The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

Exploration adhesion properties of Liquorilactobacillus and Lentilactobacillus isolated from two different sources of tepache kefir grains.

Due to the distinctive characteristics of probiotics, it is essential to pinpoint strains originating from diverse sources that prove efficacious in addressing a range of pathologies linked to dysfunction of the intestinal barrier. Nine strains of lactic acid bacteria were isolated from two different sources of tepache kefir grains (KAS2, KAS3, KAS4, KAS7, KAL4, KBS2, KBS3, KBL1 and KBL3), and were categorized to the genus Lacticaseibacillus, Liquorilactobacillus, and Lentilactobacillus by 16S rRNA gene. Kinetic behaviors of these strains were evaluated in MRS medium, and their probiotic potential was performed: resistance to low pH, tolerance to pepsin, pancreatin, bile salts, antibiotic resistance, hemolytic activity, and adhesion ability. KAS7 strain presented a higher growth rate (0.50 h-1) compared with KAS2 strain, who presented a lower growth rate (0.29 h-1). KBS2 strain was the only strain that survived the in vitro stomach simulation conditions (29.3%). Strain KBL1 demonstrated significantly higher viability (90.6%) in the in vitro intestine simulation conditions. Strain KAS2 demonstrated strong hydrophilic character with chloroform (85.6%) and xylol (57.6%) and a higher percentage of mucin adhesion (87.1%). However, strains KBS2 (84.8%) and KBL3 (89.5%) showed the highest autoaggregation values. In terms of adhesion to the intestinal epithelium in rats, strains KAS2, KAS3 and KAS4 showed values above 80%. The growth of the strains KAS2, KAS3, KAS4, KBS2, and KBL3 was inhibited by cefuroxime, cefotaxime, tetracycline, ampicillin, erythromycin, and cephalothin. Strains KBS2 (41.9% and 33.5%) and KBL3 (42.5% and 32.8%) had the highest co-aggregation values with S. aureus and E. coli. The results obtained in this study indicate that lactic acid bacteria isolated from tepache can be considered as candidates for potentially probiotic bacteria, laying the foundations to evaluate their probiotic functionality in vivo and thus to be used in the formulation of functional foods.

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies / Valor de la estimación de la velocidad de onda de pulso en comparación con SCORE en la estratificación del riesgo cardiovascular en farmacias comunitarias

Objectives Arterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. Methods Observational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. Results After nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. Conclusions More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE (AU)

Objetivos La rigidez arterial es un marcador intermedio con valor pronóstico independiente. Nuestro objetivo es valorar si la estimación de la rigidez arterial puede mejorar la estratificación del riesgo cardiovascular (CV) en comparación con SCORE. Métodos Estudio epidemiológico observacional prospectivo en el que se ofrece a pacientes consecutivos que entran en una farmacia participante la medición voluntaria de la presión arterial y de la velocidad de onda de pulso estimada por oscilometría (AGEDIO, IEM®) para estratificar su riesgo CV según SCORE o según la presencia de rigidez arterial. Resultados Tras 9 meses de reclutamiento, presentamos datos de 923 pacientes (570 mujeres, 353 hombres). Dieciséis/122 (13,1%) pacientes <40años y 72/364 (19,8%) >65años presentaron rigidez arterial patológica y fueron clasificados de alto riesgo, aun hallándose fuera del rango de edad de SCORE. De los 437 (47,3%) pacientes evaluables por SCORE, 42/437 pacientes (9,6%) mostraron rigidez elevada. Los valores de colesterol estaban disponibles en 281 de estos pacientes (64,3%). Entre ellos, según SCORE, solo 6 (2,1%) eran de la categoría de alto riesgo. Conclusiones Más de la mitad de sujetos que entran aleatoriamente en una farmacia comunitaria tenían edades situadas fuera de los rangos de SCORE, imposibilitando el cálculo del riesgo CV con SCORE. En este grupo se constató daño arterial en el 18,1%. En la otra mitad, el 9,6% presentaron daño vascular y, consecuentemente, riesgo elevado, mientras que SCORE solo detectó riesgo elevado en el 2,1%. Por tanto, la estimación de la rigidez arterial en farmacias comunitarias mejora claramente la detección de riesgo CV elevado en comparación con SCORE (AU)

Chia (Salvia hispanica L.), a Pre-Hispanic Food in the Treatment of Diabetes Mellitus: Hypoglycemic, Antioxidant, Anti-Inflammatory, and Inhibitory Properties of α-Glucosidase and α-Amylase, and in the Prevention of Cardiovascular Disease.

