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Antibiotic resistance genes (ARGs) released into the environment are an emerging human and environmental health concern, including ARGs spread in wastewater treatment effluents. In low-to-middle income countries (LMICs), an alternate wastewater treatment option instead of conventional systems are low-energy, high-rate algal ponds (HRAP) that use microalgae-bacteria aggregates (MABA) for waste degradation. Here we studied the robustness of ARG removal in MABA-based pilot-scale outdoor systems for 140 days of continuous operation. The HRAP system successfully removed 73 to 88 % chemical oxygen demand and up to 97.4 % ammonia, with aggregate size increasing over operating time. Fourteen ARG classes were identified in the HRAP influent, MABA, and effluent using metagenomics, with the HRAP process reducing total ARG abundances by up to 5-fold from influent to effluent. Parallel qPCR analyses showed the HRAP system significantly reduced exemplar ARGs (p < 0.05), with 1.2 to 4.9, 2.7 to 6.3, 0 to 1.5, and 1.2 to 4.8 log-removals for sul1, tetQ, blaKPC, and intl1 genes, respectively. Sequencing of influent, effluent and MABAs samples showed associated microbial communities differed significantly, with influent communities by Enterobacteriales (clinically relevant ARGs carrying bacteria), which were less evident in MABA and effluent. In this sense, such bacteria might be excluded from MABA due to their good settling properties and the presence of antimicrobial peptides. Microalgae-bacteria treatment systems steadily reduced ARGs from wastewater during operation time, using sunlight as the energetic driver, making them ideal for use in LMIC wastewater treatment applications.
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Microalgas , Microbiota , Purificación del Agua , Humanos , Eliminación de Residuos Líquidos , Microalgas/metabolismo , Aguas Residuales , Bacterias/genética , Antibacterianos/metabolismo , Genes BacterianosRESUMEN
Newborn screening using dried plasma spots offers preanalytical advantages over conventional cards for plasma-associated targets of interest. Herein we present dried plasma spot-based methods for measuring metabolites using a 250+ compound liquid chromatography tandem mass spectrometry library. Quality assurance reduced this library to 134, and from these, 30 compounds determined the normal newborn reference ranges.
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Biomarcadores/sangre , Cromatografía Liquida , Pruebas con Sangre Seca/métodos , Metaboloma , Tamizaje Neonatal/métodos , Espectrometría de Masas en Tándem , Conservación de la Sangre/métodos , Conservación de la Sangre/normas , Pruebas con Sangre Seca/normas , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tamizaje Neonatal/normas , Estudios Prospectivos , Valores de Referencia , Manejo de Especímenes/métodos , Manejo de Especímenes/normasRESUMEN
Establishing when, and from where, carbon, nitrogen and water were delivered to Earth is a fundamental objective in understanding the origin of habitable planets such as Earth. Yet, volatile delivery to Earth remains controversial1-5. Krypton isotopes provide insights on volatile delivery owing to their substantial isotopic variations among sources6-10, although pervasive atmospheric contamination has hampered analytical efforts. Here we present the full suite of krypton isotopes from the deep mantle of the Galápagos and Iceland plumes, which have the most primitive helium, neon and tungsten isotopic compositions11-16. Except for 86Kr, the krypton isotopic compositions are similar to a mixture of chondritic and atmospheric krypton. These results suggest early accretion of carbonaceous material by proto-Earth and rule out any combination of hydrodynamic loss with outgassing of the deep or shallow mantle to explain atmospheric noble gases. Unexpectedly, the deep-mantle sources have a deficit in the neutron-rich 86Kr relative to the average composition of carbonaceous meteorites, which suggests a nucleosynthetic anomaly. Although the relative depletion of neutron-rich isotopes on Earth compared with carbonaceous meteorites has been documented for a range of refractory elements1,17,18, our observations suggest such a depletion for a volatile element. This finding indicates that accretion of volatile and refractory elements occurred simultaneously, with krypton recording concomitant accretion of non-solar volatiles from more than one type of material, possibly including outer Solar System planetesimals.
