Chromogenic LMO2 mRNA ISH Expression Correlates with LMO2 Protein and Gene Expression and Captures Their Survival Impact in Diffuse Large B-Cell Lymphoma, NOS.

BACKGROUND: LMO2 is a relevant gene involved in B-cell ontogeny and a survival predictor of aggressive large B-cell lymphomas (aLBCL). Most studies assessing LMO2 mRNA expression have relied on microarray platforms or qRT-PCR methods, overlooking tissue morphology. In this study, we evaluate LMO2 RNA expression by chromogenic in situ hybridization (CISH) in normal tissue and in a series of 82 aLBCL. METHODS: LMO2 CISH was performed in formalin-fixed paraffin-embedded tissues, scored by three different methods, and correlated with a transcriptome panel. RESULTS: We obtained statistically significant results correlating the methods of evaluation with LMO2 protein expression and gene expression results. Normal tonsil tissue showed high levels of LMO2, particularly within the light zone of the germinal center. Conversely, in aLBCL, a notable reduction in LMO2 expression was noted, remarkably in cases carrying MYC rearrangements. Furthermore, significant results were obtained through overall survival and Cox regression survival analysis, incorporating International Prognostic Index data alongside LMO2 expression levels. CONCLUSIONS: We show a reliable method to identify LMO2 mRNA expression by CISH, effectively capturing many of the reported biologic features of LMO2.

Mutant dominant-negative rhodopsin∆I256 causes protein aggregates degraded via ERAD and prevents normal rhodopsin from proper membrane trafficking.

Dominant mutations in the rhodopsin gene (Rho) contribute to 25% of autosomal dominant retinitis pigmentosa (adRP), characterized by photoreceptor loss and progressive blindness. One such mutation, Rho ∆I256 , carries a 3-bp deletion, resulting in the loss of one of two isoleucines at codons 255 and 256. Our investigation, using recombinant expression in HEK293 and COS-7 cells, revealed that Rho ∆I256, akin to the known adRP mutation Rho P23H, induces the formation of rhodopsin protein (RHO) aggregates at the perinuclear region. Co-expression of Rho ∆I256 or Rho P23H with wild-type Rho WT, mimicking the heterozygous genotype of adRP patients, demonstrated the dominant-negative effect, as all isoforms were retained in perinuclear aggregates, impeding membrane trafficking. In retinal explants from WT mice, mislocalization of labeled adRP isoforms at the outer nuclear layer was observed. Further analysis revealed that RHO∆I256 aggregates are retained at the endoplasmic reticulum (ER), undergo ER-associated degradation (ERAD), and colocalize with the AAA-ATPase escort chaperone valosin-containing protein (VCP). These aggregates are polyubiquitinated and partially colocalized with the 20S proteasome subunit beta-5 (PSMB5). Pharmacological inhibition of proteasome- or VCP activity increased RHO∆I256 aggregate size. In summary, RHO∆I256 exhibits dominant pathogenicity by sequestering normal RHOWT in ER aggregates, preventing its membrane trafficking and following the ERAD degradation.

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem.

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a groundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.

Magnetic colloidal nanoformulations to remotely trigger mechanotransduction for osteogenic differentiation.

Nowadays, diseases associated with an ageing population, such as osteoporosis, require the development of new biomedical approaches to bone regeneration. In this regard, mechanotransduction has emerged as a discipline within the field of bone tissue engineering. Herein, we have tested the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs), obtained by the thermal decomposition method, with an average size of 13 nm, when exposed to the application of an external magnetic field for mechanotransduction in human bone marrow-derived mesenchymal stem cells (hBM-MSCs). The SPIONs were functionalized with an Arg-Gly-Asp (RGD) peptide as ligand to target integrin receptors on cell membrane and used in colloidal state. Then, a comprehensive and comparative bioanalytical characterization of non-targeted versus targeted SPIONs was performed in terms of biocompatibility, cell uptake pathways and mechanotransduction effect, demonstrating the osteogenic differentiation of hBM-MSCs. A key conclusion derived from this research is that when the magnetic stimulus is applied in the first 30 min of the in vitro assay, i.e., when the nanoparticles come into contact with the cell membrane surface to initiate endocytic pathways, a successful mechanotransduction effect is observed. Thus, under the application of a magnetic field, there was a significant increase in runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) gene expression as well as ALP activity, when cells were exposed to RGD-functionalized SPIONs, demonstrating osteogenic differentiation. These findings open new expectations for the use of remotely activated mechanotransduction using targeted magnetic colloidal nanoformulations for osteogenic differentiation by drug-free cell therapy using minimally invasive techniques in cases of bone loss.

