scholarly journals Summary and Recommendations from the National Institute of Allergy and Infectious Diseases (NIAID) Workshop “Gonorrhea Vaccines: the Way Forward”

2016 ◽  
Vol 23 (8) ◽  
pp. 656-663 ◽  
Author(s):  
Lee M. Wetzler ◽  
Ian M. Feavers ◽  
Scott D. Gray-Owen ◽  
Ann E. Jerse ◽  
Peter A. Rice ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Basic Research ◽  
Health Department ◽  
Multidrug Resistant ◽  
Current Status ◽  
Hazard Level ◽  
The One ◽  
The U.S ◽  
The Way

ABSTRACTThere is an urgent need for the development of an antigonococcal vaccine due to the increasing drug resistance found in this pathogen. The U.S. Centers for Disease Control (CDC) have identified multidrug-resistant gonococci (GC) as among 3 “urgent” hazard-level threats to the U.S. population. In light of this, on 29 to 30 June 2015, the National Institute for Allergy and Infectious Diseases (NIAID) sponsored a workshop entitled “Gonorrhea Vaccines: the Way Forward.” The goal of the workshop was to gather leaders in the field to discuss several key questions on the current status of gonorrhea vaccine research and the path forward to a licensed gonorrhea vaccine. Representatives from academia, industry, U.S. Government agencies, and a state health department were in attendance. This review summarizes each of the 4 scientific sessions and a series of 4 breakout sessions that occurred during the one and a half days of the workshop. Topics raised as high priority for future development included (i) reinvigoration of basic research to understand gonococcal infection and immunity to allow intervention in processes essential for infection; (ii) clinical infection studies to establish parallels and distinctions betweenin vitroand animal infection models versus natural human genital and pharyngeal infection and to informin silicomodeling of vaccine impact; and (iii) development of an integrated pipeline for preclinical and early clinical evaluation and direct comparisons of potential vaccine antigens and adjuvants and routes of delivery.

scholarly journals Plant tissue culture environment as a switch-key of (epi)genetic changes

2019 ◽  
Vol 140 (2) ◽  
pp. 245-257 ◽  
Author(s):  
Piotr Tomasz Bednarek ◽  
Renata Orłowska
Keyword(s):  
Tissue Culture ◽  
Plant Tissue ◽  
Basic Research ◽  
Current Status ◽  
Epigenetic Changes ◽  
Tissue Cultures ◽  
Genetic Changes ◽  
Culture Stage ◽  
Commercial Applications

Abstract The in vitro tissue cultures are, beyond all difficulties, an essential tool in basic research as well as in commercial applications. Numerous works devoted to plant tissue cultures proved how important this part of the plant science is. Despite half a century of research on the issue of obtaining plants in in vitro cultures, many aspects remain unknown. The path associated with the reprogramming of explants in the fully functioning regenerants includes a series of processes that may result in the appearance of morphological, physiological, biochemical or, finally, genetic and epigenetic changes. All these changes occurring at the tissue culture stage and appearing in regenerants as tissue culture-induced variation and then inherited by generative progeny as somaclonal variation may be the result of oxidative stress, which works at the step of explant preparation, and in tissue culture as a result of nutrient components and environmental factors. In this review, we describe the current status of understanding the genetic and epigenetic changes that occur during tissue culture.

scholarly journals Hydroxylation of Antitubercular Drug Candidate, SQ109, by Mycobacterial Cytochrome P450

2020 ◽  
Vol 21 (20) ◽  
pp. 7683
Author(s):  
Sergey Bukhdruker ◽  
Tatsiana Varaksa ◽  
Irina Grabovec ◽  
Egor Marin ◽  
Polina Shabunya ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Cytochrome P450s ◽  
Drug Candidate ◽  
Antitubercular Drug ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Methyl Group ◽  
Liver Cytochrome ◽  
The One ◽  
Effective Drugs

Spreading of the multidrug-resistant (MDR) strains of the one of the most harmful pathogen Mycobacterium tuberculosis (Mtb) generates the need for new effective drugs. SQ109 showed activity against resistant Mtb and already advanced to Phase II/III clinical trials. Fast SQ109 degradation is attributed to the human liver Cytochrome P450s (CYPs). However, no information is available about interactions of the drug with Mtb CYPs. Here, we show that Mtb CYP124, previously assigned as a methyl-branched lipid monooxygenase, binds and hydroxylates SQ109 in vitro. A 1.25 Å-resolution crystal structure of the CYP124–SQ109 complex unambiguously shows two conformations of the drug, both positioned for hydroxylation of the ω-methyl group in the trans position. The hydroxylated SQ109 presumably forms stabilizing H-bonds with its target, Mycobacterial membrane protein Large 3 (MmpL3). We anticipate that Mtb CYPs could function as analogs of drug-metabolizing human CYPs affecting pharmacokinetics and pharmacodynamics of antitubercular (anti-TB) drugs.

scholarly journals Neglected infectious diseases: Are push and pull incentive mechanisms suitable for promoting drug development research?

2013 ◽  
Vol 8 (2) ◽  
pp. 185-208 ◽  
Author(s):  
Frank Mueller-Langer
Keyword(s):  
Infectious Diseases ◽  
Research Output ◽  
Early Stage ◽  
Basic Research ◽  
Essential Medicines ◽  
Neglected Diseases ◽  
Poor Countries ◽  
The One ◽  
Drug Development Research ◽  
Push And Pull

AbstractInfectious diseases are among the main causes of death and disability in developing countries, and they are a major reason for the health disparity between rich and poor countries. One of the reasons for this public health tragedy is a lack of lifesaving essential medicines, which either do not exist or badly need improvements. In this article, we analyse which of the push and pull mechanisms proposed in the recent literature may serve to promote research into neglected infectious diseases. A combination of push programmes that subsidise research inputs through direct funding and pull programmes that reward research output rather than research input may be the appropriate strategy to stimulate research into neglected diseases. On the one hand, early-stage (basic) research should be supported through push mechanisms, such as research grants or publicly financed research institutions. On the other hand, pull mechanisms, such as prize funds that link reward payments to the health impacts of effective medicines, have the potential to stimulate research into neglected diseases.

scholarly journals Current status and challenges in drug discovery against the globally important zoonotic cryptosporidiosis

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Guan Zhu ◽  
Jigang Yin ◽  
Gregory D. Cuny
Keyword(s):  
Drug Discovery ◽  
Current Status ◽  
Watery Diarrhea ◽  
Health Concept ◽  
Parasite Biology ◽  
Pass Through ◽  
The One ◽  
Effective Drugs ◽  
Globally Distributed

AbstractThe zoonotic cryptosporidiosis is globally distributed, one of the major diarrheal diseases in humans and animals. Cryptosporidium oocysts are also one of the major environmental concerns, making it a pathogen that fits well into the One Health concept. Despite its importance, fully effective drugs are not yet available. Anti-cryptosporidial drug discovery has historically faced many unusual challenges attributed to unique parasite biology and technical burdens. While significant progresses have been made recently, anti-cryptosporidial drug discovery still faces a major obstacle: identification of systemic drugs that can be absorbed by patients experiencing watery diarrhea and effectively pass through electron-dense (ED) band at the parasite-host cell interface to act on the epicellular parasite. There may be a need to develop an in vitro assay to effectively screen hits/leads for their capability to cross ED band. In the meantime, non-systemic drugs with strong mucoadhesive properties for extended gastrointestinal exposure may represent another direction in developing anti-cryptosporidial therapeutics. For developing both systemic and non-systemic drugs, a non-ruminant animal model exhibiting diarrheal symptoms suitable for routine evaluation of drug absorption and anti-cryptosporidial efficacy may be very helpful.