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Carbono/análisis , Planeta Tierra , Evolución Planetaria , Sedimentos Geológicos/química , Criptón/análisis , Atmósfera/química , Ecuador , Evolución Química , Helio/análisis , Islandia , Isótopos/análisis , Meteoroides , Neón/análisis , Neutrones , Nitrógeno/análisis , Tungsteno/análisis , Xenón/análisisRESUMEN
INTRODUCTION: Controlling insulin-treated diabetes is challenging in low-resource settings where only Neutral Protamine Hagedorn (NPH), regular (R) and premixed insulin formulations are available, self-monitoring of blood glucose (SMBG) supplies are scarce and food insecurity is common. We examined the impact of a treatment protocol that includes sliding scale-based 70/30 insulin adjustments in Haiti. METHODS: Thirty young patients aged 11-28 years with diabetes treated with premixed 70/30 insulin twice daily were included in the study. The participants performed one or two daily self-monitoring of blood glucose (SMBG) tests and attended our diabetes clinic monthly. They were randomized to two treatment groups, with one group remaining on the 70/30 insulin formulation (group 70 [G70]) and the other group switching to self-mixed NPH + R (group NR [GNR]). Sliding scales for insulin correction doses and meal insulin doses were designed based on the total daily insulin dose (TDD), carbohydrate ratio and insulin sensitivity factor. SMBG tests and insulin were administered before the morning and evening meals. The frequency of visits to the diabetes clinic was increased to biweekly during a 14-week follow-up. RESULTS: Fifteen patients of each group were included in the analysis. Baseline characteristics, increase in total daily dose and number of missed SMBG tests and skipped meals at 14 weeks did not differ between the two groups. Hemoglobin A1c (HbA1c) decreased from 9.5% (interquartile range [IQR] 8.8, 10.5) (80.3 mmol/mol) to 8.0% (IQR 7.1%, 9.0%) (63.9 mmol/mol) in G70 (p = 0.01), and from 10.6% (IQR 8.1,% 13.1)% (92.4 mmol/mol) to 9.0% (IQR 7.6%, 9.6%) (74.9 mmol/mol) in GNR (p = 0.10), with no significant between-group difference in reductions (p = 0.12). No serious acute complications were reported. Stopping the use of sliding scales and resuming monthly visits increased HbA1c to values not significantly different from baseline in both groups after 15 weeks. CONCLUSION: The use of sliding scales adjusted for missed SMBG tests and skipped meals, and frequent clinic visits that focus on patient self-management education significantly improved glycemic control in the patients with youth-onset diabetes in our study treated with premixed 70/30 human insulin in a low-resource setting.
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Background The objective of this study was to determine the demographic and clinical features of youth supported by member associations of the Federación Mexicana de Diabetes and the Life for a Child Program (LFAC). Methods An analysis of 2017 Annual Clinical Data Sheets of 306 subjects from five Mexican centers was performed. Results Type 1 diabetes (T1D) was diagnosed in 292 subjects; 54.6% were female, with six diagnosed aged <6 months (genetic tests not yet conducted). Type 2 diabetes (T2D) or other types were diagnosed in 11 and three subjects, respectively. T1D diagnosis age ranged 0.0-22.6 years with a peak at 8 years. The mean ± standard deviation (SD) diabetes duration was 5.3 ± 3.5 years (range 0.0-21.0 years), with a mean ± SD subject age at check-up of 13.3 ± 4.3 years. Of the T1D subjects, 1.0%, 6.7%, 13.7% and 78.6% were receiving 1, 2, 3 and ≥4 insulin injections/day with a mean ± SD daily dose of 0.92 ± 0.34 U/kg. The median number of blood glucose tests/week was 40. The mean/median hemoglobin A1c (HbA1c) levels for those with duration ≥6 months were 8.7/8.4% (72/68 mmol/mol) and were higher in adolescents vs. children. Elevated body mass index SD, triglycerides (≥150 mg/dL) and non-high-density lipoprotein (HDL)-cholesterol (≥130 mg/dL) were common: 7.6%, 11.0% and 12.7% (n = 288, 218 and 180, respectively). Serum creatinine levels were normal in all tested subjects (n = 194). Conclusions Youth with diabetes in less-resourced families in Mexico are achieving reasonable glycemia. Most T1D patients use a basal bolus insulin regimen and test blood glucose several times daily. Some subjects have adverse vascular risk factor profiles. Further attention is needed to prevent chronic complications. Monogenic diabetes is very likely in some youth, and genetic testing is indicated.
