Don’t Peak Too Early : Evidence for an ACL Injury Prevention Mechanism of the 11+ Program

Funding Information: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (award number R01AR072034). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by grant R37-HD037985 from the National Institute of Health. This work was supported by the Ice-landic Research Fund, grant numbers 120410021, 903271305, 1203250031, and 185359051. Funding Information: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (award number R01AR072034). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by grant R37-HD037985 from the National Institute of Health. This work was supported by the Icelandic Research Fund, grant numbers 120410021, 903271305, 1203250031, and 185359051. Publisher Copyright: © 2022, North American Sports Medicine Institute. All rights reserved.Background The 11+ program prevents anterior cruciate ligament (ACL) injuries in athletes through unknown mechanisms. Purpose The aim of the current study was to evaluate the effects of The 11+ intervention program, performed by female soccer players during a single season, on the frequency of Early Peaks during athletic tasks. Methods Three teams (69 players) of collegiate female soccer athletes (Divisions I and II) were recruited. Two teams (49 players) volunteered to perform The 11+ three times per week for one season (~22 weeks plus three weeks pre-season), and one team (20 players) served as controls. The athletes performed three repetitions of a cutting maneuver, side shuffle direction change, and forwards to backwards running direction change before and after the competitive season and were recorded using marker-based 3D motion capture. Knee valgus moment time series were calculated for each repetition with inverse kinematics and classified as either “Very Early Peak”, “Early Peak” or “other” using cluster analysis. The classification was based timing of the peak relative to the timing of ACL injuries. The effect of the intervention on the frequency of Very Early Peaks and Early Peaks was evaluated with a mixed Poisson regression controlling for the movement task and pre-season frequency. Results The 11+ intervention reduced the frequency of Early Peak knee valgus moment in one intervention team (coefficient =-1.16, p = 0.004), but not the other (coefficient =-0.01, p = 0.977). No effect was observed on the frequency of Very Early Peak knee valgus moment. Conclusions Reduced frequency of knee valgus moment Early Peak during athletic tasks may explain the mechanism by which The 11+ program decreases risk of ACL injury. Prospective studies with a much larger sample size are required to establish a link between Early Peak knee valgus moments and risk of ACL injury. Level of evidence 2b.Peer reviewe

Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer

Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR-26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers (36 luminal A-like, 13 luminal B-like, 5 HER2-enriched, 16 basal-like) and 18 normal mammoplasty tissues. Significantly reduced expression of miR-29c distinguished basal-like breast cancers from other breast cancer molecular subtypes. The expression of aberrant DNA hypermethylation was determined in a subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched and 16 basal-like) through examination of methylation-sensitive biomarker gene expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33 (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal-like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1; HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%) basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished levels of ≥6 regulatory miRs. The results show that i) reduced expression of miR-29c is characteristic of basal-like breast cancers, ii) miR and methylation-sensitive gene expression patterns identify two subsets of basal-like breast cancers, and iii) the subset of basal-like breast cancers with reduced expression of multiple regulatory miRs express aberrant DNA hypermethylation. Together, these findings strongly suggest that the molecular mechanism governing the DNMT3b-mediated aberrant DNA hypermethylation in primary breast cancer involves the loss of post-transcriptional regulation of DNMT3b by regulatory miRs

Markerless motion capture: What clinician-scientists need to know right now

National Institutes of Health R37-HD037985 provided tuition and stipend support for NI’s work. NIH R01-AR072034 provided stipend support for HBS and tuition and stipend support for KDS’s work. NIH F31-AR078580 and Foundation for Physical Therapy Research PODS II Scholarship provided tuition and stipend support for EKA's work.Peer reviewe

The effect of periodontal therapy on lymphocyte blastogenesis to plaque associated microorganisms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66105/1/j.1600-0765.1983.tb00340.x.pd

Blinding Techniques in Randomized Controlled Trials of Laser Therapy: An Overview and Possible Solution

Low-level laser therapy has evidence accumulating about its effectiveness in a variety of medical conditions. We reviewed 51 double blind randomized controlled trials (RCTs) of laser treatment. Analysis revealed 58% of trials showed benefit of laser over placebo. However, less than 5% of the trials had addressed beam disguise or allocation concealment in the laser machines used. Many of the trials used blinding methods that rely on staff cooperation and are therefore open to interference or bias. This indicates significant deficiencies in laser trial methodology. We report the development and preliminary testing of a novel laser machine that can blind both patient and operator to treatment allocation without staff participation. The new laser machine combines sealed preset and non-bypassable randomization codes, decoy lights and sound, and a conical perspex tip to overcome laser diode glow detection

Barriers and facilitators associated with implementing interventions to support oral anticancer agent adherence in academic and community cancer center settings

