Unfilled gaps by polß lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway.

Base excision repair (BER) involves the tightly coordinated function of DNA polymerase ß (polß) and DNA ligase I (LIG1) at the downstream steps. Our previous studies emphasize that defective substrate-product channeling, from gap filling by polß to nick sealing by LIG1, can lead to interruptions in repair pathway coordination. Yet, the molecular determinants that dictate accurate BER remains largely unknown. Here, we demonstrate that a lack of gap filling by polß leads to faulty repair events and the formation of deleterious DNA intermediates. We dissect how ribonucleotide challenge and cancer-associated mutations could adversely impact the ability of polß to efficiently fill the one nucleotide gap repair intermediate which subsequently results in gap ligation by LIG1, leading to the formation of single-nucleotide deletion products. Moreover, we demonstrate that LIG1 is not capable of discriminating against nick DNA containing a 3'-ribonucleotide, regardless of base-pairing potential or damage. Finally, AP-Endonuclease 1 (APE1) shows distinct substrate specificity for the exonuclease removal of 3'-mismatched bases and ribonucleotides from nick repair intermediate. Overall, our results reveal that unfilled gaps result in impaired coordination between polß and LIG1, defining a possible type of mutagenic event at the downstream steps where APE1 could provide a proofreading role to maintain BER efficiency.

Liquid Biopsies for Monitoring Medulloblastoma: Circulating Tumor DNA as a Biomarker for Disease Progression and Treatment Response.

Pediatric brain tumors, including medulloblastoma (MB), represent a significant challenge in clinical oncology. Early diagnosis, accurate monitoring of therapeutic response, and the detection of minimal residual disease (MRD) are crucial for improving outcomes in these patients. This review aims to explore recent advancements in liquid biopsy techniques for monitoring pediatric brain tumors, with a specific focus on medulloblastoma. The primary research question is how liquid biopsy techniques can be effectively utilized for these purposes. Liquid biopsies, particularly the analysis of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF), are investigated as promising noninvasive tools. This comprehensive review examines the components of liquid biopsies, including ctDNA, cell-free DNA (cfDNA), and microRNA (miRNA). Their applications in diagnosis, prognosis, and MRD assessment are critically assessed. The review also discusses the role of liquid biopsies in categorizing medulloblastoma subgroups, risk stratification, and the identification of therapeutic targets. Liquid biopsies have shown promising applications in the pediatric brain tumor field, particularly in medulloblastoma. They offer noninvasive means of diagnosis, monitoring treatment response, and detecting MRD. These biopsies have played a pivotal role in subgroup classification and risk stratification of medulloblastoma patients, aiding in the identification of therapeutic targets. However, challenges related to sensitivity and specificity are noted. In conclusion, this review highlights the growing importance of liquid biopsies, specifically ctDNA analysis in CSF, in pediatric brain tumor management, with a primary focus on medulloblastoma. Liquid biopsies have the potential to revolutionize patient care by enabling early diagnosis, accurate monitoring, and MRD detection. Nevertheless, further research is essential to validate their clinical utility fully. The evolving landscape of liquid biopsy applications underscores their promise in improving outcomes for pediatric brain tumor patients.

Dermatological Manifestations in Patients With Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) is a progressive disease and has multiple clinical manifestations; when CKD reaches the end stage, at least one cutaneous manifestation appears due to some increased toxin levels or a constant proinflammatory state. Nonspecific manifestations include pruritus, xerosis, pigmentation disorders, acquired ichthyosis, purpuric spots, and nail disorders. Some specific manifestations are bullous dermatoses, acquired perforating dermatoses (APD), eruptive xanthoma, access site infections, calcifying disorders, and nephrogenic systemic fibrosis (NSF). All these cutaneous changes negatively impact patients; early recognition and diagnosis of these dermatoses will make a difference in their quality of treatment. Exploring a patient's skin is fundamental to suspect some diseases and increased toxin levels; pruritus occurs when uremic toxins are raised, and nail disorders are associated with hypoalbuminemia. This review provides the clinician with information on the clinical manifestations that occur in CKD, including epidemiology, pathophysiology, clinical manifestations, diagnosis, histopathology, treatment, and life impact of the dermatoses in CKD.

Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review.

Tranexamic acid (TXA), a fibrinolytic agent, effectively inhibits plasminogen activation, thereby reducing fibrinolysis and hemorrhage. This study focused on its application in trauma patients undergoing emergency surgery, a critical area due to trauma's significant role in mortality. Our investigation involved a meticulous screening of randomized controlled trials from databases including Scopus, PubMed, Web of Science, and Cochrane. The findings indicate that TXA intervention is promising in enhancing outcomes for trauma patients. However, the drug's effectiveness may vary based on the specific nature of the medical condition. In summary, robust evidence suggests that TXA can diminish blood loss, lower transfusion rates, reduce complications, and improve hemoglobin and hematocrit levels in surgical patients. Consequently, TXA should be considered a crucial medication, readily available to mitigate morbidity and mortality in surgical settings. Future research should explore factors influencing TXA's effectiveness in traumatic brain injury cases and across a broad spectrum of surgical scenarios in diverse patient populations. This would further guide clinicians in refining and optimizing the use of TXA.

Azathioprine hypersensitivity: A Sweet-like syndrome.

INTRODUCTION: Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules, papules, and pustules. CASE PRESENTATION: A 35-year-old woman with systemic lupus erythematosus presented with complaints of generalized maculopapular rash, facial swelling, and bilateral lower extremity edema with a duration of 4 days and a 2-day history of constitutional symptoms within 2 weeks of the beginning of azathioprine therapy to treat existing lupus nephritis (class 2/3). DISCUSSION: Patients who experience azathioprine hypersensitivity syndrome can present with erythema nodosum, small-vessel vasculitis, acute generalized exanthematous pustulosis, Sweet syndrome, and nonspecific dermatosis. The following signs and symptoms are used as criteria to diagnose drug-induced Sweet syndrome: (a) abrupt onset of painful erythematous plaques, (b) histopathological evidence of dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (c) temperature higher than 39.7°C, (d) temporal relationship between drug ingestion and clinical presentation, and (e) temporal resolution of lesions after drug withdrawal. Our patient met three out of five criteria and was diagnosed with Sweet-like syndrome. CONCLUSION: Our case highlights the uncommonly presented azathioprine-induced Sweet-like syndrome that occurs abruptly after the commencement of the offending drug. This diagnosis can be established through basic laboratory workup and skin biopsy findings.

vitíligo, estrés psicológico y bioquímica del cerebro: Una revisión sistemática desde la neurociencia

Objetivo: El propósito de este estudio es establecer los mecanismos de la actividad Bioquímica a través del Estrés Psicológico que influyen en la enfermedad del vitiligo desde una perspectiva neurocientifica, mediante una revisión sistemática de la literatura de los últimos 5 años. Método: La búsqueda sistemática se llevó a cabo en las bases de datos Scopus, PubMed y Web of Science para identificar los estudios que describan la enfermedad de Vitiligo, el estrés psicológico y la bioquímica del cerebro, se establecieron criterios de inclusión y exclusión para la selección de los artículos, así mismo, se evaluó su calidad y pertinencia. Resultados: La revisión sistemática arrojó 15.503 artículos, 70 fueron preseleccionados de acuerdo a lo informado en el resumen y validados para lectura completa. Para la síntesis narrativa se utilizaron 23 artículos científicos. Conclusión: La enfermedad de vitiligo guarda una estrecha relación con el estrés psicológico y está acompañado de un desequilibrio bioquímico que conduce a un proceso inflamatorio y destructivo de los melanocitos de la piel.

Objective: The purpose of this study is to establish the mechanisms of biochemical activity through psychological stress that influence vitiligo disease from a neuroscientific perspective, through a systematic review of the literature of the last 5 years. Method: Systematic search was carried out in the Scopus, PubMed and Web of Science databases to identify studies describing Vitiligo disease, psychological stress and brain biochemistry, inclusion and exclusion criteria were established for the selection of articles, their quality and relevance were evaluated. Results: The systematic review yielded 15,503 articles, of which 70 were pre-selected as reported in the summary and validated for full reading. For the narrative synthesis 23 scientific articles were used. Conclusion: Vitiligo disease is closely related to psychological stress and is accompanied by a biochemical imbalance that leads to an inflammatory and destructive process of skin melanocytes.

