated patients submitted to a coronary artery bypass graft surgery

<p>Abstract</p> <p>Background</p> <p>The PEEP-ZEEP technique is previously described as a lung inflation through a positive pressure enhancement at the end of expiration (PEEP), followed by rapid lung deflation with an abrupt reduction in the PEEP to 0 cmH₂O (ZEEP), associated to a manual bilateral thoracic compression.</p> <p>Aim</p> <p>To analyze PEEP-ZEEP technique's repercussions on the cardio-respiratory system in immediate postoperative artery graft bypass patients.</p> <p>Methods</p> <p>15 patients submitted to a coronary artery bypass graft surgery (CABG) were enrolled prospectively, before, 10 minutes and 30 minutes after the technique. Patients were curarized, intubated, and mechanically ventilated. To perform PEEP-ZEEP technique, saline solution was instilled into their orotracheal tube than the patient was reconnected to the ventilator. Afterwards, the PEEP was increased to 15 cmH₂O throughout 5 ventilatory cycles and than the PEEP was rapidly reduced to 0 cmH₂O along with manual bilateral thoracic compression. At the end of the procedure, tracheal suction was accomplished.</p> <p>Results</p> <p>The inspiratory peak and plateau pressures increased during the procedure (p < 0.001) compared with other pressures during the assessment periods; however, they were within lung safe limits. The expiratory flow before the procedure were 33 ± 7.87 L/min, increasing significantly during the procedure to 60 ± 6.54 L/min (p < 0.001), diminishing to 35 ± 8.17 L/min at 10 minutes and to 36 ± 8.48 L/min at 30 minutes. Hemodynamic and oxygenation variables were not altered.</p> <p>Conclusion</p> <p>The PEEP-ZEEP technique seems to be safe, without alterations on hemodynamic variables, produces elevated expiratory flow and seems to be an alternative technique for the removal of bronchial secretions in patients submitted to a CABG.</p

Characterization of complex networks: A survey of measurements

Each complex network (or class of networks) presents specific topological features which characterize its connectivity and highly influence the dynamics of processes executed on the network. The analysis, discrimination, and synthesis of complex networks therefore rely on the use of measurements capable of expressing the most relevant topological features. This article presents a survey of such measurements. It includes general considerations about complex network characterization, a brief review of the principal models, and the presentation of the main existing measurements. Important related issues covered in this work comprise the representation of the evolution of complex networks in terms of trajectories in several measurement spaces, the analysis of the correlations between some of the most traditional measurements, perturbation analysis, as well as the use of multivariate statistics for feature selection and network classification. Depending on the network and the analysis task one has in mind, a specific set of features may be chosen. It is hoped that the present survey will help the proper application and interpretation of measurements.Comment: A working manuscript with 78 pages, 32 figures. Suggestions of measurements for inclusion are welcomed by the author

GROWTH OF CERRADO NATIVE SPECIES AND OF Vetiveria zizanioides IN COLLUVIUM OF GULLIES