Purpose The goal of this study is to determine barriers and facilitators to the implementation of medication adherence interventions to support cancer patients taking novel, targeted oral anticancer agents (OAAs). Methods We conducted qualitative interviews using a semi-structured guide from the Consolidated Framework for Implementation Research (CFIR). We used purposive sampling to identify clinicians (physicians, pharmacists, nurse practitioners, nurses) and administrators (leadership from medicine, pharmacy, and nursing) who delivered care and/or oversee care delivery for patients with chronic leukemia prescribed an OAA. Results A total of 19 individuals participated in an interview (12 clinicians and 7 administrators), with 10 primarily employed by an academic cancer center; 5 employed by the community cancer center; and 4 employed by the integrated health-system specialty pharmacy. Barriers identified included low awareness of adherence interventions, difficulty in adherence measurement, complexity of designing and implementing a structured adherence intervention, and competing priorities. Facilitators identified included support of hospital administrators, value for pharmacists, and willingness to embrace change. Participants also made recommendations moving forward including standardizing workflow, designating champions, iterating implementation strategies, and improving communication between clinicians and with patients. Conclusion Individual and system level factors were identified as determinants of implementation effectiveness of medication adherence interventions. A multidisciplinary advisory panel will be assembled to design comprehensive and actionable strategies to refine and implement a structured intervention to improve medication adherence in cancer patients

Zinc finger protein ZBTB20 expression is increased in hepatocellular carcinoma and associated with poor prognosis

<p>Abstract</p> <p>Background</p> <p>Our previous studies showed that ZBTB20, a new BTB/POZ-domain gene, could negatively regulate α feto-protein and other liver-specific genes, concerning such as bio-transformation, glucose metabolism and the regulation of the somatotropic hormonal axis. The aim of this study is to determine the potential clinical implications of ZBTB20 in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>Quantitative real-time RT-PCR and Western blot analyses were used to detect expression levels of ZBTB20 in 50 paired HCC tumorous and nontumorous tissues and in 20 normal liver tissues. Moreover, expression of ZBTB20 was assessed by immunohistochemistry of paired tumor and peritumoral liver tissue from 102 patients who had undergone hepatectomy for histologically proven HCC. And its relationship with clinicopathological parameters and prognosis was investigated.</p> <p>Results</p> <p>Both messenger RNA and protein expression levels of ZBTB20 were elevated significantly in HCC tissues compared with the paired non-tumor tissues and normal liver tissues. Overexpressed ZBTB20 protein in HCC was significantly associated with vein invasion (<it>P </it>= 0.016). Importantly, the recurrence or metastasis rates of HCCs with higher ZBTB20 expression were markedly greater than those of HCCs with lower expression (<it>P </it>= 0.003, <it>P </it>= 0.00015, respectively). Univariate and multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. The disease-free survival period and over-all survival period in patients with overexpressed ZBTB20 in HCC was significantly reduced.</p> <p>Conclusions</p> <p>The expression of ZBTB20 is increased in HCC and associated with poor prognosis in patients with HCC, implicating ZBTB20 as a candidate prognostic marker in HCC.</p

Sour Ageusia in Two Individuals Implicates Ion Channels of the ASIC and PKD Families in Human Sour Taste Perception at the Anterior Tongue

BACKGROUND:The perception of sour taste in humans is incompletely understood at the receptor cell level. We report here on two patients with an acquired sour ageusia. Each patient was unresponsive to sour stimuli, but both showed normal responses to bitter, sweet, and salty stimuli. METHODS AND FINDINGS:Lingual fungiform papillae, containing taste cells, were obtained by biopsy from the two patients, and from three sour-normal individuals, and analyzed by RT-PCR. The following transcripts were undetectable in the patients, even after 50 cycles of amplification, but readily detectable in the sour-normal subjects: acid sensing ion channels (ASICs) 1a, 1beta, 2a, 2b, and 3; and polycystic kidney disease (PKD) channels PKD1L3 and PKD2L1. Patients and sour-normals expressed the taste-related phospholipase C-beta2, the delta-subunit of epithelial sodium channel (ENaC) and the bitter receptor T2R14, as well as beta-actin. Genomic analysis of one patient, using buccal tissue, did not show absence of the genes for ASIC1a and PKD2L1. Immunohistochemistry of fungiform papillae from sour-normal subjects revealed labeling of taste bud cells by antibodies to ASICs 1a and 1beta, PKD2L1, phospholipase C-beta2, and delta-ENaC. An antibody to PKD1L3 labeled tissue outside taste bud cells. CONCLUSIONS:These data suggest a role for ASICs and PKDs in human sour perception. This is the first report of sour ageusia in humans, and the very existence of such individuals ("natural knockouts") suggests a cell lineage for sour that is independent of the other taste modalities