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BACKGROUND: Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use. METHODS: Through a combination of screening and rational design, we identified a cardiac reprogramming cocktail that can be encoded in a single adeno-associated virus. We also created a novel adeno-associated virus capsid that can transduce cardiac fibroblasts more efficiently than available parental serotypes by mutating posttranslationally modified capsid residues. Because a constitutive promoter was needed to drive high expression of these cell fate-altering reprogramming factors, we included binding sites to a cardiomyocyte-restricted microRNA within the 3' untranslated region of the expression cassette that limits expression to nonmyocytes. After optimizing this expression cassette to reprogram human cardiac fibroblasts into induced cardiomyocyte-like cells in vitro, we also tested the ability of this capsid/cassette combination to confer functional benefit in acute mouse myocardial infarction and chronic rat myocardial infarction models. RESULTS: We demonstrated sustained, dose-dependent improvement in cardiac function when treating a rat model 2 weeks after myocardial infarction, showing that cardiac reprogramming, when delivered in a single, clinically relevant adeno-associated virus vector, can support functional improvement in the postremodeled heart. This benefit was not observed with GFP (green fluorescent protein) or a hepatocyte reprogramming cocktail and was achieved even in the presence of immunosuppression, supporting myocyte formation as the underlying mechanism. CONCLUSIONS: Collectively, these results advance the application of cardiac reprogramming gene therapy as a viable therapeutic approach to treat chronic heart failure resulting from ischemic injury.
Subject(s)
MicroRNAs , Myocardial Infarction , Rats , Mice , Humans , Animals , Dependovirus/genetics , Myocytes, Cardiac/metabolism , Myocardial Infarction/therapy , Myocardial Infarction/drug therapy , MicroRNAs/genetics , MicroRNAs/metabolism , Genetic Therapy/methods , Green Fluorescent Proteins/genetics , Cellular Reprogramming , Fibroblasts/metabolismABSTRACT
OBJECTIVE: Coronary artery abnormalities (CA) occur in patients with hypoplastic left heart syndrome (HLHS) and may be associated with higher mortality and heart transplantation (HT). We aimed to determine whether fetuses with HLHS and prenatal CA have a higher risk of death or HT. METHODS: We performed a retrospective review of fetal echocardiograms with HLHS from 2011 to 2018. We excluded fetuses with ventricular septal defects, elective termination, death in utero, planned postnatal non-intervention, or absent follow-up data. Presence or absence of CA was determined by review of serial fetal echocardiograms. Survival analysis was used to evaluate the relationship between prenatal CA and death or HT. RESULTS: Of 86 patients with fetal HLHS, 11 had prenatal diagnosis of CA. Of these, six required HT and five died (one after undergoing HT); only one remains alive without HT. Of those without prenatal CA (n = 75), 25 died and 7 underwent HT. Patients with prenatal diagnosis of HLHS and CA had a significantly increased likelihood of death or HT (p-value <0.05). CONCLUSION: Prenatal diagnosis of CA in our cohort of patients with HLHS was associated with increased risk of death or HT. These data have significance for prenatal counseling and postnatal management.
Subject(s)
Heart Transplantation , Hypoplastic Left Heart Syndrome , Coronary Vessels , Female , Gestational Age , Heart Transplantation/adverse effects , Humans , Hypoplastic Left Heart Syndrome/complications , Hypoplastic Left Heart Syndrome/diagnostic imaging , Hypoplastic Left Heart Syndrome/surgery , Pregnancy , Probability , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
The establishment of a reference method for the determination of the allergen protein content in a processed food material has been explored. An analytical approach was developed to enable the comparability of food allergen measurement results expressed in a decision-relevant manner. A proof of concept is here presented, resulting in quantity values for the common measurand, namely 'mass of total allergen protein per mass of food'. The quantities are determined with SI traceability to enable the comparability of reported results. A method for the quantification of total milk protein content in an incurred baked food at a concentration level clinically relevant is presented. The strategy on how to obtain the final analytical result is outlined. Challenges associated with this method are discussed, in particular the optimal extraction of the marker proteins, the complete digestion and release of the peptides in an equimolar fashion, the use of conversion factors to translate the amount of measured proteins into total milk protein and the estimation of the uncertainty contributions as well as of the combined uncertainty of the final result. The implementation of such a reference method for the determination of the total allergen content in a processed food is an important step, which will provide comparable measurement data of relevance to risk assessors. Graphical abstract.
