Food Chemicals and Epigenetic Targets: An Epi Food Chemical Database.

There is increasing awareness of epigenetics's importance in understanding disease etiologies and developing novel therapeutics. An increasing number of publications in the past few years reflect the renewed interest in epigenetic processes and their relationship with food chemicals. However, there needs to be a recent study that accounts for the most recent advances in the area by associating the chemical structures of food and natural product components with their biological activity. Here, we analyze the status of food chemicals and their intersection with natural products in epigenetic research. Using chemoinformatics tools, we compared quantitatively the chemical contents, structural diversity, and coverage in the chemical space of food chemicals with reported epigenetic activity. As part of this work, we built and curated a compound database of food and natural product chemicals annotated with structural information, an epigenetic target activity profile, and the main source of the food chemical or natural product, among other relevant features. The compounds are cross-linked with identifiers from other major public databases such as FooDB and the collection of open natural products, COCONUT. The compound database, the "Epi Food Chemical Database", is accessible in HTML and CSV formats at https://github.com/DIFACQUIM/Epi_food_Chemical_Database.

Dietary inflammatory index and lower glomerular filtration rate in Mexican adults.

We hypothesized that higher scores on the dietary inflammatory index (DII) would be associated with a lower glomerular filtration rate (GFR). This cross-sectional study included 2098 participants from Mexican Teachers Cohort Study, the Health Workers Cohort Study, and the Comitán Study belonging to the RenMex consortium. Energy-adjusted DII scores were estimated using a semi-quantitative food frequency questionnaire (FFQ). eGFR was estimated by the CKD Epidemiology Collaboration equation. Quantile regression models and ordered regression models were estimated to assess the associations of interest. Median age of study participants was 47 years, median eGFR was 102.9 mL/min/1.73m2, and the median energy-adjusted DII was 0.89 (range, -2.25, +4.86). The median eGFR was lower in participants in the highest percentile of DII compared to those in the lowest percentile (103.8 vs 101.4). We found that continuous and categorical energy-adjusted DII scores were associated with lower eGFR, especially at the lower percentiles. In adjusted ordered logistic regression, we found that the highest DII category was associated with 1.80 times the odds of belonging to the mildly decreased eGFR category or moderately decreased eGFR category compared lowest DII category (OR: 1.80, 95%CI 1.35, 2.40). A high DII score was associated with a lower eGFR among the Mexican population. Additional studies are crucial to validate these findings and explore potential strategies to reduce the consumption of pro-inflammatory foods as a preventive approach for chronic kidney disease (CKD).

Association between soft drinks intake and low glomerular filtration rate in Mexican adults: Results from RenMex.

BACKGROUND & AIMS: To evaluate the association between soft drinks (SDs) consumption and estimated glomerular filtration rate (eGFR) in a Mexican adult population. METHODS: We used data from the RenMex consortium (n = 2095) that included the Mexican Teachers Cohort Study (34-65 years), the Health Workers Cohort Study (18-90 years), and the Comitán Study (19-91 years). In this cross-sectional study, we assessed SDs consumption (cola and flavored soda) using a food frequency questionnaire (FFQ) and estimated eGFR using the CKD Epidemiology Collaboration equation. Quantile regression was used to assess the association between SDs consumption and eGFR with eGFR as a continuous variable. Multinomial logistic regression models were used for eGFR categories derived from quantile regression (mildly decreased eGFR, ≥72.9-87.9 mL/min/1.73 m2 and moderately decreased eGFR, <72.9 mL/min/1.73 m2). RESULTS: Mean age of study participants was 47.2 years, 67.5% were women, and 12.2% had diabetes. eGFR was <60 mL/min/1.73 m2 in 3.7% of study participants. Mildly decreased eGFR was present in 14.8%, and moderately decreased eGFR was present in 10.1% of study participants. Quantile regression results showed that SDs consumption was associated with lower eGFR at the 10th, 25th, 50th and 75th percentile. Based on the final adjusted multinomial model, ≥7 servings/week was positively associated with moderately decreased eGFR relative to <1 serving/week (Relative Risk Ratio = 1.95; 95% CI: 1.07-3.57). CONCLUSION: Our results suggest that higher SDs consumption is associated with lower eGFR. Encouraging healthy dietary choices should be part of the management and prevention of CKD.

