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Background Microvascular structural alteration and dysfunction is a hallmark of arterial hypertension. So far, the visualization and the quantification of renal microcirculation in humans has been hampered by the lack of non-nephrotoxic and non-invasive radiologic techniques. Contrast-enhanced ultrasonography (CEUS) is an appealing method to investigate renal microcirculation and has not been investigated in this setting. We aimed to compare renal microcirculation in normotensive (NT) and hypertensive (HT) participants using CEUS at rest and during a sympathetic stress test. Methods We measured the renal perfusion index (PI, primary outcome), the renal resistive index (RRI), beat-to-beat systemic hemodynamics and plasma catecholamines before and during a 2-min cold pressor test (CPT) in NT and HT participants. Linear mixed model analysis was used to compare the effect of the CPT on the variables of interest. Results Seventy-three participants (32 HT) with normal kidney function were included. HT participants had a lower baseline PI compared with NT participants [median (interquartile range) 1476 (959–2155) arbitrary units (a.u.) vs 2062 (1438–3318) a.u. P  < .001]. The CPT increased blood pressure, heart rate and catecholamines in all participants. The increase in PI observed in NT during the CPT was blunted in HT [+504 (117–920) a.u. vs +1159 (678–2352) a.u in NT, interaction P  = .013]. Age, sex and body mass index did not modify these results. Conclusions HT patients had a lower basal renal cortical perfusion. During the cold pressor test, HT participants had a smaller increase in the PI, suggesting that renal cortical flow reserve is impaired. [ABSTRACT FROM AUTHOR]

Shallow firn cores, in addition to a near-basal ice core, were recovered in 2018 from the Quelccaya ice cap (5470 m a.s.l) in the Cordillera Vilcanota, Peru, and in 2017 from the Nevado Illimani glacier (6350 m a.s.l) in the Cordillera Real, Bolivia. The two sites are ~450 km apart. Despite meltwater percolation resulting from warming, particle-based trace element records (e.g. Fe, Mg, K) in the Quelccaya and Illimani shallow cores retain well-preserved signals. The firn core chronologies, established independently by annual layer counting, show a convincing overlap indicating the two records contain comparable signals and therefore capture similar regional scale climatology. Trace element records at a ~1–4 cm resolution provide past records of anthropogenic emissions, dust sources, volcanic emissions, evaporite salts and marine-sourced air masses. Using novel ultra-high-resolution (120 μm) laser technology, we identify annual layer thicknesses ranging from 0.3 to 0.8 cm in a section of 2000-year-old radiocarbon-dated near-basal ice which compared to the previous annual layer estimates suggests that Quelccaya ice cores drilled to bedrock may be older than previously suggested by depth-age models. With the information collected from this study in combination with past studies, we emphasize the importance of collecting new surface-to-bedrock ice cores from at least the Quelccaya ice cap, in particular, due to its projected disappearance as soon as the 2050s. [ABSTRACT FROM AUTHOR]

Microdialysis membranes (3 mm length x 200 [micro]m i.d.) have been used to extract volatile analytes from aqueous samples into the gas phase and interfaced with fast gas chromatography. Gas-phase extracts generated from aqueous samples reach steady-state concentrations and are transported to the detector in 5 s. The recovery of the system ranges from 1.28% for toluene to less than 0.1% for ethanol. The lowest detectable concentration without preconcentration was 5 mM for most compounds using a flame ionization detector, and as low as 0.01 mM for more volatile hydrophobic analytes. When interfaced with a fast GC system, changes in aqueous phase concentrations were monitored with a temporal resolution of 10 s.

Angiotensin peptides (ANGs) play a central role in the renin–angiotensin–aldosterone system, rendering them interesting biomarkers associated with hypertension. Precise quantification of circulating ANGs holds the potential to assess the activity of angiotensin-converting enzyme (ACE), a key protease targeted by widely prescribed drugs, namely ACE inhibitors. This ability could pave the way for personalised medicine, offering insights into the prescription of inhibitors targeting either the proteases or the receptors within the system. Despite recent developments in liquid chromatography–mass spectrometry (LC-MS) methods for measuring circulating ANG concentrations, comprehensive stability studies of ANGs in human plasma are absent in the literature, raising concerns about the reliability of measured concentrations and their link to clinical conditions. To address this critical gap, we conducted an exhaustive evaluation of the pre-analytical stability of ANG1–10, ANG1–9, ANG1–8, ANG1–7, and ANG1–5. By employing surfactants to mitigate non-specific adsorption and a dedicated mix of protease inhibitors to limit protease activity, we established an MS-based assay for these five peptides. We used this method to quantify circulating concentrations of ANGs in the plasma of 11 healthy donors and 3 patients under kidney dialysis. Our findings revealed that ANG1–10 and ANG1–8 circulate at concentrations ranging from 1 to 10 pM in healthy subjects and exhibit a high degree of correlation. Notably, ANG1–9, ANG1–7, and ANG1–5 were undetectable in any of the 14 patients, despite a sub-picomolar limit of detection. This strikingly contrasts with the reference concentrations reported in the literature, which typically fall within the picomolar range. In light of these discrepancies, we strongly advocate for rigorous pre-analytical considerations and comprehensive stability studies to ensure reliable results. We emphasise the pivotal role of heightened pre-analytical awareness within the clinical chemistry community, and we hope for continued growth in this critical area. • A comprehensive stability study of angiotensin peptides (ANGs) is provided. • This method allows the detection of sub-picomolar ANGs concentrations. • ANGs are very sensitive to protease activity, resulting in fast metabolism. • We measured ANGs concentrations lower than previously reported in literature. [ABSTRACT FROM AUTHOR]

The pre-analytical step preceding peptide extraction from the plasma matrix is crucial since peptides are often cleaved in vivo and ex vivo by several specific and nonspecific proteases. Kowalka et al.[1] recently validated a new Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) assay for PYY1-36 and PYY3-36 in human plasma using three different guidelines: the 2018 Food and Drug Administration (FDA) guideline for bioanalytical method validation, the 2014 Clinical and Laboratory Standards Institute (CLSI) C62-A guideline and the penultimate 2011 European Medicines Agency (EMA) guideline on bioanalytical method validation updated in 2015. [Extracted from the article]

Driving under the influence of alcohol and drugs (DUID) is a major field of study to improve road safety. In Switzerland, during controls whether or not they follow an accident, the police can request toxicological analysis targeted either on alcohol only (ALC cases), or on drugs and alcohol (DUID cases). To evaluate both the drugs consumption on the road and whether or not these requests are well correlated with toxicological results, we built a database recording 4003 offenders (3443 males, 550 females) over a two-year period (2018-2019) in Western Switzerland. ALC case samples were then analyzed to target other substances than ethanol. We found one or more psychoactive drugs in 89% of DUID cases and alcohol alone was found in 56% of ALC cases. In ALC cases, alcohol alone was found in 72% of non-accident cases and in 52% of accident cases. This highlights an influence of accident context, inducing a too high suspicion of alcohol after accidents, and therefore an underestimation of the prevalence of other drugs. The most frequently detected drugs in DUID cases were cannabinoids (58%), ethanol (30%), cocaine (21%), benzodiazepines (11%), amphetamines (7%), opiates (6%), and antidepressants (5%). For the ALC cases, the drugs found were ethanol (84%), cannabinoids (13%), benzodiazepines (9%), antidepressants (6%), opiates (5%), cocaine (4%), methadone (3%), and amphetamines (1%). Prescription drugs, such as benzodiazepines, were common in accidents (22%) but rare in non-accidents DUID cases (5%). Thus, these drugs highly impact driving skills while being hard to suspect. This is of first concern as prescription drugs are largely found in poly-drug consumption, especially in combination with alcohol in accident cases. This emphasizes the emerging issue of prescription drugs and should motivate a strategy of prevention focused on the noxious effect of combining alcohol and prescription drugs on driving skills. [ABSTRACT FROM AUTHOR]