Medicine and Health Sciences Commons^™

Comparison Of Endoscopic Tympanoplasty With Microscopic Tympanoplasty In Anterior Tympanic Membrane Perforation, Mohammad Mousa Abdelghafor Mousa, Ahmed Mahmoud Khalifa, Yahia Muhammad Dawood

Al-Azhar International Medical Journal

Background: Chronic otitis media is the most prevalent cause of tympanic membrane perforation. In these cases, tympanoplasty attempts to restore hearing mechanisms and close the perforation.

Aim and objectives: To compare the functional and surgical results of microscopic and endoscopic tympanic membrane repair in patients with anterior tympanic membrane perforation.

Subjects and Methods: Forty patients with anterior tympanic membrane perforations that required tympanoplasty (type-I) were included in this comparative prospective single-masked study. These patients were selected from patients reporting to the Otorhinolaryngology outpatient clinics at Al-Azhar University hospitals (Al-Hussein and Sayed Galal). Patients were divided randomly into two equal groups: …

Assessment Of Juxta Papillary Retinal Fiber Layer In Normal Blood Pressure, Controlled And Uncontrolled Hypertensive Patients, Moataz Abdelbadea Ahmed, Hassan Mohamed Hegazy, Ezzat Nabil Abbas

Al-Azhar International Medical Journal

Background: Renal vascular damage resulting from hypertension (HTN) is referred to as hypertensive retinopathy (HR). Generally, symptoms manifest later in the illness. Changes in the vascular wall, arteriovenous nicking, arteriolar constriction, flame-shaped hemorrhages, yellow hard exudates, cotton-wool spots, and optic disk edema are seen in the funduscopic examination.

Aim: To investigate alterations in the juxta papillary retinal nerve fiber layer (RNFL) in cases with uncontrolled systemic HTN compared to controlled systemic HTN and normotensive eyes utilizing Spectral Domain Optical Coherence Tomography (SD-OCT).

Patients and Methods: A twelve-month cross-sectional trial was conducted on cases with localized defects in RNFL and normal …

Comparative Study Between Arthroscopic And Radiological Findings In Staging Of Kienbock's Disease, Ahmed Mohamed Zak, Abd El Hakim Abd Allah Massoud, Mohamed Amer Mohamed

Al-Azhar International Medical Journal

Background: Avascular necrosis of the lunate, known as Kienbock's Disease, manifests as progressive wrist discomfort and atypical carpal motion. Kienbock disease possesses the capacity to result in significant wrist degeneration and impaired wrist function ultimately. Management of Kienböck's disease depends on the radiological stage of the disease.

Aim and objectives: To assess the wrist arthroscopically in cases with Kienbock disease and compare the imaging and wrist arthroscopy findings in grading Kienbock's disease and in making the management decision.

Patients and methods: This prospective study was conducted on ten cases of Kienbock's disease at Al-Azhar University Hospitals. Aiming to correlate radiographic …

Effectiveness Of Ultrasound-Guided Erector Spinae Plane Block Vs. Modified Pectoral Nerves Block For Postoperative Pain In Modified Radical Mastectomy, Hamed Ahmed Sanad, Tamer Mohamed Ahmed Ewieda, Ahmed Magdy Mohamed Ebied

Al-Azhar International Medical Journal

Background: Globally, breast cancer is the most prevalent malignancy amongst females. The principal symptom of a syndrome denoting the presence of pain in and around the site of mastectomy for a duration exceeding three months after the procedure is chronic post-mastectomy pain (PMP)

Aim and objectives: To compare Erector Spinae Plane Block modified pectoral nerves block following modified radical mastectomy regarding postoperative pain relief.

Subjects and methods: This prospective, randomized, masked clinical trial was performed at Al-Azhar University Hospitals for Boys in Cairo. This research was performed on (60) individuals subjected to 2 groups: Group A: Erector Spinae Plane Block …

Freestyle Perforator Propellar Flaps For Gluteal And Perigluteal Pressure Ulcers Reconstruction, Magdy Ahmed Abd Elmoktader Abd Alkarem, Moustafa Sayed Ahmed Meky, Ahmed Mohamad Tag El-Din

Al-Azhar International Medical Journal

Background: Pressure ulcers frequently occur in the gluteal region, particularly in paraplegic patients with a high risk of recurrence. For this reason, future reconstructive treatments should be considered when choosing flaps for reconstructive surgery. Both the upper and superior gluteal artery perforator flaps (IGAP and SGAP) are examples of neural perforator flaps; first and second perforators from profundal femoris artery perforator (PFAP) are popular perforator flaps in the treatment of gluteal pressure sores.

Objective: To assess the gluteal and para-gluteal regions by providing different sizes and designs of perforator propeller flaps to reconstruct gluteal pressure ulcers.

Material and methods: A …

Role Of Imaging In Evaluation Of Deep Venous Thrombosis And Pulmonary Embolism In Covid-19 Patients, Ahmed Mohamed Eldeeb, Ali Abd Elhady El-Sayed, Mohamad Fawzy Mahmoud Allam

Al-Azhar International Medical Journal

Background: As of June 30, 2020, COVID-19, the coronavirus illness, continues to pose a hazard to public health worldwide, accounting for over 500,000 deaths and over 10 million cases.

Objective: To characterize the imaging results of COVID-19-positive patients who had acute venous thromboembolic events in the pulmonary or lower limb venous circulation and ascertain the frequency of thromboembolic consequences in COVID-19-positive patients.

Patients and Methods: This prospective study involved 30 patients with proven COVID-19 infection who first developed thromboembolic symptoms at Dar-Elshefaa Specialty Hospital. Six months were dedicated to the research.

Results: In the present investigation, the mean BMI of …

Comparing Outcomes Of Lateral Internal Sphincterotomy And Laser Sphincterolysis In The Management Of Chronic Anal Fissure, Ahmed Ragab Sabek, Ibrahim Hamdy Bayan, Mohamed Ibrahim Monier

Al-Azhar International Medical Journal

Background: Anal fissure is a frequent peri-anal condition causing bleeding, itching, and pain due to poor endodermal perfusion due to high resting anal pressure.

Objectives: To compare laser sphincterolysis vs. open lateral sphincterotomy in the management of chronic anal fissures.

Patients and methods: This research was done on 100 cases and was separated into two groups: Open LIS Group (N=55) and Laser Group (N=45).

Results: Our findings showed a statistically significant difference in Wexner Score between the studied groups in Continent, Gas, and Liquid, while there was no statistically significant variance among the studied groups as regarded as Solid. Moreover, …

Clinical Value Of Auditory Steady State Response Versus Tone Burst Abr For Evaluation Of Severe To Profound Hearing Loss In Children, Gehan Abd-Al-Rahman El-Zarea, Ahmed Ismail Abbas, Ahmed Mohamed Eldeeb

Al-Azhar International Medical Journal

Background: Hearing makes it possible to identify and distinguish objects in the world based on the sounds they make, making sound-based communication feasible.

Aim and objectives: To identify the accurate threshold of hearing in young children with severe to profound hearing loss. It also aimed to support the choice of cochlear implant candidate or hearing aid fitting, as well as early treatment during the crucial phase for speech and language perception, to enhance the development and performance of each individual.

Patients and methods: Sixty participants participated in this case-control study, which took place at Al-Azhar University Hospitals' audio-vestibular unit and …

Assessment Of Intra Renal Arterial Resistivity Index (Ri) In Primary Hypertensive Patients And Its Correlation With Those Of Normotensive Population, Moftah Ali Almgrhi, Abdel-Moniem Sayed Raghib, Hytham Mohammed Nafady, Tarek Fakhr-Elddin Ahmed

Al-Azhar International Medical Journal

Background: The rising prevalence of primary hypertension (HTN) necessitates the development of novel indicators for the early identification of hypertensive nephropathy. Doppler sonography offers non-invasive techniques to study renal hemodynamics.

Objectives: This research aimed to assess the resistivity index (RI) in the renal arteries of individuals with primary HTN and determine its connection with RI values in the normotensive population.

Methods: This research used a case-control cross-sectional analytical observational design and included a sample of 60 individuals, ranging in age from 35 to 70, of both genders, who had primary HTN and normotensive individuals. The patients were separated into two …

Methotrexate Intravitreal Injection During Rhegmatogenous Retinal Detachment Repair Surgery To Prevent Proliferative Vitreoretinopathy, Hassan Mohammed Hegazy, Mostafa Osman Hussein, Mahmoud Deif

Al-Azhar International Medical Journal

Background and Purpose: The only therapy for Proliferative vitreoretinopathy (PVR) is surgical, and the functional prognosis is poor. Methotrexate (MTX) can effectively neutralise components of PVR pathologic cascade. The purpose of this study was to determine the effectiveness of intravitreal methotrexate during surgical repair of rhegmatogenous retinal detachment.

Subjects and Methods: Prospective, randomized, comparative, and interventional study. Setting: Research Institute of Ophthalmology and Al Azhar hospitals.The study included 30 eyes assigned into two groups. In Group A, 15 patients received intravitreal methotrexate injections. Group B, 15 patients had PPV without intravitreal methotrexate injection.Patients were subjected to a complete preoperative ophthalmic …

Study Of The Association Between Thyroid Hormonal Abnormalities And Polycystic Ovary Syndrome Among Egyptian Females, Abdellah Hussein Elsadek, Ahmed Ali Hassan Ali, Bassem Ragab Abdel-Aziz, Mohamed Ahmed Anwar Shaheen, Ismail Atia Khalil Elfauomy

Al-Azhar International Medical Journal

Background: Polycystic Ovary Syndrome (PCOS) is marked by hyperandrogenism, anovulation with menstrual irregularities, and morphologic polycystic ovarian alterations. The implicated hormonal abnormalities may extend to other endocrine glands.

Aim of the Work: To investigate whether thyroid hormone abnormalities and PCOS are related in Egyptian women.

Patients and Methods: There were 500 women in the cohort diagnosed with PCOS based on the 2003 Rotterdam Criteria. Clinical, menstrual, and reproductive factors and ovarian morphology were analyzed in relation to the underlying thyroid gland's clinical and hormonal status.

Results: The prevalence of amenorrhea, oligomenorrhea, and hirsutism/acne was found to be 16.2%, 54.8%, and …

Comparative Study Of Fentanyl, And Dexmetomidine As An Adjuvant To Propofol For Colonoscopy, Ayman Ahmed Moawad, Ahmed Mahmoud Mohamed Mohamed El-Garhy, Mohamed Mohamed Salah Eldin Shamloul

Al-Azhar International Medical Journal

Background: Colonoscopy induces considerable discomfort and anxiety. Administration of a single anesthetic agent may result in insufficient sedation and pain relief, leading to excessive drug consumption and an escalation in unwanted side effects.

Aim: The study's objective effectiveness of the propofol-fentanyl and propofol-dexmedetomidine combinations in patients having colonoscopy .

Method: colonoscopy patients prospective, randomized, double-blinded, controlled trial conducted on 66 patients undergoing elective colonoscopy. Patients were assigned randomly into two equal groups. Group 1 received Fentanyl 1 µ/kg, combined with propofol 2 mg/kg bolus dose and 9 - 12 mg/kg/hr maintenance in the first 15 minutes, then propofol 6 - …

Post-Operative Analgesia In Inguinal Hernia Repair By Quadratus Lumborum Versus Transversalis Fascia Block, Sohair Farag Mohamed, Mohamed Ahmed El Badawy, Ahmed Abdelsalam Shoukry El Hadidi

Al-Azhar International Medical Journal

Background: Surgeries for inguinal hernias are common. Post-operative pain caused by traditional analgesics has worsened.

Aim and objectives: To evaluate the efficacy of two postoperative pain relief techniques for patients having a unilateral inguinal hernia repaired: a transmuscular quadratus lumborum block and an ultrasound-guided transversalis fascia plane block.

Patients and Methods: This single-masked upcoming randomized clinical study for pain control post-operative patients was conducted on 50 patients divided into two groups [QL versus TS] with anesthesiologists’ companionship in American physical states I and II, aged 21–45 years old, who underwent unilateral repair of an inguinal hernia at Police and Al. …

Comparative Analysis Of Doxycycline And Ayurvedic Herbs To Target Metastatic Breast Cancer: An In-Silico Approach, Acharya Balkrishna, Rashmi Mittal, Rohan Malik, Hariom Verma, Kuldeep Singh Mehra, Hariom Chaturvedi, Okeshwar Okeshwar, Swami Ishdev, Ajay Kumar, Vedpriya Arya

BioMedicine

Background: Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient’s quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.

