Publications by authors named "Nicole E Brown"

Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes.

View Article and Find Full Text PDF
Article Synopsis
  • Ectopic pregnancies can lead to serious complications in the first trimester, and hospital protocols requiring specific β-hCG levels for diagnostic testing may cause delays in diagnosis and treatment.
  • A study reviewed 519 cases of ectopic pregnancies, finding that 22.9% showed rupture on ultrasound and 55.7% required surgical management, with a significant portion presenting with β-hCG levels below the usual threshold of 1,500 mIU/mL.
  • The relationship between ectopic pregnancy size and β-hCG levels was weak, indicating that reliance on β-hCG for diagnosis could overlook cases with lower hormone levels but serious complications.
View Article and Find Full Text PDF

The in vitro differentiation of pluripotent stem cells into human intestinal organoids (HIOs) has served as a powerful means for creating complex three-dimensional intestinal structures. Owing to their diverse cell populations, transplantation into an animal host is supported with this system and allows the temporal formation of fully laminated structures, including crypt-villus architecture and smooth muscle layers that resemble native human intestine. Although the endpoint of HIO engraftment has been well described, here we aim to elucidate the developmental stages of HIO engraftment and establish whether it parallels fetal human intestinal development.

View Article and Find Full Text PDF
Article Synopsis
  • A standardized method called possible poor treatment response (PPTR) was developed to assess efficacy endpoints in a trial comparing rifapentine-based regimens for treating pulmonary tuberculosis (TB).
  • The PPTR process involved defining specific triggers that required standardized evaluations, including gathering multiple sputum samples for microbiological testing.
  • In the study of 2,343 participants, 19.4% experienced PPTR events, predominantly microbiological, which helped differentiate outcomes and support unbiased assessments of treatment efficacy in TB trials.
View Article and Find Full Text PDF
Article Synopsis
  • * Researchers developed a method to incorporate human immune cells into HIOs by transplanting them into mice with a humanized immune system, enabling the study of immune interactions.
  • * The study found that human immune cells migrate to the HIOs and respond to microbial exposure, activating the immune response and providing a new model for researching intestinal diseases.
View Article and Find Full Text PDF

Background: Recently, several invasive meningococcal disease (IMD) outbreaks caused by Neisseria meningitidis have occurred among people experiencing homelessness (PEH). However, overall IMD risk among PEH is not well described. We compared incidence and characteristics of IMD among PEH and persons not known to be experiencing homelessness (non-PEH) in the United States.

View Article and Find Full Text PDF

Background: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.

View Article and Find Full Text PDF
Article Synopsis
  • - A study was conducted on nursing home residents who were infected with SARS-CoV-2 to analyze immune responses in both plasma and gingival crevicular fluid (GCF) during and after their infection.
  • - 14 residents participated, with antibody levels measured at multiple time points; results showed that most participants had robust immune responses, with key antibodies detected in both plasma and GCF.
  • - The findings suggest that GCF could be a noninvasive and effective way to monitor immune responses to SARS-CoV-2, especially in individuals who may have difficulty with blood draws.
View Article and Find Full Text PDF
Article Synopsis
  • A study aimed to estimate how many people in the US have SARS-CoV-2 antibodies due to past infection or vaccination, revealing that both factors significantly reduce the risk of getting COVID-19 again.
  • The research involved over 1.5 million blood samples collected from donors across all US states and territories between July 2020 and May 2021, providing a broad representation of the population.
  • The results indicated that seroprevalence estimates were notably higher than reported COVID-19 case rates, suggesting many more people may have been infected than documented.
View Article and Find Full Text PDF

A pneumococcal disease outbreak caused by Streptococcus pneumoniae serotype 12F occurred in a state prison in Alabama, USA. Among 1,276 inmates, 40 cases were identified (3 confirmed, 2 probable, 35 suspected). Close living quarters, substance use, and underlying conditions likely contributed to disease risk.

View Article and Find Full Text PDF

Background: Since the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease epidemiology has changed, and racial disparities have not been recently described.

Methods: Active population- and laboratory-based surveillance for H.

View Article and Find Full Text PDF

Introduction: With the growing use of online study management systems and rapid availability of data, timely data review and quality assessments are necessary to ensure proper clinical trial implementation. In this report we describe central monitoring used to ensure protocol compliance and accurate data reporting, implemented during a large phase 3 clinical trial.

Material And Methods: The Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) study A5349 (S31) is an international, multi-site, randomized, open-label, controlled, non-inferiority phase 3 clinical trial comparing two 4-month regimens to a standard 6 month regimen for treatment of drug-susceptible tuberculosis (TB) among adolescents and adults with a sample size of 2500 participants.

View Article and Find Full Text PDF

After returning from Europe to the United States, on March 1, 2020, a symptomatic teacher received positive test results for severe acute respiratory syndrome coronavirus 2. Of the 21 students exposed to the teacher in the classroom, serologic results suggested past infection for 2. Classroom contact may result in virus transmission.

View Article and Find Full Text PDF

Background: We previously described the development of human intestinal organoids from pluripotent stem cells, as well as their in vivo maturation when transplanted into the mouse kidney capsule. While sufficient for certain aspects of study, this model has limitations. Herein, we describe an alternative model of human intestinal organoids transplantation into the mouse mesentery.

