The State of Asthma Research: Considerable Advances, but Still a Long Way to Go.
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ABSTRACT:
SUBMITTER: Martinez FD
PROVIDER: S-EPMC6376619 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC7328323 | biostudies-literature
Project description:Zika virus (ZIKV) is a mosquito-borne flavivirus that spread throughout the American continent in 2015 causing considerable worldwide social and health alarm due to its association with ocular lesions and microcephaly in newborns, and Guillain-Barré syndrome (GBS) cases in adults. Nowadays, no licensed vaccines or antivirals are available against ZIKV, and thus, in this very short time, the scientific community has conducted enormous efforts to develop vaccines and antivirals. So that, different platforms (purified inactivated and live attenuated viruses, DNA and RNA nucleic acid based candidates, virus-like particles, subunit elements, and recombinant viruses) have been evaluated as vaccine candidates. Overall, these vaccines have shown the induction of vigorous humoral and cellular responses, the decrease of viremia and viral RNA levels in natural target organs, the prevention of vertical and sexual transmission, as well as that of ZIKV-associated malformations, and the protection of experimental animal models. Some of these vaccine candidates have already been assayed in clinical trials. Likewise, the search for antivirals have also been the focus of recent investigations, with dozens of compounds tested in cell culture and a few in animal models. Both direct acting antivirals (DAAs), directed to viral structural proteins and enzymes, and host acting antivirals (HAAs), directed to cellular factors affecting all steps of the viral life cycle (binding, entry, fusion, transcription, translation, replication, maturation, and egress), have been evaluated. It is expected that this huge collaborative effort will produce affordable and effective therapeutic and prophylactic tools to combat ZIKV and other related still unknown or nowadays neglected flaviviruses. Here, a comprehensive overview of the advances made in the development of therapeutic measures against ZIKV and the questions that still have to be faced are summarized.
| S-EPMC6789873 | biostudies-literature
Project description:Brugada syndrome (BrS) is an arrhythmogenic disorder which was first described in 1992. This disease is a channelopathy characterized by ST-segment elevations in the right precordial leads and is susceptible to sudden death. BrS is a fatal disease with gender and age preferences. It occurs mainly in young male subjects with a structurally normal heart and silently progresses to sudden death with no significant symptoms. The prevalence of BrS has been reported in the ranges of 5-20 per 10 000 people. The disease is more prevalent in Asia. Nowadays, numerous variations in 23 genes have been linked to BrS since the first gene SCN5A has been associated with BrS in 1998. Not only can clinical specialists apply these discoveries in risk assessment, diagnosis and personal medicine, but also forensic pathologists can make full use of these variations to conduct death cause identification. However, despite the progress in genetics, these associated genes can only account for approximately 35% of the BrS cases while the etiology of the remaining BrS cases is still unexplained. In this review, we discussed the prevalence, the genes associated with BrS and the application of molecular autopsy in forensic pathology. We also summarized the present obstacles, and provided a new insight into the genetic basis of BrS.
| S-EPMC6197104 | biostudies-literature
Project description:Hepatitis C virus (HCV) is a major global health problem with high morbidity and mortality. About 185 million people are living with HCV, of which 80% are living in low and middle income countries. With the development of new highly effective treatments for HCV, it is considered that the eradication of HCV may only be one step away. The major problem with new treatment options is its high price. The price of sofosbuvir-based treatment for one patient in the United States is US$85000-110000, while the actual production cost of a 12 wk direct-acting antiviral regimen is less than US$250. Another major hindrance in HCV eradication is the lack of quality management of blood transfusion screens. Due to the lack of HCV screening, 75% of people in the United States with HCV infection are unaware of their positive HCV status. The control of massive HCV pandemic will require a significant financial investment, political will, and support from medical, pharmaceutical, and civil organizations around the globe.
