Physical Activity and Children's Episodic Memory: A Meta-Analysis.

PURPOSE: The purpose of this review was to evaluate the effects of physical activity on children's free recall, cued recall, and recognition episodic memory and to explore potential moderating factors. METHODS: The following databases were searched: PubMed, ERIC, APA Psych Info, CINHAL, SPORTDiscus, and Google Scholar. Studies were included if: (1) participants were aged 4-18 years, (2) participants were typically developed, (3) participants were randomized to groups, (4) interventions employed gross movements, (5) sedentary group was used for control, (6) memory tests were quantitative, and (7) employed acute or chronic intervention. RESULTS: 14 studies met inclusion criteria resulting in the analysis of data from 7 free recall, 7 cued recall, and 8 recognition memory tests. Physical activity was found to have a positive influence on tests free (g = 0.56), cued recall (g = 0.67), and no influence on tests of recognition (g = 0.06). While some moderator analyses were significant, the authors do not consider these results to be meaningful in application. CONCLUSIONS: The effects of acute and chronic physical activity enhance specific aspects of long-term episodic memory. These findings suggest physical activity interventions developed for children may be expected to benefit some, but not all, types of memory processing.

Limited Utility of Reverse Algorithm Syphilis Testing in HIV Clinic Among Men Who Have Sex With Men.

BACKGROUND: The reverse algorithm for syphilis diagnosis consists of a treponemal antibody screening immunoassay followed by confirmatory nontreponemal antibody testing. It is increasingly used in the United States despite studies suggesting limited cost-effectiveness in high-prevalence groups. METHODS: In this retrospective cross-sectional study, we included men who have sex with men tested with the reverse algorithm in an Alabama HIV clinic between March 2015 and February 2017. Trep-Sure enzyme immunoassay (EIA) was used for the initial screen, followed by reflex nontreponemal reactive rapid plasma reagin (RPR) testing of specimens with positive results. Sociodemographic and clinical data were extracted from the electronic medical record and stratified according to EIA screen positivity. Quantitative EIA antibody index values were collected to assess test performance at various thresholds. RESULTS: Among 1693 men tested for syphilis with the reverse algorithm in HIV clinic, 808 (48%) had a positive initial EIA screen. A majority (53%) of men with subsequent RPR testing had a nonreactive RPR (EIA+/RPR-), and 19% (19/98) of these EIA+/RPR- samples tested had a negative confirmatory Treponema pallidum particle agglutination testing result. Analysis of quantitative EIA index values using a receiver operating characteristics curve suggested that a threshold >8 (rather the current threshold of antibody index 1.2) improved the performance of the test. CONCLUSIONS: Among men who have sex with men tested in HIV clinic, the syphilis reverse algorithm was inefficient because of high rates of prior syphilis and false-positive EIA screening. Frequent syphilis screening in high-prevalence populations is an important part of the US epidemic response, and the traditional algorithm is preferred.

Interplay between T cell receptor binding kinetics and the level of cognate peptide presented by major histocompatibility complexes governs CD8+ T cell responsiveness.

Through a rational design approach, we generated a panel of HLA-A*0201/NY-ESO-1(157-165)-specific T cell receptors (TCR) with increasing affinities of up to 150-fold from the wild-type TCR. Using these TCR variants which extend just beyond the natural affinity range, along with an extreme supraphysiologic one having 1400-fold enhanced affinity, and a low-binding one, we sought to determine the effect of TCR binding properties along with cognate peptide concentration on CD8(+) T cell responsiveness. Major histocompatibility complexes (MHC) expressed on the surface of various antigen presenting cells were peptide-pulsed and used to stimulate human CD8(+) T cells expressing the different TCR via lentiviral transduction. At intermediate peptide concentration we measured maximum cytokine/chemokine secretion, cytotoxicity, and Ca(2+) flux for CD8(+) T cells expressing TCR within a dissociation constant (K(D)) range of ∼1-5 µM. Under these same conditions there was a gradual attenuation in activity for supraphysiologic affinity TCR with K(D) < ∼1 µM, irrespective of CD8 co-engagement and of half-life (t(1/2) = ln 2/k(off)) values. With increased peptide concentration, however, the activity levels of CD8(+) T cells expressing supraphysiologic affinity TCR were gradually restored. Together our data support the productive hit rate model of T cell activation arguing that it is not the absolute number of TCR/pMHC complexes formed at equilibrium, but rather their productive turnover, that controls levels of biological activity. Our findings have important implications for various immunotherapies under development such as adoptive cell transfer of TCR-engineered CD8(+) T cells, as well as for peptide vaccination strategies.

The effects of physical activity timing and complexity on episodic memory: A randomized controlled trial.

The role of two types of acute physical activity (PA) bouts were assessed on young adults' free-recall and recognition memory in two experiments, which differed in the temporal relation of PA and word encoding. Before or following training on the Rey Auditory Verbal Learning Task, participants performed a simple two-step dance, a complex four-step dance, or remained seated. Hypotheses proposed that PA prior to encoding and complex PA would enhance PA's mnemonic benefits. Memory assessed post-PA, 24 h, and 7 days after training indicated that timing and complexity of PA did not impact free-recall or recognition memory. Findings differ from a previous study showing complex PA benefited motor learning more than simple PA (Tomporowski & Pendleton, 2018). The inconsistency may be due to different working memory processes underlying consolidation and retrieval of procedural or episodic information. Theory-based explanations regarding memory storage and retrieval are proposed to elucidate this selective process.

Evidence for a TCR affinity threshold delimiting maximal CD8 T cell function.

Protective adaptive immune responses rely on TCR-mediated recognition of Ag-derived peptides presented by self-MHC molecules. However, self-Ag (tumor)-specific TCRs are often of too low affinity to achieve best functionality. To precisely assess the relationship between TCR-peptide-MHC binding parameters and T cell function, we tested a panel of sequence-optimized HLA-A(*)0201/NY-ESO-1(157-165)-specific TCR variants with affinities lying within physiological boundaries to preserve antigenic specificity and avoid cross-reactivity, as well as two outliers (i.e., a very high- and a low-affinity TCR). Primary human CD8 T cells transduced with these TCRs demonstrated robust correlations between binding measurements of TCR affinity and avidity and the biological response of the T cells, such as TCR cell-surface clustering, intracellular signaling, proliferation, and target cell lysis. Strikingly, above a defined TCR-peptide-MHC affinity threshold (K(D) < approximately 5 muM), T cell function could not be further enhanced, revealing a plateau of maximal T cell function, compatible with the notion that multiple TCRs with slightly different affinities participate equally (codominantly) in immune responses. We propose that rational design of improved self-specific TCRs may not need to be optimized beyond a given affinity threshold to achieve both optimal T cell function and avoidance of the unpredictable risk of cross-reactivity.

Exploratory evaluation of tolerability, performance, and cosmetic acceptance of dexpanthenol-containing dermo-cosmetic wash and sun-care products for tattoo aftercare.

Background and Aims: Tattoo prevalence has significantly increased over the last decades. Proper tattoo aftercare, such as cleansing, moisturizing, and protection against sunlight, is essential to prevent complications and to keep the beauty of the tattoo. The tolerability, performance, and cosmetic acceptability of two dexpanthenol-containing dermo-cosmetic products, a wash and a sun-care, were investigated on tattooed skin in two separate trials. Methods: Two single-center, exploratory, open-label cosmetic studies were conducted between August and November 2020 to evaluate the dexpanthenol-containing dermo-cosmetic products. In the first study, healthy adults applied the 2.5% dexpanthenol-containing wash right after their tattoo session daily for 14 consecutive days. In the second study, healthy adults applied the 2.5% dexpanthenol-containing sun-care sun protection factor 50+ cream on existing tattoos that were daily exposed to sunlight for 28 consecutive days. Clinical examination by a dermatologist and self-assessment through subject questionnaires were used to assess the tolerability, acceptance, ease of use, and cosmetic outcomes of both products. Additionally, transepidermal water loss and moisturization assessments were performed to evaluate skin hydration after use of the sun-care product. Results: Both study products were well tolerated, and no product related adverse events were reported during the studies. At least 90% of the study participants appreciated the performance of the dexpanthenol-containing wash and sun-care product, including moisturizing properties, relief of unpleasant sensations, and preservation of the cosmetic appearance of the tattoo. For the sun-care, it was shown that its application supported maintaining the skin barrier of tattooed skin, while keeping it hydrated. Conclusion: The 2.5% dexpanthenol-containing wash and sun-care products are well tolerated and appreciated by tattooed subjects. Hence, they represent valid options for tattoo aftercare in line with current recommendations and practice.

Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues.

Naturally acquired immune responses against human cancers often include CD8(+) T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1(157-165)-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with alpha-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1(157-165) peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of alphabeta TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.

Role of age and sex on dual tasking using a treadmill desk while performing cognitive tests.

BACKGROUND: Treadmill desks have been used extensively to increase physical activity and decrease sedentary time in the work environment. However, dual tasking, such as simultaneously walking and performing a cognitive task, may result in diminished performance in one or both tasks. RESEARCH QUESTION: Do age and sex impact ability to dual task while using a treadmill desk at a preferred walking speed?. METHODS: A total of n = 24 younger (range of 18-24 years, mean age = 21.1 ± 1.6 years) and n = 25 older (range of 45-65 years, mean age = 53.0 ± 5.1 years) adults self-selected a comfortable walking speed ranging from 0.5 to 2.0 mph and performed the Stroop Color & Word test (measuring Inhibition) and the Sternberg Test of Working Memory (measuring Working Memory) while walking at their chosen speed on a treadmill desk and while seated. Testing was performed in two separate sessions with the order counterbalanced. Step length, stride length, gait cycle time, and coefficient of variation (CV) for each were measured using OptoGait software, and both reaction time and accuracy for the two cognitive tests were assessed. Dual Task Cost (DTC) was calculated by using the formula (Single task score - Dual task score)/Single task score)*100. RESULTS: Younger adults had faster reaction time compared to older adults for both Working Memory and Inhibition tests (p < 0.05), and both males and females had slower reaction time for the Working Memory test when seated compared to walking (p < 0.05). For DTC, older adults had greater stride length CV during the Working Memory task (32.0 % vs 19.6 %), and regardless of age or sex, DTC for gait was greater than for cognition. SIGNIFICANCE: These data provide evidence that while aging does decrease reaction time while dual tasking, few age differences and no sex differences were found in dual task cost. However, dual tasking results in diminished gait DTC compared to cognition DTC regardless of age or sex.

Is pregnancy brain real? Comparison of dual task cost during overground walking in pregnant versus control women.

BACKGROUND: Many pregnant women report that their memory is impaired compared to non-pregnancy, but results of studies of cognitive abilities are mixed. The effect of pregnancy on dual tasking, or performance of two tasks simultaneously, has not been studied, however. RESEARCH QUESTION: What is the effect of walking overground at a self-selected speed while also performing a cognitive task on gait and cognitive performance during 3rd trimester of pregnancy compared to non-pregnant controls? METHODS: A total of n = 22 3rd trimester pregnant women (mean 33.3 ± 3.3 weeks gestation, age 32.1 ± 4.7 years) and n = 21 non-pregnant controls (age 31.9 ± 3.3 years) were recruited to participate. All participants performed single task walking on a GAITRite gait analysis system and performed three cognitive tests while walking: serial 3 and 7 subtraction tests and a phoneme monitoring test. Participants completed the same assessments while seated and order of the testing was counterbalanced. Dual task cost (DTC) was calculated using the formula (Single task score - Dual task score)/Single task score)*100. Independent t-tests or Mann Whitney U tests were used to compare the two groups depending on normality of data. RESULTS: There were no significant differences in cognitive test performance between control and pregnant women while walking or seated (p > 0.05). There were no significant differences between groups for DTC during any cognitive tests, but DTC was significantly greater for walking velocity in pregnant women compared to controls for serial 3 (p < 0.001) and serial 7 (p = 0.005) but not phoneme monitoring (p = 0.061). SIGNIFICANCE: Pregnant women had elevated cost of dual tasking, though the decrements were not in cognitive tests but in gait, specifically with greater DTC of walking velocity. This suggests that pregnant women modify their walking velocity to preserve cognitive function during activities requiring focus on both cognitive and physical tasks.

Walking Cadence during Moderate-Intensity Physical Activity in Pregnant Women.

