scholarly journals Male Contraceptive Development: Update on Novel Hormonal and Nonhormonal Methods

2019 ◽  
Vol 65 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Jill E Long ◽  
Min S Lee ◽  
Diana L Blithe
Keyword(s):  
Early Stage ◽  
Single Agent ◽  
Unmet Need ◽  
Pharmaceutical Research ◽  
Development Program ◽  
World Health ◽  
Male Contraception ◽  
Male Contraceptive ◽  
Contraceptive Agents ◽  
Health Organization

Abstract BACKGROUND Development of new methods of male contraception would address an unmet need for men to control their fertility and could increase contraceptive options for women. Pharmaceutical research and development for male contraception was active in the 1990s but has been virtually abandoned. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports the majority of hormonal male contraceptive development. Nonhormonal methods are also in development but are at earlier stages. CONTENT Several hormonal male contraceptive agents have entered clinical trials. Single-agent products being evaluated include dimethandrolone undecanoate, 11β-methyl-nortestosterone dodecyl carbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone® gel and testosterone gel in a single application will begin in 2018. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect either sperm production or sperm function have been identified. Targeted pathways include the retinoic acid pathway, bromodomain and extraterminal proteins, and pathways for Sertoli cell–germ cell adhesion or sperm motility. Druggable targets include CatSper, the sperm Na+/K+-exchanger, TSSK, HIPK4, EPPIN, and ADAMs family proteins. Development of a procedure to reversibly block the vas deferens (initially developed in India in the 1980s) is undergoing early stage research in the US under the trade name Vasalgel™. SUMMARY NICHD has supported the development of reversible male contraceptive agents. Other organizations such as the World Health Organization and the Population Council are pursuing male contraceptive development, but industry involvement remains dormant.

scholarly journals Update on novel hormonal and non-hormonal male contraceptive development

2021 ◽  
Author(s):  
Jill E Long ◽  
Min S Lee ◽  
Diana L Blithe
Keyword(s):  
Single Agent ◽  
Development Program ◽  
World Health ◽  
Male Contraception ◽  
Efficacy Trial ◽  
Stages Of Development ◽  
Male Contraceptive ◽  
New Methods ◽  
Contraceptive Agents ◽  
Health Organization

Abstract Background The advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male contraception has been dormant since the 1990’s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development. Non-hormonal methods are in earlier stages of development. Content Several hormonal male contraceptive agents have entered clinical trials. Novel single agent products being evaluated include Dimethandrolone Undecanoate (DMAU), 11β-methyl-nortestosterone dodecylcarbonate (11β-MNTDC), and 7α-methyl-19-nortestosterone (MENT). A contraceptive efficacy trial of Nestorone® (NES)/testosterone (T) gel is underway. Potential non-hormonal methods are at preclinical stages of development. Many non-hormonal male contraceptive targets that affect sperm production, sperm function, or sperm transport have been identified. Summary NICHD supports development of reversible male contraceptive agents. Other organizations such as the World Health Organization, the Population Council, and The Male Contraception Initiative are pursuing male contraceptive development, but industry involvement remains limited.

scholarly journals Impact on refractive surgery due to increasing use of personal protection equipment: Insights from EUROCOVCAT group

2021 ◽  
pp. 112067212110186
Author(s):  
Arthur B Cummings ◽  
Cian Gildea ◽  
Antoine P Brézin ◽  
Boris E Malyugin ◽  
Ozlem Evren Kemer ◽  
...  
Keyword(s):  
Refractive Surgery ◽  
Unmet Need ◽  
World Health ◽  
Eye Care ◽  
Personal Protection Equipment ◽  
Social Distancing ◽  
Vision Correction ◽  
Emerging Issues ◽  
Health Organization ◽  
Motivating Factor

Since the World Health Organization declared COVID-19 to be a pandemic on 11th March 2020, changes to social and sanitary practices have included significant issues in access and management of eye care during the COVID-19 pandemic. Additionally, the fear of loss, coupled with social distancing, lockdown, economic instability, and uncertainty, have led to a significant psychosocial impact that will have to be addressed. In the current COVID-19 pandemic, personal protective equipment such as face masks or face coverings have become a daily necessity. While “mass masking” along with hand hygiene and social distancing became more widespread, new issues began to emerge – particularly in those who wore spectacles as a means of vision correction. As we began to see routine patients again after the first lockdown had been lifted, many patients visited our clinics for refractive surgery consultations with a primary motivating factor of wanting spectacle independence due to the fogging of their spectacles as a result of wearing a mask. In this article, we report on new emerging issues in eye care due to the widespread use of masks and on the new unmet need in the corneal and cataract refractive surgery fields.

