96 research outputs found
Research Article
Background. Elucidation of a pathogen's antimicrobial susceptibility requires subculture after the organism is first isolated. This takes several days, requiring patients to be treated with broad-spectrum antibiotics. This approach contributes to the development of bacterial resistance. Methods. Microtiter wells were coated with a polyclonal antibody targeting the pathogen of interest. Bacterial suspensions were added in the presence/absence of selected antibiotics. After washing, captured bacteria were detected. Findings. Group B streptococcus (GBS), Enterococcus faecalis, and Neisseria gonorrhoeae were each detected at 10 5 bacteria/mL following a 20-minute incubation period. Susceptibility to select antibiotics was discernable following a 6-hour incubation period (GBS and Enterococcus). Sensitivity was increased to 10 −2 bacteria/mL for GBS, 10 −1 bacteria/mL for E. faecalis, and 10 1 bacteria/mL for N. gonorrhoeae following 18-24-hour culture. Conclusion. This novel assay allows for the highly sensitive and specific identification of a pathogen and simultaneous determination of its antimicrobial susceptibility in a reduced time
Validação de Dados Anemométricos a Partir de Padrões Espaço-Temporais de Vento em Superfície
Diferentes fatores podem comprometer a confiabilidade de dados anemométricos medidos em campo, podendo alterar as medições, tornando-as incorretas. A disponibilização de dados de torres anemométricas requer que estes sejam submetidos a um rigoroso processo de controle de qualidade, cujo objetivo é identificar dados inconsistentes ou suspeitos. O desenvolvimento de um conjunto de critérios de validação destes dados é elemento crítico de sua avaliação. Neste estudo foi aplicado a técnica de análise fatorial em componentes principais (ACP) para avaliar padrões espaço-temporais do campo velocidade do vento em superfície sobre o norte do Nordeste brasileiro, cujo objetivo foi particularizar a variabilidade do regime de vento sobre a região, tornando os critérios de validação mais precisos durante a análise destes. Os resultados mostram que as maiores contribuições do regime eólico ocorrem sobre o litoral Cearense e Potiguar durante o semestre setembro-fevereiro, período menos chuvoso da região. A partir destes resultados foi possível regionalizar os valores fixados nos algoritmos de validação das séries de dados observados, uma vez que passou-se a conhecer seu comportamento sazonal e distribuição espacial
Inflammasome activation during spontaneous preterm labor with intraâ amniotic infection or sterile intraâ amniotic inflammation
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146295/1/aji13049.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146295/2/aji13049_am.pd
Supplementation to Support Immune Function to Clear Persistent Human Papillomavirus Infections
OBJECTIVE: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC
STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 months followed by 6 months of placebo (N = 25). Every 3 months, patients were evaluated with HPV DNA and HPV RNA testing as well as a blood sample collected to evaluate a panel of immune markers including interferon-alpha, interferon-beta (IFN-β), interferon-gamma (IFN-γ), IgG1, T lymphocytes, and natural killer (NK) cell levels. At the completion of the 12-month study period, patients on the placebo arm were given the option to continue on the study to receive AHCC supplementation unblinded for 6 months with the same follow-up appointments and testing as the intervention arm.
RESULTS: Fifty women with high-risk HPV were enrolled, and 41 completed the study. Fourteen (63.6%) of the 22 patients in the AHCC supplementation arm were HPV RNA/HPV DNA negative after 6 months, with 64.3% (9/14) achieving a durable response defined as being HPV RNA/HPV DNA negative 6 months off supplementation. On the placebo arm, two (10.5%) of 19 patients were HPV negative at 12 months. In the twelve placebo arm patients who elected to continue on the unblinded study, 50% (n = 6) were HPV RNA/HPV DNA negative after 6 months of AHCC supplementation. At the time of completion of the study, there were a total of 34 patients (22 blinded and 12 unblinded) who had received AHCC supplementation with an overall response rate of 58.8% that cleared HPV persistent infections. At the time of enrollment, the mean IFN-β level was 60.5 ± 37.6 pg/ml in women with confirmed persistent HPV infections. Suppression of IFN-β to less than 20 pg/ml correlated with an increase in T lymphocytes and IFN-γ and durable clearance of HPV infections in women who received AHCC supplementation.
