Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Therapeutics

Theses/Dissertations

2023

Institution
Keyword
Publication

Articles 1 - 27 of 27

Full-Text Articles in Medicine and Health Sciences

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian Dec 2023

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Biomedical Engineering: Graduate Reports and Projects

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …


Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist Nov 2023

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …


Evidenced-Based Practice Competency Assessment For Competency-Based Orientation Protocol To Improve Competency Level Among Medical-Surgical Nurses, Maryann Ornelas Aug 2023

Evidenced-Based Practice Competency Assessment For Competency-Based Orientation Protocol To Improve Competency Level Among Medical-Surgical Nurses, Maryann Ornelas

Student Scholarly Projects

Practice Problem: Within a 12-month period, high incidences of severe post-spinal surgical complications resulted in a host of concerns in this clinical site when patients either returned to the operating room for spine revision or increased the length of stay.

PICOT: The PICOT question that guided this project was: "In Medical Surgical (Med-Surg) nurses (P), how would a Competency-Based Orientation (CBO) protocol with the inclusions of four critical elements of postoperative spinal care [POSC] (I) compared to the usual postoperative practice (C) enhance competency level in Med-Surg nurses when delivering postoperative practice at an inpatient setting (O) over 10 weeks …


The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas Jul 2023

The Combined Effects Of Physical Exercise And Cognitive Training On Gait Speed And Primary Motor Cortex Metabolism In Individuals With Mild Cognitive Impairment: A 1h-Mrs Analysis, Jack Thomas Emsey Elkas

Electronic Thesis and Dissertation Repository

Mild cognitive impairment (MCI) is a transitional stage before dementia. Altered gait in MCI has been associated with progression to dementia. Using magnetic resonance spectroscopy, a relationship between primary motor cortex (M1) neurochemistry and dual task gait speed has been reported in MCI. Interventional research suggests exercise, cognitive training, and vitamin D supplementation may benefit MCI, yet the combined effect of these treatments on gait speed and M1 metabolism is unknown. Participants with MCI (N=75) were assigned to one of five intervention arms and dual task cost on gait speed and M1 metabolism was assessed before and five months after …


The Meaning Of A Choice, Julie-Louise Zeitoun Jun 2023

The Meaning Of A Choice, Julie-Louise Zeitoun

Masters Theses

If you are disabled or disadvantaged, you will be dismissed and stifled. Few people will actively care for your struggles. As a person with autism, I was deeply fearful of the persecution I had faced throughout my life; it was a fear that followed me with terrifying determination. I desperately wanted to blend into society. So I designed myself to be devoid of any weakness, and productivity was the way I chose to conceal any difficulties I faced. It was a way to measure my success — a way to measure my normalcy.

Standard medical textiles are generic, cumbersome devices. …


Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams Jun 2023

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …


Retinoids And Their Clinical Benefits To Treating Cutaneous T-Cell Lymphoma, Baker Kendrick May 2023

Retinoids And Their Clinical Benefits To Treating Cutaneous T-Cell Lymphoma, Baker Kendrick

Honors Theses

Cutaneous T-Cell Lymphoma (CTCL) is a deadly form on non-Hodgkin lymphoma that primarily affects the skin. Non-Hodgkin lymphoma means that the lymphoma does not have the presence of Reed-Sternberg lymphocytes. A lymphoma, also known as lymphatic cancer, affects the lymphoid tissues, which plays a major role in the immune system. Lymphoid organs include the lymph nodes, thymus, spleen, and bone marrow. Lymphatic fluid, also known as lymph, travels through the bloodstream to transport lymphocytes, a type of white blood cell, to and from lymphatic organs. Due to a high concentration of lymphocytes in the skin, lymphoma primarily affects cutaneous areas. …


Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong May 2023

Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong

Dissertations & Theses (Open Access)

Three of the major problems facing cancer therapeutics are 1) drug resistance, the intrinsic or acquired ability of cancer cells to evade the effect of the therapies used to treat them; 2) heterogeneity among individual patients’ disease at the molecular level and the resulting variability in therapeutic response; and 3) the limitations of genomics biomarkers in matching patients to the most effective therapy. One possible solution to drug resistance is the use of combination therapies rather than monotherapies. Use of multiple drugs, each with a different mechanism of action, lowers the chances that the cancer cells will develop or have …


Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar May 2023

Pkpd-Model Based Preclinical Characterization Of The Activity Of Spectinamide 1599 Against Mycobacterial Subpopulations. And The Identification Of Potential Partners For Combination Therapy, Zaid Hanif Temrikar

Theses and Dissertations (ETD)

Tuberculosis is one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent prior to COVID19. Mycobacterium tuberculosis (Mtb) is the causative agent of TB. The interaction between Mtb and the immune system leads to development of diverse environmental niches and physiology within the lung of the TB patients. Mtb is thought to adapt and thrive in such an environment by transforming to different phenotypic variants. Such variants are difficult to kill and are thought to prolong TB pharmacotherapy. Spectinamide 1599 is a synthetic modification of spectinomycin that has demonstrated excellent …


Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage Apr 2023

Mechanism-Driven Approaches And Novel Constructs For High Purity Rna Synthesis, Kithmie Malagodapathiranage

Doctoral Dissertations

RNA is poised to revolutionize medicine. By simply changing the sequence, one therapeutic can be converted into a wholly new one, with little or no change in manufacturing and formulation. While a single mRNA vaccine produced at massive scale can treat billions, the re-codability of RNA will also enable the widespread growth of personalized medicines. T7 RNA polymerase is highly efficient at the synthesis of therapeutic RNA, but is known to produce unintended RNA impurities during synthesis. These products arise from the encoded RNA rebinding the enzyme such that its 3’ end serves as a primer for extension. This leads …


The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton Apr 2023

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …


Accuracy Of Therapeutic Drug Monitoring In Vancomycin And The Pharmacist Role: A Retrospective Case-Series, Kateryna Parkhomenko Apr 2023

Accuracy Of Therapeutic Drug Monitoring In Vancomycin And The Pharmacist Role: A Retrospective Case-Series, Kateryna Parkhomenko

Senior Theses

Vancomycin is a mainstay of therapy for treating virulent and resistant infections, especially methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin requires therapeutic drug monitoring (TDM) for optimal dosing and treatment. This requires pharmacists to calculate a dosing regimen that correlates to appropriate goal vancomycin concentrations in the blood. Dosing vancomycin can be difficult, as it varies on a patient’s weight, renal function, age, etc. Doses may have to be adjusted in response to out-of-range concentrations, which requires further pharmacy calculations. Inaccurate dosing poses a risk to patient safety and places a resource and time burden on pharmacists. If vancomycin dosing methods …


Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley Apr 2023

Investigation Of Clinically Relevant Fluconazole Resistance Mechanisms In The Fungal Pathogen Candida Parapsilosis, Laura Anne Doorley

Theses and Dissertations (ETD)

Invasive candidiasis is a severe fungal infection associated with significant morbidity and mortality, particularly among the critically ill and immunocompromised. Candida parapsilosis is the most common non-albicans species causing invasive Candida infections in pediatric and neonatal populations worldwide and is particularly common in the countries of South America, Western Asia, Mediterranean Europe, and Southern Africa. For many of these countries, fluconazole and other triazoles are the first line antifungal agents used for effective treatment of invasive Candida infection. Until recently, rates of fluconazole resistance among C. parapsilosis isolates were relatively low, therefore the determination of clinically relevant resistance mechanisms in …


Moral Injury To Inform Analysis Of Post-Traumatic Stress Disorder, Amanda Julia Manea Apr 2023

Moral Injury To Inform Analysis Of Post-Traumatic Stress Disorder, Amanda Julia Manea

Senior Theses

Post-traumatic stress disorder (PTSD) is a mental health condition that almost one out of ten veterans struggle with. Although the National Center for PTSD has made extensive progress in characterizing and developing new treatments for PTSD, most veterans still experience symptoms of PTSD following treatment. Novel avenues of investigation, such as developing algorithms to review electronic health record (EHR) data and better understanding moral injury, are being pursued to address the gap that still exists when it comes to treating veterans. Moral injury is the individual evaluation of exposure to a potentially morally injurious event (PMIE) and can lead to …


A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang Apr 2023

A Design, Development, And Evaluation Of Bio-Patch For Myocardial Tissue Repair, Yaya Zhang

Theses and Dissertations (ETD)

Introduction. Ischemic heart disease (IHD) is a major concern of human health issue. The structural repair and functional recovery of injured hearts is a major challenge in the clinical setting. Preclinical studies over last 10 years have demonstrated the potential of using stem cells to treat IHD, but the efficacy of this therapy is jeopardized by uncontrollable migration and low survival of the injected stem cells. An approach based on tissue engineering enabling target-specific stem cell delivery such as cardiac patches has emerged as an alternative solution for stem cell therapy for IHD. It employs scaffold materials to engulf various …


Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage Feb 2023

Synthesis And Biomedical Applications Of Hollow Iron Oxide Nanoparticles, Aloka S. Paragoda Arachchilage

Dissertations, Theses, and Capstone Projects

Nano-scale materials have gained much attention during the past few decades due to the stark differences in their properties compared to bulk material. Thus, they are being studied for a myriad of applications ranging from harnessing solar energy to diagnostics. This thesis focuses on the synthesis of hollow iron oxide nanoparticles using Galvanic replacement reactions and their application in drug delivery. Moreover, the use of a peptide precursor for the enhancement of exosomes is also discussed.

Chapter 1 discusses a simple and economical Galvanic approach used for the synthesis of hollow one-dimensional iron oxide nanotubes. In the initial reaction, the …


Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson Feb 2023

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …


Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi Feb 2023

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …


Mesenchymal Stem Cell Use In The Treatment Of Osteoarthritis: A Literature Review, Samantha Arrizon, Nolan Barnes, Teresa Del Toro, Lei Wena Herme, Vanessa Mendoza, Thi Tran, Reeta Zamro Jan 2023

Mesenchymal Stem Cell Use In The Treatment Of Osteoarthritis: A Literature Review, Samantha Arrizon, Nolan Barnes, Teresa Del Toro, Lei Wena Herme, Vanessa Mendoza, Thi Tran, Reeta Zamro

Physician Assistant Studies | Literature Reviews

Mesenchymal stem cell (MSC) therapies have been growing in popularity in research due to their anti-inflammatory, immunomodulatory, and regenerative properties. Many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat osteoarthritis, also known as “wear and tear” arthritis. As the average life expectancy increases, with age people are more prone to developing this disease, therefore, increasing its prevalence. This condition is progressive and will lead to functional decline, decreased quality of life, and increased medical costs. Our focus is to discuss the efficacy of mesenchymal stem cell injections in alleviating pain, improving functionality, and slowing …


Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren Jan 2023

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …


Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam Jan 2023

Combining Novel Direction Modulated Brachytherapy Tandem-And-Ovoids Applicators For Treatment Planning Of Multi-Institutional Cervical Cancer Cases: Removing Needles In Intracavitary-Interstitial Techniques, Sharmin Alam

Theses and Dissertations

Lack of standard guidelines for optimal needle insertion during high-dose-rate (HDR) intracavitary-interstitial (IC-IS) brachytherapy of the cervix means a sophisticated and technical skillset of inserting needles next to IC applicators must be developed to enhance plan quality. This study sought to evaluate the performance of two separate direction modulated brachytherapy (DMBT) tandem applicators used in conjunction with one set of novel DMBT ovoids, to effectively obviate the need for IS needles.

A cohort of 32 retrospective clinical HDR brachytherapy plans was re-planned with Varian’s BrachyVision® treatment planning system, using VEGO® inverse optimization algorithm, with dose heterogeneity accounted for …


Deciphering The Salivary Microbiome In Crohn’S Disease Patients With Different Factors Contributing To Dysbiosis, Hala Elzayat Jan 2023

Deciphering The Salivary Microbiome In Crohn’S Disease Patients With Different Factors Contributing To Dysbiosis, Hala Elzayat

Theses

Crohn’s Disease (CD) is a chronic Inflammatory Bowel Disease (IBD), common in the UAE. Microbiota is necessary to maintain a balanced gut environment which is essential for good health. Dysbiosis can predispose to many diseases including CD. The oral cavity has the second largest and most diverse microbiota after the gut harboring over 700 species of bacteria. This study aims to investigate the alterations in the salivary microbiome in patients with CD compared to Healthy controls (HC). It also aims to compare CD patients for salivary microbiome complexity and diversity according to different factors that can contribute to dysbiosis, including …


Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey Jan 2023

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (90Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …


Investigating The Physiological Use Of An Organ-On-A-Chip Device Through The Design And Fabrication Of A Micro-Electrical Blood-Brain Barrier (Μe-Bbb) System, Amrita Srinivasan, Kiana Aran, Jonalyn Herce, Noor Chaudhry, Allexa Ortiz Jan 2023

Investigating The Physiological Use Of An Organ-On-A-Chip Device Through The Design And Fabrication Of A Micro-Electrical Blood-Brain Barrier (Μe-Bbb) System, Amrita Srinivasan, Kiana Aran, Jonalyn Herce, Noor Chaudhry, Allexa Ortiz

CMC Senior Theses

Aging is considered the main risk factor for various neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Aging is associated with an increase in neuroinflammation, which is a significant contributor to cognitive impairment observed in these age-related neurodegenerative diseases. However, studying brain behavior remains a challenge due to the complex nature of isolating brain tissue from an organism. Modeling the brain allows for further study of these neurodegenerative diseases. Organ-on-a- chip (OoC), a system containing engineered or natural tissues grown within microfluidic chips, has emerged as a promising tool for mimicking human physiology in a controlled microenvironment. A …


Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry Jan 2023

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …


How Sleep Disturbances Affect Those With Borderline Personality Disorder And The Implications For Treatment, Molly L. Schmanke Jan 2023

How Sleep Disturbances Affect Those With Borderline Personality Disorder And The Implications For Treatment, Molly L. Schmanke

Regis University Student Publications (comprehensive collection)

This thesis argues that there is limited research on Borderline Personality Disorder’s comorbidity with sleep disorders, and by pointing out the gaps in knowledge this will encourage researchers and doctors to consider this topic as important in the health care field. Sleep disorders can be anything from reduced total sleep time, fragmented sleep, and changes in sleep architecture, and all of these can cause and be caused by disruption of the circadian clock. There are various ways in which circadian clock disruption can cause diseases, cancer, and mental disorders through genes, sleep, and the environment. Borderline Personality Disorder comorbid with …


Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar Jan 2023

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …