Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions.

ABSTRACT: Astrocytes are the most abundant type of glial cell In the central nervous system. Upon Injury and inflammation, astrocytes become reactive and undergo morphological and functional changes. Depending on their phenotypic classification as A1 or A2, reactive astrocytes contribute to both neurotoxic and neuroprotective responses, respectively. However, this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries. Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles, which emphasizes the heterogeneous nature of their reactivity. Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types, releasing cytokines, and influencing the immune response. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior, as evidenced by in silico, in vitro, and in vivo results. In astrocytes, inflammatory cues trigger a cascade of molecular events, where nuclear factor-κΒ serves as a central mediator of the pro-inflammatory responses. Here, we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation. We highlight the involvement of various signaling pathways that regulate astrocyte reactivity, including the PI3K/AKT/ mammalian target of rapamycin (mTOR), αvß3 integrin/PI3K/AKT/connexin 43, and Notch/ PI3K/AKT pathways. While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage, evidence suggests that activating this pathway could also yield beneficial outcomes. This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation. The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior. The findings should then be validated using in vivo models to ensure real-life relevance. The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage, although further studies are required to fully comprehend its role due to varying factors such as different cell types, astrocyte responses to inflammation, and disease contexts. Specific strategies are clearly necessary to address these variables effectively.

Unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety during the COVID-19 pandemic.

OBJECTIVE/BACKGROUND: Unmet needs in perinatal mental healthcare are an important public health issue particularly in the context of a stressful life event such as the COVID-19 pandemic but data on the extent of this problem are needed. AIM: The aim of this study is to determine the (1) proportion of women with clinically significant symptoms of perinatal depression, anxiety or comorbid symptoms of depression and anxiety, receiving mental healthcare overall and by country and (2) factors associated with receiving mental healthcare. METHOD: Women in the perinatal period (pregnancy or up to 6 months postpartum) participating in the Riseup-PPD-COVID-19 cross-sectional study, reported on sociodemographic, social support health-related factors, and COVID-19 related factors, and on symptoms of depression (Edinburgh Postnatal Depression Scale [EPDS]) and anxiety (Generalised Anxiety Disorder [GAD-7]) using self-report questionnaires. Clinically significant symptoms were defined as EPDS ≥ 13 for depression and GAD-7 ≥ 10 for anxiety. Mental healthcare was defined as self-reported current mental health treatment. RESULTS: Of the 11 809 participants from 12 countries included in the analysis, 4 379 (37.1%) reported clinically significant symptoms of depression (n = 1 228; 10.4%; EPDS ≥ 13 and GAD-7 ⟨ 10), anxiety (n = 848; 7.2%; GAD-7 ≥ 10 and EPDS ⟨ 13) or comorbid symptoms of depression and anxiety (n = 2 303; 19.5%; EPDS ≥ 13 and GAD-7 ≥ 10). Most women with clinically significant symptoms of depression, anxiety, or comorbid symptoms of depression and anxiety were not receiving mental healthcare (89.0%). Variation in the proportion of women with clinically significant symptoms of depression and/or anxiety reporting mental healthcare was high (4.7% in Turkey to 21.6% in Brazil). Women in the postpartum (vs. pregnancy) were less likely (OR 0.72; 95% CI 0.59-0.88), whereas women with previous mental health problems (vs. no previous mental health problems) (OR 5.56; 95% CI 4.41-7.01), were more likely to receive mental healthcare. CONCLUSION: There are high unmet needs in mental healthcare for women with clinically significant symptoms of perinatal depression and/or anxiety across countries during the COVID-19 pandemic. Studies beyond the COVID-19 pandemic and covering the whole range of mental health problems in the perinatal period are warranted to understand the gaps in perinatal mental healthcare.

Parasitic findings on threatened pudu deer from Central Chile accounts first genetic characterization of lice parasitizing P. puda in Chile and the first molecular report of Taenia hydatigena metacestodes in this species.

