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Julianna H Prim,1–3,* Sangtae Ahn,1,2,* Maria I Davila,1 Morgan L Alexander,1,2 Karen L McCulloch,3,4,* Flavio Fröhlich1,2,5–8,* 1Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 2Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 3Department of Allied Health Sciences, Human Movement Science Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 4Division of Physical Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 5Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 6Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 7Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; 8Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA*These authors contributed equally to this workCorrespondence: Flavio FröhlichUniversity of North Carolina at Chapel Hill 116 Manning Dr, Mary Ellen Jones Building 6018, Chapel Hill, NC 27599, USATel +1 919 966 4584Email flavio_frohlich@med.unc.eduBackground: Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients.Objective: To evaluate if non-invasive brain stimulation modulates the ANS, we analyzed HRV metrics collected in a previously published study of transcranial alternating current stimulation (tACS) for the modulation of CLBP through enhancing alpha oscillations. We hypothesized that tACS would increase RSA.Methods: A randomized, crossover, double-blind, sham-controlled pilot study was conducted to investigate the effects of 10Hz-tACS on metrics of ANS balance calculated from electrocardiogram (ECG). ECG data were collected for 2 mins before and after 40 mins of 10Hz-tACS or sham stimulation.Results: There were no significant changes in RSA or other frequency-domain HRV components from 10Hz-tACS. However, exploratory time-domain HRV analyses revealed a significant increase in the standard deviation of normal intervals between R-peaks (SDNN), a measure of ANS balance, for 10Hz-tACS relative to sham.Conclusion: Although tACS did not significantly increase RSA, we found in an exploratory analysis that tACS modulated an integrated HRV measure of both ANS branches. These findings support the further study of how the ANS and alpha oscillations interact and are modulated by tACS.ClinicalTrials.gov: Transcranial Alternating Current Stimulation in Back Pain – Pilot Study, NCT03243084.Keywords: low back pain, autonomic nervous system, heart rate variability, transcranial alternating current stimulation

Premenstrual dysphoric disorder (PMDD), a more severe manifestation of premenstrual syndrome (PMS), is characterized by emotional, behavioral, and physical symptoms that begin in the mid-to-late luteal phase of the menstrual cycle, when estradiol and progesterone levels precipitously decline, and remit after the onset of menses. Remotely monitoring physiologic variables associated with PMDD depression symptoms, such as heart rate variability (HRV), sleep, and physical activity, holds promise for developing an affective state prediction model. Switching into and out of depressive states is associated with an increased risk of suicide, and therefore, monitoring periods of affective switching may help mitigate risk. Management of other chronic health conditions, including cardiovascular disease and diabetes, has benefited from remote digital monitoring paradigms that enable patients and physicians to monitor symptoms in real-time and make behavioral and medication adjustments. PMDD is a chronic condition that may benefit from real-time, remote monitoring. However, clinical practice has not advanced to monitoring affective states in real-time. Identifying remote monitoring paradigms that can detect within-person affective state change may help facilitate later research on timely and efficacious interventions for individuals with PMDD. This narrative review synthesizes the current literature on behavioral and physiological correlates of PMDD suitable for remote monitoring during the menstrual cycle. The reliable measurement of heart rate variability (HRV), sleep, and physical activity, with existing wearable technology, suggests the potential of a remote monitoring paradigm in PMDD and other depressive disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brown, Bondy, Prim, Dichter and Schiller.)

The perimenopausal transition is marked by an increased risk for affective dysregulation and major depressive disorder (MDD), with hormone replacement therapy using estradiol (E2) showing promise for alleviating symptoms of perimenopausal-onset MDD (PO-MDD). Although E2's effectiveness is recognized, its mechanisms underlying mood symptom modulation remain to be fully elucidated. Building on previous research suggesting that E2 may influence mood by altering cortico-subcortical connectivity, this study investigated the effects of transdermal E2 on resting-state functional connectivity (rsFC) in perimenopausal women with and without PO-MDD, focusing on rsFC changes using seed regions within reward and emotion processing networks. In this pharmaco-fMRI study, 16 participants with PO-MDD and 18 controls underwent rsFC analysis before and after three weeks of transdermal E2 administration. Pre-E2 results showed that the PO-MDD group, compared to controls, exhibited increased connectivity between the right amygdala (seed) and medial prefrontal cortex and anterior cingulate cortex, and decreased connectivity with the supplementary motor area. Comparing groups on change from pre-E2 to post-E2 revealed several significant E2-induced changes in connectivity between the PO-MDD and control groups: PO-MDD showed increased connectivity between the right caudate nucleus (seed) and left insula, and decreased connectivity between the right putamen (seed) and left hippocampus, and the right amygdala (seed) and left ventromedial prefrontal cortex. Notably, changes in connectivity were predictive of symptom trajectories across anhedonia, depressive mood, somatic, and vasomotor domains in the PO-MDD group. These findings enrich our understanding of PO-MDD by highlighting distinct rsFC patterns characteristic of the disorder and their shifts in response to E2 treatment, suggesting potential neural mechanisms underlying E2's mood-modulating effects., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Published by Elsevier B.V.)

The objectives of this retrospective observational study were to investigate the association between BCS at 21 d before calving with prepartum and postpartum DMI, energy balance (EB), and milk yield. Data from 427 multigravid cows from 11 different experiments conducted at the University of Florida (Gainesville, FL) were used. Cows were classified according to their BCS at 21 d before calving as fat (BCS ≥ 4.00; n = 83), moderate (BCS = 3.25-3.75; n = 287), and thin (BCS ≤ 3.00; n = 57). Daily DMI from -21 to -1 and from +1 to +28 DIM was individually recorded. Energy balance was calculated as the difference between net energy for lactation consumed and required. Dry matter intake in fat cows was lower than that in moderate and thin cows both prepartum (fat = 9.97 ± 0.21, moderate = 11.15 ± 0.14, and thin = 11.92 ± 0.22 kg/d) and postpartum (fat = 14.35 ± 0.49, moderate = 15.47 ± 0.38, and thin = 16.09 ± 0.47 kg/d). Dry matter intake was also lower for moderate cows compared with thin cows prepartum, but not postpartum. Energy balance in fat cows was lower than in moderate and thin cows both prepartum (fat = -4.16 ± 0.61, moderate = -1.20 ± 0.56, and thin = 0.88 ± 0.62 Mcal/d) and postpartum (fat = -12.77 ± 0.50, moderate = -10.13 ± 0.29, and thin = -6.14 ± 0.51 Mcal/d). Energy balance was also lower for moderate cows compared with thin cows both prepartum and postpartum. There was a quadratic association between BCS at 21 d before calving and milk yield. Increasing BCS from 2.5 to 3.5 was associated with an increase in daily milk yield of 6.0 kg and 28 d cumulative milk of 147 kg. Increasing BCS from 3.5 to 4.5 was associated with a decrease in daily milk yield of 4.4 kg and 28 d cumulative milk of 116 kg. In summary, a moderate BCS at 21 d before calving was associated with intermediate DMI and EB pre- and postpartum but greater milk yield compared with thinner and fatter cows. Our findings indicate that a moderate BCS is ideal for ensuring a successful lactation., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Physical Therapists affiliated with Intrepid Spirit Centers evaluate and treat Active Duty Service Members (ADSM) who have duty-limiting post-concussion symptoms to improve the ability to perform challenging tasks associated with military service. The Complex Assessment of Military Performance (CAMP) is a test battery that more closely approximates the occupational demands of ADSM without specific adherence to a particular branch of service or military occupational specialty. Subtasks were developed with military collaborators to include high level skills that all service members must be able to perform such as reacting quickly, maintaining visual stability while moving and changing positions, and scanning for, noting, and/or remembering operationally relevant information under conditions of physical exertion., Objective: The purpose of this observational longitudinal study is to: 1- establish typical performance parameters for ADSM on the CAMP test battery 2- determine the element of the CAMP battery that demonstrate the greatest differences from standard performance and serve as predictors for successful return to duty and 3- develop clinician-facing feedback algorithms and displays and 4-develop materials for clinical dissemination. This ongoing multi-site study is currently funded through the CDMRP and has been approved by the Naval Medical Center Portsmouth IRB., Methods: ADSM undergoing post-concussion rehabilitation at the Intrepid Spirit Centers will be tested within one week of their initial Physical Therapy evaluation and after completing Physical Therapy. Control participants will include males, females, and ADSM from the Special Operations community. Participants will complete an intake form that includes questions about demographics, military service, deployment and concussion history, and profile and duty status. Other measures include those that explore concussion symptoms, sleep quality, post-traumatic stress, and perceptions of resilience. The CAMP includes three separate 10-15 minute tasks. Movement is recorded by wearable inertial sensors and heart rate variability is recorded with a POLAR10 monitor. The "Run-Roll" task requires rapid position changes, combat rolls and quick running forwards and backwards while carrying a simulated weapon. Visual stability before and after the task is also performed. The "Dual-Task Agility" task includes rapid running with and without a weighted vest and a working memory task. The "Patrol Exertion" task requires repeated stepping onto an exercise step while watching a virtual patrol video. Additional tasks include monitoring direction of travel, observing for signs of enemy presence, and reacting to multiple auditory signals embedded in the video., Discussion: Measures that evaluate relevant skills are vital to support safe return to duty for ADSM who may be exposed to imminent danger as part of training or mission demands. The CAMP is designed to be an ecologically valid and clinically feasible assessment that may be more sensitive to capturing subtle impairments that impact duty performance as test skills are integrated into dual and multi-tasks that reflect occupational demands. Assessment results may serve as a more robust indicator of readiness for full return to duty after concussion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Wearable devices offer a unique opportunity to provide real-time monitoring of affective switching (the mood transition into and out of dysregulated affective state), a critical window to detect and prevent depression and suicide. To model affective switching, we studied premenstrual dysphoric disorder (PMDD): a depressive disorder with a regularly occurring monthly trigger. Results supported feasibility of smartwatch monitoring protocol and preliminary evidence that objective physiological and behavioral metrics were associated with affective state.

