Members of the NF-kappaB family expressed in zones of active neurogenesis in the postnatal and adult mouse brain

The ReL/NF-kappaB family of transcription factors is implicated in cell proliferation, cell death, cell migration and cell interactions. Here, we examined by immunohistochemistry the expression pattern of various members of this family during postnatal telencephalon development and during adulthood, and we used neuronal and glial markers to identify the cells types where they are expressed. Distinct Rel/NF-kappaB proteins are highly expressed postnatally in the subventricular zone and in the rostral migratory stream. In particular, Rel A and p50 are expressed in radial glial cells, in migrating neuron precursors and in a population belonging to the astrocytic lineage. Rel B, on the other hand, is only expressed in migrating neuron precursors, whereas c-Rel is present in a few cells located at the edges of the rostral migratory stream. The expression of Rel A and p50 persists into adulthood, particularly in subventricular zone astrocyte-like cells and in migrating neuron precursors, respectively. The selective expression of NF-kappaB members in the postnatal subventricular zone and rostral migratory stream and their persistence into adulthood in regions of ongoing neurogenesis suggests possible mechanisms linking NF-kappaB expression with cell proliferation and migration. Their presence in actively proliferating progenitor cells, detected by BrdU staining, further suggests that NF-kappaB may be part of a signaling pathway that is important for neurogenesis. (C) 2004 Elsevier B.V. All rights reserved

p 300predictive value of circulating tumor derived dna ctdna in patients with locally advanced rectal cancer larc treated with neoadjuvant chemoradiotherapy ct rt preliminary results

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Joint modelling of bivariate longitudinal data : Application to the recovery of sexual function and urinary continence

(E0871) The following methodological issues occur in the context of the longitudinal study of sexual dysfunction and urinary incontinence after radical prostatectomy: (i) high dropout rate due to the extremely sensitive nature of the investigated outcomes; (ii) correlation between the two outcomes; (iii) non-linearity of the recovery trajectories. To address all these issues, we propose the use of a joint modelling approach, including a bivariate linear mixed model with splines for the two outcomes and a proportional hazards model for the time to dropout. We applied the model to data from consecutive patients underwent robotic-assisted radical prostatectomy at European institute of oncology from May 2015 to July 2016. Preand post-surgical sexual and urinary functional conditions were evaluated using the expanded prostate cancer index composite questionnaire. Six hundred forty three patients were included in the analysis. At one year after surgery, only 55% of patients returned the questionnaire. Parameters estimation was based on the maximisation of the likelihood function achieved through the implementation of an EM algorithm. A Gauss Hermite approximation was also used for some of the integrals involved. To assess the effect of nonrandom dropout mechanisms on the parameter estimates, we calculated the index of local sensitivity to non-ignorability

Radiological Features of Male Breast Neoplasms: How to Improve the Management of a Rare Disease

The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35-81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid-partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing

Atypical Ductal Hyperplasia and Lobular In Situ Neoplasm: High-Risk Lesions Challenging Breast Cancer Prevention

Simple Summary This retrospective study investigates histopathological outcomes, upgrade rates, and disease-free survival (DFS) in high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN 1 and 2), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. Focusing on 320 patients who underwent stereotactic VABB, with 246 individuals diagnosed with ADH (120) or LIN (126), the study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The study underscores the importance of a multidisciplinary approach, acknowledging the evolving role of VABB, and emphasizes the need for careful follow-up, particularly for lobular lesions. It offers valuable insights for clinicians navigating the complex landscape of high-risk breast lesions, advocating for heightened awareness and vigilance in managing these lesions and contributing to the ongoing refinement of clinical strategies in BC care.Abstract This retrospective study investigates the histopathological outcomes, upgrade rates, and disease-free survival (DFS) of high-risk breast lesions, including atypical ductal hyperplasia (ADH or DIN1b) and lobular in situ neoplasms (LIN), following Vacuum-Assisted Breast Biopsy (VABB) and surgical excision. The study addresses the challenge posed by these lesions due to their association with synchronous or adjacent Breast Cancer (BC) and increased future BC risk. The research, comprising 320 patients who underwent stereotactic VABB, focuses on 246 individuals with a diagnosis of ADH (120) or LIN (126) observed at follow-up. Pathological assessments, categorized by the UK B-coding system, were conducted, and biopsy samples were compared with corresponding excision specimens to determine upgrade rates for in situ or invasive carcinoma. Surgical excision was consistently performed for diagnosed ADH or LIN. Finally, patient follow-ups were assessed and compared between LIN and ADH groups to identify recurrence signs, defined as histologically confirmed breast lesions on either the same or opposite side. The results reveal that 176 (71.5%) patients showed no upgrade post-surgery, with ADH exhibiting a higher upgrade rate to in situ pathology than LIN1 (Atypical Lobular Hyperplasia, ALH)/LIN2 (Low-Grade Lobular in situ Carcinoma, LCIS) (38% vs. 20%, respectively, p-value = 0.002). Considering only patients without upgrade, DFS at 10 years was 77%, 64%, and 72% for ADH, LIN1, and LIN2 patients, respectively (p-value = 0.92). The study underscores the importance of a multidisciplinary approach, recognizing the evolving role of VABB. It emphasizes the need for careful follow-up, particularly for lobular lesions, offering valuable insights for clinicians navigating the complex landscape of high-risk breast lesions. The findings advocate for heightened awareness and vigilance in managing these lesions, contributing to the ongoing refinement of clinical strategies in BC care