Taxas de germina\ue7\ue3o de sementes, sobreviv\ueancia e crescimento de plantas, par\ue2metros estes avaliados no presente estudo, s\ue3o informa\ue7\uf5es essenciais para a caracteriza\ue7\ue3o do potencial biol\uf3gico de esp\ue9cies para uso em processos de recupera\ue7\ue3o de \ue1reas degradadas. A falta de conhecimento sobre tais aspectos em esp\ue9cies nativas t\ueam justificado o uso de plantas ex\uf3ticas na revegeta\ue7\ue3o de vo\ue7orocas em todo o Brasil. Entretanto, especialmente em locais sujeitos \ue0 grande sazonalidade clim\ue1tica e sobre solos oligotr\uf3ficos, esp\ue9cies ex\uf3ticas nem sempre apresentam bom desempenho, levando o empreendimento de revegeta\ue7\ue3o ao insucesso ou elevando consideravelmente a necessidade de aplica\ue7\ue3o de tratos culturais. Com o objetivo de ampliar os conhecimentos sobre o potencial biol\uf3gico para revegeta\ue7\ue3o em vo\ue7orocas de plantas nativas do cerrado e de uma gram\uednea ex\uf3tica, que vem sendo amplamente usada em projetos de conten\ue7\ue3o de eros\ue3o, pl\ue2ntulas e touceiras das esp\ue9cies nativas Cratylia argentea (Desv.) Kuntze e Echinolaena inflexa (Poir.) Chase, e da ex\uf3tica Vetiveria zizanioides (L.) Nash foram transferidas para o col\ufavio de uma vo\ue7oroca no munic\uedpio de Ouro Preto - MG, onde permaneceram durante a esta\ue7\ue3o seca de 2010 sem aplica\ue7\ue3o de fertilizantes ou irriga\ue7\ue3o. Em blocos ao acaso, parcelas de 1 x 1 m receberam aleatoriamente quatro tratamentos de plantio: touceiras de Echinolaena inflexa ou de Vetiveria zizanioides; e touceiras destas gram\uedneas em cons\uf3rcio com a leguminosa arbustiva Cratylia argentea. Todas as gram\uedneas e 73% das pl\ue2ntulas da leguminosa sobreviveram. Como esperado, a cobertura verde de Echinolaena Inflexa diminuiu ao longo da esta\ue7\ue3o seca, tendo, entretanto, rebrotado ap\uf3s as primeiras chuvas. Vetiveria zizanioides manteve a \ue1rea foliar ativa e apresentou crescimento significativo no per\uedodo. Cratylia argentea apresentou altas taxas de germina\ue7\ue3o de sementes e de crescimento, entretanto, nodula\ue7\ue3o ocorreu em apenas dois indiv\uedduos. Assim, n\ue3o houve influ\ueancia da leguminosa no crescimento das gram\uedneas. Os resultados indicam que tanto as esp\ue9cies nativas do cerrado como a gram\uednea ex\uf3tica possuem alto potencial para revegeta\ue7\ue3o em col\ufavio de vo\ue7oroca, tendo sobrevivido ao per\uedodo cr\uedtico de seca e sobre substrato oligotr\uf3fico sem adi\ue7\ue3o de fertilizantes ou irriga\ue7\ue3o.Rates of seed germination, plant survival and growth, as measured in the present study, are essential parameters to characterize the biological potential of species for the restoration of degraded areas. The lack of knowledge about these aspects in native species has justified the use of exotic plants in Brazilian gullies revegetation. However, especially in places subject to highly seasonal climate and on oligotrophic soils, exotic species do not always perform well, leading to revegetation failure or significantly increasing the cultivation care needs. To improve the knowledge concerning to the biological potencial of cerrado native species and of an exotic grass which has been used for erosion contention, in the present study, seedlings and clumps of native cerrado species, Cratylia argentea (Desv.) Kuntze and Echinolaena inflexa (Poir.) Chase, and of the exotic grass Vetiveria zizanioides (L.) Nash, were transferred to a gully colluvium in Ouro Preto, Minas Gerais state, where they remained during the dry season of 2010 without application of fertilizers or irrigation. In randomized block design, plots of 1 x 1 m received four planting treatments: clumps of Echinolaena inflexa or Vetiveria zizanioides, and clumps of these grasses intercropped with the legume Cratylia argentea. All grasses and 73% of the legume seedlings survived. As expected, the green cover of Echinolaena inflexa decreased throughout the dry season, however, showing regrowth after the first rains. Leaf area of Vetiveria zizanioides remained active and grew significantly in the period. Cratylia argentea showed high rates of germination and growth; however, nodulation occurred in only two individuals. Thus, there was no influence of the legume on grasses growth. Results indicate that both native species and the exotic grass tested are potential successful plants for gullies replanting. Plants survived and grew on low nutrient substrate and during the critical period of drought without any fertilizer or irrigation application