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Introduction: Pomelo (柚 in Mandarin) (Citrus grandis L. Osbeck), a long-used fruit in Asia and China, is commonly used in traditional Chinese medicine. Pomelo is also a culturally significant fruit tree in Vietnam, renowned for its culinary and medicinal value. Young pomelo fruits possess high levels of flavonoids, but their research significance remains limited. Due to its relatively unknown potential, young pomelo is usually discarded during gardening maintenance leading to waste. This study aims to determine the naringin content and investigate the ameliorative effect on lipid profile of young pomelo extracts. Methods: Two mouse models of hyperlipidemia, specifically tyloxapol and a high-fat diet (HFD) model, were utilized to assess the effects of young pomelo extracts. Tyloxapol decreases the clearance of lipoprotein and leads to acute endogenous hyperlipidemia, while a high fat diet causes obesity among mice. The hypolipidemic effect of young pomelo extract was assessed through the level of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c), while its ameliorative effect was assessed through physical changes of mice and histological changes of their livers. Results: In the tyloxapol model, the naringin-rich young pomelo extracts exhibited promising effects in the treatment of hyperlipidemia. Notably, they significantly reduced total cholesterol, triglycerides, and LDL-c levels while elevating HDL-c levels. In the HFD model, the young pomelo extracts demonstrated similar effects on the biochemical lipid profiles. Moreover, the young pomelo extracts possess a protective effect against HFD-induced hepatosteatosis and hepatic necroinflammation. These findings align with existing literature, highlighting the potential utilization of young pomelo fruits. Discussion: The findings have significant implications for the development of novel therapeutic approaches targeting obesity and related metabolic disorders. Furthermore, the study contributes to promoting sustainable agriculture practices by emphasizing the utilization of young pomelo fruits that would otherwise go to waste. Overall, this study provides valuable insights into establishing a high-fat diet-induced obesity model, tyloxapol-induced hyperlipidemia and demonstrates the potential of young pomelo as a rich source of naringin.

In this study, we apply the Deep Deterministic Policy Gradient (DDPG) algorithm in reinforcement learning to control a double inverted pendulum on a cart (DIPC)- a high order single input-multi output (SIMO) system . The simulation results demonstrate DDPG’s stability and effectiveness in achieving swing-up and balance, showing its potential for tackling challenging control tasks in robotics.

Introdução: A Leucemia Mieloide Crônica (LMC) é uma malignidade hematológica caracterizada pela translocação recíproca entre os cromossomos 9 e 22, resultando na formação do cromossomo Philadelphia (Ph). Na ausência de tratamento, inevitavelmente evolui para uma crise blástica, caracterizada pela presença de blastos mieloides. Apenas 20-30% dos casos evolui com surgimento de blastos linfoides e, ainda mais raros são os casos que cursam com o surgimento blastos de diferentes linhagens hematopoiéticas. Objetivo: Relatar o caso raro de paciente com histórico de LMC evoluindo com crise blástica de fenótipo misto – blastos indiferenciados e diferenciação basofílica, eritroide e linfoide B. Metodologia: Amostras de aspirado medular de paciente do sexo masculino, 52 anos, portador de LMC com t(9;22) foram analisadas em imunofenotipagem multiparamétrica por citometria de fluxo e cariótipo de medula óssea por bandeamento G no Núcleo Técnico Operacional (NTO) do Grupo Pardini. Resultados: A análise de cariótipo revelou um perfil complexo com t(9;22)(q34;q11.2) nas 20 células analisadas, dentre outras alterações numéricas e estruturais – translocações evidenciando evolução clonal (+der(22) t(9;22)) e a trissomia do cromossomo 21, em 18 das 20 células analisadas. A análise imunofenotípica revelou a presença de 4 blastos de fenótipo distintos: 53% com fenótipo mais indiferenciado (CD34++ / CD117++ / HLADR++ / CD13+ / CD36+ / CD33+ / CD7-/+), 10% com diferenciação basofílica (CD123++ / CD9++ / CD203c+), 18% com diferenciação eritroide (CD36++ / CD71++ / CD105+) e 19% com diferenciação linfoide B (CD19++ / cCD79a+ / cCD22+ / TdT++). Conclusão: A combinação entre o estudo do perfil cromossômico e imunofenotípico do aspirado medular detectou a evolução da doença crônica para a fase blástica de fenótipo altamente complexo. Esse tipo de caracterização se torna indispensável posto que a presença de blastos de múltiplas linhagens celulares indica um prognóstico desfavorável e requer um tratamento com protocolos quimioterápicos diferenciados.

Acute Megakaryoblastic Leukaemia (AMKL - FAB M7) is a rare hematological neoplasm that affects megakaryocytes. It accounts for 1% to 2% of adult AML cases, with an extremely poor prognosis, resulting in an overall survival of less than one year. While it was classified as AML-M7 by the French-American-British Group in 1985, its diagnosis has become more accurate with the development and application of flow cytometry immunophenotyping. According to the current WHO criteria, the diagnosis is established with the presence of ≥20% blasts among nucleated cells in the bone marrow, with >50% of these being of megakaryocytic lineage, expressing at least one or more of the platelet glycoproteins: CD41 (glycoprotein IIb), CD61 (glycoprotein IIIa), or CD42b (glycoprotein Ib). Between 20% and 30% of patients often present splenomegaly and hepatomegaly, without lymphadenopathy, although superficial lymphadenopathy has been described. Patients exhibit cytopenias, frequently thrombocytopenia, though some develop thrombocytosis. Megakaryoblasts are usually medium to large blasts, with round or slightly irregular or indented nuclei, fine reticular chromatin, and 1 to 3 nucleoli. The cytoplasm is basophilic, often agranular, and may show distinct blebs or pseudopod formation. We report a case of a 22-year-old male patient with fever, prostration, asthenia, dry cough, and abdominal pain radiating to the chest. Physical examination revealed splenomegaly and inguinal lymphadenopathy. The initial suspicion was primary mediastinal lymphoma due to chest imaging abnormalities. The patient had significant alterations in lactate dehydrogenase (LDH) and in complete blood count. The bone marrow was hypercellular, with hypoplasia of the erythroblastic, granulocytic, and megakaryoblastic series, and with the presence of 58.5% medium-sized cells, a high nucleus-to-cytoplasmic (N/C) ratio, euchromatin with presence of, sometimes irregular, nucleoli. Cytogenetic analysis revealed a complex karyotype with various numerical and structural alterations. BCR::ABL1 fusion research was negative. Immunophenotyping analysis showed large and medium-sized blasts with complex cytoplasmic characteristics, expressing myeloid phenotypic markers, and aberrant expression of CD7 and CD56 antigens, as well as CD41 and CD61. The key to diagnosing rare and challenging cases such as adult AMKL lies in correlating patient clinical information with robust laboratory test results that require in-depth knowledge, such as flow cytometry immunophenotyping. Furthermore, in these cases, physicians should have access to these test results as quickly as possible to make timely and accurate therapeutic decisions.

Introdução: A técnica de imunofenotipagem por citometria de fluxo possui diversas aplicações clínico-laboratoriais, sendo considerada o padrão-ouro para o diagnóstico da maioria das doenças oncohematológicas. A utilização da citometria de fluxo para o diagnóstico e acompanhamento de quadros de infecção (viral e bacteriana) é ainda limitado à detecção de patógenos, avaliação do perfil imune linfocitário e avaliação de citocinas/quimiocinas pró-inflamatórias (CBA). Objetivo: Relatar um caso clínico raro com detecção de alterações fenotípicas por citometria de fluxo em paciente com quadro reacional à infecção/inflamação crônica. Metodologia: Realização de imunofenotipagem multiparamétrica por citometria de fluxo em amostra de sangue periférico de paciente do sexo masculino, 69 anos de idade, com histórico de miocardite pós infecção viral (zika vírus) e abscesso dentário. A hipótese diagnóstica foi Leucemia Aguda e apresentava os seguintes sintomas clínico-laboratoriais: Dor torácica, dispneia, perda ponderal, febre alta, leucocitose com anemia (Hb: 9,1), neutropenia e monocitose, além da presença de células monocitoides atípicas circulantes. Resultados: Após análise celular realizada por citometria de fluxo e avaliação de 24 marcadores imunofenotípicos, foi constatada a presença de neutropenia com superexpressão do antígeno CD64 (receptor Fc de baixa afinidade para IgG) e monocitose madura (72,2%) com predomínio total de monócitos intermediários (CD14++/CD16+), os quais apresentam maior capacidade fagocitária, maior perfil pró-inflamatório e melhor eficácia na apresentação antigênica. Além disso, os monócitos apresentaram perda da expressão do antígeno CD13 (proteína de adesão célula-endotélio) e aumento do parâmetro de SSC-A (granulosidade citoplasmática). Discussão: O exame de imunofenotipagem por citometria de fluxo foi capaz de detectar alterações celulares e fenotípicas indicativas de resposta imune celular, mediada majoritariamente por monócitos/macrófagos, secundária a um quadro infeccioso/inflamatório crônico causado pela associação de miocardite e abscesso dentário. Conclusão: O presente trabalho sugere a importância do uso de citometria de fluxo como exame auxiliar em pacientes com suspeita de quadro reacional/infeccioso.

Objetivos: Na Fundação Hemopa, o teste Geenius HIV 1/2 Confirmatory Assay (Bio-Rad) é utilizado para resolução de casos discordantes na triagem simultânea sorológico-molecular para a detecção do Vírus da Imunodeficiência Humana (HIV). O objetivo é determinar a frequência de teste suplementar positivo em casos de teste sorológico reagente com teste molecular indetectável para HIV, assim como, descrever o perfil de gênero, idade, resultado sorológico quantitativo e qualitativo dos anticorpos detectados nos indivíduos confirmados. Material e métodos: No período de janeiro de 2021 a fevereiro de 2023, foram avaliadas 145 amostras por Imunocromatografia Geenius HIV 1/2 Confirmatory Assay, um ensaio qualitativo que utiliza antígenos imobilizados (gp36, gp140, p31, gp160, p24 e gp41) para confirmação e diferenciação de anticorpos individuais para HIV- 1/2. Todas as amostras selecionadas tinham sorologia Anti-HIV reagente (valor do “cut off” > 0,8) com a detecção de anticorpos realizada através do ensaio Alinity i HIV Ag/Ab combo reagent kit (Abbott) com a metodologia de quimioluminescência e/ou ensaio Eclesys HIV Duo (Roche) com a metodologia de eletroquimioluminescência, e amostras HIV NAT indetectáveis, através do Kit NAT HIV/HCV (Bio-Manguinhos), utilizando a metodologia de PCR em tempo real, com limite de detecção de 85 cópias/mL. Resultados: Entre as 145 amostras com sorologia reagente e NAT indetectável, 3,45% (5/145) foram reagentes no teste confirmatório, das quais 80% (4/5) eram do gênero masculino, 20 % (1/5) feminino, a média de idade foi de 33 anos (21-55 anos), DP+ 13,4, a média da sorologia foi de 581.218 (351.500-1.056), DP+ 284.340 e em relação aos anticorpos detectados qualitativamente, todos apresentaram anticorpos contra as proteínas do envelope gp160 e gp41, enquanto para a p31 60% (3/5) e p24 80% (4/5). Discussão: O esclarecimento de casos de discordância entre teste sorológico e molecular é de fundamental importância para esclarecer a infecção pelo vírus, visto que, na ausência de RNA viral faz-se necessário descartar reações cruzadas ou inespecificidade da técnica. As amostras demonstraram uma resposta imunológica específica para o HIV, contando com a quantificação de anticorpos e a detecção de anticorpos específicos contra proteínas e peptídeos do envelope viral, como a gp41 e gp160, além de proteínas e peptídeos associadas à replicação viral, como p31 e p24. Assim, pode-se confirmar que estes indivíduos apresentam uma resposta imunológica pós-exposição ao HIV, ainda que na ausência de detecção viral por técnica molecular. Conclusão: A não detecção do material genético do HIV no teste molecular com confirmação sorológica de exposição ao vírus pode ser observada em indivíduos em tratamento antirretroviral e mais raramente em casos de indivíduos que podem ser controladores de elite, que mesmo sem tratamento mantém uma carga viral indetectável e contagem de linfócitos TCD4+estável, ou ainda em casos de possíveis mutações para a região alvo do teste molecular, inviabilizando a amplificação genômica. Considerando que as amostras em questão tratam-se de doadores de sangue, é questionável a possibilidade destes serem indivíduos sabidamente positivos em tratamento, que busquem o hemocentro como buscador de teste, cuja característica seria a omissão de informações na triagem com objetivo de monitorar a infecção.

Abstract Background Pathogenic gain of function variants in Valosin-containing protein (VCP) cause a unique disease characterized by inclusion body myopathy with early-onset Paget disease of bone and frontotemporal dementia (also known as Multisystem proteinopathy (MSP)). Previous studies in drosophila models of VCP disease indicate treatment with VCP inhibitors mitigates disease pathology. Earlier-generation VCP inhibitors display off-target effects and relatively low therapeutic potency. New generation of VCP inhibitors needs to be evaluated in a mouse model of VCP disease. In this study, we tested the safety and efficacy of a novel and potent VCP inhibitor, CB-5083 using VCP patient-derived myoblast cells and an animal model of VCP disease. Methods First, we analyzed the effect of CB-5083 in patient-derived myoblasts on the typical disease autophagy and TDP-43 profile by Western blot. Next, we determined the maximum tolerated dosage of CB-5083 in mice and treated the 2-month-old VCPR155H/R155H mice for 5 months with 15 mg/kg CB-5083. We analyzed motor function monthly by Rotarod; and we assessed the end-point blood toxicology, and the muscle and brain pathology, including autophagy and TDP-43 profile, using Western blot and immunohistochemistry. We also treated 12-month-old VCPR155H/+ mice for 6 months and performed similar analysis. Finally, we assessed the potential side effects of CB-5083 on retinal function, using electroretinography in chronically treated VCPR155H/155H mice. Results In vitro analyses using patient-derived myoblasts confirmed that CB-5083 can modulate expression of the proteins in the autophagy pathways. We found that chronic CB-5083 treatment is well tolerated in the homozygous mice harboring patient-specific VCP variant, R155H, and can ameliorate the muscle pathology characteristic of the disease. VCP-associated pathology biomarkers, such as elevated TDP-43 and p62 levels, were significantly reduced. Finally, to address the potential adverse effect of CB-5083 on visual function observed in a previous oncology clinical trial, we analyzed retinal function in mice treated with moderate doses of CB-5083 for 5 months and documented the absence of permanent ocular toxicity. Conclusions Altogether, these findings suggest that long-term use of CB-5083 by moderate doses is safe and can improve VCP disease-associated muscle pathology. Our results provide translationally relevant evidence that VCP inhibitors could be beneficial in the treatment of VCP disease.

To date, research on social capital in Indigenous contexts has been scarce. In this quantitative study, our objectives were to (1): Describe bonding social capital within four distinct First Nations communities in Canada, and (2) Explore the associations between bonding social capital and self-rated health in these communities. With community permission, cross-sectional data were drawn from the Canadian Alliance for Healthy Hearts and Minds study. Four reserve-based First Nations communities were included in the analysis, totaling 591 participants. Descriptive statistics were computed to examine levels of social capital among communities and logistic regression analyses were performed to identify social capital predictors of good self-rated health. Age, sex, education level, and community were controlled for in all models. Across the four communities in this study, areas of common social capital included frequent socialization among friends and large and interconnected family networks. Positive self-rated health was associated with civic engagement at federal or provincial levels (OR=1.65, p

