Digital Commons Network^™

Evaluation Of Drug Use In Inpatient Care: A Retrospective Study At A Tertiary Hospital In Bandung, Indonesia (2024), Aliya Rosyidah Fitrianti, Athoya Delarosa, Husna Muharram Ahadi, Imam Adi Wicaksono, Falerina Puspita

Pharmacology and Clinical Pharmacy Research

Rational drug use is a critical component of improving healthcare quality. However, irrational prescribing remains a significant concern, particularly in developing countries like Indonesia. This study evaluates drug use patterns at a Type B hospital in Bandung using WHO standard: average number of drugs per prescription, percentage of generic drugs, antibiotics, injections, and adherence to the National Formulary. A retrospective, descriptive observational method was applied, using 2024 inpatient Drug Use Evaluation (DUE) data. Findings reveal an average of 3.4 drugs per prescription—slightly above the WHO standard (≤ 3.3); 68.4% of prescriptions used generic drugs (meeting the WHO standard ≥ 59%); …

Comparative Analysis Of The Quality Of Life Of Schizophrenic Patients On Antipsychotic Treatment Between Aripiprazole Monotherapy And Combination Of Risperidone-Clozapine At Mental Hospital In West Java, Taufiqurahman Taufiqurahman, Sani Asmi Ramdani Lestari, Ardilla Kemala Dewi

Pharmacology and Clinical Pharmacy Research

Quality of life (QoL) is a critical outcome measure in schizophrenia management, yet antipsychotic side effects may negatively impact patients' well-being. Objective: This study aimed to compare the QoL of schizophrenia patients receiving aripiprazole monotherapy versus a risperidone-clozapine combination at West Java Mental Hospital. An analytical observational study with a cross-sectional design was conducted at the outpatient clinic of West Java Mental Hospital from March to May 2025. The Indonesian version of the WHOQOL-BREF questionnaire was used to assess QoL. A total of 58 outpatients with schizophrenia who met the inclusion criteria were enrolled, comprising 28 patients in the aripiprazole …

Expanding The Mutation Spectrum Of Non-Syndromic Retinitis Pigmentosa In Consanguineous Pakistani Families: Unraveling Novel Pathogenic Variants In Rp1, Pde6b, And Prcd Genes For Precision Diagnosis, Tayyaba Shan, Nimra Mukhtar, Sayyed Hammad Ullah, Asad Ullah, Asfandyar Ahmad Khan, Yumei Li, Meng Wang, Raeesa Tehreem, Amtul Aziz, Kiran Afshan, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

No abstract provided.

Inhibition Of Epac1 Prevents Neuronal Death Mediated By Diesel Exhaust Particles In Ferroptotic Cell Death Conditions, Hong Yan, Leshan Zhang, Ana L Manzano-Covarrubias, Phoeja S Gadjdjoe, Anja Land, Christina H J T M Van Der Veen, Teresa Mitchell-Garcia, Heba A Fayyaz, Marco Venema, Christoffer Åberg, Marieke Van Der Hart, Frank Lezoualc'h, Xiaodong Cheng, Amalia M Dolga, Martina Schmidt

The Brown Foundation: Institute of Molecular Medicine

Air pollution is a growing hazard to global health. Epidemiological studies have reported a potential role of air pollutant exposure in the development or aggravation of neurodegenerative diseases. However, the underlying mechanisms are ill-defined. Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of cell death that drives neuronal loss in neurodegenerative diseases. Our previous studies reported the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and EPAC (exchange protein directly activated by cAMP) in ferroptotic cell death. Here, we investigated the effects of diesel exhaust particles (DEP) in mouse hippocampal (HT22) neuronal cells. Our data showed that toxicity induced by …

The Right Time For A Synapse To Change: Windows And Mechanisms Of Multiday Training Trials, Rong-Yu Liu, Yili Zhang, Roberta Calvo, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Although learning over multiple days is more effective than a single day of training, the underlying cellular mechanisms of repeated training trials remain poorly understood. With a combination of empirical and computational approaches, we determined a critical time window for a second stimulus block of a multiday training protocol to augment long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse and long-term enhancement of neuronal excitability (LTEE), two cellular correlates of learning and memory. A second stimulus block delivered 24 h after the first block significantly enhanced LTF and LTEE, but was without effect at 18 or 32 h. This …

Erratum To ``Childhood Obesity: Global Burden, Multifactorial Etiologies, Biological Mechanisms, And Emerging Interventions For Prevention And Management'' [Saudi Medical Journal 2026; 47(2):183–194], Fahad H. Baali

Saudi Medical Journal

In the manuscript entitled: ``Childhood Obesity: Global Burden, Multifactorial Etiologies, Biological Mechanisms, and Emerging Interventions for Prevention and Management'' Published in Saudi Med J 2026; Vol. 47(2): 183–194. doi: 10.15537/1658-3175.1001
The tables included in the published version were incorrect due to a production error.

