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Full-Text Articles in Chemical Actions and Uses

Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye Jan 2024

Stevens-Johnson Syndrome From Combined Allopurinol And Angiotensin-Converting Enzyme Inhibitors: A Narrative Review, Isabella M. Fabian, Kirsten Maddox, Cameron Robicheaux, Rahib K. Islam, Ahmed Anwar, Bradley Dorius, Christopher L. Robinson, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive …


Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye Aug 2023

Topiramate (Topamax): Evolving Role In Weight Reduction Management: A Narrative Review, Irza Wajid, Alexis Vega, Katherine Thornhill, Jack Jenkins, Chandler Merriman, Debbie Chandler, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, …


Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari Jul 2023

Targeting Mcl-1 By A Small Molecule Nsc260594 For Triple-Negative Breast Cancer Therapy, Shengli Dong, Margarite D. Matossian, Hassan Yousefi, Maninder Khosla, Bridgette M. Collins-Burow, Matthew E. Burow, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased …


High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin Jul 2023

High Glucose-Upregulated Pd-L1 Expression Through Ras Signaling-Driven Downregulation Of Ptrh1 Leads To Suppression Of T Cell Cytotoxic Function In Tumor Environment, Chenggang Gao, Jiaoshun Chen, Jianwei Bai, Haoxiang Zhang, Yanyi Tao, Shihong Wu, Hehe Li, Heshui Wu, Qiang Shen, Tao Yin

School of Graduate Studies Faculty Publications

Background: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. Methods: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding …


Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun Jul 2023

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …


Reasons For Ineligibility For Clinical Trials Of Patients With Medication-Resistant Epilepsy, Wesley T. Kerr, Hai Chen, Mariana Figuera Losada, Christopher Cheng, Tiffany Liu, Jaqueline French Mar 2023

Reasons For Ineligibility For Clinical Trials Of Patients With Medication-Resistant Epilepsy, Wesley T. Kerr, Hai Chen, Mariana Figuera Losada, Christopher Cheng, Tiffany Liu, Jaqueline French

School of Medicine Faculty Publications

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for …


A Modern Multimodal Pain Protocol Eliminates The Need For Opioids For Most Patients Following Total Knee Arthroplasty: Results From A Retrospective Comparative Cohort Study, Leland Van Deventer, Amy Bronstone, Claudia Leonardi, Matthew Bennett, Peter Yager, Vinod Dasa Feb 2023

A Modern Multimodal Pain Protocol Eliminates The Need For Opioids For Most Patients Following Total Knee Arthroplasty: Results From A Retrospective Comparative Cohort Study, Leland Van Deventer, Amy Bronstone, Claudia Leonardi, Matthew Bennett, Peter Yager, Vinod Dasa

School of Medicine Faculty Publications

Purpose: Modern multimodal analgesia has been shown to significantly reduce opioid use following total knee arthroplasty (TKA). This study was conducted to determine if changing TKA discharge opioid prescriptions from automatic to upon request resulted in more opioid free recoveries without compromising pain control. Methods: Between December 2019 and August 2021, an orthopedic surgeon performed 144 primary unilateral TKAs; patients received the same multimodal analgesia protocol except for postoperative opioid prescribing. The first consecutively-treated cohort automatically received an opioid prescription following discharge (automatic group) and the second cohort received opioid prescriptions only upon request (upon request group). Opioid prescription data …


H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam Feb 2023

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …


Colchicine, Covid-19 And Hematological Parameters: A Meta-Analysis, Musharraf Sarwar, Zahid Ali, Mahnoor Fatima, Zouina Sarfraz, Azza Sarfraz, Ivan Cherrez-Ojeda Oct 2021

Colchicine, Covid-19 And Hematological Parameters: A Meta-Analysis, Musharraf Sarwar, Zahid Ali, Mahnoor Fatima, Zouina Sarfraz, Azza Sarfraz, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: Colchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients.
Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, …


Retrospective Review Of Anticoagulation Regimens Used For The Prevention Of Venous Thromboembolisms In Critically Ill Patients Infected With Sars-Cov-2, Tony Nguyen, Heidi Clarke Dec 2020

Retrospective Review Of Anticoagulation Regimens Used For The Prevention Of Venous Thromboembolisms In Critically Ill Patients Infected With Sars-Cov-2, Tony Nguyen, Heidi Clarke

All Publications

No abstract provided.


A Comparison Of 4-Year Total Medical Care Costs, Adverse Outcomes, And Opioid/Prescription Analgesic Use For 3 Knee Osteoarthritis Pain Treatments: Intra-Articular Hyaluronic Acid, Intra-Articular Corticosteroids, And Knee Arthroplasty., John Mackowiak, John T Jones, Vinod Dasa Dec 2020

A Comparison Of 4-Year Total Medical Care Costs, Adverse Outcomes, And Opioid/Prescription Analgesic Use For 3 Knee Osteoarthritis Pain Treatments: Intra-Articular Hyaluronic Acid, Intra-Articular Corticosteroids, And Knee Arthroplasty., John Mackowiak, John T Jones, Vinod Dasa

School of Medicine Faculty Publications

To compare the medical costs associated with treatments for knee osteoarthritis (OA): intra-articular corticosteroids (ICS) and intra-articular hyaluronic acid (IHA) primarily, and ICS/IHA vs knee arthroplasty (TKA) secondarily. This was a retrospective analysis of an insurance claims database. Eligible members had diagnosed OA and no claims for ICS, IHA, or TKA during the 6–18-month look-back period. Cohorts of interest over the 4-year observation period were: patients who received ICS only, those who received IHA only, and those who received TKA only. Outcomes assessed included: (1) total allowed medical costs, (2) claims for pre-specified, treatment-related adverse outcomes and costs, and (3) …


Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr. Nov 2019

Budesonide Enhances Agonist-Induced Bronchodilation In Human Small Airways By Increasing Camp Production In Airway Smooth Muscle, Cynthia J. Koziol-White, Timothy B. Johnstone, Maia L. Corpuz, Gaoyuan Cao, Sarah Orfanos, Vishal Parikh, Brian Deeney, Omar Tliba, Rennolds S. Ostrom, Ian Dainty, Reynold A. Panettieri Jr.