Subject(s)
Allergens/analysis , Food Analysis/methods , Milk Proteins/analysis , Milk/chemistry , Amino Acid Sequence , Animals , Calibration , Chromatography, Liquid/methods , Humans , Limit of Detection , Milk Proteins/chemistry , Peptides/analysis , Peptides/chemistry , Proof of Concept Study , Reference Standards , Reproducibility of Results , Tandem Mass Spectrometry/methods , UncertaintyABSTRACT
Coral reefs are home to a variety of species, and their preservation is a popular study area; however, monitoring them is a significant challenge, for which the use of robots offers a promising answer. The purpose of this study is to analyze the current techniques and tools employed in coral reef monitoring, with a focus on the role of robotics and its potential in transforming this sector. Using a systematic review methodology examining peer-reviewed literature across engineering and earth sciences from the Scopus database focusing on "robotics" and "coral reef" keywords, the article is divided into three sections: coral reef monitoring, robots in coral reef monitoring, and case studies. The initial findings indicated a variety of monitoring strategies, each with its own advantages and disadvantages. Case studies have also highlighted the global application of robotics in monitoring, emphasizing the challenges and opportunities unique to each context. Robotic interventions driven by artificial intelligence and machine learning have led to a new era in coral reef monitoring. Such developments not only improve monitoring but also support the conservation and restoration of these vulnerable ecosystems. Further research is required, particularly on robotic systems for monitoring coral nurseries and maximizing coral health in both indoor and open-sea settings.
Subject(s)
Anthozoa , Coral Reefs , Environmental Monitoring , Robotics , Environmental Monitoring/methods , Animals , Conservation of Natural Resources/methods , EcosystemABSTRACT
BACKGROUND: People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. METHODS: We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. FINDINGS: Among 14â238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100â000 person-years (95% CI 59·4-87·6) and median follow-up of 9·5 years (IQR 4·4-15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per µL (IR 105·0 person-years, 95% CI 82·0-132·5) and lowest among those with counts of more than 350 cells per µL (2·9 person-years, 0·1-16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1-211·7) among those with a CD4 count of less than 200 cells per µL, 37·6 person-years (16·2-74·1) among those with a count of 200-350 cells per µL, and 4·8 person-years (0·1-26·9) among those with a count of more than 350 cells per µL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per µL (IR 4·8 person-years, 95% CI 0·1-26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per µL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per µL (adjusted IR ratio 0·03, 95% CI 0·00-0·25; p=0·0010) or 200-350 cells per µL (0·30, 0·17-0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7-206·9; p=0·0010) and people with HIV aged 45-59 years of 21·6 (3·0-156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9-137·5; p<0·0001). INTERPRETATION: A nadir CD4 count threshold below 350 cells per µL, particularly less than 200 cells per µL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. FUNDING: Catalan Health Department, Generalitat de Catalunya.
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BACKGROUND: Obesity is a multifactorial chronic disease with a high, increasing worldwide prevalence. Genetic causes account for 7% of the cases in children with extreme obesity. DATA SOURCES: This narrative review was conducted by searching for papers published in the PubMed/MEDLINE, Embase and SciELO databases and included 161 articles. The search used the following search terms: "obesity", "obesity and genetics", "leptin", "Prader-Willi syndrome", and "melanocortins". The types of studies included were systematic reviews, clinical trials, prospective cohort studies, cross-sectional and prospective studies, narrative reviews, and case reports. RESULTS: The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight. However, several important aspects of the pathophysiology of obesity remain unknown. Genetic causes of obesity can be grouped into syndromic, monogenic, and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years, hyperphagia, or a family history of extreme obesity. A microarray study, an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose. There are three therapeutic levels: lifestyle modifications, pharmacological treatment, and bariatric surgery. CONCLUSIONS: Genetic study technologies are in constant development; however, we are still far from having a personalized approach to genetic causes of obesity. A significant proportion of the affected individuals are associated with genetic causes; however, there are still barriers to its approach, as it continues to be underdiagnosed. Video Abstract (MP4 1041807 KB).