Southern pudu (Pudu puda) is a threatened endemic deer of the temperate forests of Chile. In recent years pudu populations rates have decreased mainly due to anthropogenic causes including forest loss and landscape fragmentation. In this context, the parasitic fauna of Chilean pudu has been scarcely investigated. The aim of this study was to determine the parasitic status of rescued pudu n = 13 from its natural habitat in Central Chile (Maule region) during March 2022 and June 2023 by applying morphological, histopathological, and molecular analyses. As result, we report the presence of transmission of parasites from dogs to pudus as showed by the presence of metacestodes of the parasite Taenia hydatigena on omentum, liver, and pleura of pudus during postmortem examinations, being the first molecular report on the presence of this parasite on Chilean pudu. Meanwhile, ectoparasite examinations determined the presence of chewing and sucking lice on pudu exemplars here analysed. Molecular and phylogenetic analysis of lice revealed new insights on Bovicola and Anoplura lice parasitizing P. puda in Chile, equally being the first genetic characterization of lice parasitizing pudu exemplars in Chile. In addition, parasite loads of lice and metacestodes were analysed. However, no statistically significance was observed when comparing environmental and individual traits influence on parasite load variation. Overall, the study area is the northern limit of habitat distribution of this specie in Chile and we here provide novel information on pudu deer parasites, thus making a useful and valuable contribution to the parasitological knowledge on this threatened species.

Miositis aguda asociada a infección por virus influenza. Serie de casos en un hospital pediátrico / Acute myositis associated with influenza infection. Case series in a pediatric hospital

La miositis aguda benigna asociada a influenza es una complicación esporádica. En Argentina, en el año 2022, hubo un aumento temprano de la circulación de influenza y del número total de las notificaciones, con la aparición de miositis secundarias. Serie clínica retrospectiva de nueve pacientes pediátricos que consultaron por dolor e impotencia funcional de extremidades inferiores, y enzimas musculares elevadas, en el hospital Pedro de Elizalde de la Ciudad Autónoma de Buenos Aires, entre agosto y octubre del 2022. En todos se detectó infección por virus influenza y se recuperaron sin secuelas. La miositis aguda benigna es una entidad infrecuente en la infancia, cuyo diagnóstico es predominantemente clínico y de recuperación ad integrum. Debe ser sospechada en pacientes con clínica compatible en contexto de alta circulación viral. La vigilancia epidemiológica aporta herramientas para identificar los virus circulantes y sus posibles complicaciones.

Benign acute myositis associated with influenza is a sporadic complication. In Argentina, in 2022, there was an early increase in influenza circulation and the total number of notifications, with the appearance of secondary myositis. Retrospective clinical series of nine pediatric patients who consulted for pain and functional impotence of the lower extremities, and elevated muscle enzymes, at the Pedro de Elizalde hospital in the Autonomous City of Buenos Aires, between August and October 2022. In all of them, infection by influenza virus and recovered without sequelae. Benign acute myositis is a rare entity in childhood, whose diagnosis is predominantly clinical and recovery ad integrum. It should be suspected in patients with compatible symptoms in a context of high viral circulation. Epidemiological surveillance provides tools to identify circulating viruses and their possible complications.

Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy.

Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer.

Caveolin-1 (CAV1) is a protein that in breast cancer increases with disease progression. Extracellular vesicles (EVs) from breast cancer cells with CAV1 also contain Tenascin C (TNC) protein, but the importance of TNC remained to be defined. EVs were identified by size, microscopy and protein analysis. The effects of EVs on breast cancer cells were studied using cells and experiments in animals. CAV1 expression promotes TNC inclusion into EVs, which increased the aggressiveness of recipient breast cancer cells. In animals, only EVs with TNC increased features associated with cancer spread, while EVs lacking TNC reduced tumor growth.

