Pharmacy and Pharmaceutical Sciences Commons^™

Tracing Antibacterial Compounds From Kaledang (Artocarpus Lanceifolius Roxb.) Stem Bark, Hamsidar Hasan, Tety Tuloli, Syamsul Bahri, La Ode Aman

Pharmaceutical Sciences and Research

Artocarpus lanceifolius Roxb. or kaledang is a species of the mulberry family, Moraceae. Several extracts from its family have been reported to have antibacterial activity. Thus, it is necessary to determine compounds that have nature as antibacterial to be raw materials for antibacterial herbal medicines. The purpose of the study was to trace compounds that have antibacterial activity from Artocarpus lanceifolius stem bark. The study method was extraction by graded maceration, fractionation with column vacuum chromatography (CVC), isolation by radial chromatography, determination of antibacterial activity by agar diffusion method using the Gram positive and Gram negative bacteria. The characterization …

Antimicrobial Activity Of Crude Fractions Of Gossypium Barbadense Leaves And Isolation Of Stigmasterol, Maryam Saddiq, Ahmed Salisu, Kamaluddeen Kabir, Yusuf Hassan

Pharmaceutical Sciences and Research

Plants have been used in traditional medicine in different parts of the world to treat several diseases. Many studies have confirmed their medicinal values, which have led to the isolation and characterization of various potential drug candidates. This study focuses on the antimicrobial activity of crude fractions of Gossypium barbadense leaves and the isolation of active compound. The pulverized plant leave was soaked in ethanol (98% v/v), and a solvent-based fractionation was carried out using n-hexane, chloroform, ethyl acetate, and ethanol. The obtained crude fractions were screened for antimicrobial activity against four (4) clinical isolates: Escherichia coli, Pseudomonas …

Subchronic Toxicity Study Of Sterculia Rubiginosa Zoll. Ex Miq. Leaves Extract, Rini Prastiwi, Ester Hidayati, Riska Anggraini, Cut Mauliza, Ita Anggraini, Ema Dewanti

Pharmaceutical Sciences and Research

Ki hampelas (Sterculia rubiginosa Zoll. Ex Miq.) is traditionally used as an antiasthma. It also reported has antioxidant and nephroprotective activity. This study was conducted to evaluate the subchronic toxicity of the leaf extract of ki hampelas. The extract was orally administered to male and female Sprague-Dawley rats at doses of 50, 200, and 400 mg/kg bodyweight (BW) per day for 28 days. The rats were divided into four groups, consist of consist of normal group (Na CMC 0.5%), dose 1 (50 mg/kg BW), dose 2 (200 mg/kg BW), and dose 3 (400 mg/ kg BW) of extract. The …

Antioxidant Activities Of Roja Herbal Tea: Combination Of Rosella Flower (Hibiscus Sabdariffa L.) And Ginger Rhizome (Zingiber Officinale Rosc.), Wahyu Widowati, Teresa Liliana Wargasetia, Teddy Marcus Zakaria, Michael Sebastian Gunadi, Nathanael Halim, Sherly Santiadi, Hanna Sari Widya Kusuma, Nida Firyal Fauziyah

Pharmaceutical Sciences and Research

Herbal teas and plant-based medicines have been widely used worldwide for their therapeutic and healing qualities. Rosella (Hibiscus sabdariffa L.) has various benefits in preventing digestive problems, liver disease, fever, and others. Ginger (Zingiber officinale Rosc.) or known as jahe in Indonesia is believed to benefit numerous clinical conditions linked to oxidative stress, including pancreatitis, hypertension, diabetic kidney disease, Alzheimer’s disease, and tumor development. They have been utilized in traditional medical practice to treat conditions such as fever, nausea, and headaches. In this study, we aimed to determine the antioxidant activities of rosella flower tea, ginger tea, and …

Colon Targeted Delivery Dosage Forms For Probiotics: A Review, Gede Anom Anjasmara, Pietradewi Hartrianti, Raditya Iswandana