Subject(s)
Leptin , Obesity, Morbid , Child , Humans , Child, Preschool , Leptin/genetics , Prospective Studies , Cross-Sectional Studies , Obesity , Obesity, Morbid/genetics , Melanocortins/geneticsABSTRACT
Aqueous solutions of four pharmaceutical compounds, belonging to the group of emergent contaminants of water: atenolol (ATL), hydrochlorothiazide (HCT), ofloxacin (OFX) and trimethoprim (TMP), have been treated with different oxidation systems, mainly, photocatalytic oxidation, ozonation and photocatalytic ozonation. TiO2 has been used as semiconductor for photocatalytic reactions both in the presence of air, oxygen or ozone-oxygen gas mixtures. Black light lamps mainly emitting at 365 nm were the source of radiation. In all cases, the influence of some variables (concentrations of semiconductor, ozone gas and pharmaceuticals and pH) on the removal of pharmaceuticals, total polyphenol content (TPC) and total organic carbon (TOC) was investigated. A discussion on the possible routes of pharmaceutical and intermediates (as TPC and TOC) elimination has been developed. Thus, OFX TiO2/UVA degradation mechanism seems to develop through the participation of non-hydroxyl free radical species. Furthermore, the presence of OFX inhibits the formation of hydroxyl radicals in the photocatalytic process. The most effective processes were those involving ozone that lead to complete disappearance of parent compounds in less than 30 min for initial pharmaceutical concentrations lower than 2.5 mg L(-1). In the ozonation systems, regardless of the pH and the presence of TiO2, pharmaceuticals are degraded through their direct reaction with ozone. Photocatalytic ozonation was the most efficient process for TPC and TOC removals (≥ 80% and ≥60% elimination after 2 h of treatment, respectively) as well as in terms of the ozone consumption efficiency (1, 5.5 and 4 mol of ozone consumed per mol of TOC mineralized, at pH 4, 7 and 9, respectively). Weakly acid conditions (pH 4) resulted to be the most convenient ones for TPC and TOC removal by photocatalytic ozonation. This was likely due to formation of hydroxyl radicals through the ozonide generated at these conditions.
Subject(s)
Atenolol/chemistry , Hydrochlorothiazide/chemistry , Ofloxacin/chemistry , Ozone/chemistry , Trimethoprim/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Atenolol/analysis , Environmental Restoration and Remediation/methods , Hydrochlorothiazide/analysis , Hydrogen-Ion Concentration , Ofloxacin/analysis , Oxidation-Reduction , Oxygen/chemistry , Photochemical Processes , Semiconductors , Titanium/chemistry , Trimethoprim/analysis , Ultraviolet Rays , Water Pollutants, Chemical/analysisABSTRACT
Inconsistent quantification results obtained from various analytical methods for food allergen testing hamper an accurate quantitative risk assessment and its regulatory implementation. In order to overcome such problems, a concept aiming at ensuring the comparability of quantitative food allergen measurement results is presented here. It is based on an approach called reference measurement system for food allergens, which uses a commonly agreed reference, namely the 'mass fraction of total protein of the allergenic ingredient in food'. The necessary system components are outlined, consisting of a primary reference measurement method, a certified reference material and a reference laboratory. This metrology-based concept can be applied to quantify various food allergens determined with different analytical procedures. The example of 'milk in cookies' is used to demonstrate the approach.
Subject(s)
Food Hypersensitivity , Humans , Risk Assessment , Food Hypersensitivity/prevention & control , Allergens , Reference Standards , CalibrationABSTRACT
A newborn presented with tetralogy of Fallot (TOF), right aortic arch (RAA), and isolated left brachiocephalic artery. The RAA supplied the right common carotid artery, right vertebral artery, and right subclavian artery, in that order. The left common carotid and left subclavian arteries were in continuity with no aortic origin. Ultrasound demonstrated retrograde flow in the left vertebral artery supplying antegrade flow to the diminutive left subclavian artery (ie, "steal phenomenon"). The patient underwent repair of TOF without intervention on the left common carotid or left subclavian arteries and is being followed conservatively.
Subject(s)
Situs Inversus , Tetralogy of Fallot , Infant, Newborn , Humans , Tetralogy of Fallot/complications , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Subclavian Artery/diagnostic imaging , Subclavian Artery/surgeryABSTRACT
Intersex, the appearance of female characteristics in male gonads, has been identified in a wide range of aquatic species worldwide, yet the underpinning molecular etiology remains uncharacterized. The presence of intersex has been shown to be a widespread phenomenon in bivalve, S. plana, populations from the southwest coast of the U.K., as well as inducible in an experimental exposure regime using endocrine disrupting compounds (EDCs). Herein, we use the suppressive subtractive hybridization approach to isolate differentially expressed transcripts in S. plana males exhibiting intersex. Transcripts involved in cell signaling, cell cycle control, energy production/metabolism, microtubule assembly, and sperm physiology are all highlighted as differentially expressed in intersex male clams. These provide both an insight into the molecular mechanisms of action involved in the development of intersex, as well as facilitating potential molecular-level "early warning" biomarkers of the condition.