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Biomarcadores/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Renta/estadística & datos numéricos , Atención Dirigida al Paciente/normas , Factores Socioeconómicos , Adolescente , Adulto , Glucemia/análisis , Niño , Preescolar , Estudios Transversales , Diabetes Mellitus Tipo 1/economía , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Lactante , Recién Nacido , Masculino , México/epidemiología , Pronóstico , Adulto JovenRESUMEN
PURPOSE: Ovarian cancer is the most fatal of all gynecologic cancers, with a high relapse rate regardless of stage. Women treated for ovarian cancer, therefore, likely have supportive care needs that extend well beyond the time frame of first-line therapy. Unfortunately, there is minimal data describing these needs. The purpose of this qualitative study is to understand the supportive care needs of women with ovarian care at the end of treatment. METHODS: To better understand the issues faced by women with ovarian cancer, we conducted a public Twitter chat in collaboration with gynecologic cancer social media (#gyncsm). Both quantitative and qualitative analyses were performed. RESULTS: The chat occurred over a 1-hour time frame on Twitter and resulted in more than 300 unique and original tweets from 43 participants during the chat and an additional 60 unique participants following the chat. Survivors and physicians represented 32% and 11% of participants, respectively; caregivers, advocates, and other clinicians represented the remaining participants. Participants noted deep interest in receiving support during survivorship and dissatisfaction with currently available resources. Sentiment analysis showed that participants viewed the support from social media in a positive light and also revealed negative sentiment around the lack of support from health care providers at the end of treatment. CONCLUSIONS: Themes derived from the Twitter chat revealed the unique experiences of individuals with ovarian cancer after treatment, including a heightened sense of vulnerability. Understanding these themes represents an opportunity for clinicians to better understand and address the needs of this patient community.
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OBJECTIVES: To determine incidence, mortality, and clinical status of youth with diabetes at the Centro Vivir con Diabetes, Cochabamba, Bolivia, with support from International Diabetes Federation Life for a Child Program. METHODS: Incidence/mortality data analysis of all cases (<25 year (y)) diagnosed January 2005-February 2017 and cross-sectional data (December 2015). RESULTS: Over 12.2 years, 144 cases with type 1 diabetes (T1D) were diagnosed; 43.1% were male. Diagnosis age was 0.3-22.2 y; peak was 11-12 y. 11.1% were <5 y; 29.2%, 5-<10 y; 43.1%, 10-<15 y; 13.2%, 15-<20 y; and 3.5%, 20-<25 y. The youngest is being investigated for monogenic diabetes. Measured incidence in Cercado Province (Cochabamba Department) was 2.2/100,000 children < 15 y/y, with ≈80% ascertainment, giving total incidence of 2.7/100,000 children < 15 y/y. Two had died. Crude mortality rate was 2.3/1000 patient years. Clinical data on 141 cases <35 y: mean/median HbA1c was 8.5/8.2% (69/62 mmol/mol), levels higher in adolescents. Three were on renal replacement therapy; four others had substantial renal impairment. Elevated BMI, triglycerides, and cholesterol were common: 19.1%, 18.3%, and 39.1%, respectively. CONCLUSIONS: Bolivia has low T1D incidence. Reasonable glycemic control is being achieved despite limited resources; however, some have serious complications and adverse cardiovascular risk factor profiles. Further attention is needed for complications.
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Diabetes Mellitus Tipo 1/epidemiología , Salud Urbana , Adolescente , Adulto , Bolivia/epidemiología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Niño , Preescolar , Estudios de Cohortes , Costo de Enfermedad , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/mortalidad , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/mortalidad , Cardiomiopatías Diabéticas/epidemiología , Cardiomiopatías Diabéticas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Mortalidad , Factores de Riesgo , Adulto JovenRESUMEN
The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases remains to be determined.
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Mucosa Gástrica/inmunología , Gastritis/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Bacterianas/genética , Bután , Línea Celular , República Dominicana , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/fisiopatología , Redes Reguladoras de Genes , Islas Genómicas , Genotipo , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba , Adulto JovenRESUMEN
Increased resistance of Helicobacter pylori to clarithromycin and metronidazole has resulted in recommendation to substitute fluoroquinolones for eradication therapy. The aims of the study were to determine the prevalence and changes in primary levofloxacin resistance related to H. pylori gyrA sequences. The study utilized H. pylori strains isolated from patients undergoing gastroscopy in Bogotá, Colombia from 2009 to 2014. Levofloxacin susceptibility was assessed by agar dilution. Mutations in gyrA sequences affecting the quinolone resistance-determining region (QRDR) were evaluated by direct sequencing. Overall, the mean prevalence of primary levofloxacin resistance was 18.2% (80 of 439 samples). Resistance increased from 11.8% (12/102) in 2009 to 27.3% (21/77) in 2014 (p = 0.001). gyrA mutations in levofloxacin resistant strains were present in QRDR positions 87 and 91. The most common mutation was N87I (43.8%, 35/80) followed by D91N (28.8%, 23/80) and N87K (11.3%, 9/80). Levofloxacin resistance increased markedly in Colombia during the six-year study period. Primary levofloxacin resistance was most often mediated by point mutations in gyrA, with N87I being the most common QRDR mutation related to levofloxacin resistance.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Levofloxacino/farmacología , Adolescente , Adulto , Anciano , Colombia/epidemiología , Girasa de ADN/genética , Femenino , Helicobacter pylori/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) is one of the most common bacterial infections in humans and this infection can lead to gastric ulcers and gastric cancer. H. pylori is one of the most genetically variable human pathogens and the ability of the bacterium to bind to the host epithelium as well as the presence of different virulence factors and genetic variants within these genes have been associated with disease severity. Nicaragua has particularly high gastric cancer incidence and we therefore studied Nicaraguan clinical H. pylori isolates for factors that could contribute to cancer risk. METHODS: The complete genomes of fifty-two Nicaraguan H. pylori isolates were sequenced and assembled de novo, and phylogenetic and virulence factor analyses were performed. RESULTS: The Nicaraguan isolates showed phylogenetic relationship with West African isolates in whole-genome sequence comparisons and with Western and urban South- and Central American isolates using MLSA (Multi-locus sequence analysis). A majority, 77 % of the isolates carried the cancer-associated virulence gene cagA and also the s1/i1/m1 vacuolating cytotoxin, vacA allele combination, which is linked to increased severity of disease. Specifically, we also found that Nicaraguan isolates have a blood group-binding adhesin (BabA) variant highly similar to previously reported BabA sequences from Latin America, including from isolates belonging to other phylogenetic groups. These BabA sequences were found to be under positive selection at several amino acid positions that differed from the global collection of isolates. CONCLUSION: The discovery of a Latin American BabA variant, independent of overall phylogenetic background, suggests hitherto unknown host or environmental factors within the Latin American population giving H. pylori isolates carrying this adhesin variant a selective advantage, which could affect pathogenesis and risk for sequelae through specific adherence properties.
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Adhesinas Bacterianas/genética , Helicobacter pylori/clasificación , Helicobacter pylori/genética , Adhesinas Bacterianas/química , Adolescente , Adulto , Anciano , Secuencia de Aminoácidos , Antígenos Bacterianos/genética , Femenino , Variación Genética , Genoma Bacteriano , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Tipificación de Secuencias Multilocus , Nicaragua , Filogenia , Factores de Virulencia/química , Factores de Virulencia/genética , Adulto JovenRESUMEN
The outcomes of Helicobacter pylori infection vary geographically. H pylori strains, disease presentation, and environments differ markedly in Bhutan and Dominican Republic. The aims were to compare the strains, histology, and expression of interleukin (IL) 8 and IL-10 from gastric mucosa from the 2 countries. H pylori status was assessed by the combination of rapid urease test, culture, and histology. Histology was evaluated using the updated Sydney System, and cytokines in gastric biopsies were measured using real-time polymerase chain reaction (PCR). There were 138 subjects from Bhutan and 155 from Dominican Republic. The prevalence of H pylori infection was 65% and 59%, respectively. The genotype of cagA was predominantly East Asian type in Bhutan versus Western type in Dominican Republic. Gastritis severity was significantly higher in H pylori-infected subjects from Bhutan than those from Dominican Republic. IL-8 expression by H pylori infection was 5.5-fold increased in Bhutan versus 3-fold in Dominican Republic (P < .001); IL-10 expression was similar. IL-8 expression levels among H pylori-infected cases tended to be positively correlated with polymorphonuclear leucocyte and monocyte infiltration scores in both countries. IL-8 expression among those with grade 2 and 3 polymorphonuclear leucocyte and monocyte infiltration was significantly higher in Bhutan than in Dominican Republic. The difference in IL-8 expression in the 2 countries is reflected in the different disease pattern between them. Whether the dominant factor is differences in H pylori virulence, in host-H pylori-environmental interactions, genetic factors or all remains unclear. However, severity of inflammation appears to be a critical factor in disease pathogenesis. We compared IL-8 messenger RNA levels between the high gastric cancer risk country, Bhutan (mainly East Asian-type H pylori), and the lower gastric cancer risk country, Dominican Republic (mainly Western-type H pylori).
