Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure ...remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone. We investigated the effect of chronic activation of the carotid BR on hemodynamic and neurohormonal parameters and on mortality in dogs with chronic heart failure. Fifteen dogs were instrumented to record hemodynamics. Electrodes were applied around the carotid sinuses to allow for activation of the BR. After 2 weeks of pacing (250 bpm), electrical carotid BR activation was initiated in 7 dogs and continued for the remainder of the study. The start of BR activation was used as a time reference point for the remaining 8 control dogs that did not receive BR activation. Survival was significantly greater for dogs undergoing carotid BR activation compared with control dogs (68.1+/-7.4 versus 37.3+/-3.2 days, respectively; P<0.01), although arterial pressure, resting heart rate, and left ventricular pressure were not different over time in BR-activated versus control dogs. Plasma norepinephrine was lower in dogs receiving BR activation therapy 31 days after the start of BR activation (401.9+/-151.5 versus 1121.9+/-389.1 pg/mL in dogs not receiving activation therapy; P<0.05). Plasma angiotensin II increased less in dogs receiving activation therapy (plasma angiotensin II increased by 157.4+/-58.6 pg/mL in control dogs versus 10.1+/-14.0 pg/mL in dogs receiving activation therapy; P<0.02). We conclude that chronic activation of the carotid BR improves survival and suppresses neurohormonal activation in chronic heart failure.
Posttraumatic stress disorder (PTSD) is common among U.S. military veterans and is associated with increased risk of suicidal thoughts and behaviors. Crisis response planning (CRP), a brief safety ...planning-type intervention, has been shown to rapidly reduce suicidal ideation and suicide attempts in emergency and acute care settings. CRP’s effectiveness when combined with trauma-focused therapies remains unknown. In this randomized pragmatic clinical trial with one-year follow-up, 157 U.S. military personnel and veterans were randomly assigned to receive CRP or self-guided safety planning (SP) prior to beginning massed cognitive processing therapy (CPT) for PTSD. Among 51 (32.5 % of sample) participants endorsing suicidal ideation at baseline, reductions in the severity of suicidal ideation were significantly larger and faster in CRP (F(11,672)= 15.8, p < .001). Among 106 participants denying suicidal ideation at baseline, 8.5 % of CRP participants versus 11.9 % of SP participants (OR=0.69, 95 % CI=0.19–2.52) reported new-onset suicidal ideation during any follow-up assessment. PTSD symptoms significantly reduced over time with no differences between groups. Results support the effectiveness of CRP for rapidly reducing suicidal ideation and managing suicide risk during outpatient treatment for PTSD.
•Evidence supporting the effectiveness of safety planning-type interventions is limited.•Crisis response planning (CRP) has been shown to reduce suicidal ideation and attempts.•Veterans with PTSD randomly received either CRP or a safety plan before treatment.•Reductions in suicidal ideation were significantly larger in CRP.•Fewer participants in CRP reported new-onset suicidal ideation and suicide attempts.
During orthodontic treatment, pain and discomfort of the oral mucosa can be experienced as a result of trauma from the appliances caused by increased friction between mucosal tissue and the surface ...of the brackets. Currently, orthodontists have few remedies to prevent or relieve this mucosal irritation. The orthodontist can give the patient wax to cover the brackets as a prophylactic measure or to use as needed on specific irritating appliances. Orthodontic wax contains no analgesic components. The purpose of this study was to determine the efficacy of an orthodontic wax containing benzocaine that is released over time in a controlled manner. This randomized, prospective, double-blind, clinical trial compared patients' responses to the wax with benzocaine and the currently used unmedicated orthodontic wax. Seventy patients, 35 in each treatment group, were instructed to apply the wax in a specific manner, and their pain levels were recorded at 6 different time points. The pain levels were analyzed with a repeated-measure analysis of variance (ANOVA) model with factors of treatment (medicated wax vs unmedicated wax) and times (6 levels). Post-hoc pair-wise comparisons were made on the basis of the Fisher least significant difference procedure. The results of this study clearly indicated that the pain profile over time of the group that received the wax containing benzocaine was significantly different from that of the subjects who received the unmedicated wax. The medicated group had significantly lower pain levels at every time point after the first hour (P <.0003 in each case) compared with the unmedicated group. The medicated wax was effective immediately and continued to reduce pain in greater magnitude than did the unmedicated wax. A wax applied to orthodontic brackets that slowly and continuously releases benzocaine is significantly more effective at reducing the pain associated with mucosal irritation than is the current option used by most orthodontists. (Am J Orthod Dentofacial Orthop 2002;122:359-65)
Bolted connections that allow for slippage are widely used on roadside structures. Due to limitations in existing analysis tools, non-linear finite-element analysis was used to develop detailed ...modeling techniques for bolted joints that slip in one direction when loaded in shear. Because bolt preload, and thus clamping forces, is very critical in determining joint slippage behavior, two modeling techniques were developed: (1) a discrete-spring based clamping model with several rigid parts, and (2) a stress based clamping model with deformable elements. Both techniques were used to simulate physical testing of a bolted joint undergoing slippage. Simulation results compared fairly well with test results. Very good accuracy was achieved when using finely meshed deformable elements for all parts. Of course, the cost of increased accuracy has significantly increased computational time.