The objective was to unravel the peripartum immune and metabolic changes associated with metritis in Holstein cows. Holstein cows (n = 128) had blood collected at -14, 0, 3, and 7 d relative to parturition (DRP). Flow cytometry was used to evaluate blood leukocyte counts, proportions, and activation. Total cells, live cells, single cells, monocytes (CD172α + /CD14 + ), polymorphonuclears (CD172α + /CD14 - /SSC high ), B-cells (CD21 + /MHCII + ), CD4 + T-cells (CD4 + ), CD8 + T-cells (CD8 + ), and γδ T-cells (γδTCR + ) were evaluated. Both CD62L and CD11b were used as markers of cell activation. Major histocompatibility complex class II was used as a marker of antigen presentation in monocytes. A Milliplex Bovine Cytokine/Chemokine 08-plex kit was used to evaluate plasma concentrations of IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The body weight (BW) change prepartum was calculated as the difference between calving BW and prepartum BW divided by the number of days between measurements. Plasma fatty acids (FA) were measured at -14 and 0 DRP using untargeted gas chromatography with time-of-flight mass spectrometry. Data were analyzed by ANOVA for repeated measures. Cows that developed metritis (n = 57) had greater prepartum BW, prepartum BW loss, and greater FA concentrations at calving. Plasma FA at calving was positively correlated with IL-1β. Cows that developed metritis had persistent systemic inflammation, which was demonstrated by greater B-cell activation, greater pro-inflammatory cytokine concentrations, and greater cell damage pre- and postpartum. Postpartum, we observed greater polymorphonuclear cell activation and extravasation but lesser monocytes and CD4 + T-cells activation and extravasation, which suggests postpartum immune tolerance. Greater prepartum adiposity in cows that developed metritis may lead to systemic inflammation pre- and postpartum and immune tolerance postpartum, which may lead to failure to prevent bacterial infection, and development of puerperal metritis., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objective of this study was to identify metabolites associated with metritis and use them for identification of cellular mechanisms affected during transition into lactation. Holstein cows (n = 104) had blood collected in the prepartum period (d -14 ± 6 relative to calving), at calving (d 0), and at the day of metritis diagnosis (d 7 ± 2 after calving). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 52). Cows with metritis were paired with herdmates without metritis (n = 52) based on days in milk. The metabolome of plasma samples was evaluated using untargeted gas chromatography time-of-flight mass spectrometry. Univariate analyses included t-tests and fold change analyses. Metabolites with false discovery rate adjusted P ≤ 0.10 on t-tests were used for partial least squares discriminant analysis coupled with permutational analysis using 2,000 permutations. Metabolites with false discovery rate adjusted P ≤ 0.10 on t-tests were also used for enriched pathway analyses and identification of cellular processes. Cows that developed metritis had affected cellular processes associated with lower amino acid metabolism in the prepartum period, greater lipolysis, cell death, and oxidative stress at calving and at metritis diagnosis, and greater leukocyte activation at calving, but lower immune cell activation at metritis diagnosis. In summary, cows that developed metritis had plasma metabolomic changes associated with greater lipolysis, oxidative stress, and a dysregulated immune response which may predispose cows to metritis development., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The pubertal transition is characterized by pronounced sex hormone fluctuation, refinement of affective neural circuitry, and an increased risk of depression in female adolescents. Sex hormones, including testosterone, exert modulatory effects on frontal-limbic brain networks and are associated with emotion dysregulation and depressive symptoms. Weekly changes in hormones predict affective symptoms in peripubertal female adolescents, particularly in the context of stress; however, the biobehavioral mechanisms underlying hormone change and mood relationships during the pubertal transition have yet to be determined and was the objective of the present study. Forty-three peripubertal female adolescents (ages 11-14) collected 8-weekly salivary hormone (estrone, testosterone) samples and mood assessments to evaluate hormone-mood relationships, followed by a biobehavioral testing session with psychosocial stress and EEG. Within-person correlations between weekly hormone changes and corresponding mood were performed to determine individual differences in mood sensitivity to weekly hormone change. Increased frontal theta activity indexing emotion reactivity, reduced cortisol reactivity, and reduced vagal efficiency predicted the strength of the relationship between testosterone and mood. Further, testosterone-sensitivity strength was associated with the enhancement of negative affect following stress testing. Results identify divergent frontal theta and stress responses as potential biobehavioral mechanisms underlying mood sensitivity to peripubertal testosterone fluctuation.

Introduction: Return-to-duty (RTD) readiness assessment for service members (SM) following concussion requires complex clinical considerations. The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a functional assessment which improves on previous laboratory-based RTD assessments., Methods: Sixty-four SM diagnosed with concussion and 60 healthy control (HC) SM participated in this study. Group differences were analyzed to validate the POWAR-TOTAL. The High-level Mobility Assessment Test (HiMAT) was used to examine concurrent construct validity. An exploratory logistic regression analysis examined predictive validity., Results: The groups were demographically well-matched except for educational level. POWAR-TOTAL measures were statistically significantly different between the groups with moderate to large effect sizes. Concussed participants were less likely to be able to complete all trials of the POWAR-TOTAL. Motor scores correlated highly with HiMAT scores. POWAR-TOTAL motor task performance and membership in the control group was significantly associated with self-reported physical readiness to deploy., Conclusion: The POWAR-TOTAL is a clinically feasible, military relevant assessment that is sensitive to differences between concussed and HC SM. This analysis supports the discriminant and construct validity of the POWAR-TOTAL, and may be useful for medical providers evaluating RTD readiness for SM who have sustained a concussion., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The COVID-19 pandemic has created an epidemic of distress-related mental disorders such as depression, while simultaneously necessitating a shift to virtual domains of mental health care; yet, the evidence to support the use of virtual interventions is unclear., Objective: The purpose of this study was to evaluate the efficacy of virtual interventions for depressive disorders by addressing three key questions: (1) Does virtual intervention provide better outcomes than no treatment or other control conditions (ie, waitlist, treatment as usual [TAU], or attention control)? (2) Does in-person intervention provide better outcomes than virtual intervention? (3) Does one type of virtual intervention provide better outcomes than another?, Methods: We searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021. We included randomized controlled trials of adults with depressive disorders that tested a virtual intervention and used a validated depression measure. Primary outcomes were defined as remission (ie, no longer meeting the clinical cutoff for depression), response (ie, a clinically significant reduction in depressive symptoms), and depression severity at posttreatment. Two researchers independently selected studies and extracted data using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias was evaluated based on Agency for Healthcare and Research Quality guidelines. We calculated odds ratios (ORs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes., Results: We identified 3797 references, 24 of which were eligible. Compared with waitlist, virtual intervention had higher odds of remission (OR 10.30, 95% CI 5.70-18.60; N=619 patients) and lower posttreatment symptom severity (SMD 0.81, 95% CI 0.52-1.10; N=1071). Compared with TAU and virtual attention control conditions, virtual intervention had higher odds of remission (OR 2.27, 95% CI 1.10-3.35; N=512) and lower posttreatment symptom severity (SMD 0.25, 95% CI 0.09-0.42; N=573). In-person intervention outcomes were not significantly different from virtual intervention outcomes (eg, remission OR 0.84, CI 0.51-1.37; N=789). No eligible studies directly compared one active virtual intervention to another., Conclusions: Virtual interventions were efficacious compared with control conditions, including waitlist control, TAU, and attention control. Although the number of studies was relatively small, the strength of evidence was moderate that in-person interventions did not yield significantly better outcomes than virtual interventions for depressive disorders., (©Crystal Edler Schiller, Julianna Prim, Anna E Bauer, Linda Lux, Laura Claire Lundegard, Michelle Kang, Samantha Hellberg, Katherine Thompson, Theresa Webber, Adonay Teklezghi, Noah Pettee, Katherine Gaffney, Gabrielle Hodgins, Fariha Rahman, J Nikki Steinsiek, Anita Modi, Bradley N Gaynes. Originally published in JMIR Mental Health (https://mental.jmir.org), 09.01.2023.)

Introduction: Determining the risk of recurrence of primary spontaneous pneumothorax is challenging. The objective of this study was to develop a risk assessment model to predict the probability of recurrence in patients with spontaneous pneumothorax., Methods: A retrospective study was performed of all episodes of pneumothorax diagnosed in the last 12 years in a hospital, in patients not initially submitted to surgery. Logistic regression was used to estimate the probability of recurrence. Based on a set of variables, a predictive model was built with its corresponding ROC curve to determine its discrimination power and diagnostic precision., Results: Of the 253 patients included, 128 (50.6%) experienced recurrence (37% within the first year). Recurrence was detected within 110 days in 25% of patients. The median of time to recurrence for the whole population was 1120 days. The presence of blebs/bullae was found to be a risk factor of recurrence (OR: 5.34; 95% CI: 2.81-10.23; p=0.000), whereas chest drainage exerted protective effect (OR: 0.19; 95% CI: 0.08-0.40; p=0.000). The variables included in the regression model constructed were hemoglobin and leukocyte count in blood, treatment received, and presence of blebs/bullae, with a fair discriminative power to predict recurrence [AUC=0.778 (95% CI: 0.721-0.835)]., Conclusion: The overall recurrence rate was high and was associated with the presence of blebs/bullae, failure to perform an active intervention (chest drainage) and low levels of hemoglobin and leukocytes in blood. Recurrence rarely occurs later than three years after the first episode. Once validated, this precision model could be useful to guide therapeutic decisions., (Copyright © 2020 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Many aspects of the bovine immune system remain poorly characterized, which poses an obstacle to improving dairy cow health. Herein, we describe two flow cytometry panels that included antibodies against CD8α, CD4, TCR-δ, CD172α, CD14, MHCII, CD21, CD62L, and CD11b. These panels were used to characterize the phenotype of leukocyte subpopulations from the peripheral blood of 30-day old Holstein calves and Holstein cows at 260 d of gestation and calving. No leukocyte subset differences were found between the pre- and post-partum cows. However, calf leukocytes presented a higher proportion of CD3 + lymphocytes, γδ T-cells, CD8 + γδ T-cells, and monocytes when compared with mature cows. Conversely, cow lymphocytes had a higher proportion of CD4 + and CD8 + T-cells, and B-cells than calf lymphocytes. The proportion of CD4 + T-cells and B-cells expressing CD62L was greater in calves than in cows, while cow B-cells expressed greater levels of CD11b than calf B-cells. In contrast, calf polymorphonuclear cells (PMN) and monocytes expressed greater levels of CD11b compared to cows. Moreover, calf monocytes expressed higher levels of MHCII compared with those of cows. Collectively, our data provides a resource to better understand the bovine immune system as well as immune-related diseases that affect dairy cattle., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives were to determine the effect of supplementing 2 sources of vitamin D, cholecalciferol (CH) or calcidiol (CA), at 1 (1mg) or 3 mg/d (3mg) prepartum on concentrations of vitamin D metabolites in plasma, measures of innate immune function, and leukocyte mRNA expression. Parous Holstein cows (n = 99) were assigned to a daily treatment administered as top-dress containing either 1 or 3 mg of CH (CH1 or CH3) or of CA (CA1 or CA3) from 250 d of gestation until calving. Plasma concentrations of vitamin D, immune cell population in blood, cell adhesion markers, and granulocyte phagocytosis and oxidative burst were evaluated pre- and postpartum. The mRNA expression in leukocytes was determined at 270 d of gestation