Subject(s)
Bivalvia/drug effects , Bivalvia/genetics , Endocrine Disruptors/adverse effects , Water Pollutants, Chemical/adverse effects , Animals , Disorders of Sex Development/chemically induced , Disorders of Sex Development/genetics , Down-Regulation/drug effects , Female , Gene Expression Profiling , Male , RNA, Messenger/genetics , Transcriptome/drug effects , Up-Regulation/drug effectsABSTRACT
Background: The consumption of wheat/gluten is associated with adverse reactions for human health. Gluten and fructans are identified as the major compounds triggering and worsening adverse reactions to wheat, which are increasing, and as a consequence, avoidance of gluten/wheat is the common strategy of many individuals of the western population. Although bread is a product of daily consumption, there is a lack of information on the gluten and fructan contents and the influence of artisanal or industrial processes. Objective: The aim of this study is to carry out a comparative characterization between artisan bakeries and hypermarkets in Spain for gluten and fructan contents in daily sold breads. Design: A total of 48 types of bread highly consumed in Spain sold in artisan bakeries (long fermentation) and hypermarkets (short fermentations) were selected for comparing the gluten and fructan contents. Methods such as reverse phase-high performance liquid chromatography (RP-HPLC), R5 monoclonal antibody (moAb), and fructans protocols were used for the quantification of these compounds. Results: Great variation for the content of gluten and fructans has been found between all bread categories. Although breads produced using long fermentation (artisan bakeries) contain significantly lower gluten, they have higher fructans than those using short fermentations (hypermarkets). Durum wheat breads had the lowest content of gluten. Moreover, spelt breads from artisan bakeries had the lowest content of fructans but not those from hypermarkets. Discussion: In this study, we report the comparative characterizarion of the breads of the Spanish market. These food products presented variation in the amount of gluten and fructans, ligated in most of the cases to the nature of the providers: artisan bakeries against hypermarkets. Depending on the type of bread, the differences for the daily consumption of gluten and fructan can be 4.5 and 20 times, respectively. Conclusions: We found strong differences for gluten and fructan contents among breads. These information may contribute to designing strategies to improve the management of gluten and fructans in bread.
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Interlaboratory comparisons (ILC) in the food allergens field mainly rely on the use of consensus values per applied methodology or even per type of an ELISA test kit. Results suggest good reproducibility; however, possible biases may not be recognized since metrological traceability to an independent reference is lacking. The work presented here utilizes isotope dilution mass spectrometry (IDMS) to assign a reference value of the total cow's milk protein (TCMP) content in a baked cookie and its associated uncertainty. TCMP consists of several individual proteins, of which five (representing 92%) served us as markers for TCMP. Per marker, one to four proteotypic peptides were selected for the quantification. These were synthesized, and the mass fractions of respective reference solutions were determined with peptide-impurity-corrected amino acid analysis to establish traceability to SI units. Stable isotope labelled ("heavy") analogues of the proteotypic peptides were also synthesized and blended with extracts of the test material or the reference solutions for IDMS. Through careful measurement design minimizing biases, well-defined model equations were developed, allowing appropriate estimation of the associated uncertainty. The determined reference value of 11.8 ± 1.1 mg TCMP/kg cookie was used for scoring of a novel ILC.
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OBJECTIVES: To determine the health status, exercise capacity, and health related quality of life (HRQoL) of COVID-19 associated acute respiratory distress syndrome (ARDS) survivors, 8 months after diagnosis. METHODS: All eligible patients were interviewed and underwent a physical examination, chest X-ray, and 6 min walk test (6MWT). Scales to evaluate post-traumatic stress disorder, depression, anxiety, and HRQoL were applied. RESULTS: Of 1295 patients, 365 suffered ARDS and 166 survived to hospital discharge. Five died after discharge and 48 were lost to follow-up. Of the 113 remaining patients, 81% had persistent symptoms. More than 50% of patients completed less than 80% of the theoretical distance on the 6MWT, 50% had an abnormal X-ray and 93% of patients developed psychiatric disorders. Mean SF-36 scores were worse than in the general population. After multivariate regression analysis, female sex, non-Caucasian race, and Charlson index>2 were independent risk factors for a worse mental health component summary score on the SF-36, and age was associated with a better prognosis. Female sex and chronic obstructive pulmonary disease were independently associated with a worse physical component summary score. CONCLUSION: COVID-19 associated ARDS survivors have long-term consequences in health status, exercise capacity, and HRQoL. Strategies addressed to prevent these sequelae are needed.
Subject(s)
COVID-19 , Respiratory Distress Syndrome , Female , Humans , Quality of Life , Respiratory Distress Syndrome/epidemiology , SARS-CoV-2 , SurvivorsABSTRACT
Monitoring of tropane alkaloids is regulated in the European Union in cereal-based foods for infants and young children, tea and herbal infusions. The European Commission's Joint Research Centre (JRC) developed an improved LC-MS/MS analytical method using a pentafluorophenyl column, validated it and conducted two proficiency tests targeting these food categories. A subset of the data gathered from laboratories that used the JRC method was additionally exploited to derive interlaboratory performance characteristics. The method showed fit-for-purpose figures of merit. The LOQs for atropine and scopolamine were around 0.4 and 1.2 µg/kg in cereal products, and in tea and herbal infusions, respectively. Uncertainties varied from 15 to 25%. The reproducibility varied from 11 to 38% for scopolamine and from 17 to 44% for atropine at levels ranging from 0.18 to 18.8 and 1.2-54.0 µg/kg, respectively. Recoveries ranged from 71 to 96%. These performance parameters render the method a good candidate for standardisation.
Subject(s)
Alkaloids/analysis , Edible Grain/chemistry , Tea/chemistry , Tropanes/analysis , Alkaloids/chemistry , Atropine/analysis , Chromatography, High Pressure Liquid , Humans , Limit of Detection , Reproducibility of Results , Scopolamine/analysis , Tandem Mass Spectrometry/methods , Tropanes/chemistryABSTRACT
Increasing demand for organic products and their premium prices make them an attractive target for fraudulent malpractices. In this study, a large-scale comparative metabolomics approach was applied to investigate the effect of the agronomic production system on the metabolite composition of carrots and to build statistical models for prediction purposes. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) was applied successfully to predict the origin of the agricultural system of the harvested carrots on the basis of features determined by liquid chromatography-mass spectrometry. When the training set used to build the OPLS-DA models contained samples representative of each harvest year, the models were able to classify unknown samples correctly (100% correct classification). If a harvest year was left out of the training sets and used for predictions, the correct classification rates achieved ranged from 76% to 100%. The results therefore highlight the potential of metabolomic fingerprinting for organic food authentication purposes.
Subject(s)
Daucus carota , Food, Organic , Discriminant Analysis , Mass Spectrometry , MetabolomicsABSTRACT
INTRODUCTION: Total parenteral nutrition (TPN) provides vital intravenous nutrition for patients who cannot tolerate enteral nutrition but is susceptible to medical errors due to its formulation, ordering, and administrative complexities. At Johns Hopkins All Children's Hospital, 22% of TPN orders required clarification of errors and averaged 10 minutes per order for error correction by pharmacists. Quality improvement methodology improved patient safety by standardizing TPN formulations and incorporating TPN ordering processes into the electronic medical record. METHODS: A multidisciplinary group of providers developed standardized TPN solutions for neonatal and pediatric patients. Inclusion, exclusion, and discontinuation criteria were defined. The primary outcome measure was reducing TPN ordering error rate, and secondary outcomes were improving TPN ordering and processing time along with reducing blood draws. Through multiple plan-do-study-act cycles, we standardized TPN solutions, incorporated them in the electronic medical record, monitored blood draws, and evaluated resource efficiency. Data were analyzed using chi-square tests of independence and t tests for 2 independent samples. RESULTS: The TPN ordering error rate significantly decreased from baseline of 22% to 3.2% over the final quarter of the study period, χ2 (1, N = 2,467) = 89.13, P < 0.001. Order processing time fell from 10 to 5 minutes by project end. The average number of blood draws decreased significantly from 6.2 (SD = 3.12) blood draws to 4.3 (SD = 2.13) in the last quarter of the study, t (506) = 5.97, P < 0.001. CONCLUSIONS: Standardizing TPN and transitioning to electronic ordering effectively and significantly reduced ordering errors and processing time. It also substantially improved resource efficiency by reducing the number of blood draws.
