Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohn's disease in an Australian population

BACKGROUND: The first major Crohn's disease (CD) susceptibility gene, NOD2, implicates the innate intestinal immune system and other pattern recognition receptors in the pathogenesis of this chronic, debilitating disorder. These include the Toll-like receptors, specifically TLR4 and TLR5. A variant in the TLR4 gene (A299G) has demonstrated variable association with CD. We aimed to investigate the relationship between TLR4 A299G and TLR5 N392ST, and an Australian inflammatory bowel disease cohort, and to explore the strength of association between TLR4 A299G and CD using global meta-analysis. METHODS: Cases (CD = 619, ulcerative colitis = 300) and controls (n = 360) were genotyped for TLR4 A299G, TLR5 N392ST, and the 4 major NOD2 mutations. Data were interrogated for case-control analysis prior to and after stratification by NOD2 genotype. Genotype-phenotype relationships were also sought. Meta-analysis was conducted via RevMan. RESULTS: The TLR4 A299G variant allele showed a significant association with CD compared to controls (P = 0.04) and a novel NOD2 haplotype was identified which strengthened this (P = 0.003). Furthermore, we identified that TLR4 A299G was associated with CD limited to the colon (P = 0.02). In the presence of the novel NOD2 haplotype, TLR4 A299G was more strongly associated with colonic disease (P < 0.001) and nonstricturing disease (P = 0.009). A meta-analysis of 11 CD cohorts identified a 1.5-fold increase in risk for the variant TLR4 A299G allele (P < 0.00001). CONCLUSIONS: TLR 4 A299G appears to be a significant risk factor for CD, in particular colonic, nonstricturing disease. Furthermore, we identified a novel NOD2 haplotype that strengthens the relationship between TLR4 A299G and these phenotypes.     

Profiling of β-Lactam Selectivity for Penicillin-Binding Proteins in Streptococcus pneumoniae D39

Selective fluorescent β-lactam chemical probes enable the visualization of the transpeptidase activity of penicillin-binding proteins (PBPs) at different stages of bacterial cell division. To facilitate the development of new fluorescent probes for PBP imaging, we evaluated 20 commercially available β-lactams for selective PBP inhibition in an unencapsulated derivative of the D39 strain of Streptococcus pneumoniae. Live cells were treated with β-lactam antibiotics at different concentrations and subsequently incubated with Bocillin FL (Boc-FL; fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems (doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six of the nine penicillin compounds were coselective for PBP2x and PBP3. In contrast, the seven cephalosporin compounds tested display variability in their PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of S. pneumoniae cultures with a sublethal concentration of cefuroxime that inhibited 60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in formation of elongated cells. In contrast, treatment of S. pneumoniae cultures with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3 activity and less than 30% of other PBPs resulted in no discernible morphological changes. Additionally, correlation of the MIC and IC₅₀s for each PBP, with the exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.     

Social Support From the Athletic Trainer and Symptoms of Depression and Anxiety at Return to Play

Context:

Few empirical studies have examined social support from athletic trainers (ATs) and its buffering effect during injury recovery.

Objective:

To examine the effect of social support received from ATs during injury recovery on reported symptoms of depression and anxiety at return to play among a cohort of collegiate athletes.

Design:

Cohort study.

Setting:

Two Big 10 Conference universities.

Patients or Other Participants:

A total of 594 injuries sustained by 387 collegiate athletes (397 injuries by 256 males, 197 injuries by 131 females) on 9 sports teams.

Main Outcome Measure(s):

Data were collected during the 2007–2011 seasons. Social support was measured using the 6-item Social Support Questionnaire. Symptoms of depression were assessed using the Center for Epidemiological Studies Depression Scale. Anxiety was measured by the State-Trait Anxiety Inventory. We used generalized estimation equation regression models to examine the effect of the social support from ATs on the odds of symptoms of depression and anxiety at return to play.

Results:

In 84.3% (n = 501) of injury events, injured athletes received social support from ATs during their recovery. Of these, 264 (53.1%) athletes reported being very satisfied with this social support. Whether or not athletes received social support from ATs during recovery did not affect the symptoms of depression or anxiety experienced at return to play. However, compared with athletes who were dissatisfied with the social support received from ATs, athletes who were very satisfied or satisfied with this social support were 87% (95% confidence interval = 0.06, 0.30) and 70% (95% confidence interval = 0.13, 0.70) less likely to report symptoms of depression at return to play, respectively. Similar results were observed for anxiety.

Conclusions:

Our findings support the buffering effect of social support from ATs and have important implications for successful recovery in both the physical and psychological aspects for injured athletes.Key Words: collegiate athletes, psychological distress, coping, injury recovery

Key Points

• More than 80% of injured athletes in this study relied on social support from their athletic trainers during their recovery.
• Athletes who reported higher levels of satisfaction with the social support from their athletic trainers during recovery were less likely to experience symptoms of depression and anxiety at return to play.
• However, whether or not injured athletes received social support from athletic trainers during their injury recovery did not correlate with psychological outcomes at return to play.

