Perceived Instability, Pain, and Psychological Factors Predict Function and Disability in Individuals with Chronic Ankle Instability

Context: Chronic ankle instability (CAI) is associated with residual instability, pain, decreased function, and increased disablement. Injury-related fear has been associated with CAI, although its relationship to other impairments is unclear. The Fear-Avoidance Model is a theoretical framework hypothesizing a relationship between injury-related fear, chronic pain, pain catastrophizing, and disability. It has been useful in understanding fear\u27s influence in other musculoskeletal conditions but has yet to be studied in those with CAI. Objective: To explore relationships between instability, pain catastrophizing, injury-related fear, pain, ankle function, and global disability in individuals with CAI. Design: Cross-Sectional Study Setting: Anonymous online survey Patients or Other Participants: A total of 259 people, recruited via e-mail and social media, with a history of ankle sprain completed the survey; of those, 126 participants (age=32.69±4.38, female=84.92%, highly active=73.81%) were identified to have CAI and were included in the analysis. Main Outcome Measure(s): Demographics included gender identity, age, and physical activity level. Assessments encompassed the Identification of Functional Ankle Instability (instability), the Pain Catastrophizing Scale (pain catastrophizing), the Tampa Scale of Kinesiophobia-11 (injury-related fear), a numeric pain rating scale and activity-based question (pain presence), the Quick-FAAM (ankle function), and the modified Disablement in the Physically Active Scale (disability). Relationships between variables were explored through correlation and regression analyses. Results: After controlling for instability and pain, pain catastrophizing and injury-related fear were significantly related to function and disability ratings in individuals with CAI. Together, the variables predicted 48.7% (P\u3c.001) variance in function and 44.2% (P\u3c.001) variance in disability. Conclusions: Greater instability, pain, greater pain catastrophizing, and greater injury-related fear were predictive of decreased function and greater disability in those with CAI. This is consistent with the hypothesized relationships in the Fear-Avoidance Model, although further investigation is needed to determine causality of these factors in the development of CAI

Drosophila Activated Cdc42 Kinase Has an Anti-Apoptotic Function

Activated Cdc42 kinases (Acks) are evolutionarily conserved non-receptor tyrosine kinases. Activating somatic mutations and increased ACK1 protein levels have been found in many types of human cancers and correlate with a poor prognosis. ACK1 is activated by epidermal growth factor (EGF) receptor signaling and functions to regulate EGF receptor turnover. ACK1 has additionally been found to propagate downstream signals through the phosphorylation of cancer relevant substrates. Using Drosophila as a model organism, we have determined that Drosophila Ack possesses potent anti-apoptotic activity that is dependent on Ack kinase activity and is further activated by EGF receptor/Ras signaling. Ack anti-apoptotic signaling does not function through enhancement of EGF stimulated MAP kinase signaling, suggesting that it must function through phosphorylation of some unknown effector. We isolated several putative Drosophila Ack interacting proteins, many being orthologs of previously identified human ACK1 interacting proteins. Two of these interacting proteins, Drk and yorkie, were found to influence Ack signaling. Drk is the Drosophila homolog of GRB2, which is required to couple ACK1 binding to receptor tyrosine kinases. Drk knockdown blocks Ack survival activity, suggesting that Ack localization is important for its pro-survival activity. Yorkie is a transcriptional co-activator that is downstream of the Salvador-Hippo-Warts pathway and promotes transcription of proliferative and anti-apoptotic genes. We find that yorkie and Ack synergistically interact to produce tissue overgrowth and that yorkie loss of function interferes with Ack anti-apoptotic signaling. Our results demonstrate how increased Ack signaling could contribute to cancer when coupled to proliferative signals

Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss

The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells

Preventive Training Program Feedback Complexity, Movement Control, and Performance in Youth Athletes

Context: Preventive training programs (PTPs) reduce injury risk by improving movement control. Corrective feedback is important; however, many cues at once may be too complicated for athletes. Objective: To compare movement control and long-jump (LJ) changes in youth athletes participating in a season-long PTP, with simplified feedback, traditional feedback, or a warmup of the coaches\u27 choosing. Design: Cluster-randomized controlled trial. Setting: Soccer fields. Patients or Other Participants: A total of 420 athletes (simplified feedback = 173, traditional feedback = 118, and control = 129; age = 11 ± 3 years). Intervention(s): Teams were randomized into the simplified PTP, traditional PTP, or control group. Simplified and traditional PTPs lasted 10 to 12 minutes and used the same exercises. The simplified PTP provided only sagittal-plane feedback (eg, “get low”), and the traditional PTP provided feedback targeting all motion planes (eg, “don\u27t let your knees cave inward”). Research assistants administered the PTP warmups 2 to 3 times/week for the season. Control team coaches chose and ran their own warmup strategies. Main Outcome Measure(s): Participants completed 4 sessions (preseason [PRE], postseason [POST] at approximately 8 weeks after PRE, retention 1 [R1] at 6 weeks postseason, and retention 2 [R2] at 12 weeks postseason). They performed 3 trials of a jump-landing task, which was evaluated using the Landing Error Scoring System (LESS) and 2 recorded standing LJ trials at each test session. A time series panel was used to evaluate group differences across time points for the LESS and LJ. Results: Change score analyses revealed improvements in the LESS score from PRE to POST for all groups. Improvements from PRE were retained at R1 and R2 for the intervention groups (simplified and traditional). The traditional group demonstrated better LJ performance at POST (P \u3c .001) and R1 (P = .049) than the simplified or control group. Conclusions; Simplified cues were as effective as traditional cues in improving LESS scores from PRE to POST season. Participating in PTPs, regardless of their complexity, likely provides movement benefits

The Effects of Physical Exercise on Salivary microRNA Levels

Diagnosing concussions provides challenges for healthcare professionals due to current diagnostic protocols utilizing subjective input from patients. Recent studies have shown relationships between specific salivary microRNA levels and concussions, but it is unknown if this is due to concussive forces or physical exertion. Analysis of this distinction may contribute to further confirming the relationship of concussions and microRNA, improving techniques for objective assessments of concussion. Objective: To measure the effects of physical exertion through exercise on specific salivary microRNA. Methods: Twenty non-intercollegiate athletes (10:M, 10:F) were recruited for this case series. After ensuring the participants received a minimum of 6-hours of sleep the previous night, a baseline salivary sample was taken with the p-157: Nucleic acid stabilization kit (DNA Genotek; Ottawa, Canada). Participants completed a graded exercise test on a treadmill following the Bruce Protocol (VO2-Max). Participants began walking and investigators gradually increased the intensity at regular 3-minute intervals. Intensity increases were achieved by increasing both the speed and incline of the treadmill until maximal physical exhaustion was achieved. Physiological measures were measured to ensure safety. Immediately following the graded exercise test, a second salivary sample was collected. All samples were sent to Quadrant Biosciences for analysis and NextGen sequencing. Upon receiving normalized data from Quadrant Biosciences (Syracuse, NY), investigators performed paired t-tests (α Conclusions: The findings of this study reinforce the relationship between 6 salivary microRNA and concussions. The body of evidence of the aforementioned salivary microRNA’s relationship to concussions is strengthened as no significant differences were found, indicating the concentration of the 6 salivary microRNA are not affected by exercise.https://digitalcommons.odu.edu/gradposters2020_healthsciences/1001/thumbnail.jp

Pre-vaccination prevalence of anogenital and oral human papillomavirus in young HIV-infected men who have sex with men.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325

Relation Between Age and Unplanned Readmissions After Percutaneous Coronary Intervention (Findings from the Nationwide Readmission Database))

Acknowledgements: We are grateful to the Healthcare Cost and Utilization Project (HCUP) and the HCUP Data Partners for providing the data used in the analysis. List of Supports/Grants Information: The study was supported by a grant from the Research and Development Department at the Royal Stoke Hospital. This work is conducted as a part of PhD for CSK which is supported by Biosensors International.Peer reviewedPostprin

Parabacteroides distasonis:intriguing aerotolerant gut anaerobe with emerging antimicrobial resistance and pathogenic and probiotic roles in human health

Parabacteroides distasonis is the type strain for the genus Parabacteroides, a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as Bacteroides distasonis, the strain was re-classified to form the new genus Parabacteroides in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (P. acidifaciens, P. chartae, P. chinchillae, P. chongii, P. distasonis, P. faecis, P. goldsteinii, P. gordonii, P. johnsonii, and P. merdae) and 5 'not validly named' (P. bouchesdurhonensis, P. massiliensis, P. pacaensis, P. provencensis, and P. timonensis) by the List of Prokaryotic names with Standing in Nomenclature. The Parabacteroides genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of P. distasonis on human and animal health

Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis

Objective: To compare the effects of interleukin 6 receptor blockers, tocilizumab and sarilumab, with or without corticosteroids, on mortality in patients with covid-19. Design: Systematic review and network meta-analysis. Data sources: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses (up to 9 June 2021). Review methods: Trials in which people with suspected, probable, or confirmed covid-19 were randomised to interleukin 6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. The analysis used a bayesian framework and assessed the certainty of evidence using the GRADE approach. Results from the fixed effect meta-analysis were used for the primary analysis. Results: Of 45 eligible trials (20 650 patients) identified, 36 (19 350 patients) could be included in the network meta-analysis. Of 36 trials, 27 were at high risk of bias, primarily due to lack of blinding. Tocilizumab, in combination with corticosteroids, suggested a reduction in the risk of death compared with corticosteroids alone (odds ratio 0.79, 95% credible interval 0.70 to 0.88; 35 fewer deaths per 1000 people, 95% credible interval 52 fewer to 18 fewer per 1000; moderate certainty of evidence), as did sarilumab in combination with corticosteroids, compared with corticosteroids alone (0.73, 0.58 to 0.92; 43 fewer per 1000, 73 fewer to 12 fewer; low certainty). Tocilizumab and sarilumab, each in combination with corticosteroids, appeared to have similar effects on mortality when compared with each other (1.07, 0.86 to 1.34; eight more per 1000, 20 fewer to 35 more; low certainty). The effects of tocilizumab (1.12, 0.91 to 1.38; 20 more per 1000, 16 fewer to 59 more; low certainty) and sarilumab (1.07, 0.81 to 1.40; 11 more per 1000, 38 fewer to 55 more; low certainty), when used alone, suggested an increase in the risk of death. Conclusion: These findings suggest that in patients with severe or critical covid-19, tocilizumab, in combination with corticosteroids, probably reduces mortality, and that sarilumab, in combination with corticosteroids, might also reduce mortality. Tocilizumab and sarilumab, in combination with corticosteroids, could have similar effectiveness. Tocilizumab and sarilumab, when used alone, might not be beneficial.This project is supported by two Canadian Institutes of Health Research grants (VR4-172738; MM1-174897). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.publishedVersio

A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.Seventh Framework Programme (European Commission) (Grant HEALTH-F5-2010-258236-SYSCOL)Seventh Framework Programme (European Commission) (Grant HEALTH-F2-2011-259015-COLTHERES)Cellex FoundationOlga Torres FoundationEuropean Research Council (EPINORC Project Grant Agreement 268626)Spain. Ministerio de Economia y Competividad (MINECO Project SAF2011-22803)Institute of Health Carlos III (RTICC Grant RD12/0036/0039