Maternal Exposure to Arsenic and Its Impact on Maternal and Fetal Health: A Review.

Arsenic exposure is a significant public health issue, with harmful effects caused by its use in commercial products such as car batteries, pesticides, and herbicides. Arsenic has three main compounds: inorganic, organic, and arsine gas. Inorganic arsenic compounds in water are highly toxic. The daily intake of arsenic from food and beverages is between 20 and 300 mcg/day. Arsenic is known for its carcinogenic properties and is classified as a human carcinogen by different institutions. Exposure can lead to oxidative stress, DNA damage, and epigenetic deregulation, which can cause endocrine disorders, altered signal transduction pathways, and cell proliferation. In addition, arsenic can easily cross the placenta, making it a critical concern for maternal and fetal health. Exposure can lead to complications such as gestational diabetes, anemia, low birth weight, miscarriage, and congenital anomalies. Female babies are particularly vulnerable to the negative impact of arsenic exposure, with a higher risk of low weight for gestational age and congenital cardiac anomalies. Therefore, it is crucial to monitor and regulate the levels of arsenic in drinking water and food sources to prevent these adverse health outcomes. Further research is necessary to fully understand the impact of arsenic exposure on human health, especially during pregnancy and infancy, by implementing preventative measures and monitoring the levels of arsenic in the environment.

A phase 3, randomised, double-blind, placebo-controlled clinical trial evaluation of the efficacy and safety of a SARS-CoV-2 recombinant spike RBD protein vaccine in adults (ABDALA-3 study).

Background: The pandemic of COVID-19 raised the urgent need for safe and efficacious vaccines against SARS-CoV-2. We evaluated the efficacy and safety of a new SARS-CoV-2 virus receptor-binding domain (RBD) vaccine. Methods: A phase 3, multicentre, randomised, double-blind, placebo-controlled trial was carried out at 18 clinical sites in three provinces of the south-eastern region of Cuba. Subjects (healthy or those with controlled chronic diseases) aged between 19 and 80 years, who gave written informed consent were eligible. Subjects were randomly assigned (1:1, in blocks) to two groups: placebo, and 50 µg RBD vaccine (Abdala). The product was administered intramuscularly, 0.5 mL in the deltoid region, in a three-dose immunization schedule at 0-14-28 days. The organoleptic characteristics and presentations of the vaccine and placebo were identical. All participants (subjects, clinical researchers, statisticians, laboratory technicians, and monitors) remained blinded during the study period. The main endpoint was to evaluate the efficacy of the Abdala vaccine in the prevention of symptomatic COVID-19. The trial is registered with the Cuban Public Registry of Clinical Trials, RPCEC00000359. Findings: Between March 22 to April 03, 2021, 48,290 subjects were included (24,144 and 24,146 in the placebo and Abdala groups, respectively) in the context of predominant D614G variant circulation. The evaluation of the main efficacy outcomes occurred during May-June 2021, starting at May 3rd, in the context of high circulation of mutant viruses, predominantly VOC Beta. The incidence of adverse reactions for individuals in the placebo and Abdala vaccine groups were 1227/24,144 (5.1%) and 1621/24,146 (6.7%), respectively. Adverse reactions were mostly mild, and from the injection site, which resolved in the first 24-48 h. No severe adverse events with demonstrated cause-effect relationship attributable to the vaccine were reported. Symptomatic COVID-19 disease was confirmed in 142 participants in the placebo group (78.44 incidence per 1000 person-years, 95% confidence interval [CI], 66.07-92.46) and in 11 participants in Abdala vaccine group (6.05 incidence per 1000 person years; 95% CI 3.02-10.82). The Abdala vaccine efficacy against symptomatic COVID-19 was 92.28% (95% CI 85.74-95.82). Moderate/serious forms of COVID-19 occurred in 30 participants (28 in the placebo group and only 2 in the Abdala vaccine group) for a vaccine efficacy of 92.88% (95% CI 70.12-98.31). There were five critical patients (of which four died), all in the placebo group. Interpretation: The Abdala vaccine was safe, well tolerated, and highly effective, fulfilling the WHO target product profile for COVID-19 vaccines. Those results, along with its immunization schedule and the advantage of easy storage and handling conditions at 2-8 °C, make this vaccine an option for the use in immunization strategies as a key tool for the control of the pandemic. Funding: Centre for Genetic Engineering and Biotechnology (CIGB), Havana, Cuba.

The role of SPECT/CT in painful, noninfected knees after knee arthroplasty: a systematic review and meta-analysis-a diagnostic test accuracy review.

PURPOSE: The aim of this systematic review was to present the current evidence on the clinical use of single-photon emission computed tomography/computed tomography (SPECT/CT) in the evaluation of noninfected painful knees after knee arthroplasty. METHODS: Embase, PubMed, Google Scholar, Ovid, Scopus, Science Direct and the Cochrane Database of Systematic Reviews were searched from database inception to May 2022 following the PRISMA guidelines. As a primary outcome, we defined the role of SPECT/CT in the diagnostic approach to noninfected painful knee arthroplasty; as a secondary objective, we described the noninfection-related factors linked to painful knee arthroplasty. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio values and other indicators were calculated; receiver operating characteristic (ROC) curve analysis results and a summary of the areas under the curve (AUCs) from the included studies were reported. A Fagan plot, likelihood ratio plot and Deeks' funnel plot were generated and analysed. Methodological quality was assessed using the QUADAS-2 tool, and the certainty of evidence was assessed by the GRADE approach. RESULTS: A total of 493 publications were identified, of which eight met the inclusion criteria, with a final pooled sample size of 308 patients. The pooled sensitivity and specificity of SPECT/CT in diagnosing the source of pain in painful knee prostheses were 0.86 (95% CI: 0.75-0.93) and 0.90 (95% CI: 0.79-0.96), respectively, with pooled +LR and -LR values of 8.9 (95% CI: 4.11-19.19) and 0.15 (95% CI: 0.09-0.28). The pooled diagnostic odds ratio was 57.35, and the area under the curve was 0.94. SPECT/CT highly accurately identified different sources of pain, such as loosening of the prosthetic components, patellofemoral overloading, instability, malalignment of the components and degeneration of the patellofemoral compartment. The confidence of the estimates was moderate according to the GRADE approach. CONCLUSION: With demonstrated high sensitivity and specificity, as a diagnostic tool, SPECT/CT can identify the source of pain in painful knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment (level of evidence III). These findings have significant clinical repercussions, such as in changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome. We moderately recommend the use of SPECT/CT for identifying the source of pain after knee arthroplasty according to the GRADE assessment. This review was preregistered in Prospero under code CRD42022320457.

Prevalence of Anemia and Iron Deficiency in Women of Reproductive Age in Cuba and Associated Factors.

This study aims to evaluate the prevalence of anemia and iron deficiency in women of reproductive age and the association with inflammation, global overweight, adiposity, and menorrhagia. A sample design of women of reproductive age from the Eastern, Central, and Havana Regions was carried out. Biochemical determinations of hemoglobin, serum ferritin, soluble transferrin receptors, leukocytes, C-reactive protein, alpha-1 acid glycoprotein, and homocysteine were performed. Serum ferritin was also adjusted by inflammation. Nutritional status was assessed, and menstrual characteristics were collected by survey. A total of 742 women were studied. The prevalence of anemia was 21.4%, iron storage deficiency at 16.0%, and erythropoietic dysfunction at 5.4%, with inflammation at 47.0% and elevated homocysteine at 18.6%. Global overweight was 46.2% and increased adiposity at 58.4%. Anemia is associated with iron deposition deficiency (OR = 3.023 (1.816-5.033)) and with erythropoietic deficiency (OR = 5.62 (3.03-10.39)), but not with inflammation, global overweight, and adiposity. Global overweight was found to be associated with inflammation (OR = 2.23 (1.41-3.53)). Anemia was associated with heavy menstrual bleeding (OR = 1.92 (1.34-2.76)). Homocysteine was associated with inflammation (OR = 2.05 (1.08-3.90)), but not with anemia. In conclusion, anemia in Cuba is classified as a moderate public health problem, but not iron deficiency. A high prevalence of overweight and obesity was found, associated with inflammation, but not with anemia or iron deficiency. Heavy menstrual bleeding is a factor associated with anemia.