Salud mental perinatal en pandemia por covid-19: un estudio con puérperas en dos provincias Argentinas / Perinatal Mental Health in COVID-19 Pandemic: A Study with Postpartum Women in Two Argentine Provinces

RESUMEN INTRODUCCIÓN: La salud mental perinatal está relacionada con los procesos fisiológicos, psicológicos y socioculturales implicados en la concepción, embarazo, parto, puerperio y vínculo temprano, e incluye a la díada madre-bebé. El objetivo de este trabajo fue indagar el impacto de la pandemia por COVID-19 en la salud mental perinatal, específicamente con relación a la depresión posparto (DPP) y las diversas preocupaciones que manifestaron las mujeres en este contexto. MÉTODOS: Se realizó un estudio de corte transversal a través de una encuesta cara a cara con preguntas abiertas y cerradas. Se trabajó con una muestra no probabilística en tres hospitales (dos de la provincia de Entre Ríos y uno de la provincia de Buenos Aires). RESULTADOS: El 68% de las mujeres mostraron indicadores de DPP evaluada con la Escala de Edimburgo, es decir, manifestaron haberse sentido infelices y con dificultades para dormir, con miedo, tristeza, preocupación y pensamientos negativos, en la última semana. Existen relaciones significativas entre la depresión puerperal, el hospital, la cantidad de personas con las que conviven las puérperas y el estado de salud. DISCUSIÓN: Esta investigación permitió generar información útil para mejorar prácticas, intervenciones y políticas que redunden en garantía de derechos en salud mental perinatal.

ABSTRACT INTRODUCTION: Perinatal mental health is related to the physiological, psychological and sociocultural processes involved in conception, pregnancy, childbirth, puerperium and early bonding, and includes the mother-baby dyad. The objective of this work was to investigate the impact of the COVID-19 pandemic on perinatal mental health, specifically in relation to postpartum depression (PPD) and the various concerns expressed by women in this context. METHODS: A cross-sectional study was conducted through a face-to-face survey with open and closed questions. It used a non-probabilistic sample in three hospitals (two from the province of Entre Ríos and one from the province of Buenos Aires). RESULTS: Sixty-eight percent of the women showed indicators of PPD according to the Edinburgh Scale, that is, they stated that they felt unhappy and had difficulty sleeping, with fear, sadness, worry and negative thoughts, in the last week. There are significant relationships between PPD, the hospital, the number of people with whom postpartum women live, and health status. DISCUSSION: This research generated useful information to improve practices, interventions and policies guaranteeing rights in perinatal mental health.

Effect of Physiological Fluid on the Photothermal Properties of Gold Nanostructured.

Colloidal gold particles have been extensively studied for their potential in hyperthermia treatment due to their ability to become excited in the presence of an external laser. However, their light-to-heat efficiency is affected by the physiologic environment. In this study, we aimed to evaluate the ability of gold sphere, rod, and star-shaped colloids to elevate the temperature of blood plasma and breast cancer-simulated fluid under laser stimulation. Additionally, the dependence of optical properties and colloid stability of gold nanostructures with physiological medium, particle shape, and coating was determined. The light-to-heat efficiency of the gold particle is shape-dependent. The light-to-heat conversion efficiency of a star-shaped colloid is 36% higher than that of sphere-shaped colloids. However, the raised temperature of the surrounding medium is the lowest in the star-shaped colloid. When gold nanostructures are exited with a laser stimulation in a physiological fluid, the ions/cations attach to the surface of the gold particles, resulting in colloidal instability, which limits electron oscillation and diminishes the energy generated by the plasmonic excitation. Fluorescein (Fl) and polyethylene glycol (PEG) attached to gold spheres enhances their colloidal stability and light-to-heat efficiency; post-treatment, they remand their optical properties.

Protein kinase B (AKT) upregulation and Thy-1-αvß3 integrin-induced phosphorylation of Connexin43 by activated AKT in astrogliosis.

