Citations

Pulmonary function (PF) may be influenced by a deterioration of cardiac function. As such, resting measures of PF may be prognostically useful in heart failure patients (HF). This study examined the prognostic value of resting PF in a cohort of HF. This included 113 patients (enrolled 1999‐2005, EF=28±11%; age=55±12yr; 62% male) followed for 64±34mo with death confirmed via the SSI & Mayo Clinic registry. PF included, forced vital capacity, FVC; diffusing capacity, DLCO; forced expiratory volume, FEV1; alveolar volume, VA. Patients were divided in tertiles according to PF with survival analysis via Log‐rank Mantel‐Cox Test with Chi squared analysis (Chi‐sq). Groups for FVC: 1)=80, 2)81‐97, 3)=98, %pre (Chi‐sq 21.5, p<0.01). Bonferonni correction (BC) suggested differences (diff) between groups 1 & 2 and 1 & 3 (p=0.01) with no diff (ND) between 2 & 3 (p=0.62). Groups for FEV1: 1)=77, 2)78‐95, 3)=96, %pre (Chi‐sq 16.3, p<0.01). BC suggested diff between groups 1 & 2 (p=0.02) and 1 & 3 (p<0.01). Groups for DLCO: 1)=75, 2)76‐90, 3)=91, %pre (Chi‐sq=8.2, p=0.02). BC suggested diff between groups 1 & 3 (p=0.003) with ND between 1 & 2 or 2 & 3 (p>0.05). Groups for VA: 1)=87, 2)88‐97, 3)=98, %pre (Chi‐sq=8.9, p=0.01). BC suggested diff between 1 & 3 (p<0.01) with ND between 1 & 2 or 2 & 3 (p>0.05). In a well defined cohort of HF patients, resting measures of PF appear to be predictive of all cause mortality. NIH HL71478

Diabetics tend to have inadequate fruit consumption, elevated plasma glucose and insulin, and increased cardiovascular disease risk. Dried fruit may represent one way to increase fruit consumption among diabetics. Polydextrose is a commonly used soluble fiber and bulking agent providing very little available carbohydrate energy. The glycemic and insulinemic response of type 2 diabetics (n=13) to a single serving of white bread (57g; 160 Cal; 1 g fiber), raw cranberries (RC; 55g; 21 Cal; 1 g fiber), sweetened dried cranberries‐original (SCDO; 40g, 138 Cal; 2.1g fiber), and SDC‐less sugar (SDCLS; 40g; 113 Cal; 1.8g fiber + 10g polydextrose) was measured in a single cross‐over design. Plasma glucose (mg/dl) and insulin ( μU/ml) was measured prior to consumption, then 30, 60 and 120 minutes postprandially. Plasma glucose peaked at 30 or 60 min following bread, RC, SDCO, and SDCLS at 175 ± 10, 127 ± 7, 175 ± 10 and 158 ± 9 min, respectively, and remained significantly elevated 120 min following bread consumption. Peak plasma insulin for SDCO (15 ± 2) and RC (10 ± 1) was significantly less than bread (22 ± 2) or SDCO (22 ± 4), and remained slightly elevated at 120 minutes. The area under the curve values reflected similar changes. SDCLS consumption could be useful for improving fruit consumption by type 2 diabetics in a manner that provides glycemic and insulinemic benefits. Sponsor: Ocean Spray Cranberries Inc.

Introduction: Statin dose guidelines for PAD patients are based on coronary artery disease and stroke data. The aim of our study was to determine the effect of statin dose (based on 2013 ACC/AHA guidelines) on PAD outcomes of amputation and mortality. Methods: Patients with PAD in the Veterans Affairs database were identified from 2003-2014. The exposure was highest statin dose usage (none, low-moderate and high intensity) around diagnosis of PAD (within 1 year). The outcomes were risk of incident amputation (below knee or above knee) and mortality at 1, 3 and 5 years. The effect of statin dose on the two outcomes was also analyzed using Cox proportional hazards modeling to adjust for covariates. Results: In 208,275 patients with PAD [Males: 98.1%; Mean age: 67.4 yrs (SD 9.9)], 17,643 amputations and 99,951 deaths occurred in a median follow up of 5.2 years. Almost a quarter (27.7%) of patients were not on a statin while 30.4% were on simvastatin 80 mg (no longer recommended due to drug toxicity). The risk of incident amputation declined significantly at the high intensity statin dose as seen in Table 1. In Cox models adjusting for age, gender, race, comorbidities, cholesterol levels and creatinine, the high intensity statins were associated with lower amputation risk and mortality as compared to no statin [HR 0.67; 95% CI (0.63, 0.72) and HR 0.71; 95% CI (0.68, 0.73), respectively]. Low-moderate-dose statins also had significant but smaller reductions in risk of amputation and mortality [HR amputation 0.78 (0.75, 0.82), HR death 0.78 (0.77, 0.80)]. Conclusion: This is one of the largest population based studies to examine the effect of statins on long-term PAD outcomes and the first to explore the dose-dependent effect of statins on amputation and mortality. High intensity statins are associated with a significant reduction in limb loss and mortality in PAD patients followed by a smaller risk reduction by low-moderate intensity statins as compared to no statin therapy.

