1,721,094 research outputs found
Role of phenotypic investigation in the era of routine genotypic HIV-1 drug resistance testing
No full textThe emergence of drug resistance can seriously compromise HIV type-1 therapy and decrease therapeutic options. Resistance testing is highly recommended to guide treatment decisions and drug activity can be accurately predicted in the clinical setting through genotypic assays. While phenotypic systems are not suitable for monitoring drug resistance in routine laboratory practice, genotyping can misclassify unusual or complex mutational patterns, particularly with recently approved antivirals. In addition, phenotypic assays remain fundamental for characterizing candidate antiretroviral compounds. This review aims to discuss how phenotypic assays contributed to and still play a role in understanding the mechanisms of resistance of both licensed and investigational HIV type-1 inhibitors
Does home blood pressure allow for a better assessment of the white-coat effect than ambulatory blood pressure?
No full textBACKGROUND:
The difference between clinic and ambulatory blood pressure (BP) is a poor estimate of the true white-coat effect (WCE) measured with beat-to-beat recording.
METHOD:
We investigated whether the difference between clinic and home BP (home WCE) was a better estimate of true WCE than ambulatory WCE. In 73 young hypertensives, ambulatory WCE was calculated as the difference between clinic BP and the mean of two 24-h BP recordings, and home WCE as the difference between clinic and home BP (HBP) measured over 6 months. All individuals underwent beat-to-beat BP monitoring with the Finometer. During the recording, a white-coat test (true WCE) and a public speaking test were performed.
RESULTS:
Ambulatory WCE correlated with home WCE (P 0.21). Individuals were divided into two groups according to whether BP response to the doctor's visit was above (WCH+) or below (WCH-) the median. WCH+ patients had similar clinic and ambulatory BPs to WCH- but showed a higher BP response to public speaking.
CONCLUSION:
As previously observed for ambulatory WCE, home WCE does not reflect the true BP reaction to doctor's visit. BP response to psychosocial stressors is increased in individuals with hyperreactivity to doctor's measurement but not in individuals with white-coat hypertension identified with either ambulatory or HBP measurement
Blood Pressure Hyperreactivity to Standing: a Predictor of Adverse Outcome in Young Hypertensive Patients
Get PDFThe prognostic significance and the mechanisms of blood pressure (BP) hyperreactivity to standing remain controversial. This study aims to evaluate the association of orthostatic hyperreactivity with major adverse cardiovascular and renal events in a cohort of young hypertensive subjects. We studied 1207 untreated subjects screened for stage I hypertension with a mean age of 33.1±8.6 years. The orthostatic BP change was calculated as the difference between 6 standing and 6 supine BP readings obtained during 2 separate visits. Hyperreactivity to standing was defined as the standing-supine systolic BP difference in the top decile. The mean difference in the whole group was -2.5±7.3/4.6±5.4 mm Hg. Ambulatory hypertension evaluated with 24-hour recordings was more common in Hyperreactors than Normoreactors (90.8% versus 76.4%, P=0.001). In 630 participants in whom 24-hour urinary catecholamines were measured, epinephrine/creatinine ratio was higher in hyperreactors (118.4±185.6 versus 77.0±90.1 nmol/mol, P=0.005). During a 17.2-year follow-up, 105 major adverse cardiovascular and renal events were accrued. In a multivariate Cox model, hyperreactivity to standing was an independent predictor of major adverse cardiovascular and renal events with a hazard ratio of 1.97 (95% CI, 1.10-3.52). Hyperreactivity remained an independent predictor of adverse events even when ambulatory BP data and incident hypertension during follow-up were included in the Cox model (hazard ratio, 1.94 [95% CI, 1.10-3.44]). Our data indicate that in young-to-middle-age hypertensive subjects an exaggerated systolic BP response to standing is associated with sympatho-adrenergic hyperreactivity and is an independent predictor of major adverse cardiovascular and renal events. Orthostatic BP assessment gives the advantage of simple acquisition and provides prognostic information on top of ambulatory BP
Rectangular cuffs may overestimate blood pressure in individuals with large conical arms.
No full textOBJECTIVES: : Although the upper arm has the shape of a truncated cone, cylindrical cuffs and bladders are currently used for blood pressure (BP) measurement. The aim of this study was to ascertain whether cylindrical and tronco-conical cuffs provide different readings according to arm size and shape.
DESIGN: : We studied 220 individuals with arm circumference ranging from 22 to 42.5 cm. Four different cylindrical and four different tronco-conical bladders of appropriate size were used. Sequential same-arm measurements were performed in triplicate by two observers using the two cuffs in a random order. In 100 individuals, the actual pressure transmitted to the arm surface by the two cuffs at the central point was also measured.
