Episodic-like memory: New perspectives from a behavioral test in rats

In order to have a tool to empirically test the ideas derived from a theoretical model, we extended a protocol for evaluation of episodic-like memory in rats, based on the triad "what, where, context" for definition of memories. As with the computational model, our intention was for the animal being tested to store a specific number of object-place-context configurations as different memories, which would then be retrievable from cues. The aim of this work was to evaluate the influence of the number of configurations to be memorized on the performance of the task. Sixty-five Wistar male rats were evaluated. In accordance with previous work, for two configurations, the recognition index was indicative of recognition of the element mismatching the original memory (mean = 0.28; SEM = 0.12). The recognition index for three configurations was lower (mean = 0.15; SEM = 0.10), evidencing less recall with increasing requirements. The results also showed a trend toward recognition of novelty for the first and the last memory when evaluating three configurations (a "U" shape in the exploratory preference's curve), showing the primacy and recency effects typical of memory both in humans and animals. Nonetheless, the data presented a high inter-subject variability which makes the test non-robust for small groups. However, if used before and after a treatment for a same subject, we suggest that the protocol presented in this work can be a useful behavioral test for the evaluation of episodic-like memory in rats in terms of a variable task demand.Fil: Weisz, Victoria I.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Rios, Mariana B.. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; ArgentinaFil: Argibay, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Italiano. Instituto de Ciencias Básicas y Medicina Experimental; Argentin

Decoupling the shape parameter to assess gold nanorod uptake by mammalian cells

The impact of nanoparticles (NPs) upon biological systems can be fundamentally associated with their physicochemical parameters. A further often-stated tenet is the importance of NP shape on rates of endocytosis. However, given the convoluted parameters concerning the NP–cell interaction, it is experimentally challenging to attribute any findings to shape alone. Herein we demonstrate that shape, below a certain limit, which is specific to nanomedicine, is not important for the endocytosis of spherocylinders by either epithelial or macrophage cells in vitro. Through a systematic approach, we reshaped a single batch of gold nanorods into different aspect ratios resulting in near-spheres and studied their cytotoxicity, (pro-)inflammatory status, and endocytosis/exocytosis. It was found that on a length scale of ∼10–90 nm and at aspect ratios less than 5, NP shape has little impact upon their entry into either macrophages or epithelial cells. Conversely, nanorods with an aspect ratio above 5 were preferentially endocytosed by epithelial cells, whereas there was a lack of shape dependent uptake following exposure to macrophages in vitro. These findings have implications both in the understanding of nanoparticle reshaping mechanisms, as well as in the future rational design of nanomaterials for biomedical applications

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma

We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.Medicin

Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Objective: To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results: There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion: In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%

Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

<p>Abstract</p> <p>Objective</p> <p>To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.</p> <p>Study design</p> <p>Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.</p> <p>Results</p> <p>21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications.</p> <p>Conclusion</p> <p>Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.</p

Gamma entrainment frequency affects mood, memory and cognition: an exploratory pilot study

Here we provide evidence with an exploratory pilot study that through the use of a Gamma 40 Hz entrainment frequency, mood, memory and cognition can be improved with respect to a 9-participant cohort. Participants constituted towards three binaural entrainment frequency groups: the 40 Hz, 25 Hz and 100 Hz. Participants attended a total of eight entrainment frequency sessions twice over the duration of a 4-week period. Additionally, participants were assessed based on their cognitive abilities, mood as well as memory, where the cognitive and memory assessments occurred before and after a 5-min binaural beat stimulation. The mood assessment scores were collected from sessions 1, 4 and 8, respectively. With respect to the Gamma 40 Hz entrainment frequency population, we observed a mean improvement in cognitive scores, elevating from 75% average to 85% average upon conclusion of the experimentation at weak statistical significance (α = 0.10, p = 0.076). Similarly, memory score improvements at a greater significance (α = 0.05, p = 0.0027) were noted, elevating from an average of 87% to 95%. In pertinence to the mood scores, a negative correlation across all populations were noted, inferring an overall increase in mood due to lower scores correlating with elevated mood. Finally, correlation analysis revealed a stronger R2 value (0.9838) within the 40 Hz group between sessions as well as mood score when compared across the entire frequency group cohort