Is EEG Entropy a Useful Measure for Alzheimer's Disease?

BACKGROUND: The number of individuals diagnosed with Alzheimer's disease (AD) has increased, and it is estimated to continue rising in the coming years. The diagnosis of this disease is challenging due to variations in onset and course, its diverse clinical manifestations, and the indications for measuring deposit biomarkers. Hence, there is a need to develop more precise and less invasive diagnostic tools. Multiple studies have considered using electroencephalography (EEG) entropy measures as an indicator of the onset and course of AD. Entropy is deemed suitable as a potential indicator based on the discovery that variations in its complexity can be associated with specific pathologies such as AD. METHODOLOGY: Following PRISMA guidelines, a literature search was conducted in 4 scientific databases, and 40 articles were analyzed after discarding and filtering. RESULTS: There is a diversity in entropy measures; however, Sample Entropy (SampEn) and Multiscale Entropy (MSE) are the most widely used (21/40). In general, it is found that when comparing patients with controls, patients exhibit lower entropy (20/40) in various areas. Findings of correlation with the level of cognitive decline are less consistent, and with neuropsychiatric symptoms (2/40) or treatment response less explored (2/40), although most studies show lower entropy with greater severity. Machine learning-based studies show good discrimination capacity. CONCLUSIONS: There is significant difficulty in comparing multiple studies due to their heterogeneity; however, changes in Multiscale Entropy (MSE) scales or a decrease in entropy levels are considered useful for determining the presence of AD and measuring its severity.

Factor B Inhibition with Iptacopan in Recurrent C3 Glomerulopathy Following Kidney Transplant: A Report of Two Cases.

C3 glomerulopathy is a rare disease caused by fluid phase dysregulation of the alternative complement pathway. Currently, treatment depends on clinical and histological severity and includes nephroprotection, unspecific immunosuppression, and terminal complement blockers (C5), without having an etiological treatment approved. C3 glomerulopathy has high recurrence rates after kidney transplantation with a high risk of graft loss. Fortunately, new molecules are being developed that specifically target the proximal alternative complement pathway, such as iptacopan, a factor B inhibitor that showed promising results in native kidneys and cases of transplant recurrence in a phase 2 clinical trial. We present 2 "real-world" cases of C3 glomerulopathy recurrence in kidney allografts treated with iptacopan, with initial excellent clinical response and safety profile, especially with early introduction. We also present follow-up biopsies that showed no C3 deposition during factor B inhibition. Our cases suggest that proximal blockade of the alternative complement pathway can be effective and safe in the treatment of C3 glomerulopathy recurrence in kidney transplantation, bringing other questions such as dual blockade (eg, in C3 and C5), the optimal patient profile to benefit from factor B inhibition or treatment duration and its potential use in other forms of membranoproliferative glomerulonephritis (eg, immune complex-mediated).

["If you are a woman, read this, it's good for you": the advertising of medicines targeted at mothers in the Colombian press, 1903-1945]. / "Si usted es mujer lea esto que le conviene": la publicidad de medicamentos de patentes dirigidos a las madres en la prensa colombiana, 1903-1945.

This article analyses the advertising of patent medicine directed at mothers, which circulated in newspapers between 1903 and 1945. It demonstrates that these advertisings played an important role in shaping women as a consumer demographic, promoting a scientific approach to motherhood intertwined with health challenges. The methodology employed included the analysis of advertisements in the newspapers El Tiempo, La Prensa, Rigoletto, El Faro and Evolución. Additionally, it examines the historiography of the subject in Colombia and other latitudes. The conclusion of this study asserts that motherhood was a significant target for pharmaceutical industries, leading to a commercial concept of motherhood.

