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

Exploitation promotes earlier sex change in a protandrous patellid limpet, Patella aspera Röding, 1798

Exploitation of organisms can prompt the reduction in the number and size of target populations consequently affecting reproductive output and replenishment. Here, we investigated the effects of exploitation on the population structure of a protandrous patellid limpet, Patella aspera, an overexploited Macaronesian endemic. Timed dives were used to collect animals across eleven islands of Macaronesia. Individuals were inspected for sex, size, and gonad stage. Using catch effort (time per person) per island coastal perimeter as a surrogate for exploitation intensity, we found that limpet abundance (CPUE) and mean size tended to decrease with exploitation intensity. When considering the sex of animals separately, the size of the largest male, but not females, decreased with exploitation. In contrast, the size of the smallest male remained relatively consistent, whereas the size of the smallest female decreased significantly with exploitation. As exploitation is mostly targeting larger individuals, results suggest that males are compensating the removal of larger females, by undergoing sex change at smaller and presumably earlier sizes. These results have wider implications for the conservation of P. aspera, as a reduction in female size will likely affect the numbers of oocytes produced, hence fecundity. Regulations promoting the protection of the larger-sized animals should be enforced to safeguard the replenishment of the population

Dental Occlusion in a Split Amazon Indigenous Population: Genetics Prevails over Environment

Background: Studies examining human and nonhuman primates have supported the hypothesis that the recent increase in the occurrence of misalignment of teeth and/or incorrect relation of dental arches, named dental malocclusion, is mainly attributed to the availability of a more processed diet and the reduced need for powerful masticatory action. For the first time on live human populations, genetic and tooth wear influences on occlusal variation were examined in a split indigenous population. The Arara-Iriri people are descendants of a single couple expelled from a larger village. In the resultant village, expansion occurred through the mating of close relatives, resulting in marked genetic cohesion with substantial genetic differences. Methodology/Principal Findings: Dental malocclusion, tooth wear and inbreeding coefficient were evaluated. The sample examined was composed of 176 individuals from both villages. Prevalence Ratio and descriptive differences in the outcomes frequency for each developmental stage of the dentition were considered. Statistical differences between the villages were examined using the chi-square test or Fisher’s exact statistic. Tooth wear and the inbreeding coefficient (F) between the villages was tested with Mann-Whitney statistics. All the statistics were performed using two-tailed distribution at p#0.05. The coefficient inbreeding (F) confirmed the frequent incestuous unions among the Arara-Iriri indigenous group. Despite the tooth wear similarities, we found a striking difference in occlusal patterns between the two Arara villages. In the original village, dental malocclusion was present in about one third of the population; whilst in the resultant village, the occurrence was almost doubled. Furthermore, the morphological characteristics of malocclusion were strongly different between the groups. Conclusions/Significance: Our findings downplay the widespread influence of tooth wear, a direct evidence of what an individual ate in the past, on occlusal variation of living human populations. They also suggest that genetics plays the most important role on dental malocclusion etiology

Preseason Training Improves Perception of Fatigue and Recovery From a Futsal Training Session.

Purpose: To compare the posttraining recovery timeline of elite Brazilian futsal athletes before (Pre-PS) and after 10 weeks of the preseason (Post-PS) period of high-intensity technical–tactical training. Methods: At the start (n = 13) and at the end of the preseason (n = 7), under-20 male futsal players undertook fitness testing for maximal aerobic power, the countermovement jump (CMJ), and the 10-m sprint with change of direction. Furthermore, at both Pre-PS and Post-PS, the players participated in a training session where performance and psychophysiological measures were recorded before, immediately, 3, 24, and 48 hours postsession. The measures included CMJ, 10-m sprint, creatine kinase, Total Quality Recovery Scale, and Brunel Mood Scale. Effect size (ES) analyses compared fitness and posttraining recovery values for each parameter at Pre-PS versus Post-PS. Results: Only trivial ES (−0.02 to 0.11) was evident in maximal aerobic power, CMJ, and 10-m sprint at Post-PS compared with Pre-PS. For the timeline of recovery, only trivial and small ESs were evident for the 10-m sprint (−0.12 to 0.49), though CMJ recovery was improved at 3 hours (0.87) and 48 hours (1.27) at Post-PS and creatine kinase was lower at 48 hours (−1.33) at Post-PS. Perception of recovery was improved in Post-PS at 3 hours (1.50) and 24 hours postsession (0.92). Furthermore, perception of effort was lower immediately after the session (−0.29), fatigue was lower at 3 hours (−0.63), and vigor responses were improved in all postseason assessments (0.59 to 1.13). Conclusion: Despite minimal changes in fitness, preseason training attenuated players' perception of effort and fatigue and improved their recovery profile following a high-intensity technical–tactical training session

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU