Deleting the ribosomal prolyl hydroxylase OGFOD1 protects mice against diet-induced obesity and insulin resistance.

Type 2 diabetes predisposes patients to heart disease, which is the primary cause of death across the globe. Type 2 diabetes often accompanies obesity and is defined by insulin resistance and abnormal glucose handling. Insulin resistance impairs glucose uptake and results in hyperglycemia, which damages tissues such as kidneys, liver, and heart. 2-oxoglutarate (2-OG)- and iron-dependent oxygenases (2-OGDOs), a family of enzymes regulating various aspects of cellular physiology, have been studied for their role in obesity and diet-induced insulin resistance. However, nothing is known of the 2-OGDO family member 2-oxoglutarate and iron-dependent prolyl hydroxylase domain containing protein 1 (OGFOD1) in this setting. OGFOD1 deletion leads to protection in cardiac ischemia-reperfusion injury and cardiac hypertrophy, which are two cardiac events that can lead to heart failure. Considering the remarkable correlation between heart disease and diabetes, the cardioprotection observed in OGFOD1-knockout mice led us to challenge these knockouts with high-fat diet. Wildtype mice fed a high-fat diet developed diet-induced obesity, insulin resistance, and glucose intolerance, but OGFOD1 knockout mice fed this same diet were resistant to diet-induced obesity and insulin resistance. These results support OGFOD1 down-regulation as a strategy for preventing obesity and insulin handling defects.

Contributing to the management of viral infections through simple immunosensing of the arachidonic acid serum level.

A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.

Bringing to Light the Importance of the miRNA Methylome in Colorectal Cancer Prognosis Through Electrochemical Bioplatforms.

This work reports the first electrochemical bioplatforms developed for the determination of the total contents of either target miRNA or methylated target miRNA. The bioplatforms are based on the hybridization of the target miRNA with a synthetic biotinylated DNA probe, the capture of the formed DNA/miRNA heterohybrids on the surface of magnetic microcarriers, and their recognition with an antibody selective to these heterohybrids or to the N6-methyladenosine (m6A) epimark. The determination of the total or methylated target miRNA was accomplished by labeling such secondary antibodies with the horseradish peroxidase (HRP) enzyme. In both cases, amperometric transduction was performed on the surface of disposable electrodes after capturing the resulting HRP-tagged magnetic bioconjugates. Because of their increasing relevance in colorectal cancer (CRC) diagnosis and prognosis, miRNA let-7a and m6A methylation were selected. The proposed electrochemical bioplatforms showed attractive analytical and operational characteristics for the determination of the total and m6A-methylated target miRNA in less than 75 min. These bioplatforms, innovative in design and application, were applied to the analysis of total RNA samples extracted from cultured cancer cells with different metastatic profiles and from paired healthy and tumor tissues of patients diagnosed with CRC at different stages. The obtained results demonstrated, for the first time using electrochemical platforms, the potential of interrogating the target miRNA methylation level to discriminate the metastatic capacities of cancer cells and to identify tumor tissues and, in a pioneering way, the potential of the m6A methylation in miRNA let-7a to serve as a prognostic biomarker for CRC.

Predictive risk model of recurrence of acute diverticulitis after the first episode.

INTRODUCTION: The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is important to individualize risk factors and develop predictive tools for their identification. MATERIALS AND METHODS: This prospective observational study included 368 patients who were diagnosed with AD between 2016 and 2021 in a tertiary general university hospital during their first episode and who had a good response to antibiotic, percutaneous, or peritoneal lavage treatment. Univariate and multivariate Cox regression analyses of the variables associated with recurrence were performed. Subsequently, a predictive risk score was developed and validated through survival studies. RESULTS: After a median follow-up of 50 months, there were 71 (19.3%) cases of recurrence out of a total of 368 patients. The mean time of recurrence was 15 months, and 73.3% of cases of recurrence occurred before 2 years of follow-up. Recurrence was independently associated with presentation with colonic perforation in the antimesenteric location (HR 3.67 95% CI [1.59-8.4]) and a CRP level greater than 100 mg/dl (HR 1.69 95% CI [1.04-2.77). A score with 5 variables was created that differentiated two risk groups: intermediate risk (0-3 points), with 19% recurrence and high risk (more than 3 points), with 42% recurrence. CONCLUSIONS: The risk of recurrence after the first episode of diverticulitis can be estimated using predictive scores. The detection of high-risk patients facilitates the individualization of follow-up and treatment.