scholarly journals Applications of Raman Spectroscopy in Bacterial Infections: Principles, Advantages, and Shortcomings

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Wang ◽  
Wei Liu ◽  
Jia-Wei Tang ◽  
Jun-Jiao Wang ◽  
Qing-Hua Liu ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Antibiotic Resistance ◽  
Infectious Diseases ◽  
Bacterial Infections ◽  
Bacterial Pathogens ◽  
Basic Research ◽  
Label Free ◽  
Clinical Implementation ◽  
Label Free Detection

Infectious diseases caused by bacterial pathogens are important public issues. In addition, due to the overuse of antibiotics, many multidrug-resistant bacterial pathogens have been widely encountered in clinical settings. Thus, the fast identification of bacteria pathogens and profiling of antibiotic resistance could greatly facilitate the precise treatment strategy of infectious diseases. So far, many conventional and molecular methods, both manual or automatized, have been developed for in vitro diagnostics, which have been proven to be accurate, reliable, and time efficient. Although Raman spectroscopy (RS) is an established technique in various fields such as geochemistry and material science, it is still considered as an emerging tool in research and diagnosis of infectious diseases. Based on current studies, it is too early to claim that RS may provide practical guidelines for microbiologists and clinicians because there is still a gap between basic research and clinical implementation. However, due to the promising prospects of label-free detection and noninvasive identification of bacterial infections and antibiotic resistance in several single steps, it is necessary to have an overview of the technique in terms of its strong points and shortcomings. Thus, in this review, we went through recent studies of RS in the field of infectious diseases, highlighting the application potentials of the technique and also current challenges that prevent its real-world applications.

scholarly journals Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial

mSphere ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Anna Giammanco ◽  
Cinzia Calà ◽  
Teresa Fasciana ◽  
Michael J. Dowzicky
Keyword(s):  
Health Care ◽  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Acinetobacter Baumannii ◽  
Multidrug Resistant ◽  
Current Status ◽  
Gram Negative ◽  
Content Type ◽  
Trial Test

ABSTRACT Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide. Multidrug-resistant (MDR) Gram-negative organisms are a burden on the global health care system. The Tigecycline Evaluation and Surveillance Trial (TEST) is an ongoing global study designed to monitor the in vitro activities of tigecycline and a panel of marketed antimicrobials against a range of clinically significant pathogens. In this study, in vitro data are presented for MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, and Enterobacter cloacae isolates collected from 2004 to 2014. In total, 13% (21,967/170,759) of isolates displayed multidrug resistance globally, with the highest rates recorded among A. baumannii (overall rate, 44% [8,294/18,741], increasing from 23% [309/1,323] in 2004 to 63% [447/712] in 2014). Other multidrug resistance rates ranged from 2.5% for K. oxytoca (203/8,000) to 12% for P. aeruginosa and K. pneumoniae (3,951/32,786 and 3,895/32,888, respectively), and rates among these pathogens remained stable during the study period. Against MDR E. coli, Klebsiella spp., and E. aerogenes, the lowest rates of resistance were to tigecycline (0.2%, 6%, and 12%, respectively), and the lowest MIC90 value against A. baumannii was observed for tigecycline (2 mg/liter; MIC range, ≤0.008 to ≥32 mg/liter). The only significant change in resistance to tigecycline during the study period was for MDR E. coli (P < 0.01), among which eight resistant isolates were identified globally from 2009 to 2013. In summary, these results show that tigecycline retained in vitro activity against the majority of MDR Gram-negative organisms presented here, but the rising rates of MDR A. baumannii highlight the need for the continued monitoring of global multidrug resistance. IMPORTANCE Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Acinetobacter baumannii, Pseudomonas aeruginosa, and members of the Enterobacteriaceae, during this time. Our results show that tigecycline retained in vitro activity against many MDR Gram-negative pathogens over the study period, while rates of MDR A. baumannii increased globally. Using these findings, we hope to highlight the current status of multidrug resistance in medical facilities worldwide.

scholarly journals Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus

2018 ◽  
Vol 4 (4) ◽  
pp. 129 ◽  
Author(s):  
Sevtap Arikan-Akdagli ◽  
Mahmoud Ghannoum ◽  
Jacques Meis
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Current Status ◽  
Clinical Implications ◽  
Azole Resistance ◽  
Candida Auris

Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus.

scholarly journals Antimicrobial Activity of Some Essential Oils against Methicillin-Susceptible and Methicillin-Resistant Staphylococcus pseudintermedius-Associated Pyoderma in Dogs

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1782 ◽  
Author(s):  
Francesca Paola Nocera ◽  
Simone Mancini ◽  
Basma Najar ◽  
Fabrizio Bertelloni ◽  
Luisa Pistelli ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oils ◽  
Multidrug Resistant ◽  
Therapeutic Approaches ◽  
Cinnamomum Zeylanicum ◽  
Staphylococcus Pseudintermedius ◽  
Methicillin Resistant ◽  
Resistant Strains ◽  
The One

This study aimed to test in vitro the antimicrobial activity of 11 essential oils (EOs) against four methicillin-resistant Staphylococcus pseudintermedius (MRSP) and four methicillin-susceptible S. pseudintermedius (MSSP) clinical isolates. The obtained findings demonstrated a clear in vitro efficacy of some tested EOs against both MRSP and MSSP strains. Particularly, modal minimum inhibitory concentration (MIC) values ranging from 1:2048 v/v for Melissa officinalis against an MSSP strain to 1:256 v/v for Cymbopogoncitratus against all MRSP strains were observed. The best results, highlighting a modal MIC value of 1:1024 v/v for all tested isolates, was provided by Cinnamomum zeylanicum. Intriguingly, Cinnamomum zeylanicum showed, in many cases, a correspondence between minimum bactericidal concentration (MBC) and MIC values, indicating that the inhibiting dose is also often bactericidal. Moreover, a mild antibacterial and bactericidal activity against both MRSP and MSSP isolates was detected for the other tested EOs. Considering the zoonotic potential of S. pseudintermedius and the increased dissemination of multidrug-resistant strains, the employment of EOs could be useful for the treatment of canine pyoderma. Since antibiotic resistance has become the most urgent issue, from the perspective of the One Health initiative, alternative therapeutic approaches are desirable to limit the use of antibiotics or to improve the efficacy of conventional therapies.

The Diffusion of an Organisational Innovation: Adopting ‘Patient-Focused Care’ in an N.H.S. Hospital Trust

2002 ◽  
Vol 6 (2) ◽  
pp. 213-232 ◽  
Author(s):  
Chris Howorth ◽  
Frank Mueller ◽  
Charles Harvey
Keyword(s):  
Decision Makers ◽  
Local Context ◽  
Policy Makers ◽  
Organisational Innovation ◽  
Policy Context ◽  
Hospital Trust ◽  
The One ◽  
Context Specific ◽  
The U.S ◽  
The Way

This paper deals with the diffusion and adoption of an organisational innovation, ‘Patient Focused Care’, at a British Hospital Trust. We will be discussing how PFC emerged in the U.S. context, was propagated by policy-makers, and judged worth adopting by organisational decision-makers. In providing an analysis of the case, we are attempting to bridge the gap between the policy context on the one hand, the organisational context on the other hand. The paper shows the importance of the ‘local’ context in shaping the adoption of a ‘global’ organisational innovation. The ‘appropriation process’ will play out in context-specific ways in terms of conflicts between managers and expert professionals; the way the ‘foreignness’ of the innovation plays out; and the way public policy-makers can influence the appropriation process. Most importantly, the paper intends to show how the cognitive boundaries of the N.H.S. as an ‘organisational field’ are beginning to move beyond national borders.

Sign in / Sign up

Export Citation Format

Share Document