RESULTS: : Upper arm shape was tronco-conical in all of the individuals. In a multiple regression, conicity was related to arm circumference (P < 0.001) and length (P = 0.001). Arm conicity and size were independently related to the between-cuff SBP (P = 0.001 and 0.002, respectively) and DBP (P = 0.001 and <0.001, respectively) discrepancies. In the group with arm circumference of 37.5-42.5 cm, the cylindrical cuff overestimated BP measured with the tronco-conical cuff by 2.0 ± 0.4/1.8 ± 0.3 mmHg (P = 0.001 and <0.001). In this group, 15% of individuals found hypertensive with the cylindrical cuff were normotensive when assessed with the conical cuff. Differences as great as 9.7/7.8 mmHg were found in individuals with large arms and slant angle equal to or less than 83°.
CONCLUSION: : In obese people, the upper arm may have a pronounced tronco-conical shape and cylindrical cuffs may overestimate BP. Tronco-conical cuffs should be used for BP measurement in individuals with large arms
Synergies between industry and nature – An emergy evaluation of a biodiesel production system integrated with ecological systems
No full textTechno-ecological synergy (TES) is a framework that encourages integration of technological and ecological systems. Specifically, it incorporates the role of natural capital in engineering assessment and design by quantifying both demand and supply of ecosystem services. Emergy can provide valuable support to improve and interpret TES evaluation, as it is a methodology particularly useful for evaluating systems at the biosphere–technosphere interface. The present study evaluates how the TES framework based on emergy can shed new light by comparing conventional technological alternatives and ecological alternatives for meeting a particular ecosystem service demand. Both the demand and supply of ecosystem services are quantified in consistent units of emergy to obtain aggregated TES metrics. Specifically it was found that additional equipment to treat air pollutants have a higher emergy investment as compared to the forest ecosystem, while the technological unit to treat wastewater requires less emergy as compared to the horizontal subsurface flow wetland, its ecological counterpart. This new approach is tested by application to a biodiesel production plant and by calculating emergy metrics. This work shows that emergy can provide a fundamental improvement to the current TES framework, as it provides an aggregated metric for multiple ecosystem services
Validation of the A&D BP UB-542 wrist device for home blood pressure measurement according to the European Society of Hypertension International Protocol revision 2010.
Get PDFOBJECTIVE: The objective of this study was to determine the accuracy of the A&D BP UB-542 wrist device for home blood pressure (BP) measurement according to the International Protocol of the European Society of Hypertension (ESH).
METHODS: Device evaluation was carried out in 33 patients. The mean age was 50.9±10.1 years, the mean systolic BP was 141.6±22.8 mmHg (range 92 : 189), the mean diastolic BP was 89.2±11.4 mmHg (range 62 : 120), the mean arm circumference was 28.8±3.2 cm (range 23-35), and the mean wrist circumference was 17.1±1.4 cm (range 14-19.5). The protocol requirements were followed precisely.
RESULTS: The device passed all requirements, fulfilling the standards of the protocol. On average, the device overestimated the systolic BP by 1.8±7.2 mmHg and diastolic BP by 1.6±5.7 mmHg.
CONCLUSION: These data show that the A&D BP UB-542 wrist device met the requirements for validation by the International Protocol and can be recommended for clinical use in the adult population
Diagnostic and Prognostic meaning of Gated Stress Cardiac Single-Photon Emission Computed Tomography Imaging (gated SPECT) in patients with Left Bundle-Brunch Block (LBBB) and without Coronary Artery Disease (CAD)
No full textTargeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge
Get PDFThe RNA-dependent RNA polymerase (RdRp) is an essential enzyme for the viral replication process, catalyzing the viral RNA synthesis using a metal ion-dependent mechanism. In recent years, RdRp has emerged as an optimal target for the development of antiviral drugs, as demonstrated by recent approvals of sofosbuvir and remdesivir against Hepatitis C virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively. In this work, we overview the main sequence and structural features of the RdRp of emerging RNA viruses such as Coronaviruses, Flaviviruses, and HCV, as well as inhibition strategies implemented so far. While analyzing the structural information available on the RdRp of emerging RNA viruses, we provide examples of success stories such as for HCV and SARS-CoV-2. In contrast, Flaviviruses' story has raised attention about how the lack of structural details on catalytically-competent or ligand-bound RdRp strongly hampers the application of structure-based drug design, either in repurposing and conventional approaches
Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy
No full textNon-nucleoside reverse transcriptase inhibitor (NNRTI) therapy failed in 30 patients with the typical human immunodeficiency virus type 1 reverse transcriptase K103N mutation, detected using standard genotyping. Following discontinuation of NNRTI therapy for a median of 55.9 weeks and a decrease of K103N mutant species to undetectable levels in plasma RNA, minority K103N species remained detectable, by allele-specific PCR, for longer periods of time and at higher frequency, in peripheral blood mononuclear cell (PBMC) DNA than in plasma RNA (76.7% and 46.7% of samples with residual K103N species detected at median frequencies of 18.0% and 3.8%, respectively). Analysis of PBMC DNA should be considered when searching for residual K103N mutant species in patients previously exposed to NNRTIs
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