Methods: Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated …

In Vitro And In Silico Evaluation Of Andrographis Paniculata Ethanolic Crude Extracts On 3 Fatty Acid Synthase Expression On Breast Cancer Cells, Nur Amanina Johari, Nur Anisa Sapi’I, Alvin Lu Jiunn Hieng, Nurriza Ab Latif, Syazwani Itri Amran, Rosnani Hasham, Khairunadwa Jemon

BioMedicine

Background Fatty acid synthase (FASN), a key rate-limiting enzyme in the fatty acid biosynthesis pathway has been identified to be overexpressed in breast cancer. This overexpression has been affiliated with poor prognosis and resistance to chemotherapeutics. Consequently, FASN has come into focus as an appealing potential target for breast cancer treatment. Available FASN inhibitors, however, are unstable and have been correlated with adverse side effects. Objective This present study aims to investigate the potential of Andrographis paniculata ethanolic crude extract (AP) as a potent FASN inhibitor in breast cancer cells. Materials & Methods This study used MTT assay and flow …

Zinc Oxide Nanoparticles-Doped Curcumin-Assisted Recovery Of Rheumatoid Arthritis And Antioxidant Status In Experimental Rabbits, Shanza Azeez, Mishal Fatima, Ouz Gul, Huzaifa Rehman, Muhammad Aslam Shad, Haq Nawaz

BioMedicine

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and synovial joint destruction.

Aims: The current study investigated the possible beneficial effect of zinc oxide nanoparticles-doped curcumin (ZnONPs-DC) on the recovery of RA and antioxidant status of experimental rabbits.

Methods: RA was induced in experimental rabbits by injecting complete Freund's adjuvant and collagen type-II emulsion (100 µL/kg body weight) in the base of their tail. Arthritic rabbits were orally treated with ZnONPs, curcumin, and ZnONPs-DC (250 µL/kg body weight). Serum samples from the control and study groups were collected before and after RA induction and after treatment. …

Protection Of Gueichih-Fuling-Wan On Cerebral Ischemia-Induced Brain Injury In Rodents Is Mediated By Trans-Cinnamaldehyde Via Inhibition Of Neuroinflammation And Apoptosis, Yuh-Fung Chen, Kuo-Jen Wu, Chi-Chung Kuo, Huei-Yann Tsai

BioMedicine

Background: Stroke is the leading cause of mortality and morbidity worldwide, and an effective therapeutic strategy for the prevention of patients with cerebral ischemiainduced brain injury is lacking. Traditional Chinese medicine with neuroprotective activities might be beneficial and provide alternative therapeutic opportunities for cerebral ischemia.Purposes: This study aimed to evaluate the neuroprotection and possible mechanisms of Gueichih-Fuling-Wan (GFW), its’ constitutive herbs, and their active compounds on cerebral ischemia/reperfusion (I/R)-induced brain injury in rodents.Methods: Various doses of extracts (0.25, 0.5, and 1.0 g/kg) of GFW and five constituent herbs (Cinnamomi Cortex, CC; Poria cocos, PC; Paeonia lactifloa, PL; Paeonia suffruticosa, PS …

Glutaminase - A Potential Target For Cancer Treatment, Josephine Anthony, Sureka Varalakshmi, Ashok Kumar Sekar, Nalini Devarajan, Balamurugan Janakiraman, Rajendran Peramaiyan

BioMedicine

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of …

Unveiling The Power Of Flavonoids: A Dynamic Exploration Of Their Impact On Cancer Through Matrix Metalloproteinases Regulation, Peramaiyan Rajendran

BioMedicine

Cancer is a prominent contributor to mortality rates globally, with its progression and spread being the primary factors underlying this assertion. Despite advancements in cancer therapy, the existing therapeutic strategies are rendered useless as a result of their toxicity and the development of chemoresistance. Hence, it is imperative to assess alternate therapy modalities, and natural compounds present a promising prospect due to their demonstrated anticancer capabilities in several research models. This article provides an overview of the regulatory mechanisms involved in the expression of metalloproteinases (MMPs) and explores the potential therapeutic function of flavonoids as agents with anticancer activity that …

Phytochemical Composition Of Clinacanthus Nutans Based On Factors Of Environment, Genetics And Postharvest Processes: A Review, Nurul Hamizah Sabindo, Rusidah Mat Yatim, Kannan Thirumulu Ponnuraj

BioMedicine

Herpes simplex, varicella-zoster lesions, skin rashes, diabetes, snake bites and insect bites have all been treated by using Clinacanthus nutans (C. nutans). The pharmacological effects of C. nutans are influenced by the presence of terpenoids, flavonoids, alkaloids, phenolic acids, saponins, glycosides, steroids and tannins. This review focused on the phytochemical makeup, which varies geographically and is a subject of scarcely existing knowledge. C. nutans served as the primary search term, while the keywords “phytochemicals”, “chemical component” and “phytochemistry” were used to search the literature in the Google Scholar, PubMed, Scopus and Web of Science databases. The articles pertinent to the …

Molecular Classification And Biomarkers Of Outcome With Immunotherapy In Extensive-Stage Small-Cell Lung Cancer: Analyses Of The Caspian Phase 3 Study, Mingchao Xie, Miljenka Vuko, Jaime Rodriguez-Canales, Johannes Zimmermann, Markus Schick, Cathy O'Brien, Luis Paz-Ares, Jonathan W Goldman, Marina Chiara Garassino, Carl M Gay, John V Heymach, Haiyi Jiang, J Carl Barrett, Ross A Stewart, Zhongwu Lai, Lauren A Byers, Charles M Rudin, Yashaswi Shrestha

Student and Faculty Publications

BACKGROUND: We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

METHODS: 805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue …

Validation Of A Blood-Based Protein Biomarker Panel For A Risk Assessment Of Lethal Lung Cancer In The Physicians' Health Study, Lulu Song, Ehsan Irajizad, Andrew Rundle, Howard D Sesso, John Michael Gaziano, Jody V Vykoukal, Kim-Anh Do, Jennifer B Dennison, Edwin J Ostrin, Johannes F Fahrmann, Frederica Perera, Samir Hanash

Student and Faculty Publications

This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61-0.92) and 0.69 (95% CI: 0.56-0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. …

The Effect Of A Dynamic Lighting Schedule On Neurobehavioral Performance During A 45-Day Simulated Space Mission, Leilah Grant, Brianne Kent, Shadab Rahman, Melissa St Hilaire, Crystal Kirkley, Kevin Gregory, Toni Clark, John Hanifin, Laura Barger, Charles Czeisler, George Brainard, Steven Lockley, Erin Flynn-Evans

Department of Neurology Faculty Papers

Study Objective: We previously reported that during a 45-day simulated space mission, a dynamic lighting schedule (DLS) improved circadian phase alignment and performance assessed once on selected days. This study aimed to evaluate how DLS affected performance on a 5-minute psychomotor vigilance task (PVT) administered multiple times per day on selected days.

Methods: Sixteen crewmembers (37.4 ± 6.7 years; 5F) underwent six cycles of 2 × 8-hour/night followed by 5 × 5-hour/night sleep opportunities. During the DLS (n = 8), daytime white light exposure was blue-enriched (∼6000 K; Level 1: 1079, Level 2: 76 melanopic equivalent daytime illuminance (melEDI) lux) …

Neurorehabilitation With Vagus Nerve Stimulation: A Systematic Review, Radha Korupolu, Alyssa Miller, Andrew Park, Nuray Yozbatiran

Student and Faculty Publications

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and …

An International Phantom Study Of Inter-Site Variability In Technetium-99m Image Quantification: Analyses From The Target Radioembolization Study, Grace Keane, Rob Van Rooij, Marnix Lam, S Cheenu Kappadath, Bilal Kovan, Stephanie Leon, Matthew Dreher, Kirk Fowers, Hugo De Jong

Student and Faculty Publications

BACKGROUND: Personalised multi-compartment dosimetry based on [

RESULTS: Regarding the LSF, inter-site variation with planar site-specific protocols was minimal, as determined by comparing computed LSF between sites (interquartile range 9.6-10.1%). A standardised protocol did not improve variation (interquartile range 8.4-9.0%) but did improve mean accuracy compared to the site-specific protocols (5.0% error for standardised protocol vs 8.8% error for site-specific protocols). Regarding the CRC, inter-system variation was notable for site-specific SPECT protocols and could not be improved by the standardised protocol (CRC interquartile range for 37 mm sphere 0.5-0.7 and 0.6-0.8 respectively), however the standardised protocol did improve accuracy of …