Pilot Monitoring of Lead in Umbilical Cord Blood of Newborns Associated With the Use of Glazed Ceramics from Guanajuato, Mexico.

The use of lead-glazed pottery for cooking and storing food, a widespread practice in Mexico, represents a risk of exposure to lead from the human intrauterine stage. Therefore, a pilot study was carried out by means of the measurement of lead in umbilical cord blood by inductively coupled plasma mass spectrometry (ICP-MS) including 69 newborns from the Mexican state capital of Guanajuato, Guanajuato City, where the use of glazed clay is still widespread. Lifestyle and sociodemographic data were collected by interviewing the participating mothers. Hematological parameters and the anthropometry of the newborns and their mothers were analyzed; likewise, the G177C polymorphism in the ALAD gene was genotyped by PCR-RFLP as a marker of genetic vulnerability to lead. The geometric mean of lead in umbilical cord blood was 0.7 µg/dL (< limit of detection = 0.01-28.22). Boys presented higher values than girls (p = 0.03). Only 5.8% of these were above the safety value of the US Centers for Disease Control and Prevention (CDC) of 3.5 µg/dL. Correlations among lead concentrations, maternal age, weeks of gestation, newborn anthropometry, and hematological parameters were not found; however, the participating mothers who reported using glazed ceramics for cooking or storing food had the highest cord-blood lead concentrations (p = 0.04). Regarding genotyping, 97% had ALAD 1, while 3% had ALAD 1, 2; unfortunately, the sample size did not allow analysis of genetic vulnerability to lead. The preparation and conservation of food in handcrafted clay pottery increased the risk of having cord-blood lead values higher than those recommended by the CDC of 3.5 µg/dL (OR = 5; 95% CI:1.3-23; p = 0.01). Our preliminary results suggest that there continues to be intrauterine exposure to lead in Guanajuato.

Assessing the relationship between energy-related methane emissions and the burden of cardiovascular diseases: a cross-sectional study of 73 countries.

The energy industry significantly contributes to anthropogenic methane emissions, which add to global warming and have been linked to an increased risk of cardiovascular diseases (CVD). This study aims to evaluate the relationship between energy-related methane emissions and the burden of CVD, measured in disability-adjusted life years (DALYs), in 2019. We conducted a cross-sectional analysis of datasets from 73 countries across all continents. The analyzed datasets included information from 2019 on environmental energy-related methane emissions, burden of DALYs due to CVD. The age-standardized prevalence of obesity in adults and life expectancy at birth were retrieved. The relationship between the variables of interest was evaluated using multiple linear regression models. In the multiple model, we observed a positive linear association between methane emissions and the log-transformed count of DALYs related to CVD. Specifically, for each unit increase in energy-related methane emissions, the burden of CVD increased by 0.06% (95% CI 0.03-0.09%, p < 0.001). The study suggests that reducing methane emissions from the energy industry could improve public health for those at risk of CVD. Policymakers can use these findings to develop strategies to reduce methane emissions and protect public health.

Constrictive pericarditis heart failure in a patient with atrial fibrillation: A diagnostic challenge.

Constrictive pericarditis is an infrequent cause of heart failure. Diagnosis is challenging and requires a high level of suspicion. Subtle echocardiographic findings, as the pericardial bounce, could be the clue to diagnosis.

Magnetic Resonance Imaging in the Study of Cardiac Masses: A Case Series.

Cardiac masses are currently studied using multimodality imaging. For diagnosis, different imaging techniques that can provide complementary information are used. Cardiac magnetic resonance imaging (MRI) has become a fundamental tool for this type of pathology owing to its ability to provide tissue characterization, spatial accuracy, and the anatomic relationships of the different structures. This study presents a series of four clinical cases with an initial diagnosis of a cardiac mass. All cases were evaluated at a single center, and patients were aged 57 to 72 years. An etiological study was conducted on all patients using different imaging techniques, including MRI. This study describes the diagnostic and therapeutic procedures of the four cases, which included two intracardiac metastases and two benign tumors. Cardiac MRI was decisive in the diagnostic process, determining the clinical decision-making in all four cases. Cardiac MRI has emerged as a pivotal technique in the diagnosis of cardiac masses. It can provide a highly accurate histological diagnosis without the need for invasive techniques.

p53 and p63 Proteoforms Derived from Alternative Splicing Possess Differential Seroreactivity in Colorectal Cancer with Distinct Diagnostic Ability from the Canonical Proteins.

Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer-related death worldwide. The detection in plasma samples of autoantibodies against specific tumor-associated antigens has been demonstrated to be useful for the early diagnosis of CRC by liquid biopsy. However, new studies related to the humoral immune response in cancer are needed to enable blood-based diagnosis of the disease. Here, our aim was to characterize the humoral immune response associated with the different p53 and p63 proteoforms derived from alternative splicing and previously described as aberrantly expressed in CRC. Thus, here we investigated the diagnostic ability of the twelve p53 proteoforms and the eight p63 proteoforms described to date, and their specific N-terminal and C-terminal end peptides, by means of luminescence HaloTag beads immunoassays. Full-length proteoforms or specific peptides were cloned as HaloTag fusion proteins and their seroreactivity analyzed using plasma from CRC patients at stages I-IV (n = 31), individuals with premalignant lesions (n = 31), and healthy individuals (n = 48). p53γ, Δ40p53ß, Δ40p53γ, Δ133p53γ, Δ160p53γ, TAp63α, TAp63δ, ΔNp63α, and ΔNp63δ, together with the specific C-terminal end α and δ p63 peptides, were found to be more seroreactive against plasma from CRC patients and/or individuals with premalignant lesions than from healthy individuals. In addition, ROC (receiver operating characteristic) curves revealed a high diagnostic ability of those p53 and p63 proteoforms to detect CRC and premalignant individuals (AUC higher than 85%). Finally, electrochemical biosensing platforms were employed in POC-like devices to investigate their usefulness for CRC detection using selected p53 and p63 proteoforms. Our results demonstrate not only the potential of these biosensors for the simultaneous analysis of proteoforms' seroreactivity, but also their convenience and versatility for the clinical detection of CRC by liquid biopsy. In conclusion, we here show that p53 and p63 proteoforms possess differential seroreactivity in CRC patients in comparison to controls, distinctive from canonical proteins, which should improve the diagnostic panels for obtaining a blood-based biomarker signature for CRC detection.

OGFOD1 modulates the transcriptional and proteomic landscapes to alter isoproterenol-induced hypertrophy susceptibility.

Cardiac hypertrophy is associated with increased translation. However, little is known of the mechanisms that regulate translation in hypertrophy. Members of the 2-oxoglutarate-dependent dioxygenase family regulate several aspects of gene expression, including translation. An important member of this family is OGFOD1. Here, we show OGFOD1 accumulates in failing human hearts. Upon OGFOD1 deletion, murine hearts showed transcriptomic and proteomic changes, with only 21 proteins and mRNAs (0.6%) changing in the same direction. Additionally, OGFOD1-KO mice were protected from induced hypertrophy, supporting a role for OGFOD1 in the cardiac response to chronic stress.

Language, Science and Globalization in the Eighteenth Century.

Asia, America, and Europe have been intellectually intertwined for centuries. Several studies have been published revealing European scholars' interest in the "exotic" languages of Asia and America, as well as in ethnographic and anthropological aspects. Some scholars such as Polymath Leibniz (1646-1716), were interested in these languages in an attempt to construct a universal language, while others tried to establish language families, like the Jesuit Hervás y Panduro (1735-1809). However, all acknowledge the importance of language and the circulation of knowledge. This paper analyzes the dissemination of the compilation of eighteenth-century multilingual lexical compilations for comparative purposes as an early globalized project. These compilations were designed by European scholars and subsequently elaborated in different languages by missionaries, explorers, and scientists in the Philippines and America. Taking the correspondence and relations between botanist Mutis (1732-1808) and bureaucrats, European scientists such as polymath Humboldt (1769-1859) and Botanist Linnaeus (1707-1778) among others, and navy officers of the scientific exploration commanded by Malaspina (1754-1809) and Bustamante y Guerra (1759-1825) into consideration, I will analyze how simultaneous projects followed a unified aim, and illustrate their substantial contribution to the study of language in the late eighteenth century.

Capillary gel electrophoresis of very high molecular weight glycoproteins. Commercial and tailor-made gels for analysis of human monomeric and secretory immunoglobulin A.