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Mucosa Gástrica/inmunología , Gastritis/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Interleucina-8/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Bután/epidemiología , Biopsia , República Dominicana/epidemiología , Ambiente , Femenino , Mucosa Gástrica/microbiología , Gastritis/diagnóstico , Gastritis/epidemiología , Gastritis/genética , Gastritis/microbiología , Marcadores Genéticos , Genotipo , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Helicobacter pylori/patogenicidad , Interacciones Huésped-Patógeno , Humanos , Interleucina-10/análisis , Interleucina-10/genética , Interleucina-8/genética , Masculino , Persona de Mediana Edad , Prevalencia , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Through its effects on gastric secretion, we hypothesized that Helicobacter pylori infection may influence oral immunization. Accordingly, we examined the association between H. pylori infection, serum pepsinogen (PG) (measures for H. pylori gastritis) and vibriocidal antibody (a correlate of protection) seroconversion following oral immunization with CVD 103-HgR live cholera vaccine among children of different ages. METHODS: Sera from 422 Chilean children who were vaccinated with a single dose of CVD 103-HgR were tested by ELISA for serum IgG antibodies to H. pylori, PG I and PG II levels and antibodies to Shigella flexneri 2a lipopolysaccharide and hepatitis A virus (as markers of low socioeconomic status and exposure to enteric pathogens). RESULTS: The likelihood of vibriocidal antibody seroconversion following vaccination with CVD 103-HgR was significantly decreased in H. pylori-seropositive children age 6 months to 4 years with PG II>8 µg/L (adjusted OR 0.14 (95% CI 0.03-0.61; P = 0.009), and also in H. pylori seropositives with lower PG II level (adjusted OR 0.34, 95% CI 0.14-0.83; P = 0.017), compared to H. pylori-seronegatives. H. pylori-seropositive children aged 5-9 years with serum PG I>30 µg/L (indicating more severe gastritis) had higher odds of vibriocidal seroconversion than those with lower PG I levels (adjusted OR 4.41, 95%CI 1.26-15.38; P = 0.02). There was no significant association between exposures to S. flexneri 2a or hepatitis A virus and vibriocidal seroconversion. CONCLUSIONS: As H. pylori gastritis progresses with increasing pediatric age in developing country venues, changes in gastric secretion ensue that we believe explain the observed differences in age-related immune responses to immunization with live oral cholera vaccine. The effect of H. pylori and changes of gastric acid secretion on the immunogenicity of various oral vaccines should be studied in different developing, transitional and industrialized country settings.
