Course-based Undergraduate Research Experiences (CUREs) in high-enrollment, introductory classes are a 37 potentially transformative approach to retaining more students in STEM majors. We developed and piloted a CURE 38 in the introductory biology courses at the University of Washington. This CURE focuses on analyzing experimental 39 evolution of antibiotic resistance in Escherichia coli and generates data on two topics relevant to clinical practice: 40 compensatory mutations and cross-drug effects. By studying mutations in central cellular machinery that confer drug 41 resistance, students not only gain insight into fundamental cellular phenomena, but also recognize the molecular 42 basis of a medically important form of evolutionary change, connecting genetics, microbiology, and evolution.

The fear of missing out (FoMO) is characterized in the literature as a fear that others are having rewarding experiences while one is missing out, and a constant need to keep connected with one’s social network. Driven by Social Determination Theory (SDT) FoMO has been linked with Problematic Social Networking Sites use (PSNSU), negative affectivity (NA), self-esteem (SE) and sleep disturbances. The present study reports findings from 512 individuals (79.1% women, mean age 30.5 years, SD= 8.61). Structural equation modelling (SEM) suggests that the duration of SNSs use and the numbers of SNSs platforms actively used partially mediated the relationship between FoMO and PSNSU. In turns, PSNSU partially mediated the relationship between FoMO and NA. Furthermore, the present study has extended the literature by incorporating the Vulnerability Model in the FoMO concept, identifying that SE partially mediated the relationship between FoMO and NA, while NA fully mediated the relationship between FoMO and sleeping disturbances. Accordingly, the present has extended previous research findings in showing exercise as a potential protective factor to prevent against FoMO. Practical and theoretical implications are discussed.

After a Century it is time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling as an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where roles of driver and recipient cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility and cognition. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in illness and injury. Like a Phoenix, lactate rises again in importance in 21^st Century Biology.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

This study explores the intriguing relationship between personality traits, self-rated fitness (SRF), and physical activity (PA) variables among German university students (N = 4,244), and sheds light on the impact of personality on adherence to PA guidelines. Employing an online cross-sectional study, the short-form of the Big Five Inventory-2 assessed five domains of personality traits (Extraversion, Negative Emotionality, Agreeableness, Conscientiousness, and Open-Mindedness). PA, including sitting time, was assessed using the International Physical Activity Questionnaire (short-form). SRF and muscle-strengthening activities (MSA) were assessed with one item each. Multiple linear and logistic regression analyses examined associations of individual personality trait domains and all domains combined with SFR, PA variables, and adherence to PA guidelines, controlling for sociodemographic, behavioral, and (mental) health covariates. Most reliably, Extraversion and Conscientiousness revealed positive associations with PA variables, while Negative Emotionality yielded inverse relationships with PA variables. For instance, each unit increase in Extraversion corresponded to additional 17 minutes weekly MSA. Contrary, daily sitting time was unrelated to personality. Of note, high Open-Mindedness was associated with lower odds for adhering to current PA guidelines. The findings have implications for developing targeted interventions that promote a physically active lifestyle and support students' well-being and academic success.

Athletes living with and beyond cancer can continue to train and, in some cases, compete during treatment. Following cancer treatment, athletes can return to competitive sport but need to learn to adapt their physical strength and training to lingering effects of cancer. It is critical for oncology healthcare providers to use the principles of assess, refer and advise to exercise oncology programs that are appropriate for the individual. Managing side effects of treatment is key to being able to train during and immediately following cancer treatment. Keen attention to fatigue is important at any point in the cancer spectrum to avoid overtraining and optimize the effects of training.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

Abstract: This article provides a brief review of the ontogeny of chondrocytes and the pathophysiology of osteoarthritis (OA), and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of mesenchymal stem cells for successful transplantation therapy. In response to exercise chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins and antiinflammatory cytokines and decrease their production of proinflammatory cytokines and matrix degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise increases peripheral blood recruitment of bone marrow-derived mesenchymal stem cells (BM-MSC) and upregulates BM-MSC expression of osteogenic and chondrogenic genes, osteogenic micro-RNAs, and osteogenic growth factors. Rodent experiments are uniform in demonstrating that exercise enhances the osteogenic potential of BM-MSC while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and interferon (INF)-γ while increasing their production anti-osteoclastogenic cytokines IL-10 and transforming growth factor (TGF)-β. In conclusion, physical exercise done both by stem cell donors and recipients may improve the outcome of mesenchymal stem cell transplantation.

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Gulf War Ill-ness (GWI) and control subjects had fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction Methods: Activated midbrain nuclei were inferred by re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI had greater activation during cognition than ME/CFS in left pedunculotegmental nucleus. Postexercise ME/CFS had greater activation than GWI for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI indicating reciprocal patterns of activation. Controls had no changes. Conclusions: Exercise caused opposite effects with increased activation in ME/CFS but decreased activation in GWI indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

Technological advances in game-mediated robotics provide an opportunity to engage children with cerebral palsy (CP) and other neuromotor disabilities in more frequent and intensive therapy by making personalized, programmed interventions available 24/7 in children’s homes. Though shown to be clinically effective and feasible to produce, little is known of the subjective factors impacting acceptance of what we term assistive/rehabilitative (A/R) gamebots by their target populations. This research describes the conceptualization phase of an effort to develop a valid and reliable instrument to guide the design of A/R gamebots. We conducted in-depth interviews with 8 children with CP and their families who had trialed an exemplar A/R gamebot, PedBotHome, for 28 days in their homes. The goal was to understand how existing theories and instruments were either appropriate or inappropriate for measuring the subjective experience of A/R gamebots. Key findings were the importance of differentiating the use case of therapy from that of assistance in rehabilitative technology assessment, the need to incorporate the differing perspectives of children with CP and those of their parents into A/R gamebot evaluation, and the potential conflict between the goals of preserving the quality of the experience of game play for the child while also optimizing the intensity and duration of therapy provided during play.

Throughout this paper the effects of injuries on athletes are highlighted in different aspects. Exertional compartment syndrome is a specific injury related to athletes that is thoroughly explored in this paper through an analysis of the anatomy, symptoms, diagnosis and treatments of the syndrome. Exertional compartment syndrome is an exercise-induced muscle and nerve condition that causes pain, swelling as well as disability in the affected muscles of the lower leg. This syndrome commonly develops in young athletes involved in sports with excessive running and repetitive impact such as track and field, soccer, basketball and lacrosse. Exertional compartment syndrome is commonly misdiagnosed as other less severe injuries such as shin splints, which is symptomatic of pain along the tibia bone of the lower leg caused by overuse. The misdiagnosis of exertional compartment syndrome allows the syndrome to worsen and intensify resulting in the only effective treatment to be fasciotomy, a surgical procedure to release the pressure within the compartment of the lower leg. There is no definitive protocol developed for patients after fasciotomy is performed. Athletes experiencing similar symptoms after surgery are usually treated for their symptoms rather than the syndrome as a whole, which does not have a high degree of success. The development of a definitive protocol utilizing the techniques of manual therapy, mobility stretching and corrective strength training can improve the adverse effects of exertional compartment syndrome as well as restore functionality to the athlete. Raising awareness of this syndrome in athletics will be effective in treating the athlete early on in order to avoid severe effects and invasive procedures.

The responses of inflammatory cytokines and brain-derived neurotrophic factor (BDNF) to a high-intensity interval training (HIIT) session were compared between 7 postmenopausal (57±2 y) and 8 premenopausal females (44±3 y) during the luteal phase of their menstrual cycle, when estrogen and progesterone are highest, and. HIIT consisted of 10 x 1 min running intervals (90% maximum heart rate) separated by 1 min recovery intervals. Blood samples were collected at baseline (fasted), pre-exercise (postprandial), and 0, 30 and 90 min post-HIIT and analyzed for interleukin (IL-6) and 10 (IL-10), tumour necrosis factor-alpha (TNF-α) and BDNF. IL-6 significantly increased from pre-exercise to 0 min post-HIIT in postmenopausal (+40%, p=0.01) but 30 min post-HIIT in premenopausal females (+60%, p=0.02). IL-6 remained elevated at 90 min post-HIIT in premenopausal (+104%, p=0.05) and to a higher degree in postmenopausal (+385%, p<0.001). IL-10 showed no response. TNF-α increased from pre- to 0 min post-HIIT (+10%, p=0.05), then decreased to below pre-exercise at 30 min (-10%, p=0.02) and 90 min (-5%, p=0.04) in both groups. BDNF increased immediate post-HIIT in premenopausal (+60%, p<0.001) but not postmenopausal females. The differences in IL-6 and BDNF response to HIIT between pre and postmenopausal females provide evidence of the role of female reproductive hormones in the regulation of these exercise-induced responses.

Hispanics are disproportionately affected by low rates of physical activity and high rates of chronic diseases. Hispanics generally and Mexican Americans specifically are underrepresented in research on physical activity and its impact on mental well-being. Some community-based interventions have been effective in increasing physical activity among Hispanics. This study examined data from a sample of low-income Hispanic participants in free community exercise classes to characterize the association between self-reported frequency of exercise class attendance, intensity of physical activity, and participant well-being. As part of two cross-sectional samples recruited from a stratified random sample of community exercise classes, 302 participants completed a questionnaire consisting of a modified version of the Godin-Shephard Leisure-Time Exercise Questionnaire (LTEQ) and the Mental Health Continuum Short Form (MHC-SF). Adjusted binary logistic regression analyses indicated that those who achieve moderate and strenuous self-reported physical activity have 130% higher odds (p = 0.0422) of positive mental well-being after adjustment for age, attendance, and self-reported health. This study provides evidence that physical activity intensity and time are associated with flourishing mental health among Hispanics. The study provides insight into the planning and development of community-based physical activity programming tailored to low-income populations.

We examined special roles of the Central Nervous System (CNS) in an attempt to resolve the puzzle that chronic diseases cannot be cured by medicine. By exploring a skill-learning model, we found that the CNS is able to remember certain information reflecting biochemical and cellular (B&C) processes in the body. From the skill using ability, we found that the CNS is able to control basic B&C processes that drive and power the skill. From the ability to adjust forces and force direction of a physical act, we found that the CNS is able to adjust B&C processes that drive the physical act. From this adjustment capability, we further inferred that the CNS must also store information on the baseline B&C processes. As a whole, we found that the CNS can maintain information on baseline B&C processes, up-regulate or down-regulate the processes, and make comparisons in performing its regulatory functions. We found that chronic diseases are the results of deviated baseline B&C processes. Per the proved hypothesis, the CNS maintains deviated baseline B&C processes, and thus protects the body states of fully developed diseases. We then used the three CNS roles to explain that cancer progresses with increasing malignancy, cancer quickly returns after a surgery, cancer cells repopulate after chemotherapy and radiotherapy, cancer develops drug resistance inevitably, immune cells rebound after suppression, generally poor benefits of cancer drugs such as beta-blockers, etc. We further showed that long-term exercises generally push most, if not all, baseline B&C processes in diametrical opposing directions against the diseased B&C processes, implying that exercises play unique roles in reversing chronic diseases. Finally, we proposed several strategical approaches to resetting the CNS’ state memory as the essential condition for curing chronic diseases.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.