Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470190

RESUMO

AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by impaired gut-brain interaction. Considering the paucity of evidence in the Indian setting, the current study was conducted to determine the sociodemographics, clinical profiles, management practices, and patients' perception among newly diagnosed patients with IBS. METHODS: This was a cross-sectional, single-visit, observational, non-interventional, epidemiological study conducted across 12 centres. The primary objective was evaluation of sociodemographic and clinical profiles. The key secondary objective was assessment of gastrointestinal symptom severity including evaluation of anxiety and depression using the hospital anxiety and depression scale (HADS) scores. Knowledge, attitude, and practices (KAP) were evaluated as an exploratory objective. RESULTS: Out of 300 enrolled patients, 120 (40%) were aged 31-45 years (mean age: 38.55±12.45 years), and 204 were men (68%). Overall, 40% of patients belonged to the upper-middle-class, with a Kuppuswamy score of 16-25. Most patients (91%) did not work in night shifts. Only 13% of patients performed more than recommended physical activity. Stress and food were the leading triggers for IBS (29%). Abdominal pain and diarrhoea as cardinal symptoms were reported by 43.3% and 33.0% patients, respectively. Borderline abnormal anxiety and depression were reported by 21.3% and 26.7% of patients, respectively. KAP assessment revealed that 56.0% of patients had poor knowledge, 26.3% had moderate knowledge, and 17.7% had good knowledge about IBS; nevertheless, 43% of patients maintained high levels of precaution towards managing symptoms. CONCLUSION: Given the limited knowledge about IBS in India among newly diagnosed patients, strategies to enhance awareness about the condition are warranted.


Assuntos
Síndrome do Intestino Irritável , Adulto , Ansiedade/epidemiologia , Ansiedade/etiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Humanos , Índia/epidemiologia , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
2.
Clin Epigenetics ; 13(1): 23, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33516250

RESUMO

BACKGROUND: The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. RESULTS: Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3' portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. CONCLUSIONS: These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3' portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3' portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.

3.
Appl Environ Microbiol ; 86(24)2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-32917755

RESUMO

Hospital wastewater is an increasingly recognized reservoir for resistant Gram-negative organisms. Factors involved in establishment and persistence of Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) in hospital wastewater plumbing are unclear. This study was conducted at a hospital with endemic KPCOs linked to wastewater reservoirs and robust patient perirectal screening for silent KPCO carriage. Over 5 months, both rooms occupied and rooms not occupied by KPCO-positive patients were sampled at three wastewater sites within each room (sink drain, sink P-trap, and toilet or hopper). Risk factors for KPCO positivity were assessed using logistic regression. Whole-genome sequencing (WGS) identified environmental seeding by KPCO-positive patients. A total of 219/475 (46%) room sampling events were KPCO positive in at least one wastewater site. KPCO-positive patient exposure was associated with increased risk of environmental positivity for the room and toilet/hopper. Previous positivity and intensive care unit room type were consistently associated with increased risk. Tube feeds were associated with increased risk for the drain, while exposure to patients with Clostridioides difficile was associated with decreased risk. Urinary catheter exposure was associated with increased risk of P-trap positivity. P-trap heaters reduced risk of P-trap and sink drain positivity. WGS identified genomically linked environmental seeding in 6 of 99 room occupations by 40 KPCO-positive patients. In conclusion, KPCO-positive patients seed the environment in at least 6% of opportunities; once positive for KPCOs, wastewater sites are at greater risk of being positive subsequently. Increased nutrient exposure, e.g., due to tube food disposal down sinks, may increase risk; frequent flushing may be protective.IMPORTANCE Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are bacteria that are resistant to most antibiotics and thus are challenging to treat when they cause infections in patients. These organisms can be acquired by patients who are hospitalized for other reasons, complicating their hospital stay and even leading to death. Hospital wastewater sites, such as sink drains and toilets, have played a role in many reported outbreaks over the past decade. The significance of our research is in identifying risk factors for environmental positivity for KPCOs, which will facilitate further work to prevent transmission of these organisms to patients from the hospital environment.


Assuntos
Proteínas de Bactérias/análise , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , Águas Residuárias/microbiologia , beta-Lactamases/análise , Hospitais , Humanos , Infecções por Klebsiella/microbiologia , Virginia/epidemiologia , Águas Residuárias/análise
4.
Water Res ; 176: 115707, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32224328

RESUMO

Antimicrobial resistance has been recognized as a threat to human health. The role of hospital sinks acting as a reservoir for some of the most concerning antibiotic resistant organisms, carbapenemase producing Enterobacterales (CPE) is evident but not well understood. Strategies to prevent establishment, interventions to eliminate these reservoirs and factors which drive persistence of CPE are not well established. We use a uniquely designed sink lab to transplant CPE colonized hospital sink plumbing with an aim to understand CPE dynamics in a controlled setting, notably exploiting both molecular and culture techniques. After ex situ installation the CPE population in the sink plumbing drop from previously detectable to undetectable levels. The addition of nutrients is followed by a quick rebound in CPE detection in the sinks after as many as 37 days. We did not however detect a significant shift in microbial community structure or the overall resistance gene carriage in longitudinal samples from a subset of these transplanted sinks using whole shotgun metagenomic sequencing. Comparing nutrient types in a benchtop culture study model, protein rich nutrients appear to be the most supportive for CPE growth and biofilm formation ability. The role of nutrients exposure is determining factor for maintaining a high bioburden of CPE in the sink drains and P-traps. Therefore, limiting nutrient disposal into sinks has reasonable potential with regard to decreasing the CPE wastewater burden, especially in hospitals seeking to control an environmental reservoir.


Assuntos
Klebsiella pneumoniae , beta-Lactamases , Proteínas de Bactérias , Humanos , Nutrientes
5.
Curr Opin Ophthalmol ; 31(2): 132-138, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922979

RESUMO

PURPOSE OF REVIEW: This review will provide an update on surgical techniques, outcomes, and complications for two new translimbal bleb-forming surgical glaucoma devices. RECENT FINDINGS: The XEN Gel Microstent and PreserFlo MicroShunt comprise a category of subconjunctival microinvasive glaucoma surgery developed with the aim of improving the predictability and safety profile of bleb-forming procedures. Both devices are made of noninflammatory material which limits postsurgical inflammation and scarring and have a valve-less intrinsic flow-limiting design, which decreases the risk of hypotony. There are various techniques of implantation for the XEN Gel Microstent each with their own advantages and disadvantages. SUMMARY: These devices have demonstrated promising outcomes in early experimental literature with similar intraocular pressure-lowering effects to traditional incisional surgery such as trabeculectomy or tube shunt surgery, but with fewer risks. Future randomized, prospective studies should be done to compare these gel stents and microshunts both to each other and to other traditional glaucoma surgeries.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/cirurgia , Stents , Túnica Conjuntiva/cirurgia , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Implantação de Prótese , Tonometria Ocular , Trabeculectomia
6.
Eur J Med Chem ; 185: 111800, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706639

RESUMO

Anti-virulence approaches in the treatment of Pseudomonas aeruginosa (PA)-induced infections have shown clinical potential in multiple in vitro and in vivo studies. However, development of these compounds is limited by several factors, including the lack of molecules capable of penetrating the membrane of gram-negative organisms. Here, we report the identification of novel structurally diverse compounds that inhibit PqsR and LasR-based signaling and diminish virulence factor production and biofilm growth in two clinically relevant strains of P. aeruginosa. It is the first report where potential anti-virulent agents were evaluated for inhibition of several virulence factors of PA. Finally, co-treatment with these inhibitors significantly reduced the production of virulence factors induced by the presence of sub-inhibitory levels of ciprofloxacin. Further, we have analyzed the drug-likeness profile of designed compounds using quantitative estimates of drug-likeness (QED) and confirmed their potential as hit molecules for further development.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Desenho de Fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Ciprofloxacina/síntese química , Ciprofloxacina/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Virulência/efeitos dos fármacos , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/biossíntese
7.
J Curr Glaucoma Pract ; 13(2): 62-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564795

