Exercise induced hypoalgesia during different intensities of a dynamic resistance exercise: A randomized controlled trial.

INTRODUCTION: Exercise produces an immediate lessening of pain sensitivity (Exercise-Induced Hypoalgesia (EIH)) in healthy individuals at local and distant sites, possibly through a shared mechanism with conditioned pain modulation (CPM). Dynamic resistance exercise is a recommended type of exercise to reduce pain, yet limited research has examined the effects of intensity on EIH during this type of exercise. Therefore, the primary purpose of this study is to compare changes in PPT at a local and distant site during a leg extension exercise at a high intensity, a low intensity, or a quiet rest condition. A secondary purpose is to examine if CPM changes after each intervention. The final purpose is to examine if baseline pain sensitivity measures are correlated with response to each intervention. METHODS: In a randomized controlled trial of 60 healthy participants, participants completed baseline pain sensitivity testing (heat pain threshold, temporal summation, a cold pressor test as measure of CPM) and were randomly assigned to complete a knee extension exercise at: 1) high intensity (75% of a 1 Repetition Maximum (RM), 2) low intensity (30% 1RM), or 3) Quiet Rest. PPT was measured between each set at a local (quadriceps) and distant (trapezius) site during the intervention. CPM was then repeated after the intervention. To test the first purpose of the study, a three-way ANOVA examined for time x site x intervention interaction effects. To examine for changes in CPM by group, a mixed-model ANOVA was performed. Finally, a Pearson Correlation examined the association between baseline pain sensitivity and response to each intervention. RESULTS: Time x site x intervention interaction effects were not significant (F(5.3, 150.97) = 0.87, p = 0.51, partial eta2 = 0.03). CPM did not significantly change after the interventions (time x intervention F(1,38) = 0.81, p = 0.37, partial eta2 = 0.02. EIH effects at the quadriceps displayed a significant, positive moderate association with baseline HPT applied over the trapezius (r = 0.61, p<0.01) and TS (r = 0.46, p = 0.04). DISCUSSION: In healthy participants, PPT and CPM did not significantly differ after a leg extension exercise performed at a high intensity, low intensity, or quiet rest condition. It is possible pre-intervention CPM testing with a noxious stimuli may have impaired inhibitory effects frequently observed during exercise but future research would need to examine this hypothesis.

Through the Lens of Movement-Evoked Pain: A Theoretical Framework of the "Pain-Movement Interface" to Guide Research and Clinical Care for Musculoskeletal Pain Conditions.

Over 120 million Americans report experiencing pain in the past 3 months. Among these individuals, 50 million report chronic pain and 17 million report pain that limits daily life or work activities on most days (ie, high-impact chronic pain). Musculoskeletal pain conditions in particular are a major contributor to global disability, health care costs, and poor quality of life. Movement-evoked pain (MEP) is an important and distinct component of the musculoskeletal pain experience and represents an emerging area of study in pain and rehabilitation fields. This focus article proposes the "Pain-Movement Interface" as a theoretical framework of MEP that highlights the interface between MEP, pain interference, and activity engagement. The goal of the framework is to expand knowledge about MEP by guiding scientific inquiry into MEP-specific pathways to disability, high-risk clinical phenotypes, and underlying individual influences that may serve as treatment targets. This framework reinforces the dynamic nature of MEP within the context of activity engagement, participation in life and social roles, and the broader pain experience. Recommendations for MEP evaluation, encompassing the spectrum from high standardization to high patient specificity, and MEP-targeted treatments are provided. Overall, the proposed framework and recommendations reflect the current state of science in this emerging area of study and are intended to support future efforts to optimize musculoskeletal pain management and enhance patient outcomes. PERSPECTIVE: Movement-evoked pain (MEP) is a distinct component of the musculoskeletal pain experience and emerging research area. This article introduces the "Pain-Movement Interface" as a theoretical framework of MEP, highlighting the interface between MEP, pain interference, and activity engagement. Evaluating and treating MEP could improve rehabilitation approaches and enhance patient outcomes.

"Figuring out your place at a school like this:" Intersectionality and sense of belonging among STEM and non-STEM college students.

BACKGROUND: Students' sense of belonging in college-an individual's feelings of contentment, mattering, importance, and "finding one's place" in a social setting-can influence choice of major and career trajectory. We contribute to the belongingness literature through a mixed methods intersectional study of students attending a STEM-focused public university we call Meadow State University (MSU). We assess the potential for students' intersecting social identities to differentially influence their experiences with intersectional oppression-subjection to multiple systems of oppression due to simultaneous membership in more than one marginalized group-that, in turn, may influence their college pathways. In addition, we explore whether intersectional differences affect sense of belonging differently in STEM and non-STEM majors. We employ a mixed-methods approach, informed by critical quantitative methods and in-depth interviews. We utilize quantitative institutional data measuring college satisfaction, expressed as "willingness to return" to the same university, for over 3,000 students during two academic years (2013-14 and 2016-17). Survey data explores college satisfaction as an indicator of intersectional differences in student experiences. Then, we analyze 37 in-depth interviews, collected between 2014-2016 at the same institution, to further contextualize the intersectional variation suggested by survey results. RESULTS: Willingness to return is influenced by major, as well as academic, social, and campus belonging. Moreover, the extent to which these factors affected outcomes additionally varied by race/ethnicity, gender, family income, other background factors, and the ways these factors may intersect. Important components of academic belonging included faculty-student interactions, perceptions of academic support, and a privileging of STEM degree programs and students over non-STEM students and their degree programs at MSU. Faculty responsiveness and high impact practices like internships played an important role, particularly in STEM programs. Taken together, our findings demonstrate that, particularly for students of color and those subject to intersectional oppression due to multiple marginalized identities, satisfaction with academics did not always outweigh deficiencies in other areas of campus life shaping belongingness. CONCLUSIONS: Our mixed-methods approach contributes insights into how and why students' background, individual choices, and institutional practices concurrently-and intersectionally-influence their ability to form a sense of belonging on campus. Structural changes are required to end practices that support intersecting systems of oppression by favoring White, upper-income men as the "default" STEM students in the U.S. Our research supports growing evidence that institutions must actively build models of inclusion for underrepresented and marginalized groups that address inequitable and unjust practices, providing transformative mentoring and educational guidance that attends to intersectional oppression, in order to effectively support the next generation of women and scholars of color.

Innovations in the Assessment of Skeletal Muscle Health: A Glimpse into the Future.

Skeletal muscle is the largest organ system in the human body and plays critical roles in athletic performance, mobility, and disease pathogenesis. Despite growing recognition of its importance by major health organizations, significant knowledge gaps remain regarding skeletal muscle health and its crosstalk with nearly every physiological system. Relevant public health challenges like pain, injury, obesity, and sarcopenia underscore the need to accurately assess skeletal muscle health and function. Feasible, non-invasive techniques that reliably evaluate metrics including muscle pain, dynamic structure, contractility, circulatory function, body composition, and emerging biomarkers are imperative to unraveling the complexities of skeletal muscle. Our concise review highlights innovative or overlooked approaches for comprehensively assessing skeletal muscle in vivo. We summarize recent advances in leveraging dynamic ultrasound imaging, muscle echogenicity, tensiomyography, blood flow restriction protocols, molecular techniques, body composition, and pain assessments to gain novel insight into muscle physiology from cellular to whole-body perspectives. Continued development of precise, non-invasive tools to investigate skeletal muscle are critical in informing impactful discoveries in exercise and rehabilitation science.

Biopsychosocial contributors to irritability in individuals with shoulder or low back pain.

OBJECTIVES: Irritability is a foundational clinical reasoning concept in rehabilitation to evaluate reactivity of the examination and treatment. While originally theorized to reflect tissue damage, a large body of evidence supports pain is a biopsychosocial experience impacted by pain sensitivity and psychological factors. Therefore, the purpose of this study was to examine biopsychosocial contributors to irritability. METHODS: 40 patients with shoulder (n = 20) and low back (n = 20) pain underwent Quantitative Sensory Testing (QST) (Pressure Pain Threshold, Heat Pain Threshold, Conditioned Pain Modulation, Temporal Summation), completed pain-related psychological questionnaires, an Exercise-Induced Hypoalgesia protocol, and standardized irritability assessment based on Clinical Practice Guidelines. Participants were then categorized as irritable or not irritable based on Maitland's criteria and by irritability level based on Clinical Practice Guidelines. An independent samples t-test examined for differences in QST and psychological factors by irritability category. A MANOVA examined for differences in QST and psychological factors by irritability level (high, moderate, low). RESULTS: Significantly lower heat and pressure pain thresholds at multiple locations (p < 0.05), as well as less efficient conditioned pain modulation (p = 0.02), were demonstrated in individuals categorized as irritable. Heat and pressure pain thresholds were also significantly lower in patients with high irritability compared to other levels. Significantly higher depression and anger, as well as lower self-efficacy, were reported in individuals with an irritable presentation. DISCUSSION/CONCLUSION: Biopsychosocial factors, including widespread hyperalgesia and elevated psychological factors, may contribute to an irritable presentation.

Effect of a Standardized Training Program to Enhance the Therapeutic Alliance in Patients with Low Back Pain: A Mixed-Methods Analytical Approach.

BACKGROUND: Therapeutic alliance improves pain, disability, and quality of life outcomes. The purpose of this study was to investigate the effectiveness of a training protocol aimed at enhancing the therapeutic alliance in patients with chronic low back pain. METHODS: 19 physical therapists (DPT) and 16 student physical therapists (SPT) completed a therapeutic alliance training course with a quantitative questionnaire completed before and after the training along with a follow-up qualitative interview. Quantitative results were analyzed for differences resulting from participation in the training, while qualitative results were analyzed via interview transcription analysis by independent researchers blinded to the participants. RESULTS: All three groups (SPT/DPT combined, SPT, DPT) demonstrated a significant improvement in feeling comfortable in building a strong therapeutic alliance (p<0.01). The themes of Training Enhances Consciousness, Communication is Key, and Personalized Approach emerged from qualitative interviews indicating that the course was valuable in improving their approach to therapeutic alliance, communication, and individualized interventions contribute to a successful therapeutic alliance. CONCLUSION: The results of this study demonstrate the efficacy of therapeutic alliance training and suggest potential to enhance therapeutic alliance through a training protocol.

The Association Between the Patient Self-Report Survey for the Assessment of Fibromyalgia with Pain Sensitivity and Psychological Factors in Individuals with Musculoskeletal Pain.

Purpose: The Patient Self-Report Survey for the Assessment of Fibromyalgia may potentially be a method for subgrouping patients with musculoskeletal pain who have a nociplastic pain presentation. Limited research has explored the convergent validity of this questionnaire against psychophysical measures of pain sensitivity and psychological factors in individuals with musculoskeletal pain. Therefore, the purpose of this study is to examine the strength of the association between total scores on the Patient Self-Report Survey for the Assessment of Fibromyalgia with clinical, pain sensitivity, and psychological factors. Patients and Methods: As a secondary analysis of a cross-sectional study, participants with shoulder (n = 20) or low back pain (n = 20) completed Quantitative Sensory Testing (QST), pain-related psychological questionnaires, and the Patient Self-Report Survey for the Assessment of Fibromyalgia. A Spearman correlation determined the association between total scores on the Patient Self Report Survey for the Assessment of Fibromyalgia with psychological factors and pain sensitivity behaviorally assessed with QST. Results: Negative psychological factors demonstrate moderate to strong positive associations with the Patient Self-Report Survey for the Assessment of Fibromyalgia (rho range = 0.36-0.80), suggesting greater negative psychological factors were observed in patients with higher severity of fibromyalgia symptoms. Pain sensitivity factors demonstrated weak to moderate negative associations with The Patient Self-Report Survey for the Assessment of Fibromyalgia (PPT rho range=-0.36- -0.41), suggesting that elevated pain sensitivity was observed in individuals with higher severity of nociplastic pain symptoms. Conclusion: Collectively, this supports the convergent validity of the Patient Self-Report Survey for the Assessment of Fibromyalgia with psychological and pain sensitivity factors in patients with musculoskeletal pain.

Novel methods of immunogenic antigen selection for serological diagnosis of Parelaphostrongylus tenuis infection.

This paper outlines methods used to identify novel antigens for use in the development of serological assays. Specifically, we applied these methods to a neurogenic parasitic nematode of cervids called Parelaphostrongylus tenuis. This parasite is of particular concern in both wild and domestic ungulates as it causes significant neurological signs and definitive diagnosis is only possible post-mortem, necessitating the development of serologic assays for antemortem diagnosis. Proteins extracted from P. tenuis organisms were affinity isolated using antibodies enriched from seropositive moose (Alces alces). The proteins were analyzed using mass spectrometry and liquid chromatography to obtain amino acid sequences that were then cross-referenced to open reading frames predicted from an assembled transcriptome. An antigen of interest was assessed for immunogenic epitopes and subsequently synthesized into 10-mer synthetic overlapping peptides representing these regions. These synthetic peptides were then assessed for reactivity against positive and negative moose sera and demonstrated potential use as a serological assay in diagnostic laboratories. Known negative moose sera revealed significantly lower optical density when compared to the positive samples (p < 0.05). This method serves as a pipeline for the construction of diagnostic assays of pathogens in both human and veterinary medicine.

