22689 research outputs found
Sort by
EXPLORING FACTORS ASSOCIATED WITH BEDAQUILINE ADHERENCE AMONG MDR TB AND HIV PATIENTS ENROLLED IN A CLUSTER-RANDOMIZED TRIAL OF NURSE CASE MANAGEMENT IN SOUTH AFRICA
Get PDFAbstract
Introduction
In South Africa, the dual epidemic of tuberculosis (TB) and HIV, compounded by drug-resistant TB strains, poses a significant public health challenge. Recent developments in treatment, particularly the introduction of bedaquiline, have offered hope in managing multidrug-resistant tuberculosis (MDR-TB). This study assesses how bedaquiline adherence impacts MDR-TB treatment outcomes, using adherence factors and nurse case management to enhance success for MDR-TB/HIV co-infected patients, advancing TB control nationally and globally.
Methods
This study was a secondary analysis of data from a cluster-randomized trial in South Africa to evaluate the effectiveness of intensive nurse case management on MDR-TB treatment outcomes. Including individuals aged 13 and above undergoing MDR-TB treatment, this analysis focused on those receiving bedaquiline as part of their regimen. This study sample was narrowed to HIV-positive participants who initiated bedaquiline, had an available 24-week HIV viral load result, and adhered to all-oral MDR-TB treatment guidelines. Statistical analyses used descriptive statistics and binary logistic regression to explore the relationship between various demographic and clinical variables and HIV viral suppression as a proxy for medication adherence.
Results
This study involved 99 people with MDR-TB and HIV co-infection. The median age was 35 years (interquartile range [IQR] = 29-43); 52% were female, and 74% achieved viral suppression by the 24-week follow-up. A substantial portion (66%) were unemployed, and 35.4% resided in townships. The majority (69%) had never smoked, 68% did not drink alcohol prior to their diagnosis and 46% of the participants had positive culture test at baseline. Multivariable adjustment revealed that employment (aOR 4.14, 95% CI: .14-14.97) and having no prior TB episode (aOR 3.88, 95% CI: 1.13-13.36) significantly increased the odds of viral suppression, suggesting better medication adherence among these groups.
Conclusion
This analysis highlights the crucial role of socioeconomic and clinical factors in influencing medication adherence in people with MDR-TB and HIV co-infection. Incorporating these factors into comprehensive care strategies could improve adherence and outcomes. Targeted interventions are needed to address the complex needs of patients with MDR-TB and HIV to enhance their treatment experience and quality of life
Developing a Filter Changeout Procedure for Paint Booth Maintenance
Get PDFFilter changeouts are a vital step in maintaining paint booths used to protect workers from inhalation of aerosolized paint particles. The rate at which filters become loaded with paint depends on paint booth design, paint specifications (e.g., density, specific gravity), and painting activity in each booth. In an aerospace facility, ventilation assessments were performed in four paint booths to determine filter changeout schedules. Pressure drop readings were plotted against volumetric flow rates to determine when airflow falls below 100 cfm/ft2 - per the recommendations made by American Conference of Governmental Industrial Hygienists (ACGIH) - and were fitted to a linear regression for each booth. One concern identified is minimal changes in air flow over time in three out of four of the booths. Therefore, it is recommended to reassess the current ventilation assessment methodology, including a review of ventilation plans for the appropriate booths. Findings indicate potential opportunities for improvement in the current filter change out procedure that can continue to keep workers safe – particularly regarding monitoring strategies and maintenance steps. Although this study poses potential issues that may arise while operating paint booths in the Paint Lab and suggests actions to address and prevent them, continued data collection and investigation are necessary next steps for developing a procedure for filter changeouts
Polymer-Based Pressure Transduction for the Implementation of Autonomous Self-Powered and Extended-Runtime Sensing Platforms
No full textEnergy and sensing are used by systems to do useful work. When access to energy is limited, the performance of the system is limited in its complexity, duration, or both when sensing capability is compromised, the capability and usefulness of the system is decreased. By focusing on improving and combining these aspects with respect to the application context, the efficacy of implemented tranducers can be improved. Furthermore, if a single transducer can be used for both energy harvesting and sensing, the operation modes can be multiplexed in time, increasing the run time of the system and decreasing the maintenance needed by the platform.
This work aims to increase the capability of energy harvesting, making it a viable solution in environments that are typically precluded from energy harvesting based solutions that are based on other technologies. To this end, an electret-based energy harvester with a freestanding electret and adjustable resonant frequency is implemented. This serves to increase the utilization of the electric field from the electret and realize the ability to interface with very low frequency (VLF) oscillatory/acoustic energy sources. The output voltage is in excess of 300 V, with an average output power of up to 15 μW, and frequencies as low as at least 1 Hz measured reliably.
Next, sensing fidelity is addressed via the development of two pressure transducers: a high-pressure composite-based sensor and an acoustic impedance-matched sensor (AIMS). The high-pressure composite-based sensor is developed using thermoplastic polyurethane (TPU) composite and multi-walled carbon nanotubes (MWCNTs) as a filler. Due to the nature of the transduction mechanism, filler uniformity (both in size and distribution) is especially important.
The sensor implemented is able to measure pressures up to at least 10 MPa with adjustable sensitivity and response profiles. AIMS increases signal fidelity by matching the acoustic impedance of the sensor to that of the source of the signal being measured. In this way, the energy transferred to the transduction layer is maximized, allowing the sensor to be both self-powered and able to be used as an energy harvester. This sensor also demonstrate superior ambient noise rejection by exploiting the very mechanism by which noise is most typically introduced.
Finally, the energy extraction from the EBEH and AIMS are optimized via the incorporation of a set of switches, which serve to isolate the transducer during periods of reduced power output. The actuation of the switches, mechanical or electrical, are matched to the excitation frequency of the transducer and demonstrates a significant increase in peak output power, from 12μW to 14 mW. The transducer is multiplexed between being used for sensing and energy harvesting by a custom sensing platform, demonstrating a proof-of-concept for extended-runtime and self-powered systems
DECREASED PDGF-BB IN FEMALE MICE IMPAIRS HIPPOCAMPAL VASCULATURE
No full textThe blood-brain barrier (BBB) is essential for brain health, regulating the ingress and egress of substances to maintain cerebral homeostasis. This study focuses on the role of the platelet-derived growth factor-BB (PDGF-BB) and its receptor PDGFRβ in BBB integrity, particularly under the stresses of aging in female. Dysfunctions in PDGF-BB signaling, as evidenced in various genetic mouse models, contribute to pericyte loss, microvascular issues, and BBB breakdown, which are crucial in the pathology of degenerative dementias like Alzheimer's disease. PDGF-BB dynamics is investigated in aged female mice, revealing that decreased levels correlate with Blood-Brain Barrier (BBB) permeability, marking PDGF-BB as a potential pro-aging factor. Notably, previous findings suggest that, beyond platelets, skeletal preosteoclasts significantly contribute to increased PDGF-BB levels during aging and metabolic stress. This discovery supports the hypothesis of a bone-to-brain axis influencing neurodegenerative processes through altered BBB permeability. Our research extends to examining sex-specific differences in BBB integrity, highlighting the impact of PDGF-BB levels in female mice, which provides insights into gender-dependent pathways in aging. The study underscores the necessity of considering bone-derived factors in aging research and suggests potential therapeutic targets for mitigating age-related neurological declines. This comprehensive analysis not only enhances our understanding of PDGF-BB in BBB function and aging but also opens new research avenues regarding the systemic influences on neurodegeneration, with implications for developing gender-specific treatments for age-related diseases
THE EDUCATIONAL ACHIEVEMENT GAP: A MULTIFACETED ANALYSIS
No full textThere is a significant achievement gap between affluent and impoverished students, and inequalities in educational practices in public schools have been widespread for decades. Teachers often have negative mindsets about their students from disadvantaged homes and do not believe they can succeed academically. Furthermore, many principals are not trained in graduate school for Title I leadership, and they do not know how to address the plethora of factors impacting impoverished students’ learning. This study aimed to examine the relationships between academic optimism, school climate, leadership preparedness, and academic progress to determine if organizational conditions impacted student achievement at eight schools in a large system in central Maryland. The results indicated a correlation between academic optimism, school climate, and student progress. Additionally, school leaders reported that their preparation programs were inadequate. The proposed solution to the learning disparity is a professional learning leadership coaching model that focuses on incorporating academic optimism and enabling school structures in Title I schools to help foster positive mindsets about students’ academic potential
Characterizing polygenic risk scores among a cohort of breast cancer cases and controls in the All of Us research program
