Medicine and Health Sciences Commons^™

Reliability Of Popliteal Artery Flow-Mediated Dilation In The Seated Position, Taskina Akhter

Rehabilitation Sciences Theses & Dissertations

Flow-mediated dilation (FMD) is a noninvasive measurement of endothelial function, which is a useful prognostic tool for cardiovascular disease risk. Despite its widespread use since 1992, the reproducibility of FMD varies widely between studies. This variability in reproducibility is especially significant in the case of the popliteal artery due to different methodological approaches. Studies perform popliteal FMD in various body positions, with the prone and seated positions most common. However, no studies have examined the reproducibility of both the seated and prone positions of the popliteal artery FMD. Therefore, the aim of this study is to examine the test-retest and …

Perturbation-Based Gait Training, Julia Bohlman, Ashwini Kulkarni

Undergraduate Research Symposium

Background:

Falls during walking are common in older adults and individuals with Parkinson’s disease (PD) [1]. These falls are often caused by trips [2]. Injuries caused by falls can be severe, in all age groups and populations. Given the potential severity of injuries resulting from falls, it is crucial to implement interventions aimed at preventing falls. Such interventions focus on anticipatory and/or reactive mechanisms. Perturbation-based gait training (PBT) addresses both mechanisms by intentionally destabilizing participants to induce a loss of stability, triggering a motor response to regain postural stability. PBT works on the principle of specificity. While earlier studies on …

Addressing Weight In Primary Care: Perspectives Of African American Young Adults With Serious Mental Illness, Sang Qin, Lindsay Sheehan, Janis Sayer, Kristin S. Williams, Julius Mercer, Ashley Scott, Tevin Anderson

Journal of Human Services Scholarship and Interprofessional Collaboration

Young adults with serious mental illness (SMI) experience disproportionate rates of physical illness. Morbidity and mortality are even worse for young African Americans with SMI, especially those who are overweight. Primary care physicians (PCPs) have an important role in addressing weight management. Current research explored these young patient’s perceptions of weight management and how PCPs can best address their weight concerns. Using community-based participatory research, we interviewed 25 African American aged 18-30 who were overweight and had a SMI. Results revealed 1) patient perceptions around weight and 2) patient preferences. Participants identified both positive and negative aspects of being overweight, …

Acculturation And Immigrant Parental Perceptions Concerning Sexual Communication, Kwame Owura Frimpong

Journal of Human Services Scholarship and Interprofessional Collaboration

Abstract:

Acculturation presents challenges to many immigrant parents that are adjusting to new lives in the United States. The rationale for conducting this study stemmed from the effects that acculturation can have on the wellbeing of immigrants, adversely affecting their health outcomes. The purpose of this study was to explore the perceptions of Sub-Saharan African immigrant parents concerning having a conversation with their pre-adolescent children about sexuality and sexual practices. Findings revealed communication barriers due to cultural beliefs, cultural taboos, and shame. The findings from this study are beneficial to behavioral healthcare providers that work with immigrant families, parents, and …

Machine Learning As A Tool For Early Detection: A Focus On Late-Stage Colorectal Cancer Across Socioeconomic Spectrums, Hadiza Galadima, Rexford Anson-Dwamena, Ashley Johnson, Ghalib Bello, Georges Adunlin, James Blando

Community & Environmental Health Faculty Publications

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, …

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …

Nanosecond Pulsed Electric Fields Increase Antibiotic Susceptibility In Methicillin-Resistant Staphylococcus Aureus, Alexandra E. Chittams-Miles, Areej Malik, Erin B. Purcell, Claudia Muratori

Bioelectrics Publications

Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this …

Identifying Patterns For Neurological Disabilities By Integrating Discrete Wavelet Transform And Visualization, Soo Yeon Ji, Sampath Jayarathna, Anne M. Perrotti, Katrina Kardiasmenos, Dong Hyun Jeong

Computer Science Faculty Publications

Neurological disabilities cause diverse health and mental challenges, impacting quality of life and imposing financial burdens on both the individuals diagnosed with these conditions and their caregivers. Abnormal brain activity, stemming from malfunctions in the human nervous system, characterizes neurological disorders. Therefore, the early identification of these abnormalities is crucial for devising suitable treatments and interventions aimed at promoting and sustaining quality of life. Electroencephalogram (EEG), a non-invasive method for monitoring brain activity, is frequently employed to detect abnormal brain activity in neurological and mental disorders. This study introduces an approach that extends the understanding and identification of neurological disabilities …

An Ewas Of Dementia Biomarkers And Their Associations With Age, African Ancestry, And Ptsd, Mark W. Miller, Erika J. Wolf, Xiang Zhao, Mark W. Logue, Sage E. Hawn

Psychology Faculty Publications

Background

Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Methods

Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which …

Infusing Machine Learning And Computational Linguistics Into Clinical Notes, Funke V. Alabi, Onyeka Omose, Omotomilola Jegede

Mathematics & Statistics Faculty Publications

Entering free-form text notes into Electronic Health Records (EHR) systems takes a lot of time from clinicians. A large portion of this paper work is viewed as a burden, which cuts into the amount of time doctors spend with patients and increases the risk of burnout. We will see how machine learning and computational linguistics can be infused in the processing of taking clinical notes. We are presenting a new language modeling task that predicts the content of notes conditioned on historical data from a patient's medical record, such as patient demographics, lab results, medications, and previous notes, with the …

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

Plasma Protein Signatures Of Adult Asthma, Gordon J. Smilnak, Yura Lee, Abhijnan Chattopadhyay, Annah B. Wyss, Julie D. White, Sinjini Sikdar, Jianping Jin, Andrew J. Grant, Alison A. Motsinger-Reif, Jian-Liang Li, Mikyeong Lee, Bing Yu, Stephanie J. London

Mathematics & Statistics Faculty Publications

Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.

Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with …

Tailored Micromagnet Sorting Gate For Simultaneous Multiple Cell Screening In Portable Magnetophoretic Cell-On-Chip Platforms, Jonghwan Yoon, Yumin Kang, Hyeonseol Kim, Abbas Ali, Keonmok Kim, Sri Ramulu Torati, Mi-Young Im, Changyeop Jeon, Byeonghwa Lim, Cheolgi Kim

Bioelectronics Publications

Conventional magnetophoresis techniques for manipulating biocarriers and cells predominantly rely on large-scale electromagnetic systems, which is a major obstacle to the development of portable and miniaturized cell-on-chip platforms. Herein, a novel magnetic engineering approach by tailoring a nanoscale notch on a disk micromagnet using two-step optical and thermal lithography is developed. Versatile manipulations are demonstrated, such as separation and trapping, of carriers and cells by mediating changes in the magnetic domain structure and discontinuous movement of magnetic energy wells around the circumferential edge of the micromagnet caused by a locally fabricated nano-notch in a low magnetic field system. The motion …

Recent Progress In Microrna Detection Using Integrated Electric Fields And Optical Detection Methods, Logeeshan Velmanickam, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Low-cost, highly-sensitivity, and minimally invasive tests for the detection and monitoring of life-threatening diseases and disorders can reduce the worldwide disease burden. Despite a number of interdisciplinary research efforts, there are still challenges remaining to be addressed, so clinically significant amounts of relevant biomarkers in body fluids can be detected with low assay cost, high sensitivity, and speed at point-of-care settings. Although the conventional proteomic technologies have shown promise, their ability to detect all levels of disease progression from early to advanced stages is limited to a limited number of diseases. One potential avenue for early diagnosis is microRNA (miRNA). …

Cigarette Smoking Behaviors And Nicotine Dependence At The Intersection Of Sexual Identity And Sex In The United States: Findings From The National Survey On Drug Use And Health, Ollie Ganz, Jonathan A. Schulz, Sarah J. Ehlke, Jessica L. King Jensen, Andrea C. Villanti

Psychology Faculty Publications

Introduction: Cigarette smoking is disproportionately high among lesbian, gay, and bisexual (LGB) adults. Yet, collapsing these identities into a monolith can disguise important within group disparities (e.g., lesbian/gay versus bisexual female). The purpose of this study is to report recent national prevalence estimates and trends of cigarette smoking behaviors and nicotine dependence by sexual identity and sex. Methods: Data were from the 2015–2019 National Survey on Drug Use and Health (n = 210,392; adults 18+), a nationally representative, repeated cross-sectional study of substance use and mental health in the U.S. We examined bivariate and multivariable associations between sexual identity and …