Metabolic Alterations And Cellular Responses To Β-Hydroxybutyrate Treatment In Breast Cancer Cells, Hadas Fulman-Levy, Raichel Cohen-Harazi, Bar Levi, Lital Argaev-Frenkel, Ifat Abramovich, Eyal Gottlieb, Sarah Hofmann, Igor Koman, Elimelech Nesher

Student and Faculty Publications

BACKGROUND: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells …

Differential Roles Of Key Brain Regions: Ventral Tegmental Area, Locus Coeruleus, Dorsal Raphe, Nucleus Accumbens, Caudate Nucleus, And Prefrontal Cortex In Regulating Response To Methylphenidate: Insights From Neuronal And Behavioral Studies In Freely Behaving Rats, Nachum Dafny, Catherine Claussen, Emilee Frazier, Yin Liu

Student and Faculty Publications

A total of 3102 neurons were recorded before and following acute and chronic methylphenidate (MPD) administration. Acute MPD exposure elicits mainly increases in neuronal and behavioral activity in dose–response characteristics. The response to chronic MPD exposure, as compared to acute 0.6, 2.5, or 10.0 mg/kg MPD administration, elicits electrophysiological and behavioral sensitization in some animals and electrophysiological and behavioral tolerance in others when the neuronal recording evaluations were performed based on the animals’ behavioral responses, or amount of locomotor activity, to chronic MPD exposure. The majority of neurons recorded from those expressing behavioral sensitization responded to chronic MPD with further …

Loss Of Lpar6 And Cab39l Dysregulates The Basal-To-Luminal Urothelial Differentiation Program, Contributing To Bladder Carcinogenesis, Sangkyou Lee, Jolanta Bondaruk, Yishan Wang, Huiqin Chen, June Goo Lee, Tadeusz Majewski, Rachel D Mullen, David Cogdell, Jiansong Chen, Ziqiao Wang, Hui Yao, Pawel Kus, Joon Jeong, Ilkyun Lee, Woonyoung Choi, Neema Navai, Charles Guo, Colin Dinney, Keith Baggerly, Cathy Mendelsohn, David Mcconkey, Richard R Behringer, Marek Kimmel, Peng Wei, Bogdan Czerniak

Student and Faculty Publications

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two …

A Multicenter Study Of Venetoclax-Based Treatment For Patients With Richter Transformation Of Chronic Lymphocytic Leukemia, Paul J Hampel, Mahesh Swaminathan, Kerry A Rogers, Erin M Parry, Jan A Burger, Matthew S Davids, Wei Ding, Alessandra Ferrajoli, Jonathan M Hyak, Nitin Jain, Saad S Kenderian, Yucai Wang, William G Wierda, Jennifer A Woyach, Sameer A Parikh, Philip A Thompson

Student and Faculty Publications

Patients with chronic lymphocytic leukemia (CLL) who develop Richter transformation (RT) have a poor prognosis when treated with chemoimmunotherapy regimens used for de novo diffuse large B-cell lymphoma. Venetoclax, a BCL2 inhibitor, has single-agent efficacy in patients with RT and is potentially synergistic with chemoimmunotherapy. In this multicenter, retrospective study, we evaluated 62 patients with RT who received venetoclax-based treatment outside of a clinical trial, in combination with a Bruton tyrosine kinase inhibitor (BTKi; n=28), rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) (n=13), or intensive chemoimmunotherapy other than R-CHOP (n=21). The best overall and complete response rates were 36%/25%, 54%/46%, and …

Dissecting The Potential Mechanisms Of Histone Deacetylase 1 Dependent Macrophage Phagocytosis Of Mycobacterium Tuberculosis, Owusu A. Christian

Biotechnology Theses

Histone deacetylases (HDACs) mediate the removal of acetyl groups from the histones of chromatin and regulate the expression of the genes involved in cancer development and immune cell functions. Our previous study showed that HDAC2 enhances IL-1β production by Mycobacterium tuberculosis (Mtb) infected macrophages by promoting inflammasome activation. HDAC1, on the other hand, regulates macrophage phagocytosis of Mtb. However, the mechanisms by which HDAC1 controls macrophage phagocytosis remain unclear.

Using human monocyte-derived macrophages (MDMs) and Mtb strains, we explore the mechanism of HDAC1 in macrophage phagocytosis of Mtb. Our results showed that blocking HDAC1, either chemically or genetically, …