Este artículo analiza la publicidad de medicamentos de patentes dirigida a las madres en la prensa colombiana entre 1903 y 1945. Muestra cómo estos anuncios jugaron un papel importante al momento de moldear a la mujer como una población objeto de consumo, estableciendo una maternidad científica por medio de la medicalización. La metodología incluyó el análisis de los avisos publicitarios en los periódicos El Tiempo, La Prensa, Rigoletto, El Faro y Evolución. Igualmente, dialogó con la historiografía de la temática producida en Colombia y otras latitudes. Concluyó que la maternidad fue un nicho importante para la venta de medicamentos, provocando la conformación de una idea comercial de lo materno.

Breast cancer survivors suffering from lymphedema: What really do affect to corporeality/body image? A qualitative study.

Breast cancer-related lymphedema is currently one of the most serious complications that most affect the quality of life of women undergoing breast cancer. The aim of this study was to explore in-depth the experience of women who suffer from lymphoedema after breast cancer and how does this condition affect corporeality, with no judgements. For this purpose, a qualitative methodology was followed. In-depth interviews, interviewer's field notes and participants' letters were used for data collection. The participants were twenty Spanish women with lymphoedema after overcome a breast cancer in the past. Healthcare specialists with experience in the topic were also included. Results showed 2 main categories: "From cancer to lymphedema, another disease another disease" and "Potential for transition and transformation towards a new way of life". As a conclusion, the difficulty in accessing adequate treatment, the need for greater awareness of lymphedema and the importance of the emotional and psychological dimension of this chronic disease. Highlighting the attitudes that these women develop for self-care and the concept of new corporeality. After breast cancer, women with lymphedema experience a drastic change that affects all areas of their lives. The adaptation process, and the search for resources and aid, play a fundamental role in overcoming this process.

Recurrent familial case of early childhood sudden death: Complex post mortem genetic investigations.

INTRODUCTION: Sudden Unexplained Death in Childhood (SUDC) needs to be fully assessed considering its impact on the family, parents and siblings. Inborn Errors of Metabolism (IEM) such as Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) should be taken into consideration when SUDC occurres. Our aim is to present a family with two successive SUDC and to discuss the post-mortem genetics investigations revealing an IEM implication. CASES REPORT: A complete autopsy with genetic testing was performed when the proband, a 4-year-old girl, died. A few years previously, her older brother had died at the same age and off the same condition. Years later, his exhumation was necessary in order to perform a post-mortem diagnosis.The two siblings were revealed to have had the same pathogenic genotype of the ACADM gene, heterozygous substitutions in ACADM (NM_000016.5): c.985 A>G p.(Lys329Glu) and c.347 G>A p.(Cys116Tyr). In addition, they also both carried a VUS in TECRL, a gene implicated in Catecholaminergic Polymorphic Tachycardia Ventricular (CPVT) and SUDC. CONCLUSION: We illustrate the importance of exome analyses for investigating unexplained sudden death, especially in children, with the possible impact for genetic counselling in the family. The finding of the implication of ACADM gene in this case, raises likely responsibility of the public health system in countries such as France, who delayed implementation of new born screening for these conditions. Exome analyses in this case detected unexpected complexity in interpretation linked to the identification of a second candidate gene for SUDC.

Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement behavior in rodent models of cocaine use disorder. Output from the mPFC is modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets (PNNs). Here we tested whether chondroitinase ABC (ABC)- mediated removal of PNNs prevented the acquisition or reconsolidation of a cocaine self-administration memory. ABC injections into the dorsal mPFC prior to training attenuated the acquisition of cocaine self-administration. Also, ABC given 3 days prior to but not 1 hr after memory reactivation blocked cue-induced reinstatement. However, reduced reinstatement was present only in rats given a novel reactivation contingency, suggesting that PNNs are required for the updating of a familiar memory. In naive rats, ABC injections into mPFC did not alter excitatory or inhibitory puncta on PV cells but reduced PV intensity. Whole-cell recordings revealed a greater inter-spike interval 1 hr after ABC, but not 3 days later. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during novel memory reactivation revealed that ABC in the mPFC prevented reward-associated increases in beta and gamma activity as well as phase-amplitude coupling between the dHIP and mPFC. Together, our findings show that PNN removal attenuates the acquisition of cocaine self-administration memories and disrupts reconsolidation of the original memory when combined with a novel reactivation session. Further, reduced dHIP/mPFC coupling after PNN removal may serve as a key biomarker for how to disrupt reconsolidation of cocaine memories and reduce relapse.

