The silent epidemic of exclusive university licensing policies on compounds for neglected diseases and beyond.
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ABSTRACT:
SUBMITTER: Chen CE
PROVIDER: S-EPMC2846921 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
Publications
The silent epidemic of exclusive university licensing policies on compounds for neglected diseases and beyond.
Chen Connie E CE Gilliland C Taylor CT Purcell Jay J Kishore Sandeep P SP
PLoS neglected tropical diseases 20100330 3
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Project description:The Neglected Diseases section will no longer focus on chronic tropical infections, but on other neglected health problems that have a major global burden.
| S-EPMC2253615 | biostudies-literature
Project description:BackgroundChronic diseases, such as heart disease, cancer, and diabetes, are the leading causes of death and disability. Loneliness is linked to a greater risk of chronic disease. However, the lack of loneliness may change this relationship.MethodsThe 4th Survey of the Aged Population in Urban and Rural China (SSAPUR) was performed. 222,179 people over 60 years old were recruited. Chronic disease was defined by self-reported tumble incidents using the fourth SSAPUR questionnaire. We found that the residuals were well normally distributed. Subsequently, we analyzed the association between each studied factor and chronic disease by univariate logistic regression analysis. Finally, we stratified the population by age, gender, and urban and rural.Results77,448 individuals experienced loneliness, while 137,593 did not. Loneliness correlated significantly with urban-rural classification, age, and gender (P < 0.001). There was a significant association between chronic diseases and loneliness (P < 0.05). Compared to lonely individuals, those with low level of loneliness had a lower incidence of gastric diseases (OR = 0.752, 95% CI, 0.736-0.769, P < 0.001), osteoarthritis (OR = 0.685, 95% CI, 0.673-0.697, P < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 0.678, 95% CI, 0.659-0.698, P < 0.001), asthma (OR = 0.608, 95% CI, 0.583-0.633, P < 0.001), malignant tumors (OR = 0.892, 95% CI, 0.822-0.968, P = 0.006), and reproductive system diseases (OR = 0.871, 95% CI, 0.826-0.918, P < 0.001).ConclusionIn summary, loneliness is an important risk factor in the occurrence and development of chronic diseases in the elderly in China, and it has adverse effects on hypertension, stomach disease, cataract or glaucoma, osteoarthrosis, chronic lung disease, asthma, malignant tumor, and reproductive system diseases.
| S-EPMC11346041 | biostudies-literature
Project description:The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in "CCR5 research" are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.
| S-EPMC7260533 | biostudies-literature
Project description:Simulating the spread of infectious diseases in human communities is critical for predicting the trajectory of an epidemic and verifying various policies to control the devastating impacts of the outbreak. Many existing simulators are based on compartment models that divide people into a few subsets and simulate the dynamics among those subsets using hypothesized differential equations. However, these models lack the requisite granularity to study the effect of intelligent policies that influence every individual in a particular way. In this work, we introduce a simulator software capable of modeling a population structure and controlling the disease's propagation at an individualistic level. In order to estimate the confidence of the conclusions drawn from the simulator, we employ a comprehensive probabilistic approach where the entire population is constructed as a hierarchical random variable. This approach makes the inferred conclusions more robust against sampling artifacts and gives confidence bounds for decisions based on the simulation results. To showcase potential applications, the simulator parameters are set based on the formal statistics of the COVID-19 pandemic, and the outcome of a wide range of control measures is investigated. Furthermore, the simulator is used as the environment of a reinforcement learning problem to find the optimal policies to control the pandemic. The obtained experimental results indicate the simulator's adaptability and capacity in making sound predictions and a successful policy derivation example based on real-world data. As an exemplary application, our results show that the proposed policy discovery method can lead to control measures that produce significantly fewer infected individuals in the population and protect the health system against saturation.
| S-EPMC9894541 | biostudies-literature
Project description:A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.
| S-EPMC4965013 | biostudies-literature
Project description:CD40 signaling in classical type 1 dendritic cells (cDC1s) is required for CD8 T cell-mediated tumor rejection, but the underlying mechanisms are incompletely understood. Here, we identified CD40-induced genes in cDC1s, including Cd70, Tnfsf9, Ptgs2 and Bcl2l1, and examined their contributions to anti-tumor immunity. cDC1-specific inactivation of CD70 and COX-2, and global CD27 inactivation, only partially impaired tumor rejection or tumor-specific CD8 T cell expansion. Loss of 4-1BB, alone or in Cd27-/- mice, did not further impair anti-tumor immunity. However, cDC1-specific CD40 inactivation reduced cDC1 mitochondrial transmembrane potential and increased caspase activation in tumor-draining lymph nodes, reducing migratory cDC1 numbers in vivo. Similar impairments occurred during in vitro antigen presentation by Cd40-/- cDC1s to CD8+ T cells, which were reversed by re-expression of Bcl2l1. Thus, CD40 signaling in cDC1s not only induces costimulatory ligands for CD8+ T cells but also induces Bcl2l1 that sustains cDC1 survival during priming of anti-tumor responses.
| S-EPMC9896965 | biostudies-literature
Project description:BackgroundEnglish alcohol policy is implemented at local government level, leading to variations in how it is put into practice. We evaluated whether differences in the presence or absence of cumulative impact zones and the 'intensity' of licensing enforcement--both aimed at regulating the availability of alcohol and modifying the drinking environment--were associated with harm as measured by alcohol-related hospital admissions.MethodsPremises licensing data were obtained at lower tier local authority (LTLA) level from the Home Office Alcohol and Late Night Refreshment Licensing data for 2007-2012, and LTLAs were coded as 'passive', low, medium or highly active based on whether they made use of cumulative impact areas and/or whether any licences for new premises were declined. These data were linked to 2009-2015 alcohol-related hospital admission and alcohol-related crime rates obtained from the Local Alcohol Profiles for England. Population size and deprivation data were obtained from the Office of National Statistics. Changes in directly age-standardised rates of people admitted to hospital with alcohol-related conditions were analysed using hierarchical growth modelling.ResultsStronger reductions in alcohol-related admission rates were observed in areas with more intense alcohol licensing policies, indicating an 'exposure-response' association, in the 2007-2015 period. Local areas with the most intensive licensing policies had an additional 5% reduction (p=0.006) in 2015 compared with what would have been expected had these local areas had no active licensing policy in place.ConclusionsLocal licensing policies appear to be associated with a reduction in alcohol-related hospital admissions in areas with more intense licensing policies.
| S-EPMC4789824 | biostudies-literature
Project description:Chronic pain is highly prevalent among older adults where it is associated with significant suffering, disability, social isolation, and greater costs and burden to health care systems. Pharmaceutical treatment of chronic pain in older adults is usually only partially effective and is often limited by side effects including urinary retention, constipation, sedation, cognitive impairment, and increased risk of falls. Since older adults are underrepresented in clinical trials testing treatments for chronic pain, the potential impacts of polypharmacy and frailty on reported outcomes and side effect profiles are largely unknown. Thus, for current treatments, providers and patients must balance anticipated benefits of pain reduction with the known and unknown risks of treatment. Chronic pain is also a risk factor for premature death as well as accelerated cognitive decline, suggesting potential shared mechanisms between persistent pain (or its treatment) and dementia. Cognitive decline and dementia may also impact pain perception and the ability to report pain, complicating treatment decisions. Associations between persistent pain and the risks of premature death and accelerated cognitive decline make estimates for chronic pain in these populations particularly challenging. Future research is needed to improve estimates for chronic pain in older adults, to elucidate underlying mechanisms of pain with aging, and to develop and advance safer, more effective treatment options for chronic pain in older adults.
| S-EPMC6538291 | biostudies-literature
Project description:BackgroundThe neglected tropical diseases (NTDs) cause significant morbidity and mortality worldwide. Due to the growth in international travel and immigration, NTDs may be diagnosed in countries of the western world, but there has been no specific focus in the literature on imported NTDs.MethodsRetrospective study of a cohort of immigrants and travelers diagnosed with one of the 13 core NTDs at a Tropical Medicine Referral Unit in Spain during the period April 1989-December 2007. Area of origin or travel was recorded and analyzed.ResultsThere were 6168 patients (2634 immigrants, 3277 travelers and 257 VFR travelers) in the cohort. NTDs occurred more frequently in immigrants, followed by VFR travelers and then by other travelers (p<0.001 for trend). The main NTDs diagnosed in immigrants were onchocerciasis (n = 240, 9.1%) acquired mainly in sub-Saharan Africa, Chagas disease (n = 95, 3.6%) in immigrants from South America, and ascariasis (n = 86, 3.3%) found mainly in immigrants from sub-Saharan Africa. Most frequent NTDs in travelers were: schistosomiasis (n = 43, 1.3%), onchocerciasis (n = 17, 0.5%) and ascariasis (n = 16, 0.5%), and all were mainly acquired in sub-Saharan Africa. The main NTDs diagnosed in VFR travelers were onchocerciasis (n = 14, 5.4%), and schistosomiasis (n = 2, 0.8%).ConclusionsThe concept of imported NTDs is emerging as these infections acquire a more public profile. Specific issues such as the possibility of non-vectorial transmission outside endemic areas and how some eradication programmes in endemic countries may have an impact even in non-tropical western countries are addressed. Recognising NTDs even outside tropical settings would allow specific prevention and control measures to be implemented and may create unique opportunities for research in future.
| S-EPMC2910704 | biostudies-literature
Project description:Neglected diseases are typically characterized as those for which adequate drug treatment is lacking, and the potential return on effort in research and development (R&D), to produce new therapies, is too small for companies to invest significant resources in the field. In recent years various incentives schemes to stimulate R&D by pharmaceutical firms have been considered. Broadly speaking, these can be classified either as 'push' or 'pull' programs. Hybrid options, that include push and pull incentives, have also become increasingly popular. Supporters and critics of these various incentive schemes have argued in favor of their relative merits and limitations, although the view that no mechanism is a perfect fit for all situations appears to be widely held. For this reason, the debate on the advantages and disadvantages of different approaches has been important for policy decisions, but is dispersed in a variety of sources. With this in mind, the aim of this paper is to contribute to the understanding of the economic determinants behind R&D investments for neglected diseases by comparing the relative strength of different incentive schemes within a simple economic model, based on the assumption of profit maximizing firms. The analysis suggests that co-funded push programs are generally more efficient than pure pull programs. However, by setting appropriate intermediate goals hybrid incentive schemes could further improve efficiency.
| S-EPMC3526606 | biostudies-literature