Chemical Multiverse and Diversity of Food Chemicals.

Food chemicals have a fundamental role in our lives, with an extended impact on nutrition, disease prevention, and marked economic implications in the food industry. The number of food chemical compounds in public databases has substantially increased in the past few years, which can be characterized using chemoinformatics approaches. We and other groups explored public food chemical libraries containing up to 26,500 compounds. This study aimed to analyze the chemical contents, diversity, and coverage in the chemical space of food chemicals and additives and, from here on, food components. The approach to food components addressed in this study is a public database with more than 70,000 compounds, including those predicted via omics techniques. It was concluded that food components have distinctive physicochemical properties and constitutional descriptors despite sharing many chemical structures with natural products. Food components, on average, have large molecular weights and several apolar structures with saturated hydrocarbons. Compared to reference databases, food component structures have low scaffold and fingerprint-based diversity and high structural complexity, as measured by the fraction of sp3 carbons. These structural features are associated with a large fraction of macronutrients as lipids. Lipids in food components were decompiled by an analysis of the maximum common substructures. The chemical multiverse representation of food chemicals showed a larger coverage of chemical space than natural products and FDA-approved drugs by using different sets of representations.

The influence of asthma on neuroinflammation and neurodevelopment: From epidemiology to basic models.

Asthma is a highly heterogeneous inflammatory disease that can have a significant effect on both the respiratory system and central nervous system. Population based studies and animal models have found asthma to be comorbid with a number of neurological conditions, including depression, anxiety, and neurodevelopmental disorders. In addition, maternal asthma during pregnancy has been associated with neurodevelopmental disorders in the offspring, such as autism spectrum disorders and attention deficit hyperactivity disorder. In this article, we review the most current epidemiological studies of asthma that identify links to neurological conditions, both as it relates to individuals that suffer from asthma and the impacts asthma during pregnancy may have on offspring neurodevelopment. We also discuss the relevant animal models investigating these links, address the gaps in knowledge, and explore the potential future directions in this field.

Biocatalysts Based on Immobilized Lipases for the Production of Fatty Acid Ethyl Esters: Enhancement of Activity through Ionic Additives and Ion Exchange Supports.

Ionic additives affect the structure, activity and stability of lipases, which allow for solving common application challenges, such as preventing the formation of protein aggregates or strengthening enzyme-support binding, preventing their desorption in organic media. This work aimed to design a biocatalyst, based on lipase improved by the addition of ionic additives, applicable in the production of ethyl esters of fatty acids (EE). Industrial enzymes from Thermomyces lanuginosus (TLL), Rhizomucor miehei (RML), Candida antárctica B (CALB) and Lecitase®, immobilized in commercial supports like Lewatit®, Purolite® and Q-Sepharose®, were tested. The best combination was achieved by immobilizing lipase TLL onto Q-Sepharose® as it surpassed, in terms of %EE (70.1%), the commercial biocatalyst Novozyme® 435 (52.7%) and was similar to that of Lipozyme TL IM (71.3%). Hence, the impact of ionic additives like polymers and surfactants on both free and immobilized TLL on Q-Sepharose® was assessed. It was observed that, when immobilized, in the presence of sodium dodecyl sulfate (SDS), the TLL derivative exhibited a significantly higher activity, with a 93-fold increase (1.02 IU), compared to the free enzyme under identical conditions (0.011 IU). In fatty acids ethyl esters synthesis, Q-SDS-TLL novel derivatives achieved results similar to commercial biocatalysts using up to ~82 times less enzyme (1 mg/g). This creates an opportunity to develop biocatalysts with reduced enzyme consumption, a factor often associated with higher production costs. Such advancements would ease their integration into the biodiesel industry, fostering a greener production approach compared to conventional methods.

Characterizing the neuroimmune environment of offspring in a novel model of maternal allergic asthma and particulate matter exposure.

Inflammation during pregnancy is associated with an increased risk for neurodevelopmental disorders (NDD). Increased gestational inflammation can be a result of an immune condition/disease, exposure to infection, and/or environmental factors. Epidemiology studies suggest that cases of NDD are on the rise. Similarly, rates of asthma are increasing, and the presence of maternal asthma during pregnancy increases the likelihood of a child being later diagnosed with NDD such as autism spectrum disorders (ASD). Particulate matter (PM), via air pollution, is an environmental factor known to worsen the symptoms of asthma, but also, PM has been associated with increased risk of neuropsychiatric disorders. Despite the links between asthma and PM with neuropsychiatric disorders, there is a lack of laboratory models investigating combined prenatal exposure to asthma and PM on offspring neurodevelopment. Thus, we developed a novel mouse model that combines exposure to maternal allergic asthma (MAA) and ultrafine iron-soot (UIS), a common component of PM. In the current study, female BALB/c mice were sensitized for allergic asthma with ovalbumin (OVA) prior to pregnancy. Following mating and beginning on gestational day 2 (GD2), dams were exposed to either aerosolized OVA to induce allergic asthma or phosphate buffered saline (PBS) for 1 h. Following the 1-h exposure, pregnant females were then exposed to UIS with a size distribution of 55 to 169 nm at an average concentration of 176 ± 45 µg/m3) (SD), or clean air for 4 h, over 8 exposure sessions. Offspring brains were collected at postnatal days (P)15 and (P)35. Cortices and hippocampal regions were then isolated and assessed for changes in cytokines using a Luminex bead-based multiplex assay. Analyses identified changes in many cytokines across treatment groups at both timepoints in the cortex, including interleukin-1 beta (IL-1ß), and IL-17, which remained elevated from P15 to P35 in all treatment conditions compared to controls. There was a suppressive effect of the combined MAA plus UIS on the anti-inflammatory cytokine IL-10. Potentially shifting the cytokine balance towards more neuroinflammation. In the hippocampus at P15, elevations in cytokines were also identified across the treatment groups, namely IL-7. The combination of MAA and UIS exposure (MAA-UIS) during pregnancy resulted in an increase in microglia density in the hippocampus of offspring, as identified by IBA-1 staining. Together, these data indicate that exposure to MAA, UIS, and MAA-UIS result in changes in the neuroimmune environment of offspring that persist into adulthood.

Syphilis Mimicking Malignant Pulmonary Tumor With Nodal and Bone Metastasis on 18 F-FDG PET/CT.

ABSTRACT: A 52-year-old man suffering left pleuritic pain underwent a chest CT showing a subpleural pulmonary nodule in the left upper lobe. Because of the possibility of a lung tumor, he was referred for 18 F-FDG PET/CT. The scan revealed FDG uptake in the pulmonary nodule, in an upper right paratracheal lymph node, and at 4 destructive bone lesions. Pathologic examination after pulmonary biopsy manifested only the presence of inflammatory cells. Further clinical history research proved risky sexual behavior with a positive syphilis serology test. A follow-up PET/CT 7 months after penicillin therapy showed a complete metabolic response of all the lesions.

Asthma as an Inflammatory Reason of Tracheobronchial PSMA Uptake.

ABSTRACT: A 53-year-old man with persisting increased serum prostate-specific antigen level (9.53 ng/mL) and repeated negative prostate biopsies was referred for a PET/CT with 68 Ga-PSMA-11. The PET/CT revealed focal uptake in the prostate suggestive of localized prostate cancer. Incidentally, it also showed a diffuse uptake in the tracheobronchial tree suspicious for a benign etiology. Because of the clinical history of asthma exacerbation in the previous week, further supplementary studies were performed showing a pathological fractional exhaled nitric oxide level (92 ppb; reference values, <25 ppb) and mild airway obstruction in the spirometry. These findings confirmed asthma as an inflammatory etiology of the tracheobronchial PSMA uptake.