and 3 d postpartum for genes involved in cell migration, pathogen recognition receptors, cell signaling, cytokines, antimicrobial mechanisms, oxidative burst, and Ca and vitamin D metabolism. Concentrations of vitamin D 3 increased in cows fed CH, whereas those of 25-hydroxyvitamin D 3 increased in cows fed CA. Percentage of granulocytes from total leukocytes differed with amount of vitamin D pre- (1mg = 24.5 vs. 3mg = 37.9%) and postpartum (1mg = 22.0 vs. 3mg = 31.0%), thus shifting mononuclear cells in the opposite direction pre- (1mg = 75.5 vs. 3mg = 62.1%) and postpartum (1mg = 78.0 vs. 3mg = 69.0%). Granulocytes displaying phagocytosis (1mg = 69.0 vs. 3mg = 62.9%) and intensity of phagocytosis prepartum (1mg = 7.46 vs. 3mg = 7.28) tended to be less in cows fed 3mg compared with 1mg. During prepartum, CA increased mRNA expression of genes related to cell adhesion and migration (CD44, ICAM1, ITGAL, ITGB1, LGALS8, SELL), pathogen recognition receptor (NOD2, TLR2, TLR6), cell signaling (FOS, JUN, NFKB2), cytokine signaling (IL1B, IL1R1, IL1RN), antimicrobial mechanisms (CTSB, LYZ), and Ca metabolism (ATP2B1, STIM1, TRPV5) compared with CH. Similarly, postpartum, CA increased mRNA expression of genes related to cell adhesion and migration (CXCR2, SELL, TLN1), cell signaling (AKT2), cytokines (CCL2, IL1R1, ILRN), antimicrobial mechanisms (DEFB3), oxidative burst (RAC2), and calcium metabolism (CALM3) compared with CH. Feeding additional vitamin D in the last 3 wk of gestation changed the profile of blood leukocytes and attenuated granulocyte phagocytosis during the transition period, whereas supplementing CA prepartum increased mRNA expression of genes involved in immune cell function, including genes related to pathogen recognition and antimicrobial effects of leukocytes., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call the RNA Editing DAmage Response (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution., (© 2021. The Author(s).)

Context: Little research has examined health-related quality of life in former National Football League (NFL) players., Objective: Examine the association of musculoskeletal injury history and current self-reported physical and mental health in former NFL players., Setting: Cross-sectional questionnaire., Patients or Other Participants: Historical cohort of 2,103 former NFL players that played at least one season between 1940 and 2001., Intervention: Players were grouped by self-reported professional career musculoskeletal injury history and whether injuries affected current health: (1) no musculoskeletal injury history; (2) musculoskeletal injury history, currently affected by injuries; and (3) musculoskeletal injury history, not currently affected by injuries., Main Outcome Measure: The Short Form 36 Measurement Model for Functional Assessment of Health and Well-Being (SF-36) yielded physical and mental health composite scores (PCS and MCS, respectively); higher scores indicated better health. Multivariable linear regression computed mean differences (MD) among injury groups. Covariates included demographics, playing history characteristics, surgical intervention for musculoskeletal injuries, and whether injury resulted in premature end to career. MD with 95% CI excluding 0.00 were deemed significant., Results: Overall, 90.3% reported at least one musculoskeletal injury during their professional football careers, of which 74.8% reported being affected by their injuries at time of survey completion. Adjusting for covariates, mean PCS in the "injury and affected" group was lower than the "no injury" (MD = -3.2; 95% CI: -4.8, -1.7) and "injury and not affected" groups (MD = -4.3; 95% CI: -5.4, -3.3); mean MCS did not differ., Conclusion: Many players reported musculoskeletal injuries, highlighting the need for developing and evaluating injury management interventions.

Objectives of the experiment were to determine the length of exposure to an acidogenic diet that would elicit changes in acid-base balance, mineral digestion, and response to parathyroid hormone (PTH)-induced changes in blood Ca and vitamin D 3 in prepartum dairy cows. Nonlactating parous Holstein cows (n = 20) at 242 d of gestation were blocked by lactation (1 or >1) and pretreatment dry matter (DM) intake and, within block, they were randomly assigned to a diet with a dietary cation-anion difference (DCAD) of +200 mEq/kg of DM (DCAD +200) or an acidogenic diet with -150 mEq/kg of DM (DCAD -150). Water and DM intake were measured and blood was sampled daily. Urine was sampled every 3 h for 36 h, and then daily. During PTH challenges on d 3, 8, and 13, cows received i.v. PTH 1-34 fragment at 0.05 µg/kg of body weight every 20 min for 9 h to mimic the pulsatile release of endogenous PTH. Blood was sampled at 0 h, and hourly thereafter until 10 h, and at 12, 18, 24, 36, and 48 h relative to each challenge. Acid-base measures and concentrations of ionized Ca (iCa) in whole blood, and total Ca, Mg, P, and vitamin D metabolites in plasma were evaluated. On d 2 and 7, Ca, Mg, and P balances were evaluated. Cows fed DCAD -150 had smaller blood pH (7.431 vs. 7.389) and HCO 3 - (27.4 vs. 22.8 mM) compared with DCAD +200, and metabolic acidosis in DCAD -150 was observed 24 h after dietary treatments started. Concentrations of iCa begin to increase 24 h after feeding the acidogenic diet, and it was greater in DCAD -150 compared with DCAD +200 by 3 d in the experiment (1.23 vs. 1.26 mM). During the PTH challenges, cows fed DCAD -150 had greater concentration of iCa and area under the curve for iCa than those fed DCAD +200 (48.2 vs. 50.7 mmol/L × hour), and there was no interaction between treatment and challenge day. Concentration of 1,25-dihydroxyvitamin D 3 in plasma did not differ during the PTH challenge, but change in 1,25-dihydroxyvitamin D 3 relative to h 0 of the challenge was smaller in cows fed DCAD -150 than cows fed DCAD +200 (44.1 vs. 32.9 pg/mL). Urinary loss of Ca was greater in cows fed DCAD -150 compared with DCAD +200 (1.8 vs. 10.8 g/d); however, because digestibility of Ca increased in cows fed DCAD -150 (19.7 vs. 36.6%), the amount of Ca retained did not differ between treatments. Diet-induced metabolic acidosis was observed by 24 h after dietary treatment started, resulting in increases in concentration of iCa in blood observed between 1 and 3 d. Collectively, present results indicate that tissue responsiveness to PTH and changes in blood concentrations of iCa and digestibility of Ca are elicited within 3 d of exposure to an acidogenic diet. The increased apparent digestibility of Ca compensated for the increased urinary loss of Ca resulting in similar Ca retention., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

RNA polymerase II is recruited to DNA double-strand breaks (DSBs), transcribes the sequences that flank the break and produces a novel RNA type that has been termed damage-induced long non-coding RNA (dilncRNA). DilncRNAs can be processed into short, miRNA-like molecules or degraded by different ribonucleases. They can also form double-stranded RNAs or DNA:RNA hybrids. The DNA:RNA hybrids formed at DSBs contribute to the recruitment of repair factors during the early steps of homologous recombination (HR) and, in this way, contribute to the accuracy of the DNA repair. However, if not resolved, the DNA:RNA hybrids are highly mutagenic and prevent the recruitment of later HR factors. Here recent discoveries about the synthesis, processing, and degradation of dilncRNAs are revised. The focus is on RNA clearance, a necessary step for the successful repair of DSBs and the aim is to reconcile contradictory findings on the effects of dilncRNAs and DNA:RNA hybrids in HR., (© 2020 The Authors. BioEssays published by Wiley Periodicals, Inc.)

Traumatic tracheobronchial injuries occur in 1% of patients with thoracic trauma, most of them dying at the site of the trauma. In this case report, we present a 26-year-old female patient admitted to the ICU due to a blunt chest trauma causing life threatening hypoxaemia and acidosis; deciding to implant percutaneous venovenous extracorporeal membrane oxygenation. The use of percutaneous venovenous extracorporeal membrane oxygenation, implemented with a lower anticoagulation target, allowed the diagnosis and treatment of a bronchopleural fistula under conditions of respiratory and hemodynamic stability without haemorrhagic complications, obtaining a fast and adequate assistance achieving the survival of the patient., (Copyright © 2019 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)