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Vacunas contra el Cólera/inmunología , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Pepsinógeno A/sangre , Administración Oral , Niño , Preescolar , Chile , Vacunas contra el Cólera/administración & dosificación , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , HumanosRESUMEN
Resistance of Helicobacter pylori to clarithromycin is the most common cause of treatment failure in patients with H. pylori infections. This study describes the MICs and the presence of 23S rRNA mutations of H. pylori isolates from Bogotá, D.C., Colombia. H. pylori were isolated from gastric biopsies from patients with functional dyspepsia. Clarithromycin susceptibility was investigated by agar dilution and strains were considered resistant if the MIC was ≥ 1 µg/ml. DNA sequences of the 23S rRNA gene of strains resistant and sensitive to clarithromycin were determined to identify specific point mutations. Clarithromycin resistance was present in 13.6% of patients by agar dilution. The A2143G, A2142G and A2142C mutations were found in 90.5, 7.1, and 2.4% of H. pylori strains with resistance genotype.The resistant phenotype was associated with 23S rRNA resistance genotype in 85.7% of isolates. The point mutations in 23S rRNA were well correlated with MICs values for clarithromycin.
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Claritromicina/farmacología , Farmacorresistencia Bacteriana/genética , Genotipo , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Pruebas de Sensibilidad Microbiana , Fenotipo , Adulto , Anciano , Antibacterianos/farmacología , Colombia , Análisis Mutacional de ADN , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Persona de Mediana Edad , Mutación , ARN Ribosómico 23S/genética , Adulto JovenRESUMEN
Numerous studies have quantified antibiotic resistance genes (ARG) in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water column and sediment samples during the dry- and wet-seasons to assess how seasonal and other factors influence ARG transport down the Almendares River (Havana, Cuba). Eight locations were sampled and stream flow estimated during both seasons; qPCR was used to quantify four tetracycline, two erythromycin, and three beta-lactam resistance genes. ARG concentrations were higher in wet-season versus dry-season samples, which combined with higher flows, indicated much greater ARG transport downstream during the wet-season. However, water column ARG levels were more spatially variable in the dry-season than the wet-season, with the proximity of waste outfalls strongly influencing local ARG levels. Results confirm that dry-season sampling provides a useful picture of the impact of individual waste inputs on local stream ARG levels, whereas the majority of ARGs in this tropical river were transported downstream during the wet-season, possibly due to re-entrainment of ARG from sediments.
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Considerable debate exists over the primary cause of increased antibiotic resistance (AR) worldwide. Evidence suggests increasing AR results from overuse of antibiotics in medicine and therapeutic and nontherapeutic applications in agriculture. However, pollution also can influence environmental AR, particularly associated with heavy metal, pharmaceutical, and other waste releases, although the relative scale of the "pollution" contribution is poorly defined, which restricts targeted mitigation efforts. The question is "where to study and quantify AR from pollution versus other causes to best understand the pollution effect". One useful site is Cuba because industrial pollution broadly exists; antibiotics are used sparingly in medicine and agriculture; and multiresistant bacterial infections are increasing in clinical settings without explanation. Within this context, we quantified 13 antibiotic resistance genes (ARG; indicators of AR potential), 6 heavy metals, 3 antibiotics, and 17 other organic pollutants at 8 locations along the Almendares River in western Havana at sites bracketing known waste discharge points, including a large solid waste landfill and various pharmaceutical factories. Significant correlations (p < 0.05) were found between sediment ARG levels, especially for tetracyclines and ß-lactams (e.g., tet(M), tet(O), tet(Q), tet(W), bla(OXA)), and sediment Cu and water column ampicillin levels in the river. Further, sediment ARG levels increased by up to 3 orders of magnitude downstream of the pharmaceutical factories and were highest where human population densities also were high. Although explicit links are not shown, results suggest that pollution has increased background AR levels in a setting where other causes of AR are less prevalent.