Introdução: O linfoma intravascular de grandes células B (LIVGCB) é um tipo raro de linfoma extranodal de grandes células B, caracterizado pelo crescimento seletivo de células do linfoma na luz dos vasos, em particular capilares, com exceção de artérias e veias maiores. Manifesta-se de forma agressiva com sobrevida curta na maioria dos casos. O diagnóstico é baseado na biópsia da lesão e no estudo anatomopatológico e imunohistoquímico das células neoplásicas e a expressão de CD20 forte e constante é quase a regra. Proteínas antiapoptóticas, principalmente blc-2 e galectina-3 são positivas. O tratamento é baseado em quimioterapia associada ou não a rituximabe. Este relato descreve o caso de uma paciente, feminina, 70 anos, internada em novembro de 2020 com queixa de cefaleia frontal intensa associada a piora de déficit motor prévio em dimídio esquerdo. Possuía antecedentes de tabagismo, enfisema pulmonar, câncer de pulmão tratado e labirintopatia. A internação foi decorrente de quadro neurológico que mimetizava um acidente vascular cerebral e, durante a investigação, foi encontrado um forame oval patente que foi tratado por via endovascular. A paciente seguiu com novos eventos neurológicos, com pioras radiológicas à RNM que, em um segundo momento, foi considerado AVC embólico associado à endocardite. Apesar do tratamento antiagregante e antibioticoterapia, os eventos neurológicos persistiram, com surgimento de novos déficits, convulsões e rebaixamento sensorial. Os hemogramas mostravam linfopenia e plaquetopenia. Mielograma, imunofenotipagem e cariótipo foram normais. Tomografias de tórax e abdome eram normais, assim como PET CT. RNM de encéfalo mostrava múltiplos focos de restrição à difusão de permeio, compatíveis com edema citotóxico e a múltiplos focos de deposição de hemossiderina sugestiva de vasculopatia inflamatória. A partir da evolução desfavorável foi decidido realizar biopsia do tecido cerebral. O estudo imunohistoquímico revelou CD20+, Bcl2+, CD31+, CD68+, CD3+, CD30- e CD15+ Ki67+ compatível com LIVGCB em tecido cerebral. Iniciado tratamento quimioterápico com metotrexate em altas doses. A paciente evoluiu com choque séptico durante a neutropenia do 2°ciclo, sem que pudéssemos observar recuperação neurológica. Discussão: Dois padrões clínicos de LIVGCB são reconhecidos, o padrão clássico, predominantemente de países ocidentais que apresentam frequência alta de envolvimento do sistema nervoso central (SNC) e pele, e o associado a síndrome hemofagocítica, com envolvimento da medula óssea, febre, hepatoesplenomegalia e trombocitopenia, sendo este o tipo predominante nos países asiáticos. A ocorrência de células LIVGCB em esfregaços de sangue periférico não ocorre na maioria dos casos (90%-95% dos casos), mesmo sendo esta uma peculiaridade da doença, a localização dos linfócitos neoplásicos dentro dos vasos. Entre as citopenias, a trombocitopenia geralmente está associada a infiltração da medula óssea e envolvimento hepatoesplênico, no caso estava normal. Conclusão: O LIVGCB de SNC representa imenso desafio diagnóstico, uma vez que é sempre confundido com outras condições clínicas mais frequentes e não há sinais, sintomas ou mesmo imagens radiológicas patognomônicas dessa condição e a hematoscopia direta é, em quase sua totalidade, negativa. Deve haver um elevado grau de suspeita clínica para que seja realizada a biópsia em momento adequado em que não haja comprometimento clínico e/ou neurológico irreversível.

Introdução: Anemia ferropriva é considerada um problema de saúde pública mundial, atingindo principalmente crianças na primeira infância, e se não tratada pode gerar problemas intelectuais e cognitivos irreversíveis, ao mesmo tempo em que acarreta um custo maior para a saúde pública. O diagnóstico precoce é essencial para que o tratamento seja feito com segurança. Objetivo: Obter dados da prevalência da anemia ferropriva em crianças na primeira infância. Materiais e métodos: Trata-se de uma pesquisa exploratória através de uma revisão bibliográfica evidenciando a prevalência da anemia ferropriva em diversas regiões do Brasil. Resultados: Foram incluídos nesta revisão 51 estudos realizados com crianças menores 60 meses no período de 20 anos, desses quatro na região Norte, 18 na região Nordeste, seis na região Sul, 18 na região Sudeste e cinco na região Centro Oeste, com uma amostra total de 22.096 indivíduos analisados. A prevalência de anemia ferropriva observada nestes estudos foi de 40,3%. Conclusão: Devido à alta taxa de anemia ferropriva encontrada da população de estudo é de grande a importância ações de prevenção já que se trata de um problema de saúde pública nacional. Faltam pesquisas de âmbito nacional com maior número de amostras significativa, para que de fato seja direcionado recursos financeiros possibilitando a criação de estratégias, com o intuito de informar, prevenir e controlar a anemia ferropriva.