Navigating New Normals: Student Perceptions, Experiences, And Mental Health Service Utilization In Post-Pandemic Academia, Hadiza Galadima, Anne Dumadag, Cara Tonn

Community & Environmental Health Faculty Publications

This study explores the profound impacts of the COVID-19 pandemic on higher education, focusing on shifts in learning experiences and students’ intentions to utilize mental health services post-pandemic. Utilizing Andersen’s Behavioral Model of Health Services Use, this study assesses perceptions from a stratified random sample of college students on post-pandemic learning experiences and mental health service utilization intentions. Findings reveal a positive reception to university initiatives and a preference for ongoing virtual classes. There is an evident increase in, and varying intentions for, using mental health services, shaped by demographics, employment, and prior service utilization. Younger and female students showed …

Hsp70 Is A Critical Regulator Of Hsp90 Inhibitor's Effectiveness In Preventing Hcl-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Betsy Gregory, Michael Osei-Nkansah, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Exposure to hydrochloric acid (HCl) can provoke acute and chronic lung injury. Because of its extensive production for industrial use, frequent accidental exposures occur, making HCl one of the top five chemicals causing inhalation injuries. There are no Food and Drug Administration (FDA)-approved treatments for HCl exposure. Heat shock protein 90 (HSP90) inhibitors modulate transforming growth factor-β (TGF-β) signaling and the development of chemical-induced pulmonary fibrosis. However, little is known on the role of Heat Shock Protein 70 (HSP70) during injury and treatment with HSP90 inhibitors. We hypothesized that administration of geranylgeranyl-acetone (GGA), an HSP70 inducer, or gefitinib (GFT), an …

Influences Of Athletic Trainers' Return-To-Activity Assessments For Patients With An Ankle Sprain, Ryan S. Mccann, Cailee E. Welch Bacon, Ashley M. B. Suttmiller, Phillip A. Gribble, Julie M. Cavallario

Rehabilitation Sciences Faculty Publications

Context: Athletic trainers (ATs) inconsistently apply rehabilitation-oriented assessments (ROASTs) when deciding return-to-activity readiness for patients with an ankle sprain. Facilitators and barriers that are most influential to ATs' assessment selection remain unknown.

Objective: To examine facilitators of and barriers to ATs' selection of outcome assessments when determining return-to-activity readiness for patients with an ankle sprain.

Design: Cross-sectional study.

Setting: Online survey.

Patients or other participants: We sent an online survey to 10 000 clinically practicing ATs. The survey was accessed by 676 individuals, of whom 574 submitted responses (85% completion rate), and 541 respondents met the inclusion criteria.

Main outcome …

The Association Of Skin Cancer Prevention Knowledge, Sun-Protective Attitudes, And Sun-Protective Behaviors In A Navy Population, Rachel Newnam, Uyen Le-Jenkins, Carolyn Rutledge, Craig Cunningham

Nursing Faculty Publications

Introduction: U.S. Navy service members are primarily between the ages of 18 and 30 years and often required to be outside for extended periods of time in geographical locations with increased and often unfamiliar ultraviolet indexes that collectively increase their risk for skin cancer. Skin cancer is the country's most common form of cancer, yet there is a paucity of skin cancer prevention literature, especially within the U.S. Navy. The purpose of this study was to describe skin cancer risk and skin cancer prevention "cues-to-action" and to determine if skin cancer prevention knowledge was associated with sun-protective attitudes (e.g., prevention …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

The Importance Of Family Oral Health Education In Promoting Children's Oral Health, Denise C. Mckinney, Melissa Sullivan

Dental Hygiene Faculty Publications

No abstract provided.

Assessments Used By Athletic Trainers To Decide Return-To-Activity Readiness In Patients With An Ankle Sprain, Ryan S. Mccann, Cailee E. Welch Bacon, Ashley M. B. Suttmiller, Phillip A. Gribble, Julie M. Cavallario

Rehabilitation Sciences Faculty Publications

Context: Athletic trainers (ATs) often care for patients with ankle sprains. Expert consensus has been established for rehabilitation-oriented assessments (ROASTs) that should be included in ankle-sprain evaluations. However, the methods ATs use to determine return-to-activity readiness after an ankle sprain are unknown.