Avances en la conservación y obtención de material selecto del Banco Nacional de Germoplasma de Prosopis, Córdoba, Argentina

El objetivo de esta revisión es presentar los avances en la conservación y en la obtención de material selecto del BNGP. El BNGP cuenta en el Banco Pasivo con 1.650 accesiones correspondientes a 1.106 árboles de nueve especies arbóreas de Prosopis y a 8 poblaciones de P. alba que se encuentran bajo estudio para constituirse en Áreas Productoras de Semillas (APS) o Rodales Semilleros (RS). Con la información del Banco de Datos desde 1986 y el aporte de investigaciones se crearon 6 RS en proceso de inscripción como Rodal Semillero, 14 APS inscriptas, 17 nuevas APS en la región del Espinal aún en estudio y 3 en el sur- oeste de Córdoba en proceso de inscripción. Los APS y RS logrados, inscriptos en INASE, se constituyen en material base para la obtención de semillas de las categorías “Fuente identificada” y “Seleccionada”, respectivamente, disponibles para abastecer a las necesidades de forestación.The objective of this review is to present the advances in conservation and procurement of se-lected material by the National Germplasm Bank of Prosopis (BNGP). The BNGP has 1,650 acces-sions in the Base Bank corresponding to 1,106 trees of 9 tree species of Prosopis and 8 populations of P. alba that are under study to become Seed Producing Areas (APS) or Seed Stands (RS). With the information from the BNGP data bank since 1986 and the contribution of investigations, 6 RS were created in the process of registration as RS, 14 registered APS, 17 new APS in the Espinal region still under study and 3 in the south-west of Cordoba in the registration process. The APS and RS achieved, registered in INASE, are constituted in base material for obtaining seeds of the cate-gories “Identifi ed source” and “Selected”, respectively, available to supply the afforestation needs.EEA La RiojaFil: Joseau, Marisa Jacqueline. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Vegetal; ArgentinaFil: Frassoni, Javier. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Vegetal; ArgentinaFil: Verzoni, G. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Vegetal; ArgentinaFil: Rodriguez Reartes, S. Universidad Nacional de Córdoba. Facultad de Ciencias Agropecuarias. Departamento de Producción Vegetal; ArgentinaFil: Verga, Anibal. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria La Rioja. Agencia De Extensión Rural La Rioja; ArgentinaFil: Lopez Lauenstein, Diego. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Fisiología y Recursos Genéticos Vegetales; Argentin

Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer

Importance: The assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event. Objective: To validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer. Design, setting, and participants: ONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019. Exposures: The ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period. Main outcomes and measures: The primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism. Results: A total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P < .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively. Conclusions and relevance: This study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis

Earth system science frontiers - an early career perspective

The exigencies of the global community toward Earth system science will increase in the future as the human population, economies, and the human footprint on the planet continue to grow. This growth, combined with intensifying urbanization, will inevitably exert increasing pressure on all ecosystem services. A unified interdisciplinary approach to Earth system science is required that can address this challenge, integrate technical demands and long-term visions, and reconcile user demands with scientific feasibility. Together with the research arms of the World Meteorological Organization, the Young Earth System Scientists community has gathered early-career scientists from around the world to initiate a discussion about frontiers of Earth system science. To provide optimal information for society, Earth system science has to provide a comprehensive understanding of the physical processes that drive the Earth system and anthropogenic influences. This understanding will be reflected in seamless prediction systems for environmental processes that are robust and instructive to local users on all scales. Such prediction systems require improved physical process understanding, more high-resolution global observations, and advanced modeling capability, as well as high-performance computing on unprecedented scales. At the same time, the robustness and usability of such prediction systems also depend on deepening our understanding of the entire Earth system and improved communication between end users and researchers. Earth system science is the fundamental baseline for understanding the Earth’s capacity to accommodate humanity, and it provides a means to have a rational discussion about the consequences and limits of anthropogenic influence on Earth. Without its progress, truly sustainable development will be impossible. © 2017 American Meteorological Society. For information regarding reuse of this content and general copyright information, consult the AMS Copyright Policy (www.ametsoc.org/PUBSReuseLicenses)

Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study

Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelatio

nicord single unit expanded umbilical cord blood transplantation ucbt final results of a multicenter phase i ii trial

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