Diabetes mellitus (DM) is considered one of the major health diseases worldwide, one that requires immediate alternatives to allow treatments for DM to be more effective and less costly for patients and also for health-care systems. Recent approaches propose treatments for DM based on that; in addition to focusing on reducing hyperglycemia, they also consider multitargets, as in the case of plants. Among these, we find the plant known as chia to be highlighted, a crop native to Mexico and one cultivated in Mesoamerica from pre-Hispanic times. The present work contributes to the review of the antidiabetic effects of chia for the treatment of DM. The antidiabetic effects of chia are effective in different mechanisms involved in the complex pathogenesis of DM, including hypoglycemic, antioxidant, and anti-inflammatory mechanisms, and the inhibition of the enzymes α-glucosidase and α-amylase, as well as in the prevention of the risk of cardiovascular disease. The tests reviewed included 16 in vivo assays on rodent models, 13 clinical trials, and 4 in vitro tests. Furthermore, chia represents advantages over other natural products due to its availability and its acceptance and, in addition, as a component of the daily diet worldwide, especially due to its omega-3 fatty acids and its high concentration of dietary fiber. Thus, chia in the present work represents a source of antidiabetic agents that would perhaps be useful in novel clinical treatments.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

Value of estimating pulse wave velocity compared to SCORE in cardiovascular risk stratification in community pharmacies.

OBJECTIVES: Arterial stiffness is considered to be an intermediate marker with independent prognostic value. The objective of this study is to assess whether the estimation of arterial stiffness can improve CV risk stratification compared to SCORE in patients at community pharmacies. METHODS: Observational prospective epidemiological study in which consecutive individuals entering a participating Community Pharmacy are offered a voluntary measurement of blood pressure and estimation of pulse wave velocity by oscillometry (AGEDIO, IEM®) to stratify their CV risk according to SCORE compared to the use of arterial stiffness. RESULTS: After nine months of recruitment, data from 923 patients (570 women, 353 men) were collected. 16/122 (13.1%) patients under 40 years and 72/364 (19.8%) over 65 years of age presented pathological stiffness and could be classified as high-risk, even though being out of the age-range of SCORE. Of the 437 (47.3%) patients who were susceptible to calculating SCORE, 42/437 patients (9.6%) presented pathological arterial stiffness. Cholesterol values were available in 281 patients (64.3%). Among them, according to SCORE, only 6 (2.1%) fell into the high-risk category. CONCLUSIONS: More than half of the subjects who randomly enter a community pharmacy had ages that make it impossible to calculate the CV risk by SCORE. Among them, arterial damage was detected in 18.1%. Of the other half, 9.6% presented arterial damage and, therefore, high CV risk, when SCORE only detected it in 2.1%. Therefore, estimating arterial stiffness in community pharmacies markedly improves detection of high CV risk compared to SCORE.

Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study.

BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).

Promising AAV.U7snRNAs vectors targeting DMPK improve DM1 hallmarks in patient-derived cell lines.

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults and affects mainly the skeletal muscle, heart, and brain. DM1 is caused by a CTG repeat expansion in the 3'UTR region of the DMPK gene that sequesters muscleblind-like proteins, blocking their splicing activity and forming nuclear RNA foci. Consequently, many genes have their splicing reversed to a fetal pattern. There is no treatment for DM1, but several approaches have been explored, including antisense oligonucleotides (ASOs) aiming to knock down DMPK expression or bind to the CTGs expansion. ASOs were shown to reduce RNA foci and restore the splicing pattern. However, ASOs have several limitations and although being safe treated DM1 patients did not demonstrate improvement in a human clinical trial. AAV-based gene therapies have the potential to overcome such limitations, providing longer and more stable expression of antisense sequences. In the present study, we designed different antisense sequences targeting exons 5 or 8 of DMPK and the CTG repeat tract aiming to knock down DMPK expression or promote steric hindrance, respectively. The antisense sequences were inserted in U7snRNAs, which were then vectorized in AAV8 particles. Patient-derived myoblasts treated with AAV8. U7snRNAs showed a significant reduction in the number of RNA foci and re-localization of muscle-blind protein. RNA-seq analysis revealed a global splicing correction in different patient-cell lines, without alteration in DMPK expression.

Spermiogenesis alterations in the absence of CTCF revealed by single cell RNA sequencing.

CTCF is an architectonic protein that organizes the genome inside the nucleus in almost all eukaryotic cells. There is evidence that CTCF plays a critical role during spermatogenesis as its depletion produces abnormal sperm and infertility. However, defects produced by its depletion throughout spermatogenesis have not been fully characterized. In this work, we performed single cell RNA sequencing in spermatogenic cells with and without CTCF. We uncovered defects in transcriptional programs that explain the severity of the damage in the produced sperm. In the early stages of spermatogenesis, transcriptional alterations are mild. As germ cells go through the specialization stage or spermiogenesis, transcriptional profiles become more altered. We found morphology defects in spermatids that support the alterations in their transcriptional profiles. Altogether, our study sheds light on the contribution of CTCF to the phenotype of male gametes and provides a fundamental description of its role at different stages of spermiogenesis.

Developing and Implementing In-Person and Virtual SoilSHOPs in Atlanta, Georgia, as a Community-Engaged Approach to Screen and Prevent Soil Lead Exposure.

Urban agriculture presents the opportunity for increased availability of local, fresh foods; however, exposure to lead soil contamination can occur through gardening in urban environments. Through a community-engaged partnership, we implemented Soil Screening, Health, Outreach and Partnerships (soilSHOPs), in-person and virtually, to screen soils for lead in Atlanta, Georgia. These soilSHOPs inform best practices for increasing awareness about lead exposure and grounding interventions in residents' lived experiences and also led the US Environmental Protection Agency to identify a Superfund site.

Community-Engaged Assessment of Soil Lead Contamination in Atlanta Urban Growing Spaces.

Urban agriculture is emerging as a method to improve food security and public health in cities across the United States. However, an increased risk of exposure to heavy metals and metalloids (HMM) exists through interaction with contaminated soil. Community-engaged research (CEnR) is one method that can promote the inclusion of all partners when studying exposures such as HMM in soil. Researchers and community gardeners co-designed this study to measure the concentrations of lead (Pb), using X-Ray Fluorescence (XRF) verified with Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) in soils from 19 urban agricultural and residential sites in the Westside of Atlanta and three rural sites in Georgia. Seventeen other HMM were measured but not included in this study, because they did not pose risks to the community comparable to elevated Pb levels. Pb concentrations were compared to the Environmental Protection Agency (EPA)'s regional screening levels (RSLs) for residential soil and the University of Georgia (UGA) extension service's low-risk levels (LRLs) for agriculture. Soils from the majority of sites had levels below EPA RSLs for Pb, yet above the UGA LRL. However, soil Pb concentrations were three times higher than the EPA RSL on some sites that contained metal refining waste or slag. Our findings led to direct action by local and federal government agencies to initiate the cleanup of slag residue. Studies involving exposures to communities should engage those affected throughout the process for maximum impact.

Adverse Drug Reactions during COVID-19 Treatment: A Comprehensive Analysis Focused on Hospitalized Patients, with the Use of a Survey in Cuba in 2020.

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α2b (IFN α2b), according to the Cuban protocol. Materials and Methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI). Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs (P < 0.05). Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

Impaired Carbohydrate Metabolism and Excess of Lipid Accumulation in Offspring of Hyperandrogenic Mice.