Assembly of the core subunits of the aa(3)-type cytochrome c oxidase in mitochondria and aerobic bacteria such as Rhodobacter sphaeroides requires the association of three subunits and the formation ...of five to seven metal centers. Several assembly proteins are required for the late stages of oxidase assembly in eukaryotes; some of these are also present in Rb. sphaeroides. To investigate the role of one of these proteins, Cox11p, the mitochondrial-like oxidase of Rb. sphaeroides was overexpressed and purified from cells that lacked cox11, the gene for Cox11p. The oxidase that assembled in the absence of Cox11p lacked Cu(B) at the active site and contained greatly reduced amounts of metal at the magnesium/manganese-binding site between subunits I and II. This inactive oxidase, however, did contain hemes a and a(3), Cu(A), and all three subunits. These results indicate that Cox11p is required at a late, perhaps final, step in the assembly of cytochrome oxidase, most likely the insertion of Cu(B). Oxidase which assembled in a strain with a low copy number of cox11 appeared nearly wild type, suggesting that Cox11p is required in substoichiometric amounts for its role in oxidase assembly.
•Most hospitals record inpatient mobility using periodic observations by clinicians.•Wearable technology may provide a more complete measurement of patient mobility.•Wearable technology may not be ...feasible to use in all hospitalized patients.•Screening tools for identifying appropriate patients for this technology is needed.•Physical capacity assessments may assist clinicians as a feasible screening method.
Bedrest is toxic for inpatients and consumer grade physical activity monitors offer an economical solution to monitor patient ambulation. But these devices may not be accurate in debilitated hospitalized patients who frequently ambulate very slowly.
To determine whether measures of physical capacity can help identify inpatients for whom wearable physical activity monitors may accurately measure step count.
Prospective observational study of 54 adult inpatients with acute neurological diagnoses. Patients were assessed using 2 physical capacity assessments (Activity Measure for Post-Acute Care Inpatient Mobility Short Form AM-PAC IMSF and Katz Activities of Daily Living ADL scale). They also completed a 2-minute walk test (2MWT) wearing a consumer grade physical activity monitor.
The wearable activity monitor recorded steps (initiated) in 33 (61%) of the inpatients, and for 94% of inpatients with gait speeds >0.43 m/s. Physical capacity assessments correlated well with gait speed, AM-PAC IMSF r = 0.7, and Katz ADL r = 0.6, p < 0.05. When the physical activity monitor initiated, the mean absolute percent error (SD) comparing device calculated steps to observed steps, was 10% (13). AM-PAC IMSF (T-score >45) and Katz ADL (>5) cutoff scores identified inpatients for whom physical activity monitors initiated with a sensitivity of 94 and 91%, respectively.
Physical capacity assessments, such as AM-PAC, and Katz ADL, may be a useful and feasible screening strategy to help identify inpatients where wearable physical activity monitors can measure their mobility.