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Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Ríos/química , Contaminantes Químicos del Agua/análisis , Antibacterianos/análisis , Antiportadores/análisis , Antiportadores/genética , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Cuba , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiología , Hidrocarburos Clorados/análisis , Metales Pesados/análisis , Compuestos Orgánicos/análisis , Plaguicidas/análisis , Ríos/microbiologíaRESUMEN
OBJECTIVE: A higher incidence of infectious disease has been documented in U.S. regions bordering Mexico compared with non-border areas. We assessed the prevalence of important gastrointestinal infections in Ciudad Juarez, Mexico, and El Paso, Texas, the largest binational community along the U.S.-Mexico border. METHODS: Fecal specimens from a sample of the asymptomatic population representing all ages were tested for Helicobacter pylori (H. pylori), Cryptosporidium spp., Giardia spp., and other intestinal parasitic pathogens using flotation, immunoassays, and/or polymerase chain reaction. We also measured indicators of microbiological contamination of drinking water, hands of food preparers, and kitchen surfaces. RESULTS: Overall, of the 386 participants, H. pylori was present in 38.2%, Taenia spp. in 3.3%, Giardia spp. in 2.7%, Cryptosporidium spp. in 1.9%, Entamoeba dispar in 1.3%, and Ascaris lumbricoides and Necator americanus in 0.3% of the study subjects; Cyclospora spp. and Entamoeba histolytica were not found. H. pylori infection was associated with handwashing (prevalence ratio [PR] = 1.3, 95% confidence interval [CI] 1.0, 1.8). Taenia spp. was found more often on the U.S. side (PR=8.6, 95% CI 2.3, 30.8). We did not find an association between these infections and the occurrence of total coliforms or fecal coliforms on kitchen surfaces. In addition, Escherichia coli was not found in any drinking water sample. CONCLUSION: The study results indicated that H. pylori and Taenia spp. infections may be highly prevalent along the U.S.-Mexico border. Additional research is necessary to adequately characterize the prevalence, as well as determine whether interventions that reduce these infections are warranted.
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Infecciones por Helicobacter/epidemiología , Helicobacter pylori , Parasitosis Intestinales/epidemiología , Teniasis/epidemiología , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por Helicobacter/prevención & control , Humanos , Lactante , Recién Nacido , Parasitosis Intestinales/prevención & control , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Teniasis/prevención & control , Estados Unidos/epidemiologíaRESUMEN
The hom family of Helicobacter pylori outer-membrane proteins, especially the homB gene, has been suggested as a novel virulence factor; however, the clinical association and function of this gene are still unclear. We evaluated the presence of the homA, homB, and cagA genes in 286 strains isolated from patients in the U.S. and Colombian populations (126 with gastritis, 96 with duodenal ulcer, and 64 with gastric cancer) by PCR. The results were compared with the clinical presentation and gastric injury. The prevalence of the homB gene was significantly higher in strains isolated from gastric-cancer patients (71.9%) than in those from duodenal ulcer patients (52.1%) (P = 0.012). In a multivariate analysis, the presence of the cagA gene significantly increased the risk for developing gastric cancer and duodenal ulcer, with the presence of the homB gene acting as a factor that could distinguish gastric cancer from duodenal ulcer (adjusted odds ratio, 3.033; 95% confidence interval, approximately 1.37 to approximately 6.73). cagA status was correlated with homB status (r = 0.323; P < 0.01). A histological analysis showed that cagA status was associated with inflammation and atrophy both in the antrum and in the corpus, while homB status was associated with inflammation and atrophy in the corpus. homB gene status might be susceptible to gastric-cancer development such that the homB gene is used as a factor for discriminating the risk of gastric cancer from that of duodenal ulcer.
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Proteínas de la Membrana Bacteriana Externa/genética , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/microbiología , Helicobacter pylori/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/microbiología , Adulto , Anciano , Antígenos Bacterianos/genética , Proteínas Bacterianas/genética , Biomarcadores de Tumor , Colombia , Diagnóstico Diferencial , Femenino , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estados Unidos , Factores de Virulencia/genéticaRESUMEN
BACKGROUND AND AIMS: Outer membrane proteins of Helicobacter pylori mediate important pathogen-host interactions such as colonization, adhesion and the inflammatory response. hopQ genotypes have been suggested to be associated with increased risk of peptic ulcer. The aim of this study was to test the relation of hopQ genotype to H. pylori-related disease and histological changes in Asian and Western countries. METHODS: hopQ genotype, cagA status and vacA genotype of H. pylori isolated from patients from Asian and Western countries were determined and the results were compared with the clinical presentation and gastric histology. RESULTS: Most Asian strains possessed virulent genotypes (hopQ type I, vacA s1-m1 and cagA-positive). In Western countries, hopQ type I genotype was significantly linked with vacA s1 and m1 genotypes and cagA-positive status. Inflammatory cell infiltration and atrophy scores were significantly higher in patients with hopQ type I strains than those with type II in Western patients. However, the hopQ type I genotype was not associated with an increased risk for peptic ulcer or gastric cancer, and had no additive effects to vacA genotypes or cagA-positive status. CONCLUSION: The expression of multiple putative virulence factors in Asian strains likely explains the relatively high incidence of clinical outcomes including gastric cancer compared with other parts of the world. Although hopQ genotype did not improve the predictive value above other genotyping for development of H. pylori-related gastroduodenal diseases, the hopQ genotype might be able to add a useful virulence marker for gastroduodenal diseases.