Controversy persists regarding the safety and efficacy of an accelerated low-dose recombinant tissue-type plasminogen activator (rt-PA) regimen for reperfusion therapy in acute pulmonary embolism. This study describes the outcomes of an accelerated low-dose rt-PA regimen for the treatment of acute pulmonary embolism in Vietnamese patients. This was a case series from October 2014 to October 2020 from 9 hospitals across Vietnam. Patients presenting with acute pulmonary embolism with high to intermediate mortality risk were administered alteplase 0.6 mg per kilogram (maximum of 50 mg) over 15 min. The main outcomes were the proportion who survived to hospital discharge and at 3 months as well as in-hospital hemorrhage (major and minor according to International Society of Thrombosis and Hemhorrage definitions). A total of 80 patients were enrolled: 48 (60%) with high risk for mortality and 32 patients (40%) with intermediate risk for mortality. A total of 7 (8.8%) died in hospital. All deaths occurred in the high-risk mortality group. The 73 patients who were discharged alive remained alive at 3 months follow up. During hospitalization, 1 patient (1.3%) suffered major bleeding, and 7 (8.8%) had minor bleeding. An accelerated thrombolytic regimen with alteplase 0.6 mg/kg (maximum of 50 mg) over 15 min for acute pulmonary embolism appeared be effective and safe in a case series of Vietnamese patients.

The Null Convention Logic (NCL) based asynchronous design technique has interested researchers because this technique had overcome disadvantages of the synchronous technique, such as noise, glitches, clock skew and power. However, using the NCL-based asynchronous design method is difficult for university students and researchers because of the lack of standard NCL cell libraries. Therefore, in this paper, a novel flow is proposed to design NCL cell libraries. These libraries are used to synthesize NCL-based asynchronous designs. We chose the static NCL cell library to illustrate the proposed design solution because this library is one of the most basic NCL libraries. Static NCL cells in this library are designed based on the Process Design Kit 45nm technology and are implemented by the Virtuoso and the Design Compiler (DC) tool. In addition, the Ocean script and Electronic Design Automation (EDA) environment are used for supporting designs and simulations. A complete library of 27 NCL cells was designed to serve for study and research. We also implemented synthesis for NCL full adders using this library and compared our synthesis results with the results of other authors. The comparison results indicated that our results were a 20% improvement on power consumption.

In real life, many problems are instances of combinatorial optimization. Cross-functional team selection is one of the typical issues. The decision-maker has to select solutions among ( k h ) solutions in the decision space, where k is the number of all candidates, and h is the number of members in the selected team. This paper is our continuing work since 2018; here, we introduce the completed version of the Min Distance to the Boundary model (MDSB) that allows access to both the “deep” and “wide” aspects of the selected team. The compromise programming approach enables decision-makers to ignore the parameters in the decision-making process. Instead, they point to the one scenario they expect. The aim of model construction focuses on finding the solution that matched the most to the expectation. We develop two algorithms: one is the genetic algorithm and another based on the philosophy of DC programming (DC) and its algorithm (DCA) to find the optimal solution. We also compared the introduced algorithms with the MIQP-CPLEX search algorithm to show their effectiveness.