Pharmaceutical Sciences and Research

Encapsulation was a promising method for protecting probiotics from extreme conditions during their passage through the gastrointestinal tract and delivering probiotics to specific sites in the colon for colonization. Various dosage forms have been used in recent years to encapsulate probiotics to maintain cell viability during processing, storage, and through the digestive tract to provide health benefits. However, research related to the encapsulation of probiotics as the dosage forms for colon-targeted delivery systems was still quite limited to conventional dosage forms due to the sensitivity of probiotics to extreme conditions during the process. This review focuses on various types of …

Exploring Rosella (Hibiscus Sabdariffa L.) Calyx Extracts As Natural Dye And Antioxidants In Lip Cream Product: Formulation And Evaluation, Donna Maretta Ariestanti, Abdul Mun'im, Joshita Djajadisastra, Riska Amalia Putri Hutami, Redhalfi Fadhila, Richard Johari James

Pharmaceutical Sciences and Research

Rosella, also known as Hibiscus sabdariffa L., is a plant that contains anthocyanin compounds in its calyx, which are known for their antioxidant properties. These compounds give the plant a captivating red color and can be used as natural dyes. This study aimed to exploit anthocyanins in rosella calyx as natural dyes and antioxidants in lip cream product. The formulations employed extracts from rosella calyx, a viscous extract from maceration in 96% ethanol (F1) and a commercially available powdered rosella extract (F2). Evaluation on the formulations demonstrated that both F1 and F2 effectively maintained the color integrity of the lip …

Study Of Anti-Hyperuricemia, Anti-Inflammatory, And Anti-Nociceptive Effects Of Hylocereus Undatus Stem Bark Extract In Animal Models, Tri Wahyuni, Sartika Harka Putri, Anton Bahtiar

Pharmaceutical Sciences and Research

Dragon fruit, known as Hylocereus undantus (HU), has traditionally been utilized in Banyuwangi, East Java, Indonesia, for addressing gout and rheumatism. Despite its empirical use, there is a lack of reported pharmacological research on this plant. This study aimed to explore the properties of HU extract in treating hyperuricemia, inflammation, and pain. Adenine-potassium oxonate-induced mice were employed to evaluate anti-hyperuricemia activity, measuring uric acid, blood urea nitrogen (BUN), and creatinine serum levels. Carrageenan-induced paw edema in rats was used to assess anti-inflammatory activity, while acetic acid-induced abdominal writhing and hot plate tests were conducted to investigate anti-nociceptive effects. The results …

The Potential Of Herbal Combinations As Adjunctive Therapy For Standard Care Of Covid-19 Patients: A Lesson Learned From Indonesia, Anna Rozaliyani, Satria Pratama, Findra Setianingrum, Fenny Yunita, C. Martin Rumende

Pharmaceutical Sciences and Research

The pandemic of novel coronavirus disease (COVID-19) has become a global disaster that occurred between the end of 2019 and 2023. It caused immeasurable damage to almost all aspects of human life. The disease has opened a lot of new perspectives on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) origins and pathogenesis, the nature of the virus, the potential for new treatments, and new policies to overcome this pandemic. This review aims to know the potential of plants that are beneficial to combat the diseases, including immunomodulators in the management of COVID-19. Studies reporting COVID-19 with the keywords SARS-CoV-2, COVID-19, …

Functionalized Surface Of Plga Nanoparticles In Thermosensitive Gel To Enhance The Efficacy Of Antibiotics Against Antibiotic Resistant Infections In Endodontics: A Randomized Clinical Trial, Mona Arafa, Hadeel Moussa, Mohamed Medhat Kataia

Pharmacy

Enterococcus faecalis plays the key role in endodontic infections and is responsible for the formation of biofilm on dentin, which causes a resistance against periradicular lesions treatment, consequently the aim of this study is to use nanoparticles entrapping anibacterial agents coated with chitosan that in authors previous study showed a successful in vitro biofilm inhibition, additionally incorporated in thermoresponsive gel.to benefit nanoparticles` small size, and the positive charge of their surfaces that binds with the negatively charged surface of bacterial cell causing its destruction, in addition to the sustained release pattern of the drug based nanoparticles in gel. Therefore, Ciprofloxacin …

Utilization Of Semiconductor Nanocrystals In Cancer Diagnose And Treatment, Yasir Q. Almajidi, Ahmed A. Albadri, Mazen M. Jwaid, Yaseen T. Khalaf