Human development has ushered in an era of converging crises: climate change, ecological destruction, disease, pollution, and socioeconomic inequality. This review synthesizes the breadth of these ...interwoven emergencies and underscores the urgent need for comprehensive, integrated action. Propelled by imperialism, extractive capitalism, and a surging population, we are speeding past Earth's material limits, destroying critical ecosystems, and triggering irreversible changes in biophysical systems that underpin the Holocene climatic stability which fostered human civilization. The consequences of these actions are disproportionately borne by vulnerable populations, further entrenching global inequities. Marine and terrestrial biomes face critical tipping points, while escalating challenges to food and water access foreshadow a bleak outlook for global security. Against this backdrop of Earth at risk, we call for a global response centered on urgent decarbonization, fostering reciprocity with nature, and implementing regenerative practices in natural resource management. We call for the elimination of detrimental subsidies, promotion of equitable human development, and transformative financial support for lower income nations. A critical paradigm shift must occur that replaces exploitative, wealth-oriented capitalism with an economic model that prioritizes sustainability, resilience, and justice. We advocate a global cultural shift that elevates kinship with nature and communal well-being, underpinned by the recognition of Earth's finite resources and the interconnectedness of its inhabitants. The imperative is clear: to navigate away from this precipice, we must collectively harness political will, economic resources, and societal values to steer toward a future where human progress does not come at the cost of ecological integrity and social equity.
Multimodal analgesic strategies that reduce perioperative opioid consumption are well-supported in Enhanced Recovery After Surgery (ERAS) literature. However, the optimal analgesic regimen has not ...been established, as the contributions of each individual agent to the overall analgesic efficacy with opioid reduction remains unknown. Perioperative ketamine infusions can decrease opioid consumption and opioid-related side effects. However, as opioid requirements are drastically minimized within ERAS models, the differential effects of ketamine within an ERAS pathway remain unknown. We aim to pragmatically investigate through a learning healthcare system infrastructure how the addition of a perioperative ketamine infusion to mature ERAS pathways affects functional recovery.
The IMPAKT ERAS trial (IMpact of PerioperAtive KeTamine on Enhanced Recovery after Abdominal Surgery) is a single center, pragmatic, randomized, blinded, placebo-controlled trial. 1544 patients undergoing major abdominal surgery will be randomly allocated to receive intraoperative and postoperative (up to 48 h) ketamine versus placebo infusions as part of a perioperative multimodal analgesic regimen. The primary outcome is length of stay, defined as surgical start time until hospital discharge. Secondary outcomes will include a variety of in-hospital clinical end points derived from the electronic health record.
We aimed to launch a large-scale, pragmatic trial that would easily integrate into routine clinical workflow. Implementation of a modified consent process was critical to preserving our pragmatic design, permitting an efficient, low-cost model without reliance on external study personnel. Therefore, we partnered with leaders of our Investigational Review Board to develop a novel, modified consent process and shortened written consent form that would meet all standard elements of informed consent, yet also allow clinical providers the ability to recruit and enroll patients during their clinical workflow. Our trial design has created a platform for subsequent pragmatic studies at our institution.
NCT04625283, Pre-results.
The current study assessed the reliability and validity of the Health Care Alliance Questionnaire, which was developed using a Delphi process and embedded in an ongoing perinatal outcomes study. The ...Health Care Alliance Questionnaire exhibited content and face validity and high reliability. Results indicated concurrent validity in relation to satisfaction with practitioner and discriminant validity in relation to interpersonal sensitivity and posttraumatic stress disorder. The Health Care Alliance Questionnaire demonstrated predictive validity in relation to perceptions of practitioner’s care during labor and postpartum depression. Overall, results suggest that alliance may be an important factor in maternity care processes and outcomes. Further psychometric work is warranted.
Real-time polymerase chain reaction (PCR) has been used for quantification of intracellular mRNA levels in cell culture and tissue samples. It is an important tool for studying antimitotic drug ...effects on tubulin isotype and microtubule-interacting protein levels and for measuring differences in normal and tumor tissue samples that could have predictive or prognostic applications. Both quantitative and comparative methods are valuable approaches; however, the selection of either approach requires an understanding of their benefits and challenges. In this chapter, we provide detailed protocols for real-time PCR experiments, discuss issues to consider in selecting real-time PCR methodologies, and give examples utilizing either quantitative or comparative approaches.
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