scholarly journals Analysis of Separability of COVID-19 and Pneumonia in Chest X-ray Images by Means of Convolutional Neural Networks

Proceedings ◽  
2020 ◽  
Vol 54 (1) ◽  
pp. 31
Author(s):  
Joaquim de Moura ◽  
Lucía Ramos ◽  
Plácido L. Vidal ◽  
Jorge Novo ◽  
Marcos Ortega
Keyword(s):  
Neural Networks ◽  
Convolutional Neural Networks ◽  
Clinical Symptoms ◽  
Early Stage ◽  
World Health ◽  
Complete Analysis ◽  
Screening Process ◽  
X Ray ◽  
Chest X Ray ◽  
Health Organization

The new coronavirus (COVID-19) is a disease that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On 11 March 2020, the coronavirus outbreak has been labelled a global pandemic by the World Health Organization. In this context, chest X-ray imaging has become a remarkably powerful tool for the identification of patients with COVID-19 infections at an early stage when clinical symptoms may be unspecific or sparse. In this work, we propose a complete analysis of separability of COVID-19 and pneumonia in chest X-ray images by means of Convolutional Neural Networks. Satisfactory results were obtained that demonstrated the suitability of the proposed system, improving the efficiency of the medical screening process in the healthcare systems.

scholarly journals Barriers and Solutions to Developing Future Therapies for Pulmonary Hypertension

2018 ◽  
Vol 17 (4) ◽  
pp. 159-165
Author(s):  
Brian Graham ◽  
Peter Fernandes ◽  
Sue Gu
Keyword(s):  
Clinical Trials ◽  
Pulmonary Hypertension ◽  
Phase 1 ◽  
Unmet Need ◽  
Orphan Drugs ◽  
World Health ◽  
Vasodilator Therapy ◽  
Scarce Resources ◽  
Pulmonary Arterial ◽  
Health Organization

Pulmonary hypertension (PH) and its subset, pulmonary arterial hypertension (PAH), are rare diseases with a significant unmet need. Between the 1980s and 2010s, the 5-year survival rate for PAH after diagnosis improved from 34% to 65%,12 but remains unacceptably low. Since the introduction of vasodilator therapy, 34 important advances have been made in the understanding of the disease pathophysiology and development of targeted therapies. There are now 14 US Food and Drug Administration (FDA)-approved therapies that target 3 distinct pathways that contribute to PAH, and additional therapeutic targets are currently under investigation in phase 1, 2, and 3 clinical trials.5 However, there have been major challenges in PH medication development to date, including: 1) only one medication approved for pediatric PAH; 2) focusing on vasodilator therapy rather than targeting the underlying pathogenesis of the disease; 3) no medications approved for PH World Health Organization (WHO) Groups 2, 3, and 5; and 4) several recent high-profile clinical failures after promising preclinical studies.The focus and goal of the PH research community should be directed at identifying new options and solutions for patients. The field must ensure that the approaches used for clinical trials to develop orphan drugs maximize the scarce resources available for recruiting subjects, and are directed toward making safe and effective therapies available in a timely manner. Therefore, there is a critical need to coordinate and harmonize innovative approaches within the field, including strengthening translational research to deliver promising candidates and optimize the designs, endpoints, and biomarkers to conduct safe and efficient clinical trials.

scholarly journals Giant Cell Urothelial Carcinoma of Bladder

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Harshima Disvini Wijesinghe ◽  
Ajith Malalasekera
Keyword(s):  
Urothelial Carcinoma ◽  
Giant Cell ◽  
Early Stage ◽  
Giant Cells ◽  
World Health ◽  
World Health Organization Classification ◽  
Health Organization

Giant cell urothelial carcinoma is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumours. It is an aggressive tumour with a poor prognosis that usually presents at an advanced stage. It is characterized histologically by pleomorphic giant cells. We discuss a case of giant cell urothelial carcinoma presenting at an early stage in a previously well 62-year-old woman. Histology showed a tumour comprising pancytokeratin positive bizarre mononuclear and multi-nuclear giant cells admixed with areas of conventional urothelial carcinoma and carcinoma in situ. Three-month follow-up cystoscopy and magnetic resonance imaging showed no evidence of recurrence or pelvic lymphadenopathy.