Acclimation to high altitude was characterized in nine non‐athletic college aged students aged 19 to 24 during a trek in the Himalayas. A three minute step test (40.6 cm step and a 24 step/minute rate) was performed at 1654 (am, day 1), 3696 (pm, day 1), 3865 (day 8), 3688 (day 10), 4115 (day 13) and again at 3688 meters (day 14). Resting heart rate and oxygen saturation (SaO 2 ) was measured prior to the step test and 20 seconds after exercise cessation (recovery). The heart rate difference (percent change) between pre‐ and post‐exercise cessation was used to measure hypoxic stress at altitude and significant acclimation could not be documented until day 14 (3688 m). The percent difference between pre‐ and post‐step test SaO 2 at 1654 m was significantly different from tests performed at 3696, 3865, 3688, and 4115 m. However, at day 14 (3688 m) the percent change in SaO 2 was no longer significantly different from the 1654 m value at day 1. Pre‐trip response to acute hypoxia (12.5 % O 2 ) was examined by performing the same step test at 402 m, with inconclusive results. This study suggests that 14 days are required for non‐athletic students to achieve acclimation to a step test.

Persons with metabolic syndrome could benefit from improved fruit consumption and reduced caloric intake. A cranberry fruit containing reduced titratable acidity was developed and used to create a 27% reduced calorie cranberry juice (RCCBJ) containing less added sugar (74 Cal/240 ml) relative to the 110 Cal/240 ml industry standard cranberry juice (CBJ). Subjects were recruited for metabolic syndrome (n=18; 53 16 years; BMI=34.4 ± 3.9) and their metabolic response to CBJ and RCCBJ was evaluated in single cross‐over fashion. Plasma glucose for CBJ at 0‐, 30‐, 60‐, and 120‐min was 105.6±12.3, 149.5±22.6, 127.9±30.3, and 98.6±14.6 (mg/dl). Plasma glucose for RCCBJ was 104.6±13.3, 140.3±22.5, 116.0±27.23, and 100.4±13. Plasma insulin for CBJ at 0‐, 30‐, 60‐, and 120‐ min was 10.21±5.1, 41.5±22.6, 30.3±19.7, and 12.0± (µIU/ml). Plasma insulin for RCCBJ was 12.2±8.4, 34.8±21.6, 20.7±13.9, and 12.3±9.8. For CBJ and RCCBJ plasma glucose and insulin significantly increased relative to baseline at 30‐ and 60‐min. At 60 min RCCBJ glucose and insulin were significantly less than CBJ. Plasma adiponectin and glucagon like peptide‐1 responses were also measured for CBJ and RCCBJ at 0‐, 30‐, 60‐, and 120‐min. Reduced acidity cranberry fruit was associated with RCCBJ containing 33% fewer calories and a beneficial metabolic response in persons with metabolic syndrome.

Mono‐and polyunsaturated fats in nuts, such as pistachios (PI), may improve lipoprotein and glycemic status. Overweight persons trend for dyslipidemia and high diabetes risk. The lower limits of PI consumption required for health benefits are unknown. This study determined if PI at bedtime promotes beneficial changes in metabolic status in overweight persons. Overweight subjects (n=22; 55 ± 2 yrs; 90 ± 3.6 kg; BMI 31 ± 1) were randomized to 35.4 g PI self‐administered at bedtime or control (CO; no PI) for 6 weeks. There was no difference in physical activity level between subjects receiving PI and CO. Body weight was not different in PI and CO at wk 0, 1, 2, 4, and 6. HDL cholesterol at wk 0 and 6 in PI was 49.2 ± 3.5 to 50.3 ± 3.0, and CO was 60.8 ± 3.8 and 58.0 ± 2.7 mg/dL, at wk 6 PI had improved slightly relative to CO (P= 0.12). Plasma glucose at wk 0 and 6 in PI was 104.6 ± 2.8 and 99.6 ± 2.6 mg/dL, and CO was 102.0 ± 2.8 and 101.1 ± 2.6 mg/dL, at wk 6 PI had improved slightly relative to CO (P= 0.16). Plasma insulin at wk 0 and 6 in PI was 8.5 ± 1.0 and 8.4 ± 0.9, and CO was 7.2 ± 0.7 to 8.8 ± 0.7 μU/mL, at wk 6 PI had improved slightly relative to CO (P = 0.21). Beneficial changes in HDL, glucose, and insulin probably requires slightly more than 35.4 g/d PI for 6 wks. To increase the probability of metabolic health benefits, nutritionists may wish to encourage levels of daily PI consumption higher than those administered in this study.