Immune thrombocytopenia in systemic lupus erythematosus: Prevalence, risk factors, and a novel predictive model for risk assessment.

INTRODUCTION: Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality. OBJECTIVES: To describe which factors are associated with the presence of ITP in SLE patients. METHODS: Retrospective case-control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP. RESULTS: ITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-ß2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-ß2GP1 antibodies. CONCLUSION: SLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP.

Cell-Free DNA as a Biomarker at Diagnosis and Follow-Up in 256 B and T-Cell Lymphomas.

BACKGROUND: Cell-free DNA (cfDNA) analysis has become a promising tool for the diagnosis, prognosis, and monitoring of lymphoma cases. Until now, research in this area has mainly focused on aggressive lymphomas, with scanty information from other lymphoma subtypes. METHODS: We selected 256 patients diagnosed with lymphomas, including a large variety of B-cell and T-cell non-Hodgkin and Hodgkin lymphomas, and quantified cfDNA from plasma at the time of diagnosis. We further selected 49 large B-cell lymphomas (LBCL) and analyzed cfDNA levels at diagnosis (pre-therapy) and after therapy. In addition, we performed NGS on cfDNA and tissue in this cohort of LBCL. RESULTS: Lymphoma patients showed a statistically significant higher cfDNA concentration than healthy controls (mean 53.0 ng/mL vs. 5.6 ng/mL, p < 0.001). The cfDNA concentration was correlated with lymphoma subtype, lactate dehydrogenase, the International Prognostic Index (IPI) score, Ann Arbor (AA), and B-symptoms. In 49 LBCL cases, the cfDNA concentration decreased after therapy in cases who achieved complete response (CR) and increased in non-responders. The median cfDNA at diagnosis of patients who achieved CR and later relapsed was higher (81.5 ng/mL) compared with levels of those who did not (38.6 ng/mL). A concordance of 84% was observed between NGS results in tumor and cfDNA samples. Higher VAF in cfDNA is correlated with advanced stage and bulky disease. CONCLUSIONS: cfDNA analysis can be easily performed in almost all lymphoma cases. The cfDNA concentration correlated with the characteristics of the aggressiveness of the lymphomas and, in LBCL, with the response achieved after therapy. These results support the utility of cfDNA analysis as a complementary tool in the management of lymphoma patients.

Sex Differences in the Relationship between Personal, Psychological and Biochemical Factors with Blood Pressure in a Healthy Adult Mexican Population: A Cross-Sectional Study.

Hypertension is one of the main risk factors related to cardiovascular mortality, being the levels of blood pressure (BP) related to a variety of personal, anthropometric, biochemical and psychological variables; however, the study evaluating the association of all these factors in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a sample of relatively healthy subjects has not been performed. The aim of the study was to determine the main variables associated with SBP and DPB in a sample of relatively healthy subjects. A total of 171 participants were included, in which personal, anthropometric, positive and negative psychological variables and biochemical variables were measured. We observed that men showed higher levels of SBP and DBP than women, with more differences for SBP. Among the biochemical factors and SBP, we found that albumin and monocytes were positively correlated with it, while potassium, phosphorus and eosinophils were negatively correlated with it. Additionally, schooling was a constant variable negatively correlated with SBP in all samples (global, men and women). Among psychological variables, we observed that emotional perception was negatively correlated with SBP in men's and women's samples, while autonomy was positively correlated with SBP in the men's sample; however, their association was less when compared with the personal and biochemical variables included in the multivariate model. With regard to DBP, we observed that the biochemical variables, hemoglobin, sodium, uric acid and glucose, were positively correlated with DBP in the global sample, while chloride and BUN were negatively correlated with it. In addition, many personal and behavioral variables, including BMI, age and smoking consumption frequency, also correlated with DBP in the global sample. In conclusion, BP is affected by different factors, and these affect each sex differently.