Artificial intelligence-based automated preprocessing and classification of impacted maxillary canines in panoramic radiographs.

OBJECTIVES: Automating the digital workflow for diagnosing impacted canines using panoramic radiographs (PRs) is challenging. This study explored feature extraction, automated cropping, and classification of impacted and nonimpacted canines as a first step. METHODS: A convolutional neural network with SqueezeNet architecture was first trained to classify two groups of PRs (91with and 91without impacted canines) on the MATLAB programming platform. Based on results, the need to crop the PRs was realized. Next, artificial intelligence (AI) detectors were trained to identify specific landmarks (maxillary central incisors, lateral incisors, canines, bicuspids, nasal area, and the mandibular ramus) on the PRs. Landmarks were then explored to guide cropping of the PRs. Finally, improvements in classification of automatically cropped PRs were studied. RESULTS: Without cropping, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for classifying impacted and nonimpacted canine was 84%. Landmark training showed that detectors could correctly identify upper central incisors and the ramus in ∼98% of PRs. The combined use of the mandibular ramus and maxillary central incisors as guides for cropping yielded the best results (∼10% incorrect cropping). When automatically cropped PRs were used, the AUC-ROC improved to 96%. CONCLUSIONS: AI algorithms can be automated to preprocess PRs and improve the identification of impacted canines.

Evaluation of whole-genome enrichment and sequencing of T. pallidum from FFPE samples after 75 years.

The recent developments in genomic sequencing have permitted the publication of many new complete genome sequences of Treponema pallidum pallidum, the bacterium responsible for syphilis, which has led to a new understanding of its phylogeny and diversity. However, few archived samples are available, because of the degradability of the bacterium and the difficulties in preservation. We present a complete genome obtained from a Formalin-Fixed Paraffin-Embedded (FFPE) organ sample from 1947, kept at the Strasbourg Faculty of Medicine. This is the preliminary, proof-of concept study of this collection/biobank of more than 1.5 million FFPE samples and the evaluation of the feasibility of genomic analyses. We demonstrate here that even degraded DNA from fragile bacteria can be recovered from 75-year-old FFPE samples and therefore propose that such collections as this one can function as sources of biological material for genetic studies of pathogens, cancer, or even the historical human population itself.

Enhanced expression of parvalbumin and perineuronal nets in the medial prefrontal cortex after extended-access cocaine self-administration in rats.

The medial prefrontal cortex (mPFC) drives cocaine-seeking behaviour in rodent models of cocaine use disorder. Parvalbumin (PV)-containing GABAergic interneurons powerfully control the output of the mPFC, yet few studies have focused on how these neurons modulate cocaine-seeking behaviour. Most PV neurons are surrounded by perineuronal nets (PNNs), which regulate the firing of PV neurons. We examined staining intensity and number of PV and PNNs after long-access (6 h/day) cocaine self-administration in rats followed by either 8-10 days extinction ± cue-induced reinstatement or short-term (1-2 days) or long-term (30-31 days) abstinence ± cue-induced reinstatement. The intensity of PNNs was increased in the prelimbic and infralimbic PFC after long-term abstinence in the absence of cue reinstatement and after cue reinstatement following both daily extinction sessions and after a 30-day abstinence period. PV intensity was increased after 30 days of abstinence in the prelimbic but not infralimbic PFC. Enzymatic removal of PNNs with chondroitinase ABC (ABC) in the prelimbic PFC did not prevent incubation of cue-induced reinstatement but decreased cocaine-seeking behaviour at both 2 and 31 days of abstinence, and this decrease at 31 days was accompanied by reduced c-Fos levels in the prelimbic PFC. Increases in PNN intensity have generally been associated with the loss of plasticity, suggesting that the persistent and chronic nature of cocaine use disorder may in part be attributed to long-lasting increases in PNN intensity that reduce the ability of stimuli to alter synaptic input to underlying PV neurons.

