Distribution and virulence of Escherichia coli harboring cyclomodulins and supplementary virulence genes isolates from clinical and environmental samples.

This study aimed to determine the prevalence of cyclomodulins (cdt, cnf, pks and cif) in Escherichia coli (E. coli) isolated from clinical and environmental samples, the presence of supplementary virulence genes (SVG), antibiotic resistance, and in vitro cytotoxicity. 413 E. coli were isolated from clinical (stool from obese subjects, normal weight subjects, children with diarrhea, and children without diarrhea; and urine from pregnant and non-pregnant women with urinary tract infections) and environmental (water and different foods) samples. PCR was performed to identify E. coli pathotypes, the four cyclomodulins, and 18 SVG; virulence score, cytotoxic assay, and antibiotic resistance assay were performed. Fifteen percent of E. coli were positive for cyclomodulins and were found in all isolation sources; however, in children with diarrhea, they were more frequent. The most frequent cyclomodulin was cdt. More DEC strains harbor cyclomodulins than non-DEC, and cyclomodulins were most frequent among aEPEC pathotype. SVG ehaC was associated with cyclomodulin-positive strains. Cyclomodulin-positive E. coli had a higher virulence score but no significant cytotoxic activity. They were slightly more resistant to antibiotics. In conclusion, cyclomodulins-positive E. coli was widely distributed in humans, food, and the environment, and they were associated with SVG ehaC, suggesting that these genes may play a role in the pathogenesis of the cyclomodulins. However, more research is needed.

Virulence-associated genes and antimicrobial resistance patterns in bacteria isolated from pregnant and nonpregnant women with urinary tract infections: the risk of neonatal sepsis.

Uropathogenic Escherichia coli (UPEC) is classified as the major causative agent of urinary tract infections (UTIs). UPEC virulence and antibiotic resistance can lead to complications in pregnant women and (or) newborns. Therefore, the aim of this study was to determine the etiological agents of UTIs, as well as to identify genes related to virulence factors in bacteria isolated from pregnant and nonpregnant women. A total of 4506 urine samples were collected from pregnant and nonpregnant women. Urine cultures were performed, and PCR was used to identify phylogroups and virulence-related genes. Antibiotic resistance profiles were determined. The incidence of UTIs was 6.9% (pregnant women, n = 206 and nonpregnant women, n = 57), and UPEC belonging to phylogroup A was the most prevalent. The presence of genes related to capsular protection, adhesins, iron acquisition, and serum protection in UPEC was associated with not being pregnant, while the presence of genes related to adhesins was associated with pregnancy. Bacteria isolated from nonpregnant women were more resistant to antibiotics; 36.5% were multidrug resistant, and 34.9% were extensively drug resistant. Finally, UTIs were associated with neonatal sepsis risk, particularly in pregnant women who underwent cesarean section while having a UTI caused by E. coli. In conclusion, UPEC isolated from nonpregnant women carried more virulence factors than those isolated from pregnant women, and maternal UTIs were associated with neonatal sepsis risk.

Predictores de fenómeno de no reflujo en infarto agudo del miocardio con elevación del segmento ST / Predictors in no-reflow phenomenon in acute myocardial infarction with ST-segment elevation

Resumen Antecedentes: El fenómeno de «no reflujo¼ (NR) es una de las complicaciones más temidas tras una intervención coronaria percutánea (ICP) en el tratamiento del infarto de miocardio con elevación del segmento ST (IAMCEST) por su elevada morbimortalidad. Objetivo: Describir los factores predictores para el fenómeno de NR en un grupo de sujetos con IAMCEST tratados con ICP. Método: Se estudiaron 103 casos de IAMCEST a los que se les realizó una ICP. Los sujetos se dividieron de acuerdo con la presencia del fenómeno de NR. Se estudió mediante un análisis multivariante la edad, el sexo, presencia de comorbilidades, el peso y otros parámetros clínicos y de laboratorio como predictores del fenómeno de NR. Resultados: En este estudio, el análisis con regresión logística identificó como factores independientes para el desarrollo de fenómeno de NR el flujo TIMI basal ≤ 2 (razón de momios [OR]6.03; intervalo de confianza del 95% [IC 95%]: 0.9-11.8; p = 0.04), estadio enfermedad renal según KDIGO (Kidney Disease Improving Global Outcomes) ≥ 3 (OR 3.49; IC 95%: 1.2-2.6; p = 0.02) y nivel de glucosa ≥ 180 mg/dl(OR 2.61; IC 95%: 1.0-2.4; p = 0.04). Conclusiones: El fenómeno de NR sigue siendo un reto para la morbimortalidad a corto y a largo plazo en el IAMCEST. Los factores identificados pueden ser utilizados para la estratificación de los casos con IAMCEST y riesgo de fenómeno de NR previo a la ICP.