Gemcitabine as a Single Agent in the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

1999 ◽  
Vol 17 (12) ◽  
pp. 3786-3792 ◽  
Author(s):  
A. Fosså ◽  
A. Santoro ◽  
W. Hiddemann ◽  
L. Truemper ◽  
N. Niederle ◽  
...  
Keyword(s):  
Partial Response ◽  
Confidence Interval ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
World Health ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Health Organization ◽  
Hodgkin's Lymphomas

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of ≤ 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m2 was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.

scholarly journals Looking at the Bigger Picture—Considering the Hurdles in the Struggle against Nanoplastic Pollution

Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2536
Author(s):  
Sophie M. Briffa
Keyword(s):  
Environmental Concern ◽  
Early Stage ◽  
Ecological Impact ◽  
Health Impact ◽  
World Health ◽  
One Dimension ◽  
Environmental Persistence ◽  
The World ◽  
Health Organization ◽  
Changes Over Time

Plastics are considered one of the most serious environmental global concerns as they are ubiquitous and contribute to the build-up of pollution. In August 2020, the BBC reported that scientists found 12–21 million tonnes of tiny plastic fragments floating in the Atlantic Ocean. After release into the environment, plastics from consumer items, such as cosmetics and biomedical products, are subject to degradation and break down into microplastics (<5 mm in diameter) and eventually into nanoplastics (<100 nm in at least one dimension). Given their global abundance and environmental persistence, exposure of humans and animals to these micro- and nano- plastics is unavoidable. “We urgently need to know more about the health impact of microplastics because they are everywhere”, says Dr Maria Neira, Director at the World Health Organization. Nanoplastics are also an emerging environmental concern as little is known about their generation, degradation, transformation, ageing, and transportation. Owing to their small size, nanoplastics can be trapped by filter-feeding organisms and can enter the food chain at an early stage. Therefore, there is a gap in the knowledge that vitally needs to be addressed. This minireview considers how nanoplastic research can be made more quantifiable through traceable and trackable plastic particles and more environmentally realistic by considering the changes over time. It considers how nanoplastic research can use industrially realistic samples and be more impactful by incorporating the ecological impact.

scholarly journals Medical Image Classification for Coronavirus Disease (COVID-19) Using Convolutional Neural Networks

2021 ◽  
pp. 2740-2747
Author(s):  
Ehsan Ali Al-Zubaidi ◽  
Maad M. Mijwil
Keyword(s):  
Neural Networks ◽  
Convolutional Neural Networks ◽  
Medical Image ◽  
Early Stage ◽  
World Health ◽  
Elapsed Time ◽  
The World ◽  
Medical Image Classification ◽  
Serious Disease ◽  
Health Organization

     The coronavirus is a family of viruses that cause different dangerous diseases that lead to death. Two types of this virus have been previously found: SARS-CoV, which causes a severe respiratory syndrome, and MERS-CoV, which causes a respiratory syndrome in the Middle East. The latest coronavirus, originated in the Chinese city of Wuhan, is known as the COVID-19 pandemic. It is a new kind of coronavirus that can harm people and was first discovered in Dec. 2019. According to the statistics of the World Health Organization (WHO), the number of people infected with this serious disease has reached more than seven million people from all over the world. In Iraq, the number of people infected has reached more than twenty-two thousand people until April 2020. In this article, we have applied convolutional neural networks (ConvNets) for the detection of the accuracy of computed tomography (CT) coronavirus images that assist medical staffs in hospitals on categorization chest CT-coronavirus images at an early stage. The ConvNets are able to automatically learn and extract features from the medical image dataset. The objective of this study is to train the GoogleNet ConvNet architecture, using the COVID-CT dataset, to classify 425 CT-coronavirus images. The experimental results show that the validation accuracy of GoogleNet in training the dataset is 82.14% with an elapsed time of 74 minutes and 37 seconds.

scholarly journals Oral Cancer

2021 ◽  
Author(s):  
Xue Xiao ◽  
Zhou Wang
Keyword(s):  
Oral Cancer ◽  
Early Stage ◽  
Premalignant Lesions ◽  
World Health ◽  
Screening Strategies ◽  
The World ◽  
Advanced Stages ◽  
Health Organization ◽  
Optimized Treatment ◽  
Developed World

Oral cancer is a frequent head and neck cancer in developing countries and some developed world. According to the World Health Organization classification 2017, oral cancer influences the anatomical subsites including buccal mucosa, the anterior two-third of the tongue, lip, palate, vestibule, alveolus, floor of the mouth, and gingivae. A variety of premalignant lesions are related with the development of oral cancer, such as leukoplakia, erythroplakia, et al. The predominant histological type of oral cancer is squamous cell carcinoma (SCC). Tobacco and alcohol consumption are regarded as critical etiological factors. Due to the unspecific symptoms in early stage, the majority are diagnosed in advanced stages. Despite the development of medicine over decades, the mortality rate of oral cancer remains high, indicating the importance of optimized treatment and screening strategies.

scholarly journals Myelodysplastic/Myeloproliferative Neoplasms Unclassified (MDS/MPN-U) Overlap: Can We Alter the Natural History?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3125-3125 ◽  
Author(s):  
Kaitlin Hendrix ◽  
Najla Alali ◽  
Eric Padron ◽  
David Sallman ◽  
Alan F. List ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloproliferative Neoplasms ◽  
Unmet Need ◽  
Low Risk ◽  
World Health ◽  
Cell Transplant ◽  
Sequencing Data ◽  
Modest Improvement ◽  
Baseline Characteristics ◽  
Health Organization

Abstract Introduction: The 2008 World Health Organization classification recognized a unique overlap category that combines features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The least well characterized of the 4 overlap diseases is a rare entity known as MDS/MPN Unclassifiable (MDS/MPN-U), comprising <5% of myeloid disorders. The outcome of this subtype has been reported to be poor. The response to and impact of hypomethylating agents (HMA) on outcome is not well studied. Methods: We identified MDS/MPN-U patients within the Moffitt MDS database, baseline characteristics were reviewed, and responses to HMA utilizing IWG 2006 response criteria were assessed. The Kaplan-Meier method was applied to estimate overall survival (OS). Results: Among 127 patients with MDS/MPN-U, 62 patients received HMA treatment. There was no difference in baseline characteristics among those who received HMA or not, except that those treated with HMA were less likely to have low risk disease by IPSS, MD Anderson model or very low risk by revised IPSS (R-IPSS). Among 16 patients who had NextGen sequencing data, the 5 most common mutations were ASXL-1 (56%), TET2 (31%), JAK2 (33%), SRSF2 (25%), as well as SETBP1, DNMT3A, and EZH2(19%). The best overall response to HMA (hematological improvement [HI] or better) according to the International Working Group (IWG) 2006 criteria was 26%. Only 11 patients (low risk) underwent allogeneic stem cell transplant (allo-SCT) with no improvement or decrease in OS. The median OS was 33 months (mo). Among patients with IPSS low/int-1 risk disease, the median OS was 39 and 33 mo respectively for those treated with HMA vs. HMA untreated. (p=0.50). For Int-2/high risk IPSS, the median OS was 11 and 5 mo for those who received HMA and those who did not. (p=0.02). Based on R-IPSS the median OS for very low/low risk was 47 and 39 mo respectively for those treated with HMA and without (p=0.96), for intermediate risk, the median OS was 39 and 25 mo respectively (p 0.75), and for high and very high risk the median OS was 13 and 5 mo respectively for those treated with HMA and those who did not. (p < 0.005). The median OS for patients with HI+, stable disease or progressive disease was 68, 59, and 36 mo respectively (p=0.08). Conclusions: Treatment with HMA is associated with modest improvement in OS among higher risk MDS/MPN-U, reinforcing the unmet need to improve outcomes in this group. Targeted therapy may prove to be of benefit as allo-SCT does not appear to be beneficial for patients even with low risk disease. Furthermore, these data demonstrate the need for prospective analysis of the outcomes of allo-SCT in patients with MDS/MPN-U to determine potential benefit to high risk patients. Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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