RESUMO

Aim: Whether pupillary expansion during phacoemulsification causes a change in postoperative intraocular pressure (IOP) is currently unknown. However, a growing proportion of patients can present with concurrent glaucoma and cataracts, which poses an increased risk of having small pupils and makes finding the answer to this question imperative for treating physicians. Materials and methods: This was a retrospective, observational cohort study which utilized data from 2008 to 2016 from the University Hospital, Newark, New Jersey, USA. All patients with primary open-angle glaucoma (POAG) who underwent phacoemulsification with pupillary expansion were considered for inclusion. Cases were subsequently excluded if they had prior incisional glaucoma surgery, if phacoemulsification was combined with another surgery, or if they had any incisional surgery in the eye 1 year preoperatively or postoperatively. The control group was made up of patients without POAG. The primary outcome was IOP. Results: Thirty-seven eyes from 31 glaucoma patients and 29 eyes from 28 control patients met inclusion criteria. The mean IOP in the POAG group increased from 15.0 ± 4.6 mm Hg to 15.9 ± 3.5 mm Hg after 1 year, whereas the control group decreased from 14.1 ± 3.6 mm Hg to 11.9 ± 3.9 mm Hg. Multivariate analysis showed that glaucoma was associated with a 5.56 mm Hg increase in IOP at 12 months postoperatively. The average number of glaucoma medications decreased significantly from 1.7 ± 1.4 at the baseline to 1.3 ± 1.3 after 1 year. Conclusion: In contrast with non-POAG patients, no significant drop in the mean IOP was noted after complex cataract surgery for this cohort of glaucoma patients, although medication burden significantly decreased and VA improved significantly. Clinical significance: Phacoemulsification with intraoperative pupillary expansion in POAG patients may not decrease IOP after 12 months but it can decrease the number of anti-glaucoma medications they take. How to cite this article: Bargoud AR, Parikh H, et al. Outcomes of Complex Cataract Surgery in Patients with Primary Open-angle Glaucoma. J Curr Glaucoma Pract 2019;13(2):62-67.

8.
Open Forum Infect Dis ; 6(7): ofz266, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31281862

RESUMO

Background: Glucose hydrogen breath testing is a noninvasive test for small intestine bacterial overgrowth (SIBO). A positive glucose hydrogen breath test is common in children from low-income countries and has been found to be associated with malnutrition as measured by stunted growth. The microbiome associated with positive breath testing is relatively unstudied. Methods: We performed 16 S V4 rDNA microbiome analysis on the stool of 90 Bangladeshi children aged 2 years from an impoverished neighborhood who were tested at the same time for SIBO by glucose hydrogen breath testing. Data were analyzed by linear discriminant analysis effect size with SIBO as the outcome. Any selected genera were tested individually by Wilcoxon's rank-sum test to ensure that linear discriminant analysis effect size results were not outlier-skewed. Results: Linear discriminant analysis effect size analysis identified Lactobacillus (linear discriminate analysis score, 4.59; P = .03) as over-represented in 15 out of the 90 children who were SIBO positive. Conclusions: These results suggest that glucose hydrogen breath test positivity in children from low-income settings may be due to an upper intestinal Lactobacillus bloom, potentially explaining the association of SIBO with the gut damage and inflammation that leads to malnutrition.

9.
J Clin Microbiol ; 57(10)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31340992

RESUMO

With multidrug-resistant (MDR) Enterobacterales on the rise, a nontoxic antimicrobial agent with a unique mechanism of action such as fosfomycin seems attractive. However, establishing accurate fosfomycin susceptibility testing for non-Escherichia coli isolates in a clinical microbiology laboratory remains problematic. We evaluated fosfomycin susceptibility by multiple methods with 96 KPC-producing clinical isolates of multiple strains and species collected at a single center between 2008 and 2016. In addition, we assessed the presence of fosfomycin resistance genes from whole-genome sequencing (WGS) data using NCBI's AMRFinder and custom HMM search. Susceptibility testing was performed using a glucose-6-phosphate-supplemented fosfomycin Etest and Kirby-Bauer disk diffusion (DD) assays, and the results were compared to those obtained by agar dilution. Clinical Laboratory and Standards Institute (CLSI) breakpoints for E. coli were applied for interpretation. Overall, 63% (60/96) of isolates were susceptible by Etest, 70% (67/96) by DD, and 88% (84/96) by agar dilution. fosA was detected in 80% (70/88) of previously sequenced isolates, with species-specific associations and alleles, and fosA-positive isolates were associated with higher MIC distributions. Disk potentiation testing was performed using sodium phosphonoformate to inhibit fosA and showed significant increases in the zone diameter of DD testing for isolates that were fosA positive compared to those that were fosA negative. The addition of sodium phosphonoformate (PPF) corrected 10/14 (71%) major errors in categorical agreement with agar dilution. Our results indicate that fosA influences the inaccuracy of susceptibility testing by methods readily available in a clinical laboratory compared to agar dilution. Further research is needed to determine the impact of fosA on clinical outcomes.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Fosfomicina/farmacologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , beta-Lactamases/genética , Proteínas de Bactérias/biossíntese , Genoma Bacteriano , Humanos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , beta-Lactamases/biossíntese
10.
J Infect Dis ; 220(5): 852-861, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31111902

RESUMO

BACKGROUND: Mechanisms linking herpes simplex virus type 2 (HSV-2) with human immunodeficiency virus (HIV) are not fully defined. We tested the hypothesis that HSV-2 and HIV dual infection is associated with cervicovaginal inflammation and/or vaginal dysbiosis. METHODS: Genital tract samples were obtained weekly over a 12-week period from 30 women seropositive (+) for HIV and HSV-2 and 15 women each who were seropositive for one or seronegative (-) for both viruses. Immune mediators, antimicrobial activity, and microbial composition and diversity were compared. RESULTS: Significant differences in the concentrations of interferon-γ (P = .002), tumor necrosis factor-α (P = .03), human beta defensin 1 (P = .001), secretory leukocyte protease inhibitor (P = .01), and lysozyme (P = .03) were observed across the 4 groups (Kruskal-Wallis). There were also significant differences in vaginal microbial alpha diversity (Simpson index) (P = .0046). Specifically, when comparing HIV-1+/HSV-2+ to HIV-1-/HSV-2- women, a decrease in Lactobacillus crispatus and increase in diverse anaerobes was observed. The number of genital HSV outbreaks was greater in HIV+ versus HIV- women (39 versus 12) (P = .04), but there were no significant differences when comparing outbreak to non-outbreak visits. CONCLUSIONS: Increased microbial diversity and cervicovaginal inflammation in HIV and HSV-2 dually infected women may adversely impact genital health and, in the absence of antiretroviral therapy, facilitate HIV shedding.


Assuntos
Genitália Feminina/microbiologia , Infecções por HIV/complicações , Herpes Genital/imunologia , Herpesvirus Humano 2/imunologia , Imunidade nas Mucosas/imunologia , Microbiota/fisiologia , Vagina/microbiologia , Adulto , Anti-Infecciosos/farmacologia , Coinfecção/virologia , Disbiose , Feminino , Herpes Genital/epidemiologia , Herpes Genital/virologia , Humanos , Interferon gama , Lactobacillus , Pessoa de Meia-Idade , Muramidase , Inibidor Secretado de Peptidases Leucocitárias , Fator de Necrose Tumoral alfa , Vagina/virologia , Eliminação de Partículas Virais , beta-Defensinas
11.
Nat Med ; 25(6): 1012-1021, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142849

RESUMO

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.


Assuntos
Microbiota , Nascimento Prematuro/microbiologia , Vagina/microbiologia , Adulto , Afro-Americanos , Biodiversidade , Estudos de Coortes , Citocinas/metabolismo , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Recém-Nascido , Mediadores da Inflamação/metabolismo , Estudos Longitudinais , Metagenômica , Microbiota/genética , Microbiota/imunologia , Nascimento Prematuro/etiologia , Nascimento Prematuro/imunologia , Fatores de Risco , Estados Unidos , Vagina/imunologia , Adulto Jovem
12.
Nat Med ; 25(6): 1001-1011, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31142850

RESUMO

The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.


Assuntos
Microbiota , Gravidez/fisiologia , Vagina/microbiologia , Adulto , Afro-Americanos , Biodiversidade , Estudos de Coortes , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Microbiota/genética , Microbiota/fisiologia , Classe Social
13.
Plasmid ; 103: 1-8, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30928702

RESUMO

As the spread of antimicrobial resistance (AMR) genes becomes an increasing global threat, improved understanding of mobile genetic elements which contribute to the spread of antimicrobial resistance genes, becomes more critical. We created transconjugants from the mating of three chromosomally isogenic Klebsiella pneumoniae carbapenemase (blaKPC) positive Citrobacter freundii isolates with a laboratory strain of Escherichia coli and evaluated the movement of small cryptic plasmids (SCPs), p3223 and p1916, when larger blaKPC-plasmids were transferred. In all of the 143 transconjugants, multiple plasmids, both large and small, transferred with each mating. When two blaKPC-plasmids were present in the host, frequently (87%; 98/113) both would be transferred during mating. p3223 is found in a wide range of bacterial hosts that harbor AMR genes; p1916 has been identified in only a limited number of publicly available sequences to date. From our evaluation, there is still much to learn about SCPs, and the high rate of co-transfer of multiple plasmids from real-world carbapenemase-producing Enterobacteriales.


Assuntos
Proteínas de Bactérias/genética , Citrobacter freundii/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , Plasmídeos/química , beta-Lactamases/genética , Proteínas de Bactérias/metabolismo , Citrobacter freundii/metabolismo , Conjugação Genética , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Escherichia coli/metabolismo , Expressão Gênica , Frequência do Gene , Klebsiella pneumoniae/metabolismo , Tipagem de Sequências Multilocus , Plasmídeos/metabolismo , beta-Lactamases/metabolismo
15.
J Perinatol ; 39(6): 824-836, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858609

RESUMO

OBJECTIVE: Evidence supports an inverse association between vitamin D and bacterial vaginosis (BV) during pregnancy. Furthermore, both the vaginal microbiome and vitamin D status correlate with pregnancy outcome. Women of African ancestry are more likely to experience BV, to be vitamin D deficient, and to have certain pregnancy complications. We investigated the association between vitamin D status and the vaginal microbiome. STUDY DESIGN: Subjects were assigned to a treatment (4400 IU) or a control group (400 IU vitamin D daily), sampled three times during pregnancy, and vaginal 16S rRNA gene taxonomic profiles and plasma 25-hydroxyvitamin D [25(OH)D] concentrations were examined. RESULT: Gestational age and ethnicity were significantly associated with the microbiome. Megasphaera correlated negatively (p = 0.0187) with 25(OH)D among women of African ancestry. Among controls, women of European ancestry exhibited a positive correlation between plasma 25(OH)D and L. crispatus abundance. CONCLUSION: Certain vaginal bacteria are associated with plasma 25(OH)D concentration.


Assuntos
Microbiota , Vagina/microbiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Feminino , Idade Gestacional , Humanos , Gravidez , Vaginose Bacteriana/etnologia , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitaminas/administração & dosagem
16.
Artigo em Inglês | MEDLINE | ID: mdl-30910889

RESUMO

Several emerging pathogens have arisen as a result of selection pressures exerted by modern health care. Klebsiella quasipneumoniae was recently defined as a new species, yet its prevalence, niche, and propensity to acquire antimicrobial resistance genes are not fully described. We have been tracking inter- and intraspecies transmission of the Klebsiella pneumoniae carbapenemase (KPC) gene, bla KPC, between bacteria isolated from a single institution. We applied a combination of Illumina and PacBio whole-genome sequencing to identify and compare K. quasipneumoniae from patients and the hospital environment over 10- and 5-year periods, respectively. There were 32 bla KPC-positive K. quasipneumoniae isolates, all of which were identified as K. pneumoniae in the clinical microbiology laboratory, from 8 patients and 11 sink drains, with evidence for seven separate bla KPC plasmid acquisitions. Analysis of a single subclade of K. quasipneumoniae subsp. quasipneumoniae (n = 23 isolates) from three patients and six rooms demonstrated seeding of a sink by a patient, subsequent persistence of the strain in the hospital environment, and then possible transmission to another patient. Longitudinal analysis of this strain demonstrated the acquisition of two unique bla KPC plasmids and then subsequent within-strain genetic rearrangement through transposition and homologous recombination. Our analysis highlights the apparent molecular propensity of K. quasipneumoniae to persist in the environment as well as acquire carbapenemase plasmids from other species and enabled an assessment of the genetic rearrangements which may facilitate horizontal transmission of carbapenemases.