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder of unknown etiology. Hyperandrogenism (HA) is the main diagnostic criteria for PCOS, in addition to being a risk factor for developing several disorders throughout the patient's life, including pregnancy. However, the impact on offspring is little known. Therefore, the aim of this work was to evaluate the effect of maternal HA on glucose metabolism and hepatic lipid accumulation in adult offspring. We used Balb/c mice treated with dehydroepiandrosterone (DHEA) for 20 consecutive days. The ovary of DHEA-treated mice showed hemorrhagic bodies, an increased number of atretic follicles, and greater expression of genes related to meiotic cell cycle and DNA repair. The DHEA offspring (O-DHEA) had low birth weight, and some pups showed malformations. However, O-DHEA individuals gained weight rapidly, and the differences between them and the control group became significantly greater in adulthood. Moreover, O-DHEA presented higher serum glucose after a 6 h fast and a larger area under glucose, insulin, and pyruvate tolerance test curves. Oil Red O staining showed a more significant accumulation of fat in the liver but no changes in serum cholesterol and triacylglycerol levels. In summary, our results show that HA, induced by DHEA, affects gene expression in oocyte, which in turn generates defects in embryonic development, insulin resistance, and alteration in hepatic gluconeogenesis and lipid metabolism in O-DHEA, thereby increasing the risk of developing metabolic diseases.

El distrés oxidativo y sus implicaciones moleculares en algunas enfermedades infecciosas: una revisión / Oxidative distress and its molecular implication for some infectious diseases: A review

Introducción: Las especies reactivas de oxígeno, nitrógeno y azufre (ERONS) se generan continuamente en la fisiología de los organismos. Como parte de la respuesta de las células inmunitarias frente a los patógenos podrían aumentar y producir distrés oxidativo, citotoxicidad y daño de los órganos. El reconocimiento de las implicaciones moleculares de las ERONS todavía es un campo de investigación en desarrollo. Objetivo: Describir los aspectos moleculares relacionados con el metabolismo oxidativo y algunos patógenos (virus, parásitos, bacterias y hongos) en relación con las infecciones. Métodos: Se identificaron 520 documentos relacionados con los criterios de búsqueda en las bases de datos LILACS, Science Direct, SciELO, EMBASE, PubMed e Infomed, con los buscadores Google y Google académico. De estos, fueron analizados 78 documentos publicados a partir de 1980 al 2021 en español o inglés y organizados en 7 subtemas. Información, análisis y síntesis: Los agentes infecciosos y el hospedero interactúan produciendo ERONS que pueden superar los sistemas de defensa antioxidantes e influyen en el distrés oxidativo. Los procesos biológicos asociados al estado redox se relacionan con los factores de transcripción Nrf2 y NF-κB. Ambos permiten una respuesta celular entre la susceptibilidad y la resistencia a los agentes infecciosos, por lo que pueden iniciar o acelerar procesos fisiopatológicos en el organismo. En general la respuesta redox en la fisiopatología infecciosa está interconectada con la reprogramación metabólica, las respuestas antimicrobianas e inflamatorias y la disfunción celular o de tejido. Conclusiones: Los eventos moleculares redox pueden participar en diversas enfermedades infecciosas, mediando diferentes respuestas o trastornos asociados.

Introduction: Reactive oxygen/nitrogen/sulfur species (RONSS) are continuously generated in the physiology of organisms. As part of the immune cell response to pathogens, they may increase and lead to oxidative stress, cytotoxicity and organ damage. Recognizing the molecular implications of RONSS is still a developing field of research. Objective: To describe the molecular aspects related to oxidative metabolism and some pathogens (viruses, parasites, bacteria and fungi) in relation to infections. Methods: Based on the search criteria, 520 documents were identified in LILACS, Science Direct, SciELO, EMBASE, PubMed and Infomed databases, using the search engines Google and Google Scholar. Of these, 78 documents published from 1980 to 2021 in Spanish or English and organized into seven subtopics were analyzed. Information, analysis and synthesis: Infectious agents and the host interact to produce RONSS that can overcome antioxidant defense systems influencing on oxidative stress. Biological processes associated with the redox state are related to the transcription factors Nrf2 and NF-κB. Both generate a cellular response between susceptibility and resistance to infectious agents, thus they can initiate or accelerate pathophysiological processes in the organism. In general, the redox response in infectious pathophysiology is interconnected with metabolic reprogramming, antimicrobial and inflammatory responses, and cellular or tissue dysfunction. Conclusions: Molecular redox events may be involved in various infectious diseases, where different associated responses or disorders mediate.