Caracterización clínica-epidemiológica de COVID-19

Las epidemias y las pandemias son eventos de ocurrencia natural. La aparición de una nueva enfermedad infecciosa supone siempre una situación compleja, sobre todo si lo hace como una epidemia de extensión o gravedad significativa, con el objetivo de describir las características clínico-epidemiológicas en pacientes confirmados con COVID-19. Se realizó un estudio descriptivo y retrospectivo sobre las características clínico-epidemiológicas de los 161 pacientes diagnosticados con esta enfermedad, en el municipio Yara, de la provincia Granma durante el período comprendido de junio de 2020-2021. Se estudiaron las variables: edad, sexo, lugar de infección, presencia o no de síntomas y signos, antecedentes patológicos personales, área de salud y consejo popular. El 60,8% de los afectados fueron del sexo femenino con 98 pacientes y el grupo de 30-44 años de edad quedó representado por 50 pacientes (31.0%); en 150 casos, la transmisión fue mayormente autóctona (93,1%) y asintomática en 86 casos para el 53,4%. De los pacientes sintomáticos fueron las manifestaciones respiratorias, los principales síntomas con 70 casos para el 93,3%, 63 pacientes tenían antecedentes personales de hipertensión arterial (39,1%). El área de salud que más casos notificó fue "Luis Enrique de la Paz" con 106 pacientes para el 65,8% y Yara el consejo popular más afectado con 72 casos (44,7%), la mayoría de los pacientes fueron del sexo femenino, predominó la transmisión autóctona y la presentación asintomática. La epidemia en el municipio Yara se comportó similar al resto del país.

Epidemics and pandemics are naturally occurring events. The emergence of a new infectious disease is always a complex situation, especially when it occurs as an epidemic of significant spread or severity. The aim of this study was to describe the clinical-epidemiologic characteristics of patients confirmed with COVID-19. A descriptive and retrospective study was carried out on the clinical-epidemiological characteristics of 161 patients diagnosed with this disease, in the municipality of Yara, province of Granma. The following variables were studied: age, sex, site of infection, presence or not of symptoms and signs, personal pathological antecedents, health area and locality. Out of the total, 98 patients were female (60.8%), and the age group 30-44 years was represented by 50 patients (31.0%). Transmission was generally autochthonous in 150 cases (93.1%), and asymptomatic in 86 cases (53.4%). Among the symptomatic patients, respiratory manifestations were the main symptom in 70 cases (93.3%). Also, 63 patients had a personal medical history of hypertension (39.1%). Luis Enrique de la Paz was the health area that reported the most cases with 106 patients (65.8%), and Yara was the most affected locality with 72 cases (44.7%). The majority of patients were female; and autochthonous transmission and asymptomatic presentation predominated. The epidemic in Yara municipality behaved alike in the whole country.

Epidemias e pandemias são eventos naturais. O surgimento de uma nova doença infecciosa é sempre uma situação complexa, especialmente se for uma epidemia de extensão ou gravidade significativa, com o objetivo de descrever as características clínico-epidemiológicas em pacientes confirmados com COVID-19. Foi realizado um estudo descritivo e retrospectivo sobre as características clínico-epidemiológicas dos 161 pacientes diagnosticados com essa doença, no município de Yara, província de Granma, no período de junho de 2020 a 2021, as variáveis foram estudadas: idade, sexo, local de infecção, presença ou não de sintomas e sinais, história patológica pessoal, área de saúde e conselho popular. O 60,8% dos acometidos eram do sexo feminino com 98 pacientes e a faixa etária de 30 a 44 anos foi representada por 50 pacientes (31,0%); Em 150 casos, a transmissão foi predominantemente autóctone (93,1%) e assintomática em 86 casos para 53,4%, entre os sintomáticos foram manifestações respiratórias, sendo os principais sintomas 70 casos para 93,3%, 63 pacientes tinham história pessoal de hipertensão arterial (39,1%). A área de saúde que mais registrou casos foi "Luis Enrique de la Paz" com 106 pacientes para 65,8% e Yara o município popular mais afetado com 72 casos (44,7%), a maioria dos pacientes era do sexo feminino, de transmissão autóctone e apresentação assintomática. A epidemia no município de Yara se comportou de forma semelhante ao resto do país.