Assuntos
Klebsiella/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Resistência a Múltiplos Medicamentos/genética , Hospitais , Humanos , Klebsiella/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo
17.
Cureus ; 11(1): e3846, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30891386

RESUMO

Platypnea-orthodeoxia syndrome (POS) has been defined as shortness of breath and hypoxemia in the upright position that improves with dorsal decubitus. This is a rare disorder caused by right-to-left shunts due to a persistent foramen ovale or pulmonary arteriovenous malformations. Hepatopulmonary syndrome can present with POS in the presence of pulmonary vasodilation and pulmonary arteriovenous communications in patients with liver disease. We report a case where the diagnosis of POS was made incidentally in a patient with cryptogenic liver cirrhosis. After other causes of hypoxemia were excluded, the diagnosis of right-to-left pulmonary shunt was confirmed by late opacification of the left heart chambers seen in a transthoracic echocardiogram. Interestingly, computerized tomography (CT) of the chest with contrast demonstrated a very prominent pulmonary vascular pattern extending to the periphery of the lungs. POS is a rare cause of hypoxemia that requires a high level of suspicion, and exclusion of more common causes of hypoxemia.

18.
BMJ Case Rep ; 20182018 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-30297489

RESUMO

A 57-year-old woman with a history of asthma, hypertension and substance abuse disorder was admitted to the medical intensive care unit with hypercapnic respiratory failure. After the history was obtained, patient admitted heroin use earlier that day. The initial physical examination revealed right eye ptosis, diplopia, fatigability of neck flexion and extension. She also presented with wheezing and a prolonged expiratory phase. Pupils were 4 mm, with sluggish response to light bilaterally. CT chest with contrast showed a large mediastinal mass. Three different processes coexisted in this patient: simultaneous occurrence of a myasthenia gravis crisis, asthma exacerbation and a component of heroin use. This case highlights a series of overlapping clinical features that could lead to potential confounding and misdiagnosis. Respiratory symptoms improved after initial treatment for asthma exacerbation, but ptosis, diplopia and fatigability of neck muscles persisted.


Assuntos
Asma/diagnóstico , Dependência de Heroína , Miastenia Gravis/diagnóstico , Síndrome do Desconforto Respiratório/diagnóstico , Asma/complicações , Blefaroptose/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Hipercapnia/etiologia , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Síndrome do Desconforto Respiratório/complicações
19.
BMC Med Genet ; 19(1): 181, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290772

RESUMO

BACKGROUND: Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth, a complication that is more common in African Americans. Attempts to identify genetic loci associated with preterm birth using genome-wide association studies (GWAS) have only been successful with large numbers of cases and controls, and there has yet to be a convincing genetic association to explain racial/ethnic disparities. Indeed, the search for ancestry-specific variants associated with preterm birth has led to the conclusion that spontaneous preterm birth could be the consequence of multiple rare variants. The hypothesis that preterm birth is due to rare genetic variants that would go undetected in standard GWAS has been explored in the present study. The detection and validation of these rare variants present challenges because of the low allele frequency. However, some success in the identification of fetal loci/genes associated with preterm birth using whole genome sequencing and whole exome sequencing (WES) has recently been reported. While encouraging, this is currently an expensive technology, and methods to leverage the sequencing data to quickly identify and cost-effectively validate variants are needed. METHODS: We developed a WES data analysis strategy based on neonatal genomic DNA from PPROM cases and term controls that was unencumbered by preselection of candidate genes, and capable of identifying variants in African Americans worthy of focused evaluation to establish statistically significant associations. RESULTS: We describe this approach and the identification of damaging nonsense variants of African ancestry in the DEFB1 and MBL2 genes that encode anti-microbial proteins that presumably defend the fetal membranes from infectious agents. Our approach also enabled us to rule out a likely contribution of a predicted damaging nonsense variant in the METTL7B gene. CONCLUSIONS: Our findings support the notion that multiple rare population-specific variants in the fetal genome contribute to preterm birth associated with PPROM.