A comprehensive review of the benefits of drinking craft beer: Role of phenolic content in health and possible potential of the alcoholic fraction.

Currently, there is greater production and consumption of craft beer due to its appreciated sensory characteristics. Unlike conventional beer, craft beers provide better health benefits due to their varied and high content of phenolic compounds (PCs) and also due to their alcohol content, but the latter is controversial. The purpose of this paper was to report on the alcoholic fraction and PCs present in craft beers and their influence on health. Despite the craft beer boom, there are few studies on the topic; there is a lot of field to explore. The countries with the most research are the United States > Italy > Brazil > United Kingdom > Spain. The type and amount of PCs in craft beers depends on the ingredients and strains used, as well as the brewing process. It was determined that it is healthier to be a moderate consumer of alcohol than to be a teetotaler or heavy drinker. Thus, studies in vitro, with animal models and clinical trials on cardiovascular and neurodegenerative diseases, cancer, diabetes and obesity, osteoporosis and even the immune system suggest the consumption of craft beer. However, more studies with more robust designs are required to obtain more generalizable and conclusive results. Finally, some challenges in the production of craft beer were detailed and some alternative solutions were mentioned.

Adjusting Iron Deficiency for Inflammation in Cuban Children Aged Under Five Years: New Approaches Using Quadratic and Quantile Regression.

INTRODUCTION: Ferritin is the best biomarker for assessing iron deficiency, but ferritin concentrations increase with inflammation. Several adjustment methods have been proposed to account for inflammation's effect on iron biomarker interpretation. The most recent and highly recommended method uses linear regression models, but more research is needed on other models that may better define iron status in children, particularly when distributions are heterogenous and in contexts where the effect of inflammation on ferritin is not linear. OBJECTIVE: Assess the utility and relevance of quadratic regression models and quantile quadratic regression models in adjusting ferritin concentration in the presence of inflammation. METHODS: We used data from children aged under five years, taken from Cuba's national anemia and iron deficiency survey, which was carried out from 2015-2018 by the National Hygiene, Epidemiology and Microbiology Institute. We included data from 1375 children aged 6 to 59 months and collected ferritin concentrations and two biomarkers for inflammation: C-reactive protein and α-1 acid glycoprotein. Quadratic regression and quantile regression models were used to adjust for changes in ferritin concentration in the presence of inflammation. RESULTS: Unadjusted iron deficiency prevalence was 23% (316/1375). Inflammation-adjusted ferritin values increased iron-deficiency prevalence by 2.6-4.5 percentage points when quadratic regression correction model was used, and by 2.8-6.2 when quantile regression was used. The increase when using the quantile regression correction model was more pronounced and statistically significant when both inflammation biomarkers were considered, but adjusted prevalence was similar between the two correction methods when only one biomarker was analyzed. CONCLUSIONS: The use of quadratic regression and quantile quadratic regression models is a complementary strategy in adjusting ferritin for inflammation, and is preferable to standard regression analysis when the linear model's basic assumptions are not met, or when it can be assumed that ferritin-inflammation relationships within a subpopulation may deviate from average trends.

Phenolic compounds versus SARS-CoV-2: An update on the main findings against COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 remains an international concern. Although there are drugs to fight it, new natural alternatives such as polyphenols are essential due to their antioxidant activity and high antiviral potential. In this context, this review reports the main findings on the effect of phenolic compounds (PCs) against SARS-CoV-2 virus. First, the proven activity of PCs against different human viruses is briefly detailed, which serves as a starting point to study their anti-COVID-19 potential. SARS-CoV-2 targets (its proteins) are defined. Findings from in silico, in vitro and in vivo studies of a wide variety of phenolic compounds are shown, emphasizing their mechanism of action, which is fundamental for drug design. Furthermore, clinical trials have demonstrated the effectiveness of PCs in the prevention and as a possible therapeutic management against COVID-19. The results were complemented with information on the influence of polyphenols in strengthening/modulating the immune system. It is recommended to investigate compounds such as vitamins, minerals, alkaloids, triterpenes and fatty acids, and their synergistic use with PCs, many of which have been successful against SARS-CoV-2. Based on findings on other viruses, synergistic evaluation of PCs with accepted drugs against COVID-19 is also suggested. Other recommendations and limitations are also shown, which is useful for professionals involved in the development of efficient, safe and low-cost therapeutic strategies based on plant matrices rich in PCs. To the authors' knowledge, this manuscript is the first to evaluate the relationship between the antiviral and immunomodulatory (including anti-inflammatory and antioxidant effects) activity of PCs and their underlying mechanisms in relation to the fight against COVID-19. It is also of interest for the general population to be informed about the importance of consuming foods rich in bioactive compounds for their health benefits.