Mortalidad por tumores malignos

El cáncer constituye un serio problema de salud para la humanidad, ocupa la primera causa de morbimortalidad a nivel mundial y una de las principales causas de muerte en Cuba. Se realizó un estudio descriptivo, retrospectivo, con el objetivo de describir la mortalidad por tumores malignos en el municipio Yara, en el período enero-junio de 2022. El universo quedó constituido por 262 fallecidos y la muestra del estudio lo constituyeron los 54 fallecidos con código de causa básica de muerte por tumores malignos en el período de tiempo antes señalado, datos obtenidos a través del registro primario de defunciones del Departamento de estadística del Centro Municipal de Higiene y Epidemiología. Se utilizaron métodos de estadística descriptiva principalmente el porcentaje, se confeccionaron cuadros de distribución de frecuencia, Se determinaron las tasas de mortalidad bruta y por causa. En el período analizado ocurrieron 54 defunciones por tumores malignos, el grupo de edad más afectado fueron los mayores de 75, predominó el sexo masculino, el área de salud "Luis Enrique de la Paz Reina" aportó el mayor número de fallecidos, la zona rural prevaleció sobre la urbana, las localizaciones más frecuentes: próstata, pulmón, colon-recto, el mayor número de las defunciones ocurrieron en el domicilio. En el municipio Yara los tumores malignos ocupan la segunda causa de mortalidad, el mayor número de fallecidos ocurrió en pacientes de la tercera edad, el tumor de próstata fue el más representativo.

Cancer represents a serious health problem for humanity. It occupies the first cause of morbimortality world wide, and one of the main causes of death in Cuba. A descriptive, retrospective study was conducted in the municipality of Yara, in the period January-June 2022.The objective of this research was to describe mortality due to malignant tumors. The universe was constituted by 262 deceased. The sample of the study was constituted by the 54 deceased with code of the basic cause of death by malignant tumors in the aforementioned period. These data were obtained through the primary register of deaths of the Department of Statistics of the Municipal Center of Hygiene and Epidemiology. Descriptive statistical methods were used, mainly percentages. Frequency distribution tables were prepared, and crude mortality rates and mortality rates by cause were determined. During the period analyzed, 54 deaths occurred due to malignant tumors. The most affected age group was those older than 75 years, the male sex predominated. The "Luis Enrique de la Paz Reina" health area contributed the highest number of deaths. The rural area prevailed over the urban area. The most frequent locations were: prostate, lung and colon-rectum. The highest number of deaths occurred at home. In the municipality of Yara, malignant tumors are the second cause of mortality. Moreover, the highest number of deaths occurred in elderly patients, and prostate tumor was the most representative.

O cancro representa um grave problema de saúde para a humanidade. Ocupa a primeira causa de morbimortalidade em todo o mundo, e uma das principais causas de morte em Cuba. Foi realizado um estudo descritivo e retrospetivo no município de Yara, no período de janeiro a junho de 2022, como objetivo de descrever a mortalidade por tumores malignos. O universo foi constituído por 262 falecidos. A amostra do estudo foi constituída pelos 54 falecidos com código da causa básica de morte por tumores malignos no período supracitado. Estes dados foram obtidos através do registo primário de óbitos do Departamento de Estatística do Centro Municipal de Higiene e Epidemiologia. Foram utilizados métodos estatísticos descritivos, principalmente percentuais. Foram elaboradas tabelas de distribuição de freqüência e determinadas as taxas brutas de mortalidade e as taxas de mortalidade por causas. Durante o período analisado, ocorreram 54 mortes por tumores malignos, sendo o grupo etário mais afetado o dos maiores de 75 anos e predominando o sexo masculino. A área de saúde "Luis Enrique de la Paz" foi a que contribuiu com o maior número de mortes. A zona rural prevaleceu sobre a zona urbana. As localizações mais frequentes foram: próstata, pulmão e cólon-reto. O maior número de mortes ocorreu no domicílio. No município de Yara, os tumores malignos são a segunda causa de mortalidade. Alémdisso, o maior número de óbitos ocorreu em pacientes idosos, sendo o tumor de próstata o mais representativo.

