A Switch from Glial to Neuronal Gene Expression Alterations in the Spinal Cord of SIV-infected Macaques on Antiretroviral Therapy.

Despite antiretroviral therapy (ART), HIV-associated peripheral neuropathy remains one of the most prevalent neurologic manifestations of HIV infection. The spinal cord is an essential component of sensory pathways, but spinal cord sampling and evaluation in people with HIV has been very limited, especially in those on ART. The SIV/macaque model allows for assessment of the spinal cord at key time points throughout infection with and without ART. In this study, RNA was isolated from the spinal cord of uninfected, SIV+, and SIV + ART animals to track alterations in gene expression using global RNA-seq. Next, the SeqSeek platform was used to map changes in gene expression to specific cell types. Pathway analysis of differentially expressed genes demonstrated that highly upregulated genes in SIV-infected spinal cord aligned with interferon and viral response pathways. Additionally, this upregulated gene set significantly overlapped with those expressed in myeloid-derived cells including microglia. Downregulated genes were involved in cholesterol and collagen biosynthesis, and TGF-b regulation of extracellular matrix. In contrast, enriched pathways identified in SIV + ART animals included neurotransmitter receptors and post synaptic signaling regulators, and transmission across chemical synapses. SeqSeek analysis showed that upregulated genes were primarily expressed by neurons rather than glia. These findings indicate that pathways activated in the spinal cord of SIV + ART macaques are predominantly involved in neuronal signaling rather than proinflammatory pathways. This study provides the basis for further evaluation of mechanisms of SIV infection + ART within the spinal cord with a focus on therapeutic interventions to maintain synaptodendritic homeostasis.

Characterization of heterogeneous skin constructs for full thickness skin regeneration in murine wound models.

An autologous heterogeneous skin construct (AHSC) has been developed and used clinically as an alternative to traditional skin grafting techniques for treatment of cutaneous defects. AHSC is manufactured from a small piece of healthy skin in a manner that preserves endogenous regenerative cellular populations. To date however, specific cellular and non-cellular contributions of AHSC to the epidermal and dermal layers of closed wounds have not been well characterized given limited clinical opportunity for graft biopsy following wound closure. To address this limitation, a three-part mouse full-thickness excisional wound model was developed for histologic and macroscopic graft tracing. First, fluorescent mouse-derived AHSC (mHSC) was allografted onto non-fluorescent recipient mice to enable macroscopic and histologic time course evaluation of wound closure. Next, mHSC-derived from haired pigmented mice was allografted onto gender- and major histocompatibility complex (MHC)-mismatched athymic nude mouse recipients. Resulting grafts were distinguished from recipient murine skin via immunohistochemistry. Finally, human-derived AHSC (hHSC) was xenografted onto athymic nude mice to evaluate engraftment and hHSC contribution to wound closure. Experiments demonstrated that mHSC and hHSC facilitated wound closure through production of viable, proliferative cellular material and promoted full-thickness skin regeneration, including hair follicles and glands in dermal compartments. This combined macroscopic and histologic approach to tracing AHSC-treated wounds from engraftment to closure enabled robust profiling of regenerated architecture and further understanding of processes underlying AHSC mechanism of action. These models may be applied to a variety of wound care investigations, including those requiring longitudinal assessments of healing and targeted identification of donor and recipient tissue contributions.