Capillary gel electrophoresis (CGE) has been widely used for analysis of proteins according to their size. However, to our knowledge, this technique has not been optimized to immunoglobulin A (IgA) analysis, a protein of current and emerging high interest in several fields. IgA is the first barrier of human body against pathogens. This protein in human milk and colostrum is essential for immune protection of newborns and treatment of milk for storage in Human Milk Banks may alter IgA. The emerging use of IgA as therapeutic treatment also encourages the development of analysis methods for this class of immunoglobulins. IgA is far more heterogeneously glycosylated and complex than the well-studied IgG molecules. IgA in serum is mainly monomeric (mIgA) with about 160 kDa, while in secretions such as saliva, milk, colostrum, etc, secretory immunoglobulin A (sIgA) is the predominant form. This is a dimer where both monomers are linked by the J-chain and the secretory component accounting all together for a MW higher than 400 kDa including the glycans. This size is far from the 225 kDa MW for which commercial CGE kits are intended. The general rules governing CGE behavior of analytes cannot be directly applied to every protein. Addressing studies directed specifically to target proteins is specially needed for the large size and highly complex target analytes of this study. In this work the effect of several factors on CGE analysis of human serum and colostrum IgA is studied. The feasibility of performing analysis of both IgA classes using a commercial CGE kit is shown. In addition, this work introduces another novelty by preparing tailor-made reproducible gel buffers and to characterize them in terms of dynamic viscosity, conductivity, and electroosmotic flow mobility in bare fused silica capillaries. The possibility of analyzing mIgA and sIgA in less than 10 min using these tailor-made gels is demonstrated. Inter-day variation (RSD) for the main peak of sIgA is 0.25% for migration time (tm) and 0.27% for percentage corrected peak area (Acorr).

Functional neurological symptoms as initial presentation of Creutzfeldt-Jakob disease: case series.

BACKGROUND: Functional Neurological Disorders (FND) are common in clinical practice. It is recognized that FND may present at onset or during the course of other neurological diseases (functional comorbidity). CASES: We report a clinical series of three patients who initially presented positive signs of a functional movement disorder (FMD) and were later diagnosed with a Creutzfeldt-Jakob disease (CJD). All patients presented with unilateral functional tremor, two patients also had functional limb weakness. All patients progressed to an asymmetric corticobasal syndrome, fulfilling clinical criteria of CJD. They had a rapid progression and died within 2-3 months. CONCLUSIONS: FND may be the initial clinical presentation of neurodegenerative diseases reflecting a dysfunction across brain circuits that are involved in the pathophysiology of FND. A positive diagnosis of FND is essential as it is an adequate examination and a close follow-up of these patients in neurology clinics.

NanoAdventure: Development of a Text-Based Adventure Game in English, Spanish, and Chinese for Communicating about Nanotechnology and the Nanoscale.

Video games and immersive, narrative experiences are often called upon to help students understand difficult scientific concepts, such as sense of scale. However, the development of educational video games requires expertise and, frequently, a sizable budget. Here, we report on the use of an interactive text-style video game, NanoAdventure, to communicate about sense of scale and nanotechnology to the public. NanoAdventure was developed on an open-source, free-to-use platform with simple coding and enhanced with free or low-cost assets. NanoAdventure was launched in three languages (English, Spanish, Chinese) and compared to textbook-style and blog-style control texts in a randomized study. Participants answered questions on their knowledge of nanotechnology and their attitudes toward nanotechnology before and after reading one randomly assigned text (textbook, blog, or NanoAdventure game). Our results demonstrate that interactive fiction is effective in communicating about sense of scale and nanotechnology as well as the relevance of nanotechnology to a general public. NanoAdventure was found to be the most "fun" and easy to read of all text styles by participants in a randomized trial. Here, we make the case for interactive "Choose Your Own Adventure" style games as another effective tool among educational game models for chemistry and science communication.

Intervenciones para la exploración del pie en pacientes diabéticos, en Atención Primaria: Una revisión sistemática de Guías de Práctica Clínica / Interventions for foot examination in diabetic patients in primary care: a review of clinical practice guidelines

Objetivo principal: Identificar la mejor evidencia disponible sobre inter venciones efectivas para la exploración y estratificación del PD. Metodología: Revisión de Guías de Práctica Clínica con recomendacio nes acerca de la exploración y estratifi cación del PD. Resultados principales: Recopi lamos las intervenciones que son más efectivas para diagnosticar precozmente el PD en A.P recogidas de 10 GPC. In cluyen la evaluación visual de los pies, la valoración de la neuropatía diabética pe riférica mediante monofilamento de Semmes-Weinstein de 10 g, diapasón de 128 Hz y exploración del reflejo aquíleo, y la valoración de la enfermedad arterial periférica mediante la palpación de pul sos periféricos y determinación del índice tobillo brazo. Posteriormente estratifica ción del riesgo de desarrollar un PD. Conclusión principal: La monitori zación de las extremidades inferiores debe formar parte de los planes de cui dados de los pacientes diabéticos. Se deberían establecer unidades especiali zadas en atención al PD y poder derivar desde AP a estos pacientes (AU)