Evidence has established that a cadence of 100 steps/min is indicative of the moderate intensity threshold of 3 metabolic equivalents (METs), but this has only been described in non-pregnant individuals. As metabolic alterations are well established during pregnancy, the purpose of this study was to determine if the walking cadence equivalent to 3 METs in pregnant women is similar to non-pregnant populations. Pregnant females (n = 29; age = 30.3 ± 3.2 years, gestational age = 23.9 ± 6.6 weeks) in their second or third trimester (>12 weeks gestation) completed three stages of treadmill walking for 5 min at different standardized walking speeds: 2.5, 3.0, and 3.5 miles per hour (mph). Oxygen consumption (VO2) and heart rate (HR) were measured each minute and METs were calculated for each stage. Real-time continuous monitoring of walking cadence was evaluated by an OptoGait gait analysis system. Following the three standardized speed stages, participants completed an additional stage walking at a speed that elicited 100 steps/min; VO2 and HR were also collected. A one-sample t-test was used to compare MET values at each stage to the heuristic 3 MET cutoff, and Pearson correlation coefficient was calculated to evaluate the relationship between cadence and METs. Mean cadence increased linearly across the three stages (2.5 mph = 103.7 ± 4.5, 3.0 mph = 112.5 ± 5.3, and 3.5 mph = 120.4 ± 6.2 steps/min), as did METs (2.5 mph = 2.7 ± 1.7, 3.0 mph = 3.2 ± 0.8, and 3.5 mph = 4.3 ± 1.8 METs) regardless of trimester. The average treadmill speed at which women walked at 100 steps/min was 2.4 ± 0.4 mph which elicited an oxygen consumption of 9.5 mL•kg-1•min-1, or 2.7 ± 0.7 METs. There was no significant difference between METs at 3.0 mph and the conventional 3 MET cut point for moderate-intensity PA (p < 0.05). There was a moderate and significant relationship between METs and cadence (2nd trimester: r = 0.51; 3rd trimester: r = 0.42). Current data indicate for the first time that the traditionally used 3 MET cutoff for moderate-intensity activity is appropriate for pregnant women despite metabolic alterations associated with pregnancy. This may have important implications for exercise prescription in pregnant populations.

Dexpanthenol in Wound Healing after Medical and Cosmetic Interventions (Postprocedure Wound Healing).

With the availability of new technologies, the number of subjects undergoing medical and cosmetic interventions is increasing. Many procedures (e.g., ablative fractional laser treatment) resulting in superficial/minor wounds require appropriate aftercare to prevent complications in wound healing and poor cosmetic outcome. We review the published evidence of the usefulness of topical dexpanthenol in postprocedure wound healing and the associated mechanisms of action at the molecular level. A search in the PubMed and Embase databases was performed to query the terms dexpanthenol, panthenol, superficial wound, minor wound, wound healing, skin repair, and postprocedure. Search results were categorized as clinical trials and in vitro studies. In vitro and clinical studies provided evidence that topically applied dexpanthenol promotes superficial and postprocedure wound healing. Latest findings confirmed that dexpanthenol upregulates genes that are critical for the healing process. The gene expression data are of clinical relevance as evidenced by prospective clinical studies indicating that topical dexpanthenol accelerates wound healing with rapid re-epithelialization and restoration of skin barrier function following skin injury. It can therefore be inferred that topical dexpanthenol represents an appropriate and state-of-the-art treatment option for superficial postprocedure wounds, especially when applied early after the superficial skin damage.

Cross-reactivity patterns of T cells specific for iodinated contrast media.

BACKGROUND: Approximately 3% of patients exposed to iodinated contrast media develop delayed hypersensitivity reactions. OBJECTIVE: We wanted to better understand the molecular basis of contrast media cross-reactivity. METHODS: Cross-reactivity was assessed by skin testing and measurement of T-cell activation (CD69 upregulation) and proliferation ((3)H-thymidine uptake, 5,6-carboxyfluorescein diacetate succinimidyl ester staining) of PBMCs, T-cell lines, and T-cell clones of 2 patients with delayed hypersensitivity reactions to iohexol and iomeprol, respectively. Thirteen different contrast media and potassium iodide were compared. RESULTS: Skin testing and analyses of PBMCs, T-cell lines, and clones showed broad cross-reactivity in both patients. Broad as well as more restricted cross-reactivity patterns were found in iohexol-specific and iomeprol-specific CD4(+) T-cell clones, whereas 1 iomeprol-specific CD8(+) T-cell clone showed no cross-reactivity at all. The reactivity to equimolar concentrations of iohexol and its dimer iodixanol was very similar, suggesting that the dimer was not more stimulatory than its monomer. Consistently low reactivity to iobitridol was found in both patients, but never to iodide. A frequency analysis of contrast medium-specific peripheral T cells gave values between 0.6 % (iomeprol) and 0.05 % (iobitridol). CONCLUSION: Clinically observed cross-reactivity between different contrast media is a result of the presence of contrast media-specific T cells, some of which show a broad cross-reactivity pattern. Iodide ions, known to be present at low concentration in contrast media solutions, do not seem to be the causative moiety. CLINICAL IMPLICATIONS: Detailed in vitro analysis might help identify noncross-reactive contrast media.