CONCLUSION: Results from this phase II study demonstrated that AHCC 3 g once daily was effective to support the host immune system to eliminate persistent HPV infections and was well tolerated with no significant adverse side effects reported. The duration of AHCC supplementation required beyond the first negative result needs more evaluation to optimize success for durable outcomes. The suppression of the IFN-β level to less than 20 pg/ml correlated with clearance of HPV infections and merits further evaluation as a clinical tool for monitoring patients with HPV infections
Human βâ defensinâ 1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intraâ amniotic infection
ProblemHuman βâ defensins (HBDs) are antimicrobial peptides that participate in the soluble innate immune mechanisms against infection. Herein, we determined whether HBDâ 1 was present in amniotic fluid during normal pregnancy and whether its concentrations change with intraâ amniotic inflammation and/or infection.Method of StudyAmniotic fluid was collected from 219 women in the following groups: (a) midtrimester who delivered at term (n = 35); (b) term with (n = 33) or without (n = 17) labor; (c) preterm labor with intact membranes who delivered at term (n = 29) or who delivered preterm with (n = 19) and without (n = 29) intraâ amniotic inflammation and infection or with intraâ amniotic inflammation but without infection (n = 21); and (d) preterm prelabor rupture of membranes (pPROM) with (n = 19) and without (n = 17) intraâ amniotic inflammation/infection. Amniotic fluid HBDâ 1 concentrations were determined using a sensitive and specific ELISA kit.Results(a) HBDâ 1 was detectable in all amniotic fluid samples; (b) amniotic fluid concentrations of HBDâ 1 were changed with gestational age (midtrimester vs term no labor), being higher in midtrimester; (c) amniotic fluid concentrations of HBDâ 1 were similar between women with and without spontaneous labor at term; (d) among patients with spontaneous preterm labor, amniotic fluid concentrations of HBDâ 1 in women with intraâ amniotic inflammation/infection and in those with intraâ amniotic inflammation without infection were greater than in women without intraâ amniotic inflammation or infection who delivered preterm or at term; and (e) the presence of intraâ amniotic inflammation and infection in patients with pPROM did not change amniotic fluid concentrations of HBDâ 1.ConclusionHBDâ 1 is a physiological constituent of amniotic fluid that is increased in midtrimester during normal pregnancy and in the presence of culturable microorganisms in the amniotic cavity. These findings provide insight into the soluble host defense mechanisms against intraâ amniotic infection.Amniotic fluid concentrations of human beta defensinâ 1 (HBDâ 1) in women with spontaneous preterm labor and intact membranes. Red lines indicate medians with interquartile ranges.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146360/1/aji13031.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146360/2/aji13031_am.pd
The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/1/aji12827.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/2/aji12827_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142907/3/aji12827-sup-0001-FigS1.pd
From Bench to Bedside: Evaluation of AHCC Supplementation to Modulate the Host Immunity to Clear High-Risk Human Papillomavirus Infections
Objective: There is currently no effective medicine or supplement for clearance of high risk- human papillomavirus (HR-HPV) infections. We have taken a systematic approach evaluating the potential use of AHCC supplementation to support clearance of HR-HPV infections. The primary objective of this research was to evaluate AHCC supplementation to modulation of the host immune system to clear HR-HPV infections from bench to bedside.Methods: Cervical cancer cells, CaSki (HPV16+), HeLa(HPV18+), SiHa(HPV16/18+), and C-33A(HPV−), were treated in vitro with AHCC 0.42 mg/mL daily x7 days then observed x7 days with daily sample collection. A confirmatory study in cervical cancer mouse models, SiHa(HPV16/18+) and C-33A(HPV−), was conducted: mice were divided into three groups per cell line then dosed with AHCC 50 mg/kg/d (N = 10), or vehicle alone (N = 10), or no supplementation (N = 10) for a total of 90 days followed by 30 days of observation. Tumors were measured 3x/week and blood samples collected bi-weekly to evaluate interferon (IFN) alpha(α), beta(β), and gamma(γ) and immunoglobulin G(IgG) by immunoassays. Tumors were evaluated for HR-HPV expression by PCR. Two pilot studies of 10 patients each were conducted in women with confirmed persistent HR-HPV+ infections. The 1st study evaluated AHCC 3g from 5 weeks up to 6 months and 2nd study evaluated AHCC 1g < 8 months. HR-HPV DNA status and the immune panel were monitored at each visit.Results: HR-HPV clearance was observed in vitro and confirmed in the animal studies as a durable response. Four of six (66.7%) patients had confirmed HR-HPV clearance after 3–6 months of AHCC 3g. Similarly, 4 of 9 (44%) patients had confirmed HR-HPV clearance after 7 months of AHCC 1g. Suppression of IFNβ <25 pg/mL was observed in those clearing the HR-HPV infection.Conclusion: Pre-clinical in vitro and in vivo studies demonstrated durable clearance of HR-HPV infections. The preliminary data from the two pilot studies suggested that AHCC supplementation supports the host immune system for successful clearance of HR-HPV infections. A confirmatory phase II randomized, double-blinded, placebo-controlled study is ongoing
Novel Ancestry-Specific Primary Open-Angle Glaucoma Loci and Shared Biology With Vascular Mechanisms and Cell Proliferation
Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis
Quantum-centric Supercomputing for Materials Science: A Perspective on Challenges and Future Directions
Computational models are an essential tool for the design, characterization,
and discovery of novel materials. Hard computational tasks in materials science
stretch the limits of existing high-performance supercomputing centers,
consuming much of their simulation, analysis, and data resources. Quantum
computing, on the other hand, is an emerging technology with the potential to
accelerate many of the computational tasks needed for materials science. In
order to do that, the quantum technology must interact with conventional
high-performance computing in several ways: approximate results validation,
identification of hard problems, and synergies in quantum-centric
supercomputing. In this paper, we provide a perspective on how quantum-centric
supercomputing can help address critical computational problems in materials
science, the challenges to face in order to solve representative use cases, and
new suggested directions.Comment: 60 pages, 14 figures; comments welcom
Mapping child growth failure across low- and middle-income countries
Child growth failure (CGF), manifested as stunting, wasting, and underweight, is associated with high 5 mortality and increased risks of cognitive, physical, and metabolic impairments. Children in low- and middle-income countries (LMICs) face the highest levels of CGF globally. Here we illustrate national and subnational variation of under-5 CGF indicators across LMICs, providing 2000–2017 annual estimates mapped at a high spatial resolution and aggregated to policy-relevant administrative units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the World Health 10 Organization’s ambitious Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and rates of progress exist across regions, countries, and within countries; our maps identify areas where high prevalence persists even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where subnational disparities exist and the highest-need populations reside, these geospatial estimates can support policy-makers in planning locally 15 tailored interventions and efficient directing of resources to accelerate progress in reducing CGF and its health implications
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