Acetate Causes Alcohol Hangover Headache in Rats

Background: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache. Methods: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats. Results: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate increased nociceptive behaviors suggesting that acetate, not acetaldehyde, accumulation results in hangover-like hypersensitivity in our model. Since adenosine accumulation is a result of acetate formation, we administered an adenosine antagonist that blocked hypersensitivity. Discussion: Our study shows that acetate contributes to hangover headache. These findings provide insight into the mechanism of hangover headache and the mechanism of headache induction

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Secretome of mesenchymal stem cells and its impact on Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible loss of lung function that stem from two mechanisms, inflammation and senescence. Crosstalk between these two mechanisms accelerate the development of COPD, thus targeting these two pathways may offer benefits in the treatment of COPD. Growing amount of evidence have shown that mesenchymal stem cells as a promising candidate for the treatment of COPD. Over the years, many studies conducted to decipher the therapeutic effect of MSC in COPD and the mechanisms involve, in the hope of utilizing these cells as new therapeutic strategy for COPD. However, the cell-based therapy by using the MSC presented with many obstacles including low engraftment at the site of injury, the risk of microvascular occlusion, unwanted differentiation, and also the risk of malignant transformation. Recently, recently researchers begin to look at the possibility of using MSC derived extracellular vesicles as an alternative to MSC. Here we review the effect of MSC and MSC derived EV in modulating inflammation, and senescence in COPD. We also review current treatment and the side effect in COPD, and senolytic drugs, a new therapeutic strategy targeting the senescent cells

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

A Multiyear Approach to Student-Driven Investigations in Exercise Physiology

Many undergraduate institutions offer individual research opportunities for upper-level students in independent study courses and summer undergraduate research programs. These are necessarily limited to a small number of students. Greater numbers of students can benefit from incorporating student-directed investigative experiences into laboratories in standard courses. In human performance investigations, any single course may not offer sufficient numbers of subjects to adequately test hypotheses comparing population groups or to examine longitudinal trends. In this exercise physiology course, exercise testing was conducted in three areas: 1) techniques of body composition analysis, 2) field tests for the estimation of maximal oxygen consumption, and 3) maximal anaerobic and aerobic power. All students enrolled over a 10-yr period participated as subjects and as testers. Working in small research groups, students added their results to those from previous years, generated a variety of hypotheses (correlations between tests, subgroup differences, etc.), and tested them statistically using the complete data set of 217 subjects. They then engaged in collaborative writing and peer review to prepare formal papers on their results. The multiyear approach allowed students to situate their work within and contribute to the accumulation of a large database and to practice essential scientific skills of hypothesis formation, data collection and analysis, collaborative work, and scientific communication. In addition, due to the larger number of subjects available to analyze, students observed statistically significant differences between test groups in the multiyear database that they were unable to demonstrate when conducting analysis on a single course. Finally, the large number of subjects and statistical power offered by the use of the database provides distinct pedagogical advantages

Implementing and Evaluating a Peer-Led Team Learning Approach in Undergraduate Anatomy and Physiology

A Peer-Led Team Learning (PLTL) program was implemented in a first-year, undergraduate Anatomy and Physiology course sequence to examine the student perceptions of the program and determine the effects of PLTL on student performance. PLTL was integrated into four sections of Anatomy and Physiology I and II in the fall 2010 and spring 2011 semesters. Students (N = 127, 70% completing the courses) completed a perceptual survey of the PLTL program, which was inserted into the Student Assessment of Learning Gains (SALG) online instrument. Across the four sections, students uniformly felt several dimensions of PLTL use provided moderate, good, or great help in their overall learning of course content and promoting discussion and collaboration with other students and engaging them in active learning. Within the two sections of Anatomy and Physiology I, quiz grades were compared between PLTL and non-PLTL years. Significant increases in scores were seen on some but not all material in this course on the basis of content quizzes. The results of the PLTL program thus support the hypothesis of increased student perception of learning and support an increase in student performance with certain content in the course

Does Active Learning Improve Students\u27 Knowledge of and Attitudes Toward Research Methods?

We incorporated an active, collaborative-based research project in our undergraduate Research Methods course for first-year sports medicine majors. Working in small groups, students identified a research question, generated a hypothesis to be tested, designed an experiment, implemented the experiment, analyzed the data, and presented their findings to the college community. We used a survey to assess students\u27 perception of and attitudes about research and research methods before and after the semester. In addition, students reflected on the research experiment through a weekly discussion and dialogue on Blackboard. Students were responsible for a final oral presentation and a poster presentation. Incorporating a participatory, collaborative, and active learning component to this course allowed students to grasp relevant research methodology theories and principles, acquire competency in research methodology techniques, develop interpersonal and professional skills, and improve their attitude regarding science and the research process. The results suggest participation in a research project can be an effective way to enhance first-year student learning and attitudes regarding research methodology