Was similar to a previous study involving 301 healthy individuals (0.25 cm2) [58] and areas ranging from 0.28?.35 cm2 have been previously reported in healthy young adults [31]. The higher area of echogenicity in the current study is likely due to differences in the Tubastatin-A ultrasound manufacturer, transducer properties (1? MHz versus 2.5 MHz), greater propensity for the ultrasound beam to penetrate bone (97.5 versus 77?2 ) [24,52,53,58], and improvements in ultrasound resolution over time. Such factors did not contribute to the between group difference observed in the current study because all subjects were tested with a Philips iU22 buy Emixustat (hydrochloride) system and s5? transducer. The between group difference in substantia nigra echogenicity is also unlikely due to the ultrasound operator. All subjects were tested by one operator and the measurements collected by this operator were consistent with those collected immediately after by a second operator. The reliability and reproducibility statistics were comparable to those published previously [63,64] and a subset of images was viewed by a third person for confirmation of image quality. However, a limitation of the current study is that the operator was not blinded to the individual’s drug history.ConclusionsThe results of the current study suggest that some individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson’s disease later in life [36] and our result supports recent epidemiological data suggesting that methamphetamine use is associated with increased risk (hazard ratio = 2.65) of developing Parkinson’s disease [65]. Further research is required to determine if the observed abnormality in stimulant users is associated with subtle movement dysfunction.AcknowledgmentsThe authors would like to thank Ms Verity Pearson-Dennett for assistance with data collection and Dr Eva Betz for assistance with recruitment of volunteers.Author ContributionsConceived and designed the experiments: GT JW. Performed the experiments: GT SF CN CD. Analyzed the data: GT SF CN. Contributed reagents/materials/analysis tools: PS BC DB. Wrote the paper: GT CN SF CD PS BC DB JW.
Brain (also known as B-type) natriuretic peptide (BNP) has been used as a biomarker of heart failure for more than a decade [1]. Indeed, guidelines for the treatment of heart failure 
recommend measurement BNP before making a diagnosis [2,3]. During the process by which BNP is secreted from cardiac myocytes, its 108amino acid precursor, proBNP, is cleaved to form the 32-amino acid peptide BNP and the 76-amino acid peptide N-terminal proBNP fragment (NT-proBNP) [4]. Recent studies have shown that in addition to BNP and the NT-proBNP, levels of uncleaved proBNP are also considerably increased in plasma of patients with heart failure [5,6,7]. This is noteworthy in part because theimmunoassay system currently being used to measure BNP levels also detects proBNP, as the anti-BNP antibody cross-reacts with proBNP. Consequently, the present assay system actually measures not the active BNP level, but the total BNP (BNP+proBNP) level [8]. It is important to know the proBNP level and/or proBNP/total BNP ratio in heart failure, because proBNP has much less ability to induce cGMP production (about 13?7 ) than BNP, and higher levels of the low-activity proBNP may be associated with the development of heart failure [7]. Consistent with that idea, we recen.Was similar to a previous study involving 301 healthy individuals (0.25 cm2) [58] and areas ranging from 0.28?.35 cm2 have been previously reported in healthy young adults [31]. The higher area of echogenicity in the current study is likely due to differences in the ultrasound manufacturer, transducer properties (1? MHz versus 2.5 MHz), greater propensity for the ultrasound beam to penetrate bone (97.5 versus 77?2 ) [24,52,53,58], and improvements in ultrasound resolution over time. Such factors did not contribute to the between group difference observed in the current study because all subjects were tested with a Philips iU22 system and s5? transducer. The between group difference in substantia nigra echogenicity is also unlikely due to the ultrasound operator. All subjects were tested by one operator and the measurements collected by this operator were consistent with those collected immediately after by a second operator. The reliability and reproducibility statistics were comparable to those published previously [63,64] and a subset of images 
was viewed by a third person for confirmation of image quality. However, a limitation of the current study is that the operator was not blinded to the individual’s drug history.ConclusionsThe results of the current study suggest that some individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson’s disease later in life [36] and our result supports recent epidemiological data suggesting that methamphetamine use is associated with increased risk (hazard ratio = 2.65) of developing Parkinson’s disease [65]. Further research is required to determine if the observed abnormality in stimulant users is associated with subtle movement dysfunction.AcknowledgmentsThe authors would like to thank Ms Verity Pearson-Dennett for assistance with data collection and Dr Eva Betz for assistance with recruitment of volunteers.Author ContributionsConceived and designed the experiments: GT JW. Performed the experiments: GT SF CN CD. Analyzed the data: GT SF CN. Contributed reagents/materials/analysis tools: PS BC DB. Wrote the paper: GT CN SF CD PS BC DB JW.
Brain (also known as B-type) natriuretic peptide (BNP) has been used as a biomarker of heart failure for more than a decade [1]. Indeed, guidelines for the treatment of heart failure recommend measurement BNP before making a diagnosis [2,3]. During the process by which BNP is secreted from cardiac myocytes, its 108amino acid precursor, proBNP, is cleaved to form the 32-amino acid peptide BNP and the 76-amino acid peptide N-terminal proBNP fragment (NT-proBNP) [4]. Recent studies have shown that in addition to BNP and the NT-proBNP, levels of uncleaved proBNP are also considerably increased in plasma of patients with heart failure [5,6,7]. This is noteworthy in part because theimmunoassay system currently being used to measure BNP levels also detects proBNP, as the anti-BNP antibody cross-reacts with proBNP. Consequently, the present assay system actually measures not the active BNP level, but the total BNP (BNP+proBNP) level [8]. It is important to know the proBNP level and/or proBNP/total BNP ratio in heart failure, because proBNP has much less ability to induce cGMP production (about 13?7 ) than BNP, and higher levels of the low-activity proBNP may be associated with the development of heart failure [7]. Consistent with that idea, we recen.