Distribution of Escherichia coli Pathotypes along an Urban-Rural Gradient in Ecuador.

Diarrheal diseases are a leading cause of mortality and morbidity in low- and middle-income countries. Diarrhea is associated with a wide array of etiological agents including bacterial, viral, and parasitic enteropathogens. Previous studies have captured between- but not within-country heterogeneities in enteropathogen prevalence and severity. We conducted a case-control study of diarrhea to understand how rates and outcomes of infection with diarrheagenic pathotypes of Escherichia coli vary across an urban-rural gradient in four sites in Ecuador. We found variability by site in enteropathogen prevalence and infection outcomes. Any pathogenic E. coli infection, coinfections, diffuse adherent E. coli (DAEC), enteroinvasive E. coli (EIEC), and rotavirus were significantly associated with acute diarrhea. DAEC was the most common pathotype overall and was more frequently associated with disease in urban areas. Enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) were more common in rural areas. ETEC was only associated with diarrhea in one site. Phylogenetic analysis revealed that associations with disease were not driven by any single clonal complex. Higher levels of antibiotic resistance were detected in rural areas. Enteropathogen prevalence, virulence, and antibiotic resistance patterns vary substantially by site within Ecuador. The variations in E. coli pathotype prevalence and virulence in this study have important implications for control strategies by context and demonstrate the importance of capturing within-country differences in enteropathogen disease dynamics.

Clinical experience of electroconvulsive therapy with anaesthetic and muscle relaxant at the Clínica Universidad de La Sabana: 2009-2017.

INTRODUCTION: Electroconvulsive therapy is an effective and safe procedure, which is indicated mainly in patients with both unipolar and bipolar depressive episodes, mania and schizophrenia, when they do not respond to other treatments. OBJECTIVE: To describe the demographic, social and clinical properties of a group of patients treated with electroconvulsive therapy (ECT) with anaesthetic and muscular relaxant at the Universidad de La Sabana Clinic for a period of 8 years. METHODS: The databases and records of the procedures were reviewed from 1 January 2009 to 31 December 2017. An analysis was performed with descriptive statistics. RESULTS: In this period, 1322 procedures were performed on 143 patients (54.5% women) with an associated diagnosis of major depression in 57%. The number of treatments per person was 9.2 and complications occurred in 3.8%, without any of them requiring invasive management. CONCLUSIONS: Electroconvulsive therapy is performed safely in patients and with different parameters in terms of age, gender and diagnosis, in comparison to other countries in Latin America and the world. It is important to join efforts in research that allow a more complete overview of the characteristics of its application in the country.

Increased aridity is associated with stronger tradeoffs in ponderosa pine vital functions.

Trees must allocate resources to core functions like growth, defense, and reproduction. These allocation patterns have profound effects on forest health, yet little is known about how core functions trade off over time, and even less is known about how a changing climate will impact tradeoffs. We conducted a 21-year survey of growth, defense, and reproduction in 80 ponderosa pine individuals spanning eight populations across environmental gradients along the Colorado Front Range, USA. We used linear mixed models to describe tradeoffs among these functions and to characterize variability among and within individuals over time. Growth and defense were lower in years of high cone production, and local drought conditions amplified year-to-year tradeoffs between reproduction and growth, where trees located at sites with hotter and drier climates showed stronger tradeoffs between reproduction and growth. Our results support the environmental stress hypothesis of masting, which predicts that greater interannual variation in tree functions will be associated with more marginal environments, such as those that are prone to drought. With warming temperatures and increased exposure to drought stress, trees will be faced with stronger interannual tradeoffs, which could lead to further decreases in growth and defensive efforts, ultimately increasing risks of mortality.

Moonlight-like proteins are actually cell wall components in Pseudocercospora fijiensis.

The fungal cell wall protects fungi against threats, both biotic and abiotic, and plays a role in pathogenicity by facilitating host adhesion, among other functions. Although carbohydrates (e.g. glucans, chitin) are the most abundant components, the fungal cell wall also harbors ionic proteins, proteins bound by disulfide bridges, alkali-extractable, SDS-extractable, and GPI-anchored proteins, among others; the latter consisting of suitable targets which can be used for fungal pathogen control. Pseudocercospora fijiensis is the causal agent of black Sigatoka disease, the principal threat to banana and plantain worldwide. Here, we report the isolation of the cell wall of this pathogen, followed by extensive washing to eliminate all loosely associated proteins and conserve those integrated to its cell wall. In the HF-pyridine protein fraction, one of the most abundant protein bands was recovered from SDS-PAGE gels, electro-eluted and sequenced. Seven proteins were identified from this band, none of which were GPI-anchored proteins. Instead, atypical (moonlight-like) cell wall proteins were identified, suggesting a new class of atypical proteins, bound to the cell wall by unknown linkages. Western blot and histological analyses of the cell wall fractions support that these proteins are true cell wall proteins, most likely involved in fungal pathogenesis/virulence, since they were found conserved in many fungal pathogens.

Experiencia clínica de la terapia electroconvulsiva con anestesia y relajación en la Clínica Universidad de La Sabana: 2009-2017

Introducción: La terapia electroconvulsiva es un procedimiento efectivo y seguro, el cual se indica principalmente a pacientes con episodios depresivos tanto unipolares como bipolares, manía y esquizofrenia, cuando no responden a otros tratamientos. Objetivo: Describir las propiedades demográficas, sociales y clínicas de un grupo de pacientes tratados con terapia electroconvulsiva con anestesia y relajación (TECAR) en la Clínica Universidad de La Sabana por un periodo de 8 arios. Métodos: Se revisan las bases de datos y los registros de los procedimientos desde el 1 de enero de 2009 hasta el 31 de diciembre de 2017. Se realiza un análisis con estadística descriptiva. Resultados: En este periodo se realizaron 1.322 procedimientos a 143 pacientes, el 54,5% de ellos mujeres, y con diagnóstico asociado de depresión mayor en el 57% de los pacientes. El número de tratamientos por persona fue 9,2 y en el 3,8% se presentaron complicaciones, sin que se requiriese tratamiento invasivo en ninguna de ellas. Conclusiones: La terapia electroconvulsiva se aplica con seguridad a los pacientes y con parámetros diversos en cuanto a edad, sexo y diagnóstico más frecuente, en comparación con otros países de Latinoamérica y el mundo. Es importante sumar esfuerzos en investigación que permitan tener un panorama más completo de las características de su aplicación en el país.

Electroconvulsive therapy is an effective and safe procedure, which is indicated mainly in patients with both unipolar and bipolar depressive episodes, mania and schizophrenia, when they do not respond to other treatments. Objective: To describe the demographic, social and clinical properties of a group of patients treated with electroconvulsive therapy (ECT) with anaesthetic and muscular relaxant at the Universidad de La Sabana Clinic for a period of 8 years. Methods: The databases and records of the procedures were reviewed from 1 January 2009 to 31 December 2017. An analysis was performed with descriptive statistics. Results: In this period, 1,322 procedures were performed on 143 patients (54.5% women) with an associated diagnosis of major depression in 57%. The number of treatments per person was 9.2 and complications occurred in 3.8%, without any of them requiring invasive management. Conclusions: Electroconvulsive therapy is performed safely in patients and with different parameters in terms of age, gender and diagnosis, in comparison to other countries in Latin America and the world. It is important to join efforts in research that allow a more complete overview of the characteristics of its application in the country.

Nutritional Composition of Breakfast in Children and Adolescents with and without Celiac Disease in Spain-Role of Gluten-Free Commercial Products.

Eating a nutritionally balanced breakfast can be a challenge when following a gluten-free diet (GFD). We assessed the ingredients and nutrient composition of 364 gluten-free breakfast products (GFPs) and 348 gluten-containing counterparts (GCCs), and we analysed the nutritional quality of breakfast in a group of Spanish children and adolescents with celiac disease (CD) (n = 70), as compared to controls (n = 67). Food intakes were estimated using three 24 h dietary records. The composition of GFPs and GCCs was retrieved from the package labels of commercially available products. Most participants (98.5%) ate breakfast daily, and only one person in each group skipped breakfast once. The breakfast contribution of the total daily energy was 19% in participants with CD and 20% in controls. CD patients managed a balanced breakfast in terms of energy (54% from carbohydrates; 12% from proteins; 34% from lipids) and key food groups (cereals, dairy, fruits), but their intake of fruits needs improvement. Compared to controls, breakfast in the CD group provided less protein and saturated fat, a similar amount of carbohydrates and fibre, and more salt. Fibre is frequently added to GFPs, but these contain less protein because of the flours used in formulation. Gluten-free bread contains more fat and is more saturated than is GCC. Sugars, sweets, and confectionery contribute more to energy and nutrient intakes in participants with CD, while grain products do so in controls. Overall, breakfast on a GFD can be adequate, but can be improved by GFPs reformulation and a lower consumption of processed foods.

Acompañamiento creativo para el duelo por muerte en contexto hospitalario: Laexperiencia en un Hospital en Bogotá / Apoio criativo ao luto pela morte no contexto hospitalar: a experiência em umhospital de Bogotá / Creative support for death grief in a hospital context: the experience in a Bogotá hospital

The article presents the results of a participatory research process based on the arts, whichsought to incorporate art and creativity in seven units of a high-complexity university hospital, forsupport at the end of life and bereavement. This was done through the provision of kits with materials with creative potential and the development of awareness and creation workshops with healthand administrative staff, patients, and family members. The process was produced through participant observation and field diaries. Informal, semi-structured interviews and a discussion groupwere also conducted to identify the main barriers and facilitators of the proposal. We conclude that,in order to integrate this type of resources and for care centered on the person and families, healthservices require deep transformations that include death as a significant experience, giving space totheir own mourning and emotions, which would reduce Fatigue due to inflammation is very frequent in health personnel confronted with death in a systematic way. The project was approved bythe respective ethics committee.(AU)

El artículo presenta los resultados de un proceso de investigación participativa basadaen las artes, en el que se buscó incorporar el arte y la creatividad en siete unidades de un hospitaluniversitario de alta complejidad, para el acompañamiento en final de vida y duelo. Esto se hizo através de la disposición de kits con materiales con potencial creativo y el desarrollo de talleres desensibilización y creación con personal sanitario, administrativo, pacientes y familiares. El procesose registró a través de observación participante y diarios de campo. También se realizaron reunionesperiódicas, entrevistas informales, semiestructuradas de seguimiento y un grupo de discusión paraidentificar las principales barreras y facilitadores de la propuesta. Concluimos que, para poderintegrar este tipo de recursos y para una atención centrada en la persona y las familias, los serviciosde salud requieren transformaciones de fondo que incluyan la muerte como experiencia significante, dando espacio a sus propios duelos y emociones, lo que reduciría la fatiga por compasiónmuy frecuente en personal de salud enfrentado a la muerte de manera sistemática. El proyecto contócon la aprobación del comité de ética respectivo.(AU)

