Synthesis, physicochemical characterization and neuroprotective evaluation of novel 1-hydroxypyrazin-2(1H)-one iron chelators in an in vitro cell model of Parkinson's disease.

Iron dysregulation, dopamine depletion, cellular oxidative stress and α-synuclein protein mis-folding are key neuronal pathological features seen in the progression of Parkinson's disease. Iron chelators endowed with one or more therapeutic modes of action have long been suggested as disease modifying therapies for its treatment. In this study, novel 1-hydroxypyrazin-2(1H)-one iron chelators were synthesized and their physicochemical properties, iron chelation abilities, antioxidant capacities and neuroprotective effects in a cell culture model of Parkinson's disease were evaluated. Physicochemical properties (log ß, log D7.4, pL0.5) suggest that these ligands have a poorer ability to penetrate cell membranes and form weaker iron complexes than the closely related 1-hydroxypyridin-2(1H)-ones. Despite this, we show that levels of neuroprotection provided by these ligands against the catecholaminergic neurotoxin 6-hydroxydopamine in vitro were comparable to those seen previously with the 1-hydroxypyridin-2(1H)-ones and the clinically used iron chelator Deferiprone, with two of the ligands restoring cell viability to ≥89% compared to controls. Two of the ligands were endowed with additional phenol moieties in an attempt to derive multifunctional chelators with dual iron chelation/antioxidant activity. However, levels of neuroprotection with these ligands were no greater than ligands lacking this moiety, suggesting the neuroprotective properties of these ligands are due primarily to chelation and passivation of intracellular labile iron, preventing the generation of free radicals and reactive oxygen species that otherwise lead to the neuronal cell death seen in Parkinson's disease.

Assessment of Hypertension Using Clinical Electrocardiogram Features: A First-Ever Review.

Hypertension affects an estimated 1.4 billion people and is a major cause of morbidity and mortality worldwide. Early diagnosis and intervention can potentially decrease cardiovascular events later in life. However, blood pressure (BP) measurements take time and require training for health care professionals. The measurements are also inconvenient for patients to access, numerous daily variables affect BP values, and only a few BP readings can be collected per session. This leads to an unmet need for an accurate, 24-h continuous, and portable BP measurement system. Electrocardiograms (ECGs) have been considered as an alternative way to measure BP and may meet this need. This review summarizes the literature published from January 1, 2010, to January 1, 2020, on the use of only ECG wave morphology to monitor BP or identify hypertension. From 35 articles analyzed (9 of those with no listed comorbidities and confounders), the P wave, QTc intervals and TpTe intervals may be promising for this purpose. Unfortunately, with the limited number of articles and the variety of participant populations, we are unable to make conclusions about the effectiveness of ECG-only BP monitoring. We provide 13 recommendations for future ECG-only BP monitoring studies and highlight the limited findings in pregnant and pediatric populations. With the advent of convenient and portable ECG signal recording in smart devices and wearables such as watches, understanding how to apply ECG-only findings to identify hypertension early is crucial to improving health outcomes worldwide.

Integrated models of care for people who inject drugs and live with hepatitis C virus: A systematic review.

BACKGROUND: Despite the key role that people who inject drugs (PWID) play in the hepatitis C virus (HCV) epidemic, HCV treatment rates among this population have been historically low. Integrated models of HCV and substance use care have the potential to overcome some barriers to access; however, the evidence base is uncertain. This systematic review assesses the impacts of integrated HCV and substance use services on engagement in HCV care among PWID. METHODS: We searched five databases up to December 2018 to identify original quantitative studies evaluating the impacts of co-location of HCV and substance use services on engagement in the HCV cascade of care among adult PWID. We conducted a narrative synthesis, categorizing models based on patient entry point (a: HCV facility, b: substance use disorder (SUD) facility, and c: other facilities), and levels of integrated services offered (a: HCV/substance use testing only, b: HCV/substance use treatment, and c: testing/treatment + other services). RESULTS: A total of 46 articles corresponding to 44 original studies were included. Almost all studies (n = 42) were conducted in high-income countries and only six studies in the Direct-Acting Antiviral (DAA) era. Twenty-six studies discussed the integration of services at SUD facilities, one at HCV facilities, and seventeen at other facilities. Analysis of included studies indicated that overall integrated care resulted in improved engagement in HCV care (e.g., testing, treatment uptake and cure). However, the quality of evidence was predominantly low to moderate. CONCLUSIONS: Available evidence suggests that integration of HCV and substance use services may improve engagement along the continuum of HCV care among PWID. Given limitations in data quality, and very few studies conducted in the DAA era and in low- and middle-income settings, further research is urgently needed to inform strategies to optimize HCV care access and outcomes among PWID globally.

Integrating hepatitis C and addiction care for people who inject drugs in the era of direct-acting antiviral therapy.

As new, more tolerable and effective hepatitis C virus (HCV) treatments are available, there is a global need to consider how to maximize treatment access for groups who are most affected by HCV. A substantial number of people who inject drugs (PWID) are living with HCV, yet only a minority have received treatment. HCV treatment programs that are integrated into community-based addiction care may be a successful way to overcome barriers and increase access and uptake of HCV treatment for this population. Examples of successful HCV and addiction care integration in the community have been documented. However, potential challenges to integration exist and include changing healthcare provider roles, lack of stimulant use research and restrictive drug policies. Successful engagement of PWID in HCV care is critical step towards the elimination of HCV infection. Further research and efforts are needed in order to reach this goal.