[Deshabituación al consumo de tabaco desde las oficinas de farmacia mediante planes multidisciplinares.] / Smoking cessation from pharmacies through multidisciplinary plans.

OBJECTIVE: Tobacco is the most consumed drug in the world and each year it causes the death of more than eight million people. The pharmacist is the healthcare professional most accessible to smokers, therefore they are essential in the treatment and prevention of smoking. The study´s aim was to implement a multidisciplinary anti-smoking program in a pharmacy and evaluate the effect of pharmaceutical care on smoking cessation. METHODS: The study was carried out in two army pharmacies located in Spain and Lebanon in which a smoking cessation plan was developed in 2020 and 2021. As the requirements for participants selection, all those patients in the area of influence of pharmacies that agreed to participate in the program were accepted, with a sample size of thirty-eight people. The patients underwent an addiction, motivation and smoking habit test, and a descriptive analysis of the data provided was carried out, using the chi-square test for the comparison of values. Only those with a probability value less than 0.05 are considered statistically significant. RESULTS: The multidisciplinary work allowed treatment with prescription drugs. The study shows that 63% of patients managed to quit smoking. CONCLUSIONS: Pharmacies can implement and lead smoking cessation programs that facilitate cessation and adherence to treatments. The classification of patients according to their history of smoking is key to carrying out an adequate and personalized treatment.

OBJETIVO: El tabaco es la droga más consumida en el mundo y cada año provoca la muerte de más de ocho millones de personas. El farmacéutico es el profesional de la salud más accesible a los fumadores, por lo que es fundamental en el tratamiento y prevención del tabaquismo. El objetivo de este estudio fue implantar un programa antitabaco multidisciplinar en una oficina de farmacia y evaluar el efecto de la atención farmacéutica en la cesación del consumo de tabaco. METODOS: El estudio se realizó en dos farmacias del Ejército de Tierra situadas en España y Líbano en las que se desarrolló un plan de deshabituación al consumo de tabaco durante los años 2020 y 2021. Como criterio de selección de participantes se aceptó a todos aquellos pacientes del área de influencia de las farmacias que aceptasen participar en el programa, siendo el tamaño muestral de treinta y ocho personas. Los pacientes se sometieron a test de adicción, motivación y hábito de consumo de tabaco, y se realizó un análisis descriptivo de los datos aportados, usando el test de chi-cuadrado para la comparación de valores, considerándose estadísticamente significativos solo aquellos con un valor de probabilidad inferior a 0,05. RESULTADOS: El trabajo multidisciplinar permitió el tratamiento con medicamentos mediante prescripción médica. El 63% de los pacientes del estudio consiguieron dejar de fumar. CONCLUSIONES: Las oficinas de farmacia pueden implantar y liderar programas de deshabituación al consumo de tabaco que faciliten la cesación y la adhesión a los tratamientos. La clasificación de los pacientes según su historial de tabaquismo resulta clave para realizar un tratamiento adecuado y personalizado.

Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A Case-Control Study.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI).

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.

Deshabituación al consumo de tabaco desde las oficinas de farmacia mediante planes multidisciplinares / Smoking cessation from pharmacies through multidisciplinary plans

Fundamentos: El tabaco es la droga más consumida en el mundo y cada año provoca la muerte de más de ocho millones depersonas. El farmacéutico es el profesional de la salud más accesible a los fumadores, por lo que es fundamental en el tratamientoy prevención del tabaquismo. El objetivo de este estudio fue implantar un programa antitabaco multidisciplinar en una oficina defarmacia y evaluar el efecto de la atención farmacéutica en la cesación del consumo de tabaco. Métodos: El estudio se realizó en dos farmacias del Ejército de Tierra situadas en España y Líbano en las que se desarrolló unplan de deshabituación al consumo de tabaco durante los años 2020 y 2021. Como criterio de selección de participantes se aceptó atodos aquellos pacientes del área de influencia de las farmacias que aceptasen participar en el programa, siendo el tamaño muestralde treinta y ocho personas. Los pacientes se sometieron a test de adicción, motivación y hábito de consumo de tabaco, y se realizóun análisis descriptivo de los datos aportados, usando el test de chi-cuadrado para la comparación de valores, considerándoseestadísticamente significativos solo aquellos con un valor de probabilidad inferior a 0,05. Resultados: El trabajo multidisciplinar permitió el tratamiento con medicamentos mediante prescripción médica. El 63% de lospacientes del estudio consiguieron dejar de fumar. Conclusiones: Las oficinas de farmacia pueden implantar y liderar programas de deshabituación al consumo de tabaco quefaciliten la cesación y la adhesión a los tratamientos. La clasificación de los pacientes según su historial de tabaquismo resulta clavepara realizar un tratamiento adecuado y personalizado.(AU)

