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•Prompt initiation of diuretic therapy was not correlated with faster decongestion in acute heart failure.•The timing of decongestion but not diuretics was associated with better biomarker trajectories.•Residual congestion rather than the timing of decongestion or diuretics predicted prognosis. Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase–associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase–associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

Measurement of cardiac biomarkers has become routine for the care of patients with heart failure (HF). While troponin and natriuretic peptides are well-entrenched in the guidelines, soluble ST2 (sST2) is a novel biomarker that has shown consistent performance and is ready for clinical use. Multiple studies support the use of sST2 in both acute and chronic HF for prognostication. We suggest a novel scheme to guide HF management based on ambulatory sST2 levels.

Introduction Previous observation identified both hypotension and arterial aging, indexed as Pulse Wave Velocity (PWV), as significant determinants of cognitive decline in older subjects. Aim To investigate the role of PWV as a determinant of hypotension in older patients. Methods A cohort of 344 subjects came to our Outpatient Clinic, free of cancer, acute myocardial infarction or stroke, atrial fibrillation, renal, hepatic or cardiac failure, secondary hypertension, or thyroid disease. Results Hypotension occurred in 49% of participants. SBP levels (OR 0.79, 95% CI 0.67–0.84, p < 0.01), PWV (OR 0.86, 95% CI 0.77–0.94, p < 0.01), and use of beta-blockers (OR 2.42, 95% CI 1.09–5.36, p < 0.05), were independent determinants of the risk of hypotension. Conclusions Hypotension is a quite common phenomenon in older subjects. Its prevention requires a more accurate management of hypertension aimed at better identifying which older subjects in whom intensive BP control may be harmful and those who may benefit from it.

Purpose of Review To discuss the current status of the stethoscope as a vector for infection and possible interventions to promote stethoscope disinfection. Recent Findings Anywhere from 70 to 100% of stethoscopes are contaminated after a physical examination with bacterial counts of stethoscopes comparable to those of the physician’s dominant hand. Disinfection with alcohol agents can reduce the number of pathogens and risk of transmission, which is recommended by guidelines. However, only 0–11% of healthcare providers disinfected their stethoscope before patient contact and 0–24% disinfected after the contact. The effectiveness of educational programs with visual reminders and supplying disinfectants is uncertain. Summary Stethoscopes commonly harbor bacteria and can serve as a vector for transmission of infectious diseases. Only a minority of healthcare providers actually disinfect their stethoscope. There is a clear need for strategies to alter physicians’ recognition and behavior for stethoscope disinfection.

Giles-Sims reviews \"Family Violence Across the Lifespan\" by Olga W. Barnett, Cindy L. Miller-Perrin, and Robin D. Perrin.

The company declared a 5c-a-share final dividend, up from 3c last year. The partly franked dividend will be paid on October 3 to shareholders registered on or before September 19. In July last year, Origin bought CitiPower's retail business for $137 million and in January this year, it spent $89 million to buy the Mt Stuart power plant in Townsville, Queensland.

Cardiovascular risk factors, including elevated blood pressure (BP) and central arterial stiffness (CAS), an early vascular aging (EVA) characteristic, are associated with cognitive decline and dementia. In adult Dahl salt-sensitive (DSS) rats, consuming a normal salt (NS; 0.5% NaCl) diet, EVA and cognitive impairment progress with age. Previously, we demonstrated that senolytic treatment with Quercetin (QRC), a natural flavonoid with antioxidant, anti-inflammatory, and senolytic properties, combined with Dasatinib (DAS), a tyrosine kinase inhibitor, reduced EVA and improved cognitive function in adult DSS males. We hypothesized that QRC and DAS will affect EVA and heart parameters and improve cognitive function in DSS females. Six-month old DSS female rats were treated with placebo (control group, n = 11), or QRC (100 mg/kgBW/day; n = 13), or a combination of QRC+DAS (n = 12) for 6 months. DAS (1mg/kgBW/day) was added for the final 2 months to the QRC+DAS group. All treatments were supplemented to a standard NS diet. Systolic BP (SBP), pulse wave velocity (PWV, an index of CAS), echocardiography, cognitive function (visuospatial attention test and cross maze), and anxiety-like behavior (open field and elevated plus maze) were evaluated following treatment or placebo. At 12 months of age, neither QRC nor QRC+DAS chronic treatments affected SBP or PWV compared to controls. However, both treatments improved heart function, with increased ejection fraction and fractional shortening. QRC+DAS treatment reduced left ventricle relative wall thickness (LV-RWT) versus controls. Cognitive function did not differ significantly among groups. The rats in both QRC and QRC+DAS groups exhibited reduced anxiety-like behavior spending more time in open arms. Number of correct attention test responses negatively correlated with LV-RWT (r=-0.813, p = 0.004) and positively with cardiac output (r=0.760, p = 0.02) in the QRC group; and negatively correlated with LV-RWT (r=-0.683, p = 0.021) and positively correlated with ejection fraction (r=0.577, p = 0.063) in the QRC+DAS group, suggesting a link between cardiac structure and attentional performance. Chronic senolytic treatments with QRC or QRC+DAS protected heart function and reduced anxiety-like behavior but did not affect EVA in adult DSS females. The correlation between cardiac remodeling and attention test performance highlights a potential heart-brain interaction. Supported by NIA/NIH/IRP.

Glioblastoma multiforme (GBM), the most common and malignant central nervous system tumor in humans, is highly proliferative and resistant to apoptosis. Stat3, a latent transcription factor being activated by aberrant cytokine or growth factor signaling, acts as a suppressor of apoptosis in a number of cancer cells. Here we report that GBM tumors and cell lines contain high levels of constitutively activated Stat3 when compared with normal human astrocytes, white matter, and normal tissue adjacent to tumor. The persistent activation of Stat3 is in part, attributable to an autocrine action of interleukin-6 in the GBM cell line U251. Janus kinase inhibitor AG490 inhibits Stat3 activation with a concomitant reduction in steady-state levels of Bcl-X(L), Bcl-2 and Mcl-1 proteins and induces apoptosis in U251 cells as revealed by Poly (ADP-ribose) polymerase cleavage and Annexin-V staining. Expression of a dominant negative mutant Stat3 protein or treatment with AG490 markedly reduces the proliferation of U251 cells by inhibiting the constitutive activation of Stat3. These results provide evidence that constitutive activation of Stat3 contributes to the pathogenesis of glioblastoma by promoting both proliferation and survival of GBM cells. Therefore, targeting Stat3 signaling may provide a potential therapeutic intervention for GBM.

Early vascular aging (EVA), manifesting as increases in central arterial stiffness and BP, is associated with cognitive impairment in humans. EVA and cognitive impairment occurs in Dahl salt-sensitive (DSS) rats consuming a normal salt (NS) diet with an advancing age. Quercetin (QRC), a flavonoid with anti-oxidant, anti-inflammatory and senolytic properties, previously shown to reduce salt-sensitive hypertension in DSS. We hypothesized that QRC will not only reduce EVA but will also improve cognitive function in DSS consuming NS diet. Six month old male DSS rats were assigned to two groups: a control group (n = 12) on a normal salt diet (0.5% NaCl) and an experimental group (n = 24) receiving the same diet supplemented with QRC (100 mg/kg BW/daily) for a 3-month period. Systolic and diastolic blood pressure (SBP, DBP), pulse wave velocity (PWV, an index of CAS), echocardiography, and visuospatial attention test were assessed before and after QRC treatment or placebo. Before treatment, no differences existed between groups. From 6 to 9 months of age in the control group, SBP, DBP, and PWV increased, while heart rate (HR) and ejection fraction (EF) showed a borderline decrease, and attention behavior showed a borderline increase for 1.0s of stimulus duration and no change for shorter visual stimulus, 0.2s (Figure and Table). QRC treatment reduced SBP, PWV, and increased EF and attention. The QRC effect was to increase the number of correct responses for 0.2s of stimulus and was negatively correlated with PWV (Pearson r = -0.420, P = 0.02) but not with BP, indicating that CAS is linked to cognitive function. QRC supplementation demonstrated the ability to reduce EVA and enhance cognition in DSS rats, as indicated by attention behavior. Despite BP and CAS reflecting EVA, the association between attention decline and PWV, but not BP, implies that CAS is linked to cognitive function through mechanisms not directly related to BP. Further exploration is required to understand the mechanistic basis of QRC effects on EVA in DSS rats. Supported by NIA/NIH/IRP.

Photobiomodulation (PBM) therapy, using low intensity near-infrared light is a noninvasive form of treatment with no side effects can be used to treat Alzheimer's disease (AD). In a double-transgenic mouse model of AD (APPswe/PS1dE9), chronic PBM therapy has been shown to reduce Aβ plaques accumulation in specific regions of the brain, including the neocortex and hippocampus. The aim of this study was to analyze the effects of PBM therapy on brain cortex neuroprotective gene expression and behavior in this APPswe/PS1dE9 mouse model. Six-month old male AD (AD-PBM, n = 7) and wild type litter mate mice (WT-PBM, n = 8) were exposed to near-infrared light (wavelength 850 nm, 4.5 J/cm2, 3min/day, 5 days/week) for 6 months. Control mice (AD-CNT, n = 7; WT-CNT, n = 7) were placed under the PBM apparatus without turning the light on for 3min/day, 5 days/week. Motor function was assessed with treadmill-based gait analysis, with metrics including hind propel, hind stance and hind step angle (DigiGait), and open field test (OFT; anxiety-like behavior) following 6 months of treatment. Gene expression sampled from cortex was analyzed by qPCR. Data were analyzed by 2-way ANOVA. In the AD group, PBM therapy significantly increased the expression of neuroprotective genes TGFb1, INFG, EGFR and MMP2, but did not affect the expression of these genes in WT (Fig. 1A-D). In the gait analysis, PBM groups significantly reduced hind step angle in AD, but not WT (Fig. 1E). In the OFT, genotype had a significant effect on the amount of distance and time spent in the center of the arena (Table); non-treated WT mice exhibited lower anxiety level vs. non-treated AD mice (Fig. 1F). PBM did not have a significant effect, but the percent of distance spent in the center out of total distance had an increasing trend (Fig. 1F) indicating a trend in a reduction of anxiety in the AD group. Two-way ANOVA analysis results are presented in Table 1. PBM therapy significantly increased neuroprotective cortical gene expression and improved motor function in AD mice. It is possible that PBM treatment contributes to the upregulation of neuroprotective genes that reduced anxiety behavior and improved motor function.