Evaluation of Pain and Distress and Therapeutic Interventions for Rectal Prolapse in Mice to Reduce Early Study Removal

2021 ◽  
Author(s):  
Cara M Mitchell ◽  
Gregory W Salyards ◽  
Betty R Theriault ◽  
George P Langan ◽  
Kerith R Luchins
Keyword(s):  
Rectal Prolapse ◽  
Research Study ◽  
Treatment Options ◽  
Therapeutic Interventions ◽  
Study Endpoint ◽  
Petroleum Jelly ◽  
Ongoing Research ◽  
Treatment Groups ◽  
Animal Number ◽  
Pathogen Testing

Rectal prolapse (RP) is a common clinical condition in mice, that does not have a recognized or documented standard ofcare. At our institution, an average of 240 mice develop RP each year. Our practice has been to recommend euthanasia uponidentifying a RP based on its appearance as a painful or distressful condition. This study aimed to assess treatment options that would maintain the RP mucosa and allow mice to reach their study endpoint, and to evaluate the perception of this condition as a painful or distressful event. This study used 120 mice with spontaneous RP, concurrently assigned to ongoing research protocols. Mice were randomly assigned to 1 of 3 treatment groups: petroleum jelly, lidocaine jelly, or no treatment. Fecal samples were collected for pathogen testing, and all mice received an initial base score, followed by weekly blind scores. Upon euthanasia, RP tissue was collected for histopathology. Of the 120 mice identified with RP, 47 mice were breeders; 28% successfully produced 22 additional litters after developing RP. Seventy-three were nonbreeders, with 92% reaching their research study endpoint. No statistically significant differences were detected between the 3 treatment groups based on gross mucosal health, pain and distress, or histopathology. In this study, none of the mice in any group were euthanized based on the RP endpoint scoring criteria. These findings demonstrate that treatment is unnecessary for RP, and mice with RP did not show signs of pain or distress. In adherence to the 3Rs, this study supports animal number reduction and clinical refinement, allowing mice with RPs to reach their intended research study endpoints or produce additional litters.

scholarly journals B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

2021 ◽  
Vol 14 (1) ◽  
pp. 37
Author(s):  
Jan Traub ◽  
Leila Husseini ◽  
Martin S. Weber
Keyword(s):  
B Cells ◽  
Neuromyelitis Optica ◽  
Plasma Cells ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Complement Factor ◽  
Major Subset ◽  
Spectrum Disorders

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

scholarly journals Mitochondrial Dysfunction in Atrial Fibrillation—Mechanisms and Pharmacological Interventions

2021 ◽  
Vol 10 (11) ◽  
pp. 2385
Author(s):  
Paweł Muszyński ◽  
Tomasz A. Bonda
Keyword(s):  
Atrial Fibrillation ◽  
Mitochondrial Dysfunction ◽  
Treatment Options ◽  
Therapeutic Interventions ◽  
Energy Deficit ◽  
Functional Changes ◽  
Electrical Instability ◽  
Ionic Fluxes ◽  
Prevention Methods ◽  
Invasive Techniques

Despite the enormous progress in the treatment of atrial fibrillation, mainly with the use of invasive techniques, many questions remain unanswered regarding the pathomechanism of the arrhythmia and its prevention methods. The development of atrial fibrillation requires functional changes in the myocardium that result from disturbed ionic fluxes and altered electrophysiology of the cardiomyocyte. Electrical instability and electrical remodeling underlying the arrhythmia may result from a cellular energy deficit and oxidative stress, which are caused by mitochondrial dysfunction. The significance of mitochondrial dysfunction in the pathogenesis of atrial fibrillation remains not fully elucidated; however, it is emphasized by the reduction of atrial fibrillation burden after therapeutic interventions improving the mitochondrial welfare. This review summarizes the mechanisms of mitochondrial dysfunction related to atrial fibrillation and current pharmacological treatment options targeting mitochondria to prevent or improve the outcome of atrial fibrillation.

