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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 , Purificação da Água , Humanos , Eliminação de Resíduos Líquidos , Microalgas/metabolismo , Águas Residuárias , Bactérias/genética , Antibacterianos/metabolismo , Genes BacterianosRESUMO
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/sangue , Cromatografia Líquida , Teste em Amostras de Sangue Seco/métodos , Metaboloma , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem , Preservação de Sangue/métodos , Preservação de Sangue/normas , Teste em Amostras de Sangue Seco/normas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal/normas , Estudos Prospectivos , Valores de Referência , Manejo de Espécimes/métodos , Manejo de Espécimes/normasRESUMO
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/análise , Planeta Terra , Evolução Planetária , Sedimentos Geológicos/química , Criptônio/análise , Atmosfera/química , Equador , Evolução Química , Hélio/análise , Islândia , Isótopos/análise , Meteoroides , Neônio/análise , Nêutrons , Nitrogênio/análise , Tungstênio/análise , Xenônio/análiseRESUMO
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/análise , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Renda/estatística & dados numéricos , Assistência Centrada no Paciente/normas , Fatores Socioeconômicos , Adolescente , Adulto , Glicemia/análise , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/economia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Prognóstico , Adulto JovemRESUMO
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/epidemiologia , Saúde da População Urbana , Adolescente , Adulto , Bolívia/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Efeitos Psicossociais da Doença , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/mortalidade , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/mortalidade , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Mortalidade , Fatores de Risco , Adulto JovemRESUMO
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/imunologia , Gastrite/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/genética , Butão , Linhagem Celular , República Dominicana , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/fisiopatologia , Redes Reguladoras de Genes , Ilhas Genômicas , Genótipo , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima , Adulto JovemRESUMO
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/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Levofloxacino/farmacologia , Adolescente , Adulto , Idoso , Colômbia/epidemiologia , DNA Girase/genética , Feminino , Helicobacter pylori/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Prevalência , Adulto JovemRESUMO
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.