View Article and Find Full Text PDF
Article Synopsis
  • Calmodulin (CaM) is an important intracellular calcium transducer that influences various cellular activities, including gap junction regulation by interacting with connexins.
  • This study presents the first direct evidence of CaM binding to connexin45 (Cx45) in live cells, showing that this interaction depends on calcium levels and can be inhibited by a specific CaM blocker.
  • Researchers identified a specific binding site on Cx45 and observed how the interaction changes the properties of CaM, enhancing its sensitivity to calcium in a unique way compared to other connexins.
View Article and Find Full Text PDF

Background: Bilateral tubal ectopic pregnancies are a rare subset of ectopic pregnancy that can pose a diagnostic dilemma for clinicians. There is no distinct clinical presentation for bilateral tubal ectopic pregnancies, although they are typically associated with assistive reproductive techniques. In addition, there is no single diagnostic feature to help clinicians delineate bilateral tubal ectopic pregnancies from other types of ectopic pregnancy prior to passing the discriminatory zone (such as heterotopic pregnancy or twin ectopic [two gestational sacs in one tube]).

View Article and Find Full Text PDF
Article Synopsis
  • Elfamycins are a lesser-known group of antibiotics that interrupt the translation process by affecting EF-Tu function, primarily used in labs to study these mechanisms rather than as effective medications.* -
  • Their poor pharmacokinetic properties and solubility have limited their utility as therapies, but the increasing problem of antibiotic resistance is prompting a reevaluation of their potential.* -
  • Research efforts include discovering new natural variants and improving existing compounds, with LFF571, a modified version of GE2270 A, successfully completing phase 2 clinical trials, indicating a promising future for elfamycins in antibiotic treatment.*
View Article and Find Full Text PDF
Article Synopsis
  • - The text discusses the potential of using human pluripotent stem cells (hPSCs) to create organs and study human development and diseases.
  • - It specifically focuses on human intestinal organoids (HIOs) as a way to explore small intestine development and related health issues.
  • - A method for transplanting HIOs into immunocompromised mice is outlined, emphasizing key steps for successful integration and the implications for bioengineering human small intestine.
View Article and Find Full Text PDF
Article Synopsis
  • * RGS14 recruits to the plasma membrane to interact with GPCRs and is involved in regulating G protein signaling, though its exact effects on G signaling are less understood compared to conventional RGS proteins like RGS4.
  • * Experimental comparisons showed that both RGS14 and RGS4 act as GTPase activating proteins (GAPs) to enhance G deactivation speed, but RGS14’s GPR motif operates independently
View Article and Find Full Text PDF
Article Synopsis
  • Bioluminescence resonance energy transfer (BRET) is a method used to study how proteins interact with each other by using specific light-emitting tags that show energy transfer when proteins are close together.
  • The protocol described involves using two known proteins, Gαi1 and RGS14, tagged with Renilla luciferase and yellow fluorescent protein, to measure BRET in HEK 293 cells.
  • The procedure includes calculating the ratio of acceptor to donor tags and understanding net BRET, highlighting how BRET can help explore protein interaction dynamics in live cells in real-time.
View Article and Find Full Text PDF
Article Synopsis
  • RGS14 has specific sites that bind to both active (GTP-bound) and inactive (GDP-bound) forms of Gα subunits, with distinct domains for each state.
  • Research showed that RGS14 can form a stable complex with inactive Gαi1-GDP and is recruited to the plasma membrane by activated Gαo-AlF4(-), indicating dynamic interactions in live cells.
  • The study demonstrates that RGS14 can engage both forms of Gα subunits at once, suggesting a role in integrating G protein signals to influence synaptic plasticity in neurons.
View Article and Find Full Text PDF
Article Synopsis
  • - RGS14 is a versatile protein that connects G protein and H-Ras signaling pathways, featuring a domain that helps regulate GTP hydrolysis and motifs that interact with inactive G proteins.
  • - The study reveals that RGS14 preferentially binds to activated H-Ras-GTP, enhancing its cellular function while being influenced by inactive Gα(i1)-GDP and GPCRs.
  • - Bioluminescence resonance energy transfer (BRET) experiments show strong interactions between RGS14 and H-Ras at the plasma membrane, indicating that inactive Gα(i1)-GDP increases this binding and helps form a signaling complex regulated by GPCRs.
View Article and Find Full Text PDF
Article Synopsis
  • Children with Pierre Robin sequence (PRS) often face serious feeding and breathing issues, and G-tubes are used to help provide nutrition.
  • A study of 37 kids with PRS who underwent G-tube insertion showed successful placements, with some minor complications and most kids gaining or maintaining weight over an average of 2 years.
  • G-tubes were found to be a safe and effective way to support children with PRS until they could start feeding by mouth.
View Article and Find Full Text PDF

Resistance to the anti-HER2 monoclonal antibody trastuzumab is a major problem in the treatment of HER2-overexpressing metastatic breast cancer. Growth differentiation factor 15 (GDF15), which is structurally similar to TGF beta, has been reported to stimulate phosphorylation of HER2. We tested the hypothesis that GDF15-mediated phosphorylation of HER2 reduces the sensitivity of HER2-overexpressing breast cancer cell lines to trastuzumab.

View Article and Find Full Text PDF