BACKGROUND: In response to brain injury or inflammation, astrocytes undergo hypertrophy, proliferate, and migrate to the damaged zone. These changes, collectively known as "astrogliosis", initially protect the brain; however, astrogliosis can also cause neuronal dysfunction. Additionally, these astrocytes undergo intracellular changes involving alterations in the expression and localization of many proteins, including αvß3 integrin. Our previous reports indicate that Thy-1, a neuronal glycoprotein, binds to this integrin inducing Connexin43 (Cx43) hemichannel (HC) opening, ATP release, and astrocyte migration. Despite such insight, important links and molecular events leading to astrogliosis remain to be defined. METHODS: Using bioinformatics approaches, we analyzed different Gene Expression Omnibus datasets to identify changes occurring in reactive astrocytes as compared to astrocytes from the normal mouse brain. In silico analysis was validated by both qRT-PCR and immunoblotting using reactive astrocyte cultures from the normal rat brain treated with TNF and from the brain of a hSOD1G93A transgenic mouse model. We evaluated the phosphorylation of Cx43 serine residue 373 (S373) by AKT and ATP release as a functional assay for HC opening. In vivo experiments were also performed with an AKT inhibitor (AKTi). RESULTS: The bioinformatics analysis revealed that genes of the PI3K/AKT signaling pathway were among the most significantly altered in reactive astrocytes. mRNA and protein levels of PI3K, AKT, as well as Cx43, were elevated in reactive astrocytes from normal rats and from hSOD1G93A transgenic mice, as compared to controls. In vitro, reactive astrocytes stimulated with Thy-1 responded by activating AKT, which phosphorylated S373Cx43. Increased pS373Cx43 augmented the release of ATP to the extracellular medium and AKTi inhibited these Thy-1-induced responses. Furthermore, in an in vivo model of inflammation (brain damage), AKTi decreased the levels of astrocyte reactivity markers and S373Cx43 phosphorylation. CONCLUSIONS: Here, we identify changes in the PI3K/AKT molecular signaling network and show how they participate in astrogliosis by regulating the HC protein Cx43. Moreover, because HC opening and ATP release are important in astrocyte reactivity, the phosphorylation of Cx43 by AKT and the associated increase in ATP release identify a potential therapeutic window of opportunity to limit the adverse effects of astrogliosis.

"I Study When All My Family is Asleep". Gender, Time and Space in Online Education in the COVID-19 Pandemic, / "Eu Estudo Enquanto Toda Minha Família Está Dormindo". Gênero, Tempo e Espaço na Educação Online na Pandemia de Covid-19

Abstract The COVID-19 pandemic has radically altered the ways of working, studying, and interacting globally, forcing people and communities to reinterpret their daily activities. This study analyzes the changes experienced by working mothers who began distance studies at an Argentine university during the second year of the pandemic. Results indicated how spaces and time were transformed, and gender inequalities deepened. The pandemic, above all, impacted the positions and negotiations that working mothers managed to establish to continue studying in a virtual university environment. In these cases, conquering time and space for learning is, at the same time, an act of acceptance and innovation as a woman.

Resumo A pandemia do COVID-19 alterou radicalmente as formas de trabalhar, estudar e interagir globalmente, forçando pessoas e comunidades a recriar os significados de suas atividades diárias. Este estudo analisa as mudanças vivenciadas por mães trabalhadoras que iniciaram seus estudos a distância em uma universidade argentina, durante o segundo ano da pandemia. Os resultados indicam como os espaços e tempos se transformam e as desigualdades de gênero se aprofundam. A pandemia, sobretudo, impactou as posições e as negociações que as mulheres mães conseguem estabelecer para continuar estudando em ambiente universitário virtual. Nesses casos, conquistar tempo e espaço para aprender é, ao mesmo tempo, um ato de aceitação e inovação como mulher.

Extracellular vesicles from gastric epithelial GES-1 cells infected with Helicobacter pylori promote changes in recipient cells associated with malignancy.

Chronic Helicobacter pylori (H. pylori) infection is considered the main risk factor for the development of gastric cancer. Pathophysiological changes in the gastric mucosa initiated by this bacterium can persist even after pharmacological eradication and are likely attributable also to changes induced in non-infected cells as a consequence of intercellular communication via extracellular vesicles (EVs). To better understand what such changes might entail, we isolated EVs from immortalized normal gastric GES-1 cells infected (EVHp+) or not with H. pylori (EVHp-) by ultracentrifugation and characterized them. Infection of GES-1 cells with H. pylori significantly increased the release of EVs and slightly decreased the EV mean size. Incubation with EVHp+ for 24 h decreased the viability of GES-1 cells, but increased the levels of IL-23 in GES-1 cells, as well as the migration of GES-1 and gastric cancer AGS cells. Furthermore, incubation of GES-1 and AGS cells with EVHp+, but not with EVHp-, promoted cell invasion and trans-endothelial migration in vitro. Moreover, stimulation of endothelial EA.hy926 cells for 16 h with EVHp+ promoted the formation of linked networks. Finally, analysis by mass spectrometry identified proteins uniquely present and others enriched in EVHp+ compared to EVHp-, several of which are known targets of hypoxia induced factor-1α (HIF-1α) that may promote the acquisition of traits important for the genesis/progression of gastric pre-neoplastic changes associated with H. pylori infection. In conclusion, the harmful effects of H. pylori infection associated with the development of gastric malignancies may spread via EVs to non-infected areas in the early and later stages of gastric carcinogenesis.

[Celiac crisis and acute tetany in pediatrics. Case report]. / Crisis celíaca y tetania aguda en pediatría. Reporte de un caso.

Celiac disease is an immune-mediated systemic disease with a wide spectrum of clinical presentations. The term celiac crisis describes the acute and potentially fatal form. Clinically it is characterized by severe diarrhea, dehydration, and metabolic disturbances. The case of a 7-year-old male patient attending the ward with tetany, lower limb edema, steatorrhea and weight loss of 8 months of evolution is reported, with analytical findings of hypocalcemia, hypomagnesemia, hypokalemia and coagulopathy. The diagnosis of celiac crisis was made on the basis of serological and clinical findings compatible with celiac disease in the context of severe metabolic abnormalities and acute malnutrition, later confirmed by pathological anatomy. The importance of this report lies in reviewing the characteristics of this serious entity, which requires a high index of suspicion for its diagnosis.

Mini-mycetoma due to Nocardia asteroides: a short report from Mexico.

An illustrative case of mini-mycetoma in a 54-year-old female agricultural worker from Mexico.

A Possible Trait and Status Marker in Bipolar Disorder: The Electroretinogram-Pattern.

The similarity between retinal cells and neurons of the central nervous system allows non-invasive methods to study retinal function, such as the Electroretinogram-Pattern (PERG) to be postulated as possible biomarkers, useful and safe in the study of psychiatric pathologies such as Bipolar Disorder (BD). The objective of the present study is to characterize the differences in the results in the PERG of patients with BD and healthy subjects, as well as to evaluate a possible correlation between these results and the affective decompensations of the manic pole in the group of bipolar patients.

Angioleiomioma en cavidad oral «una neoplasia rara en un sitio poco común¼. Reporte de un caso y revisión de la literatura / Angioleiomyoma in the oral cavity «a rare neoplasm in an unusual site¼. Case report and literature review

El angioleiomioma (AL) es una neoplasia benigna, bien circunscrita y de crecimiento lento, que representa 5% de las neoplasias de tejidos blandos y cuya etiología es desconocida. Se origina del músculo liso, mayormente de las paredes de los vasos sanguíneos; su localización es más frecuente en extremidades, siendo raros en la región de cabeza y cuello, y más aún en cavidad bucal. Histológicamente la lesión se caracteriza por ser un nódulo bien encapsulado con proliferación de fascículos de músculo liso maduro alrededor de la luz de los vasos sanguíneos, cuyas células suelen ser positivas a marcadores de inmunohistoquímica como alfa actina de músculo liso, desmina, HHF35, miosina, calponina y H-caldesmon. El tratamiento actual es la escisión quirúrgica completa con una tasa de recurrencia prácticamente nula. El objetivo es resaltar la importancia del diagnóstico y el manejo correcto de las lesiones intraorales a través de la presentación de un caso clínico de un leiomioma vascular localizado en región nasolabial, además de hacer la revisión de la literatura correspondiente (AU)

The angioleiomyoma (AL) is a benign neoplasm, well circumscribed and slow growing, that represents 5% of the soft tissue neoplasms, whose etiology is unknown. It originates from smooth muscle, mostly from the walls of blood vessels; regarding its location, it more frequently appears in the extremities, being rare in the head and neck region, and even more so in the oral cavity. Histologically, the lesion is characterized by being a well encapsulated nodule with proliferation of mature smooth muscle bundles around the lumen of the blood vessels, whose cells are usually positive for immunohistochemical markers such as alpha smooth muscle actin, desmin, HHF35, myosin, calponin and H-caldesmon. The current treatment is complete surgical excision having zero recurrence rate. The objective of the following article is to educate on the importance of correct diagnosis and management of intraoral lesions through the presentation of a clinical case of a vascular leiomyoma located in the nasolabial region, in addition to reviewing the corresponding literature (AU)

Crisis celíaca y tetania aguda en pediatría. Reporte de un caso / Celiac crisis and acute tetany in pediatrics. Case report

RESUMEN La enfermedad celíaca es una enfermedad sistémica inmunomediada, con un gran espectro de presentaciones clínicas. El término crisis celíaca describe la forma aguda y potencialmente fatal. Clínicamente se caracteriza por diarrea severa, deshidratación y alteraciones metabólicas. Se reporta el caso de un paciente masculino de 7 años de edad que asiste a guardia con tetania, edema en miembros inferiores, esteatorrea y pérdida de peso de 8 meses de evolución, con hallazgos analíticos de hipocalcemia, hipomagnesemia, hipopotasemia y coagulopatía. El diagnóstico de crisis celíaca se realizó sobre la base de hallazgos serológicos y clínicos compatibles con enfermedad celíaca en el contexto de anomalías metabólicas graves y desnutrición aguda, confirmado posteriormente por anatomía patológica. La importancia de este reporte radica en repasar las características de esta grave entidad, que requiere un elevado índice de sospecha para su diagnóstico.

ABSTRACT Celiac disease is an immune-mediated systemic disease with a wide spectrum of clinical presentations. The term celiac crisis describes the acute and potentially fatal form. Clinically it is characterized by severe diarrhea, dehydration, and metabolic disturbances. The case of a 7-year-old male patient attending the ward with tetany, lower limb edema, steatorrhea and weight loss of 8 months of evolution is reported, with analytical findings of hypocalcemia, hypomagnesemia, hypokalemia and coagulopathy. The diagnosis of celiac crisis was made on the basis of serological and clinical findings compatible with celiac disease in the context of severe metabolic abnormalities and acute malnutrition, later confirmed by pathological anatomy. The importance of this report lies in reviewing the characteristics of this serious entity, which requires a high index of suspicion for its diagnosis.

A high-fat diet during pregnancy impairs memory acquisition and increases leptin receptor expression in the hippocampus of rat offspring.

