Trans-cerebral HCO3- and PCO2 exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO(3)(−)]) and carbon dioxide tension (PCO(2)) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO(2) (PaCO(2)) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO(3)(−)] increased by 0.15 ± 0.05 mmol ⋅ l(−1) per mmHg elevation in PaCO(2) across a wide physiological range (35 to 60 mmHg PaCO(2); P < 0.001). The narrowing of the venous-arterial [HCO(3)(−)] and PCO(2) differences with respiratory acidosis were both related to the hypercapnia-induced elevations in cerebral blood flow (CBF) (both P < 0.001; subset n = 27); thus, trans-cerebral [HCO(3)(−)] exchange (CBF × venous-arterial [HCO(3)(−)] difference) was reduced indicating a shift from net release toward net uptake of [HCO(3)(−)] (P = 0.004). Arterial [HCO(3)(−)] was reduced by −0.48 ± 0.15 mmol ⋅ l(−1) per nmol ⋅ l(−1) increase in arterial [H(+)] with exercise-induced acidosis (P < 0.001). There was no relationship between the venous-arterial [HCO(3)(−)] difference and arterial [H(+)] with exercise-induced acidosis or CBF; therefore, trans-cerebral [HCO(3)(−)] exchange was unaltered throughout exercise when indexed against arterial [H(+)] or pH (P = 0.933 and P = 0.896, respectively). These results indicate that increases and decreases in systemic [HCO(3)(−)] – during acute respiratory/exercise-induced metabolic acidosis, respectively – differentially affect cerebrovascular acid-base balance (via trans-cerebral [HCO(3)(−)] exchange)

Exploring the contribution of general self-efficacy to the use of self-care symptom management strategies by people living with HIV infection

General self-efficacy (GSE), the expectation that one is able to perform a behavior successfully, may differentiate those who are able to successfully utilize self-care symptom management strategies (SCSMS). This subanalysis (n = 569) of an international 12 site longitudinal randomized controlled trial (RCT) (n = 775), investigated GSE as an important factor determining symptom burden, SCSMS, engagement with the provider, and medication adherence over time, and identified differences in those with high and low GSE ratings concerning these variables. Parametric and nonparametric repeated-measures tests were employed to assess GSE and the perceived effectiveness of SCSMS for anxiety, depression, diarrhea, fatigue, nausea, and neuropathy. Symptom burden, engagement with the provider, and antiretroviral adherence were analyzed with regard to GSE. Our data indicated that there were differences in the perceived symptom burden over time of HIV infected individuals by GSE. Those individuals with higher GSE had fewer symptoms and these symptoms were perceived to be less intense than those experienced by the low GSE group. There were few meaningful differences in the SCSMS used by those with high versus low GSE other than the use of illicit substances in the low GSE group. The low GSE group was also significantly ( p= \u3c 0.001) less engaged with their healthcare providers. Given the difference in substance use by perceived GSE, and the importance of engagement with the healthcare provider, more attention to the resolution of the concerns of those with low GSE by healthcare providers is warranted

Th1 Disabled Function in Response to TLR4 Stimulation of Monocyte-Derived DC from Patients Chronically-Infected by Hepatitis C Virus

Background: Lack of protective antibodies and inefficient cytotoxic responses are characteristics of chronic hepatitis C infection. A defect in dendritic cell (DC) function has thus been suspected, but this remains a controversial issue. Methods and Findings: Here we show that monocyte-derived DC (MoDC) from chronically-infected patients can mature in response to TLR1/2, TLR2/6 or TLR3 ligands. In contrast, when stimulated with the TLR4 ligand LPS, MoDC from patients show a profound defect in inducing IFNc secretion by allogeneic T cells. This defect is not due to defective phenotypic maturation or to the presence of HCV-RNA in DC or monocytes but is correlated to reduced IL-12 secretion by DC. Restoration of DC ability to stimulate IFNc secretion can be obtained by blocking MEK activation in DC, indicating that MEK/ ERK pathway is involved in the Th1 defect of MoDC. Monocytes from HCV patients present increased spontaneous secretion of cytokines and chemokines, especially MIP-1b. Addition of MIP-1b on healthy monocytes during differentiation results in DC that have Th1 defect characteristic of MoDC from HCV patients, suggesting that MIP-1b secretion by HCV monocytes participates in the Th1 defect of DC. Conclusions: Our data indicate that monocytes from HCV patients are activated in vivo. This interferes with their differentiation into DC, leading to deficient TLR4 signaling in these cells that are enable to induce a Th1 response. Thi

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Powerful Teaching : Unleash the Science of Learning

Unleash powerful teaching and the science of learning in your classroom Powerful Teaching: Unleash the Science of Learning empowers educators to harness rigorous research on how students learn and unleash it in their classrooms. In this book, cognitive scientist Pooja K. Agarwal, Ph.D., and veteran K–12 teacher Patrice M. Bain, Ed.S., decipher cognitive science research and illustrate ways to successfully apply the science of learning in classrooms settings. This practical resource is filled with evidence-based strategies that are easily implemented in less than a minute—without additional prepping, grading, or funding! Research demonstrates that these powerful strategies raise student achievement by a letter grade or more; boost learning for diverse students, grade levels, and subject areas; and enhance students'higher order learning and transfer of knowledge beyond the classroom. Drawing on a fifteen-year scientist-teacher collaboration, more than 100 years of research on learning, and rich experiences from educators in K–12 and higher education, the authors present highly accessible step-by-step guidance on how to transform teaching with four essential strategies: Retrieval practice, spacing, interleaving, and feedback-driven metacognition. With Powerful Teaching, you will: Develop a deep understanding of powerful teaching strategies based on the science of learning Gain insight from real-world examples of how evidence-based strategies are being implemented in a variety of academic settings Think critically about your current teaching practices from a research-based perspective Develop tools to share the science of learning with students and parents, ensuring success inside and outside the classroom Powerful Teaching: Unleash the Science of Learning is an indispensable resource for educators who want to take their instruction to the next level. Equipped with scientific knowledge and evidence-based tools, turn your teaching into powerful teaching and unleash student learning in your classroom.Chapter 1: Discover the Power Behind Power Tools ; Chapter 2: Build a Foundation with Retrieval Practice ; Chapter 3: Empower Teaching with Retrieval Practice Strategies ; Chapter 4: Energize Learning with Spacing and Interleaving ; Chapter 5: Engage Students with Feedback-Driven Metacognition ; Chapter 6: Combine Power Tools and Harness Your Toolbox ; Chapter 7: Keeping It Real: Use Power Tools to Tackle Challenges, Not Add to Them ; Chapter 8: Foster a Supportive Environment: Use Power Tools to Reduce Anxiety and Strengthen Community ; Chapter 9: Spark Conversations with Students About the Science of Learning ; Chapter 10: Spark Conversations with Parents About the Science of Learning ; Chapter 11: Powerful Professional Development for Teachers and Leaders ; Chapter 12: Do It Yourself Retrieval Guide

Use of a brief version of the self-compassion inventory with an international sample of people with HIV/AIDS.

The objective of this study was to extend the psychometric evaluation of a brief version of the Self-Compassion Scale (SCS). A secondary analysis of data from an international sample of 1967 English-speaking persons living with HIV disease was used to examine the factor structure, and reliability of the 12-item Brief Version Self-Compassion Inventory (BVSCI). A Maximum Likelihood factor analysis and Oblimin with Kaiser Normalization confirmed a two-factor solution, accounting for 42.58% of the variance. The BVSCI supported acceptable internal consistencies, with 0.714 for the total scale and 0.822 for Factor I and 0.774 for Factor II. Factor I (lower self-compassion) demonstrated strongly positive correlations with measures of anxiety and depression, while Factor II (high self-compassion) was inversely correlated with the measures. No significant differences were found in the BVSCI scores for gender, age, or having children. Levels of self-compassion were significantly higher in persons with HIV disease and other physical and psychological health conditions. The scale shows promise for the assessment of self-compassion in persons with HIV without taxing participants, and may prove essential in investigating future research aimed at examining correlates of self-compassion, as well as providing data for tailoring self-compassion interventions for persons with HIV

Foundations of academic knowledge

This chapter assesses the acquisition of academic knowledge and skills in domains including literacy, numeracy, sciences, arts and physical education. It examines how learning trajectories arise from complex interactions between individual brain development and sociocultural environments. Teaching literacy and numeracy to all students is a goal of most school systems. While there are some fundamental skills children should grasp to succeed in these domains, the best way to support each student’s learning varies depending on their individual development, language, culture and prior knowledge. Here we explore considerations for instruction and assessment in diferent academic domains. To accommodate the fourishing of all children, fexibility must be built into education systems, which need to acknowledge the diverse ways in which children can progress through learning trajectories and demonstrate their knowledge

Unhealthy substance-use behaviors as symptom-related self-care in persons with HIV/AIDS.

Unhealthy substance-use behaviors, including a heavy alcohol intake, illicit drug use, and cigarette smoking, are engaged in by many HIV-positive individuals, often as a way to manage their disease-related symptoms. This study, based on data from a larger randomized controlled trial of an HIV/AIDS symptom management manual, examines the prevalence and characteristics of unhealthy behaviors in relation to HIV/AIDS symptoms. The mean age of the sample (n = 775) was 42.8 years and 38.5% of the sample was female. The mean number of years living with HIV was 9.1 years. The specific self-reported unhealthy substance-use behaviors were the use of marijuana, cigarettes, a large amount of alcohol, and illicit drugs. A subset of individuals who identified high levels of specific symptoms also reported significantly higher substance-use behaviors, including amphetamine and injection drug use, heavy alcohol use, cigarette smoking, and marijuana use. The implications for clinical practice include the assessment of self-care behaviors, screening for substance abuse, and education of persons regarding the self-management of HIV

Unhealthy substance-use behaviors as symptom-related self-care in persons with HIV/AIDS

The prevalence of symptoms in HIV disease can be associated with HIV disease itself, comorbid illness, and/or antiretroviral therapy. Unhealthy substance use behaviors, particularly substance-use behaviors including heavy alcohol intake, marijuana use, other illicit drug use, and cigarette smoking, are engaged in by many HIV-positive individuals, often as a way to manage disease-related symptoms. This study is a secondary data analysis of baseline data from a larger randomized-controlled trial of an HIV/AIDS Symptom Management Manual. In the present study, the prevalence and characteristics of unhealthy substance use behaviors in relation to HIV/AIDS symptoms are examined. Subjects were recruited from a variety of settings which provide HIV/AIDS care and treatment. The mean age of the sample (n=775) was 42.8 years (SD=9.6) and nearly thirty-nine percent (38.5%) of the sample was female. The racial demographics of the sample were: 28% African American, 28% Hispanic, 21% White/Caucasian, 16% African from Kenya or South Africa, 1% Asian, and 5% self-described as “Other.” The mean number of years living with HIV was reported to be 9.1 years (SD=6.6).Specific self-reported unhealthy substance-use behaviors were use of marijuana (n= 111; 14.3%), cigarette smoking (n=355; 45.8%), heavy alcohol use (n= 66; 8.5%), and illicit drugs (n= 98; 12.6%). A subset of individuals who identified high levels of specific symptoms also reported significantly higher substance use behaviors including amphetamine and injection drug use in addition to heavy alcohol use, cigarette smoking, and marijuana use. Implications for clinical practice include assessment of self-care behaviors, screening for substance abuse, and education of persons related to self-management across the trajectory of HIV disease