Novel treatment options in advanced adenoid cystic carcinoma of the breast.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13071-e13071
Author(s):  
Evan Wenig ◽  
Reumu E. Birhiray
Keyword(s):  
Disease Control ◽  
Adenoid Cystic Carcinoma ◽  
Metastatic Disease ◽  
Triple Negative ◽  
Treatment Options ◽  
Locally Advanced ◽  
Therapeutic Options ◽  
Breast Mass ◽  
Ongoing Research ◽  
Adenoid Cystic

e13071 Background: Adenoid cystic carcinoma (ACC) accounts for less than 0.1% of all breast cancer cases. The disease typically remains localized and indolent, and frequently occurs with triple negative status. Methods: In patients with locally advanced or metastatic disease, chemotherapy for triple negative breast carcinoma is seldom effective. Thus new treatment paradigms are desired. Drug targeted analysis derived from next generation sequencing and identification of driver mutations may offer a bright future in treatment options in chemo-resistant malignancy. Results: A 53 year old woman presented with breast mass and mastectomy with stage pT3N0M0 triple negative ACC of the breast resulting in observation. She later relapsed with chest wall disease, resulting in resection and radiation therapy. Shortly thereafter, she relapsed with pulmonary metastatic disease. She was treated with carboplatin and doxorubicin which were discontinued due to disease progression. Liquid assay revealed an IDH2 mutation, prompting treatment with enasidenib with ongoing evidence of disease control at 4 months. Patient tolerated treatment well without grade 3 or 4 adverse reactions. A 48 year old woman presented with an increasing 9.5 cm unresectable breast mass without distant metastasis. Pathology showed triple negative ACC of the breast, resulting in chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with clinically progressive disease. She represented with necrotic and ulcerating changes of the breast. Foundational genomic testing showed an FGFR2 mutation. After four months of treatment with erdafitinib, she had resolution of pain and cessation of pain medication. Her therapy led to a grade 2 adverse event related to hyperphosphatemia. She underwent surgical resection with negative margins. Conclusions: These examples illustrate a potential treatment paradigm for a rare malignancy for which there is no standard of care. Here we present two desperate cases, one of which had a driver mutation of IDH2, and the other FGFR2 for which there are targeted therapies approved in other disease states. The use of these two agents resulted in clinical benefit. A patient with metastatic disease treated with enasidenib has ongoing disease control for over 4 months with minimal adverse reaction. A patient with advanced local disease requiring narcotics and gabapentin for pain control treated with erdafitinib had significant symptomatic control with successful cessation of pain medications and ability to undergo potentially curable mastectomy with negative margins despite progression on prior chemotherapy. In summary, ongoing research of ACC of the breast will be required. Alternative therapeutic options related to targeted treatment may offer promise to clinical outcomes in the future. For cases of locally advanced or metastatic disease, the use of targeted therapy may offer new therapeutic options.

scholarly journals CURRENT PHARMACOLOGICAL STATUS OF CARDIOPROTECTIVE PLANTS AGAINST ISOPROTERENOL INDUCED MYOCARDIAL INFARCTION

2018 ◽  
Vol 11 (4) ◽  
pp. 17
Author(s):  
Syeda Nishat Fathima ◽  
Vasudeva Murthy S
Keyword(s):  
Myocardial Infarction ◽  
Lifestyle Modification ◽  
Treatment Options ◽  
Surgical Techniques ◽  
Cardiac Biomarkers ◽  
Therapeutic Interventions ◽  
Current Status ◽  
Plant Parts ◽  
Heart Muscle Cells ◽  
Modern Era

 Objective: Cardiovascular diseases are the major cause of morbidity and mortality in the modern era. Myocardial infarction is a condition where there is a significant decrease or block in the blood (oxygen) supply to the part of heart, leading to degeneration of a portion of the myocardium which triggers a cascade of cellular, inflammatory and biochemical events, leading eventually to the irreversible death (necrosis) of heart muscle cells. Various therapeutic interventions, including lifestyle modification, pharmacological treatment options, and surgical techniques are available. The present review focus on the plants that have been evaluated for cardioprotective activity against isoproterenol-induced myocardial infarction.Method: The current status of Cardioprotective plants was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2017 for publications on medicinal plants used against isoproterenol-induced myocardial infarction. Isoproterenol, Isoprenaline, myocardial infarction, cardioprotective were used as keywords for the searching.Result: A total of 117 different plant parts and their extracts have till now been published to possess cardioprotection against isoproterenol-induced myocardial infarction. Isoproterenol a beta-adrenergic receptors agonist causes severe stress in myocardium resulting in the infarct-like lesion and produced cardiotoxic effects by elevating the levels of cardiac biomarkers and causing changes in ECG. Plant-based medicines with their antioxidant, antiapoptotic, antihyperlipidemic, platelet antiaggregatory, anti-lipid peroxidation property provide substantial evidence for the management of Ischemia.Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants that have cardioprotective activity against isoproterenol-induced myocardial infarction.

scholarly journals Natural Compounds in Sex Hormone-Dependent Cancers: The Role of Triterpenes as Therapeutic Agents

2021 ◽  
Vol 11 ◽  
Author(s):  
Codruţa Şoica ◽  
Mirela Voicu ◽  
Roxana Ghiulai ◽  
Cristina Dehelean ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Active Role ◽  
Structural Features ◽  
Sex Hormone ◽  
Ongoing Research ◽  
New Treatment ◽  
Highly Correlated

Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.

scholarly journals Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e048647
Author(s):  
Fabian Proft ◽  
Murat Torgutalp ◽  
Burkhard Muche ◽  
Valeria Rios Rodriguez ◽  
Maryna Verba ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Treatment Period ◽  
Group Treatment ◽  
Activity Index ◽  
Treatment Options ◽  
Study Endpoint ◽  
Primary Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Axial Involvement

IntroductionPsoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA.Methods and analysesThis is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint.Ethics and disseminationThe study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted.Trial registration numberNCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.

Speculations on the post-pandemic university campus – a global inquiry

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Jay Deshmukh
Keyword(s):  
Higher Education ◽  
Teaching And Learning ◽  
Design Research ◽  
Research Study ◽  
Physical Space ◽  
Well Being ◽  
Virtual Classroom ◽  
Human Interaction ◽  
Ongoing Research ◽  
Content Type

PurposeThe pandemic-induced global shift to remote learning calls for rethinking the foundations of design for higher education. This watershed moment in global health and human interaction has accelerated changes in higher education that were long emergent and amplified specific deficiencies and strengths in pedagogical models, causing institutions to reevaluate current structures and operations of learning and campus life as they question their vision and purpose. Since physical space has largely been taken out of the equation of university life, it is evident that fresh design research related to this new normal is required.Design/methodology/approachThis qualitative research study speculates on new possibilities for the future of campus, based upon insights and inferences gained from one-on-one interviews with faculty and students in multiple countries about their personal experiences with the sudden shift to the virtual classroom. The longer the mode of physical distancing stretched through Spring 2020, these phone and web-enabled dialogues – first with faculty (teachers) and then with students (learners) – lead to a deeper, more nuanced understanding of how the notion of the campus for higher education was itself morphing in ways expected and unexpected.FindingsAt the heart of this study lies the question – Has COVID-19 killed the campus? This study suggests that it has not. However, campuses are now on a path of uneven evolution, and risk shedding the good with the extraneous without eyes-wide-open rethinking and responsive planning. This two-part qualitative analysis details the experiments and strategies followed by educators and students as the pandemic changed their ways of teaching and learning. It then speculates out-of-the-norm possibilities which campuses could explore as they navigate the uncertainty of future terms and address paradigm shifts questioning what defines a post-secondary education.Research limitations/implicationsThis paper draws inferences from discussions limited to the first 100 days of the pandemic. This on-the-ground aspect as the pandemic continues is its strength and its limitation. As Fall 2020 progresses across global campuses, new ideas and perspectives are already reinforcing or upending some of this paper's speculations. This researcher is already engaged in new, currently-ongoing research, following up with interviewees from Spring 2020, as well as bringing in new voices to delve deeper into the possibilities discussed in this paper. This follow-up research is shaping new thinking which is not reflected in this paper.Originality/valueDesign practitioners have long-shaped campuses on the belief that the built “environment is the third teacher” and that architecture fosters learning and shapes collective experience. Educators recognize that a multiplicity of formal and informal interactions occur frequently and naturally across campus, supporting cognitive and social development, collegiality and well-being. Even today's digital-native-students perceive the inherent value of real interpersonal engagement for meaningful experiences. This research study offers new planning and design perspectives as institutional responses to the pandemic continue to evolve, to discover how design can support what lies at the core of the campus experience.

