IMPORTANCE Mobile applications (apps) may help improve hypertension self-management. OBJECTIVE To investigate the effect of an artificial intelligence smartphone coaching app to promote home monitoring and hypertension-related behaviors on systolic blood pressure level compared with a blood pressure tracking app. DESIGN, SETTING, AND PARTICIPANTS This was a 2-group, open, randomized clinical trial.
Tissue culture infections of CD4-positive human T cells by human immunodeficiency virus type 1 (HIV-1) proceed in three stages: (i) a period following the initiation of an infection during which no detectable virus is produced; (ii) a phase in which a sharp increase followed by a peak of released progeny virions can be measured; and (iii) a final period when virus production declines. In this study, we have derived equations describing the kinetics of HIV-1 accumulation in cell culture supernatants during multiple rounds of infection. Our analyses indicated that the critical parameter affecting the kinetics of HIV-1 infection is the infection rate constant k = Inn/ti, where n is the number of infectious virions produced by one cell (about 10(2)) and ti is the time required for one complete cycle of virus infection (typically 3 to 4 days). Of particular note was our finding that the infectivity of HIV-1 during cell-to-cell transmission is 10(2) to 10(3) times greater than the infectivity of cell-free virus stocks, the inocula commonly used to initiate tissue culture infections. We also demonstrated that the slow infection kinetics of an HIV-1 tat mutant is not due to a longer replication time but reflects the small number of infectious particles produced per cycle.
For high-intensity cycle ergometer exercise, the relation between power (P) and its tolerable duration (t) has been well characterized by the hyperbolic relationship: (P-thetaF) t = W', or P = W' (1/t)+thetaF, where thetaF may be termed the 'fatigue threshold'. The curvature constant (W') reflects a constant amount of work which is postulated to be equivalent to a finite energy store that relates to the oxygen-deficit: phosphagen pool, anaerobic glycolysis and oxygen stores. Compared to thetaF, the physiological nature of W' has received little consideration. The purpose of this study was therefore to establish the parameters of the power-duration curve (thetaF and W') for subjects in normal glycogen (NG) and glycogen depleted (GD) states. Seven healthy male subjects (aged 22 to 41 years) each performed four high-intensity square-wave exercise bouts on an electrically braked cycle ergometer under two different muscular glycogen content conditions, i.e. NG and GD states. Subjects performed the following exercise on the evening before the trial day to induce the GD state. Initially, they performed a 75-min cycling exercise at 60% of VO2max. After a 5-min rest period, they subsequently repeated a 1-min cycling bout at 115% of VO2max (separated by 1-min rest periods) until the subject could no longer maintain the prescribed pedal rate for the full minute. Subjects then reported to the laboratory after an overnight fast and performed a single high-intensity exercise bout. The GD procedure was repeated four times at 1-week intervals. In the GD state, the respiratory exchange ratio (RER) (VO2/VCO2) value during a recumbent control period prior to the trial was significantly lower than that in the NG state [GD: 0.84+/-0.02, NG: 0.94+/-0.04, mean +/- SD]. There was no significant difference for thetaF between GD and NG state [NG: 197.1+/-31.9 W, GD: 190.6+/-28.2 W]. W' in contrast was significantly reduced by the GD procedure [NG: 12.83+/-2.21 kJ, GD: 10.33+/-2.41 kJ]. The present results indicate that the muscular glycogen store seems to be an important determinant of the curvature constant (W') of the power-duration curve for cycle ergometry.
Tetherin, also known as BST-2/CD317/HM1.24, is an antiviral cellular protein that inhibits the release of HIV-1 particles from infected cells. HIV-1 viral protein U (Vpu) is a specific antagonist of human tetherin that might contribute to the high virulence of HIV-1. In this study, we show that three amino acid residues (I34, L37, and L41) in the transmembrane (TM) domain of human tetherin are critical for the interaction with Vpu by using a live cell-based assay. We also found that the conservation of an additional amino acid at position 45 and two residues downstream of position 22, which are absent from monkey tetherins, are required for the antagonism by Vpu. Moreover, computer-assisted structural modeling and mutagenesis studies suggest that an alignment of these four amino acid residues (I34, L37, L41, and T45) on the same helical face in the TM domain is crucial for the Vpu-mediated antagonism of human tetherin. These results contribute to the molecular understanding of human tetherin-specific antagonism by HIV-1 Vpu.
Lim et al. demonstrate that protein deacetylase, Sirtuin 1, promotes autoimmunity by deacetylating RORγt increasing its transcriptional activity and promoting Th17 differentiation and function. Blockade or loss of Sirtuin 1 results in protection from multiple sclerosis-like disease in mice.
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