| S-EPMC4649134 | biostudies-literature
Project description:Caspases are an evolutionary conserved family of cysteine-dependent proteases that are involved in many vital cellular processes including apoptosis, proliferation, differentiation and inflammatory response. Dysregulation of caspase-mediated apoptosis and inflammation has been linked to the pathogenesis of various diseases such as inflammatory diseases, neurological disorders, metabolic diseases, and cancer. Multiple caspase inhibitors have been designed and synthesized as a potential therapeutic tool for the treatment of cell death-related pathologies. However, only a few have progressed to clinical trials because of the consistent challenges faced amongst the different types of caspase inhibitors used for the treatment of the various pathologies, namely an inadequate efficacy, poor target specificity, or adverse side effects. Importantly, a large proportion of this failure lies in the lack of understanding various caspase functions. To overcome the current challenges, further studies on understanding caspase function in a disease model is a fundamental requirement to effectively develop their inhibitors as a treatment for the different pathologies. Therefore, the present review focuses on the descriptive properties and characteristics of caspase inhibitors known to date, and their therapeutic application in animal and clinical studies. In addition, a brief discussion on the achievements, and current challenges faced, are presented in support to providing more perspectives for further development of successful therapeutic caspase inhibitors for various diseases.
| S-EPMC8519909 | biostudies-literature
Project description:Mammalian cell surfaces are modified with complex arrays of glycans that play major roles in health and disease. Abnormal glycosylation is a hallmark of cancer; terminal sialic acid and fucose in particular have high levels in tumor cells, with positive implications for malignancy. Increased sialylation and fucosylation are due to the upregulation of a set of sialyltransferases (STs) and fucosyltransferases (FUTs), which are potential drug targets in cancer. In the past, several advances in glycostructural biology have been made with the determination of crystal structures of several important STs and FUTs in mammals. Additionally, how the independent evolution of STs and FUTs occurred with a limited set of global folds and the diverse modular ability of catalytic domains toward substrates has been elucidated. This review highlights advances in the understanding of the structural architecture, substrate binding interactions, and catalysis of STs and FUTs in mammals. While this general understanding is emerging, use of this information to design inhibitors of STs and FUTs will be helpful in providing further insights into their role in the manifestation of cancer and developing targeted therapeutics in cancer.
| S-EPMC8433944 | biostudies-literature
Project description:Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.
| S-EPMC8769280 | biostudies-literature
Project description:Brachycephalic syndrome (BS) is a pathophysiological disorder caused by excessive soft tissue within the upper airways of short-nosed dog breeds, causing obstruction of the nasal, pharyngeal and laryngeal lumen, resulting in severe respiratory distress. As the prevalence of BS appears to be high among some of the affected breeds, there is an urgent need for breeding efforts to improve the health status of those dogs. In the present study, we evaluated correlations between morphometric and other phenotypic characteristics and BS in a population of 69 French bulldogs from Denmark to identify parameters that could serve as a basis for breeding against BS. Furthermore, the genetic variation was monitored to determine whether it would be possible to breed based on these characteristics without simultaneously causing a critical reduction in genetic variation. Six phenotypic characteristics were correlated with the Brachycephalic Syndrome Functional (BSF) score. Among the morphometric risk factors, nostril stenosis (NS) and neck girth (NG) had the highest impact on the BSF score, accounting for 32% and 4% of the variation, respectively. The genetic variation in the population was comparable to other pure breeds, i.e. estimated and observed heterozygosity was 0.60 and the average inbreeding coefficient was 0.01. If only dogs with Grades 1 and 2 NS (no or only mild NS) were selected for breeding the mean BSF score would be reduced significantly. However, it would result in the exclusion of 81% of the population for breeding and this is not prudent. Excluding only dogs with severe stenosis (Grade 4) would exclude 50% of the population without any adverse impact on genetic variation within the population. Although exclusion of dogs with Grade 4 would result in an apparent reduction in the mean BSF score, this reduction is not significant. As NS accounts for 32% of the variation in BSF score, a possible long term strategy to reduce the prevalence of the BS in French bulldogs would seem to be a selection scheme that first excluded dogs with the most severe NS from breeding, gradually moving towards selecting dogs with lower NS grades. According to our findings there is no viable short term solution for reducing the prevalence of BS in the French bulldog population.