Cardiovascular risk factors and comorbidities in people living with HIV: A cross-sectional multicenter study from Colombia comorbidities in a Colombian PLWHIV population.

INTRODUCTION: HIV is an independent risk factor for cardiovascular diseases (CVD). There is insufficient information regarding comorbidities and cardiovascular risk factors in the Colombian HIV population. The aim of this study is to describe the prevalence of cardiovascular risk factors and comorbidities in patients from the HIV Colombian Group VIHCOL. METHODS: This is a multicenter, cross-sectional study conducted in the VIHCOL network in Colombia. Patients 18 years or older who had at least 6 months of follow-up were included. A stratified random sampling was performed to estimate the adjusted prevalence of cardiovascular risk factors and comorbidities. RESULTS: A total of 1616 patients were included. 83.2% were men, and the median age was 34 years. The adjusted prevalence for dyslipidemia, active tobacco use, hypothyroidism, and arterial hypertension was 51.2% (99% CI: 48.0%-54.4%), 7.6% (99% CI: 5.9%-9.3%), 7.4% (99% CI: 5.7%-9.1%), and 6.3% (99% CI: 4.8%-7.9%), respectively. CONCLUSIONS: In this Colombian HIV cohort, there is a high prevalence of modifiable CVD risk factors such as dyslipidemia and active smoking. Non-pharmacological and pharmacological measures for the prevention and management of these risk factors should be reinforced.

Ecological and Health Risk Assessments of an Abandoned Gold Mine (Remance, Panama): Complex Scenarios Need a Combination of Indices.

The derelict Remance gold mine is a possible source of pollution with potentially toxic elements (PTEs). In the study area, diverse mine waste has been left behind and exposed to weather conditions, and poses risks for soil, plants and water bodies, and also for the health of local inhabitants. This study sought to perform an ecological and health risk assessment of derelict gold mining areas with incomplete remediation, including: (i) characterizing the geochemical distribution of PTEs; (ii) assessing ecological risk by estimating the pollution load index (PLI) and potential ecological risk index (RI); (iii) assessing soil health by dehydrogenase activity; and iv) establishing non-carcinogenic (HI) and carcinogenic risks (CR) for local inhabitants. Soil health seems to depend on not only PTE concentrations, but also on organic matter (OM). Both indexes (PLI and RI) ranged from high to extreme near mining and waste accumulation sites. As indicated by both the HI and CR results, the mining area poses a health risk for local inhabitants and particularly for children. For this reason, it will be necessary to set up environmental management programs in the areas that are most affected (tailings and surrounding areas) and accordingly establish the best remediation strategies to minimize risks for the local population.

Atmospheric degradation of 3-ethoxy-1-propanol by reactions with Cl, OH and NO3.

An experimental kinetic and mechanistic study of the reactions of 3-ethoxy-1-propanol (CH3CH2OCH2CH2CH2OH) with Cl atoms and OH and NO3 radicals has been carried out at room temperature and atmospheric pressure. FTIR (Fourier Transform Infrared Spectroscopy) and GC-MS (Gas Chromatography/Mass Spectrometry) were used as detection techniques. The rate coefficients were measured with a relative method (units cm3 molecule-1 s-1): (3.46 ± 0.22) × 10-10, (3.48 ± 0.19) × 10-11 and (1.08 ± 0.07) × 10-14 for Cl, OH and NO3 reactions, respectively. Qualitative and quantitative products analysis was carried out and formaldehyde, ethyl formate, ethyl 3-hydroxypropanoate and nitrated compounds were positively identified. A reaction mechanism has been proposed which involves attack by the oxidant at the methylene group in the α-position to an oxygen atom of the ether or alcohol groups, followed by the subsequent reactions of the resulting radicals. The tropospheric reactivity of 3-ethoxy-1-propanol (3E1P) has been compared with the reactivity of other hydroxy ethers to extend our knowledge of this type of compound. The atmospheric implications for 3E1P have been established by estimating parameters such as lifetimes, global warming potential (GWP) and the Photochemical Ozone Creation Potential (POCPE). According to the calculated tropospheric lifetimes, the dominant loss process of 3E1P is its daytime reaction with the OH radical and this has an impact on a local scale.

Antifibrotic effect of novel neutrophil gelatinase-associated lipocalin inhibitors in cardiac and renal disease models.

Neutrophil gelatinase-associated lipocalin (NGAL) is involved in cardiovascular and renal diseases. Gene inactivation of NGAL blunts the pathophysiological consequences of cardiovascular and renal damage. We aimed to design chemical NGAL inhibitors and investigate its effects in experimental models of myocardial infarction (MI) and chronic kidney disease induced by 5/6 nephrectomy (CKD) on respectively 8-12 weeks old C57Bl6/j and FVB/N male mice. Among the 32 NGAL inhibitors tested, GPZ614741 and GPZ058225 fully blocked NGAL-induced inflammatory and profibrotic markers in human cardiac fibroblasts and primary mouse kidney fibroblasts. The administration of GPZ614741 (100 mg/kg/day) for three months, was able to improve cardiac function in MI mice and reduced myocardial fibrosis and inflammation. The administration of GPZ614741 (100 mg/kg/day) for two months resulting to no renal function improvement but prevented the increase in blood pressure, renal tubulointerstitial fibrosis and profibrotic marker expression in CKD mice. In conclusion, we have identified new compounds with potent inhibitory activity on NGAL-profibrotic and pro-inflammatory effects. GPZ614741 prevented interstitial fibrosis and dysfunction associated with MI, as well as tubulointerstitial fibrosis in a CKD model. These inhibitors could be used for other diseases that involve NGAL, such as cancer or metabolic diseases, creating new therapeutic options.

Anaplastic extraosseous (extramedullary) plasmacytoma in the right nostril.

Extraosseous (extramedullary) plasmacytomas are rare plasma cell neoplasms that can result in an erroneous and/or delayed diagnosis as often they are not considered in the differential diagnosis due to their rarity. Furthermore, the anaplastic type is one of the most difficult to recognize in biopsies. We report the case of a patient with an extraosseous plasmacytoma occluded in the right nostril. Its prompt and accurate diagnosis resulted in early treatment and a good outcome, despite the tumour being anaplastic with the risk of progressing into a plasma cell myeloma. The patient shows no recurrence or disease progression after 10 years of follow-up. Our case highlights the clinical and pathological characteristics of this rare disorder that should be considered in order to improve diagnostic criteria and thus early treatment. We also reviewed the pertinent literature.

Mead Production by Saccharomyces cerevisiae Safbrew T-58 and Saccharomyces bayanus (Premier Blanc and Premier Cuvée): Effect of Cowpea (Vigna unguiculata L. Walp) Extract Concentration.

This work evaluated the effect of the cowpea (Vigna unguiculata L. Walp) extract concentration on mead production. Fermentations were carried out in 500-mL Erlenmeyer flasks containing 250 mL of honey wort (30 °Brix), supplemented with 1 g L-1 of ammonium sulfate and 0.1 g L-1 of magnesium chloride and the cowpea extract (5 and 30 g L-1), inoculated with 106 cells mL-1, and incubated at 30 °C for 240 h. Higher cell growth ((cells mL-1): 11.1 × 107, 11.3 × 107, and 19.6 × 107; substrate consumption (%): 86.0, 90.0, and 85.0) and ethanol production ((v v-1 %): 15.0, 15.5, and 14.1) for yeasts Safbrew T-58, Premier Blanc, and Premier Cuvée, respectively, were obtained with 30 g L-1 of bean extract. S. bayanus Premier Blanc had the best metabolic activity with lowest glycerol production (8.5 g L-1) and highest ethanol volumetric yields (0.51-1.52 h-1) after 48 h of fermentation.