Proliferative Effects of Mesenchymal Stromal Cells on Neuroblastoma Cell Lines: Are They Tumor Promoting or Tumor Inhibiting?

BACKGROUND: Neuroblastoma is a common pediatric malignancy with poor survival for high-risk disease. Mesenchymal stromal cells (MSCs) have innate tumor-homing properties, enabling them to serve as a cellular delivery vehicle, but MSCs have demonstrated variable effects on tumor growth. We compared how placental MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) affect proliferation of neuroblastoma (NB) cells in vitro. METHODS: Indirect co-culture assessed proliferative effects of 18 MSCs (early-gestation PMSCs (n = 9), term PMSCs (n = 5), BM-MSCs (n = 4) on three high-risk NB cell lines (NB1643, SH-SY5Y, and CHLA90). Controls were NB cells cultured in media alone. Proliferation was assessed using MTS assay and measured by fold change (fc) over controls. PMSCs were sub-grouped by neuroprotective effect: strong (n = 7), intermediate (n = 3), and weak (n = 4). The relationship between MSC type, PMSC neuroprotection, and PMSC gestational age on NB cell proliferation was assessed. RESULTS: NB cell proliferation varied between MSC groups. BM-MSCs demonstrated lower proliferative effects than PMSCs (fc 1.18 vs 1.44, p < 0.001). Neither gestational age nor neuroprotection significantly predicted degree of proliferation. Proliferative effects of MSCs varied among NB cell lines. BM-MSCs had less effect on CHLA90 (fc 1.01) compared to NB1643 (fc 1.33) and SH-SY5Y (fc 1.20). Only NB1643 showed a difference between early and term PMSCs (p = 0.04). CONCLUSION: Effects of MSCs on NB cell proliferation vary by MSC source and NB cell line. BM-MSCs demonstrated lower proliferative effects than most PMSCs. MSC neuroprotection was not correlated with proliferation. Improved understanding of MSC proliferation-promoting mechanisms may provide valuable insight into selection of cells best suited as drug delivery vehicles. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Original Research.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico.

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers.

Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.

Interspecies Brain PBPK Modeling Platform to Predict Passive Transport through the Blood-Brain Barrier and Assess Target Site Disposition.

The high failure rate of central nervous system (CNS) drugs is partly associated with an insufficient understanding of target site exposure. Blood-brain barrier (BBB) permeability evaluation tools are needed to explore drugs' ability to access the CNS. An outstanding aspect of physiologically based pharmacokinetic (PBPK) models is the integration of knowledge on drug-specific and system-specific characteristics, allowing the identification of the relevant factors involved in target site distribution. We aimed to qualify a PBPK platform model to be used as a tool to predict CNS concentrations when significant transporter activity is absent and human data are sparse or unavailable. Data from the literature on the plasma and CNS of rats and humans regarding acetaminophen, oxycodone, lacosamide, ibuprofen, and levetiracetam were collected. Human BBB permeability values were extrapolated from rats using inter-species differences in BBB surface area. The percentage of predicted AUC and Cmax within the 1.25-fold criterion was 85% and 100% for rats and humans, respectively, with an overall GMFE of <1.25 in all cases. This work demonstrated the successful application of the PBPK platform for predicting human CNS concentrations of drugs passively crossing the BBB. Future applications include the selection of promising CNS drug candidates and the evaluation of new posologies for existing drugs.

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma.

BACKGROUND/AIM: Neuroblastoma is a common childhood cancer with poor survival for children with high-risk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible. MATERIALS AND METHODS: The neuroblastoma cell line NB1643 was obtained from the Children's Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x106 NB1643 cells suspended in 10 µl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis. RESULTS: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses. CONCLUSION: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

BACKGROUND: COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. OBJECTIVE: Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. METHODOLOGY: In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3 months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. RESULTS: We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. CONCLUSION: This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Fruit quality and shelf-life of Sardinian tomato (Solanum lycopersicum L.) landraces.

The conservation and characterization of landraces have key roles in the safeguarding and valorization of agrobiodiversity. Indeed, these plant genetic resources represent an important crop heritage with quality and sensory characteristics that can be of great use to consumers and industry. In addition, the preservation of genetic resources from the risk of progressive genetic erosion, and the enhancement of their potential can contribute to food security and improve the nutritional value of food. Accordingly, this study aimed to investigate a collection of Sardinian tomato landraces for parameters that have determinant roles in evaluating their responses to conservation, and therefore to consumer acceptance. Six Sardinian landraces and two commercial varieties were cultivated in a two-years off-season trial, harvested at two different maturity stages (turning, red-ripe) and characterized using 14 fruit-related quality parameters that define the marketability, nutritional value, and flavor of the fruit. Data were collected at intervals of 10 days, starting from the harvest date and over 30 days of storage under refrigeration. The simultaneous analysis of all the qualitative characteristics for the different genotypes allowed to clearly differentiate the local varieties from the commercial varieties and a few landraces emerged for their satisfactory performances, e.g. "Tamatta kaki" ad "Tamatta groga de appiccai". In particular, the "Tamatta groga de appiccai" showed satisfactory lycopene content at marketable stages (average 5.65 mg 100g-1 FF), a peculiar orange-pink color with the highest hue angle values (range: H°T0 = 72.55-H°T30 = 48.26), and the highest firmness among the landraces of the red-ripe group (range: EpT0 = 1.64-EpT30 = 0.54 N mm-1). These results highlight the potential of some of the Sardinian tomato landraces for developing new varieties or promoting their direct valorization in local markets and could considerably increase the effectiveness and efficiency of agrobiodiversity conservation strategies.

Percepción y satisfacción de estudiantes de Enfermería con la educación virtual en época de COVID-19

Objetivo: Analizar la percepción y la satisfacción con la educación en modalidad virtual de los estudiantes de la carrera de Licenciatura en Enfermería de una institución de educación superior de carácter público de la Ciudad Autónoma de Buenos Aires, Argentina, durante el segundo semestre de 2021. Metodología: Estudio analítico, transversal y cuantitativo. La muestra estuvo compuesta por 121 estudiantes, seleccionados mediante muestreo no probabilístico, quienes respondieron un instrumento conformado por 24 preguntas . Resultados: Los encuestados fueron mayormente de sexo femenino (84.30 %), con media de edad de 29.2 años (DE: 8), de tercer año (55.37 %) y con hijos (44.63 %). Respecto a la percepción sobre la modalidad virtual se halló que las clases fueron consideradas como motivantes para el aprendizaje (66.94 %), los alumnos pudieron mantener la atención entre un 75-99 % del tiempo durante la clase (38.84 %), una baja cantidad pudo realizar todas las consultas al docente (16.52 %) y la mayoría sintió nerviosismo ante la evaluación remota al mismo nivel que su contraparte presencial (52.89 %). La satisfacción global con la modalidad fue puntuada con una media de 6.9 sobre 10 y el 75.20 % los encuestados desea continuar con clases virtuales . Conclusiones: La satisfacción fue caracterizada como media. Las variables que se relacionaron con una mayor satisfacción con la educación remota son la tenencia de hijos, la mayor edad, la creencia de que se hubiese aprendido más con clases presenciales, el tiempo que perciben que pueden mantener la atención en clases virtuales, la baja sensación de nerviosismo ante la evaluación virtual y la ausencia de dificultades para la conexión a las clases sincrónicas.

Objetivo: Analisar a percepção e a satisfação com a educação na modalidade virtual dos alunos da Licenciatura em Enfermagem de uma instituição pública de ensino superior da Cidade Autônoma de Buenos Aires, Argentina durante o segundo semestre de 2021. Metodologia: Estudo analítico, transversal e quantitativo. A amostra foi composta por 121 alunos, selecionados por amostragem não probabilística, que responderam a um instrumento composto por 24 questões. Resultados: Os participantes eram maioritariamente do sexo feminino (84,30 %), com idade média de 29,2 anos (DP: 8), cursando o terceiro ano (55,37 %) e com filhos (44,63 %). Quanto à percepção sobre a modalidade virtual, constatou-se que as aulas foram consideradas em sua maioria com motivadoras para a aprendizagem (66,94 %), os alunos conseguiram manter a atenção entre 75- 99 % do tempo durante a aula (38,84 %), um baixo número conseguiu fazer todas as consultas ao professor (16,52 %) e a maioria se sentiu nervosa com a avaliação à distância no mesmo nível da presencial (52,89 %). A satisfação global com a modalidade foi pontuada com média de 6,9 sobre 10 e 75,20 % dos entrevistados desejam continuar com as aulas virtuais. Conclusões: A satisfação caracterizou-se como média. As variáveis que se relacionaram com a maior satisfação com o ensino a distância são ter filhos, a idade, a crença de que aprenderiam mais com as aulas presenciais, o tempo que percebem que conseguem manter a atenção nas aulas virtuais, a baixa sensação de nervosismo perante a avaliação virtual e a ausência de dificuldades para a conexão nas aulas síncronas.

Objective: To analyze the perception and satisfaction with education in virtual modality of Nursing Bachelor's degree students from a public higher education institution in the Autonomous City of Buenos Aires, Argentina during the second semester of 2021. Methods: Analytical, cross-sectional, and quantitative study. The sample consisted of 121 students, selected by non-probabilistic sampling, who answered an instrument made up of 24 questions. Results: The respondents were mostly female (84.30 %), with a mean age of 29.2 years (SD: 8), in their third year (55.37 %) and with children (44.63 %). Regarding the perception of the virtual modality, it was found that the classes were mostly considered as a motivating factor for learning (66.94 %), students were able to maintain their attention between 75-99 % of the time during the class (38.84 %), a low number were able to make all consultations with the teacher (16.52 %) and most of them felt nervousness before the remote evaluation at the same level as their face-to-face counterpart (52.89 %). Overall satisfaction with the modality was rated with an average of 6.9 out of 10 and 75.20 % of respondents would like to continue with virtual classes. Conclusions: Satisfaction was characterized as average. The variables that were associated with greater satisfaction with distance education are having children, older age, the belief that they would have learned more with face-to-face classes, the time they perceive they can maintain their attention in virtual classes, the low feeling of nervousness before the virtual evaluation, and the absence of difficulties in connecting to synchronous classes.

Simultaneous improvement of grain yield and grain protein concentration in durum wheat by using association tests and weighted GBLUP.

KEY MESSAGE: Simultaneous improvement for GY and GPC by using GWAS and GBLUP suggested a significant application in durum wheat breeding. Despite the importance of grain protein concentration (GPC) in determining wheat quality, its negative correlation with grain yield (GY) is still one of the major challenges for breeders. Here, a durum wheat panel of 200 genotypes was evaluated for GY, GPC, and their derived indices (GPD and GYD), under eight different agronomic conditions. The plant material was genotyped with the Illumina 25 k iSelect array, and a genome-wide association study was performed. Two statistical models revealed dozens of marker-trait associations (MTAs), each explaining up to 30%. phenotypic variance. Two markers on chromosomes 2A and 6B were consistently identified by both models and were found to be significantly associated with GY and GPC. MTAs identified for phenological traits co-mapped to well-known genes (i.e., Ppd-1, Vrn-1). The significance values (p-values) that measure the strength of the association of each single nucleotide polymorphism marker with the target traits were used to perform genomic prediction by using a weighted genomic best linear unbiased prediction model. The trained models were ultimately used to predict the agronomic performances of an independent durum wheat panel, confirming the utility of genomic prediction, although environmental conditions and genetic backgrounds may still be a challenge to overcome. The results generated through our study confirmed the utility of GPD and GYD to mitigate the inverse GY and GPC relationship in wheat, provided novel markers for marker-assisted selection and opened new ways to develop cultivars through genomic prediction approaches.

Opinions, Attitudes and Factors Related to SARS-CoV-2 Vaccine Uptake in Eight South American Countries.

This article presents attitudes and practices regarding COVID-19 vaccination in the South American population. The study collected data from a self-administered survey distributed through social media platforms between February and April 2022 (N = 6555). The survey included questions related to participants' sociodemographic background, flu vaccination practices, sources of information about COVID-19, and opinions regarding pandemic management and vaccination against SARS-CoV-2. The respondents agreed with the statement that COVID-19 vaccines were necessary (86.4%), effective (79.8%), safe (79.1%), and should be mandatory (64%). Overall, 83.4% accepted vaccination and 12.3% refused it completely. Main rejection reasons were safety (65.8%) and efficacy (54.9%) issues, and rushed development and approvals (49.1%). Vaccine uptake was associated with being ≥60 years, being a healthcare worker, previous influenza vaccine uptake, adherence to preventive measures, the death of ≥1 close people from COVID-19, and being informed through mass media or health authorities' channels. Vaccine uptake inversely correlated with male gender, low educational level, and use of closed social networks for COVID-19 information purposes. This study provides valuable insights into COVID-19 vaccination attitudes and practices in South America that may be used to promote vaccine uptake in the region. Higher COVID-19 vaccination acceptance among people with previously acquired prevention habits reinforces the importance of routine health promotion strategies.

Periodontitis exacerbation during pregnancy in mice: Role of macrophage migration inhibitory factor as a key inductor.

OBJECTIVE: The present study was designed to investigate the role of macrophage migration inhibitory factor (MIF) in the exacerbation of pregestational periodontal disease (PGPD). BACKGROUND: Periodontitis (PT) is a severe stage of periodontal disease characterized by inflammation of the supporting tissues of the teeth, which usually worsens during pregnancy. MIF is a proinflammatory cytokine that is significantly elevated in periodontitis, both at the beginning and at the end of pregnancy. Although periodontitis usually presents with greater severity during pregnancy, the participation of MIF in the evolution of periodontitis has not been established. METHODS: To analyze the relevance of MIF in the exacerbation of PGPD, we employed a model of PGPD in WT and Mif-/- mice, both with a BALB/c genetic background. PT was induced with nylon suture ligatures placed supramarginally around the second upper right molar. For PGPD, PT was induced 2 weeks before mating. We evaluated histological changes and performed histometric analysis of the clinical attachment loss, relative expression of MMP-2 and MMP-13 by immunofluorescence, and relative expression of the cytokines mif, tnf-α, ifn-γ, and il-17 by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our data revealed that periodontal tissue from PGPD WT mice produced a twofold increase in MIF compared with PT WT mice. Moreover, the evolution of periodontitis in Mif-/- mice was less severe than in PGDP WT mice. Periodontal tissue from Mif-/- mice with PGPD produced 80% less TNF-α and no IFN-γ, as well as 50% lower expression of matrix metalloproteinase (MMP)-2 and 25% less MMP-13 compared to WT PGDP mice. CONCLUSIONS: Our study suggests that MIF plays an important role in the exacerbation of periodontitis during pregnancy and that MIF is partially responsible for the inflammation associated with the severity of periodontitis during pregnancy.

Improving the efficiency of free kappa light chains as diagnostic biomarker of Multiple Sclerosis by using a novel algorithm.

BACKGROUND: Intrathecal immunoglobulin synthesis (ITS) plays a crucial role in the diagnosis of multiple sclerosis (MS). Traditionally, the gold standard method for detecting ITS has been through the analysis of oligoclonal bands (OCB). However, the paradigm has shifted with the introduction of the free kappa light chains (FKLC) method. In fact, a recent consensus recommends evaluating FKLC index (FKLCi) as the primary approach and reserving oligoclonal bands with borderline results. The objective of our study is to investigate the diagnostic efficiency of combining FKLC with other methods to predict ITS while minimizing the reliance on OCB. METHODS: A total of 192 patients were included in the study, consisting of 145 individuals diagnosed with multiple sclerosis (pwMS) and 46 with other neurological diseases (controls). Among the MS cases, 100 patients were assigned to the Training Cohort (TC), while an external Validation Cohort (VC) comprised of 45 MS patients was established. Diagnostic efficiency was assessed for FKLCi, OCB, Link index, and the Reiber formula for IgG and FKLC. Optimal cutoff values for Link index and FKLCi were also determined. The last procedure was developed for diverse algorithms using the parameters mentioned above, which included the optimal cutoffs previously obtained. The calculations were conducted independently for both the TC and the VC, as well as for a composite cohort formed by combining data from all patients (OC) RESULTS: One algorithm, named KRO, was developed based on the determination of FKLCi and Reiber Formula as the primary diagnostic parameters. For cases where the FKLCi result was mildly increased, OCB was utilized as a supplementary test. The KRO algorithm demonstrated superior diagnostic accuracy in the OC (89%), resulting in a reduction of OCB consumption by 91%. DISCUSSION: The KRO algorithm demonstrated superior sensitivity and accuracy although lower specificity and NPV compared to the use of FKLCi and OCB alone. The present research aligns with the new consensus recommendations regarding the diagnostic approach. Our findings indicate that employing a combined marker approach via KRO could prove to be a proficient screening tool for multiple sclerosis. This approach also holds the potential to address inherent limitations associated with each individual marker. However, to further validate and solidify the efficacy of our algorithm, additional studies involving larger cohorts are warranted.

CBD Inhibits In Vivo Development of Human Breast Cancer Tumors.

Inflammation is a critical component of cancer development. Previously, we showed in vitro that IL-1ß treatment of non-invasive human breast cancer MCF-7 cells promoted their transition to a malignant phenotype (6D cells). This epithelial-mesenchymal transition was reverted by exposure to cannabidiol (CBD). We show in a murine model that subcutaneous inoculation of 6D cells induced formation and development of tumors, the cells of which keep traits of malignancy. These processes were interrupted by administration of CBD under two schemes: therapeutic and prophylactic. In the therapeutic scheme, 6D cells inoculated mice developed tumors that reached a mean volume of 540 mm3 at 45 days, while 50% of CBD-treated mice showed gradual resorption of tumors. In the prophylactic scheme, mice were pre-treated for 15 days with CBD before cells inoculation. The tumors formed remained small and were eliminated under continuous CBD treatment in 66% of the animals. Histological and molecular characterization of tumors, from both schemes, revealed that CBD-treated cells decreased the expression of malignancy markers and show traits related with apoptosis. These results confirm that in vivo CBD blocks development of breast cancer tumors formed by cells induced to malignancy by IL-1ß, endorsing its therapeutic potential for cancer treatment.

Screening for late-onset Pompe disease in Internal Medicine departments in Spain.

BACKGROUND: The screening of high-risk populations using dried blood spots (DBS) has allowed the rapid identification of patients with Pompe disease, mostly in Neurology departments. The aim of the study was to determine the prevalence of late-onset Pompe disease (LOPD) among patients not previously diagnosed or tested for this entity despite presenting possible signs or symptoms of the disease in Internal Medicine departments in Spain. METHODS: This epidemiological, observational, cross-sectional, multicenter study included a single cohort of individuals with clinical suspicion of LOPD seen at Internal Medicine departments in Spain. The diagnosis of LOPD was initially established on the basis of the result of DBS. If decreased enzyme acid-alpha-1,4-glucosidase (GAA) activity was detected in DBS, additional confirmatory diagnostic measurements were conducted, including GAA activity in lymphocytes, fibroblasts, or muscle and/or genetic testing. RESULTS: The diagnosis of LOPD was confirmed in 2 out of 322 patients (0.6%). Reasons for suspecting LOPD diagnosis were polymyositis or any type of myopathy of unknown etiology (in one patient), and asymptomatic or pauci-symptomatic hyperCKemia (in the other). The time between symptom onset and LOPD diagnosis was 2.0 and 0.0 years. Both patients were asymptomatic, with no muscle weakness. Additionally, 19.7% of the non-LOPD cases received an alternative diagnosis. CONCLUSIONS: Our study highlights the existence of a hidden population of LOPD patients in Internal Medicine departments who might benefit from early diagnosis and early initiation of potential treatments.

Colonización genitourinaria por Streptococcus agalactiae y perfil de sensibilidad en mujeres gestantes

Introducción: Streptococcus agalactiae, también conocido como estreptococo beta-hemolítico del grupo B de Lancefield, adquiere relevancia durante el embarazo debido a la posibilidad de transmisión al recién nacido. Las normas internacionales sugieren realizar tamizaje vagino-anal entre las 35 y 37 semanas de gestación. Objetivo: Determinar prevalencia de colonización por Streptococcus agalactiae en muestras cérvico-vaginales de embarazadas entre 35 y 37 semanas, y en urocultivos de gestantes de cualquier edad gestacional ingresadas en el hospital ginecobstetrico provincial, así como su perfil de sensibilidad. Materiales y métodos: Se realizó un estudio observacional, descriptivo y exploratorio, de corte transversal, entre enero y agosto de 2021, en el Hospital Provincial Docente Ginecobstétrico José Ramón López Tabrane, de la ciudad de Matanzas. El universo estuvo conformado por todas las gestantes de cualquier trimestre a las que se les realizó urocultivo, y estudio microbiológico cérvico-vaginal entre las 35 y 37 semanas de gestación, cumplidos previamente criterios de inclusión. Resultados: El 18,61 % presentó cultivos positivos para Streptococcus agalactiae. Predominó la presencia de positividad en gestantes no diabéticas; se encontró un 18,75 % de urocultivos positivos. Predominaron los aislamientos sensibles a eritromicina y clindamicina, con un 63 %, seguidos de la resistencia inducible a clindamicina (MLSBi), con un 19 %. Conclusiones: El diagnóstico microbiológico de Streptococcus agalactiae en gestantes, es de vital importancia para la prevención de sepsis puerperal y neonatal. A pesar de que los resultados de este estudio muestran perfiles de sensibilidad adecuados, su monitorización permanente garantizaría el diagnóstico precoz de cepas resistentes, dado el ligero incremento del fenotipo (MLSBi) identificado.