Características clínicas de pacientes cubanos con infección por virus Zika / Clinical characteristics of Cuban patients infected with Zika virus

Introducción: La enfermedad del Zika es causada por el virus de igual nombre, un arbovirus transmitido principalmente por la picadura del mosquito Aedes. Existe riesgo de reintroducción y circulación autóctona del virus Zika en Cuba, por tanto, constituye una problemática vigente. Objetivo: Caracterizar el comportamiento clínico de la infección por virus Zika en pacientes ingresados en el Instituto de Medicina Tropical Pedro Kourí (IPK). Método: Se realizó un estudio descriptivo de corte trasversal con componente analítico, en pacientes con diagnóstico de Zika ingresados en el IPK en el periodo de noviembre de 2016 a mayo de 2017. Se analizaron variables sociodemográficas, clínicas, biomédicas y microbiológicas. Resultados: En los pacientes confirmados con virus Zika, las manifestaciones clínicas significativas (p ≤ 0,05) fueron prurito y adenomegalias; con una duración de la erupción cutánea significativamente superior. En cuanto a los estudios de confirmación mediante reacción en cadena de la polimerasa en tiempo real, la muestra de orina tuvo valores de positividad significativamente superiores a las de suero desde el comienzo del cuadro clínico. Conclusiones: Los casos autóctonos de Zika estudiados presentaron un cuadro clínico donde predominaron el prurito y las adenomegalias. Esto permitió realizar un diagnóstico presuntivo y diferencial ante otros pacientes con síndrome febril. El diagnóstico microbiológico para confirmación de esta arbovirosis fue realizado mediante técnicas moleculares. En la mayoría de los casos las muestras de orina demostraron ser de gran utilidad desde los primeros días luego de la fecha de inicio de los síntomas.

Introduction: Zika is caused by the virus of the same name, an arbovirus transmitted mainly by the bite of the Aedes mosquito. The risk of reintroduction and autochthonous circulation of Zika virus in Cuba remains; therefore, it is considered a current problem. Objective: To characterize the clinical behavior of Zika virus infection in patients admitted to the Institute of Tropical Medicine Pedro Kourí (IPK). Methods: It was conducted a cross-sectional, descriptive study with an analytic component in patients with a diagnosis of Zika admitted to IPK from November 2016 to May 2017. Sociodemographic, clinical, biomedical and microbiological variables were analyzed. Results: In patients confirmed with Zika virus, the main clinical manifestations (p≤ 0.05) were pruritus and adenomegaly; with significantly longer duration of rash. Regarding confirmation studies by real-time polymerase chain reaction, the urine sample had significantly higher positivity values than the serum samples from the onset of the clinical picture. Conclusions: Pruritus and adenomegaly prevailed in the autochthonous cases of Zika under study. This allowed conducting a presumptive and differentiated diagnosis to other patients with a febrile syndrome. The microbiological diagnosis to confirm this arbovirus was performed by molecular methods. In the majority of cases, the urine samples were very useful from the first days after the onset of the symptoms.

Alternative CUG Codon Usage in the Halotolerant Yeast Debaryomyces hansenii: Gene Expression Profiles Provide New Insights into Ambiguous Translation.