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RESUMEN Introducción: El linfoma primario de apéndice ocurre en 0,015% de todas las neoplasias malignas de apéndice. La manifestación clínica más frecuente es apendicitis aguda y el análisis anatomo patológico es muy importante. Reporte de caso: Linfoma primario de apéndice cecal, varón de 38 años, ingresó con apendicitis aguda. Estudio histopatológico macroscópico muestra pared apendicular difusamente engrosada color blanco. Microscópicamente: linfoma de alto grado Burkitt, ACL, CD20, CD10 positivo, KI 67 positivos 95%, CD3, BCL2, EBV negativo. Post operatorio: tomografía abdomino torácica mostró tumoración de fosa iliaca derecha sin lesiones ni adenopatías en abdomen y tórax. El paciente fue tratado con dos cursos de quimioterapia y se le realizó TAC abdominal control a los 6 meses, está evidenció la tumoración inicial. A los 6 meses el paciente se encuentra estable y controlado. Conclusiones: Se enfatiza el valor del estudio histopatológico en los apéndices cecales ante la presencia de linfomas cecales primarios.
ABSTRACT Introduction: Primary lymphoma of the appendix occurs in 0.015% of all malignant neoplasms of the appendix. The most frequent clinical manifestation is acute appendicitis, and pathological analysis is very important. Case report: Primary lymphoma of the cecal appendix, a 38-year-old man was admitted with acute appendicitis. Macroscopic histopathological study shows diffusely thickened white appendage wall. Microscopically: high-grade Burkitt lymphoma, ACL, CD20, CD10 positive, KI 67 positive 95%, CD3, BCL2, EBV negative. Postoperative: thoracic abdominal tomography showed a tumor in the right iliac fossa without lesions or adenopathies in the abdomen and thorax. The patient was treated with two courses of chemotherapy and a control abdominal CT was performed at 6 months, which showed the initial tumor. At 6 months the patient is stable and controlled. Conclusion: The value of the histopathological study in cecal appendages is emphasized in the presence of primary cecal lymphomas.
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G-quadruplexes (G4s) are noncanonical DNA structures that frequently occur in the promoter regions of oncogenes, such as MYC, and regulate gene expression. Although G4s are attractive therapeutic targets, ligands capable of discriminating between different G4 structures are rare. Here, we describe DC-34, a small molecule that potently downregulates MYC transcription in cancer cells by a G4-dependent mechanism. Inhibition by DC-34 is significantly greater for MYC than other G4-driven genes. We use chemical, biophysical, biological, and structural studies to demonstrate a molecular rationale for the recognition of the MYC G4. We solve the structure of the MYC G4 in complex with DC-34 by NMR spectroscopy and illustrate specific contacts responsible for affinity and selectivity. Modification of DC-34 reveals features required for G4 affinity, biological activity, and validates the derived NMR structure. This work advances the design of quadruplex-interacting small molecules to control gene expression in therapeutic areas such as cancer.
Subject(s)
Cell Survival/physiology , G-Quadruplexes , Proto-Oncogene Proteins c-myc/metabolism , Binding Sites/genetics , Binding Sites/physiology , Blotting, Western , Cell Line , Cell Line, Tumor , Cell Survival/genetics , Humans , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Molecular Structure , Promoter Regions, Genetic/genetics , Promoter Regions, Genetic/physiology , Protein Binding/genetics , Protein Binding/physiology , Protein Structure, Secondary , Proto-Oncogene Proteins c-myc/genetics , Structure-Activity Relationship , Surface Plasmon ResonanceABSTRACT
A method validation study for the determination of ochratoxin A in black and white pepper (Piper spp.), nutmeg (Myristica fragrans), spice mix (blend of ginger, turmeric, pepper, nutmeg, and chili), cocoa powder, and drinking chocolate was conducted according to the International Harmonized Protocol of the International Union of Pure and Applied Chemistry. The method is based on the extraction of samples with aqueous methanol, followed by a cleanup of the extract with an immunoaffinity column. The determination is carried out by reversed-phase LC coupled with a fluorescence detector. The study involved 25 participants representing a cross-section of research, private, and official control laboratories from 12 European Union (EU) Member States, together with Turkey and Macedonia. Mean recoveries ranged from 71 to 85% for spices and from 85 to 88% for cocoa and drinking chocolate. The RSDr values ranged from 5.6 to 16.7% for spices and from 4.5 to 18.7% for cocoa and drinking chocolate. The RSDR values ranged from 9.5 to 22.6% for spices and from 13.7 to 30.7% for cocoa and drinking chocolate. The resulting Horwitz ratios ranged from 0.4 to 1 for spices and from 0.6 to 1.4 for cocoa and drinking chocolate according to the Horwitz function modified by Thompson. The method showed acceptable within-laboratory and between-laboratory precision for each matrix, and it conforms to requirements set by current EU legislation.