Interventions for foot examination in diabetic patients in Primary Care: A review of Clinical Practice Guidelines Main objective: To identify the best available evidence on effective in terventions in the exploration and diag nosis of DF. Methodology: Review of the Clini cal Practice Guidelines with recommen dations on the exploration and stratifica tion of DF. Main results: We compiled the interventions that are most effective for early diagnosis of DF in P.C collected in 10 CPG. They include visual assessment of their feet, assessment of diabetic pe ripheral neuropathy using a 10-g Sem mes-Weinstein monofilament, 128-Hz tuning fork, and Achilles reflex testing, assessment of peripheral arterial disease by palpation of peripheral pulses, and determination of the ankle arm index Subsequently, risk stratification of deve loping DF. Main conclusion: Monitoring of the lower extremities should be part of the care plans for diabetic patients. Spe cialized units should be established for DF care and these patients should be able to be referred from PC (AU)

¿Qué intervenciones educativas son efectivas para prevenir el pie diabético? Una Revisión de Guías de Práctica Clínica / What educational interventions are effective in preventing diabetic foot? A review of clinical practice guidelines

Objetivo principal: Identificar la mejor evidencia disponible sobre inter venciones educativas que pueden ayu dar a prevenir la aparición del Pie Diabé tico (PD) en Atención Primaria (AP). Metodología: Revisión sistemáti ca de Guías de Práctica clínica (GPC) con recomendaciones acerca de inter venciones educativas para prevenir el PD. La búsqueda se ha llevado a cabo en bases de datos de fuentes terciarias, secundarias y primarias con los descrip tores Diabetes mellitus, Pie diabético y Educación en salud. Para evaluar la cali dad de las GPC encontradas se utilizó la herramienta AGREE II. Resultados: Fueron recopiladas las intervenciones educativas que, según las 10 GPC revisadas, pueden resultar más efectivas para prevenir la aparición del PD en AP. Estas recomendaciones, han sido incluidas como actividades de los NIC (Nursing Interventions Classifica tion) relacionados con el tema. Conclusión: El resultado principal de este trabajo indica que las interven ciones educativas para prevenir la apari ción del PD deben formar parte, de ma nera inexcusable, de los planes de cui dados en los pacientes diabéticos. Son unas intervenciones que parecen ser muy costo efectivas y que, estructuradas adecuadamente, pueden contribuir a disminuir la incidencia de PD y a reducir el número de amputaciones (AU)

Main objective: Identify the best available evidence on educational inter ventions that can help prevent the ap pearance of Diabetic Foot (DF) in Pri mary Care. Methodology: Systematic review on 10 Clinical Practice Guidelines (CPG) with recommendations on education to prevent the DF. The search was carried out in databases of tertiary, secondary and primary sources with the descriptors Diabetes mellitus, Diabetic foot and Health education. The AGREE II tool was used to assess the quality of the CPGs found. Results: Were compiled the edu cational interventions that, according to the revised 10 CPG’s, are more effective in preventing the appearance of DF in Primary Care. Have been included these recommendations as NIC (Nursing Inter ventions Classification) activities related to the topic. Conclusion: The main result of this work indicates that educational inter ventions to prevent the onset of DF mus inexcusably form part of the care plans for diabetic patients. These are interven tions that appear to be very cost-effecti ve, properly structured, will help reduce the incidence of DF and reduce the num ber of amputations (AU)

Insight into the Burden of Malignant Respiratory Tumors and their Relationship with Smoking Rates and Lead Contamination in Mexico.

We aimed to report the results from the Global Burden of Disease Study 2019 related to respiratory malignant tumors (tracheal, bronchial, and lung) in Mexico. We also evaluated the relationship between the burden of these neoplasms and the proportion of daily smokers and total lead emissions in 2019. A cross-sectional analysis of ecological data was performed. The burden of these tumors was 152,189 disability-adjusted life-years (DALYs), and years of life lost (YLL) contributed to 99% of them. The highest DALYs rates (per 100,000) were observed in the states of Sinaloa, Chihuahua, Baja California Sur, Sonora, and Nayarit. We documented a linear relationship between the DALYs rates and the prevalence of daily smokers (ß = 8.50, 95% CI 1.58-15.38) and the total lead emissions (tons/year: ß = 4.04, 95% CI 0.07-8.01). If later replicated, our study would provide insight into the major relevance of regulating tobacco use and the activities associated with the production of lead dust and other hazardous contaminants.