| S-EPMC6913956 | biostudies-literature
Project description:Background: Opportunistic screening for individuals aged ?30 years at all levels of healthcare for early detection of diabetes mellitus (DM) and hypertension (HTN) is an integral strategy under the national program to control non-communicable diseases. There has been no systematic assessment of the screening process in primary care settings since its launch. The objective was to determine the number and proportion eligible for screening, number screened, diagnosed and treated for DM and HTN among persons aged ?30 years in two selected primary health centres (PHCs) in Dakshina Kannada district, Karnataka, India during March-May 2019 and to explore the enablers and barriers in the implementation of screening from the perspective of the health care providers (HCPs) and beneficiaries . Methods: This was a sequential explanatory mixed-methods study with a quantitative (cohort design) and a descriptive qualitative component (in-depth interviews and focus group discussions) with HCPs and persons seeking care. Those that were not known DM/HTN and not screened for DM/HTN in one year were used to estimate persons eligible for screening. Results: Of 2697 persons, 512 (19%) were eligible for DM screening, 401 (78%) were screened; 88/401 (22%) were diagnosed and 67/88 (76%) were initiated on treatment. Of 2697, 337 (13%) were eligible for HTN screening, 327 (97%) were screened, 55 (17%) were diagnosed with HTN; of those diagnosed, 44/55 (80%) were initiated on treatment. The documentation changes helped in identifying the eligible population. Patient willingness to undergo screening and recognition of relevance of screening were screening enablers. Overworked staff, logistical and documentation issues, inadequate training were the barriers. Conclusion: Nearly 19% were eligible for DM screening and 13% were eligible for HTN screening. The yield of screening was high. We noted several enablers and barriers. The barriers require urgent attention to reduce the gaps in delivery and uptake of services.
| S-EPMC7676396 | biostudies-literature
Project description:BACKGROUND:Poor physical activity is one of the major health care problems in Western civilizations. Various digital gadgets aiming to increase physical activity, such as activity trackers or fitness apps, have been introduced over recent years. The newest products are serious games that incorporate real-life physical activity into their game concept. Recent studies have shown that such games increase the physical activity of their users over the short term. OBJECTIVE:In this study, we investigated the motivational effects of the digital game "Pokémon Go" leading to continued use or abandonment of the game. The aim of the study was to determine aspects that motivate individuals to play augmented reality exergames and how this motivation can be used to strengthen the initial interest in physical activity. METHODS:A total of 199 participants completed an open self-selected Web-based survey. On the basis of their self-indicated assignment to one of three predefined user groups (active, former, and nonuser of Pokémon Go), participants answered various questions regarding game experience, physical activity, motivation, and personality as measured by the Big Five Inventory. RESULTS:In total, 81 active, 56 former, and 62 nonusers of Pokémon Go were recruited. When asked about the times they perform physical activity, active users stated that they were less physically active in general than former and nonusers. However, based on a subjective rating, active users were more motivated to be physically active due to playing Pokémon Go. Motivational aspects differed for active and former users, whereas fan status was the same within both groups. Active users are more motivated by features directly related to Pokémon, such as catching all possible Pokémon and reaching higher levels, whereas former users stress the importance of general game quality, such as better augmented reality and more challenges in the game. Personality did not affect whether a person started to play Pokémon Go nor their abandonment of the game. CONCLUSIONS:The results show various motivating elements that should be incorporated into augmented reality exergames based on the game Pokémon Go. We identified different user types for whom different features of the game contribute to maintained motivation or abandonment. Our results show aspects that augmented reality exergame designers should keep in mind to encourage individuals to start playing their game and facilitate long-term user engagement, resulting in a greater interest in physical activity.
| S-EPMC5399220 | biostudies-literature