Objectives: To understand how patients and family members experience dehumanizing or humanizing treatment when in the ICU. Design: Qualitative study included web-based focus groups and open-ended surveys posted to ICU patient/family social media boards. Focus groups were audio recorded and transcribed. Social media responses were collected and organized by stakeholder group. Data underwent qualitative analysis. Setting: Remote focus groups and online surveys. Patients: ICU patient survivors, family members, and ICU teams. Interventions: Not available. Measurements and Main Results: Semi-structured questions and open-ended survey responses. We enrolled 40 patients/family members and 31 ICU team members. Focus groups and surveys revealed three primary themes orienting humanizing/dehumanizing ICU experiences: 1) communication, 2) outcomes, and 3) causes of dehumanization. Dehumanization occurred during “communication” exchanges when ICU team members talked “over” patients, made distressing remarks when patients were present, or failed to inform patients about ICU-related care. “Outcomes” of dehumanization were associated with patient loss of trust in the medical team, loss of motivation to participate in ICU recovery, feeling of distress, guilt, depression, and anxiety. Humanizing behaviors were associated with improved recovery, well-being, and trust. “Perceived causes” of dehumanizing behaviors were linked to patient, ICU team, and healthcare system factors. CONCLUSIONS: Behaviors of ICU clinicians may cause patients and families to feel dehumanized when in the ICU. Negative behaviors are noticed by patients and families, possibly contributing to poor outcomes including mental health, recovery, and lack of trust in ICU teams. Supporting ICU clinicians may enable a more empathic environment and in turn more humanizing clinician-patient encounters.

Pulse Decomposition Analysis (PDA) offers new insights into factors altering the arterial pressure pulse contour. PDA premise is that peripheral arterial pressure pulse envelope consists of distinct component pressure pulses, a left ventricular ejection and its reflections. Two PDA parameters appear to be particularly useful in quantifying the pulse contour. P2P1 is the ratio of second component pulse and primary ejection pulse amplitudes. T13 is the temporal delay between the third component pulse and the primary ejection pulse. P2P1 and T13 parameters were used to examine pressure pulse contour changes in 81 healthy subjects (18–27 yrs; BMI 27.5 ± 2.6) undergoing a Stroop mental stress test, cycle ergometer stress tests (3 min; 50W and 100W), and post‐exercise recovery. Digital pressure pulse contours were recorded/quantified using PDA formalism. Relative to baseline, P2P1 increased 8% post‐Stroop (individual variation 0% to 15%), T13 increased 4%, (individual variation 0% to 8%). Exercise decreased P2P1 21 ± 14%, while the T13 change was 19 ± 15%. PDA‐based pulse propagation model quantifies physical changes that arterial pulse reflection sites undergo. Peripheral arterial pressure pulse appears to be due to the primary ejection pulse and two major reflections. Two reflection sites in the central arteries appear to be responsible for the “reflected” wave part of the pulse contour.

Human papillomaviruses (HPVs) replicate in the nucleus and modulate several host cell pathways to create a favorable environment for viral reproduction. The HPV E6 proteins utilize the host ubiquitin‐proteosome pathway to target several cellular proteins for degradation. Several HPV proteins are substrates for sumoylation, so the objective of this study was to determine if HPV E6 proteins interacted with or influenced the parallel host sumoylation system. Transient expression of E6 caused an apparent general reduction in the overall level of host sumoylation. To explore the mechanistic basis, we examined the effect of E6 proteins on Ubc9, the sole sumoylation conjugation enzyme. HPV E6 proteins reduced intracellular levels of Ubc9, without affecting transcript levels, so a direct effect on Ubc9 protein stability is likely. Consistent with typical E6‐mediated proteasomal degradation, E6 bound to Ubc9 in vitro, and required E6AP for reduction of Ubc9 levels. To examine the effect of E6 on sumoylated proteins in more detail, a fluorescent 2‐dimensional gel system was used to visualize sumoylated proteins. Stable expression of E6 resulted in the loss of 32 sumoylated proteins out of a matched set of over 200 protein spots. Thus, E6 exerts a significant, though selective, effect on host protein sumoylation through its action on Ubc9, which likely helps to create a cellular environment conducive to viral replication. Grant Funding Source : Supported by NIH grant CA089298 to V.G.W.