Massive Toll Research Articles

A randomized, controlled study to evaluate the efficacy of intra-articular, autologous adipose tissue injections for the treatment of mild-to-moderate knee osteoarthritis compared to hyaluronic acid: a study protocol

BackgroundOsteoarthritis (OA) is a highly debilitating joint disease that causes progressive, irreversible damage to articular cartilage. OA takes a massive toll on society that has grown in recent decades, but no therapy has been shown to halt or reverse the progression of the disease. The critical need for better treatments and increased interest cellular therapies has spawned a new generation of “minimally manipulated” cell treatments. Autologous adipose tissue injections are among the most controversial of these new treatments. Despite a lack of clinical evidence, adipose tissue injections are often marketed as “stem cell” injections with wide-ranging regenerative benefits. The purpose of this study is to estimate the effect size of the treatment by comparing the efficacy of autologous fat to hyaluronic acid (HA). As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs. HA.MethodsThis is a prospective, single-center, parallel-group, randomized, controlled trial. Participants (n = 54) will receive either a single intra-articular, ultrasound-guided injection of autologous adipose tissue or a single intra-articular, ultrasound-guided injection of HA (1:1 ratio). Outcome data will be obtained at baseline, week-6 and month-6. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain domain (WOMAC-A) will be used as the primary outcome measure. Secondary clinical outcome measures include WOMAC (full), clinical anchors (pain, function, and stiffness), and the 29-point Patient-Reported Outcomes Measurement Information System (PROMIS®) profile. We will also take synovial fluid samples and assess sway velocity using a force plate, as well as analyze excess/discard adipose tissue to gain a better understanding of how intra-articular adipose tissue injections influence the biochemical environment of the joint.DiscussionGiven the widespread use of intra-articular fat injections in the United States, it is critical that randomized, controlled human studies evaluating efficacy and biological activity be performed. This study is the first step in addressing this unmet need, but it is not without limitations. The most notable limitations of this study are its small size and lack of blinding, which predisposes the study to both investigator and participant bias.Trial registrationNCT03242707 // HS-17-00365 // Registration Date (First Posted): August 8, 2018.

Metabolic Inhibitors as Antiparasitic Drugs: Pharmacological, Biochemical and Molecular Perspectives.

Human diseases caused by the infectious parasites have been one of the major problems throughout the evolutionary journey. Protozoan and metazoan parasitic infections result in a large number of deaths, disabilities and socio-economic loss worldwide to date. Despite the best efforts for developing suitable antiparasitics, these infections take a massive toll on human health. The prevalence of emerging resistance to the existing drugs, lack of efficacy and toxic side effects are as added complications. Being enlisted under 'neglected' category, serious diseases like leishmaniasis, filariasis, trypanosomiasis etc. have failed to draw attention of the governments as well as the pharmaceutical companies. Thus, target specific as well as cost-convenient therapy needs to be employed for the treatment of these diseases and selective targeting of metabolic pathways appears to be the most promising mean. In this context, quality works have been explored for screening either anti-metabolic drugs or selective targets in different groups of parasites. Moreover, complete genome sequencing and metabolomic profiling have provided the initiatives to search for new lethal targets in parasites. New metabolic targets are being reported from different organelles and other sub-cellular compartments of parasites such as mitochondrion, kinetoplast, apicoplast, glycosome, hydrogenosome, acidocalcisome, plasma membrane, cytoskeleton, etc. Herein, unique findings achieved in identifying new antimetabolic drugs or targets and studying their molecular mode of actions have been reviewed by incorporating existing and upcoming approaches. Considering the alarming scenario of diseases caused by parasites globally, this paper provides a comprehensive review to the scientific community on the development of novel interventions based on metabolic targets to combat the challenges posed by parasites.

Is There No Solution to Minimize the Aftermaths of Heat Waves? World Health Organization Comes Up with an Answer!!!

DEAR EDITOR, Worldwide, across the last five decades, the number of hot days, hot nights, and heat waves (hot weather which lasts for several days) has become more and more common.[1] In fact, considering the rate of climate change and environmental degradation on a global scale it has been anticipated that the scenario is going to worsen further with a substantial rise in the length, frequency, and intensity of heat waves.[1] Further, even though it is acknowledged that heat waves tend to affect cities more, the living standards and well-being of even rural people does take a massive toll.[1,2] Heat waves have resulted in a massive impact on the community, predominantly on the rising trends of mortality and morbidity.[3,4] In fact, in the months of May–June 2015 alone, more than 2500 and close to 1300 deaths have been reported in India and Karachi region of Pakistan.[5,6] Further, thousands of deaths and catastrophic consequences have even been attributed to heat waves across Europe and Russia in 2003 and 2010, respectively.[7] In addition, heat waves have shown detrimental effects on the infrastructure sector, clothes and food retailing, tourism, ecosystem, forest fires, and associated air pollution.[1,7] In response to the rising concerns associated with heat waves on the different dimensions of health and related sectors, the World Health Organization (WHO) and the World Meteorological Organization have jointly formulated guidelines pertaining to the Heat–Health Warning Systems (HHWS).[7] These guidelines possess global application and have been developed based on the recommendations of stakeholders from all concerned sectors (viz., climate, health, emergency-response agencies, policy makers, etc.).[7] This system can prove to be of extreme utility as heat waves lack the sudden violence of other disasters, but have become more frequent, and even result in serious consequences.[1] The HHWS can provide meteorological and/or climate-prediction-based information regarding the probability of forthcoming hot weather and thus can alert program managers and the general population to take timely actions to minimize the aftermaths of hot weather on health.[7] In fact, encouraging results have been reported among the nations which have successfully developed these early warning systems.[1,7] However, mere application of warning system will not deliver sustainable results unless it is adequately supported by earmarking a specific agency for carrying out meteorological activities with roles and responsibilities of other supportive agencies being clearly specified; effective inter-sectoral coordination with health sector taking a major lead in heat preventive efforts; linkages with existing voluntary organizations for outreach activities, especially for addressing the needs of vulnerable sections of society; involving members of community; encouraging widespread use of mass media, and communication technologies; strengthening of the existing infrastructure by ensuring proportionate funding and logistics support; establishing a comprehensive surveillance mechanism to monitor heat-related outcomes all across the nation; and advocating for development of climate-friendly urban cities.[1,2,5,7,8] To conclude, on a global scale heat wave has been associated with significant negative impact on the health standards of people and different industries, and thus it is a sincere appeal by the WHO to nations to develop HHWS to reduce the after-effects of hot weather on health.

Caenorhabditis elegans as a Model to Study the Molecular and Genetic Mechanisms of Drug Addiction.

Drug addiction takes a massive toll on society. Novel animal models are needed to test new treatments and understand the basic mechanisms underlying addiction. Rodent models have identified the neurocircuitry involved in addictive behavior and indicate that rodents possess some of the same neurobiologic mechanisms that mediate addiction in humans. Recent studies indicate that addiction is mechanistically and phylogenetically ancient and many mechanisms that underlie human addiction are also present in invertebrates. The nematode Caenorhabditis elegans has conserved neurobiologic systems with powerful molecular and genetic tools and a rapid rate of development that enables cost-effective translational discovery. Emerging evidence suggests that C. elegans is an excellent model to identify molecular mechanisms that mediate drug-induced behavior and potential targets for medications development for various addictive compounds. C. elegans emit many behaviors that can be easily quantitated including some that involve interactions with the environment. Ethanol (EtOH) is the best-studied drug-of-abuse in C. elegans and at least 50 different genes/targets have been identified as mediating EtOH's effects and polymorphisms in some orthologs in humans are associated with alcohol use disorders. C. elegans has also been shown to display dopamine and cholinergic system-dependent attraction to nicotine and demonstrate preference for cues previously associated with nicotine. Cocaine and methamphetamine have been found to produce dopamine-dependent reward-like behaviors in C. elegans. These behavioral tests in combination with genetic/molecular manipulations have led to the identification of dozens of target genes/systems in C. elegans that mediate drug effects. The one target/gene identified as essential for drug-induced behavioral responses across all drugs of abuse was the cat-2 gene coding for tyrosine hydroxylase, which is consistent with the role of dopamine neurotransmission in human addiction. Overall, C. elegans can be used to model aspects of drug addiction and identify systems and molecular mechanisms that mediate drug effects. The findings are surprisingly consistent with analogous findings in higher-level organisms. Further, model refinement is warranted to improve model validity and increase utility for medications development.