Characterizing the Neuroimmune Environment of Offspring in a Novel Model of Maternal Allergic Asthma and Particulate Matter Exposure.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by the presence of decreased social interactions and an increase in stereotyped and repetitive behaviors. Epidemiology studies suggest that cases of ASD are on the rise. Similarly, rates of asthma are increasing, and the presence of maternal asthma during pregnancy increases the likelihood of a child being later diagnosed with ASD. Particulate matter (PM), via air pollution, is an environmental factor known to worsen the symptoms of asthma, but also, PM has been associated with increased risk of neuropsychiatric disorders including ASD. Despite the links between asthma and PM with neuropsychiatric disorders, there is a lack of laboratory models investigating combined prenatal exposure to asthma and PM on offspring neurodevelopment. Thus, we developed a novel mouse model that combines exposure to maternal allergic asthma (MAA) and ultrafine iron-soot (UIS), a common component of PM. In the current study, female BALB/c mice were primed for allergic asthma with ovalbumin (OVA) prior to pregnancy. Following mating and beginning on gestational day 2 (GD2), dams were exposed to either aerosolized OVA or phosphate buffered saline (PBS) for 1 hour. Following the 1-hour exposure, pregnant females were then exposed to UIS or clean air for 4 hours. Offspring brains were collected at postnatal days (P)15 and (P)35. Cortices and hippocampal regions were then isolated and assessed for changes in cytokines using a Luminex bead-based multiplex assay. Analyses identified changes in many cytokines across treatment groups at both timepoints in the cortex, including interleukin-1 beta (IL-1ß), IL-2, IL-13, and IL-17, which remained elevated from P15 to P35 in all treatment conditions compared to controls. In the hippocampus at P15, elevations in cytokines were also identified across the treatment groups, namely interferon gamma (IFNγ) and IL-7. The combination of MAA and UIS exposure (MAA-UIS) during pregnancy resulted in an increase in microglia density in the hippocampus of offspring, as identified by IBA-1 staining. Together, these data indicate that exposure to MAA, UIS, and MAA-UIS result in changes in the neuroimmune environment of offspring that persist into adulthood.

Chronic pain characteristics in COVID-19 survivors after an ICU stay. A cross-sectional study.

BACKGROUND: The onset and characteristics of chronic pain following an intensive care unit (ICU) stay for COVID-19 have never been thoroughly investigated. STUDY DESIGN: A multicenter cohort study was conducted to describe chronic pain, according to ICD-11, among COVID-19 survivors. The chronic pain was assessed during face-to-face consultations with a pain specialist. RESULTS: Among 204 COVID-19 ICU survivors, 143 patients with mean age of 60 ± 14 years were included nine months after discharge from the ICU. More than half (54%) of patients experienced new-onset chronic pain. In total, 102 different forms of pain were reported in these patients. Secondary pain was the most frequent type, comprising musculoskeletal (40%), post-traumatic (34%), neuropathic (25%), and visceral (13%). Primary chronic pain was rare (7%). The three most common sites of pain were the shoulders, chest, and head. Pain was moderate to severe in 75% of cases, and higher intensity was associated with a greater impact on daily life. Anxiety, depression, post-traumatic stress, perceived stress, and debilitating pain were frequently associated. Intubation was more frequent in patients with chronic pain. Specialized pain centre follow-up was required for 21% of the survivors, which represented 40% of the patients who developed new-onset chronic pain. CONCLUSION: New-onset chronic pain is common after an ICU stay for COVID-19 and may manifest in various forms. Secondary pain caused by ICU management is the most frequent. Patients should undergo screening after ICU discharge to facilitate prompt, thorough, and personalized pain management. CLINICAL TRIAL REGISTRATION: NCT04940208.

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks.

Processes involving lipases in obtaining active pharmaceutical ingredients (APIs) are crucial to increase the sustainability of the industry. Despite their lower production cost, microbial lipases are striking for their versatile catalyzing reactions beyond their physiological role. In the context of taking advantage of microbial lipases in reactions for the synthesis of API building blocks, this review focuses on: (i) the structural origins of the catalytic properties of microbial lipases, including the results of techniques such as single particle monitoring (SPT) and the description of its selectivity beyond the Kazlauskas rule as the "Mirror-Image Packing" or the "Key Region(s) rule influencing enantioselectivity" (KRIE); (ii) immobilization methods given the conferred operative advantages in industrial applications and their modulating capacity of lipase properties; and (iii) a comprehensive description of microbial lipases use as a conventional or promiscuous catalyst in key reactions in the organic synthesis (Knoevenagel condensation, Morita-Baylis-Hillman (MBH) reactions, Markovnikov additions, Baeyer-Villiger oxidation, racemization, among others). Finally, this review will also focus on a research perspective necessary to increase microbial lipases application development towards a greener industry.

The Mexican Consortium of Epidemiological Studies for the Prevention, Diagnosis, and Treatment of Chronic Kidney Disease: a review of collaborating studies.

OBJECTIVE: To harmonize participants' information from five epidemiological studies. MATERIALS AND METHODS: The Mexican Consortium of Epidemiological Studies for the Prevention, Diagnosis, and Treatment of Chronic Kidney Disease (RenMex, by its Spanish acronym) was established in 2018. RenMex is a consortium of five studies: The Mexican Teachers Cohort Study; the Mexico City Diabetes Study; the Health Workers Cohort Study; the Comitán Study; and the Salt Consumption in Mexico Study, which assessed baseline serum creatinine, albumin, and C-reactive protein, all performed with standardized techniques. RESULTS: RenMex includes 3 133 participants, with a mean age of 44.8 years, 68.8% women, 10.8% with a previous medical diagnosis of type 2 diabetes, and 24.1% living with obesity. CONCLUSIONS: In the future, RenMex will work on more detailed analyses with each cohort allowed to opt in or out for each topic according to their individual data.

Maternal Allergic Asthma Induces Prenatal Neuroinflammation.

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by impaired social interactions and communication skills and repetitive or stereotyped behaviors. Rates of ASD diagnosis continue to rise, with current estimates at 1 in 44 children in the US (Maenner 2021). Epidemiological studies have suggested a link between maternal allergic asthma and an increased likelihood of having a child diagnosed with ASD. However, a lack of robust laboratory models prevents mechanistic research from being carried out. We developed a novel mouse model of maternal asthma-allergy (MAA) and previously reported that offspring from these mothers exhibit behavioral deficits compared to controls. In addition, it was shown that epigenetic regulation of gene expression in microglia was altered in these offspring, including several autism candidate genes. To further elucidate if there is neuroinflammation in the fetus following MAA, we investigated how allergic asthma impacts the maternal environment and inflammatory markers in the placenta and fetal brain during gestation. Female C57Bl/6 mice were primed with ovalbumin (OVA) prior to allergic asthma induction during pregnancy by administering aerosolized ovalbumin or PBS control to pregnant dams at gestational days (GD)9.5, 12.5, and 17.5. Four hours after the final induction, placenta and fetal brains were collected and measured for changes in cytokines using a Luminex bead-based multiplex assay. Placental MAA tissue showed a decrease in interleukin (IL)-17 in male and female offspring. There was a sex-dependent decrease in female monocyte chemoattractant protein 1 (MCP-1). In male placentas, IL-4, C-X-C motif chemokine 10 (CXCL10)-also known as interferon γ-induced protein 10 kDa (IP-10)-and chemokine (C-C motif) ligand 5 (RANTES) were decreased. In fetal brains, elevated inflammatory cytokines were found in MAA offspring when compared to controls. Specifically, interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1α (IL-1α), IL-6, and tumor necrosis factor α (TNFα) were elevated in both males and females. In contrast, a decrease in the cytokine IL-9 was also observed. There were slight sex differences after OVA exposures. Male fetal brains showed elevated levels of macrophage inflammatory protein-2 (MIP-2), whereas female brains showed increased keratinocytes-derived chemokine (KC). In addition, IL-1𝛽 and IP-10 in male fetal brains were decreased. Together, these data indicate that repeated exposure to allergic asthma during pregnancy alters cytokine expression in the fetal environment in a sex-dependent way, resulting in homeostatic and neuroinflammatory alterations in the fetal brain.

Potencial nematicida de hongos aislados de cultivos de plátano dominico hartón (Musa AAB Simmonds) del suroeste antioqueño / Nematicidal potential of fungi isolated of Plantain crops (Musa AAB Simmonds) from southwest Antioquia

RESUMEN El objetivo de este trabajo fue evaluar el potencial nematicida de aislados fúngicos provenientes de cultivos de plátano de los municipios de Andes y Jardín (Suroeste antioqueño). Se analizaron in vitro diez aislados fúngicos frente a los nematodos fitoparásitos de los géneros Meloidogyne y Radopholus. Los hongos pertenecían a los géneros Paecilomyces, Pochonia, Arthrobotrys, Lecanicillium y Metarhizium. Se realizaron pruebas metabólicas cualitativas con diversos sustratos con el fin de observar la capacidad de degradación de diferentes compuestos característicos en la estructura de huevos o juveniles de nematodos. También, se evaluó la capacidad de colonizar huevos o juveniles de Meloidogyne sp. y, la mortalidad de los aislados frente a los géneros Meloidogyne y Radopholus. Se encontró que la mayoría de los aislados fueron capaces de degradar Tween 80 (90% de los aislados), seguido de caseína (80%), gelatina (80%), Tween 20 (60%), y en menor medida quitina (40% de los aislados); además, el 30% de los aislados presentaron formación de cristales en los medios de Tween. El 70% de los aislados podían infectar huevos, mientras que el 30% restante infectaban juveniles (J2) de Meloidogyne sp., después 24 horas de incubación. En cuanto al porcentaje de mortalidad del hongo y el filtrado, se encontró que todos los aislados difieren del control (p<0.05), siendo aislados de los géneros Pochonia y Paecilomyces quienes presentaron porcentajes de mortalidad superiores al 90%.

ABSTRACT The aim of this work was to evaluate the nematicidal potential of fungal isolates from plantain crops in the municipalities of Andes and Jardín (Southwest Antioquia). Ten fungal isolates were analyzed in vitro against phytoparasitic nematodes of the genera Meloidogyne and Radopholus. The fungi belonged to the genera Paecilomyces, Pochonia, Arthrobotrys, Lecanicillium, and Metarhizium. Qualitative metabolic tests were carried out with various substrates to observe the degradation capacity of different characteristic compounds in the structure of nematode eggs or juveniles. Also, the ability to colonize eggs or juveniles of Meloidogyne sp. and, the mortality of the isolates against the genera Meloidogyne and Radopholus were evaluated. It was found that most isolates were capable of degrading Tween 80 (90% of isolates), followed by casein (80%), gelatin (80%), Tween 20 (60%), and to a lesser extent chitin (40 % of isolates); in addition, 30% of the isolates presented crystal formation in the Tween media. 70% of the isolates could infect eggs, while the remaining 30% infected juveniles (J2) of Meloidogyne sp., after 24 hours of incubation. Regarding the percentage of mortality of the fungus and the filtrate, it was found that all the isolates differ from the control (p<0.05), and some isolates of the genera Pochonia and Paecilomyces who presented mortality percentages higher than 90%.

¿Memoria oficial o literatura testimonial? El libro "Comuna 13 de Medellín, El Drama del Conflicto Armado" del policía Yoni Alexander Rendón Rendón / Is it Official Memory or Testimonial Literature? The book "Comuna 13 de Medellín. El Drama del Conflicto Armado" by the policeman Yoni Alexander Rendón Rendón

Resumen: El artículo analiza el libro "Comuna 13 de Medellín. El Drama del Conflicto Armado" publicado por Yoni Alexander Rendón Rendón, en 2007 cuando el autor era patrullero de la Policía Nacional, en una las zonas más violentas de Colombia: los barrios populares de Medellín. El libro se analizó en sus dimensiones textuales y extratextuales lo que permitió clasificarlo en el género testimonial y en algunos de los universos discursivos sobre el conflicto urbano, lo que explica su inserción exitosa en las disputas sobre la verdad de lo ocurrido en la Comuna 13 en octubre de 2002 en la operación Orión.

Abstract The article analyzes the book "Comuna 13 de Medellín. El Drama del Conflicto Armado" published by Yoni Alexander Rendón Rendón Rendón, in 2007 when the author was a patrolman of the National Police, in one of the most violent areas of Colombia: the popular neighborhoods of Medellín. The book was analyzed in its textual and extratextual dimensions, which allowed it to be classified in the testimonial genre and in some of the discursive universes on the urban conflict, which explains its successful insertion in the disputes about the truth of what happened in Comuna 13 in October 2002 in the Orion Operation.

Repeated allergic asthma in early versus late pregnancy differentially impacts offspring brain and behavior development.