Objectives: To identify ATs' methods for determining patients' return-to-activity readiness after an ankle sprain and demographic characteristics of the ATs and their methods.

Setting: Online survey.

Design: Cross-sectional study.

Patients or Other Participants: We recruited 10 000 clinically practicing ATs. A total of 676 accessed the survey, 574 submitted responses (85% completion rate), and 541 respondents met the …

Assessment Of Simultaneous Alcohol And Cannabis Use And Its Related Consequences And Cognitions In College Students: A Narrative Review, Jennifer L. Shipley, Abby L. Braitman

Psychology Faculty Publications

As rates of students using cannabis continue to rise, simultaneous use of alcohol and cannabis (such that their effects overlap; commonly referred to as simultaneous alcohol and marijuana [SAM] use) is prevalent among college students who use both substances. Although research focusing on SAM use and related cognitions and consequences continues to grow, there are no common established measures, as approaches vary across studies. This narrative review identifies current methods for assessing SAM use and measures of SAM-related consequences and cognitions (motives and expectancies) among college students, evaluates how they were developed, identifies gaps in the literature, and provides recommendations …

Quantification Of Antiviral Drug Tenofovir (Tfv) By Surface-Enhanced Raman Spectroscopy (Sers) Using Cumulative Distribution Functions (Cdfs), Marguerite R. Butler, Jana Hrncirova, Meredith Clark, Sucharita Dutta, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive spectroscopic technique that generates signal-enhanced fingerprint vibrational spectra of small molecules. However, without rigorous control of SERS substrate active sites, geometry, surface area, or surface functionality, SERS is notoriously irreproducible, complicating the consistent quantitative analysis of small molecules. While evaporatively prepared samples yield significant SERS enhancement resulting in lower detection limits, the distribution of these enhancements along the SERS surface is inherently stochastic. Acquiring spatially resolved SERS spectra of these dried surfaces, we have shown that this enhancement is governed by a power law as a function of analyte concentration. Consequently, by definition, …

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Charting And Checking For Suicidality In A Family Medicine Residency Clinic, Bridget Murphy, Stacy Ogbeide

Journal of Human Services Scholarship and Interprofessional Collaboration

Suicide is a leading cause of death in the United States, and many individuals who die by suicide are likely to have seen a primary care physician (PCP) within the month of their death. Thus, the goal of this quality improvement (QI) project was to examine suicidality documentation practices of interprofessional clinicians within a Family Medicine residency clinic, thus providing rationale for continued research and a template for other clinics to emulate. The QI project used the Plan-Do-Study-Act cycle to survey 28 Family Medicine residents, faculty, and trainees for the Plan stage of the cycle in 2022 and assessed their …

Crisis Narratives In Crisis? A Comparative Investigation Into National Covid-19 Narratives, Mouse D. Bennett

Graduate Program in International Studies Theses & Dissertations

On January 31, 2020, the World Health Organization (WHO) declared a public health emergency for only the sixth time in its history. On March 11, 2020, it was stated that COVID-19 constituted a pandemic. How did countries respond? This dissertation traces the evolution of national crisis narratives in four states and assesses their relative success. The findings of this study are that pandemic crisis narratives are not generalizable to all crisis situations but require a high level of compliance to be effective in stopping the crisis. There is no formula for government success, there are no decisive variables determining outcomes. …

Nightmares And Self-Injury Among High-Risk Adolescents: Examining The Role Of Emotion Regulation, Kinjal K. Patel

Psychology Theses & Dissertations

Self-injurious thoughts and behaviors (SITBs) are a public health concern among youth. SITB rates rise drastically during adolescence -- a critical and sensitive developmental period characterized by dramatic changes in biological and social systems. Prior research has identified distal risk factors which tell us who is at risk for SITBs. Emerging research suggests proximal risk factors may be useful to identify when an individual may be at risk for SITBs. One promising proximal risk factor for SITBs is sleep problems. Although the relation between sleep problems and SITBs has been widely documented, little is known about the short-term, proximal links …

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …