Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson’s disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1’s role as a plausible novel therapeutic target for cardiovascular disease.     

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP⁺ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP⁺-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.     

The Parkinson larynx: Tremor and videostroboscopic findings

Patients with Parkinson's disease have a high incidence of speech, voice, and laryngeal abnormalities. To characterize laryngeal abnormalities, visual-perceptual ratings of endoscopic and stroboscopic examinations of 22 patients diagnosed with idiopathic Parkinson's disease and 7 patients with Parkinson's-plus syndromes were carried out by four trained viewers. Incidence of tremor, tremor location, phase closure, phase symmetry, amplitude, and mucosal waveform were scored. Tremor was observed in one or more of these conditions—rest, normal pitch and loudness, or loud phonation—for most of the 29 patients. Fifty-five percent of the idiopathic Parkinson's disease patients had tremor, with the primary location being vertical laryngeal tremor. Sixty-four percent of the Parkinson's-plus patients had tremor, with the arytenoid cartilages being the primary location. Laryngeal tremor was observed early in the disease in these Parkinson's disease patients. The most striking stroboscopic findings for the idiopathic Parkinson's disease patients were abnormal phase closure and phase asymmetry. Amplitude and mucosal wave-form were essentially within normal limits in the majority of the idiopathic Parkinson patients.     

Episodic paroxysmal laryngospasm: Voice and pulmonary function assessment and management

Episodic paroxysmal laryngospasm (EPL) is a sign of laryngeal dysfunction, often without a specific organic etiology, which can masquerade as asthma, vocal fold paralysis, or a functional voice disorder. The intermittent respiratory distress of EPL may precipitate an apparent upper airway obstructive emergency, resulting in unnecessary endotracheal intubation, cardiopulmonary resuscitation, or tracheostomy. During 27 months, seven women and three men, ages 30–76 years, were assessed by a high diagnostic index of suspicion, an intensive history including psychosocial factors, physical examination of the airways, provocative asthma testing, and swallowing studies. Videolaryngoscopy, stroboscopy, and pulmonary flow-volume loop testing were definitive. The classic appearance was paradoxic inspiratory adduction of the anterior vocal folds with a posterior diamond-shaped glottic gap. During an attack of stridor or wheezing, attenuation of the inspiratory flow rate as depicted by the flow-volume loop suggested partial extrathoracic upper airway obstruction. Swallowing evaluation by videolaryngoscopy and videoesophagography may uncover gastroesophageal reflux disease. Hallmarks of management include patient and family education by observation of laryngoscopic videos, a specific speech therapy program, psychotherapy, and medical treatment of associated disorders. Electromyography may become a valuable future adjunct. Unlike laryngeal dystonia, patients with EPL do not benefit from botulinum toxin type A.     

关于F-正则性的注记

引进－环的Ｆ－正则根，具体讨论ｆ－正则性，得到了ｆ－正则－环的几个特征刻划以及结构定理，推广了Ｆ－正则－环的相应结果．举出ｖｏｎＮｅｕｍａｎｎ（弱、Ｆ－、ｆ－）正则的－环，而不是结合环的实例，并阐明上述几种正则性的区别．     

Metal-amyloid-β peptide interactions: a preliminary investigation of molecular mechanisms for Alzheimer''''s disease

Although humans have spent exactly 100 years combating Alzheimer's disease (AD), the molecular mechanisms of AD remain unclear. Owing to the rapid growth of the oldest age groups of the population and the continuous increase of the incidence of AD, it has become one of the crucial problems to modern sciences. It would be impossible to prevent or reverse AD at the root without elucidating its molecular mechanisms. From the point of view of metal-amyloid-β peptide (Aβ) interactions, we review the molecular mechanisms of AD, mainly including Cu2 and Zn2 inducing the aggregation of Aβ, catalysing the production of active oxygen species from Aβ, as well as interacting with the ion-channel-like structures of Aβ. Moreover, the development of therapeutic drugs on the basis of metal-Aβ interactions is also briefly introduced. With the increasingly rapid progress of the molecular mechanisms of AD, we are now entering a new dawn that promises the delivery of revolutionary developments for the control of dementias.     

Decision support system for mass dispensing of medications for infectious disease outbreaks and bioterrorist attacks

A simulation and decision support system, RealOpt^©, for planning large-scale emergency dispensing clinics to respond to biological threats and infectious disease outbreaks is described. The system allows public health administrators to investigate clinic design and staffing scenarios quickly. RealOpt^© incorporates efficient optimization technology seamlessly interfaced with a simulation module. The system's correctness and computational advantage are validated via comparisons against simulation runs of the same model developed on a commercial system. Simulation studies to explore facility layout and staffing scenarios for smallpox vaccination and for an actual anthrax-treatment dispensing exercise and post event analysis are presented. The system produces results consistent with the model built on the commercial system, but requires only a fraction of the computational time. Each smallpox scenario runs within 1 CPU minute on RealOpt^©, versus run times of over 5–10 h on the commercial system. The system's fast computational time enables its use in large-scale studies, in particular an anthrax response planning exercise involving a county with 864,000 households. The computational effort required for this exercise was roughly 30 min for all scenarios considered, demonstrating that RealOpt^© offers a very promising avenue for pursuing a comprehensive investigation involving a more diverse set of scenarios, and justifying work towards development of a robust system that can be widely deployed for use by state, local, and tribal health practitioners. Using our staff allocation and assignments for the Anthrax field exercise, DeKalb county achieved the highest throughput among all counties that simultaneously conducted the same scale of Anthrax exercise at various locations, with labor usage at or below the other counties. Indeed, DeKalb exceeded the targeted number of households, and it processed 50% more individuals compared to the second place county. None of the other counties achieved the targeted number of households. The external evaluators commented that DeKalb produced the most efficient floor plan (with no path crossing), the most cost-effective dispensing (lowest labor/throughput value), and the smoothest operations (shortest average wait time, average queue length, equalized utilization rate). The study proves that even without historical data, using our system one can plan ahead and be able to wisely estimate the required labor resources. The exercise also revealed many areas that need attention during the operations planning and design of dispensing centers. The type of disaster being confronted (e.g., biological attack, infectious disease outbreak, or a natural disaster) also dictates different design considerations with respect to the dispensing clinic, facility locations, dispensing and backup strategies, and level of security protection. Depending on the situation, backup plans will be different, and the level of security and military personnel, as well as the number of healthcare workers required, will vary. In summary, the study shows that a real-time decision support system is viable through careful design of a stand-alone simulator coupled with powerful tailor-designed optimization solvers. The flexibility of performing empirical tests quickly means the system is amenable for use in training and preparation, and for strategic planning before and during an emergency situation. The system facilitates analysis of “what-if'' scenarios, and serves as an invaluable tool for operational planning and dynamic on-the-fly reconfigurations of large-scale emergency dispensing clinics. It also allows for “virtual field exercises” to be performed on the decision support system, offering insight into operations flow and bottlenecks when mass dispensing is required for a region with a large population. The system, designed in modular form with a flexible implementation, enables future expansion and modification regarding emergency center design with respect to treatment for different biological threats or disease outbreaks. Working with emergency response departments, further fine-tuning and development of the system will be made to address different biological attacks and infectious disease outbreaks, and to ensure its practicality and usability.     

The catecholamine system in health and disease —Relation to tyrosine 3-monooxygenase and other catecholamine-synthesizing enzymes—

Catecholamines [dopamine, noradrenaline (norepinephrine), and adrenaline (epinephrine); CAs] are neurotransmitters in the central and peripheral nervous systems as well as hormones in the endocrine system. CAs in the brain play a central role in versatile functions as slow-acting neurotransmitters functioning in synaptic neurotransmission, modulating the effects of fast-acting neurotransmitters such as glutamate and γ-aminobutyric acid (GABA). In this review, I focus on recent advances in the biochemistry and molecular biology of the CA system in humans in health and disease, especially in neuropsychiatric diseases such as Parkinson’s disease (PD), in relation to the biosynthesis of CAs regulated by a pteridine-dependent monooxygenase, tyrosine 3-monooxygenase (tyrosine hydroxylase, TH) and its pteridine cofactor, tetrahydrobiopterin (BH4).     

Correlated randomness: Some examples of exotic statistical physics

One challenge of biology, medicine, and economics is that the systems treated by these sciences have no perfect metronome in time and no perfect spatial architecture-crystalline or otherwise. Nonetheless, as if by magic, out of nothing but randomness one finds remarkably fine-tuned processes in time and remarkably fine-tuned structures in space. To understand this ‘miracle’, one might consider placing aside the human tendency to see the universe as a machine. Instead, one might address the challenge of uncovering how, through randomness (albeit, as we shall see, strongly correlated randomness), one can arrive at many spatial and temporal patterns in biology, medicine, and economics. Inspired by principles developed by statistical physics over the past 50 years-scale invariance and universality-we review some recent applications of correlated randomness to fields that might startle Boltzmann if he were alive today.