Approximately 40% to 50% of collegiate athletes sustain at least 1 injury requiring medical attention or restricting participation for 1 day or more (or both) during their athletic careers.¹ In addition to negative physical consequences, these injuries often cause psychological disturbances among injured athletes, including depression and anxiety, which in turn play a role in their injury recovery.^2–4 Results from previous studies show that social support is an important coping resource for athletes dealing with psychological recovery from an injury.^5–9 Social support could “buffer” the effect of stress on injured athletes and thus indirectly influence their emotional wellbeing. In other words, social support could first help an injured athlete interpret an injury event as less stressful than he or she otherwise would, thus helping to reduce distress after an injury. Second, social support could help an injured athlete cope with the injury and improve motivation during rehabilitation.^8,9 Growing evidence also suggests that emotional social support, defined as expressions of empathy, love, trust, and caring,^10,11 may be crucial to recovery for injured collegiate athletes; other types of social support, including instrumental support (ie, provision of tangible aid and services) and informational support (ie, provision of advice, suggestions, and information), may be available to injured collegiate athletes as part of injury treatment.^10,11 However, although many universities provide psychological services to their students, including injured student–athletes, the psychologists are not always specially trained in the areas of sport and exercise and may not fulfill the injured athletes'' needs. Thus, certified athletic trainers (ATs), who are active in the day-to-day tasks of prevention, recognition, management, and rehabilitation of injuries among athletes, become an important source of emotional social support for injured athletes.¹¹Advances in sport medicine have reduced the average time required for physical healing from an athletic injury, yet a rapid physical recovery may not provide sufficient time for psychological recovery. Current practices in evaluation and management of injuries address the physical problems underlying an injury and return athletes to full participation as soon as possible, but psychological assessment or care is not usually included.^12,13 The potential discrepancy between physical healing and psychological recovery necessitates that more attention be given to the latter.¹³ We need to better understand how athletes respond to athletic injury and how external factors, such as social support, may affect athletes'' postinjury psychological status and facilitate their injury recovery. Yet relatively few empirical studies have directly examined social support from ATs and its buffering effect during injury recovery among competitive collegiate athletes.^11,12The aim of our study was 2-fold: (1) to describe the social support that injured collegiate athletes received from their ATs during their injury recovery and their satisfaction with such support and (2) to examine the effect of this social support from ATs during the recovery on reported symptoms of depression and anxiety at return to play.     

Age of Barrier Canyon-style rock art constrained by cross-cutting relations and luminescence dating techniques

Rock art compels interest from both researchers and a broader public, inspiring many hypotheses about its cultural origin and meaning, but it is notoriously difficult to date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are among the most debated examples; hypotheses about its age span the entire Holocene epoch and previous attempts at direct radiocarbon dating have failed. We provide multiple age constraints through the use of cross-cutting relations and new and broadly applicable approaches in optically stimulated luminescence dating at the Great Gallery panel, the type section of BCS art in Canyonlands National Park, southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation of the alcove containing the panel, and limits are also set by our related research dating both a rockfall that removed some figures and the rock’s exposure duration before that time. Results provide a maximum possible age, a minimum age, and an exposure time window for the creation of the Great Gallery panel, respectively. The only prior hypothesis not disproven is a late Archaic origin for BCS rock art, although our age result of A.D. ∼1–1100 coincides better with the transition to and rise of the subsequent Fremont culture. This chronology is for the type locality only, and variability in the age of other sites is likely. Nevertheless, results suggest that BCS rock art represents an artistic tradition that spanned cultures and the transition from foraging to farming in the region.Archaeology is focused upon material records, contextualized in time. Rock art is a record with the potential to provide unique insight into the dynamics and evolution of culture, but it generally lacks stratigraphic or chronologic context. Interpretation of the origin and meaning of rock art is indirect at best, or simply speculative. In the case of some pictographs, pigments may include or have enough accessory carbon for accelerator mass spectrometry (AMS) radiocarbon dating (1–4). In other special situations, such as caves, minimum age constraints have been obtained by various techniques of dating material that overlies or entombs rock art (5–7). However, most rock art remains undatable and researchers rely upon stylistic comparison and indirect associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the most compelling and debated rock art in the United States—the Barrier Canyon style (BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have failed and its age remains unknown, with widely ranging hypotheses that have remained untested until now.The continued development of dating techniques offers new possibilities for hypothesis testing. The optically stimulated luminescence (OSL) signals from mineral grains make it possible to date the deposition of most sediment that is exposed to a few seconds of full sunlight before burial, and its use in the earth and cultural sciences has greatly increased (10, 11). Among the latest applications of OSL are techniques dating the outer surfaces of rock clasts that have become shielded from light, including those with archaeological context (12–15). Recent work has furthermore used the “bleaching” profile of decreasing luminescence signal toward the surface of rock to estimate exposure time to sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new insight into past cultures and landscapes.Here, we synthesize results from three approaches to dating the type section of BCS art, the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the full alluvial stratigraphy and a rockfall event that both have incontrovertible cross-cutting relations with the rock art, and then by determining the exposure duration of a painted rock surface, we greatly narrow the window of time when the rock art was created. These approaches do not require direct sampling of rock art and have strong potential for application to other archaeological and surface processes research. Although our results are only for the type section of BCS art, and chronological variability should be expected for the style across the region, they suggest that BCS art coincides with the transition to agriculture in the northern Colorado Plateau and may not have been limited to a specific archaeological culture.