O artigo apresenta os resultados de um processo de pesquisa participativa baseado nasartes, que buscou incorporar arte e criatividade em sete unidades de um hospital universitário dealta complexidade, para apoio no final da vida e luto. Isso foi feito por meio da disponibilização dekits com materiais com potencial criativo e do desenvolvimento de oficinas de sensibilização e criação com equipe de saúde e administrativa, pacientes e familiares. O processo foi produzido pormeio de observação participante e diários de campo. Também foram realizadas entrevistas informais semiestruturadas e um grupo de discussão para identificar as principais barreiras e facilitadores da proposta. Concluímos que, para integrar este tipo de recursos e para um cuidado centradona pessoa e na família, os serviços de saúde necessitam de profundas transformações que incluama morte como uma experiência significativa, dando espaço ao seu próprio luto e emoções, o quereduziria a Fadiga por a inflamação é muito frequente em profissionais de saúde confrontados coma morte de forma sistemática. O projeto foi aprovado pelo respectivo comitê de ética.(AU)

Ceefourin-1, a MRP4/ABCC4 inhibitor, induces apoptosis in AML cells enhanced by histamine.

BACKGROUND: Ceefourin-1 is a specific MRP4/ABCC4 inhibitor with potential antileukemic activity. In this study, we evaluate the ability of ceefourin-1 alone or in combination with histamine, an approved antileukemic agent, to induce cell differentiation or apoptosis in human acute myeloid leukemic cells. We also examine ceefourin-1 toxicity in mice. METHODS: U937, HL-60, and KG1a cells were used as models for human acute myeloid leukemia. Cyclic AMP efflux was estimated by measuring intracellular and extracellular cAMP levels. Cell differentiation was assessed by levels of CD14 and CD11b by FACS, and CD88 by western blot, and by cell morphology. Apoptosis was evaluated by cleavage of caspase-3 and PARP by western blot, and by annexin V binding assay. Subacute toxicity study of ceefourin-1 was carried out in BALB/c mice. RESULTS: Ceefourin-1 inhibits cAMP exclusion in AML cells and promotes intracellular signaling via CREB. Ceefourin-1 leads AML cells to apoptosis and histamine potentiates this effect, without evidence of cell differentiation. Intraperitoneal administration of ceefourin-1 shows no important alterations in mice blood parameters, hepatic, and renal functions, nor signs of histologic damage. CONCLUSIONS: These results show that ceefourin-1 promotes apoptosis in AML cells that is enhanced by histamine. GENERAL SIGNIFICANCE: This work indicates that ceefourin-1 represents a promising molecule that could be used alone or in combination with histamine for in vivo evaluation in acute myeloid leukemia malignancies.

Rickettsia Vaccine Candidate pVAX1-OmpB24 Stimulates TCD4+INF-γ+ and TCD8+INF-γ+ Lymphocytes in Autologous Co-Culture of Human Cells.

BACKGROUND: In recent years, promising vaccination strategies against rickettsiosis have been described in experimental animal models and human cells. OmpB is considered an immunodominant antigen that is recognized by T and B cells. The aim of this study was to identify TCD4+INF-γ+ and TCD8+INF-γ+ lymphocytes in an autologous system with macrophages transfected with the vaccine candidate pVAX1-OmpB24. Lymphocytes and monocytes from 14 patients with Rickettsia were isolated from whole blood. Monocytes were differentiated into macrophages and transfected with the plasmid pVAX1-OmpB24 pVax1. Isolated lymphocytes were cultured with transfected macrophages. IFN-γ-producing TCD4+ and TCD8+ lymphocyte subpopulations were identified by flow cytometry, as was the percentage of macrophages expressing CD40+, CD80+, HLA-I and HLA-II. Also, we analyzed the exhausted condition of the T lymphocyte subpopulation by PD1 expression. Macrophages transfected with pVAX1-OmpB24 stimulated TCD4+INF-γ+ cells in healthy subjects and patients infected with R. typhi. Macrophages stimulated TCD8+INF-γ+ cells in healthy subjects and patients infected with R. rickettsii and R. felis. Cells from healthy donors stimulated with OmpB-24 showed a higher percentage of TCD4+PD1+. Cells from patients infected with R. rickettsii had a higher percentage of TCD8+PD-1+, and for those infected with R. typhi the larger number of cells corresponded to TCD4+PD1+. Human macrophages transfected with pVAX1-OmpB24 activated TCD4+IFN-γ+ and CD8+IFN-γ+ in patients infected with different Rickettsia species. However, PD1 expression played an important role in the inhibition of T lymphocytes with R. felis.

