Differential effect of denervation on free radical scavenging enzymes in slow and fast muscle of rat

To determine the effect of denervation on the free radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow twitch soleus and fast twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the mid-thigh region and the muscle tissue levels of 5 enzymes were studied 2 and 5 weeks following crush. Radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. These data represent the first systematic report of free radical scavening systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle

Stringent promoter recognition and autoregulation by the group 3 σ-factor SigF in the cyanobacterium Synechocystis sp. strain PCC 6803

The cyanobacteirum Synechocystis sp. strain PCC 6803 possesses nine species of the sigma (σ)-factor gene for RNA polymerase (RNAP). Here, we identify and characterize the novel-type promoter recognized by a group 3 σ-factor, SigF. SigF autoregulates its own transcription and recognizes the promoter of pilA1 that acts in pilus formation and motility in PCC 6803. The pilA1 promoter (PpilA1-54) was recognized only by SigF and not by other σ-factors in PCC 6803. No PpilA1-54 activity was observed in Escherichia coli cells that possess RpoF (σ28) for fragellin and motility. Studies of in vitro transcription for PpilA1-54 identified the region from −39 to −7 including an AG-rich stretch and a core promoter with TAGGC (−32 region) and GGTAA (−12 region) as important for transcription. We also confirmed the unique PpilA1-54 architecture and further identified two novel promoters, recognized by SigF, for genes encoding periplasmic and phytochrome-like phototaxis proteins. These results and a phylogenetic analysis suggest that the PCC 6803 SigF is distinct from the E. coli RpoF or RpoD (σ70) type and constitutes a novel eubacterial group 3 σ-factor. We discuss a model case of stringent promoter recognition by SigF. Promoter types of PCC 6803 genes are also summarized

Unconventional Superconductivity and Electron Correlations in Cobalt Oxyhydrate Na0.35_{0.35}CoO2_{2}⋅y\cdot yH2_{2}O

We report a precise $^{59}$Co nuclear quadrupolar resonance (NQR) measurement on the recently discovered cobalt oxyhydrate Na$_{0.35}$CoO$_{2}$$\cdot y$H$_{2}$O superconductor from $T$=40 K down to 0.2 K. We find that in the normal state the spin-lattice relaxation rate $1/T_1$ follows a Curie-Weiss type temperature ($T$) variation, $1/T_1T=C/(T-\theta)$, with $\theta$=-42 K, suggesting two-dimensional antiferromagnetic spin correlations. Below $T_c$=3.9 K, $1/T_1$ decreases with no coherence peak and follows a $T^n$ dependence with $n\simeq$2.2 down to $\sim$2.0 K but crosses over to a $1/T_1\propto T$ variation below $T$=1.4 K, which suggests non s-wave superconductivity. The data in the superconducting state are most consistent with the existence of line nodes in the gap function.Comment: submitted for publication in June '0

Inhomogeneous electronic structure probed by spin-echo experiments in the electron doped high-Tc superconductor Pr_{1.85}Ce_{0.15}CuO_{4-y}

63Cu nuclear magnetic resonance (NMR) spin-echo decay rate (T_2^{-1}) measurements are reported for the normal and superconducting states of a single crystal of Pr_{1.85}Ce_{0.15}CuO_{4-y} (PCCO) in a magnetic field B_0=9T over the temperature range 2K<T<200K. The spin-echo decay rate is temperature-dependent for T<55K, and has a substantial dependence on the radio frequency (rf) pulse parameters below T~25K. This dependence indicates that T_2^{-1} is strongly effected by a local magnetic field distribution that can be modified by the rf pulses, including ones that are not at the nuclear Larmor frequency. The low-temperature results are consistent with the formation of a static inhomogeneous electronic structure that couples to the rf fields of the pulses.Comment: 4 pages, 4 figure

Starting Antihypertensive Drug Treatment With Combination Therapy

The 2018 European Society of Cardiology/European Society of Hypertension1 and the 2020 International Society of Hypertension2 guidelines for the management of hypertension proposed that initial combination therapy with 2 antihypertensive agents in a single-pill combination (SPC) is preferred in most patients in need of blood pressure (BP) lowering treatment and should replace the long-standing concept of starting treatment with a single agent, rotating through antihypertensive drug classes, and next moving towards combining drug classes. By moving SPCs forward as the initial BP-lowering strategy, the European1 and International2 Societies of Hypertension Guideline Committees overlooked several principles in hypertension management: (1) understanding the pathophysiology of hypertension; (2) prioritizing evidence from randomized clinical trials above observational studies and expert opinion; and (3) giving consideration to the cost-effectiveness of antihypertensive drug treatment and the sustainability of health care. This article addresses these points. Sources of information included (1) guidelines issued by European,1,3,4 American,5–7 International,2,8,9 and British10–12 Expert Committees, published between 19998 and 2020,2 summarized in Table S1 in the Data Supplement; (2) a PubMed search ran on May 5, 2020, without limitations with as search terms in the abstract or title “hypertension” combined with “fixed combination” OR “hypertension” combined with “single” and “costs”; (3) the placebo-controlled trials of antihypertensive drug treatment, as identified from the reference lists of 5 systematic literature reviews,13–17 of which 2 were published by the Blood Pressure Lowering Trialists’ Collaboration14,16; (4) 3 randomized controlled trials of usual versus intensive BP control18–20; and (5) the retail costs of antihypertensive drugs on the Belgian market (https://www.bcfi.be)

What Does The Korringa Ratio Measure?

We present an analysis of the Korringa ratio in a dirty metal, emphasizing the case where a Stoner enhancement of the uniform susceptibilty is present. We find that the relaxation rates are significantly enhanced by disorder, and that the inverse problem of determining the bare density of states from a study of the change of the Knight shift and relaxation rates with some parameter, such as pressure, has rather constrained solutions, with the disorder playing an important role. Some preliminary applications to the case of chemical substitution in the Rb$_{3-x}$K$_x$C$_{60}$ family of superconductors is presented and some other relevant systems are mentioned.Comment: 849, Piscataway, New Jersey 08855 24 June 199

Isolated Diastolic Hypertension in the IDACO Study: An Age-Stratified Analysis Using 24-Hour Ambulatory Blood Pressure Measurements

The prognostic implications of isolated diastolic hypertension (IDH), as defined by 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, have not been tested using ambulatory blood pressure (BP) monitor thresholds (ie, 24-hour mean systolic BP \u3c125 mm Hg and diastolic BP ≥75 mm Hg). We analyzed data from 11 135 participants in the IDACO (International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes). Using 24-hour mean ambulatory BP monitor values, we performed Cox regression testing independent associations of IDH with death or cardiovascular events. Analyses were conducted in the cohort overall, as well as after age stratification (\u3c50 years versus ≥50 years). The median age at baseline was 54.7 years and 49% were female. Over a median follow-up of 13.8 years, 2836 participants died, and 2049 experienced a cardiovascular event. Overall, irrespective of age, IDH on 24-hour ambulatory BP monitor defined by 2017 American College of Cardiology/American Heart Association criteria was not significantly associated with death (hazard ratio, 0.95 [95% CI, 0.79–1.13]) or cardiovascular events (hazard ratio, 1.14 [95% CI, 0.94–1.40]), compared with normotension. However, among the subgroup \u3c50 years old, IDH was associated with excess risk for cardiovascular events (2.87 [95% CI, 1.72–4.80]), with evidence for effect modification based on age (P interaction \u3c0.001). In conclusion, using ambulatory BP monitor data, this study suggests that IDH defined by 2017 American College of Cardiology/American Heart Association criteria is not a risk factor for cardiovascular disease in adults aged 50 years or older but is a risk factor among younger adults. Thus, age is an important consideration in the clinical management of adults with IDH

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated with Out-of-Office Blood Pressure

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and \u3e80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P\u3c0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P≤0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension

Outcome-Driven Thresholds for Ambulatory Pulse Pressure in 9938 People Recruited from 11 Populations

Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24–h ambulatory PP, we analyzed 9938 people randomly recruited from 11 populations (47.3% women). After age stratification (≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68,853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39,923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69 and 1.40 for all cardiovascular, cardiac and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R2 statistic) to the overall risk among elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous

Ambulatory Hypertension Subtypes and 24-Hour Systolic and Diastolic Blood Pressure as Distinct Outcome Predictors in 8341 Untreated People Recruited From 12 Populations

Background—Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce. Methods and Results—We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043). Conclusions—The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors