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2019

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Articles 1681 - 1710 of 16114

Full-Text Articles in Medicine and Health Sciences

Dental Practice Success Special Issue: Compliance (November 2019), American Dental Association, Publishing Division Nov 2019

Dental Practice Success Special Issue: Compliance (November 2019), American Dental Association, Publishing Division

Dental Practice Success

No abstract provided.


Behavior Prioritization To Improve Sbc (Social And Behavior Change) Programming During A Public Health Emergency: A Call To Action, Breakthrough Research Nov 2019

Behavior Prioritization To Improve Sbc (Social And Behavior Change) Programming During A Public Health Emergency: A Call To Action, Breakthrough Research

Poverty, Gender, and Youth

As the international development community continues to manage public health challenges and emerging diseases, the need for behavior prioritization is critical. The information in this brief provides rationale for why behavior prioritization is instrumental to improve social and behavior change programming, and ends with a call to action for advocacy for behavior prioritization processes as part of social and behavior change program design, planning, and adaptation. During the Zika outbreak in Latin America, a review of USAID-supported programming in 2017 revealed more than 30 Zika preventive behaviors and messages promoted by different implementing partners, and messaging on desired behaviors was …


Electrocardiographic Findings During Standard Hands Only Cpr And Hands Only Cpr Plus Pedal Cpr In Senior Rescuers, Laura Melany Yassa Nov 2019

Electrocardiographic Findings During Standard Hands Only Cpr And Hands Only Cpr Plus Pedal Cpr In Senior Rescuers, Laura Melany Yassa

Master's Theses

The standard first aid for a heart attack resulting in cardiopulmonary arrest is effective cardiopulmonary resuscitation (CPR). Chest compressions are most commonly performed on a flat surface with the rescuer kneeling next to the victim with one hand on top of the other on the sternum and elbows straight. This technique of being on the ground may be challenging for those without the mobility and strength to get up and down from the ground. In 2005, the American Heart Association (AHA) Guidelines listed “pedal”, or heel, compression as an acceptable alternative to standard chest compressions (Trenkamp & Perez, 2015). That …


Comparison Of A Self-Audit Tool To Accrediting Health Care Agencies’ Standards Of Care In A Corrections Setting, Matthew C. Widerman Nov 2019

Comparison Of A Self-Audit Tool To Accrediting Health Care Agencies’ Standards Of Care In A Corrections Setting, Matthew C. Widerman

Doctoral Projects

Millions of individuals enter correctional facilities each year and require health services. Inmates are bound to a set of rules, wherein they are thought of as objects of surveillance, punishment, or rehabilitation, rather than as patients. In addition to standards of care defined by national accrediting bodies and state boards of practice, correctional facilities also have state laws that define expected health services for incarcerated persons. All health care providers have a responsibility to provide the highest quality care, but in prisons, patients are still inmates bound to correctional rules. Policies and procedures guide health care practices in correctional facilities, …


Isodeoxyelephantopin, A Sesquiterpene Lactone Induces Ros Generation, Suppresses Nf-Κb Activation, Modulates Lncrna Expression And Exhibit Activities Against Breast Cancer, Sumit S. Verma, Vipin Rai, Nikee Awasthee, Anupam Dhasmana, Dhanya S. Rajalaksmi, Mangalam S. Nair, Subash C. Gupta Nov 2019

Isodeoxyelephantopin, A Sesquiterpene Lactone Induces Ros Generation, Suppresses Nf-Κb Activation, Modulates Lncrna Expression And Exhibit Activities Against Breast Cancer, Sumit S. Verma, Vipin Rai, Nikee Awasthee, Anupam Dhasmana, Dhanya S. Rajalaksmi, Mangalam S. Nair, Subash C. Gupta

School of Medicine Publications

The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering …


Fine Mapping And Identification Of Serum Urate Loci In American Indians: The Strong Heart Family Study, Geetha Chittoor, Karin Haack, Poojitha Balakrishnan, Christopher Bizon, Sandra Laston, Lyle G. Best, Jean W. Maccluer, Kari E. North, Jason G. Umans Nov 2019

Fine Mapping And Identification Of Serum Urate Loci In American Indians: The Strong Heart Family Study, Geetha Chittoor, Karin Haack, Poojitha Balakrishnan, Christopher Bizon, Sandra Laston, Lyle G. Best, Jean W. Maccluer, Kari E. North, Jason G. Umans

School of Medicine Publications

While studies have reported genetic loci affecting serum urate (SU) concentrations, few studies have been conducted in minority populations. Our objective for this study was to identify genetic loci regulating SU in a multigenerational family-based cohort of American Indians, the Strong Heart Family Study (SHFS). We genotyped 162,718 single nucleotide polymorphisms (SNPs) in 2000 SHFS participants using an Illumina MetaboChip array. A genome-wide association analysis of SU was conducted using measured genotype analysis approach accounting for kinships in SOLAR, and meta-analysis in METAL. Our results showed strong association of SU with rs4481233, rs9998811, rs7696092 and rs13145758 (minor allele frequency (MAF) …


Genetic Variants Affecting Bone Mineral Density And Bone Mineral Content At Multiple Skeletal Sites In Hispanic Children, Ruixue Hou, Shelley A. Cole, Mariaelisa Graff, Karin Haack, Sandra Laston, Anthony G. Comuzzie, Nitesh R. Mehta, Kathleen Ryan, Diana L. Cousminer, Babette S. Zemel Nov 2019

Genetic Variants Affecting Bone Mineral Density And Bone Mineral Content At Multiple Skeletal Sites In Hispanic Children, Ruixue Hou, Shelley A. Cole, Mariaelisa Graff, Karin Haack, Sandra Laston, Anthony G. Comuzzie, Nitesh R. Mehta, Kathleen Ryan, Diana L. Cousminer, Babette S. Zemel

School of Medicine Publications

Context:

Osteoporosis is a major public health burden with significant economic costs. However, the correlates of bone health in Hispanic children are understudied.

Objective:

We aimed to identify genetic variants associated with bone mineral density (BMD) and bone mineral content (BMC) at multiple skeletal sites in Hispanic children.

Methods:

We conducted a cross-sectional genome-wide linkage analysis, genome-wide and exome-wide association analysis of BMD and BMC. The Viva La Familia Study is a family-based cohort with a total of 1,030 Hispanic children (4–19 years old at baseline) conducted in Houston, TX. BMD and BMC were measured by Dual-energy X-ray absorptiometry.

Results: …


A Proposal For Complementarity Between Migration And Psychoanalytical Studies In Mental Health [Una Propuesta De Complementariedad Entre Los Estudios De Migración Y Psicoanalíticos En Salud Mental], Ángel Luna, Silvia Mejia-Arango Nov 2019

A Proposal For Complementarity Between Migration And Psychoanalytical Studies In Mental Health [Una Propuesta De Complementariedad Entre Los Estudios De Migración Y Psicoanalíticos En Salud Mental], Ángel Luna, Silvia Mejia-Arango

School of Medicine Publications

The objective of this article is to discuss the epistemological foundations of psychoanalytic studies and their possibility of complementarity with migration studies based on sociology. The methodology used was the review of theoretical production about epistemology in psychoanalysis, the tradition of research in sociology, as well the migration studies focused on mental health. Among the results, important epistemological and methodological coincidences between both disciplines were found. From this, a brief proposal is presented that highlights the feasibility of generating complementary studies on migration, specifically in border contexts. It is argued that the value of this article lies in the exploration …


Energy Cost Of Slow And Normal Gait Speeds In Low And Normally Functioning Adults, Taylor W. Rowley, Chi Cho, Ann M. Swartz, John Staudenmayer, Allison S. Hyngstrom, Kevin G. Keenan, Whitney A. Welch, Scott J. Strath Nov 2019

Energy Cost Of Slow And Normal Gait Speeds In Low And Normally Functioning Adults, Taylor W. Rowley, Chi Cho, Ann M. Swartz, John Staudenmayer, Allison S. Hyngstrom, Kevin G. Keenan, Whitney A. Welch, Scott J. Strath

Physical Therapy Faculty Research and Publications

Objective

Slow walking speed paired with increased energy cost is a strong predictor for mortality and disability in older adults but has yet to be examined in a heterogeneous sample (ie, age, sex, disease status). The aim of this study was to examine energy cost of slow and normal walking speeds among low- and normal-functioning adults.

Design

Adults aged 20–90 yrs were recruited for this study. Participants completed a 10-m functional walk test at a self-selected normal walking speed and were categorized as low functioning or normal functioning based on expected age- and sex-adjusted average gait speed. Participants completed two …


Nutrinews: November, 2019, Department Of Nutrition And Dietetics, University Of North Florida Nov 2019

Nutrinews: November, 2019, Department Of Nutrition And Dietetics, University Of North Florida

NutriNews

This issue features Students Look to Give Back Food fighters and meals on wings collaboration, Celebration of Celery, Food science highlight: split pea week, Can our bodies over protect us?


Assessing The Adherence Of Obstetricians Towards Postpartum Diabetes Screening Guidelines: A Pre- And Post-Intervention Study At Secondary Care Hospital In Karachi, Pakistan, Sadiqa Munir Razzaqui, Neelofur Babar, Zaib Un Nisa Memon, Sarah Rafiq Nov 2019

Assessing The Adherence Of Obstetricians Towards Postpartum Diabetes Screening Guidelines: A Pre- And Post-Intervention Study At Secondary Care Hospital In Karachi, Pakistan, Sadiqa Munir Razzaqui, Neelofur Babar, Zaib Un Nisa Memon, Sarah Rafiq

Department of Obstetrics & Gynaecology

Objective: To assess the adherence level of obstetricians towards postpartum diabetes screening guidelines.
Methods: The quasi-experimental pre- and post-intervention study was conducted from May 2014 to April 2015 at Aga Khan Hospital for Women-Karimabad, Karachi, and comprised all obstetricians practicing at the time. All the booked women with gestational diabetes delivered in the 6 months before refresher lecture (group 1) and those delivering in the 6 months following the intervention (group 2) were included. Data was analysed using SPSS 19.
Results: Of the 550 cases, 275(50%) each were in groups 1 and 2. All pregnant women had live-birth. The intervention …


Binge Eating Disorder And The Nutrition Care Process, Kaddie Levine Nov 2019

Binge Eating Disorder And The Nutrition Care Process, Kaddie Levine

Nutrition & Dietetics Student Publications

Exploring the fundamentals of the nutrition care process in binge eating disorder patients. A student dietitian's take on binge eating disorder treatment and what to look for when making nutrition therapy recommendations.


Prenatal Yoga In Pregnancy, Ashleigh Clingenpeel Nov 2019

Prenatal Yoga In Pregnancy, Ashleigh Clingenpeel

Senior Honors Theses

Prenatal yoga has emerged as an advisable, beneficial, and supportive addition to birth preparation. Many studies have linked participation in prenatal yoga with both maternal and infant benefits. Physical benefits for the mother include decreased labor time, decreased labor pain, and improved comfort during pregnancy. Significant emotional and mental effects have also been correlated, such as lowered rates of depression and anxiety, increased self-efficacy in labor, and easier transitions into the postpartum period. Finally, prenatal yoga has demonstrated benefits to the neonate, with a greater number of vaginal deliveries, which are less traumatic for the infant, an increase in gestational …


A Diagnostic Condition And Its Implications [Physical Therapist Assistant Program], May Tom Nov 2019

A Diagnostic Condition And Its Implications [Physical Therapist Assistant Program], May Tom

Open Educational Resources

SCT 101: Introduction to Physical Therapy

Assignment Description: This assignment was designed during Learning Matters 2018-2019 Digital Communication sub-seminar. The assignment was originally a written paper based on the clinical manifestations and pathogenesis of a diagnostic condition. As the profession of physical therapy is inherently a teaching profession, an oral and digital component was incorporated to facilitate the student’s ability and confidence in oral communication and use of media. The presentation of a diagnostic condition and implication in the performance of activities for an individual can be variable depending on the individual’s physical status, medical/health history, and psychosocial status. To …


Developing A Community-Based Research Project Proposal To Build Public Health Educator Capacity: A Graduate Student Perspective., Alexander J. Baukus Nov 2019

Developing A Community-Based Research Project Proposal To Build Public Health Educator Capacity: A Graduate Student Perspective., Alexander J. Baukus

Student Papers, Posters & Projects

This article is the author's first-person perspective of completing an Applied Practice Experience (APE) at an accredited public health program. Graduate-level public health students in the United States are mandated by the Council on Education for Public Health to complete this supervised field experience to apply knowledge and concepts to real-world public health practice. For his APE, the author worked with a faculty advisor and two community groups to facilitate and submit a community-based participatory research grant proposal. This article discusses the author's experiences before, during, and after the APE. The author outlines challenges and success of working on this …


Teaching Health Education Through The Development Of Student Centered Video Assignment, Heather M. Wallace, Julia Vandermolen Nov 2019

Teaching Health Education Through The Development Of Student Centered Video Assignment, Heather M. Wallace, Julia Vandermolen

Open Access Publishing Support Funded Articles

The purpose of this study was to explore the ways in which a student centered video assignment enhanced student learning about developing and teaching a health education plan designed to address a complex public health problem. The objectives of the assignment included (1) to explore a complex public health problem, (2) practice developing a corresponding health education plan, and (3) develop and fully execute a multimedia video to deliver high impact health education and or promotion to a diverse audience. The assignment referred to as the student centered video assignment was developed and piloted at Grand Valley State University and …


Prevalence Of Malaria Reported During Summer And Winter At A Tertiary Care Hospital In Karachi, Pakistan, Fazal M. Arain, Aisha Memon, Roohi Jamal, Ahmed Raheem Buksh, Mohammad Asim Beg Nov 2019

Prevalence Of Malaria Reported During Summer And Winter At A Tertiary Care Hospital In Karachi, Pakistan, Fazal M. Arain, Aisha Memon, Roohi Jamal, Ahmed Raheem Buksh, Mohammad Asim Beg

Department of Biological & Biomedical Sciences

This study was designed to determine the prevalence and type of malaria cases that presented throughout the year 2014 in a tertiary care hospital in Karachi, Pakistan. A total of 1099 cases, (377 females, 722 males) were reported. Plasmodium vivax (P. vivax) was discovered in 93.7% cases compared to 6.3% Plasmodium falciparum (P. falciparum). Based on the highest and lowest weather temperatures, in summer (June, July and August) and in winter (December, January and February) were differentiated. The number of cases were greater during summer months compared to winter. Interestingly, the ratio of P. falciparum to P. vivax during winter …


Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha Nov 2019

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …


Scoring Morphology In Measures Of Spelling And Written Morphological Awareness: A Scoping Review, Victor A. Lugo, Kimberly A. Murphy, Emily Diehm Nov 2019

Scoring Morphology In Measures Of Spelling And Written Morphological Awareness: A Scoping Review, Victor A. Lugo, Kimberly A. Murphy, Emily Diehm

Communication Disorders & Special Education Faculty Publications

No abstract provided.


How Oxygen Availability Affects The Antimicrobial Efficacy Of Host Defense Peptides: Lessons Learned From Studying The Copper-Binding Peptides Piscidins 1 And 3, Adenrele Oludiran, David S. Courson, Malia D. Stuart, Anwar R. Radwan, John C. Putsma, Myriam L. Cotten, Erin B. Purcell Nov 2019

How Oxygen Availability Affects The Antimicrobial Efficacy Of Host Defense Peptides: Lessons Learned From Studying The Copper-Binding Peptides Piscidins 1 And 3, Adenrele Oludiran, David S. Courson, Malia D. Stuart, Anwar R. Radwan, John C. Putsma, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating the immune system function and directly killing bacteria through membrane disruption and oxidative damage. The copper-binding HDPs piscidin 1 and piscidin 3 have previously shown potent antimicrobial activity against a number of Gram-negative and Gram-positive bacterial species but have never been investigated in an anaerobic environment. Synergy between piscidins and metal ions increases bacterial killing aerobically. Here, we …


Creation Of Radiocephalic Arteriovenous Fistula In A Patient With Failed Brachiocephalic Arteriovenous Fistula, Zia Ur Rehman Nov 2019

Creation Of Radiocephalic Arteriovenous Fistula In A Patient With Failed Brachiocephalic Arteriovenous Fistula, Zia Ur Rehman

Department of Surgery Docs

Abstract are not provided by the author/publisher


Sponsorship Engagement: Leveraging Ancillary Events To Increase Title Sponsor Awareness, Amanda Greene, Natalie L. Smith, Charles W. Jones Nov 2019

Sponsorship Engagement: Leveraging Ancillary Events To Increase Title Sponsor Awareness, Amanda Greene, Natalie L. Smith, Charles W. Jones

ETSU Faculty Works

No abstract provided.


From Suffrage To The Senate: Expanding Inclusion In Women's Rights To Achieve Women's Health Equality., Frances Grimstad Nov 2019

From Suffrage To The Senate: Expanding Inclusion In Women's Rights To Achieve Women's Health Equality., Frances Grimstad

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Twenty Novel Disease Group-Specific And 12 New Shared Macrophage Pathways In Eight Groups Of 34 Diseases Including 24 Inflammatory Organ Diseases And 10 Types Of Tumors., Bin Lai, Jiwei Wang, Alexander Fagenson, Yu Sun, Jason Saredy, Yifan Lu, Gayani Nanayakkara, William Y Yang, Daohai Yu, Ying Shao, Charles Drummer, Candice Johnson, Fatma Saaoud, Ruijing Zhang, Qian Yang, Keman Xu, Kevin Mastascusa, Ramon Cueto, Hangfei Fu, Susu Wu, Lizhe Sun, Peiqian Zhu, Xuebin Qin, Jun Yu, Daping Fan, Ying H Shen, Jianxin Sun, Thomas Rogers, Eric T Choi, Hong Wang, Xiaofeng Yang Nov 2019

Twenty Novel Disease Group-Specific And 12 New Shared Macrophage Pathways In Eight Groups Of 34 Diseases Including 24 Inflammatory Organ Diseases And 10 Types Of Tumors., Bin Lai, Jiwei Wang, Alexander Fagenson, Yu Sun, Jason Saredy, Yifan Lu, Gayani Nanayakkara, William Y Yang, Daohai Yu, Ying Shao, Charles Drummer, Candice Johnson, Fatma Saaoud, Ruijing Zhang, Qian Yang, Keman Xu, Kevin Mastascusa, Ramon Cueto, Hangfei Fu, Susu Wu, Lizhe Sun, Peiqian Zhu, Xuebin Qin, Jun Yu, Daping Fan, Ying H Shen, Jianxin Sun, Thomas Rogers, Eric T Choi, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ …


Characterization And Longitudinal Assessment Of Daily Quality Assurance For An Mr-Guided Radiotherapy (Mrgrt) Linac, Kathryn Mittauer Nov 2019

Characterization And Longitudinal Assessment Of Daily Quality Assurance For An Mr-Guided Radiotherapy (Mrgrt) Linac, Kathryn Mittauer

All Publications

No abstract provided.


Preoperative Factors Related To Delayed Discharge After Total Knee Arthroplasty Removal From Inpatient-Only List, Juan Carlos Suarez, William Arguelles, Priscilla Rivera, Yvette Hernandez, Don Parris Nov 2019

Preoperative Factors Related To Delayed Discharge After Total Knee Arthroplasty Removal From Inpatient-Only List, Juan Carlos Suarez, William Arguelles, Priscilla Rivera, Yvette Hernandez, Don Parris

All Publications

No abstract provided.


Enhancing Clinical Concept Extraction With Contextual Embeddings, Yuqi Si, Jingqi Wang, Hua Xu, Kirk Roberts Nov 2019

Enhancing Clinical Concept Extraction With Contextual Embeddings, Yuqi Si, Jingqi Wang, Hua Xu, Kirk Roberts

Faculty, Staff and Student Publications

OBJECTIVE: Neural network-based representations ("embeddings") have dramatically advanced natural language processing (NLP) tasks, including clinical NLP tasks such as concept extraction. Recently, however, more advanced embedding methods and representations (eg, ELMo, BERT) have further pushed the state of the art in NLP, yet there are no common best practices for how to integrate these representations into clinical tasks. The purpose of this study, then, is to explore the space of possible options in utilizing these new models for clinical concept extraction, including comparing these to traditional word embedding methods (word2vec, GloVe, fastText).

MATERIALS AND METHODS: Both off-the-shelf, open-domain embeddings and …


A Review Of The Association Between Vitamin D And Postpartum Depression, Christa Fernando Nov 2019

A Review Of The Association Between Vitamin D And Postpartum Depression, Christa Fernando

Biomedical Sciences Undergraduate Research

Vitamin D (specifically vitamin D3) is a lipid soluble essential nutrient. It is found in few foods naturally but can be synthesized upon skin exposure to sunlight. Its intermediate structure in the blood is serum 25-hydroxyvitamin D, also called calcidiol, and is formed in the liver. Vitamin D receptors have been found in numerous areas of the brain that are involved in mood-related hormone production. It has also been found to be protective against the brain degradation of Alzheimer’s. Numerous studies have found a significant relationship between vitamin D and major depressive disorder. This review summarizes research on the connection …


Delineating The Mechanisms Of Misfolded Endoplasmic Reticulum (Er) Luminal Protein Retrotranslocation For Er-Associated Degradation, Christina Oikonomou Nov 2019

Delineating The Mechanisms Of Misfolded Endoplasmic Reticulum (Er) Luminal Protein Retrotranslocation For Er-Associated Degradation, Christina Oikonomou

Theses and Dissertations (ETD)

Secreted, plasma membrane, and resident proteins of the secretory pathway are synthesized in the endoplasmic reticulum (ER) where they undergo post-translational modifications, oxidative folding, and subunit assembly in tightly monitored processes. An ER quality control (ERQC) system oversees protein maturation and ensures that only those reaching their native state will continue trafficking into the secretory pathway to reach their final destinations. Proteins that fail quality control must be recognized and eliminated to maintain ER proteostasis. The ER-associated degradation (ERAD) was discovered nearly 30 years ago and entails the identification of improperly matured secretory pathway proteins and their retrotranslocation to the …


An Update On Pharmaceutical Strategies For Oral Delivery Of Therapeutic Peptides And Proteins, Nirnoy Dan Nov 2019

An Update On Pharmaceutical Strategies For Oral Delivery Of Therapeutic Peptides And Proteins, Nirnoy Dan

Theses and Dissertations (ETD)

Peptides and proteins are imperative for the human body and play crucial roles in governing various bio-chemical processes. Recent advances in molecular biology and biochemistry helped in understanding the role of these endogenous macromolecules in different pathological and disease conditions. Currently, small molecule drugs (< 900dalton) in comparison to the therapeutic peptides and proteins-based drugs (TPP) dominate pharmaceutical market. However, the game is changing with the recent advances of biotechnological tools like recombinant DNA technology, solid phase protein synthesis etc., which enabled large-scale production of therapeutic peptides and proteins. The Success of Human Insulin, the first FDA approved commercial recombinant protein based therapeutic in 1982, revolutionized the field of TPPs. The number of FDA approved TPPs reached about to ~239 in 2017 compared to where it was only ~130 in 2008. Rapid progress in this sector can be attributed to several advantages of proteins and peptides over small molecule drugs both financially and clinically. From a clinical perspective, proteins and peptides are inherently more specific to the target site than the small molecules drugs, which lead to less interferences with normal biological system of the patient and caused minimal off-target side effects. A handful of proteins which are used for different clinical complications are less immunogenic because they are produced in the body naturally. Furthermore, proteins and peptides also take part in several complex and complicated biological processes, which is difficult to be to be mimicked by the small molecule drugs. From a financial standpoint, median total pre-market development times were shorter for biologics (10.6 years) than the small molecules drugs (12.6 years) estimated using Merck Index. In 2009, US Congress passed the Biologics Price Competition and Innovation Act (BPCIA) which gave new biologics 12 years of guaranteed exclusivity. The most commonly utilized routes for administering TPPs are I.V, I.P or I.M injections, which largely suffer from patient compliances. There are ~350 TPPs under clinical development and among them only 2 are given orally which is Interferon-α and Human growth hormone. Currently, most efforts in both industry and academia are centered around enhancing bioavailability of orally administered TPPs which typically are less than 1%. Oral administration is the non-invasive, most preferred route of drug administration for the patients. Furthermore, oral dosage forms are cheaper to manufacture as well as to administer, because they do not need to be produced under sterile conditions or administered in clinics. However, unfavorable physicochemical characteristics of TPPs like high molecular weight, hydrophilicity, poor stability in the physiological conditions, short biological half-life, low permeability through the epithelial barrier in the small intestine put up a massive barrier in the development of orally available dosage forms of TPPs. In this review, we will discuss the challenges associated with oral delivery of TPPs and the ongoing efforts to solve them.