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1. Angiotensin receptor blockade mimics the effect of exercise on recovery after orthopaedic trauma by decreasing pain and improving muscle regeneration

   https://doi.org/10.1113/JP278991  

   Tawfik, Vivianne L. ; Quarta, Marco ; Paine, Patrick ; Forman, Thomas E. ; Pajarinen, Jukka ; Takemura, Yoshinori ; Goodman, Stuart B. ; Rando, Thomas A. ; Clark, J. David ( December 2019 , The Journal of Physiology)

   Our tibial fracture orthopaedic injury model in mice recapitulates the major manifestations of complex trauma, including nociceptive sensitization, bone fracture, muscle fibrosis and muscle fibre loss.

   Delayed exercise after complex orthopaedic trauma results in decreased muscle fibrosis and improved pain

   Losartan, an angiotensin‐receptor blocker with anti‐fibrotic abilities, recapitulates the effect of exercise on post‐injury recovery and may provide an enhanced recovery option for those who are unable to exercise after injury

   Chronic pain and disability after limb injury are major public health problems. Early mobilization after injury improves functional outcomes for patients, although when and how to implement rehabilitation strategies remains a clinical challenge. Additionally, whether the beneficial effects of exercise can be reproduced using pharmacological tools remains unknown and may benefit patients who are unable to exercise as a result of immobilization. We developed a murine model of orthopaedic trauma combining tibia fracture and pin fixation with muscle damage. Behavioural measures included mechanical nociceptive thresholds and distances run on exercise wheels. Bone healing was quantified using microcomputed tomagraphic scanning, and muscle fibre size distribution and fibrosis were followed using immunohistochemistry. We found that the model provided robust mechanical allodynia, fibrosis and a shift to smaller average muscle fibre size lasting up to 5 weeks from injury. We also observed that allowing ‘late’ (weeks 1–2) rather than ‘early’ (weeks 0–1) exercise after injury resulted in greater overall running activity and greater reversal of allodynia. In parallel, the late running paradigm was associated with reduced muscle fibrosis, earlier increase in muscle fibre diameter and a short‐term benefit in reducing callus volume. Providing the anti‐fibrotic angiotensin receptor blocker losartan to mice in drinking water reduced both allodynia and muscle fibrosis. Combining losartan and late exercise provided no additional benefit. We conclude that early healing after orthopaedic trauma must be allowed prior to the initiation of exercise to achieve optimal pain, functional and physiological outcomes and that losartan is a viable candidate for translational studies.

    

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2. Resilience, pain, and the brain: Relationships differ by sociodemographics

   https://doi.org/10.1002/jnr.24790  

   Tanner, Jared J. ; Johnson, Alisa J. ; Terry, Ellen L. ; Cardoso, Josue ; Garvan, Cynthia ; Staud, Roland ; Deutsch, Georg ; Deshpande, Hrishikesh ; Lai, Song ; Addison, Adriana ; et al ( February 2021 , Journal of Neuroscience Research)

   Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain‐related brain structures, with consideration for sex and ethnicity/race. A cross‐sectional analysis of 166 non‐Hispanic Black and non‐Hispanic White adults, 45–85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain‐related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

    

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3. From Students to Cofacilitators: Latinx Students’ Experiences in Mathematics and Computer Programming

   https://doi.org/10.1177/01614681221104104  

   LópezLeiva, Carlos A. ; Noriega, Gabino ; Celedón-Pattichis, Sylvia ; Pattichis, Marios S. ( June 2022 , Teachers College Record: The Voice of Scholarship in Education)

   Computer programming is rarely accessible to K–12 students, especially for those from culturally and linguistically diverse backgrounds. Middle school age is a transitioning time when adolescents are more likely to make long-term decisions regarding their academic choices and interests. Having access to productive and positive knowledge and experiences in computer programming can grant them opportunities to realize their abilities and potential in this field.

   This study focuses on the exploration of the kind of relationship that bilingual Latinx students developed with themselves and computer programming and mathematics (CPM) practices through their participation in a CPM after-school program, first as students and then as cofacilitators teaching CPM practices to other middle school peers.

   An after-school program, Advancing Out-of-School Learning in Mathematics and Engineering (AOLME), was held at two middle schools located in rural and urban areas in the Southwest. It was designed to support an inclusive cultural environment that nurtured students’ opportunities to learn CPM practices through the inclusion of languages (Spanish and English), tasks, and participants congruent to students in the program. Students learned how to represent, design, and program digital images and videos using a sequence of 2D arrays of hexadecimal numbers with Python on a Raspberry Pi computer. The six bilingual cofacilitators attended Levels 1 and 2 as students and were offered the opportunity to participate as cofacilitators in the next implementation of Level 1.

   This longitudinal case study focused on analyzing the experiences and shifts (if any) of students who participated as cofacilitators in AOLME. Their narratives were analyzed collectively, and our analysis describes the experiences of the cofacilitators as a single case study (with embedded units) of what it means to be a bilingual cofacilitator in AOLME. Data included individual exit interviews of the six cofacilitators and their focus groups (30–45 minutes each), an adapted 20-item CPM attitude 5-point Likert scale, and self-report from each of them. Results from attitude scales revealed cofacilitators’ greater initial and posterior connections to CPM practices. The self-reports on CPM included two number lines (0–10) for before and after AOLME for students to self-assess their liking and knowledge of CPM. The numbers were used as interview prompts to converse with students about experiences. The interview data were analyzed qualitatively and coded through a contrast-comparative process regarding students’ description of themselves, their experiences in the program, and their perception of and relationship toward CPM practices.

   Findings indicated that students had continued/increased motivation and confidence in CPM as they engaged in a journey as cofacilitators, described through two thematic categories: (a) shifting views by personally connecting to CPM, and (b) affirming CPM practices through teaching. The shift in connecting to CPM practices evolved as students argued that they found a new way of learning mathematics, in that they used mathematics as a tool to create videos and images that they programmed by using Python while making sense of the process bilingually (Spanish and English). This mathematics was viewed by students as high level, which in turned helped students gain self-confidence in CPM practices. Additionally, students affirmed their knowledge and confidence in CPM practices by teaching them to others, a process in which they had to mediate beyond the understanding of CPM practices. They came up with new ways of explaining CPM practices bilingually to their peers. In this new role, cofacilitators considered the topic and language, and promoted a communal support among the peers they worked with.

   Bilingual middle school students can not only program, but also teach bilingually and embrace new roles with nurturing support. Schools can promote new student roles, which can yield new goals and identities. There is a great need to redesign the school mathematics curriculum as a discipline that teenagers can use and connect with by creating and finding things they care about. In this way, school mathematics can support a closer “fit” with students’ identification with the world of mathematics. Cofacilitators learned more about CPM practices by teaching them, extending beyond what was given to them, and constructing new goals that were in line with a sophisticated knowledge and shifts in the practice. Assigned responsibility in a new role can strengthen students’ self-image, agency, and ways of relating to mathematics.

    

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4. A prototype closed-loop brain–machine interface for the study and treatment of pain

   https://doi.org/10.1038/s41551-021-00736-7  

   Zhang, Qiaosheng ; Hu, Sile ; Talay, Robert ; Xiao, Zhengdong ; Rosenberg, David ; Liu, Yaling ; Sun, Guanghao ; Li, Anna ; Caravan, Bassir ; Singh, Amrita ; et al ( June 2021 , Nature Biomedical Engineering)

   Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain–machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top–down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms. 

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5. Multidimensional Sleep Health Problems Across Middle and Older Adulthood Predict Early Mortality

   https://doi.org/10.1093/gerona/glad258  

   Lee, Soomi ; Mu, Christina X. ; Wallace, Meredith L. ; Andel, Ross ; Almeida, David M. ; Buxton, Orfeu M. ; Patel, Sanjay R. ; Magaziner, ed., Jay ( November 2023 , The Journals of Gerontology: Series A)

   Having multiple sleep problems is common in adulthood. Yet, most studies have assessed single sleep variables at one timepoint, potentially misinterpreting health consequences of co-occurring sleep problems that may change over time. We investigated the relationship between multidimensional sleep health across adulthood and mortality.

   Participants from the Midlife in the United States Study reported sleep characteristics in 2004–2006 (MIDUS-2; M2) and in 2013–2014 (MIDUS-3; M3). We calculated a composite score of sleep health problems across 5 dimensions: Regularity, Satisfaction, Alertness, Efficiency, and Duration (higher = more problems). Two separate models for baseline sleep health (n = 5 140; median follow-up time = 15.3 years) and change in sleep health (n = 2 991; median follow-up time = 6.4 years) to mortality were conducted. Cox regression models controlled for sociodemographics and key health risk factors (body mass index, smoking, depressive symptoms, diabetes, and hypertension).

   On average, 88% of the sample reported having one or more sleep health problems at M2. Each additional sleep health problem at M2 was associated with 12% greater risk of all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.04–1.21), but not heart disease-related mortality (HR = 1.14, 95% CI = 0.99–1.31). An increase in sleep health problems from M2 to M3 was associated with 27% greater risk of all-cause mortality (HR = 1.27, 95% CI = 1.005–1.59), and 153% greater risk of heart disease mortality (HR = 2.53, 95% CI = 1.37–4.68).

   More sleep health problems may increase the risk of early mortality. Sleep health in middle and older adulthood is a vital sign that can be assessed at medical checkups to identify those at greater risk.

    

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