Variants in the Late Cornified Envelope Gene Locus Are Associated With Elevated T-helper 17 Responses in Patients With Postinfectious Lyme Arthritis.

BACKGROUND: Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. METHODS: The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. RESULTS: Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P < .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. CONCLUSIONS: Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.

Utility of a pharmacist-managed Anticoagulation Program in patients with congenital heart disease.

BACKGROUND: Warfarin remains the preferred anticoagulant for many patients with CHD. The complexity of management led our centre to shift from a nurse-physician-managed model with many providers to a pharmacist-managed model with a centralized anticoagulation team. We aim to describe the patient cohort managed by our Anticoagulation Program and evaluate the impact of implementation of this consistent, pharmacist-managed model on time in therapeutic range, an evidence-based marker for clinical outcomes. METHODS: A single-centre retrospective cohort study was conducted to evaluate the impact of the transition to a pharmacist-managed model to improve anticoagulation management at a tertiary pediatric heart centre. The percent time in therapeutic range for a cohort managed by both models was compared using a paired t-test. Patient characteristics and time in therapeutic range of the program were also described. RESULTS: After implementing the pharmacist-managed model, the time in therapeutic range for a cohort of 58 patients increased from 65.7 to 80.2% (p < .001), and our Anticoagulation Program consistently maintained this improvement from 2013 to 2022. The cohort of patients managed by the Anticoagulation Program in 2022 included 119 patients with a median age of 24 years (range 19 months-69 years) with the most common indication for warfarin being mechanical valve replacement (n = 81, 68%). CONCLUSIONS: Through a practice change incorporating a collaborative, centralized, pharmacist-managed model, this cohort of CHD patients on warfarin had a fifteen percent increase in time in therapeutic range, which was sustained for nine years.

Effects of emotional cues on novel word learning in typically developing children in relation to broader autism traits.

Emotion can influence various cognitive processes. Communication with children often involves exaggerated emotional expressions and emotive language. Children with autism spectrum disorder often show a reduced tendency to attend to emotional information. Typically developing children aged 7 to 9 years who varied in their level of autism-like traits learned the nonsense word names of nine novel toys, which were presented with either happy, fearful, or neutral emotional cues. Emotional cues had no influence on word recognition or recall performance. Eye-tracking data showed differences in visual attention depending on the type of emotional cues and level of autism-like traits. The findings suggest that the influence of emotion on attention during word learning differs according to whether the children have lower or higher levels of autism-like traits, but this influence does not affect word learning outcomes.

Winners and losers: Recognition of spontaneous emotional expressions increases across childhood.

Research using posed emotional expressions is problematic because they lack ecological validity. Adults' recognition of spontaneous real-world expressions may require the inclusion of postural information. Whether posture improves children's recognition of real-world expressions was unknown. Younger children (n = 30; 5- to 7-year-olds), older children (n = 30; 8- to 10-year-olds), and adults (n = 30) judged whether tennis players had won or lost a point. Images showed one of three cue types: Head-only, Body-only, or Head-Body expressions. Recognition of expressions improved with age; older children and adults performed better than younger children. In addition, recognition of Body-only and Head-Body cues was better than Head-only cues for all ages. Spontaneous expression recognition improved throughout childhood and with the inclusion of postural information.

Children overclaim more knowledge than adults do, but for different reasons.

Overclaiming is the phenomenon whereby people claim more knowledge of a topic than they actually have. In adults, this behavior is related to the extent to which they consider themselves an expert on that topic and may be related to impression management. We investigated the emergence of this phenomenon by developing a child-friendly overclaiming questionnaire (OCQ)-the Child-OCQ. We measured the tendency of children (5-10 years of age old; N = 94) to claim knowledge of items that did not exist for a variety of topics (places, characters, animals, food, and musical instruments). We also examined the relationship between children's overclaiming of knowledge and their self-perceived liking of, and expertise in, the topics. To validate our scale, an adult sample (N = 51) completed both the Child-OCQ and a standardized adult OCQ, the OCQ-150, showing similar overclaiming patterns on both measures. Although overclaiming behaviors decreased throughout childhood, even children as old as 10 years were not adult-like and were more likely to overclaim knowledge than adults. In addition, we did not find strong evidence that children's perceived expertise on a topic influenced their tendency to overclaim knowledge, suggesting that the mechanisms behind the overclaiming phenomenon are different in children and do not reflect impression management until later during adolescence or adulthood.

Idea Formulation for Spoken Language Production: The Interface of Cognition and Language.

BACKGROUND: Language and communication are fundamental to the human experience, and, traditionally, spoken language is studied as an isolated skill. However, before propositional language (i.e., spontaneous, voluntary, novel speech) can be produced, propositional content or 'ideas' must be formulated. OBJECTIVE: This review highlights the role of broader cognitive processes, particularly 'executive attention', in the formulation of propositional content (i.e., 'ideas') for propositional language production. CONCLUSIONS: Several key lines of evidence converge to suggest that the formulation of ideas for propositional language production draws on executive attentional processes. Larger-scale clinical research has demonstrated a link between attentional processes and language, while detailed case studies of neurological patients have elucidated specific idea formulation mechanisms relating to the generation, selection and sequencing of ideas for expression. Furthermore, executive attentional processes have been implicated in the generation of ideas for propositional language production. Finally, neuroimaging studies suggest that a widely distributed network of brain regions, including parts of the prefrontal and parietal cortices, supports propositional language production. IMPLICATIONS: Theoretically driven experimental research studies investigating mechanisms involved in the formulation of ideas are lacking. We suggest that novel experimental approaches are needed to define the contribution of executive attentional processes to idea formulation, from which comprehensive models of spoken language production can be developed. Clinically, propositional language impairments should be considered in the context of broader executive attentional deficits.

Interactive situations reveal more about children's emotional knowledge.

Research examining children's emotion judgments has generally used nonsocial tasks that do not resemble children's daily experiences in judging others' emotions. Here, younger children (4- to 6-year-olds) and older children (7- to 9-year-olds) participated in a socially interactive task where an experimenter opened boxes and made an expression (happy, sad, scared, or disgust) based on the object inside. Children guessed which of four objects (a sticker, a broken toy car, a spider, or toy poop) was in the box. Subsequently, children opened a set of boxes and generated facial expressions for the experimenter. Children also labeled the emotion elicited by the objects and static facial expressions. Children's ability to guess which object caused the experimenter's expression increased with age but did not predict their ability to generate a recognizable expression. Children's demonstration of emotion knowledge also varied across tasks, suggesting that when emotion judgment tasks more closely mimic their daily experiences, children demonstrate broader emotion knowledge.

Cross-modal emotion recognition and autism-like traits in typically developing children.

The ability to explicitly recognize emotions develops gradually throughout childhood, and children usually have greater difficulty in recognizing emotions from the voice than from the face. However, little is known about how children integrate vocal and facial cues to recognize an emotion, particularly during mid to late childhood. Furthermore, children with an autism spectrum disorder often show a reduced ability to recognize emotions, especially when integrating emotion from multiple modalities. The current preliminary study explored the ability of typically developing children aged 7-9 years to match emotional tones of voice to facial expressions and whether this ability varies according to the level of autism-like traits. Overall, children were the least accurate when matching happy and fearful voices to faces, commonly pairing happy voices with angry faces and fearful voices with sad faces. However, the level of autism-like traits was not associated with matching accuracy. These results suggest that 7- to 9-year-old children have difficulty in integrating vocal and facial emotional expressions but that differences in cross-modal emotion matching in relation to the broader autism phenotype are not evident in this task for this age group with the current sample.

Development of emotion recognition in popular music and vocal bursts.

Previous research on the development of emotion recognition in music has focused on classical, rather than popular music. Such research does not consider the impact of lyrics on judgements of emotion in music, impact that may differ throughout development. We had 172 children, adolescents, and adults (7- to 20-year-olds) judge emotions in popular music. In song excerpts, the melody of the music and the lyrics had either congruent valence (e.g. happy lyrics and melody), or incongruent valence (e.g. scared lyrics, happy melody). We also examined participants' judgements of vocal bursts, and whether emotion identification was linked to emotion lexicon. Recognition of emotions in congruent music increased with age. For incongruent music, age was positively associated with judging the emotion in music by the melody. For incongruent music with happy or sad lyrics, younger participants were more likely to answer with the emotion of the lyrics. For scared incongruent music, older adolescents were more likely to answer with the lyrics than older and younger participants. Age groups did not differ on their emotion lexicons, nor recognition of emotion in vocal bursts. Whether children use lyrics or melody to determine the emotion of popular music may depend on the emotion conveyed.

Fcγ receptors and toll-like receptor 9 synergize to drive immune complex-induced dendritic cell maturation.

Previous in vivo studies established that inactivated Francisella tularensis immune complexes (mAb-iFt) are a more protective vaccine against lethal tularemia than iFt alone. Subsequent in vitro studies revealed enhanced DC maturation marker expression with mAb-iFt stimulation. The goal of this study was to determine the mechanism of enhanced DC maturation. Multiparameter analysis of surface marker expression and cytokine secretion demonstrates a requirement for FcγR signaling in enhanced DC maturation. MyD88 was also found to be essential for heightened DC maturation, implicating MyD88-dependent TLRs in DC maturation. Upon further study, we discovered that TLRs 2 & 4 drive cytokine secretion, but surprisingly TLR9 is required for DC maturation marker upregulation. These studies reveal a separation of DC cytokine and maturation marker induction pathways and demonstrate that FcγR-TLR/MyD88 synergy underlies the enhanced dendritic cell maturation in response to the mAb-iFt vaccine.

Sexual Selection, Agonistic Signaling, and the Effect of Beards on Recognition of Men's Anger Displays.

The beard is arguably one of the most obvious signals of masculinity in humans. Almost 150 years ago, Darwin suggested that beards evolved to communicate formidability to other males, but no studies have investigated whether beards enhance recognition of threatening expressions, such as anger. We found that the presence of a beard increased the speed and accuracy with which participants recognized displays of anger but not happiness (Experiment 1, N = 219). This effect was not due to negative evaluations shared by beardedness and anger or to negative stereotypes associated with beardedness, as beards did not facilitate recognition of another negative expression, sadness (Experiment 2, N = 90), and beards increased the rated prosociality of happy faces in addition to the rated masculinity and aggressiveness of angry faces (Experiment 3, N = 445). A computer-based emotion classifier reproduced the influence of beards on emotion recognition (Experiment 4). The results suggest that beards may alter perceived facial structure, facilitating rapid judgments of anger in ways that conform to evolutionary theory.

Mothers are sensitive to men's beards as a potential cue of paternal investment.

Mating strategy theories assert that women's preferences for androgen dependent traits in men are stronger when the costs of reduced paternal investment are lowest. Past research has shown that preferences for facial masculinity are stronger among nulliparous and non-pregnant women than pregnant or parous women. In two studies, we examine patterns in women's preferences for men's facial hair - likely the most visually conspicuous and sexually dimorphic of men's secondary sexual traits - when evaluating men's masculinity, dominance, age, fathering, and attractiveness. Two studies were conducted among heterosexual pregnant women, mothers, non-contractive and contraceptive users. Study 1 used a between-subjects sample (N = 2103) and found that mothers had significantly higher preferences for beards when judging fathering than all other women. Pregnant women and mothers also judged beards as more masculine and older, but less attractive, than non-contractive and contraceptive users. Parous women judged beards higher for age, masculinity and fathering, but lower for attractiveness, than nulliparous women. Irrespective of reproductive status, beards were judged as looking more dominant than clean-shaven faces. Study 2 used a within-subjects design (N = 53) among women surveyed during pregnancy and three months post-partum. Judgments of parenting skills were higher for bearded stimuli during pregnancy among women having their first baby, whereas among parous women parenting skills judgments for bearded stimuli were higher post-partum. Our results suggest that mothers are sensitive to beardedness as a masculine secondary sexual characteristic that may denote parental investment, providing evidence that women's mate preferences could reflect sexual selection for direct benefits.

The influence of subtle facial expressions on children's first impressions of trustworthiness and dominance is not adult-like.

Adults' first impressions of others are influenced by subtle facial expressions; happy faces are perceived as high in trustworthiness, whereas angry faces are rated as low in trustworthiness and high in threat and dominance. Little is known about the influence of emotional expressions on children's first impressions. Here we examined the influence of subtle expressions of happiness, anger, and fear on children's implicit judgments of trustworthiness and dominance with the aim of providing novel insights about both the development of first impressions and whether children are able to utilize emotional expressions when making implicit, rather than explicit, judgments of traits. In the context of a computerized storybook, children (4- to 11-year-olds) and adults selected one of two twins (two images of the same identity displaying different emotional expressions) to help them face a challenge; some challenges required a trustworthy partner, and others required a dominant partner. One twin posed a neutral expression, and the other posed a subtle emotional expression of happiness, fear, or anger. Whereas adults were more likely to select a happy partner on trust trials than on dominance trials and were more likely to select an angry partner on dominance trials than on trust trials, we found no evidence that children's choices reflected a combined influence of desirable trait and emotion. Follow-up experiments involving explicit trait judgments, explicit emotion recognition, and implicit first impression judgments in the context of intense emotional expressions provide valuable insights into the slow development of implicit trait judgments based on first impressions.

No experimental evidence for emotion-specific gaze cueing in a threat context.

We examined the utility of a gaze cueing paradigm to examine sensitivity to differences among negatively valenced expressions. Participants judged target stimuli (dangerous or safe), the location of which was cued by the gaze direction of a central face. Dawel et al. reported that gaze cueing effects (faster response times on valid vs. invalid trials) were larger when the central face displayed fear than when it displayed happiness. Our aim was to determine whether this effect was specific to fear, to all threat-related expressions (fear, anger), or to all negatively valenced expressions (fear, anger, sadness, disgust) with the aim of using this protocol to study the development of implicit discrimination of negatively valenced expressions. Across five experiments in which we varied the number of models (1 vs. 4), the number of expressions (2 vs. 5), and the country of residence of participants (Canada vs. Australia) we found no evidence that the magnitude of gaze cueing effects is modulated by expression. We discuss our failure to replicate in the context of the broader literature.

Induction of Interleukin 10 by Borrelia burgdorferi Is Regulated by the Action of CD14-Dependent p38 Mitogen-Activated Protein Kinase and cAMP-Mediated Chromatin Remodeling.

Host genotype influences the severity of murine Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi C57BL/6 (B6) mice develop mild Lyme arthritis, whereas C3H/HeN (C3H) mice develop severe Lyme arthritis. Differential expression of interleukin 10 (IL-10) has long been associated with mouse strain differences in Lyme pathogenesis; however, the underlying mechanism(s) of this genotype-specific IL-10 regulation remained elusive. Herein we reveal a cAMP-mediated mechanism of IL-10 regulation in B6 macrophages that is substantially diminished in C3H macrophages. Under cAMP and CD14-p38 mitogen-activated protein kinase (MAPK) signaling, B6 macrophages stimulated with B. burgdorferi produce increased amounts of IL-10 and decreased levels of arthritogenic cytokines, including tumor necrosis factor (TNF). cAMP relaxes chromatin, while p38 increases binding of the transcription factors signal transducer and activator of transcription 3 (STAT3) and specific protein 1 (SP1) to the IL-10 promoter, leading to increased IL-10 production in B6 bone marrow-derived monocytes (BMDMs). Conversely, macrophages derived from arthritis-susceptible C3H mice possess significantly less endogenous cAMP, produce less IL-10, and thus are ill equipped to mitigate the damaging consequences of B. burgdorferi-induced TNF. Intriguingly, an altered balance between anti-inflammatory and proinflammatory cytokines and CD14-dependent regulatory mechanisms also is operative in primary human peripheral blood-derived monocytes, providing potential insight into the clinical spectrum of human Lyme disease. In line with this notion, we have demonstrated that cAMP-enhancing drugs increase IL-10 production in myeloid cells, thus curtailing inflammation associated with murine Lyme borreliosis. Discovery of novel treatments or repurposing of FDA-approved cAMP-modulating medications may be a promising avenue for treatment of patients with adverse clinical outcomes, including certain post-Lyme complications, in whom dysregulated immune responses may play a role.

Children's visual attention to emotional expressions varies with stimulus movement.

The majority of studies of emotion perception have relied on static isolated facial expressions. These expressions differ markedly from real-world expressions that include movement and multiple cues (e.g., bodies), leaving our understanding of how expression perception develops incomplete. We examined the looking patterns of younger children (4- and 5-year-olds), older children (8- and 9-year-olds), and adults while watching dynamic video clips or static images of four different emotional expressions: happiness, sadness, anger, and fear. Expressions were presented in three conditions: face only, body only, and whole person (face and body). Children's and adults' looking patterns were affected by whether stimuli were static or dynamic and by which cues were available. Children looked to the head less for static stimuli than for dynamic stimuli, but this difference did not emerge for adults. Children and adults attended to different expression cues when presented with static images. These results demonstrate the need for increased use of dynamic stimuli in developmental studies of expression.

A narrative review of exercise-associated muscle cramps: Factors that contribute to neuromuscular fatigue and management implications.

Although exercise-associated muscle cramps (EAMC) are highly prevalent among athletic populations, the etiology and most effective management strategies are still unclear. The aims of this narrative review are 3-fold: (1) briefly summarize the evidence regarding EAMC etiology; (2) describe the risk factors and possible physiological mechanisms associated with neuromuscular fatigue and EAMC; and (3) report the current evidence regarding prevention of, and treatment for, EAMC. Based on the findings of several large prospective and experimental investigations, the available evidence indicates that EAMC is multifactorial in nature and stems from an imbalance between excitatory drive from muscle spindles and inhibitory drive from Golgi tendon organs to the alpha motor neurons rather than dehydration or electrolyte deficits. This imbalance is believed to stem from neuromuscular overload and fatigue. In concert with these findings, the most successful treatment for an acute bout of EAMC is stretching, whereas auspicious methods of prevention include efforts that delay exercise-induced fatigue. Muscle Nerve 54: 177-185, 2016.

Building emotion categories: Children use a process of elimination when they encounter novel expressions.

Recent research has indicated that language provides an important contribution to adults' conceptions of emotional expressions and their associated categories, but how language influences children's expression category acquisition has yet to be explored. Across two studies, we provide evidence that when preschoolers (2-4years) encounter a novel label, they use a process of elimination to match it with its expected expression. Children successfully used a process of elimination to match a single expression to one of several labels (Study 1) and to match a single label to one of several expressions (Study 2). These data highlight one possible mechanism that children may use to learn about the expressions they encounter and may shed light on the ways in which children's expression categories are constructed.

A facial expression of pax: Assessing children's "recognition" of emotion from faces.

In a classic study, children were shown an array of facial expressions and asked to choose the person who expressed a specific emotion. Children were later asked to name the emotion in the face with any label they wanted. Subsequent research often relied on the same two tasks--choice from array and free labeling--to support the conclusion that children recognize basic emotions from facial expressions. Here five studies (N=120, 2- to 10-year-olds) showed that these two tasks produce illusory recognition; a novel nonsense facial expression was included in the array. Children "recognized" a nonsense emotion (pax or tolen) and two familiar emotions (fear and jealousy) from the same nonsense face. Children likely used a process of elimination; they paired the unknown facial expression with a label given in the choice-from-array task and, after just two trials, freely labeled the new facial expression with the new label. These data indicate that past studies using this method may have overestimated children's expression knowledge.

Breast Cancer-Related Lymphedema and Resistance Exercise: A Systematic Review.

Nelson, NL. Breast cancer-related lymphedema and resistance exercise: a systematic review. J Strength Cond Res 30(9): 2656-2665, 2016-Breast cancer-related lymphedema (BCRL) is characterized by the accumulation of fluid in the interstitial tissues in the arm, shoulder, neck, or torso and attributed to the damage of lymph nodes during breast cancer treatments involving radiation and axillary node dissection. Resistance exercise training (RET) has recently shown promise in the management of BCRL. The aims of this review were twofold: (a) To summarize the results of recent randomized controlled trials (RCTs) investigating the effect of resistance exercise in those with, or at risk for, BCRL. (b) To determine whether breast cancer survivors can perform RET at sufficient intensities to elicit gains in strength without causing BCRL flare-up or incidence. A search was performed on the electronic databases PubMed, MEDLINE, SPORT Discus, and Science Direct, up to July 10, 2015, using the following keywords: breast cancer-related lymphedema, strength training, resistance training, systematic review, and breast cancer. Manual searches of references were also conducted for additional relevant studies. A total of 6 RCTs, involving 805 breast cancer survivors, met the inclusion criteria and corresponded to the aims of this review. The methodological quality of included RCTs was good, with a mean score 6.8 on the 10-point PEDro scale. The results of this review indicate that breast cancer survivors can perform RET at high-enough intensities to elicit strength gains without triggering changes to lymphedema status. There is strong evidence indicating that RET produces significant gains in muscular strength without provoking BCRL.