Examining the effects of amplitude-based training as a component of the plan of care in an individual with olivopontocerebellar atrophy.

BACKGROUND: Amplitude-based exercise training has been shown to be effective in the motor performance of individuals with idiopathic Parkinson's disease, with limited research investigating its effects on Parkinson plus syndromes such as olivopontocerebellar atrophy (OPCA). The purpose of this clinical case report is to examine the effects of amplitude-based training exercises on an individual with OPCA. CASE DESCRIPTION: A 68-year-old man with a 14-month history of OPCA presented to physical therapy with bradykinesia, rigidity, and postural instability. The individual participated in 34 intervention sessions. Pre- and post-test measurements were collected for the following outcome measures: Five Times Sit to Stand (FTSTS); Functional Gait Assessment (FGA); Activities-Specific Balance Confidence Scale (ABC-6); 9 Hole Peg Test (9HPT); preferred and maximal gait speed. OUTCOMES: Improvements reaching Minimum Detectable Change (MDC) or Minimal Clinically Important Difference (MCID) were recorded with a pre (Week 1) and post (Week 20) intervention: FGA score (4-point improvement (MDC95 = 4 points), preferred gait speed (0.09 meters/second improvement (MCID = 0.05 meters/second)), FTSTS (6-second improvement (MDC95 = 2.3 seconds)), and 9HPT on the dominant hand (3-second improvement (MDC95 = 2.6 seconds)). Fluctuations during the plan of care were observed for these measures, and additional outcomes did not demonstrate a worsening of function. CONCLUSION: In an individual with OPCA, amplitude-based exercise training as a component of the plan of care increased dynamic balance in walking, gait speed, and hand dexterity. However, these results need to be validated on a larger sample of individuals with OPCA through randomized controlled trials.

Characteristics and Outcomes of Patients Receiving Physical Therapy for Low Back Pain with a Nociplastic Pain Presentation: A Secondary Analysis.

Introduction: Individuals with low back pain (LBP) may be classified based on mechanistic descriptors, such as a nociplastic pain presentation (NPP). The purpose of this secondary analysis was to examine the frequency and characteristics of patients with a NPP referred to physical therapy with LBP. Additionally, we characterized patients with LBP meeting the criteria for NPP by demographic, clinical, psychological, and pain sensitivity variables. Finally, we examined short- and long-term clinical outcomes in patients with a NPP compared to those without a NPP. Materials and Methods: Patients referred to physical therapy for LBP completed the Patient Self-report Survey for the Assessment of Fibromyalgia. Participants were categorized as "LBP with NPP" or "LBP without NPP" based on the threshold established in this measure. A rank sum test examined for differences in pain-related psychological factors and pressure-pain threshold between groups. Next, a Friedman test examined if LBP intensity and disability trajectories differed by groups at one and six months after initiation of physical therapy. Results: 22.2% of patients referred to physical therapy for LBP met the criteria for a NPP. Patients with a NPP reported significantly greater disability, pain catastrophizing, depression, anxiety, and somatization compared to individuals without a NPP (p < 0.05). Pressure-pain threshold did not differ between groups (p > 0.05). Individuals with LBP with a NPP demonstrated nonsignificant, small to medium reductions in pain and disability at one and six months. Individuals experiencing LBP without a NPP demonstrated significant reductions in pain and disability in the short- and long term. Conclusion: Patients with LBP with a NPP displayed greater negative pain-related psychological factors but similar pain sensitivity compared to LBP without NPP.

Pain phenotyping and investigation of outcomes in physical therapy: An exploratory study in patients with low back pain.