BACKGROUND: Stress during pregnancy and maternal inflammation are two common prenatal factors that impact offspring development. Asthma is the leading chronic condition complicating pregnancy and a common source of prenatal stress and inflammation. OBJECTIVE: The goal of this study was to characterize the developmental impact of repeated allergic asthma inflammation during pregnancy on offspring behavioral outcomes and brain inflammation. METHODS: Pregnant female C57BL/6 mice were sensitized with ovalbumin (OVA) or PBS vehicle control and then randomly assigned to receive daily aerosol exposures to the same OVA or PBS treatment during early, gestational days (GD) 2-GD9, or late pregnancy, GD10-GD17. Maternal sera were collected after the first and last aerosol induction regimen and measured for concentrations of corticosterone, anti-OVA IgE, and cytokine profiles. Juvenile male and female offspring were assessed for locomotor and social behaviors and later as adults assessed for anxiety-like, and marble burying behaviors using a series of behavioral tasks. Offspring brains were evaluated for region-specific differences in cytokine concentrations. RESULTS: In early gestation, both PBS and OVA-exposed dams had similar serum corticosterone concentration at the start (GD2) and end (GD9) of daily aerosol inductions. Only OVA-exposed dams showed elevations in cytokines that imply a diverse and robust T helper cell-mediated immune response. Male offspring of early OVA-exposed dams showed decreases in open-arm exploration in the elevated plus maze and increased marble burying without concomitant changes in locomotor activity or social interactions. These behavioral deficits in early OVA-exposed male offspring were associated with lower concentrations of G-CSF, IL-4, IL-7, IFNγ, and TNFα in the hypothalamus. In late gestation, both PBS and OVA-exposed dams had increased corticosterone levels at the end of daily aerosol inductions (GD17) compared to at the start of inductions (GD10). Male offspring from both PBS and OVA-exposed dams in late gestation showed similar decreases in open arm exploration on the elevated plus maze compared to OVA male offspring exposed in early gestation. No behavioral differences were present in female offspring across all treatment groups. However, females of dams exposed to OVA during early gestation displayed similar reductions as males in hypothalamic G-CSF, IL-7, IL-4, and IFNγ. DISCUSSION: The inflammatory responses from maternal allergic asthma in early gestation and resulting increases in anxiety-like behavior in males support a link between the timing of prenatal insults and sex-specific developmental outcomes. Moreover, the heightened stress responses in late gestation and concomitant dampened inflammatory response to allergic asthma suggest that interactions between the maternal immune and stress-response systems shape early life fetal programming.

Melanoma mucoso nasal: una enfermedad impredecible / Mucosal melanoma of the nasal cavity: an unpredictable disease

RESUMEN El melanoma mucoso maligno es un tumor neuroectodérmico de menos del 5% de las neoplasias nasosinusales. Es un tumor de mal pronóstico clásicamente su promedio de supervivencia a cinco años es cercano al 28% y 17,5% a diez años, siendo aún peor cuando existe metástasis en cuello. Se presentan a continuación dos casos de melanoma mucoso en cavidad nasal y senos paranasales, el primero mujer 58 años con melanoma septal llevada a septotomía abierta más quimioterapia y radioterapia adyuvante, con recurrencia en cuello submaxilar derecho tratada con vaciamiento supraomohioideo actualmente sin recurrencia; el segundo hombre de 40 años con antecedente de resección melanoma septal quien presenta nuevo melanoma región etmoidal izquierda luego de su primera cirugía y es llevado a resección endoscópica transnasal sin tratamiento adyuvante por decisión del paciente.

ABSTRACT Sinonasal mucosal melanoma is a neuroectodermic tumor account less 5% of nasosinusal tumors. It has a poor prognosis with a five-year average survival near 28% and 17.5% to 10 years; if neck metastasis is even worst. Here we present two clinical cases. First one a woman 58 years old with septal melanoma who receives an open septectomy with chemotherapy and radiotherapy with submaxillary recurrence treated with supraomohyoid neck dissection. The second case, a man 40 years old with previous septal melanoma surgery who has an ethmoid sinus recurrence and receives transnasal endoscopic surgery without adjuvant therapy by patient desire.

Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons.

Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice. LTR- and LINE-1-retroelements use different mechanisms for retrotransposition, although both involve the reverse transcription of an intermediate retroelement-derived RNA. Retrotransposon activity continues to effect the germline and somatic genomes, generating interindividual variability over evolution and potentially influencing cancer and brain physiology, respectively. However, relatively little is known about the functional consequences of retrotransposition. In this study, we have synthesized and characterized reverse transcriptase inhibitors specific for mammalian LINE-1 retrotransposons, which might help deciphering the functional impact of retrotransposition in vivo.