A high-fat diet (HFD) during pregnancy influences the neurodevelopment of progeny, particularly in the hippocampus, a brain region involved in cognitive processes. The hippocampus has high levels of leptin receptors (Ob-R) that participate in synaptic plasticity. This study examined the effect of maternal HFD during gestation on Ob-R expression in the CA1 and CA3 hippocampal regions, and its relationship with spatial learning and memory in the offspring. We used 48 rat pups: 24 from dams fed a balanced diet (BD, 6.2% fat) and 24 from those fed an HFD (42% fat) during pregnancy. We recorded weight gain and food intake in each pup every day beginning on postnatal day 3 (PND 3). Memory acquisition was assessed on PND 28 and memory retention on PND 42 in the Morris water maze (MWM). Then, 12 pups per group were selected randomly and subjected to bioimpedance spectroscopy. The remaining offspring was perfused to determine Ob-R expression levels in the CA1 and CA3 hippocampal regions. Interestingly, HFD pups had significantly higher weight gain, food intake, and fat mass than BD offspring. Interestingly, the HFD group showed poor memory performance, which correlated with changes in the Ob-R expression in both hippocampal regions. These data indicate that maternal exposure to HFD impacts neurodevelopmental and cognitive functions of the offspring.

Cytomorphological features of extramammary Paget's disease of the vulva in a patient with diagnoses of squamous cell carcinoma of the cervix status post-chemoradiation, and high-grade vulvar intraepithelial neoplasia: The importance of basic principles.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare neoplasm that commonly affects post-menopausal women. It usually presents in the anogenital area where apocrine sweat glands are abundant, most commonly in the vulva. The disease is characterised by slow growth and high local recurrence rates. Clinically, EMPD presents as well-demarcated erythematous lesions or plaques that may be ulcerated. Microscopically, it shows a group of atypical cells with abundant clear cytoplasm and nuclear pleomorphism. METHODS: We present the case of a 58-year-old female with a history of poorly differentiated squamous cell carcinoma of the cervix, status post-radical-hysterectomy with bilateral salpingo-oophorectomy, and chemoradiation in 2016. The patient also had a long-standing history of vulvar pain, skin changes on her left labia, and itching. RESULTS: Punch biopsies of the vulva revealed acanthosis and acantholysis of the epidermis with an intraepidermal scattering of single, or clusters of, large cells with round/oval nuclei and abundant clear cytoplasm. The cells were positive for p16, CK19, CK7, and PAX8, supporting the diagnosis of EMPD without evidence of dysplasia. The concurrent Papanicolaou smear showed a hypercellular specimen composed of hyperchromatic tissue fragments with high nuclear-to-cytoplasmic ratios and apoptotic bodies. The presence of intracytoplasmic mucin and the tridimensionality of the fragments supported the diagnosis of adenocarcinoma. CONCLUSIONS: This study compares the histological and cytomorphological features of EMPD with high-grade squamous intraepithelial lesions, since the pathogenesis, precursor lesions, etiological associations, staging, clinical treatment, and prognosis differ substantially and may have a significant clinical impact on the patient's treatment.

Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications.

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their "traits" to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as "cell competition". This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as "the hallmarks of cancer" defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.

Neurobiological approaches of high-fat diet intake in early development and their impact on mood disorders in adulthood: A systematic review.

The early stage of development is a vulnerable period for progeny neurodevelopment, altering cytogenetic and correct cerebral functionality. The exposure High-Fat Diet (HFD) is a factor that impacts the future mental health of individuals. This review analyzes possible mechanisms involved in the development of mood disorders in adulthood because of maternal HFD intake during gestation and lactation, considering previously reported findings in the last five years, both in humans and animal models. Maternal HFD could induce alterations in mood regulation, reported as increased stress response, anxiety-like behavior, and depressive-like behavior. These changes were mostly related to HPA axis dysregulations and neuroinflammatory responses. In conclusion, there could be a relationship between HFD consumption during the early stages of life and the development of psychopathologies during adulthood. These findings provide guidelines for the understanding of possible mechanisms involved in mood disorders, however, there is still a need for more human clinical studies that provide evidence to improve the understanding of maternal nutrition and future mental health outcomes in the offspring.