Abstract Background: No-reflow (NR) phenomenon is one of the most feared complications after percutaneous coronary intervention (PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI) due to its high morbidity and mortality. Objective: To describe the predictive factors for NR phenomenon in a group of subjects with STEMI treated with PCI. Method: One hundred and three cases of STEMI who underwent PCI. The subjects were divided according to the presence of NR phenomenon. In a multivariate analysis age, gender, comorbidities, weight, and other clinical and laboratory parameters were studied as predictors of NR phenomenon were studied. Results: In this study, logistic regression analysis identified as independent factors for the development of NR phenomenon baseline TIMI flow ≤ 2 (OR 6.03; 95% CI, 0.9 to 11.8; p = 0.04), ER KDIGO ≥ 3 (OR OR 2.61; 95% CI, 1.0 to 2.4; p = 0.04). Conclusions: NR phenomenon continues to be a challenge for short and long-term morbidity and mortality in STEMI. The identified factors can be used for the stratification of cases with STEMI and risk of NR phenomenon prior to PCI.

Predictors in no-reflow phenomenon in acute myocardial infarction with ST-segment elevation.

BACKGROUND: No-reflow (NR) phenomenon is one of the most feared complications after percutaneous coronary intervention (PCI) in the treatment of ST-segment elevation myocardial infarction (STEMI) due to its high morbidity and mortality. OBJECTIVE: To describe the predictive factors for NR phenomenon in a group of subjects with STEMI treated with PCI. METHOD: One hundred and three cases of STEMI who underwent PCI. The subjects were divided according to the presence of NR phenomenon. In a multivariate analysis age, gender, comorbidities, weight, and other clinical and laboratory parameters were studied as predictors of NR phenomenon were studied. RESULTS: In this study, logistic regression analysis identified as independent factors for the development of NR phenomenon baseline TIMI flow ≤ 2 (OR 6.03; 95% CI, 0.9 to 11.8; p = 0.04), ER KDIGO ≥ 3 (OR OR 2.61; 95% CI, 1.0 to 2.4; p = 0.04). CONCLUSIONS: NR phenomenon continues to be a challenge for short and long-term morbidity and mortality in STEMI. The identified factors can be used for the stratification of cases with STEMI and risk of NR phenomenon prior to PCI.

ANTECEDENTES: El fenómeno de «no reflujo¼ (NR) es una de las complicaciones más temidas tras una intervención coronaria percutánea (ICP) en el tratamiento del infarto de miocardio con elevación del segmento ST (IAMCEST) por su elevada morbimortalidad. OBJETIVO: Describir los factores predictores para el fenómeno de NR en un grupo de sujetos con IAMCEST tratados con ICP. MÉTODO: Se estudiaron 103 casos de IAMCEST a los que se les realizó una ICP. Los sujetos se dividieron de acuerdo con la presencia del fenómeno de NR. Se estudió mediante un análisis multivariante la edad, el sexo, presencia de comorbilidades, el peso y otros parámetros clínicos y de laboratorio como predictores del fenómeno de NR. RESULTADOS: En este estudio, el análisis con regresión logística identificó como factores independientes para el desarrollo de fenómeno de NR el flujo TIMI basal ≤ 2 (razón de momios [OR]6.03; intervalo de confianza del 95% [IC 95%]: 0.9-11.8; p = 0.04), estadio enfermedad renal según KDIGO (Kidney Disease Improving Global Outcomes) ≥ 3 (OR 3.49; IC 95%: 1.2-2.6; p = 0.02) y nivel de glucosa ≥ 180 mg/dl(OR 2.61; IC 95%: 1.0-2.4; p = 0.04). CONCLUSIONES: El fenómeno de NR sigue siendo un reto para la morbimortalidad a corto y a largo plazo en el IAMCEST. Los factores identificados pueden ser utilizados para la estratificación de los casos con IAMCEST y riesgo de fenómeno de NR previo a la ICP.