Pharmacy Faculty Articles and Research

The non-genomic mechanisms by which glucocorticoids modulate β2 agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E2 (PGE2), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE2, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation …


Impact Of Contemporary Low Dose Aspirin Use And Cardiovascular Disease, Pratik Sharma, Ramona Stone Jan 2019

Impact Of Contemporary Low Dose Aspirin Use And Cardiovascular Disease, Pratik Sharma, Ramona Stone

Public Health Sciences Student Work

No abstract provided.


Retrospective Review Of Alternative Antibiotic Use In Patients With A Reported Penicillin Allergy At A Community Hospital, Rita Chamoun, Monica Tadros, Amy Montes, Heidi Clarke, Radhan Gopalani Dec 2018

Retrospective Review Of Alternative Antibiotic Use In Patients With A Reported Penicillin Allergy At A Community Hospital, Rita Chamoun, Monica Tadros, Amy Montes, Heidi Clarke, Radhan Gopalani

All Publications

No abstract provided.


Retrospective Review Of Patients Treated With Argatroban For Heparin Induced Thrombocytopenia, Jessica Justiz, Jessica Greenwood, Heidi Clarke, Radhan Gopalani Dec 2018

Retrospective Review Of Patients Treated With Argatroban For Heparin Induced Thrombocytopenia, Jessica Justiz, Jessica Greenwood, Heidi Clarke, Radhan Gopalani

All Publications

No abstract provided.


Retrospective Review Of Oral Oncolytic Agent Use Within A Community Hospital, Alyssa Donadio, Moe Shwin, Maria Figueroa, Michelle Lamarque Dec 2018

Retrospective Review Of Oral Oncolytic Agent Use Within A Community Hospital, Alyssa Donadio, Moe Shwin, Maria Figueroa, Michelle Lamarque

All Publications

No abstract provided.


Impact Of A Urinary Tract Infection Treatment Pathway On Antimicrobial Prescribing Within A Community Hospital, Alyssa Donadio, Heidi Clarke, Erika Dittmar Dec 2018

Impact Of A Urinary Tract Infection Treatment Pathway On Antimicrobial Prescribing Within A Community Hospital, Alyssa Donadio, Heidi Clarke, Erika Dittmar

All Publications

No abstract provided.


9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov Dec 2017

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.


Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari Jun 2017

Synthesis And Evaluation Of Antimicrobial Activity Of [R4w4k]-Levofloxacin And [R4w4k]-Levofloxacin-Q Conjugates, Neda Riahifard, Kathy Tavakoli, Jason Yamaki, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 g/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of …


Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi May 2017

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …


Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque May 2015

Accidental Phosphine Gas Poisoning With Fatal Myocardial Dysfunction In Two Families, Saleem Akhtar, Arshalooz Rehman, Surraya Bano, Anwarul Haque

Department of Emergency Medicine

ABSTRACT Aluminum phosphide is commonly used as a rodenticide and insecticide and is one of the most fatal poisons. The active ingredient is Phosphine gas which inhibits cytochrome oxidase and cellular oxygen utilization. The clinical symptoms are due to multiorgan involvement including cardiac toxicity which is the most common cause of mortality. Severity of clinical manifestations depends upon the amount of the gas to which a person is exposed. There is no specific antidote available. High index of suspicion and early aggressive treatment is the key to success. We report 2 cases of aluminum phosphide toxicity in 2 families due …


Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh Feb 2014

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …


Synthesis And Polarographic Analysis Of A2e, Elise Rivett Apr 2013

Synthesis And Polarographic Analysis Of A2e, Elise Rivett

Honors Program Projects

As humans age, fluorescent retinoid pigments accumulate in the retinal pigment epithelial (RPE) cells responsible for photoreceptor support. These fluorophores are of interest because they seem to contribute to diseases of the retina, particularly age-related macular degeneration, which is a leading cause of blindness in older adults in the United States and currently has no cure. One well-characterized fluorophore, A2E, can be oxidized by visible light and then generate harmful oxidative species capable of inducing programmed cell death in RPE cells. Further characterization of the redox behavior of A2E could ultimately aid the development of macular degeneration treatments designed to …


Radioprotection Of Oral Cavity Structures By S-2-(3-Aminopropylamino) Ethyl Phosphorothioate (Wr-2721), Ronald King Jul 1976

Radioprotection Of Oral Cavity Structures By S-2-(3-Aminopropylamino) Ethyl Phosphorothioate (Wr-2721), Ronald King

Masters Theses & Specialist Projects

Studies reporting a high concentration of WR-2721 in mouse salivary glands led to our studies of possible radioprotection of these glands by this drug from ionizing radiation. Oral effects of radiation in the presence of WR-2721 were studied in mice and dogs. Histological evaluation of mouse salivary glands irradiated with 1000 rads of 60Co showed essentially no difference between control and experimental animals. Almost full regeneration of the serous salivary components occurred by 6 months in both groups and neither group had changes in the mucous glands. The use of higher doses of radiation in the mouse was prevented …