Research on Link Travel Time Reliability Model Based on Massive Expressway Toll Data

Massive expressway toll data contained lots of valuable information. However, the skills of mining and analyzing toll data were limited currently. This study explored the modeling method of road network travel time reliability based on massive toll data. Firstly, this study obtained travel time data sample of each link at different months, and analyzed travel time statistical properties preliminarily. Secondly, this study used normal distribution, gamma distribution and Weibull distribution to fit travel time data sample, and different statistical indicators were involved to measure the fitting effect. Fitting results showed that normal distribution for link travel time was more rational and acceptable than the others. Thus, this study established link travel time reliability model, and proposed moment estimation method of calibrating the model parameters. In practical application, the reliability model can be used to judge traffic operating posture for expressway management department, and also can be used to forecast travel time information, to provide valuable reference on decision-making for drivers travel plan or route choice.

Dihydrofolate Reductase As A Therapeutic Target for Infectious Diseases: Opportunities And Challenges

Infectious diseases caused by parasites continue to take a massive toll on human health in the poor regions of the world. Filling the anti-infective drug-discovery pipeline has never been as challenging as it is now. The organisms responsible for these diseases have interesting biology with many potential biochemical targets. Inhibition of metabolic enzymes has been established as an attractive strategy for anti-infectious drug development. In this field, dihydrofolate reductase (DHFR) is an important enzyme in nucleic and amino acid synthesis and an extensively studied drug target over the past 50 years. The challenges for novel DHFR inhibition-based chemotherapeutics for the treatment of infectious diseases are now focused on overcoming the resistance problem as well as cost-effectiveness. Each year, the large number of literature citations attest the continued popularity of DHFR. It becomes truly the 'enzyme of choice for all seasons and almost all reasons'. Herein, we summarize the opportunities and challenges in developing novel lead based on this target.

The SARS crisis: reflections of Hong Kong nurses

Severe acute respiratory syndrome (SARS) exerted a massive toll on Hong Kong's healthcare system in 2003. This research examines front-line nurses' reflections on the time of SARS in Hong Kong in order to articulate: (1) the nature and complexity of their experience, and (2) what lessons can be learned for future disease crises. Personal reflective essays written in 2004 by seven senior nurses studying a part-time Masters in Nursing degree at a Hong Kong university were analysed using a form of content analysis. The nurses' stories report immense personal costs on nurses, on their families and on the wider community. The analysis of the narratives was used to build a model, indicating how nurses' personal lives were 'sandwiched' between, on the one hand, their commitment to families and local community and, on the other hand, their professional commitment to the needs of a health system in crisis. In dealing with future health crises, it is imperative that a multilevel approach be taken.

Tsunami spares global IT but shakes up disaster recovery plans

Despite the Asian Tsunami's massive toll of human life and devastation of local businesses in the region, the impact on the global economy and on major IT centres or networks has been relatively slight. Anyone listening merely to the financial news since 26 December would have been quite unaware that one of the worst natural disasters of recent times had just taken place, to judge from the soaring stock markets. Similarly news about IT has focused on its role in helping local businesses, delivering aid, or making donations, more than on disruption to computer services.

Oral delivery of vaccines. Formulation and clinical pharmacokinetic considerations.

In recent years, there has been a gradual acceptance of the important role of sIgA in protecting mucosal surfaces against infection with a wide range of pathogenic organisms. Since sIgA is most efficiently stimulated by local application of antigens, there has been an increasing emphasis on the role of oral immunisation. The numerous advantages of the oral route over alternative routes of administration has driven the search for effective vaccines, often despite disappointing results. Nevertheless, recent developments in recombinant DNA technology and in the formulation of antigen delivery systems have given rise to justified optimism that the next decade will see the development of several new and improved oral vaccines (table IV). These vaccines will undoubtedly come to play an important role in preventing diseases caused by a number of pathogenic organisms which are currently poorly controlled. New oral vaccines are likely to be particularly beneficial in the Third World, where intestinal infections still cause a massive toll of preventable deaths. Because of the existence of the common mucosal immune system, new oral vaccines also offer the promise of control over several sexually transmitted diseases for which there are no vaccines currently available.

Botswana's fences and the depletion of Kalahari wildlife

Over the past 20 years or more fences have been erected around the part of the Kalahari that lies in Botswana without thought about the impact on the wildlife. Over the years the fences have taken a massive toll of animals whose traditional migration routes to water have been sealed off. The authors, who have been working in the Kalahari since 1981, examine the current situation and suggest some of the possible remedies that are so urgently needed.