Extracorporeal membrane oxygenation aggravates platelet glycoprotein V shedding and δ-granule deficiency in COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy in patients with acute respiratory distress syndrome (ARDS). Hemostatic complications are frequently observed in patients on ECMO and limit the success of this therapy. Platelets are key mediators of hemostasis enabling activation, aggregation, and thrombus formation by coming in contact with exposed matrix proteins via their surface receptors such as glycoprotein (GP) VI or GPIb/V/IX. Recent research has elucidated a regulatory role of the GPV subunit. The cleaved soluble GPV (sGPV) ectodomain was identified to spatiotemporally control fibrin formation through complex formation with thrombin. OBJECTIVES: We aimed to decipher the impact of ECMO on platelet phenotype and function, including the role of GPV and plasmatic sGPV. METHODS: We recruited 36 patients with ARDS in the wake of COVID-19 pneumonia and performed a longitudinal comparison of platelet phenotype and function in non-ECMO (n = 23) vs ECMO (n = 13) compared with those of healthy controls. Patients were assessed at up to 3 time points (t1 = days 1-3; t2 = days 4-6; and t3 = days 7-14 after cannulation/study inclusion). RESULTS: Agonist-induced platelet activation was assessed by flow cytometry and revealed decreased GPIIb/IIIa activation and α-granule release in all ARDS patients. During ECMO treatment, agonist-induced δ-granule release continuously decreased, which was independently confirmed by electron microscopy and was associated with a prolonged in vitro bleeding time. GPV expression on the platelet surface markedly decreased in ECMO patients compared with that in non-ECMO patients. Plasma sGPV levels were increased in ECMO patients and were associated with poor outcome. CONCLUSION: Our data demonstrate an ECMO-intrinsic platelet δ-granule deficiency and hemostatic dysfunction beyond the underlying ARDS.

C3 concentrations can be normal in patients with C3 glomerulopathy secondary to C3 nephritic factor.

C3 glomerulopathy (C3G) is a rare kidney disease caused by the glomerular deposition of C3 fragments secondary to alternative pathway complement dysregulation. C3 nephritic factors (C3Nef) are the most common acquired cause, and their detection has treatment and prognostic implications. Although C3 concentration can be normal in the presence of C3Nef, many laboratories will only perform C3Nef testing when C3 is low. We performed a retrospective study of all positive C3Nef results from the authors' laboratory since 2015 and found that two of the four patients with positive C3Nef and biopsy-confirmed C3G had normal C3 concentrations. This may be in part due to limitations in commercial C3 testing methods which use anti-C3c antisera directed against both C3 breakdown products and native C3. A normal C3 concentration should not preclude C3Nef testing in the appropriate clinical context.

Beyond change scores: Employing an improved statistical approach to analyze the impact of entry fitness on physical performance during British Army basic training in men and women.

The aim was to use a robust statistical approach to examine whether physical fitness at entry influences performance changes between men and women undertaking British Army basic training (BT). Performance of 2 km run, seated medicine ball throw (MBT) and isometric mid-thigh pull (MTP) were assessed at entry and completion of Standard Entry (SE), Junior Entry-Short (JE-Short), and Junior Entry-Long (JE-Long) training for 2350 (272 women) recruits. Performance change was analyzed with entry performance as a covariate (ANCOVA), with an additional interaction term allowing different slopes for courses and genders (p < 0.05). Overall, BT courses saw average improvements in 2 km run performance (SE: -6.8% [-0.62 min], JE-Short: -4.6% [-0.43 min], JE-Long: -7.7% [-0.70 min]; all p < 0.001) and MBT (1.0-8.8% [0.04-0.34 m]; all p < 0.05) and MTP (4.5-26.9% [6.5-28.8 kg]; all p < 0.001). Regression models indicate an expected form of "regression to the mean" whereby test performance change was negatively associated with entry fitness in each course (those with low baseline fitness exhibit larger training improvements; all interaction effects: p < 0.001, η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ > 0.006), particularly for women. However, when matched for entry fitness, men displayed considerable improvements in all tests, relative to women. Training courses were effective in developing recruit physical fitness, whereby the level of improvement is, in large part, dependent on entry fitness. Factors including age, physical maturity, course length, and physical training, could also contribute to the variability in training response between genders and should be considered when analyzing and/or developing physical fitness in these cohorts for future success of military job-task performance.

Evolution of nasal and olfactory infection characteristics of SARS-CoV-2 variants.

SARS-CoV-2 infection of the upper airway and the subsequent immune response are early, critical factors in COVID-19 pathogenesis. By studying infection of human biopsies in vitro and in a hamster model in vivo, we demonstrated a transition in nasal tropism from olfactory to respiratory epithelium as the virus evolved. Analyzing each variant revealed that SARS-CoV-2 WA1 or Delta infect a proportion of olfactory neurons in addition to the primary target sustentacular cells. The Delta variant possessed broader cellular invasion capacity into the submucosa, while Omicron displayed enhanced nasal respiratory infection and longer retention in the sinonasal epithelium. The olfactory neuronal infection by WA1 and the subsequent olfactory bulb transport via axon were more pronounced in younger hosts. In addition, the observed viral clearance delay and phagocytic dysfunction in aged olfactory mucosa were accompanied by a decline of phagocytosis-related genes. Further, robust basal stem cell activation contributed to neuroepithelial regeneration and restored ACE2 expression postinfection. Together, our study characterized the nasal tropism of SARS-CoV-2 strains, immune clearance, and regeneration after infection. The shifting characteristics of viral infection at the airway portal provide insight into the variability of COVID-19 clinical features, particularly long COVID, and may suggest differing strategies for early local intervention.

Star-PCL shape memory polymer (SMP) scaffolds with tunable transition temperatures for enhanced utility.

Thermoresponsive shape memory polymers (SMPs) prepared from UV-curable poly(ε-caprolactone) (PCL) macromers have the potential to create self-fitting bone scaffolds, self-expanding vaginal stents, and other shape-shifting devices. To ensure tissue safety during deployment, the shape actuation temperature (i.e., the melt transition temperature or Tm of PCL) must be reduced from ∼55 °C that is observed for scaffolds prepared from linear-PCL-DA (Mn ∼ 10 kg mol-1). Moreover, increasing the rate of biodegradation would be advantageous, facilitating bone tissue healing and potentially eliminating the need for stent retrieval. Herein, a series of six UV-curable PCL macromers were prepared with linear or 4-arm star architectures and with Mns of 10, 7.5, and 5 kg mol-1, and subsequently fabricated into six porous scaffold compositions (10k, 7.5k, 5k, 10k★, 7.5k★, and 5k★) via solvent casting particulate leaching (SCPL). Scaffolds produced from star-PCL-tetraacrylate (star-PCL-TA) macromers produced pronounced reductions in Tm with decreased Mnversus those formed with the corresponding linear-PCL-diacrylate (linear-PCL-DA) macromers. Scaffolds were produced with the desired reduced Tm profiles: 37 °C < Tm < 55 °C (self-fitting bone scaffold), and Tm ≤ 37 °C (self-expanding stent). As macromer Mn decreased, crosslink density increased while % crystallinity decreased, particularly for scaffolds prepared from star-PCL-TA macromers. While shape memory behavior was retained and radial expansion pressure increased, this imparted a reduction in modulus but with an increase in the rate of degradation.

A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology.

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The "Big Five" personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness, and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses including depression, anxiety, and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Utilizing the Million Veteran Program (MVP) cohort we conducted a genome-wide association study (GWAS) in individuals of European and African ancestry. Adding other published data, we performed GWAS meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 158, 14, 3, 2, and 7 independent genome-wide significant (GWS) loci associated with neuroticism, extraversion, agreeableness, conscientiousness, and openness, respectively. These findings represent 55 novel loci for neuroticism, as well as the first GWS loci discovered for extraversion and agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT, and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

Do both anticipated relief and anticipated regret predict decisions about influenza vaccination?

OBJECTIVE: Anticipated regret has been found to predict vaccination intentions and behaviours. We examined whether anticipated relief also predicts seasonal influenza vaccination intentions and behaviour. Given claims about differences in their antecedents and function, we distinguished between counterfactual relief (relief that a worse outcome did not obtain) and temporal relief (relief that an unpleasant experience is over). DESIGN: Cross-sectional. METHODS: Unvaccinated participants (N = 295) were recruited online in November 2020. Participants completed measures of anticipated regret, anticipated counterfactual relief, and anticipated temporal relief and measures of theory of planned behaviour constructs (attitudes, norms, perceived control, and intentions). One month later, the same participants were re-surveyed and asked to report their vaccination status. RESULTS: Although all anticipated emotion measures were associated with intentions and behaviour, only anticipated counterfactual relief and regret independently predicted vaccination intentions in regression analyses. Mediation analysis showed both anticipated counterfactual relief and regret were indirectly, via intentions, associated with behaviour. CONCLUSIONS: Results suggest that, regardless of valence, counterfactual emotions predict vaccination intention and, indirectly, behaviour. Furthermore, participants may differ in their sensitivity to the anticipation of positive versus negative counterfactual emotions. These findings may permit more precise targeting of interventions to increase vaccine uptake.

Blood Lactate and Heart Rate Responses Between Active and Passive Recovery Modes Over a 15-Minute Recovery Period in Female Dancers After Kathak Dance.

Introduction: Dance is physically demanding and results in blood lactate (BL) accumulation and elevated Heart Rate (HR). Researchers recommend using either Active Recovery (AR; eg, low-to-moderate intensity-exercise) or Passive Recovery (PR; eg, complete rest) modes after activity. We compared BL and HR responses between AR or PR over a 15-minute recovery period following a Kathak dance. Methods: Twelve female dancers (31.0 ± 6.0 years; 161.5 ± 4.9 cm; 55.5 ± 5.8 kg) performed 2 dance testing sessions (Day 1 = AR, Day 2 = PR) 48 hours apart. Each session started with a 10-minute warm up followed by dancers performing four 2-minute stages of Kathak dance, with three 1-minute periods between stages where we recorded HR and their Rate of Perceived Exertion (RPE:scale = 6-20) to match the intensity of both sessions. Post-dance, we recorded dancers' BL and HR at 1, 3, 5, 10, and 15 minutes while they recovered via AR or PR. Separate 2(mode) × (time) Repeated-Measures-ANOVA followed by simple-main-effects testing and adjusted Bonferroni-pairwise-comparisons examined differences in BL and HR responses across modes and time(α = .05). Results: Dancers' HR and RPE were similar across sessions. No mode × time interaction existed in BL (F4,8 = 3.6, P = .06). BL levels were similar across modes (F1,2 = 0.5, P = .5). BL levels reduced over time (F4,8 = 6.0, P = .02), but Bonferroni-comparisons did not reveal any pairwise differences. In HR a significant mode*time interaction (F4,36 = 11.0, P = .01, η2 = .55) was observed. Both Active and Passive recovery modes achieved absolute HR levels by 15 minutes, with PR mode stabilizing within 5 minutes. Conclusions: Over a 15-minute recovery period after Kathak dance, dancers' BL and HR responses were similar across time in both AR and PR, with HR being higher in AR. Dancers' HR remained similar from 1 to 3 minute post dance recovery and then dropped over time. Thus, dancers can rest up to 3 minutes and still maintain the same elevated HR. Overall, dancers can choose either AR or PR as their recovery mode based on their individual preferences.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

BACKGROUND: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. METHODS: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. RESULTS: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. CONCLUSIONS: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

MAGT1 Deficiency Dysregulates Platelet Cation Homeostasis and Accelerates Arterial Thrombosis and Ischemic Stroke in Mice.

BACKGROUND: MAGT1 (magnesium transporter 1) is a subunit of the oligosaccharide protein complex with thiol-disulfide oxidoreductase activity, supporting the process of N-glycosylation. MAGT1 deficiency was detected in human patients with X-linked immunodeficiency with magnesium defect syndrome and congenital disorders of glycosylation, resulting in decreased cation responses in lymphocytes, thereby inhibiting the immune response against viral infections. Curative hematopoietic stem cell transplantation of patients with X-linked immunodeficiency with magnesium defect causes fatal bleeding and thrombotic complications. METHODS: We studied the role of MAGT1 deficiency in platelet function in relation to arterial thrombosis and hemostasis using several in vitro experimental settings and in vivo models of arterial thrombosis and transient middle cerebral artery occlusion model of ischemic stroke. RESULTS: MAGT1-deficient mice (Magt1-/y) displayed accelerated occlusive arterial thrombus formation in vivo, a shortened bleeding time, and profound brain damage upon focal cerebral ischemia. These defects resulted in increased calcium influx and enhanced second wave mediator release, which further reinforced platelet reactivity and aggregation responses. Supplementation of MgCl2 or pharmacological blockade of TRPC6 (transient receptor potential cation channel, subfamily C, member 6) channel, but not inhibition of store-operated calcium entry, normalized the aggregation responses of Magt1-/y platelets to the control level. GP (glycoprotein) VI activation of Magt1-/y platelets resulted in hyperphosphorylation of Syk (spleen tyrosine kinase), LAT (linker for activation of T cells), and PLC (phospholipase C) γ2, whereas the inhibitory loop regulated by PKC (protein kinase C) was impaired. A hyperaggregation response to the GPVI agonist was confirmed in human platelets isolated from a MAGT1-deficient (X-linked immunodeficiency with magnesium defect) patient. Haploinsufficiency of TRPC6 in Magt1-/y mice could normalize GPVI signaling, platelet aggregation, and thrombus formation in vivo. CONCLUSIONS: These results suggest that MAGT1 and TRPC6 are functionally linked. Therefore, deficiency or impaired functionality of MAGT1 could be a potential risk factor for arterial thrombosis and stroke.

Platelet glycoprotein V spatio-temporally controls fibrin formation.

The activation of platelets and coagulation at vascular injury sites is crucial for haemostasis but can promote thrombosis and inflammation in vascular pathologies. Here, we delineate an unexpected spatio-temporal control mechanism of thrombin activity that is platelet orchestrated and locally limits excessive fibrin formation after initial haemostatic platelet deposition. During platelet activation, the abundant platelet glycoprotein (GP) V is cleaved by thrombin. We demonstrate with genetic and pharmacological approaches that thrombin-mediated shedding of GPV does not primarily regulate platelet activation in thrombus formation, but rather has a distinct function after platelet deposition and specifically limits thrombin-dependent generation of fibrin, a crucial mediator of vascular thrombo-inflammation. Genetic or pharmacologic defects in haemostatic platelet function are unexpectedly attenuated by specific blockade of GPV shedding, indicating that the spatio-temporal control of thrombin-dependent fibrin generation also represents a potential therapeutic target to improve haemostasis.

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks), 10 term neonates, 8 infants (<2 years), 5 children (2-13 years), and 9 adults (>13 years). Blood was withdrawn at up to 3 different time points in neonates (t1: 0-2, t2: 3-7, and t3: 8-14 days after birth). We found that the expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced but correlated with decreased platelet size, indicating a normal surface density. Although CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP, or U46619 was unaltered or only slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted but showed a continuous increase until adulthood, correlating with the expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis using automated clustering revealed that neonates presented with a CD63+/PAC-1- pattern, followed by a continuous increase in CD63+/PAC-1+ platelets until adulthood. Our findings revealed that the number of platelet-monocyte and platelet-neutrophil aggregates, but not platelet-lymphocyte aggregates, is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that the platelet phenotype and function evolve continuously from neonates to adulthood.

Flexible tool set transport in Goffin's cockatoos.

The use of tool sets constitutes one of the most elaborate examples of animal technology, and reports of it in nature are limited to chimpanzees and Goffin's cockatoos. Although tool set use in Goffin's was only recently discovered, we know that chimpanzees flexibly transport tool sets, depending on their need. Flexible tool set transport can be considered full evidence for identification of a genuine tool set, as the selection of the second tool is not just a response to the outcomes of the use of the first tool but implies recognizing the need for both tools before using any of them (thus, categorizing both tools together as a tool set). In three controlled experiments, we tested captive Goffin's in tasks inspired by the termite fishing of Goualougo Triangle's chimpanzees. Thereby, we show that some Goffin's can innovate the use and flexibly use and transport a new tool set for immediate future use; therefore, their sequential tool use is more than the sum of its parts. VIDEO ABSTRACT.

Monoglyceride Lipase Deficiency Is Associated with Altered Thrombogenesis in Mice.

Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) to glycerol and one fatty acid. Among the various MG species, MGL also degrades 2-arachidonoylglycerol, the most abundant endocannabinoid and potent activator of the cannabinoid receptors 1 and 2. We investigated the consequences of MGL deficiency on platelet function using systemic (Mgl-/-) and platelet-specific Mgl-deficient (platMgl-/-) mice. Despite comparable platelet morphology, loss of MGL was associated with decreased platelet aggregation and reduced response to collagen activation. This was reflected by reduced thrombus formation in vitro, accompanied by a longer bleeding time and a higher blood volume loss. Occlusion time after FeCl3-induced injury was markedly reduced in Mgl-/- mice, which is consistent with contraction of large aggregates and fewer small aggregates in vitro. The absence of any functional changes in platelets from platMgl-/- mice is in accordance with lipid degradation products or other molecules in the circulation, rather than platelet-specific effects, being responsible for the observed alterations in Mgl-/- mice. We conclude that genetic deletion of MGL is associated with altered thrombogenesis.

Association between external training loads and injury incidence during 44 weeks of military training.

Military training is physically arduous and associated with high injury incidence. Unlike in high-performance sport, the interaction between training load and injury has not been extensively researched in military personnel. Sixty-three (43 men, 20 women; age 24 ± 2 years; stature 1.76 ± 0.09 m; body mass 79.1 ± 10.8 kg) British Army Officer Cadets undergoing 44 weeks of training at the Royal Military Academy Sandhurst volunteered to participate. Weekly training load (cumulative 7-day moderate-vigorous physical activity [MVPA], vigorous PA [VPA], and the ratio between MVPA and sedentary-light PA [SLPA; MVPA:SLPA]) was monitored using a wrist-worn accelerometer (GENEActiv, UK). Self-report injury data were collected and combined with musculoskeletal injuries recorded at the Academy medical center. Training loads were divided into quartiles with the lowest load group used as the reference to enable comparisons using odds ratios (OR) and 95% confidence intervals (95% CI). Overall injury incidence was 60% with the most common injury sites being the ankle (22%) and knee (18%). High (load; OR; 95% CI [>2327 mins; 3.44; 1.80-6.56]) weekly cumulative MVPA exposure significantly increased odds of injury. Similarly, likelihood of injury significantly increased when exposed to low-moderate (0.42-0.47; 2.45 [1.19-5.04]), high-moderate (0.48-0.51; 2.48 [1.21-5.10]), and high MVPA:SLPA loads (>0.51; 3.60 [1.80-7.21]). High MVPA and high-moderate MVPA:SLPA increased odds of injury by ~2.0 to 3.5 fold, suggesting that the ratio of workload to recovery is important for mitigating injury occurrence.

Is rumination associated with psychological distress after a cancer diagnosis? A systematic review.

Objective: The aim of this work was to review evidence on the association between psychological rumination and distress in those diagnosed with cancer. Methods: Six databases were searched for studies exploring rumination alongside overall assessments of psychological distress, depression, anxiety, or stress. Results: Sixteen studies were identified. Rumination was associated with distress cross-sectionally and longitudinally. However, once baseline depression was controlled for, the association was no longer seen. The emotional valence of ruminative thoughts and the style in which they were processed, rather than their topic, was associated with distress. Brooding and intrusive rumination were associated with increased distress, deliberate rumination had no association, and reflection/instrumentality had mixed findings. Conclusions: This review highlights that it is not necessarily the topic of content, but the style and valence of rumination that is important when considering its association with distress. The style of rumination should be the target of clinical intervention, including brooding and intrusion.

Relief in everyday life.

Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains poorly understood from the perspective of psychological science. What complicates the study of relief is that people seem to use the term to describe an emotion that occurs in two distinct situations: when an unpleasant episode is over, or upon realizing that an outcome could have been worse. This study constitutes a detailed empirical investigation of people's reports of everyday episodes of relief. A set of four studies collected a large corpus (N = 1,835) of first-person reports of real-life episodes of relief and examined people's judgments about the antecedents of relief, its relation to counterfactual thoughts, and its subsequent effects on decision making. Some participants described relief experiences that had either purely temporal or purely counterfactual precursors. Nevertheless, the findings indicated that the prototypical instance of relief appears to be one in which both these elements are present. The results also suggest that, although relief is frequently experienced in situations in which people are not responsible for the relief-inducing event, nevertheless they typically report that the experience had a positive impact on subsequent decision making. (PsycInfo Database Record (c) 2023 APA, all rights reserved).