Get PDFThe advancement of precision medicine and genome-wide association studies (GWAS) has led to researchers actively working to more comprehensively characterize genetic risk of disease. Polygenic risk scores (PRS, also known as polygenic scores (PGS)) have been developed to predict individual- and population-level genetic risk of disease. However, more work is needed to apply these PRS to diverse cohorts as the majority of them are developed with primarily European ancestry data. Our study aimed to assess the performance of PRS313 - a PRS developed for breast cancer - on a cohort of diverse individuals from the All of Us research program, particularly focusing on those with a family history of breast cancer (who have an estimated twofold increased risk of developing breast cancer in their lifetime). First, we identified 884 and 102,944 case and control cohorts respectively, and performed a random sampling of the controls to match the number of cases. Then, we scored each participant based on their genomic data and presented the findings stratified by race, ethnicity, and age group. The findings from our study showed the average PRS for the case
cohort is about two times higher than that of the control cohort. Specifically for Black participants, the average PRS is 3.45 times higher than that for White participants for cases, yet 2 times lower for controls - despite the fact that Black participants are more likely to present with aggressive stages of breast cancer than their White counterparts. This study sheds light on using PRS to understand risk of breast cancer for those with a family history of breast cancer. It also provides recommendations on how to integrate PRS with other classical models of breast cancer risk to provide participants with a holistic understanding of their health. Recommendations include adjusting PRS for race and ancestry, which has already been done by some researchers, as well as diversifying the cohorts used to build these PRS to provide better personalized medical assistance and care to more diverse populations
TOLEROGENIC MICROPARTICLES FOR ANTIGEN-SPECIFIC EXPANSION OF REGULATORY T CELLS FOR AUTOIMMUNITY AND TRANSPLANT REJECTION
No full textThe significant function of regulatory T cells (Tregs) in preserving and reestablishing immunological tolerance has generated attention in the treatment of several human diseases, including transplant rejection and type 1 diabetes. Present methods center on adoptive transfers of in vitro-produced batches of antigen-specific Tregs; nevertheless, their efficacy and usability as immunotherapy are limited by a number of safety and fabrication issues. Therefore, the development methods for the selective recruitment of suppressive Treg populations may have broad therapeutic applications. Drug delivery platforms based on polymeric particles offer surface functionalization, release kinetics, degradation, and customizable particle features. The goal of this thesis is to create and evaluate tolerogenic injectable, biodegradable microparticles, or Tol-MPs, as a safe means of treating autoimmune diseases and transplant rejection while also efficiently controlling immune cell responses.
Tolerogenic microparticles (Tol-MPs) have been designed to include surface proteins that enable selective engagement of diabeto-protective Tregs to promote their proliferation and protective activity. The three components include: 1) an MHC Class II tetramer loaded with chromogranin A, CgA, a known target in diabetes; 2) a novel IL-2/antibody fusion protein, an immunocytokine termed F5111 IC; and 3) an encapsulated immunosuppressant medication (rapamycin).
Transplantation presents an opportunity to significantly enhance an individual's quality of life and prolong their life expectancy. Although patient outcomes have improved due to advancements in transplant technology, the length of organ recipient waiting lists has increased recently. By increasing Treg potency and postponing allograft rejection, chimeric antigen receptor-Treg therapy is a major advancement in Treg therapy for transplantation. However, CAR-Tregs lose some of their tenacity two to three weeks after being infused into mice that are immunocompetent, and they are unable to regulate immunity to alloantigens or memory T cells. Combination therapies that use co-stimulation-blocking drugs or conventional immunosuppressive techniques to optimize the lifetime of CAR-Tregs are needed. At present, immunosuppressive regimens suppress Tregs by inhibiting IL-2, the critical cytokine for Treg survival. Here, we investigate the possibility of combining Tol-MPs with CAR-Tregs to enhance localized boosting and persistence. Since they can be administered locally, Tol-MPs have the potential to be a versatile clinical tool
COMPLEX DEFECT STRUCTURES IN CONFINED LIQUID CRYSTALS: EFFECTS OF PHASE TRANSITIONS AND CONFINEMENT
Get PDFIn my doctoral research, I studied the effect of geometry and confinement on liquid crystal phase transition. I explored this concept in different settings, and in particular I investigated liquid crystals confined in a capillary tube and in undulated microchannels and chiral liquid crystals (cholesteric) incorporated in a polymer network. I focused particularly on the phase transition between smectic-A and nematic (or cholesteric) liquid crystals. This delicate, second-order phase transition is often surprising because of the behaviors of the liquid crystal topological defects characteristic of each phase.
Through my investigations, I observed the emergence of novel structures at the transition between smectic-A and nematic when the liquid crystal is confined to a capillary tube. In particular, I have characterized a transient phenomenon, in which twisted defect lines appear in a nematic liquid crystal near the phase transition.
In addition, I investigated the effect of mixing low-molecular-weight liquid crystals with polymerizable mesogens, generating a liquid crystalline polymer network in the smectic phase and then heating it into a chiral nematic phase. I observed the disruption of the cholesteric texture as a function of the density of the polymer network and of the pitch of the twisted structure. The smectic polymer network can be modeled in this setting as a bulk alignment field.
Finally, I explored a combination of geometric confinement and polymerization in order to stabilize large defects in the smectic phase, which can be used as optical lenses. I observed that the polymerization of a thin smectic layer can lead to the stabilization of defects in a much thicker film, and proposed a simple technique to generate high-quality gradient-index lenses with smectic liquid crystals.
These studies offer insights that enhance our ability to control liquid crystals near the phase transition to access new defects and textures, thus improving our understanding of the phase transitions, with potential benefits for liquid crystal-based technologies
Optimization of lipid nanoparticle (LNP) formulation methods and evaluation of the product stability
Get PDFThe therapeutic use of messenger RNA (mRNA) has recently drawn increasing attention due to its safety, ease of modification, and fast manufacturing. However, mRNA molecules are fragile and vulnerable to degradation in vitro and in vivo, requiring a stable delivery platform to improve their efficacy. Lipid nanoparticles (LNPs) are one of the most popular non-viral mRNA delivery platforms and have been utilized in mRNA COVID-19 vaccines. LNPs are nanostructured carriers with multiple compartments, typically formulated by ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol (PEG)-conjugated lipids. A challenge in LNP research is the high cost of materials including lipids and mRNA. Microfluidic mixers are becoming increasingly common at the laboratory scale for producing more homogenous and reproducible LNPs, but the minimum volume of 1 mL for each batch leads to high costs and waste for small-scale optimization experiments. Here we characterized a formulation approach that utilized higher dilution to reduce material use and waste, followed by steps to concentrate the particles into smaller batches. We confirmed that the method is feasible and that the additional centrifugation to concentrate the particles for dosing does not affect LNP size and particle structure. Manual mixing has been used traditionally for LNP production but is disadvantaged by its low reproducibility and less controlled production. The project also optimized the manual LNP formulation protocol to produce stable small-scale LNP for research. We modified the protocol to a two-step mixing method and found that the aqueous volume in the first mixing step is critical to the product LNP size. This method allowed us to manually formulate stable LNPs with controlled size and low polydispersity. The stability of optimized LNPs formulated by the 2-step mixing process was confirmed by maintaining stable physicochemical characterization and protein expression in cell culture during 28 days of storage under -80 °C. However, it is noted that the same LNP lost its stability and luciferase expression when stored under -20 °C with cryoprotectant. The data presented in this thesis provide significant advances for formulating stable LNPs and minimize the cost of production for laboratory-scale settings
A Food Color Based Colorimetric Assay for Cryptococcus neoformans Laccase Activity
Get PDFCryptococcus neoformans is a fungal pathogen that is acquired by inhalation of spores, resulting in cryptococcosis mostly in immune compromised patients, such as those with HIV/AIDS. One survival mechanism of C. neoformans during infection is melanin production, which is catalyzed by laccase, and protects fungal cells against immune attack. Melanin functions as a virulence factor mainly by protecting fungal cells against the host immune system. Hence comparative assessment of laccase activity is useful for characterizing cryptococcal strains. After a serendipitous observation that culturing C. neoformans with food coloring resulted in the degradation of some dyes with phenolic structures, we associated this phenomenon with catalytic activity by C. neoformans laccase. Consequently, we investigated the color changes for the food dyes metabolized by C. neoformans laccase and explored whether this effect could be useful in the development of a colorimetric assay to measure enzyme activity and function. We developed several versions of a food dye based colorimetric laccase assay that can be used to determine whether a culture exhibits laccase activity and to compare the relative laccase activities between different C. neoformans strains. We found that phenolic color degradation was glucose dependent, which may reflect changes in the reduction properties of the media. Our food color based colorimetric assay has several advantages over the commonly used 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for laccase activity, including lower cost, no reversibility and easier application since it does not require constant monitoring. Our method has potential applications in environmental fields, for bioremediation of water, and this is an efficient test to determine laccase activity. Additionally, it could be useful for comparing laccase activity across different C. neoformans strains, determining whether laccase virulence factor expression is present