Epidemiological and clinical characteristics of pregnant women and neonates with COVID-19 in Northwest Mexico.

INTRODUCTION: The SARS-CoV-2 virus, which causes COVID-19, has spread quickly worldwide, causing millions of cases and thousands of deaths. Some risk factors in the general population are related to the development of severe COVID-19 or death, but in pregnant women and neonates, the information is limited. OBJECTIVE: To determine the epidemiological and clinical characteristics of pregnant women and neonates diagnosed with COVID-19 by RT-PCR and serological tests, and analyze the relationship between the influenza vaccination and COVID-19 symptoms in infected pregnant women in Sinaloa state. METHODS: We collected samples from 116 pregnant women and 84 neonates from the Women´s Hospital of Sinaloa. They were diagnosed with COVID-19 by RT-PCR and serological tests (IgG), and sociodemographic, clinical and laboratory parameters were recorded. RESULTS: A total of 11.2% (13/116) of the pregnant women were RT-PCR+, 25% (29/116) were IgG+ and 4.3% (5/116) were positive for both tests. Symptoms such as rhinorrhea (P = .04), cough (P = .02) and polypnea (P = .04) in pregnant women were related to COVID-19, also leukocyte index was higher in pregnant women with COVID-19 (P = .03), but the associations were lost after the Bonferroni correction. No laboratory parameters or underlying diseases were associated with COVID-19, and most infected pregnant women had mild cases. We found an association between the influenza vaccine and less common COVID-19 symptoms in pregnant women who were infected (P = .01). A total of 7.2% (6/84) of neonates were RT-PCR+, 35.7% (30/84) were IgG+, and there were no symptoms or underlying diseases associated with neonates who were infected. In conclusion, this work demonstrated that some symptoms were related to COVID-19, most pregnant women and neonates had mild cases, and the influenza vaccine could decrease the severity of COVID-19 cases in pregnant women.

Prevalence of Cyclomodulin-Positive E. coli and Klebsiella spp. Strains in Mexican Patients with Colon Diseases and Antimicrobial Resistance.

Colon diseases, such as colorectal cancer (CRC), are multifactor diseases that affect more than one million people per year; recently, the microbiota has been associated with an etiologic factor, specifically bacterial cyclomodulin positivity (CM+). Unfortunately, there are no studies from Mexico that detail the presence of bacterial CM+ in patients with colon diseases. We therefore performed a comprehensive study to investigate the associations and prevalence of cyclomodulin-positive Diarrheagenic E. coli (DEC), non-DEC, and Klebsiella spp. strains isolated from Mexican subjects with colon diseases. In this work, we analyzed 43 biopsies, 87 different bacteria were isolated, and E. coli was the most frequently noted, followed by Klebsiella spp., and Enterococcus spp. E. coli, non-DEC, and EPEC belonging to phylogroup B2 were the most prevalent. More than 80% of E. coli and Klebsiella were CM+. pks, cdt, cnf, and cif were identified. cdt was associated with non-DEC, cif and its combinations with EPEC, as well as cdt and psk with Klebsiella. Lastly, all the CM+ bacteria were resistant to at least one antibiotic (34% were MDR, and 48% XDR). In conclusion, the high prevalence of bacterial CM+ in colon disease patients suggests that these bacteria play an important role in the genesis of these diseases.

Coibacins A-D, antileishmanial marine cyanobacterial polyketides with intriguing biosynthetic origins.

Four unsaturated polyketide lactone derivatives, coibacins A-D, were isolated from a Panamanian marine cyanobacterium, cf. Oscillatoria sp. The two different types of termini observed in these co-occurring metabolites, either a methyl cyclopropyl ring as seen in curacin A or a methyl vinyl chloride similar to that observed in the jamaicamides, suggest an intriguing flexibility in the "beta branch" forming biosynthetic process. The coibacins possess selective antileishmanial activity as well as potent anti-inflammatory activity.

Honaucins A-C, potent inhibitors of inflammation and bacterial quorum sensing: synthetic derivatives and structure-activity relationships.