The halotolerant yeast Debaryomyces hansenii belongs to the CTG-Ser1 clade of fungal species that use the CUG codon to translate as leucine or serine. The ambiguous decoding of the CUG codon is relevant for expanding protein diversity, but little is known about the role of leucine-serine ambiguity in cellular adaptations to extreme environments. Here, we examine sequences and structures of tRNACAG from the CTG-Ser1 clade yeasts, finding that D. hansenii conserves the elements to translate ambiguously. Then, we show that D. hansenii has tolerance to conditions of salinity, acidity, alkalinity, and oxidative stress associated with phenotypic and ultrastructural changes. In these conditions, we found differential expression in both the logarithmic and stationary growth phases of tRNASer, tRNALeu, tRNACAG, LeuRS, and SerRS genes that could be involved in the adaptive process of this yeast. Finally, we compare the proteomic isoelectric points and hydropathy profiles, detecting that the most important variations among the physicochemical characteristics of D. hansenii proteins are in their hydrophobic and hydrophilic interactions with the medium. We propose that the ambiguous translation, i.e., leucylation or serynation, on translation of the CUG-encoded residues, could be linked to adaptation processes in extreme environments.

Generation of an induced pluripotent stem cell line NCHi003-A from a 11-year-old male with pulmonary atresia with intact ventricular septum (PA-IVS).

Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital heart defect defined by membranous or muscular atresia of the right ventricular outflow tract where patients display varying degrees of hypoplasia of the right ventricle. This condition results in cyanosis due to an inability of blood to flow from the right ventricle to the pulmonary arteries, thus requiring immediate surgical intervention after birth. An iPSC line was generated from peripheral blood mononuclear cells of a 11-year-old male patient diagnosed with PA-IVS through Sendai virus-mediated reprogramming. This disease-specific iPSC line was characterized by immunocytochemistry, STR analysis, karyotype analysis, and mycoplasma testing.

Characterization of an iPSC line NCHi006-A from a patient with hypoplastic left heart syndrome (HLHS).

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect characterized by underdeveloped structures on the left side of the heart, including hypoplasia of the left ventricle and stenosis or atresia of the aortic and mitral valves. Here, we generated an iPSC line from the peripheral blood mononuclear cells of a male patient with HLHS through Sendai virus-mediated transfection of 4 Yamanaka factors. This iPSC line exhibited normal morphology, expressed pluripotency markers, had a normal karyotype, and could differentiate into cells of three germ layers. This iPSC line can be used for studying cellular and developmental etiologies of HLHS.

LiverScreen project: study protocol for screening for liver fibrosis in the general population in European countries.

BACKGROUND: The development of liver cirrhosis is usually an asymptomatic process until late stages when complications occur. The potential reversibility of the disease is dependent on early diagnosis of liver fibrosis and timely targeted treatment. Recently, the use of non-invasive tools has been suggested for screening of liver fibrosis, especially in subjects with risk factors for chronic liver disease. Nevertheless, large population-based studies with cost-effectiveness analyses are still lacking to support the widespread use of such tools. The aim of this study is to investigate whether non-invasive liver stiffness measurement in the general population is useful to identify subjects with asymptomatic, advanced chronic liver disease. METHODS: This study aims to include 30,000 subjects from eight European countries. Subjects from the general population aged ≥ 40 years without known liver disease will be invited to participate in the study either through phone calls/letters or through their primary care center. In the first study visit, subjects will undergo bloodwork as well as hepatic fat quantification and liver stiffness measurement (LSM) by vibration-controlled transient elastography. If LSM is ≥ 8 kPa and/or if ALT levels are ≥1.5 x upper limit of normal, subjects will be referred to hospital for further evaluation and consideration of liver biopsy. The primary outcome is the percentage of subjects with LSM ≥ 8kPa. In addition, a health economic evaluation will be performed to assess the cost-effectiveness and budget impact of such an intervention. The project is funded by the European Commission H2020 program. DISCUSSION: This study comes at an especially important time, as the burden of chronic liver diseases is expected to increase in the coming years. There is consequently an urgent need to change our current approach, from diagnosing the disease late when the impact of interventions may be limited to diagnosing the disease earlier, when the patient is asymptomatic and free of complications, and the disease potentially reversible. Ultimately, the LiverScreen study will serve as a basis from which diagnostic pathways can be developed and adapted to the specific socio-economic and healthcare conditions in each country. TRIAL REGISTRATION: This study is registered on Clinicaltrials.gov ( NCT03789825 ).