Advancing Rheumatology In The Middle East: Mrc 2025 Abstracts, Martin Lee, Ahmed Zayat, Beena Hameed, Elsadeg Sharif, Fahda Al Okaily, Fehaid Alanazi, Francis Kynaston-Pearson, Khalid A. Alnaqbi, Mahmood Hachim, Mayam Al Nesf, Mira Mirashli, Mohammed Tariq, Ravi Gutta, Reem Abdwani, Saadeya Naji, Shamma Lootah, Tareq Al Araimi, Waleed Hafiz, Suad Hannawi

Saudi Medical Journal

No abstract provided.

Prevalence Of Brca1 And Brca2 Germline Mutations In Western Saudi Patients With Epithelial Tubo-Ovarian Carcinoma, Wala Mehros, Faisal Aldaheri, Anas Alqarni, Saif Aljehani, Abdulrahman Alnamlah, Alaa Althubaiti, Safaa Huneef, Hatim Jifree

Saudi Medical Journal

Objective: Ovarian cancer represents the most lethal gynecologic malignancy, the epithelial type (EOC) being the most common. BRCA gene mutations are associated with ovarian cancer, younger age at presentation, strong family history of EOC, and multiple malignancies in a single patient. This study calculated the rate of BRCA-positive EOC and compared BRCA-mutated vs non-mutated EOC cases. Methods: This retrospective cohort study, conducted at Princess Noura Oncology Center between May 2016 and December 2023, explored outcomes in BRCA-positive EOC patients. The inclusion criteria covered all EOC cases. A total of 70 patients were selected. Results: Of the 70 …

Combined Predictive Value Of Serum Ngal, Cysc, Urinary Nag, And Egfr For Sepsis-Associated Acute Kidney Injury In Patients In Icu, Yu Han, Wenna Ning, Jian Lu, Jinwei Zhu, Zhiliang Qin, Xiao Wang

Saudi Medical Journal

Objective: To evaluate critically ill patients who had sepsis and how various kidney-related measurements, including eGFR, NGAL, CysC, and the urinary enzyme NAG, predict the onset of sepsis-induced renal damage. Methods: The 135 individuals who were admitted to our sepsis intensive care within 2 years to the end of early 2024 were recruited on a prospective basis and were enrolled based on the predefined criteria. Upon admission, they were dichotomized into 2 groups of participants who developed septic-associated kidney injury (82) and without (53). A comparison of baseline laboratory analyses and blood and urine baseline examinations in the groups was …

Tumor-Associated Neutrophils In Advanced Non-Small Cell Lung Cancer Patients Predicted By Clinicopathologic Characteristics And Peripheral Blood Markers, Weiwei Hong, Xie Xiong, Chen Fang, Chuanhong Luo, Xiaoying Qian, Xinyuan Yao, Xin Ye, Biao Yu, Bingbiao Zhou, Dengying Chen, Chengsi Shu, Yong Wang, Yong Li

Saudi Medical Journal

Objectives: The process of analyzing tumor-associated neutrophils (TANs) types is complex. This study explored the relationships among clinicopathological characteristics, peripheral blood markers, and TANs. Methods: Clinical information was retrospective gathered for 115 patients in our hospital from May 2019 to May 2021, and multiplex immunofluorescence staining was utilized to access the expression of TANs and analyze the potential relationship between TANs and clinicopathological features or peripheral blood markers. Results: Among the 115 patients, the proportion of female patients within the neutrophils (N1)-low group was notably greater compared to the N1-high group (87.5% vs. 12.5%, p = 0.022). In nonsmoking patients, …

Clinical Role Of Hematologic Inflammatory Markers In The Diagnosis Of Missed Abortion, Mustafa Bakırcı, Çağlayan Ateş, Ethem S. Yalvaç

Saudi Medical Journal

Objectives: To evaluate the diagnostic value of hematological and biochemical inflammatory markers in distinguishing missed abortions from healthy pregnancies during the first trimester. Methods: This retrospective case-control study was conducted between May 2022 and May 2024, included 61 women diagnosed with missed abortion by ultrasound and 100 healthy pregnant women who acted as controls. The following inflammatory markers were calculated from routine blood and biochemistry results: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), lymphocyte-monocyte ratio (LMR), systemic immune-inflammation index (SII) and C-reactive protein-albumin ratio (CAR). Intergroup comparisons and receiver operating characteristic (ROC) curve analyses were performed. Results: The …

Integrative Approaches To Gut Microbiota: Biomarkers, Dysbiosis, And Therapeutic Potential, Zeyad M. Alharbi

Saudi Medical Journal

The human gut contains bacteria, viruses, and archaea that influence health depending on age, diet, and location. An individual harbours about 150 bacterial species. An imbalance of these microorganisms, known as dysbiosis, can negatively impact health. Commensal bacteria maintain microbial homeostasis by building short chain fatty acids. The 2-way communication channel that connects the gut and the brain is referred to as the gut-brain axis. Dysbiosis of the gut leads to some autoimmune diseases. A decline of beneficial bacteria causes the progression of rheumatoid arthritis. Gut dysbiosis increases intestinal permeability, allowing toxins and cytokines to enter the bloodstream and damage …

Emerging Nanotherapy Applications In Cancer Treatment: A Comprehensive Review, Waleed H. Mahallawi

Saudi Medical Journal

This comprehensive review synthesizes recent advances in cancer nanotherapy, focusing on 6 emerging categories: immunomodulation, gene/RNA delivery, theranostics, radiosensitization, biomimetic carriers, and artificial intelligence (AI)-guided formulations. These innovative platforms demonstrate transformative potential by overcoming key limitations of conventional cancer treatments. Immunomodulatory nanoparticles reprogram tumor microenvironments and convert immunologically ``cold'' tumors to ``hot'' responsive states. Gene delivery systems enable precise editing with >50% efficiency, while theranostic platforms integrate real-time imaging with targeted therapy. Radiosensitizers amplify local radiation dose by twofold, and biomimetic carriers achieve prolonged circulation through immune evasion. An AI-driven approaches optimize personalized formulations based on patient-specific biomarkers. Clinical evidence …

Treatment Of Odontogenic Sinusitis With Oroantral Communication And Fistula: A Systematic Review And Meta-Analysis, Rana R. Alharbi, Omar F. Alnajar, Reham E. Almahdi, Salman A. Alrougi, Remas A. Alshehri, Ruyuf A. Alotaibi, Shahad S. Alharbi, Manal A Eltahir, Yahya A. Fageeh

Saudi Medical Journal

Objective: To assess the available data regarding medicinal, surgical, and combination therapy approaches for odontogenic sinusitis linked to OAC and OAF. Oroantral communication (OAC), an atypical connection between the oral cavity and maxillary sinus, commonly arises following upper jaw procedures, trauma, or infection. Chronic odontogenic maxillary sinusitis may result from OAC developing into an oroantral fistula (OAF) if treatment is not received. Recurrent infections and functional difficulties can be avoided by managing these illnesses effectively. Methods: A systematic search was conducted in National Library of Medicine's (PubMed [MEDLINE]) and Google Scholar for studies published between 2000 and 2024. A total …

Mental Health In Relation To Parental Absence: A Systematic Review, Mohammed Barry, Abdulaziz Alyahyawi, Heba Jafar Sabbagh

Saudi Medical Journal

Objective: To evaluate the literature based on the relationship between orphaned children and mental health, compared to non-orphaned children. Mental well-being of orphaned children is a profound intricate topic that connects with broader concerns of childcare. This systematic review aims to evaluate the literature regarding the relationship between mental health and parental absence. Methods: We conducted a systematic search of PubMed, MEDLINE, and Science Direct in October 2025, with 1017 screened studies. Six studies met the inclusion criteria. Independent reviewers performed quality assessments using the Newcastle-Ottawa scale (NOS). Subsequently, a meta-analysis was performed when possible. Results: Findings indicate that orphaned …

Yap Induces A Prorenewal Metabolic State In Cardiomyocytes, Lin Liu, Jeffrey D Steimle, Chang-Ru Tsai, Fansen Meng, Yuka Morikawa, Yi Zhao, Sandra Carmichael, Xiao Li, James F Martin

Faculty, Staff and Students Publications

BACKGROUND: Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal. Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair. YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND/AIM: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

MATERIALS AND METHODS: Phosphorus (³²P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

RESULTS: A total of 35 out of the 588 genes were differentially expressed, with either log₂ ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤-1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and …

Methionine Restriction Enhances Platinum-Based Chemotherapy-Induced Immunogenic Cell Death In Triple Negative Breast Cancer Cells, Mallory Thompson, Laura Sipe Ph.D.

Departmental Honors & Graduate Capstone Projects

When cancer cells are treated with chemotherapy, they can release Damage-Associated Molecular Patterns (DAMPs) as they die that can alert and engage the immune system, a process known as an immunogenic cell death (ICD). The dying cancer cell can release certain molecules, including ATP or calreticulin, that immune cells first recognize as abnormal before initiating an anti-tumor response. However, not all chemotherapies cause the release of these beneficial signals as they kill the cell. This study aims to determine whether a specific deprivation technique, called methionine restriction, enhances the ICD process and DAMP expression when used in conjunction with chemotherapy …

Contribution Of The M1 Vs M2 Phenotype Toward Macrophage Interactions With Streptococcus Mutans, The Dominant Bacteria In The Oral Cavity, Isabelle K. Wintz

Honors Thesis

We are all exposed to numerous pathogens every day. One of the sites for pathogens to interact with our body is in the mouth. To better understand these interactions between bacteria and host immune cells, I developed an assay to study the oral bacteria Streptococcus mutans and inflammatory macrophages. Our hypothesis was that the cytokines IL-4 and IFN-y would alter macrophage phenotypes with IL-4 reducing inflammatory responses and IFN-y increasing inflammation.  To test this, we performed experiments in cell culture as a first step toward understanding the severity of the host response at the cellular and molecular levels. Our results …

Association Between Maternal Factors And Stunting Based On The Indonesia Family Life Survey 5 (Ifls-5), Charissa Otniel Sukamto, Siti Nur Fatimah, Noormarina Indraswari

Makara Journal of Health Research

Background: Stunting remains a major issue in Indonesia. Maternal factors during pregnancy are one of the key determinants in preventing stunting. This study aimed to analyze the association between maternal history during pregnancy (age, height, parity, and inter-pregnancy interval) and stunting, with a comparison between urban and rural areas.

Methods: This analytical cross-sectional study used data from 3,639 children aged 1-5 years old from the household survey of Indonesia Family Life Survey 5, conducted between late October 2014 and August 2015 within 13 provinces in Indonesia. Data was analyzed using chi-square and binary logistic regression methods.

Results: …

Knowledge Of Parents And Guardians Of Computed Tomography Examinations And Radiation Risks In Children In Malaysia, Nur Maisarah Ali Wahab, Nur Hamizah Mohd Zainudin

Makara Journal of Health Research

Background: Early exposure to computed tomography (CT) imaging during childhood increases cancer risk, emphasizing the critical need to minimize unnecessary imaging in pediatric patients. This study aimed to assess parents and guardians’ knowledge about CT examinations and their associated risk following pediatric CT.

Methods: A cross-sectional survey was conducted among parents and guardians who accompanied their children to a private hospital radiology department for CT examinations. The survey enquired about their socio-demographic, knowledge of CT examinations, and their radiation risks. Data were analyzed using descriptive analysis and the Kruskal-Wallis test.

Results: A total of 144 responses were …

Effects Of Limb Dominance On Dopaminergic Neurodegeneration In A 6-Ohda Rat Model Of Parkinson’S Disease Assessed By Immunoblotting, Jasin Aziz Porshia, Deanna Chaialee, Dipesh Pokharel, Kala Venkiteswaran, Thyagarajan Subramanian, Dilshan Beligala

ONU Student Research Colloquium

Effects of Limb Dominance on Dopaminergic Neurodegeneration in a 6-OHDA Rat Model of Parkinson’s Disease Assessed by Immunoblotting

Jasin Porshia^a , Deanna Chaialee^a , Dipesh Pokharel^b,c , Kala Venkiteswaran^{b, c, d} , Thyagarajan Subramanian^{b, c, d}, Dilshan Beligala^a

^aDepartment of Biological Sciences, Ohio Northern University, Ada, OH, USA

^bDepartment of Neurosciences and Psychiatry, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

^cDepartment of Neurology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA

^dDepartment of Neurology, Howard University, Washington, DC, …

Disruption Of The Lrrk2 Substrate Rab12 Facilitates Neurotransmission And Causes Hyperactivity In Mice, Xingjian Li, Yuanxin Chen, Huaixing Wang, Xue Zhang, Noah Guy Lewis Guiberson, Xianting Li, Jacqueline Burré, Junmin Peng, Hui Zhang, Zhenyu Yue

Department of Neuroscience Faculty Papers

RAB12 is a small GTPase and a validated substrate of LRRK2, a kinase genetically linked to Parkinson's disease (PD). While RAB12-LRRK2 signaling has been implicated in ciliogenesis and immune regulation, the neuronal function of RAB12 remains largely unexplored. Here, we investigated the role of RAB12 in synaptic physiology using Rab12 knockout (KO) mice. Rab12 KO mice developed normally but exhibited increased locomotor activity in adulthood. Electrophysiological recordings from striatal slices revealed enhanced presynaptic release probability and increased excitatory drive onto medium spiny neurons. Consistently, live-cell imaging of cultured cortical neurons revealed that Rab12 deletion facilitated, while Rab12 overexpression inhibited, synaptic …

Engineering Function In Lung Biology: Integrating Imaging, Regenerative Constructs, And Functional Biodesign, Rene A Girard, Jamie Tran, Yuqing Cai, Mary C Farach-Carson, Hadi T Nia, Allison M Greaney, Laura E Niklason, Killian Hurley, Elvin Blanco, Sinem Koc-Günel, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The lung is a uniquely demanding target for regeneration because function depends on the coordinated integration of cellular diversity, three-dimensional architecture, cyclic mechanical forces, vascular perfusion, immune surveillance, and extracellular matrix remodeling. While single-cell and spatial profiling, lineage tracing, and iPSC-derived models have transformed our understanding of lung cell states and developmental potential, these descriptive approaches have also highlighted a central bottleneck: the field still lacks broadly adopted platforms to test whether engineered tissues and regenerative interventions restore function under physiologic load. In this review, we focus on emerging technologies that enable functional biodesign in lung biology by coupling engineered …

Modeling Early Human Heart Development Using An Ipsc-Based 3d Bioprinted Model Of Embryonic Heart Tube, Linqi Jin, Christian Park, Sunder Neelakantan, Shweta Karnik, Arnab Dey, Sarah Fineman, Roshni Nandwani, Carmen J Gil, Boeun Hwang, Melissa A Cadena, Vani Sridhar, Jing Wang, Yuxiao Wu, Connor J Evans, Lan Li, Sarah Rezapourdamanab, Mehdi Salar Amoli, Martin L Tomov, Ryan K Roeder, Reza Avazmohammadi, Lakshmi Prasad Dasi, Hanjoong Jo, Eric Weeks, Holly D Bauser-Heaton, Sean M Wu, Vahid Serpooshan

Faculty, Staff and Student Publications

Human heart development depends on tightly coordinated genetic programs and biomechanical cues, yet the underlying cell-microenvironment interactions remain poorly understood because the developing heart is difficult to study in utero and accurate experimental models are lacking. Recent advances in stem cell biology and three-dimensional (3D) bioprinting now allow the construction of human tissue analogues with defined structure and function. Here we show a perfusable 3D bioprinted model of the human embryonic heart tube composed of layered myocardium, cardiac jelly, and endocardium. Human induced pluripotent stem cell-derived cardiomyocytes and endothelial cells are cultured under controlled flow conditions, producing constructs with high …

Mitochondrial Dna Replication Is Regulated By Endoplasmic Reticulum-Mitochondrial Contact Sites, The Mitochondrial Calcium Uniporter, And Manganese, Amaia Lopez De Arbina, Angelica Zamudio-Ochoa, Mikel Muñoz-Oreja, Diego Perez-Rodriguez, Laura Mosqueira-Martín, Rebecca Lasalandra, Marina Villar-Fernandez, Uxoa Fernandez-Pelayo, Laura Rodriguez-Gomez, Seungtae Lee, Francisco Gil-Bea, Nerea Osinalde, Ainara Vallejo-Illaramendi, Dmitry Temiakov, Antonella Spinazzola, Ian Holt

Department of Biochemistry and Molecular Biology Faculty Papers

Mitochondrial DNA replication occurs at contact sites between the endoplasmic reticulum (ER) and mitochondria (ERMCS). Beyond the known role of the tubular ER protein RTN4, the factors regulating this process are poorly defined. Here, we show that repressing the ER protein ERLIN2 in human fibroblasts depletes ER-mitochondrial contact sites and inhibits mitochondrial DNA replication, as does silencing RTN4 or the ER-mitochondrial tether GRP75. GRP75 or RTN4 scarcity also decreases the level of the mitochondrial calcium uniporter (MCU), whose inhibition blocks mitochondrial DNA synthesis. Because ERMCS depletion did not diminish mitochondrial calcium, and MCU complex can transport manganese, we tested whether …

Obstructive Sleep Apnea Treatment Modifies The Effectiveness Of Catheter Ablation For Atrial Fibrillation: Post Hoc Analysis Of The Cabana Trial, Matthew W Segar, Kaleb D Lambeth, Brett Doliner, Joshua R Hirsch, Abdi Rasekh, Mehdi Razavi

Faculty, Staff and Students Publications

No abstract provided.

Rhesus Macaques With An Opa1 Mutation Demonstrate Features Of Autosomal Dominant Optic Atrophy, Tracy N Jaggers, Ana Ripolles-Garcia, Ala Moshiri, Brett D Story, Jun Wang, Rui Chen, Lucy G Moore, Leandro B C Teixeira, Jaeho Shim, Ana C Raposo, Maria Isabel Casanova, Sophie M Le, Sangwan Park, Laura J Young, Soohyun Kim, Karolina P Roszak, Vanessa Ureno, Paige M Karpinen, Nayeli Echeverria, Monica Ardon, Brian C Leonard, Marguerite Knipe, Eliza Bliss-Moreau, Brad Fortune, J Timothy Stout, Jeffrey Rogers, Nicholas Marsh-Armstrong, Sara M Thomasy

Faculty, Staff and Students Publications

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy primarily caused by mutations in OPA1. We identified and defined a spontaneous nonhuman primate (NHP) model of ADOA using rhesus macaques heterozygous for a missense mutation (OPA1A8S). With ocular examinations, ophthalmic imaging, electroretinography, histopathology, immunohistochemistry, and transmission electron microscopy (TEM), we documented retinal nerve fiber layer (RNFL) thinning, retinal ganglion cell (RGC) loss and dysfunction, OPA1 mislocalization, and reduced axonal mitochondrial density in affected macaques. Our investigation revealed substantial phenotypic variability among affected macaques, shedding light on the pathogenesis of ADOA. The retinas were evaluated using techniques …

Prodromal Lewy Body Disorder Features In Rem Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy, Daniel Weintraub, Michele K York, Roseanne Dobkin, Anuprita R Nair, Ryan Kurth, David-Erick Lafontant, Chelsea Caspell-Garcia, Roy N Alcalay, Ethan G Brown, Lana M Chahine, Christopher Coffey, Tatiana Foroud, Douglas Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L Poston, Andrew Siderowf, Cristina Simonet, Tanya Simuni, Caroline M Tanner, Thomas F Tropea, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal state for Lewy body disorders and exhibits biological heterogeneity that may influence clinical expression and progression. We examined clinical features in individuals with iRBD and biomarker-defined synucleinopathy.

Methods: Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, multi-center observational study. Participants included polysomnogram (PSG)-confirmed iRBD individuals who were cerebrospinal fluid (CSF) α-synuclein seed amplification assay positive with no clinical diagnosis of Parkinson's disease or dementia with Lewy bodies, along with robust healthy controls (HCs). Clinical and biological features of prodromal PD and DLB, including mild cognitive impairment (MCI), subthreshold …

Functional Requirement For Dicer Helicase Arginine Methylation In 26 G Sirna Biogenesis And Oocyte Meiotic Program, Nick Newkirk, Shin-Yu Chen, Tokiko Furuta, Kenneth A Trimmer, Leilei Shi, Sabrina Stratton, Hongyuan Li, Xiaodong Cheng, Mark T Bedford, Swathi Arur

The Brown Foundation: Institute of Molecular Medicine

Spatiotemporal regulation of Dicer is essential for small RNA biogenesis and fertility, yet how its helicase domain is controlled remains unclear. Using Caenorhabditis elegans, we identify a regulatory role for the arginine-rich GRARR motif within helicase domain motif VI of DCR-1. Mutating conserved arginines in this sequence disrupts maternal 26 G endo-siRNA production, impairs oocyte meiosis I and II, and reduces fertility. Biochemically, an asymmetrically dimethylated DCR-1 GRA[R495*]R peptide enhances interaction with ERI-5, a tandem-Tudor protein in the ERIC complex, while loss of DCR-1(R495) diminishes this interaction in vivo. Genetically, eri-5 deletion phenocopies the dcr-1 R495K mutant, supporting a functional …