Background: Tobacco is the most consumed drug in the world and each year it causes the death of more than eight millionpeople. The pharmacist is the healthcare professional most accessible to smokers, therefore they are essential in the treatment andprevention of smoking. The study´s aim was to implement a multidisciplinary anti-smoking program in a pharmacy and evaluate theeffect of pharmaceutical care on smoking cessation. Methods: The study was carried out in two army pharmacies located in Spain and Lebanon in which a smoking cessation plan wasdeveloped in 2020 and 2021. As the requirements for participants selection, all those patients in the area of influence of pharmaciesthat agreed to participate in the program were accepted, with a sample size of thirty-eight people. The patients underwent an addiction,motivation and smoking habit test, and a descriptive analysis of the data provided was carried out, using the chi-square test for thecomparison of values. Only those with a probability value less than 0.05 are considered statistically significant.Results: The multidisciplinary work allowed treatment with prescription drugs. The study shows that 63% of patients managedto quit smoking. Conclusions: Pharmacies can implement and lead smoking cessation programs that facilitate cessation and adherence to treat-ments. The classification of patients according to their history of smoking is key to carrying out an adequate and personalized treatment.(AU)

Genomic Regions Associated with Resistance to Three Rusts in CIMMYT Wheat Line "Mokue#1".

Understanding the genetic basis of rust resistance in elite CIMMYT wheat germplasm enhances breeding and deployment of durable resistance globally. "Mokue#1", released in 2023 in Pakistan as TARNAB Gandum-1, has exhibited high levels of resistance to stripe rust, leaf rust, and stem rust pathotypes present at multiple environments in Mexico and Kenya at different times. To determine the genetic basis of resistance, a F5 recombinant inbred line (RIL) mapping population consisting of 261 lines was developed and phenotyped for multiple years at field sites in Mexico and Kenya under the conditions of artificially created rust epidemics. DArTSeq genotyping was performed, and a linkage map was constructed using 7892 informative polymorphic markers. Composite interval mapping identified three significant and consistent loci contributed by Mokue: QLrYr.cim-1BL and QLrYr.cim-2AS on chromosome 1BL and 2AS, respectively associated with stripe rust and leaf rust resistance, and QLrSr.cim-2DS on chromosome 2DS for leaf rust and stem rust resistance. The QTL on 1BL was confirmed to be the Lr46/Yr29 locus, whereas the QTL on 2AS represented the Yr17/Lr37 region on the 2NS/2AS translocation. The QTL on 2DS was a unique locus conferring leaf rust resistance in Mexico and stem rust resistance in Kenya. In addition to these pleiotropic loci, four minor QTLs were also identified on chromosomes 2DL and 6BS associated with stripe rust, and 3AL and 6AS for stem rust, respectively, using the Kenya disease severity data. Significant decreases in disease severities were also demonstrated due to additive effects of QTLs when present in combinations.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Large-scale production of superparamagnetic iron oxide nanoparticles by flame spray pyrolysis: In vitro biological evaluation for biomedical applications.

Despite the large number of synthesis methodologies described for superparamagnetic iron oxide nanoparticles (SPIONs), the search for their large-scale production for their widespread use in biomedical applications remains a mayor challenge. Flame Spray Pyrolysis (FSP) could be the solution to solve this limitation, since it allows the fabrication of metal oxide nanoparticles with high production yield and low manufacture costs. However, to our knowledge, to date such fabrication method has not been upgraded for biomedical purposes. Herein, SPIONs have been fabricated by FSP and their surface has been treated to be subsequently coated with dimercaptosuccinic acid (DMSA) to enhance their colloidal stability in aqueous media. The final material presents high quality in terms of nanoparticle size, homogeneous size distribution, long-term colloidal stability and magnetic properties. A thorough in vitro validation has been performed with peripheral blood cells and mesenchymal stem cells (hBM-MSCs). Specifically, hemocompatibility studies show that these functionalized FSP-SPIONs-DMSA nanoparticles do not cause platelet aggregation or impair basal monocyte function. Moreover, in vitro biocompatibility assays show a dose-dependent cellular uptake while maintaining high cell viability values and cell cycle progression without causing cellular oxidative stress. Taken together, the results suggest that the FSP-SPIONs-DMSA optimized in this work could be a worthy alternative with the benefit of a large-scale production aimed at industrialization for biomedical applications.

B cell receptor-induced protein dynamics and the emerging role of SUMOylation revealed by proximity proteomics.

Successful B cell activation, which is critical for high-affinity antibody production, is controlled by the B cell antigen receptor (BCR). However, we still lack a comprehensive protein-level view of the very dynamic multi-branched cellular events triggered by antigen binding. Here, we employed APEX2 proximity biotinylation to study antigen-induced changes, 5-15 min after receptor activation, at the vicinity of the plasma membrane lipid rafts, wherein BCR enriches upon activation. The data reveals dynamics of signaling proteins, as well as various players linked to the subsequent processes, such as actin cytoskeleton remodeling and endocytosis. Interestingly, our differential expression analysis identified dynamic responses in various proteins previously not linked to early B cell activation. We demonstrate active SUMOylation at the sites of BCR activation in various conditions and report its functional role in BCR signaling through the AKT and ERK1/2 axes.

Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram.

BACKGROUND: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS: The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).

Method for siRNA delivery in retina explants.

Several barriers prevent the delivery of nucleic acids to the retina and limit the application of established technologies, such as RNA interference (RNAi), in the study of retinae biology. Organotypic culture of retinal explants is a convenient method to decrease the complexity of the biological environment surrounding the retina while preserving most of its physiological features. Nevertheless, eliciting significant, non-toxic RNAi in retina explants is not straightforward. Retina explants are mainly constituted by neurons organized in discrete circuits embedded within a complex 3D extracellular matrix. About 70% of these neurons are post-mitotic ciliated cells that respond to light. Unfortunately, like the other cells of the retina, photoreceptors are refractory to transfection, and a toxic delivery of nucleic acid often results in permanent cell loss. RNAi has been applied to retina explants using electroporation, viral, and non-viral vectors but with reproducible, poor gene silencing efficiency. In addition, only a few superficial cells can be transduced/transfected in adult retina explants. Therefore, viruses are often injected into the eye of embryos prior to excision of the retina. However, embryonic explants are not the best model to study most retina diseases since even if they are viable for several weeks, the pathological phenotype often appears later in development. We describe a robust and straightforward method to elicit significant RNAi in adult retina explant using Reverse Magnetofection. This transfection method offers a simple tool for non-toxic gene knockdown of specific genes in adult retina explants by using cationic magnetic nanoparticles (MNPs) to complex and deliver short interfering-RNAs (siRNA) in retina cells under the action of a magnetic field.

Integrated transcriptomics and metabolomics analysis reveals the biomolecular mechanisms associated to the antitumoral potential of a novel silver-based core@shell nanosystem.

A combination of omics techniques (transcriptomics and metabolomics) has been used to elucidate the mechanisms responsible for the antitumor action of a nanosystem based on a Ag core coated with mesoporous silica on which transferrin has been anchored as a targeting ligand against tumor cells (Ag@MSNs-Tf). Transcriptomics analysis has been carried out by gene microarrays and RT-qPCR, while high-resolution mass spectrometry has been used for metabolomics. This multi-omics strategy has enabled the discovery of the effect of this nanosystem on different key molecular pathways including the glycolysis, the pentose phosphate pathway, the oxidative phosphorylation and the synthesis of fatty acids, among others.