Hypersensitivity reactions to quinolones.

Quinolones are one of the most important classes of antimicrobial agents discovered in the recent years and one of the most widely used classes of antibiotics in clinical medicine. Their broad spectrum of activity and pharmacokinetic properties make them ideal agents for treating a variety of infections. Their clinical importance is further demonstrated by their activity against a wide range of diseases of public health importance such as anthrax, tuberculosis, bacterial pneumonia, and sexually transmitted diseases. Like other antibiotics, quinolones can cause various, sometimes dangerous hypersensitivity reactions. The underlying pathomechanisms are only poorly understood. Some are thought to be partly non-immune mediated reactions, others are considered to be IgE- or T cell-mediated reactions. This review gives an insight into the different immunological mechanisms leading to the diverse symptoms of quinolone-induced hypersensitivity reactions, with special emphasis on the role of T cells in such reactions.

Transfection of drug-specific T-cell receptors into hybridoma cells: tools to monitor drug interaction with T-cell receptors and evaluate cross-reactivity to related compounds.

In the context of drug hypersensitivity, our group has recently proposed a new model based on the structural features of drugs (pharmacological interaction with immune receptors; p-i concept) to explain their recognition by T cells. According to this concept, even chemically inert drugs can stimulate T cells because certain drugs interact in a direct way with T-cell receptors (TCR) and possibly major histocompatibility complex molecules without the need for metabolism and covalent binding to a carrier. In this study, we investigated whether mouse T-cell hybridomas transfected with drug-specific human TCR can be used as an alternative to drug-specific T-cell clones (TCC). Indeed, they behaved like TCC and, in accordance with the p-i concept, the TCR recognize their specific drugs in a direct, processing-independent, and dose-dependent way. The presence of antigen-presenting cells was a prerequisite for interleukin-2 production by the TCR-transfected cells. The analysis of cross-reactivity confirmed the fine specificity of the TCR and also showed that TCR transfectants might provide a tool to evaluate the potential of new drugs to cause hypersensitivity due to cross-reactivity. Recombining the alpha- and beta-chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original alpha- and beta-chains were involved in drug binding. The TCR-transfected hybridoma system showed that the recognition of two important classes of drugs (sulfanilamides and quinolones) by TCR occurred according to the p-i concept and provides an interesting tool to study drug-TCR interactions and their biological consequences and to evaluate the cross-reactivity potential of new drugs of the same class.

Pharmacological interaction of drugs with immune receptors: the p-i concept.

Drug-induced hypersensitivity reactions have been explained by the hapten concept, according to which a small chemical compound is too small to be recognized by the immune system. Only after covalently binding to an endogenous protein the immune system reacts to this so called hapten-carrier complex, as the larger molecule (protein) is modified, and thus immunogenic for B and T cells. Consequently, a B and T cell immune response might develop to the drug with very heterogeneous clinical manifestations. In recent years, however, evidence has become stronger that not all drugs need to bind covalently to the MHC-peptide complex in order to trigger an immune response. Rather, some drugs may bind directly and reversibly to immune receptors like the major histocompatibility complex (MHC) or the T cell receptor (TCR), thereby stimulating the cells similar to a pharmacological activation of other receptors. This concept has been termed pharmacological interaction with immune receptors the (p-i) concept. While the exact mechanism is still a matter of debate, non-covalent drug presentation clearly leads to the activation of drug-specific T cells as documented for various drugs (lidocaine, sulfamethoxazole (SMX), lamotrigine, carbamazepine, p-phenylendiamine, etc.). In some patients with drug hypersensitivity, such a response may occur within hours even upon the first exposure to the drug. Thus, the reaction to the drug may not be due to a classical, primary response, but rather be mediated by stimulating existing, pre-activated, peptide-specific T cells that are cross specific for the drug. In this way, certain drugs may circumvent the checkpoints for immune activation imposed by the classical antigen processing and presentation mechanisms, which may help to explain the peculiar nature of many drug hypersensitivity reactions.