Analysis of retinal nerve layers in idiopathic, LRRK2-associated Parkinson's disease and unaffected carriers of G2019S mutation.

INTRODUCTION: In both prodromal and early symptomatic stages of idiopathic PD (iPD) peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) thinning have been identified. Here we assessed whether these alterations can also be detected in symptomatic and presymptomatic stages of LRRK2-PD. METHODS: 218 eyes belonging to 20 iPD, 19 LRRK2-PD (L2PD), 24 LRRK2 non-manifesting carriers (L2NMC), and 46 controls (HCs). pRNFL, mGCL thickness (squares), and Bruch's membrane opening minimum rim width were evaluated by SD-OCT. In L2NMC, 123I-ioflupane SPECT (DaT-SPECT) with semi-quantitative analysis was carried out. RESULTS: Compared to HCs, iPD patients showed significant thinning of the temporal (BMO-MRW and pRNFL), superior-temporal (BMO-MRW), inferior-temporal (BMO-MRW), superior-nasal (BMO-MRW) and central sectors (BMO-MRW) (p < 0.05), as well as in five mGCL sectors (p < 0.05). No significant differences were found between the L2PD or L2NMC and HCs. BMO-MRW thickness in its temporal-superior, superior-nasal and middle sectors was influenced by disease duration (p < 0.05) and mGCL thickness in sectors TS1, TS2, TS3, NS1 and NS3 was influenced by UPDRSIII and age (p < 0.05). CONCLUSION: LRRK2-PD is distinguished from iPD by absent or less retinal nerve involvement, both in clinical and preclinical stages.

Putative intestinal permeability markers do not correlate with cardiometabolic health and gut microbiota in humans, except for peptides recognized by a widely used zonulin ELISA kit.

BACKGROUND AND AIMS: Cardiometabolic diseases refer to a group of interrelated conditions, sharing metabolic dysfunctions like insulin resistance, obesity, dyslipidemia, and hypertension. The gut microbiota has been associated with CMD and related conditions. Alterations in the intestinal epithelium permeability triggered by chronic stress and diet could bridge gut microbiota with inflammation and CMD development. Here, we assessed the relationship between intestinal permeability and circulating SCFAs with cardiometabolic health status (CMHS) and gut microbiota in a sample of 116 Colombian adults. METHODS AND RESULTS: Plasma levels of lipopolysaccharide-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), claudin-3, and purported zonulin peptides (PZP) were measured by ELISA, whereas plasmatic levels of acetate, propionate, butyrate, isobutyrate, and valerate were measured by gas chromatography/mass spectrometry. In addition, for further statistical analysis, we took data previously published by us on this cohort, including gut microbiota and multiple CMD risk factors that served to categorize subjects as cardiometabolically healthy or cardiometabolically abnormal. From univariate and multivariate statistical analyses, we found the levels of I-FABP, LBP, and PZP increased in the plasma of cardiometabolically abnormal individuals, although only PZP reached statistical significance. CONCLUSIONS: Our results did not confirm the applicability of I-FABP, LBP, claudin-3, or SCFAs as biomarkers for associating intestinal permeability with the cardiometabolic health status in these subjects. On the other hand, the poorly characterized peptides detected with the ELISA kit branded as "zonulin" were inversely associated with cardiometabolic dysfunctions and gut microbiota. Further studies to confirm the true identity of these peptides are warranted.