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Pueblo Asiatico , Infecciones por Helicobacter/etnología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Gastropatías/etnología , Gastropatías/microbiología , Población Blanca , Antígenos Bacterianos/genética , Asia/epidemiología , Pueblo Asiatico/estadística & datos numéricos , Proteínas Bacterianas/genética , Colombia/epidemiología , Femenino , Genotipo , Infecciones por Helicobacter/patología , Helicobacter pylori/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Estómago/microbiología , Estómago/patología , Gastropatías/patología , Estados Unidos/epidemiología , Virulencia , Población Blanca/estadística & datos numéricosRESUMEN
Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorly understood. We studied the genetic relationships of H. pylori isolated from 52 individuals of two large families living in a rural community in South Africa and from 43 individuals of 11 families living in urban settings in the United Kingdom, the United States, Korea, and Colombia. A 3,406 bp multilocus sequence haplotype was determined for a total of 142 H. pylori isolates. Isolates were assigned to biogeographic populations, and recent transmission was measured as the occurrence of non-unique isolates, i.e., isolates whose sequences were identical to those of other isolates. Members of urban families were almost always infected with isolates from the biogeographic population that is common in their location. Non-unique isolates were frequent in urban families, consistent with familial transmission between parents and children or between siblings. In contrast, the diversity of H. pylori in the South African families was much more extensive, and four distinct biogeographic populations circulated in this area. Non-unique isolates were less frequent in South African families, and there was no significant correlation between kinship and similarity of H. pylori sequences. However, individuals who lived in the same household did have an increased probability of carrying the same non-unique isolates of H. pylori, independent of kinship. We conclude that patterns of spread of H. pylori under conditions of high prevalence, such as the rural South African families, differ from those in developed countries. Horizontal transmission occurs frequently between persons who do not belong to a core family, blurring the pattern of familial transmission that is typical of developed countries. Predominantly familial transmission in urban societies is likely a result of modern living conditions with good sanitation and where physical contact between persons outside the core family is limited and regulated by societal rules. The patterns observed in rural South African families may be representative of large parts of the developing world.
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Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/transmisión , Helicobacter pylori , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Colombia/epidemiología , Familia , Variación Genética , Haplotipos , Helicobacter pylori/genética , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/fisiología , Humanos , Corea (Geográfico)/epidemiología , Mosaicismo , Linaje , Prevalencia , Población Rural/estadística & datos numéricos , Sudáfrica/epidemiología , Reino Unido/epidemiología , Estados Unidos/epidemiología , Población Urbana/estadística & datos numéricosRESUMEN
A man bitten by a large coral snake (Micrurus lemniscatus helleri) in the Amazon basin of Ecuador developed persistent excruciating pain in the bitten arm. On admission to hospital less than 30 min later, he had a polymorphonuclear leucocytosis, thrombocytopenia and mildly prolonged prothrombin time/partial thromboplastin time. Not until 14 h after the bite did he develop the first signs of neurotoxicity. Despite treatment with specific antivenom 50 h after the bite, he required oxygen for respiratory failure 60 h, and 6 h of mechanical ventilation 72 h, after the bite. Over the next 38 h, he required two further intubations and periods of assisted ventilation before being airlifted to a tertiary referral hospital. Complications included bacterial pneumonia, pneumothorax, bronchial obstruction by mucus plugs and mild rhabdomyolysis. He was discharged from hospital 15 days after the bite with persistent limb weakness and urinary incontinence but eventually recovered. The interesting and unusual features of this case (severe local pain, very slow evolution of neurotoxic envenoming, persistent thrombocytopenia and mild coagulopathy) are discussed in the context of what is known of the composition of Micrurus venoms and the small clinical literature on envenoming from their bites.