Phenotypes have been proposed as a method of characterizing subgroups based on biopsychosocial factors to identify responders to analgesic treatments. This study aimed to, first, confirm phenotypes in patients with low back pain receiving physical therapy based on an a priori set of factors used to derive subgroups in other pain populations. Second, an exploratory analysis examined if phenotypes differentiated pain and disability outcomes at four weeks of physical therapy. Fifty-five participants completed psychological questionnaires and pressure pain threshold (PPT). Somatization, anxiety, and depression domains of the Symptom-Checklist-90-Revised, and PPT, were entered into a hierarchical agglomerative cluster analysis with Ward's method to identify phenotypes. Repeated measures ANOVAs assessed pain ratings and disability by phenotype at four weeks. Three clusters emerged: 1) high emotional distress and pain sensitivity (n = 10), 2) low emotional distress (n = 34), 3) low pain sensitivity (n = 11). As an exploratory study, clusters did not differentiate pain ratings or disability after four weeks of physical therapy (p's>0.05). However, trends were observed as magnitude of change for pain varied by phenotype. This supports the characterization of homogenous subgroups based on a protocol conducted in the clinical setting with varying effect sizes noted by phenotype for short-term changes in pain. As an exploratory study, future studies should aim to repeat this trial in a larger sample of patients.

Expectations affect pain sensitivity changes during massage.

BACKGROUND: Pain-inducing massage produces comparable changes in pain sensitivity as a cold pressor task, suggesting shared neurophysiological mechanisms of conditioned pain modulation. Manual therapy and conditioned pain modulation are influenced by positive and negative expectations. Therefore, the purpose of this study was to examine the effects of positive and negative expectations on pain-free and pain-inducing massage. METHODS: 56 healthy participants were randomly assigned to receive a positive or negative expectation instructional set followed by a pain-inducing or a pain-free massage. Pressure pain threshold (PPT) was measured followed by each interval of massage. A repeated measures ANCOVA controlling for post-randomization differences in sex tested for massage x expectation set x PPT interaction effects, as well as two-way interaction effects. RESULTS: A significant three-way interaction effect (p = 0.04) and time x expectation interaction effect was observed for individuals receiving pain inducing massage (p = 0.02). Individuals who received the positive expectation instructional set demonstrated significantly higher PPT at minutes 3 and 4 of massage compared to individuals who received the negative expectation instructional set. CONCLUSIONS: Expectations impact pain sensitivity changes produced during massage. Clinicians planning to provide pain-inducing massage should consider the role of expectations in modulating pain sensitivity changes.

Diagnostic and functional outcomes of adjustment disorder in U.S. active duty service members.

BACKGROUND: Adjustment disorder (AD) is a commonly diagnosed psychiatric disorder. However, little is known about its course, predictors of its diagnostic outcomes, or its association with functional impairment. Our primary aim was to examine diagnostic transitions of service members with an incident AD diagnosis (IADx) to one of three states: 1) another psychiatric diagnosis, 2) chronic AD, or 3) no psychiatric diagnosis. Secondary outcomes included predictors of diagnostic course and functional outcomes associated with follow-up diagnoses. METHODS: Health records of a random sample of 10,720 service members with an IADx were analyzed using multinomial logit regression and hazard rate model with competing risks. RESULTS: IADx transitions were 24.3 % to another psychiatric diagnosis, 8.9 % with chronic AD, and 43.7 % without a diagnosis. Nearly a quarter (23.1 %) separated from service. Deployment was the strongest predictor of transitioning to another diagnosis. Those who transitioned to another diagnosis separated at an increased rate and with more adverse outcomes. LIMITATIONS: Diagnostic findings are based on data in the electronic health record, and we could not specifically identify the stressor that precipitated an AD diagnosis. These findings describe the course of AD in military personnel and may not generalize to civilians. CONCLUSIONS: AD, as initially diagnosed, represents a heterogeneous disorder with an enduring impact across the military career for a considerable proportion of service members. As an early indicator of more severe psychiatric outcomes, an IADx may signal an opportunity for early intervention and screening, particularly in service members with a history of deployment.

Outcomes and prognosis of adjustment disorder in adults: A systematic review.

Adjustment disorder (AD) is one of the most commonly diagnosed mental health disorders and is generally conceptualized to be mild and short-lived. Despite the frequent use of AD in clinical settings, little is known about the prognosis of this condition. Our goal was to systematically review research on a range of AD outcomes in order to provide a broad characterization of AD prognosis. We conducted searches in MEDLINE, EMBASE, and PsycINFO. We included 31 cohort or randomized controlled trials with a total of 1,385,358 participants. Many patients maintained an AD diagnosis or were diagnosed with another mental health disorder months to years after initial diagnosis. Patients with AD tended to show symptom improvement at higher rates and to utilize less treatment than did patients with other disorders. AD-diagnosed groups experienced subsequent development of numerous physical conditions, such as infection, cancers, Parkinson's disease, and cardiovascular events, at higher rates than did control groups. Results were mixed regarding suicidality and occupational impairment. We rated most studies as having a moderate risk of bias. Based on limited findings, AD appears to progress as a milder disorder than do other disorders, but it not uncommonly transitions to more severe mental health states and may predict the development of future health issues, both mental and physical. Future prospective research that conforms to prognosis study guidelines is needed to better understand the course of this common disorder.

Experimental Pain Phenotype Profiles in Community-dwelling Older Adults.

OBJECTIVES: Pain sensitivity and the brain structure are critical in modulating pain and may contribute to the maintenance of pain in older adults. However, a paucity of evidence exists investigating the link between pain sensitivity and brain morphometry in older adults. The purpose of the study was to identify pain sensitivity profiles in healthy, community-dwelling older adults using a multimodal quantitative sensory testing protocol and to differentiate profiles based on brain morphometry. MATERIALS AND METHODS: This study was a secondary analysis of the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study. Participants completed demographic and psychological questionnaires, quantitative sensory testing, and a neuroimaging session. A Principal Component Analysis with Varimax rotation followed by hierarchical cluster analysis identified 4 pain sensitivity clusters (the "pain clusters"). RESULTS: Sixty-two older adults ranging from 60 to 94 years old without a specific pain condition (mean [SD] age=71.44 [6.69] y, 66.1% female) were analyzed. Four pain clusters were identified characterized by (1) thermal pain insensitivity; (2) high pinprick pain ratings and pressure pain insensitivity; (3) high thermal pain ratings and high temporal summation; and (4) thermal pain sensitivity, low thermal pain ratings, and low mechanical temporal summation. Sex differences were observed between pain clusters. Pain clusters 2 and 4 were distinguished by differences in the brain cortical volume in the parieto-occipital region. DISCUSSION: While sufficient evidence exists demonstrating pain sensitivity profiles in younger individuals and in those with chronic pain conditions, the finding that subgroups of experimental pain sensitivity also exist in healthy older adults is novel. Identifying these factors in older adults may help differentiate the underlying mechanisms contributing to pain and aging.

Alkaline nucleoplasm facilitates contractile gene expression in the mammalian heart.

Cardiac contractile strength is recognised as being highly pH-sensitive, but less is known about the influence of pH on cardiac gene expression, which may become relevant in response to changes in myocardial metabolism or vascularization during development or disease. We sought evidence for pH-responsive cardiac genes, and a physiological context for this form of transcriptional regulation. pHLIP, a peptide-based reporter of acidity, revealed a non-uniform pH landscape in early-postnatal myocardium, dissipating in later life. pH-responsive differentially expressed genes (pH-DEGs) were identified by transcriptomics of neonatal cardiomyocytes cultured over a range of pH. Enrichment analysis indicated "striated muscle contraction" as a pH-responsive biological process. Label-free proteomics verified fifty-four pH-responsive gene-products, including contractile elements and the adaptor protein CRIP2. Using transcriptional assays, acidity was found to reduce p300/CBP acetylase activity and, its a functional readout, inhibit myocardin, a co-activator of cardiac gene expression. In cultured myocytes, acid-inhibition of p300/CBP reduced H3K27 acetylation, as demonstrated by chromatin immunoprecipitation. H3K27ac levels were more strongly reduced at promoters of acid-downregulated DEGs, implicating an epigenetic mechanism of pH-sensitive gene expression. By tandem cytoplasmic/nuclear pH imaging, the cardiac nucleus was found to exercise a degree of control over its pH through Na+/H+ exchangers at the nuclear envelope. Thus, we describe how extracellular pH signals gain access to the nucleus and regulate the expression of a subset of cardiac genes, notably those coding for contractile proteins and CRIP2. Acting as a proxy of a well-perfused myocardium, alkaline conditions are permissive for expressing genes related to the contractile apparatus.

Systematic review and meta-analysis of predictors of adjustment disorders in adults.

