Background
Agonistic angiotensin II type I receptor autoantibodies (AT1RaAbs) have not been associated with functional measures or risk for adverse health outcomes. AT1RaAbs could be utilized to stratify patient risk and to identify patients who can benefit from angiotensin receptor blocker (ARB) treatment.
Methods
Demographic and physiologic covariates were measured in a discovery set of community dwelling adults from Baltimore (N=255) and AT1RaAb associations with physical function tests and outcomes assessed. A group from Chicago (N=60) was used for validation of associations and to explore the impact of ARB treatment.
Results
The Baltimore group had 28 subjects with falls, 32 frail subjects and 5 deaths. Higher AT1RaAbs correlated significantly with interleukin-6 (Spearman r = 0.33, P < 0.0001), systolic BP (Spearman r = 0.28, P < 0.0001), body mass index (Spearman r = 0.28, P < 0.0001), weaker grip strength (Spearman r = −0.34, P < 0.01), and slower walking speed (Spearman r = −0.30, P < 0.05). Individuals with high AT1RaAbs were 3.9 (95% CI 1.38–11.0) times more likely to be at high risk after adjusting for age (P<0.05).Every 1 µg/ml increase in AT1RaAbs increased the odds of falling 30% after adjusting for age, gender, BMI and BP. TThe Chicago groupgroup had 46 subjects with falls and 60 deaths.. Serum AT1RaAb levels were significantly correlated with grip strength (Spearman r = −0.57, P < 0.005), walking speed (Spearman r = −0.47, P< 0.005) and falls (Spearman r = 0.30, P < 0.05). Every 1 µg/ml increase in AT1RaAbs, decreased time to death by 9% after adjusting for age, gender, BMI and BP. Chronic treatment with ARBs was associated with better control of systolic BP and attenuation of decline in both grip strength and time to death.
Conclusions
In older individuals, higher AT1RaAb levels were associated with inflammation, hypertension and adverse outcomes. ARB treatment may blunt the harm associated with high levels of AT1RaAb.
Clinical laboratory-based nucleic acid amplification tests (NAT) play an important role in diagnosing viral infections. However, laboratory infrastructure requirements and their failure to diagnose at the point-of-need (PON) limit their clinical utility in both resource-rich and -limited clinical settings. The development of fast and sensitive PON viral NAT may overcome these limitations. The scalability of silicon microchip manufacturing combined with advances in silicon microfluidics present an opportunity for development of rapid and sensitive PON NAT on silicon microchips. In the present study, we present rapid and sensitive NAT for a number of RNA and DNA viruses on the same silicon microchip platform. We first developed sensitive (4 copies per reaction) one-step RT-qPCR and qPCR assays detecting HCV, HIV, Zika, HPV 16, and HPV 18 on a benchtop real-time PCR instrument. A silicon microchip was designed with an etched 1.3 μL meandering microreactor, integrated aluminum heaters, thermal insulation trenches and microfluidic channels; this chip was used in all on-chip experiments. Melting curve analysis confirmed precise and localized heating of the microreactor. Following minimal optimization of reaction conditions, the bench-scale assays were successfully transferred to 1.3 μL silicon microreactors with reaction times of 25 min with no reduction in sensitivity, reproducibility, or reaction efficiencies. Taken together, these results demonstrate that rapid and sensitive detection of multiple viruses on the same silicon microchip platform is feasible. Further development of this technology, coupled with silicon microchip-based nucleic acid extraction solutions, could potentially shift viral nucleic acid detection and diagnosis from centralized clinical laboratories to the PON.
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