Ionizing radiation has been successfully employed to modify the immunological properties of biomolecules. Very promising results were obtained when crude animal venoms, as well as isolated toxins, were treated with 60Co gamma rays, yielding toxoids with good immunogenicity. The achievement of modified antigens with lower toxicity and preserved or improved immunogenicity can be very useful. Ionizing radiation has already been proven to be a powerful tool to attenuate snake venom toxicity without affecting, and even increasing, their immunogenic properties. However, little is known about the modifications that irradiated molecules undergo and even less about the immunological response that such antigens elicit. In the present work, we investigated the immunological behavior of bothropstoxin-1, a K49 phospholipase, before and after irradiation. Structural modifications of the toxin were analyzed by SDS-PAGE. Isogenic mice were immunized with either the native or the irradiated toxin. The circulating antibodies were isotyped and titrated by ELISA. According to our data, irradiation promoted structural modifications in the toxin characterized by higher molecular weight forms of proteins (aggregates and oligomers). The results also indicated that irradiated toxins were immunogenic and antibodies elicited by them were able to recognize the native toxin in ELISA. These findings suggest that irradiation of toxic proteins can promote significant modifications in their structures; however they still retain many of the original antigenic and immunological properties of native proteins. Also, our data indicate that irradiated proteins induce higher titers of IgG2a and IgG2b, suggesting that Th1 cells are predominantly involved in the immune response.

This study examines the experiences of three aspiring Latina school leaders in a principal preparation program with a social justice emphasis. Employing theoretical perspectives grounded in a community-based educational leadership framework and transformational resistance theory, this study documents how coursework informed the perspectives of participants regarding educational equity and racial justice. This comparative case study takes place at a Hispanic Serving Institution and focuses on two social foundations courses spanning a 5-month period. Findings illustrate participants' capacity to (a) reframe their past experiences as P-20 students in relation to meritocracy; (b) respond to current injustices as K-12 teachers, particularly the power of language to disrupt or perpetuate inequities; and lastly (c) re-envision educational leadership as future Latina principals as deeply intertwined with communities. The research highlights a need for a broadened approach to principal preparation that fosters future leaders to consider the engagement and leadership of marginalized students and families.

Vitamin D signaling in mammary cancer stem cells (MCSCs), which are implicated in the initiation and progression of breast cancer, is poorly understood. In this study, we examined vitamin D signaling in mammospheres which are enriched in MCSCs from established breast cancer cell lines. Breast cancer cells positive for aldehyde dehydrogenase (ALDH(+)) had increased ability to form mammospheres compared to ALDH(-) cells. These mammospheres expressed MCSC-specific markers and generated transplantable xenografts in nude mice. Vitamin D receptor (VDR) was significantly down-regulated in mammospheres, as well as in ALDH(+) breast cancer cells. TN aggressive human breast tumors as well as transplantable xenografts obtained from SKBR3 expressed significantly lower levels of VDR but higher levels of CD44 expression. Snail was up-regulated in mammospheres isolated from breast cancer cells. Inhibition of VDR expression by siRNA led to a significant change in key EMT-specific transcription factors and increased the ability of these cells to form mammospheres. On the other hand, over-expression of VDR led to a down-regulation of Snail but increased expression of E-cad and significantly compromised the ability of cells to form mammospheres. Mammospheres were relatively insensitive to treatment with 1,25-dihydroxyvitamin D (1,25D), the active form of vitamin D, compared to more differentiated cancer cells grown in presence of serum. Treatment of H-Ras transformed HMLE(HRas) cells with DETA NONOate, a nitric oxide (NO)-donor led to induction of MAP-kinase phosphatase -1 (MKP-1) and dephosphorylation of ERK1/2 in the mammospheres. Combined treatment of these cells with 1,25D and a low-concentration of DETA NONOate led to a significant decrease in the overall size of mammospheres and reduced tumor volume in nude mice. Our findings therefore, suggest that combination therapy using 1,25D with drugs specifically targeting key survival pathways in MCSCs warrant testing in prospective clinical trial for treatment of aggressive breast cancer.

The question of achieving equity remains an enduring concern for K-12 teachers and school leaders. Work toward equity and social justice in K-12 schools requires the authentic participation and engagement of racially marginalized students and families. Van Lac, Érica Fernández, and Katherine Cumings Mansfield offer real-life examples of what it looks like to foster student and parent leadership with/alongside teachers and school leaders. They contend that the goals of social justice cannot fully be achieved without the active participation of those most marginalized in K-12 schools.