BACKGROUND: The diagnosis of adjustment disorder is common in clinical practice, yet there is lack of research on the etiology and epidemiology of adjustment disorders. The goal of this systematic review was to evaluate predictors of adjustment disorders in adults. METHODS: We conducted systematic searches in MEDLINE, EMBASE, and PsycINFO. We included 70 studies that examined thirteen theoretically-derived and predefined predictors of adjustment disorders with a total of 3,449,374 participants. RESULTS: We found that female gender, younger age, unemployed status, stress, physical illness and injury, low social support, and a history of mental health disorders predicted adjustment disorders. Most of these predictors differentiated individuals with adjustment disorders from individuals with no mental health disorders. Participants with adjustment disorders were more likely to have experienced accidents than were those with posttraumatic stress disorder but were less likely to have experienced assaults and abuse, neglect, and maltreatment. More research is needed to identify factors that differentiate adjustment disorders from other mental health disorders. LIMITATIONS: Because very few studies adjusted for confounders (e.g., demographic variables, mental health histories, and a variety of stressors), it was not possible to identify independent associations between predictors and adjustment disorders. CONCLUSIONS: We identified a number of factors that predicted adjustment disorders compared to no mental health diagnosis. The majority of studies were rated as moderate or high in risk of bias, suggesting that more rigorous research is needed to confirm the relationships we detected.

Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.

Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification.

Acidic environments trigger intracellular H+-sensing FAK proteins to re-balance sarcolemmal acid-base transporters and auto-regulate cardiomyocyte pH.

AIMS: In cardiomyocytes, acute disturbances to intracellular pH (pHi) are promptly corrected by a system of finely tuned sarcolemmal acid-base transporters. However, these fluxes become thermodynamically re-balanced in acidic environments, which inadvertently causes their set-point pHi to fall outside the physiological range. It is unclear whether an adaptive mechanism exists to correct this thermodynamic challenge, and return pHi to normal. METHODS AND RESULTS: Following left ventricle cryo-damage, a diffuse pattern of low extracellular pH (pHe) was detected by acid-sensing pHLIP. Despite this, pHi measured in the beating heart (13C NMR) was normal. Myocytes had adapted to their acidic environment by reducing Cl-/HCO3- exchange (CBE)-dependent acid-loading and increasing Na+/H+ exchange (NHE1)-dependent acid-extrusion, as measured by fluorescence (cSNARF1). The outcome of this adaptation on pHi is revealed as a cytoplasmic alkalinization when cells are superfused at physiological pHe. Conversely, mice given oral bicarbonate (to improve systemic buffering) had reduced myocardial NHE1 expression, consistent with a needs-dependent expression of pHi-regulatory transporters. The response to sustained acidity could be replicated in vitro using neonatal ventricular myocytes incubated at low pHe for 48 h. The adaptive increase in NHE1 and decrease in CBE activities was linked to Slc9a1 (NHE1) up-regulation and Slc4a2 (AE2) down-regulation. This response was triggered by intracellular H+ ions because it persisted in the absence of CO2/HCO3- and became ablated when acidic incubation media had lower chloride, a solution manoeuvre that reduces the extent of pHi-decrease. Pharmacological inhibition of FAK-family non-receptor kinases, previously characterized as pH-sensors, ablated this pHi autoregulation. In support of a pHi-sensing role, FAK protein Pyk2 (auto)phosphorylation was reduced within minutes of exposure to acidity, ahead of adaptive changes to pHi control. CONCLUSIONS: Cardiomyocytes fine-tune the expression of pHi-regulators so that pHi is at least 7.0. This autoregulatory feedback mechanism defines physiological pHi and protects it during pHe vulnerabilities.

Adjustment disorders: A research gaps analysis.

Adjustment disorders are among the most commonly diagnosed mental health disorders in both civilian and military clinical settings. Despite their high prevalence, adjustment disorders have received little research attention. The many gaps in our understanding of this group of disorders hinder the development of adequate, evidence-based treatment protocols. This study utilizes a systematic methodology to identify and prioritize research gaps in adjustment disorders. We used authoritative source reports to identify gaps in research domains from foundational science to services research. Subject-matter experts conducted literature searches to substantiate and refine research gaps, and stakeholders assessed the importance and impact of this work for researchers and policy-makers. We identified 254 possible research-needs statements, which were ultimately reduced to 11 final, prioritized research gaps. Two gaps addressed prevention and screening and three addressed treatment and services research. Six gaps addressed foundational science, epidemiology, and etiology research domains, highlighting the need for basic research. Until some of the basic science questions are resolved (e.g., diagnostic clarity, valid screening, and assessment measures) about adjustment disorders, we may not be able to develop adequate evidence-based interventions for the disorders, and it will be difficult to understand the trajectory of these disorders throughout treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).