Introduction: Streptococcus agalactiae, also known as Lancefield's group B beta-hemolytic streptococcus, acquires relevance during pregnancy due to the possibility of transmission to the newborn. International standards suggest performing vaginal-anal screening between 35 and 37 weeks of gestation. Objective: to determine the prevalence of colonization by Streptococcus agalactiae, in cervical-vaginal samples of pregnant women between 35 and 37 weeks, and in urine cultures of pregnant women of any gestational age admitted to the provincial gyneco-obstetric hospital, as well as their sensitivity profile. Materials and methods: an observational, descriptive and exploratory cross-sectional study was performed, between January and August 2021, at the Provincial Teaching Gyneco-obstetric Hospital Jose Ramon Lopez Tabrane of Matanzas. The universe was made up by all pregnant women of any trimester who underwent a urine culture, and a cervical-vaginal microbiologic study between 35 and 37 gestation weeks, previously meeting inclusion criteria. Results: 18.61% presented positive cultures for Streptococcus agalactiae. The presence of positivity predominated in non-diabetic women. 18.75 % of positive urine cultures were found. Erythromycin and clindamycin-sensitive isolates predominated (MLSBi), with 63%, followed by inducible resistance to clindamycin, with 19%. Conclusions: the microbiological diagnosis of Streptococcus agalactiae in pregnant women is of vital importance to prevent puerperal and neonatal sepsis. Although the results of this study show adequate sensitivity profiles, its permanent monitoring would warrantee the early diagnosis of resistant strains, given the slight increase of the phenotype (MLSBi) identified.

Typical esthetic outcomes using 5 different modalities to treat MIH affected teeth: a case series

Therapeutic options for incisors affected by Molar Incisor Hypomineralization range from very conservative procedures to those considered to be more invasive. Clinicians must select the appropriate approach, considering the outcomes of the procedures. This case series presents clinical outcomes of five female patients with aesthetic complaints associated with the Molar Incisor Hipomineralization. Macroabrasion, microabrasion and dental vital bleaching were used as combination techniques in three cases. Resin infiltration was indicated for a specific case, considering the oncoming orthodontic treatment. Composite restoration was performed in one patient with posteruptive enamel breakdown. Clinicians must select the appropriate approach according to an individualized evaluation of each case, considering factors such as the patient's expectations, dental age, psychosocial period, the severity of the condition, presence of sensitivity and the presumed aesthetic result of the selected treatment. The advantages and disadvantages of the techniques are presented.

Las opciones terapéuticas para los incisivos afectados por hipomineralización incisivo molar van desde procedimientos muy conservadores hasta los considerados más invasivos. Los clínicos deben seleccionar el enfoque adecuado, teniendo en cuenta los resultados de los procedimientos. Esta serie de casos presenta los resultados clínicos de cinco pacientes femeninas con quejas estéticas asociadas a la Hipomineralización Incisivo Molar. En tres casos se utilizaron la macroabrasión, la microabrasión y el blanqueamiento dental vital como técnicas combinadas. La infiltración de resina fue indicada para un caso específico, considerando el tratamiento de ortodoncia próximo. Se realizó una restauración con composite en un paciente con rotura posteruptiva del esmalte. Los clínicos deben seleccionar el abordaje adecuado de acuerdo con una evaluación individualizada de cada caso, considerando factores como las expectativas del paciente, la edad dental, el período psicosocial, la gravedad de la afección, la presencia de sensibilidad y el resultado estético presumible del tratamiento seleccionado. Se presentan las ventajas e inconvenientes de las técnicas.

Simulation Model of the Effect of the COVID-19 Biosecurity Protocol in the Queues for the Return to Face-to-Face Classes.

This article presents a simulation model of the effect of the COVID-19 Biosafety protocol in the Queues for the return to face-to-face classes as a basis for the return of educational activities. The restrictive measures to face the COVID-19 pandemic, greatly affected the normality of the development of activities carried out in higher education, constituting a great challenge since the measures and conditions of return and access to institutions are different from what was previously carried out before the pandemic. The objective of this article is to carry out a simulation of queues through SIMIO (Logistics process simulation software), where the number of students expected per day and the average entry times are taken into account to adjust them to an exponential distribution, from this information loaded into the simulation it is They will determine if the times increase or decrease taking into account the theory of queues and conditions presented in the study such as the probability distribution of the times of each of the processes involved in the process of accessing the University facilities.