Assuntos
Grupo com Ancestrais do Continente Africano , Códon sem Sentido , Ruptura Prematura de Membranas Fetais/genética , Predisposição Genética para Doença , Lectina de Ligação a Manose/genética , Nascimento Prematuro/genética , beta-Defensinas/genética , Adulto , Alelos , Proteínas de Transporte/genética , Estudos de Casos e Controles , Feminino , Ruptura Prematura de Membranas Fetais/etnologia , Ruptura Prematura de Membranas Fetais/patologia , Feto , Expressão Gênica , Frequência do Gene , Genoma Humano , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Polimorfismo de Nucleotídeo Único , Gravidez , Nascimento Prematuro/etnologia , Nascimento Prematuro/patologia , Sequenciamento Completo do Exoma
20.
BMC Genomics ; 19(1): 770, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355302

RESUMO

BACKGROUND: Trypanosoma conorhini and Trypanosoma rangeli, like Trypanosoma cruzi, are kinetoplastid protist parasites of mammals displaying divergent hosts, geographic ranges and lifestyles. Largely nonpathogenic T. rangeli and T. conorhini represent clades that are phylogenetically closely related to the T. cruzi and T. cruzi-like taxa and provide insights into the evolution of pathogenicity in those parasites. T. rangeli, like T. cruzi is endemic in many Latin American countries, whereas T. conorhini is tropicopolitan. T. rangeli and T. conorhini are exclusively extracellular, while T. cruzi has an intracellular stage in the mammalian host. RESULTS: Here we provide the first comprehensive sequence analysis of T. rangeli AM80 and T. conorhini 025E, and provide a comparison of their genomes to those of T. cruzi G and T. cruzi CL, respectively members of T. cruzi lineages TcI and TcVI. We report de novo assembled genome sequences of the low-virulent T. cruzi G, T. rangeli AM80, and T. conorhini 025E ranging from ~ 21-25 Mbp, with ~ 10,000 to 13,000 genes, and for the highly virulent and hybrid T. cruzi CL we present a ~ 65 Mbp in-house assembled haplotyped genome with ~ 12,500 genes per haplotype. Single copy orthologs of the two T. cruzi strains exhibited ~ 97% amino acid identity, and ~ 78% identity to proteins of T. rangeli or T. conorhini. Proteins of the latter two organisms exhibited ~ 84% identity. T. cruzi CL exhibited the highest heterozygosity. T. rangeli and T. conorhini displayed greater metabolic capabilities for utilization of complex carbohydrates, and contained fewer retrotransposons and multigene family copies, i.e. trans-sialidases, mucins, DGF-1, and MASP, compared to T. cruzi. CONCLUSIONS: Our analyses of the T. rangeli and T. conorhini genomes closely reflected their phylogenetic proximity to the T. cruzi clade, and were largely consistent with their divergent life cycles. Our results provide a greater context for understanding the life cycles, host range expansion, immunity evasion, and pathogenesis of these trypanosomatids.


Assuntos
Genoma de Protozoário , Genômica , Trypanosoma cruzi/genética , Trypanosoma rangeli/genética , Trypanosoma/genética , Biologia Computacional/métodos , Metabolismo Energético/genética , Genômica/métodos , Genótipo , Tipagem Molecular , Família Multigênica , Filogenia , Pseudogenes , Trypanosoma/classificação , Trypanosoma/metabolismo , Trypanosoma/patogenicidade , Trypanosoma cruzi/classificação , Trypanosoma cruzi/metabolismo , Trypanosoma cruzi/patogenicidade , Trypanosoma rangeli/classificação , Trypanosoma rangeli/metabolismo , Trypanosoma rangeli/patogenicidade , Virulência/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...