Honaucins A-C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-γ-butyrolactone and 4-chlorocrotonic acid, which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of both bioluminescence, a quorum-sensing-dependent phenotype, in Vibrio harveyi BB120 and lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several proinflammatory cytokines, most dramatically interleukin-1ß. Synthesis of honaucin A, as well as a number of analogs, and subsequent evaluation in anti-inflammation and quorum-sensing inhibition bioassays revealed the essential structural features for activity in this chemical class and provided analogs with greater potency in both assays.

Phylogeny-guided isolation of ethyl tumonoate A from the marine cyanobacterium cf. Oscillatoria margaritifera.

The evolutionary relationships of cyanobacteria, as inferred by their SSU (16S) rRNA genes, were used as predictors of their potential to produce varied secondary metabolites. The evolutionary relatedness in geographically distant cyanobacterial specimens was then used as a guide for the detection and isolation of new variations of predicted molecules. This phylogeny-guided isolation approach for new secondary metabolites was tested in its capacity to direct the search for specific classes of new natural products from Curaçao marine cyanobacteria. As a result, we discovered ethyl tumonoate A (1), a new tumonoic acid derivative with anti-inflammatory activity and inhibitory activity of calcium oscillations in neocortical neurons.

Malyngamide 2, an oxidized lipopeptide with nitric oxide inhibiting activity from a Papua New Guinea marine cyanobacterium.

A Papua New Guinea collection of the marine cyanobacterium cf. Lyngbya sordida yielded three known compounds as well as a new PKS-NRPS-derived malyngamide with anti-inflammatory and cytotoxic activity. Malyngamide 2 features an extensively oxidized cyclohexanone ring. Resolution of the ring core as a 6,8,9-triol rather then a 7,8,9-triol and relative configuration was based on chemical shift and bond geometry modeling in conjunction with homonuclear and heteronuclear coupling constants, NOE and ROE correlations, and other structural information. Malyngamide 2 exhibited anti-inflammatory activity in LPS-induced RAW macrophage cells (IC(50) = 8.0 µM) with only modest cytotoxicity to the mammalian cell line.

Marine natural product drug discovery: Leads for treatment of inflammation, cancer, infections, and neurological disorders.

Natural products, secondary metabolites, isolated from plants, animals and microbes are important sources for bioactive molecules that in many cases have been developed into treatments for diseases. This review will focus on describing the potential for finding new treatments from marine natural products for inflammation, cancer, infections, and neurological disorders. Historically terrestrial natural products have been studied to a greater extent and such classic drugs as aspirin, vincristine and many of the antibiotics are derived from terrestrial natural products. The need for new therapeutics in the four areas mentioned is dire. Within the last 30 years marine natural products, with their unique structures and high level of halogenation, have shown many promising activities against the inflammatory response, cancer, infections and neurological disorders. The review will outline examples of such compounds and activities.

Selective MyD88-dependent pathway inhibition by the cyanobacterial natural product malyngamide F acetate.

In response to evolutionary selective pressure, prokaryotes have developed a rich array of secondary metabolites, some of which may be inhibitory to the innate immune system and the inflammatory response in vertebrates. We utilized the RAW264.7 macrophage cell line stimulated with LPS in a nitric oxide (NO) assay to screen for compounds with immunomodulatory activities from a library of marine natural products, and found that the malyngamide structure class, found commonly in the marine cyanobacterium Lyngbya majuscula, has potent activity. Several of the malyngamides were found to possess IC50 values of 5.4-18microM. Malyngamide F acetate exhibited strong concentration-dependent anti-inflammatory activity in the NO assay with an IC50 of 7.1microM and with no cytotoxicity at the concentrations tested. Subsequent real-time PCR of selected genes revealed a unique cytokine profile after LPS stimulation (TLR4) with decreased expression of iNOS, IL-1beta, IL-6, and IL-10, but increased TNF-alpha expression. Additional experiments utilizing CpG and Poly I:C stimulation to selectively activate the MyD88-dependent and -independent pathways via TLR9 and TLR3 substantiated the finding that malyngamide F acetate selectively inhibits the MyD88-dependent pathway. To our knowledge, this is the first report of a natural product inhibiting the MyD88-dependent pathway.