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Full-Text Articles in Medicine and Health Sciences

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff Dec 2020

Oral Chemotherapy: Safe Handling In The Home, Cynthia Huff

DNP Qualifying Manuscripts

Background: According to the National Institute for Occupational Safety and Health (2016), oral anticancer agents (OAC) are hazardous drugs (HD) and require the same safe handling interventions in the home setting as in controlled health care environments. The use of a safe handling checklist for OAC administration is a way nurses can provide safe handling education to patients and caregivers and assess for understanding and competency for critical tasks. Effective home management strategies outlining caregiver protections, proper storage, administration of OACs, spill clean-up, and waste disposal could reduce exposure risks to toxic agents.

Objective: To present a safe-handling checklist and ...


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast Dec 2019

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms ...


Use Of Antidiabetic Drugs During Pregnancy Among U.S. Women With Livebirth Deliveries In The Mini-Sentinel System, Katrina Mott, Marsha E. Reichman, Sengwee Toh, Caren Kieswetter, Katherine Haffenreffer, Susan E. Andrade Nov 2019

Use Of Antidiabetic Drugs During Pregnancy Among U.S. Women With Livebirth Deliveries In The Mini-Sentinel System, Katrina Mott, Marsha E. Reichman, Sengwee Toh, Caren Kieswetter, Katherine Haffenreffer, Susan E. Andrade

Open Access Articles

BACKGROUND: As the prevalence of diabetes mellitus increases in the population, the exposure to antidiabetic drugs (ADDs) during pregnancies is expected to grow, as has been seen over the last decade. The objective of this study was to estimate the prevalence of ADD use during pregnancy among women in the Mini-Sentinel Distributed Database (MSDD) who delivered a liveborn infant.

METHODS: We identified qualifying livebirth pregnancies among women aged 10 to 54 years in the MSDD from 2001 to 2013. ADD use was estimated using outpatient pharmacy dispensing claims and days-supplied among three cohorts: all livebirth pregnancies, pregnancies among women with ...


Solenodon Genome Reveals Convergent Evolution Of Venom In Eulipotyphlan Mammals, Nicholas R. Casewell, Elinor K. Karlsson Nov 2019

Solenodon Genome Reveals Convergent Evolution Of Venom In Eulipotyphlan Mammals, Nicholas R. Casewell, Elinor K. Karlsson

Open Access Articles

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan ...


Cdr3alpha Drives Selection Of The Immunodominant Epstein Barr Virus (Ebv) Brlf1-Specific Cd8 T Cell Receptor Repertoire In Primary Infection, Larisa Kamga, Anna Gil, Inyoung Song, Robin M. Brody, Dario Ghersi, Nuray Aslan, Lawrence J. Stern, Liisa K. Selin, Katherine Luzuriaga Nov 2019

Cdr3alpha Drives Selection Of The Immunodominant Epstein Barr Virus (Ebv) Brlf1-Specific Cd8 T Cell Receptor Repertoire In Primary Infection, Larisa Kamga, Anna Gil, Inyoung Song, Robin M. Brody, Dario Ghersi, Nuray Aslan, Lawrence J. Stern, Liisa K. Selin, Katherine Luzuriaga

Open Access Articles

The T cell receptor (TCR) repertoire is an essential component of the CD8 T-cell immune response. Here, we seek to investigate factors that drive selection of TCR repertoires specific to the HLA-A2-restricted immunodominant epitope BRLF1109-117 (YVLDHLIVV) over the course of primary Epstein Barr virus (EBV) infection. Using single-cell paired TCRalphabeta sequencing of tetramer sorted CD8 T cells ex vivo, we show at the clonal level that recognition of the HLA-A2-restricted BRLF1 (YVL-BR, BRLF-1109) epitope is mainly driven by the TCRalpha chain. For the first time, we identify a CDR3alpha (complementarity determining region 3 alpha) motif, KDTDKL, resulting from an obligate ...


In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins Nov 2019

In Vivo Clonal Expansion And Phenotypes Of Hypocretin-Specific Cd4(+) T Cells In Narcolepsy Patients And Controls, Wei Jiang, James R. Birtley, Grant C. Weaver, Liying Lu, Lawrence J. Stern, Elizabeth D. Mellins

Open Access Articles

Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor alpha (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer(+)/TRAJ24(+)/CD4(+) T cells in DQ6(+) individuals with and without narcolepsy. We identify related TRAJ24(+) TCRalphabeta clonotypes encoded by identical alpha/beta gene regions from two patients and two controls. TRAJ24-G allele(+) clonotypes only expand in the two ...


Genome Editing Of Hbg1 And Hbg2 To Induce Fetal Hemoglobin, Jean-Yves Metais, Kevin Luk, Scot A. Wolfe, Shengdar Q. Tsai, Mitchell J. Weiss Nov 2019

Genome Editing Of Hbg1 And Hbg2 To Induce Fetal Hemoglobin, Jean-Yves Metais, Kevin Luk, Scot A. Wolfe, Shengdar Q. Tsai, Mitchell J. Weiss

Open Access Articles

Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress gamma-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and beta-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially ...


Anti-Crispr Acriia5 Potently Inhibits All Cas9 Homologs Used For Genome Editing, Bianca Garcia, Jooyoung Lee, Alireza Edraki, Yurima Hidalgo-Reyes, Steven Erwood, Aamir Mir, Chantel N. Trost, Uri Seroussi, Sabrina Y. Stanley, Ronald D. Cohn, Julie M. Claycomb, Erik J. Sontheimer, Karen L. Maxwell, Alan R. Davidson Nov 2019

Anti-Crispr Acriia5 Potently Inhibits All Cas9 Homologs Used For Genome Editing, Bianca Garcia, Jooyoung Lee, Alireza Edraki, Yurima Hidalgo-Reyes, Steven Erwood, Aamir Mir, Chantel N. Trost, Uri Seroussi, Sabrina Y. Stanley, Ronald D. Cohn, Julie M. Claycomb, Erik J. Sontheimer, Karen L. Maxwell, Alan R. Davidson

Open Access Articles

CRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control of Cas9 activity so that the timing, tissue specificity, and accuracy of editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors of CRISPR-Cas systems, are well suited for this purpose. A number of anti-CRISPR proteins have been shown to potently inhibit subgroups of CRISPR-Cas9 systems, but their maximal inhibitory activity is generally restricted to specific Cas9 homologs. Since Cas9 homologs vary in important properties, differing Cas9s may be optimal for particular genome-editing applications. To facilitate the practical exploitation of ...


A Cohesin Subunit Variant Identified From A Peripheral Sclerocornea Pedigree, Bi Ning Zhang, Tommy Chung Yan Chan, Pancy Oi Sin Tam, Yu Liu, Chi Pui Pang, Vishal Jhanji, Li Jia Chen, Wai Kit Chu Nov 2019

A Cohesin Subunit Variant Identified From A Peripheral Sclerocornea Pedigree, Bi Ning Zhang, Tommy Chung Yan Chan, Pancy Oi Sin Tam, Yu Liu, Chi Pui Pang, Vishal Jhanji, Li Jia Chen, Wai Kit Chu

Open Access Articles

Background: Sclerocornea is a rare congenital disorder characterized with the opacification of the cornea. Here, we report a nonconsanguineous Chinese family with multiple peripheral sclerocornea patients spanning across three generations inherited in an autosomal dominant manner.

Methods: This is a retrospective case series of a peripheral sclerocornea pedigree. Comprehensive ophthalmic examinations were conducted and assessed on 14 pedigree members. Whole-exome sequencing was used to identify the genetic alterations in the affected pedigree members. Lymphoblastoid cell lines (LCLs) were established using blood samples from the family members. Functional tests were performed with these cell lines.

Results: Six affected and eight unaffected ...


Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans Nov 2019

Evaluating Volatile Organic Compounds For Contact-Independent Antagonism Of Pseudogymnoascus Destructans

Symposium of Student Scholars

White-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans, is responsible for the extensive mortality of bats in the United States. In an effort to develop tools to reduce bat mortality attributed to WNS, an in vitro experiment was conducted to quantify the inhibitory effects of select volatile organic compounds (VOCs) as well as explore potential synergistic activities. The experiment involved exposing mycelial plugs of P. destructans to various concentrations of B23 as well as B23 and decanal together at equimolar ratios. Measurements of the plugs were taken over the course of the 13 day experiment allowing the ...


Dietary Alpha-Ketoglutarate Promotes Beige Adipogenesis And Prevents Obesity In Middle-Aged Mice, Qiyu Tian, Junxing Zhao, Qiyuan Yang, Bo Wang, Jeanene M. Deavila, Mei-Jun Zhu, Min Du Nov 2019

Dietary Alpha-Ketoglutarate Promotes Beige Adipogenesis And Prevents Obesity In Middle-Aged Mice, Qiyu Tian, Junxing Zhao, Qiyuan Yang, Bo Wang, Jeanene M. Deavila, Mei-Jun Zhu, Min Du

Open Access Articles

Aging usually involves the progressive development of certain illnesses, including diabetes and obesity. Due to incapacity to form new white adipocytes, adipose expansion in aged mice primarily depends on adipocyte hypertrophy, which induces metabolic dysfunction. On the other hand, brown adipose tissue burns fatty acids, preventing ectopic lipid accumulation and metabolic diseases. However, the capacity of brown/beige adipogenesis declines inevitably during the aging process. Previously, we reported that DNA demethylation in the Prdm16 promoter is required for beige adipogenesis. DNA methylation is mediated by ten-eleven family proteins (TET) using alpha-ketoglutarate (AKG) as a cofactor. Here, we demonstrated that the ...


Letter: When Less Is More: Dexamethasone Dosing For Brain Tumors, Minesh Mehta Nov 2019

Letter: When Less Is More: Dexamethasone Dosing For Brain Tumors, Minesh Mehta

Minesh Mehta

No abstract provided.


Natural Hiv-1 Nef Polymorphisms Impair Serinc5 Downregulation Activity, Steven W. Jin, Nirmin Alsahafi, Xiaomei T. Kuang, Shayda A. Swann, Mako Toyoda, Heinrich G. Gottlinger, Bruce D. Walker, Takamasa Ueno, Andres Finzi, Zabrina L. Brumme, Mark A. Brockman Nov 2019

Natural Hiv-1 Nef Polymorphisms Impair Serinc5 Downregulation Activity, Steven W. Jin, Nirmin Alsahafi, Xiaomei T. Kuang, Shayda A. Swann, Mako Toyoda, Heinrich G. Gottlinger, Bruce D. Walker, Takamasa Ueno, Andres Finzi, Zabrina L. Brumme, Mark A. Brockman

Open Access Articles

HIV-1 Nef enhances virion infectivity by counteracting host restriction factor SERINC5; however, the impact of natural Nef polymorphisms on this function is largely unknown. We characterize SERINC5 downregulation activity of 91 primary HIV-1 subtype B nef alleles, including isolates from 45 elite controllers and 46 chronic progressors. Controller-derived Nef clones display lower ability to downregulate SERINC5 (median 80% activity) compared with progressor-derived clones (median 96% activity) (p = 0.0005). We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B( *)08, and H116N, driven by the protective ...


#2 - Atad3a As A Novel Mitochondrial Oncogene In Head And Neck Squamous Cell Carcinoma, Caleb Jensen Nov 2019

#2 - Atad3a As A Novel Mitochondrial Oncogene In Head And Neck Squamous Cell Carcinoma, Caleb Jensen

Georgia Undergraduate Research Conference (GURC)

For patients with head and neck cancer whose tumors are HPV negative HPV(-), current therapy does not lead to significant longevity and most succumb to loco-regional recurrence of the primary tumor. We discovered that HPV(-) head and neck squamous cell carcinoma (HNSCC) highly expressed ATPase family AAA-domain containing protein 3A (ATAD3A). ATAD3A is the mitochondrial protein, which has been demonstrated as an oncogene in breast and lung cancer. However, nothing has been reported regarding its role in HNSCC. Using the HPV(-) HNSCC cell line HN12 as a cell model, we show here that knockout of ATAD3A expression by CRISPR-CAS9 in ...


#45 - The Relationship Between Media And Public Opinion Regarding Cannabis As An Opioid Substitute, Jordan Hendricks Nov 2019

#45 - The Relationship Between Media And Public Opinion Regarding Cannabis As An Opioid Substitute, Jordan Hendricks

Georgia Undergraduate Research Conference (GURC)

The purpose of this study was to determine the relationship between media and public opinion regarding cannabis as an opioid substitute. To accomplish this aim, an online survey was created and completed by college students (n=134) between 18 and 30 years of age. The survey asked questions examining participant demographic information, media consumption, and opinion towards cannabis and opioids. The data was analyzed in Excel using Chi-Square and Pearson correlation tests. The analysis showed that media and opinion on the use of cannabis as an opioid substitute were not significantly correlated (p=0.82; r=0.079). Also, a ...


Combatting The Opioid Epidemic In Texas By Holding Big Pharma Manufacturers Liable, Katherine Spiser Nov 2019

Combatting The Opioid Epidemic In Texas By Holding Big Pharma Manufacturers Liable, Katherine Spiser

St. Mary's Law Journal

Abstract forthcoming


Detecting, Preventing, And Treating Sexually Transmitted Diseases Among Adolescent Arrestees: An Unmet Public Health Need, Christopher Salvatore, Steven Belenko, Richard Dembo, Matthew Rollie, Kristina Childs Oct 2019

Detecting, Preventing, And Treating Sexually Transmitted Diseases Among Adolescent Arrestees: An Unmet Public Health Need, Christopher Salvatore, Steven Belenko, Richard Dembo, Matthew Rollie, Kristina Childs

Christopher Salvatore

Studies of detained and incarcerated adolescent offenders in the United States indicate that these juveniles have an elevated risk of sexually transmitted diseases (STDs). However, many more arrestees enter the “front end” of the juvenile justice system that is detained or incarcerated, and research into the STD risk profiles and service needs of this larger group is lacking. An expansion of STD testing (including of asymptomatic youths), prevention, and treatment is needed, as is improved knowledge about gender- and race-specific services. A pilot program in Florida has shown that juvenile justice and public health systems can collaborate to implement STD ...


Structural Organization Of The C1a-E-C Supercomplex Within The Ciliary Central Apparatus, Gang Fu, Lei Zhao, Erin Dymek, Yuqing Hou, Kangkang Song, Nhan Phan, Zhiguo Shang, Elizabeth F. Smith, George B. Witman, Daniela Nicastro Oct 2019

Structural Organization Of The C1a-E-C Supercomplex Within The Ciliary Central Apparatus, Gang Fu, Lei Zhao, Erin Dymek, Yuqing Hou, Kangkang Song, Nhan Phan, Zhiguo Shang, Elizabeth F. Smith, George B. Witman, Daniela Nicastro

Radiology Publications and Presentations

Nearly all motile cilia contain a central apparatus (CA) composed of two connected singlet microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown. Here, we integrated biochemical and genetic approaches with cryo-electron tomography to compare the CA of wild-type Chlamydomonas with CA mutants. We identified a large ( > 2 MD) complex, the C1a-e-c supercomplex, that requires the PF16 protein for assembly and contains the CA components FAP76 ...


Redirection Of Skn-1 Abates The Negative Metabolic Outcomes Of A Perceived Pathogen Infection, James D. Nhan, Christian D. Turner, Sarah M. Anderson, Chia-An Yen, Hans M. Dalton, Hilary K. Cheesman, Dana L. Ruter, Nandhitha Uma Naresh, Cole M. Haynes, Alexander A. Soukas, Read Pukkila-Worley, Sean P. Curran Oct 2019

Redirection Of Skn-1 Abates The Negative Metabolic Outcomes Of A Perceived Pathogen Infection, James D. Nhan, Christian D. Turner, Sarah M. Anderson, Chia-An Yen, Hans M. Dalton, Hilary K. Cheesman, Dana L. Ruter, Nandhitha Uma Naresh, Cole M. Haynes, Alexander A. Soukas, Read Pukkila-Worley, Sean P. Curran

Open Access Articles

Early host responses toward pathogens are essential for defense against infection. In Caenorhabditis elegans, the transcription factor, SKN-1, regulates cellular defenses during xenobiotic intoxication and bacterial infection. However, constitutive activation of SKN-1 results in pleiotropic outcomes, including a redistribution of somatic lipids to the germline, which impairs health and shortens lifespan. Here, we show that exposing C. elegans to Pseudomonas aeruginosa similarly drives the rapid depletion of somatic, but not germline, lipid stores. Modulating the epigenetic landscape refines SKN-1 activity away from innate immunity targets, which alleviates negative metabolic outcomes. Similarly, exposure to oxidative stress redirects SKN-1 activity away from ...


Doxycycline-Induced Acute Pancreatitis: A Likely Source Rarely Seen, Paul Hoffman Do, Wilco Civil Sr, Jung Yoon Do, Gurjeet Kang Do, Christopher Lozano Orpiano Do, Michael Quinn Do, Joseph Staffetti Md, Dilip Ghanekar Md, Lakshminarasimhan Venu Md, Lily N. Jones Do, Ji Kwon Do, Shaival Thakore Md Oct 2019

Doxycycline-Induced Acute Pancreatitis: A Likely Source Rarely Seen, Paul Hoffman Do, Wilco Civil Sr, Jung Yoon Do, Gurjeet Kang Do, Christopher Lozano Orpiano Do, Michael Quinn Do, Joseph Staffetti Md, Dilip Ghanekar Md, Lakshminarasimhan Venu Md, Lily N. Jones Do, Ji Kwon Do, Shaival Thakore Md

Gastroenterology

No abstract provided.


P-19 Anticancer Activity Of Heteroaromatic Cyanostilbenes, Joshua Rotich Oct 2019

P-19 Anticancer Activity Of Heteroaromatic Cyanostilbenes, Joshua Rotich

Celebration of Research and Creative Scholarship

Cancer is currently the second leading killer disease. There are many different kinds of cancer that are associated with almost every organ in the human body (e.g., brain cancer, colon cancer, breast cancer, prostate cancer, blood cancer, lung cancer, etc.).

In the Biology Department, Dr. Smith and Dr. Murray are researching glioblastoma brain cancer cells. Glioblastoma is a very invasive cancer that is highly lethal. Chances of not surviving when its at stage four is more than 98%. Detecting this cancer while it is developing is difficult because symptoms are mild headache, fatigue, nausea and slight loss of weight ...


Bta-Mir-24-3p Controls The Myogenic Differentiation And Proliferation Of Fetal, Bovine, Skeletal Muscle-Derived Progenitor Cells By Targeting Acvr1b, Xin Hu, Yishen Xing, Ling Ren, Yahui Wang, Qian Li, Xing Fu, Qiyuan Yang, Lingyang Xu, Luc Willems, Junya Li, Lupei Zhang Oct 2019

Bta-Mir-24-3p Controls The Myogenic Differentiation And Proliferation Of Fetal, Bovine, Skeletal Muscle-Derived Progenitor Cells By Targeting Acvr1b, Xin Hu, Yishen Xing, Ling Ren, Yahui Wang, Qian Li, Xing Fu, Qiyuan Yang, Lingyang Xu, Luc Willems, Junya Li, Lupei Zhang

Open Access Articles

MicroRNAs modulate a variety of cellular events, including skeletal muscle development, but the molecular basis of their functions in fetal bovine skeletal muscle development is poorly understood. In this study, we report that bta-miR-24-3p promotes the myogenic differentiation of fetal bovine PDGFRalpha(-) progenitor cells. The expression of bta-miR-24-3p increased during myogenic differentiation. Overexpression of bta-miR-24-3p significantly promoted myogenic differentiation, but inhibited proliferation. A dual-luciferase assay identified ACVR1B as a direct target of bta-miR-24-3p. Similarly, knocking down ACVR1B by RNA interference also significantly inhibited proliferation and promoted the differentiation of bovine PDGFRalpha(-) progenitor cells. Thus, our study provides a mechanism in ...


Stable Nanopalladium Hydride In Water For Sustainable And Selective Reductions, Jesse Klus, Sachin Handa Oct 2019

Stable Nanopalladium Hydride In Water For Sustainable And Selective Reductions, Jesse Klus, Sachin Handa

Posters-at-the-Capitol

The synthesis of air-stable ligand-free nanopalladium hydride (PdNHx) in water was achieved and applied to various organic transformations, including (1) reduction of heteroaromatics such as (iso)quinolines, phenanthrolines, benzotriazole, and naphthyridines, (2) regio- and chemoselective reduction of nitroarenes, (3) alkyne reductions, (4) chemoselective dehalogenation, and (5) base-free detriflation. Both the synthesis of PdNHx and the reductions were carried out under mild conditions in a micellar medium using our designer surfactant PS-750-M, which eliminates the need for toxic organic solvents and extremely high hydrogen pressure and temperature. Notably, PS-750-M is also a replacement of hazardous polar-aprotic solvents. This newer approach for ...


Brazilian Generics Market Change After Farmacia Popular Program, Andrea Damaso Bertoldi, Luisa Arueira Chaves, Dennis Ross-Degnan, Vera Lucia Luiza, Isabel Cristina Martins Emmerick, Rondineli Mendes Da Silva, Monica Rodrigues. Campos Oct 2019

Brazilian Generics Market Change After Farmacia Popular Program, Andrea Damaso Bertoldi, Luisa Arueira Chaves, Dennis Ross-Degnan, Vera Lucia Luiza, Isabel Cristina Martins Emmerick, Rondineli Mendes Da Silva, Monica Rodrigues. Campos

Open Access Articles

OBJECTIVE: To evaluate trends in the use of generic and non-generic medicines to treat hypertension and diabetes under the Farmacia Popular Program (FP) and its impact on generic medicines sales volume and market share in the Brazilian pharmaceutical market.

METHODS: This longitudinal, retrospective study used interrupted time series design to analyze changes in monthly sales volume and proportion of medicines sales (market share) for oral antidiabetic and antihypertensive medicines for generic versus non-generic products. Analyses were conducted in a combined dataset that aggregate monthly sales volumes from the Farmacia Popular program and from the QuintilesIMS (IQVIA) national market sales data ...


Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu Oct 2019

Mdt-28/Plin-1 Mediates Lipid Droplet-Microtubule Interaction Via Dlc-1 In Caenorhabditis Elegans, Kang Xie, Peng Zhang, Huimin Na, Yangli Liu, Hong Zhang, Pingsheng Liu

Open Access Articles

Ectopic lipid accumulation in lipid droplets (LD) has been linked to many metabolic diseases. In this study, DHS-3::GFP was used as a LD marker in C. elegans and a forward genetic screen was carried out to find novel LD regulators. There were 140 mutant alleles identified which were divided into four phenotypic categories: enlarged, aggregated, aggregated and small, and decreased. After genetic mapping, mutations in three known LD regulatory genes (maoc-1, dhs-28, daf-22) and a peroxisome-related gene (acox-3) were found to enlarge LDs, demonstrating the reliability of using DHS-3 as a living marker. In the screen, the cytoskeleton protein ...


Chromatin Profiling Of Cortical Neurons Identifies Individual Epigenetic Signatures In Schizophrenia, Fedor E. Gusev, Denis A. Reshetov, Amanda C. Mitchell, Tatiana V. Andreeva, Aslihan Dincer, Anastasia P. Grigorenko, Gennady Fedonin, Tobias Halene, Maria Aliseychik, Elena Filippova, Zhiping Weng, Schahram Akbarian, Evgeny I. Rogaev Oct 2019

Chromatin Profiling Of Cortical Neurons Identifies Individual Epigenetic Signatures In Schizophrenia, Fedor E. Gusev, Denis A. Reshetov, Amanda C. Mitchell, Tatiana V. Andreeva, Aslihan Dincer, Anastasia P. Grigorenko, Gennady Fedonin, Tobias Halene, Maria Aliseychik, Elena Filippova, Zhiping Weng, Schahram Akbarian, Evgeny I. Rogaev

Open Access Articles

Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia. Here, we performed analysis of open chromatin landscape of gene promoters in prefrontal cortical (PFC) neurons from schizophrenic patients. We cataloged cell-type-based epigenetic signals of transcriptional start sites (TSS) marked by histone H3-K4 trimethylation (H3K4me3) across the genome in PFC from multiple schizophrenia subjects and age-matched control individuals. One of the top-ranked chromatin alterations was found in the major histocompatibility (MHC) locus on chromosome ...


Hormonal Therapy And Preventive Care Of Transgender Patients, Angela Chu, Jana Randolph, Austin Hopkins, Victoria Cho, Sophocles Chrissobolis Oct 2019

Hormonal Therapy And Preventive Care Of Transgender Patients, Angela Chu, Jana Randolph, Austin Hopkins, Victoria Cho, Sophocles Chrissobolis

Pharmacy and Wellness Review

Transgenderism occurs when an individual's gender identity conflicts with the individual's biological sex. A variety of methods may be used in order to reconcile this disparity in transgender individuals including psychological counseling, cross-sex hormone therapy and sex reassignment surgery. The most important role for pharmacists in the treatment of transgender patients is in dispensing hormonal medications for cross-sex treatment. Hormone therapy may be used to suppress characteristics of the patient's biological sex as well as to induce development of characteristics that correlate with the patient's gender identity. In male-to-female (MtF) transgender patients, the most commonly used ...


Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter Oct 2019

Genetic Rescue Of Fragile X Syndrome Links Fmrp Deficiency To Codon Optimality-Dependent Rna Destabilization, Huan Shu, Elisa Donnard, Botao Liu, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Fragile X syndrome (FXS) is caused by inactivation of FMR1 gene and loss of its encoded product the RNA binding protein FMRP, which generally represses translation of its target transcripts in the brain. In mouse models of FXS (i.e., Fmr1 knockout animals; Fmr1 KO), deletion of Cpeb1, which encodes a translational activator, mitigates nearly all pathophysiologies associated with the disorder. Here we reveal unexpected wide-spread dys-regulation of RNA abundance in Fmr1 KO brain cortex and its rescue to normal levels in Fmr1/Cpeb1 double KO mice. Alteration and restoration of RNA levels are the dominant molecular events that drive ...


Fmrp Control Of Ribosome Translocation Promotes Chromatin Modifications And Alternative Splicing Of Neuronal Genes Linked To Autism, Sneha Shah, Gemma Molinaro, Botao Liu, Ruijia Wang, Kimberly M. Huber, Joel D. Richter Oct 2019

Fmrp Control Of Ribosome Translocation Promotes Chromatin Modifications And Alternative Splicing Of Neuronal Genes Linked To Autism, Sneha Shah, Gemma Molinaro, Botao Liu, Ruijia Wang, Kimberly M. Huber, Joel D. Richter

University of Massachusetts Medical School Faculty Publications

Silencing of FMR1 and loss of its gene product FMRP results in Fragile X Syndrome. FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wildtype tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes; and its loss results in decline of ribosome stalling on specific mRNAs. One ...


Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma Oct 2019

Ripk1 Mediates Tnf-Induced Intestinal Crypt Apoptosis During Chronic Nf-Kappab Activation, Jerry Wong, Matija Zelic, John Bertin, Michelle A. Kelliher, Monica Guma

Open Access Articles

BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- kappaB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice.

METHODS: Human IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKbeta in IEC (Ikkbeta(EE)(IEC)), Ripk1(D138N/D138N) knockin mice, and Ripk3(-/-) mice were injected with TNF or lipopolysaccharide. Enteroids were ...