Maaen Journal for Medical Sciences

In contemporary times, nanotechnology has emerged as a notably sophisticated technological discipline. It possesses an interdisciplinary and multidisciplinary nature, spanning a wide array of domains including medical science, engineering, biology, physics, materials science, and chemistry. Utilization of nanotechnology offers a significant advantage by enabling precise manipulation and control of properties to effectively address specific challenges in various applications. In the fields of science and biomedicine, there has been extensive exploration into the use of functional nanomaterials, emerging as rapidly advancing and captivating areas of research. Diverse types of nanomaterials, including silicon nanowires, quantum dots, carbon nanotubes, and gold/silver nanoparticles, which …

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Tolfenamic Acid Derivatives: A New Class Of Transcriptional Modulators With Potential Therapeutic Applications For Alzheimer’S Disease And Related Disorders, Juanetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ourarhni, Nasser H. Zawia

Pharmacy Faculty Articles and Research

The field of Alzheimer’s disease (AD) has witnessed recent breakthroughs in the development of disease-modifying biologics and diagnostic markers. While immunotherapeutic interventions have provided much-awaited solutions, nucleic acid-based tools represent other avenues of intervention; however, these approaches are costly and invasive, and they have serious side effects. Previously, we have shown in AD animal models that tolfenamic acid (TA) can lower the expression of AD-related genes and their products and subsequently reduce pathological burden and improve cognition. Using TA as a scaffold and the zinc finger domain of SP1 as a pharmacophore, we developed safer and more potent brain-penetrating analogs …

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …

Development And Evaluation Of A Nanofiber Membrane In Vitro As A Therapeutic Alternative For The Post Treatment In Breast Cancer Cell In A Murine Model, Bruno A. Valades-Aguilar, Diana Ginette Zarate-Triviño, José Raúl Rángel-López, Moises Armides Franco-Molina, Jorge Luis Menchaca-Arredondo, María Cristina Rodríguez-Padilla

Research Symposium

Worldwide female breast cancer is the most commonly diagnosed cancer, with an estimated 2.3 million new cases in 2020, reason for the need of targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles of gold (AuNps) exhibit cytotoxic properties against certain types of cancer cell lines. Nanofibers have been use in the drug delivery systems due to its degradability and high surface area. We proposed a membrane with nanometric fibers using polivinilic alcohol (PVA) and chitosan (Qts) loaded with AuNps and Doxorubicin (Doxo) with the purpose of diminish tumor regression.

PVA-Qts membrane was develop with electrospinning, the injection, …

Spanlastics Nanovesicles: An Emerging And Innovative Approach For Drug Delivery, Shaimaa N. Abd Alhammid, Hanan J. Kassab, Lina S. Hussein, Mahmood A. Haiss, Hussein K. Alkufi

Maaen Journal for Medical Sciences

The use of vesicular structures as a drug delivery method has many advantages, including extending the duration of the drug's action in circulation, enhancing drug targeting, minimizing adverse effects, and boosting the bioavailability of a variety of medications. Spanlastics, which are elastic and can transport a range of pharmaceutical substances, are thought to be a subset of nanovesicles. They have drawn interest as a potentially effective medicine delivery method. They are a preferred choice for many administration routes because of their pliable and elastic nature, which allows them to pass through various cellular membranes. Non-ionic surfactants or a mixture of …

Solid Lipid Nanoparticles (Sln): Formulation And Fabrication, Gabriella F. Punu, Yahdiana Harahap, Qonita Kurnia Anjani, Pietradewi Hartrianti, Ryan F. Donnelly, Delly Ramadon

Pharmaceutical Sciences and Research

Solid lipid nanoparticles (SLN) have emerged as a novel drug delivery system and have been utilized for delivering various kinds of drugs since the 1990s. These particles may consist of multiple solid lipids, including glycerides, waxes, and fatty acids, and can be stabilized by a wide range of surfactants. SLN have garnered significant attention from researchers due to its innovative and versatile nature. Moreover, such delivery system has numerous advantages over traditional colloidal carriers, such as liposomes, polymeric nanoparticles, and emulsions. Several research groups have been developing SLN formulations and fabrication techniques based on their intended purpose, and this research …

Evaluation Of Anti-Vegf And Pan-Retinal Photocoagulation Laser Therapies In Proliferative Diabetic Retinopathy Patients: A Systematic Review, Senyum Indrakila, Namira Putri Imani, Aiman Hilmi Asaduddin, Muzakiya Lailatul Karima, Lygia Angelica Widjaja

Pharmaceutical Sciences and Research

Diabetic retinopathy is a complication of diabetes that is one of the top five causes of blindness in those over 50. The standard treatment is pan-retinal photocoagulation, which is effective but has established side effects. Anti-vascular endothelial growth factor (anti-VEGF) therapy becomes an alternative to avoid the side effects caused by laser therapy. This systematic review aims to know the effectiveness of anti-VEGF therapy compared to the pan-retinal photocoagulation laser therapy in patients with proliferative diabetic retinopathy. This review was carried out using a systematic review checklist on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The articles reviewed …

Utilization Of Pvp-Pla Combination In Fabricating Theophylline-Loaded Filament For 3d Printing With Immediate Release Behavior, Arief Kurniawan, Silvia Surini

Pharmaceutical Sciences and Research

Fused deposition modeling (FDM), known as a highly effective 3D printing technique, holds promise as an alternative approach to tablet manufacturing. While commonly employing thermoplastic polymers as starting materials, the integration of established pharmaceutical excipients remains unexplored. Polyvinyl pyrrolidone (PVP) is a frequently used excipient known for its potential to confer immediate-release properties to drugs. However, its suitability for extrusion is hindered by its thermal and melt-rheological properties. In contrast, polylactic acid (PLA), which has robust mechanical strength and thermal plasticity, was expected to overcome PVP’s limitations. This study aims to obtain drug-loaded filaments using the combination of PVP and …

Optimization Of 3,4-Dimethoxychalcone And Rutin Containing Gel With Simplex Lattice Design And In Vitro-In Vivo Test As A Sunscreen, Hana Anisa Fatimi, Abdul Karim Zulkarnain, Marlyn Dian Laksitorini

Pharmaceutical Sciences and Research

3,4-Dimethoxychalcone and rutin, a flavonoid that contains chromophore groups, can absorb UV light and thus can be developed as a sunscreen. The objective of this study was to determine the optimum formula of 3,4-dimethoxychalcone and rutin containing gel, evaluate its physical stability, and activity of 3,4-dimethoxychalcone and rutin gel as a sunscreen through in vitro and in vivo tests. HPMC, CMC-Na, and methylcellulose were formulated into a gel base to obtain good adhesion and a clear appearance gel. Simplex Lattice Design (SLD) with Design Expert software version 10 was utilized to determine the optimum gel formulation. UVA-PF protection, photostability with …

Optimization Of Lubrication And Compression Process Parameters Of Vitamin C Film-Coated Caplets, Ernestine Arianditha Pranasti, Ratna Annisa Utami, Yuda Prasetya Nugraha

Pharmaceutical Sciences and Research

Tablet production is a very intricate process influenced by numerous process variables or parameters. This study aimed to identify the critical processing variables that affect Critical Quality Attributes (CQAs) of vitamin C film-coated caplets utilizing a statistical experimental design. A two-level complete factorial design with two central points was used to examine the process parameters that posed the greatest risk to CQAs. The process variables investigated included mesh size and duration for the lubrication process, as well as speed and main thickness for compression. Statistical results showed that mesh number, lubrication time, and their interaction significantly affect flow rate, Hausner …

Individual And Combined Effect Of Eudragit® Rs 100 And Eudragit® Rl 100 On Sustained Release Characteristics Of Ropinirole Hcl-Loaded Microparticles, Aamir Hayyat, Nabeel Siddique

Pharmaceutical Sciences and Research

Ropinirole HCl is a non-ergoline dopamine agonist which is recommended for the treatment of both Parkinson’s disease and Restless Legs Syndrome (RLS). Its half-life is about 6 hours and it is metabolized in the liver primarily by CYP1A2. Its metabolites are water-soluble and rapidly excreted from the body in urine. However, its oral bioavailability is low. Therefore, this current project aimed to produce and evaluate sustained release ropinirole microparticles coated with Eudragit^® RS 100 and RL 100 by varying polymer types and concentrations. Ropinirole microparticles were prepared by oil in oil emulsion solvent evaporation technique. Emulsifier concentration was constantly …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Advanced Mesoporous Silica Nanoparticles: Synthesis, Characteristics And Applications, Asmaa Abdelaziz Mohamed, Marwa Malik Kamil, Firas Aziz Rahi, Noor Zuhair Kbah

Maaen Journal for Medical Sciences

Recent breakthroughs in pharmaceutical delivery methods employing a range of carriers have radically transformed modern diagnostic and therapeutic practices. Mesoporous silica nanoparticles (MSNs) were created due to the demand for substances with superior thermal and chemical capabilities. These ordered porous substances have generated a lot of interest as carriers due to their distinct advantages over the competition. They may be made economically using a simple process. Moreover, the shape, pore size, and particle size may all be changed by modifying the synthesis's conditions. Investigations on MSNs as drug carriers have reportedly accelerated in recent years, highlighting the potential benefits of …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

Spending On Phased Clinical Development Of Approved Drugs By The Us National Institutes Of Health Compared With Industry, Edward W. Zhou, Matthew J. Jackson, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The launch of the Advanced Research Projects Agency for Health to advance new cures and address public concern regarding drug prices has raised questions about the roles of government and industry in drug development.

This cross-sectional study examined NIH funding for published research reporting the results of phased clinical trials of drugs approved between 2010 and 2019 and compared the findings with reported industry spending estimates. Data analysis was performed between May 2021 and August 2022 using PubMed data from January 1999 through October 2021 and NIH Research Portfolio Online Reporting Tools Expenditures and Results data from January 1999 through …

Cyclic Peptides With Antifungal Properties Derived From Bacteria, Fungi, Plants, And Synthetic Sources, Naiera M. Helmy, Keykavous Parang

Pharmacy Faculty Articles and Research

Fungal infections remain a significant concern for human health. The emergence of microbial resistance, the improper use of antimicrobial drugs, and the need for fewer toxic antifungal treatments in immunocompromised patients have sparked substantial interest in antifungal research. Cyclic peptides, classified as antifungal peptides, have been in development as potential antifungal agents since 1948. In recent years, there has been growing attention from the scientific community to explore cyclic peptides as a promising strategy for combating antifungal infections caused by pathogenic fungi. The identification of antifungal cyclic peptides from various sources has been possible due to the widespread interest in …

Computer-Aided Drug Design Of Bakuchiol-Inspired Lxrα Modulators Against Acute Lymphoblastic Leukemia, Dillon P. Cao

LSU Master's Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of pediatric malignancies. Although glucocorticoids are commonly used to treat ALL, prolonged use can lead to steroid resistance, rendering the drug regimen ineffective. Therefore, alternative treatment avenues are needed for high- risk pediatric patients that do not respond well to traditional regimens.

Liver X Receptor α (LXRα) is presented as a potential alternative drug target for pediatric patients that exhibit suboptimal response to glucocorticoids. Limitations of the current LXRα modulators such as indiscriminate isoform selectivity between LXRα and LXRβ and consequent adverse effects …

Magnetic Resonance Image-Based Estimates Of Hepatic Blood Flow In Children With And Without Obesity; Implications For Physiologically-Based Pharmacokinetic Models, Yoon Cho, Sherwin S. Chan, Chance S. Friesen, Valentina Shakhnovich

Research Days

Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.

Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.

Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence …

The Opioid Epidemic: How Genetics Play A Role In Addiction And Treatment, Kirsten Houston

Honors College Theses

The opioid epidemic is an issue within the pharmaceutical industry in the United States of America due to prescription and non-prescription substances being made available to the population. Opioids include chemical substances that affect the body and brain through opioid receptors, including the mu, kappa, and delta receptors. These substances are derived and synthesized from the poppy plant. Multiple causes have been linked to opioid abuse disorder, including but not limited to employment, income, housing, nutrition, mental health disorders, and genetics. By gathering information from previous literature, genetics may be the main cause of narcotic analgesic tolerance and abuse. Specific …