Diagnostic radiology findings and spectrum of therapeutic interventions in gynaecological and urogenital vascular anomalies

2021 ◽  
pp. 20210246
Author(s):  
Nadja Grill ◽  
Felix Struebing ◽  
Lena Krebs ◽  
Maliha Sadick
Keyword(s):  
Treatment Options ◽  
Vascular Anomaly ◽  
Vascular Anomalies ◽  
Urogenital Tract ◽  
Diagnostic Radiology ◽  
Therapeutic Interventions ◽  
Interdisciplinary Management ◽  
Interventional Treatment ◽  
Invasive Treatment ◽  
Pictorial Review

Vascular anomalies represent a rare congenital disease with manifestation at diverse anatomical sights and presenting with heterogenous symptoms. Undetected, they can progress and create acute and chronic complications with functional impairment. The manifestation in the female and male pelvis and the urogenital tract represents a multidisciplinary challenge for physicians. Especially outpatient management in gynaecology and urology is affected. Diagnostic Radiology holds an important supportive role in early diagnosis of the underlying urogenital vascular anomaly and referral to interventional radiology, either for minimal invasive treatment, or to surgery for further assessment. This pictorial review creates awareness for the spectrum of vascular anomalies of the gynaecological and urogenital tract, their characteristic imaging findings and dedicated interventional treatment options. The individual description of vascular anomalies, based on an appropriate nomenclature and classification standard, is a guide for radiologists to distinguish the underlying vascular anomaly from other vascular disorders and to accelerate diagnosis as well as therapeutic proceedings. In consequence, interdisciplinary management of patients with vascular anomalies of the female and male pelvis will benefit.

scholarly journals MLTI-14. A SYSTEMATIC REVIEW OF TREATMENT PARADIGMS FOR PATIENTS WITH BREAST CANCER AND ONE OR MORE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Yosef Ellenbogen ◽  
Karanbir Brar ◽  
Nebras Warsi ◽  
Jetan Badhiwala ◽  
Alireza Mansouri
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Brain Metastases ◽  
Treatment Options ◽  
Inclusion Criteria ◽  
Open Label ◽  
Treatment Groups ◽  
Molecular Features ◽  
Significant Difference

Abstract BACKGROUND: Upwards of 50% of patients with advanced breast cancer are diagnosed with brain metastases (BM). Treatment options for these patients have been rapidly evolving due to increased understanding of the tumor pathophysiology and its genetic underpinnings. This systematic review of randomized controlled trials (RCTs) aims to clarify the evidence guiding the treatment of brain metastases from breast cancer. METHODS: MEDLINE, EMBASE, Cochrane Controlled Register of Trials, ClincialTrials.gov, and Web of Science were searched from inception to October 2018 for RCTs comparing treatments for breast cancer BM. We screened studies, extracted data, and assessed risk of bias independently and in duplicate. Outcomes assessed were overall survival (OS), progression-free survival (PFS), and adverse events (Grade 3+). RESULTS: Among 3188 abstracts, only 3 RCTs (N=412; mean sample size per group N=54.7) meeting inclusion criteria were identified. The studies were phase II or III open-label parallel superiority trials. Inclusion criteria among these trials consisted of age >18 with radiologic evidence of >1 BM. Exclusion criteria consisted of poor-performance functional status (ECOG >2 or KPS < 70). The treatment groups included whole-brain radiation therapy (WBRT) vs WBRT + Temozolomide, WBRT vs WBRT + Efaproxiral, and Afatinib vs Vinorelbine vs investigators’ choice (86% of these patients received WBRT or SRS prior to study enrolment). While two trials found no significant difference in OS, one trial found significant improvement in OS with Efaproxiral in addition to WBRT compared to WBRT alone (HR 0.52; 95%CI 0.332–0.816). No significant differences were found with PFS or rate of adverse events amongst treatment groups. CONCLUSION: Considering the high prevalence of breast cancer BM and our improved understanding of genomic/molecular features of these tumors, a greater number of RCTs dedicated at this disease are needed.

scholarly journals Treatment options in type-2 low asthma

2020 ◽  
pp. 2000528 ◽  
Author(s):  
Timothy SC Hinks ◽  
Stewart J Levine ◽  
Guy G Brusselle
Keyword(s):  
Severe Asthma ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Occupational Exposures ◽  
Evidence Base ◽  
Type I ◽  
Eosinophilic Asthma ◽  
Ongoing Research

Monoclonal antibodies targeting IgE or the type-2 cytokines IL-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, though poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity, occupational exposures and may be driven by persistent bacterial infections and by activation of a recently-described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits which can be identified and addressed. We particularly focus on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally we review ongoing research into other pathways including TNF, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems and is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.

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