Archivum Immunologiae et Therapiae Experimentalis

Visfatin Plays a Significant Role in Alleviating Lipopolysaccharide-Induced Apoptosis and Autophagy Through PI3K/AKT Signaling Pathway During Acute Lung Injury in Mice Abstract Visfatin is involved in the body's inflammation and immune response. Inflammation could promote, while visfatin may directly or indirectly mitigate the effects of apoptosis and autophagy. Whether visfatin lessens the detrimental effects of lipopolysaccharide (LPS)-induced mouse acute lung injury (ALI) is poorly understood yet. Therefore, in the current study, the regulation mechanism of visfatin on apoptosis and autophagy was explored in Kunming mice by replicating LPS-induced inflammatory ALI model. Based on the mouse model of ALI, HE staining, TUNEL, transmission electron microscopy, immunohistochemical staining, real-time fluorescence quantitative PCR and western blot were used and the results showed that the alveolar septum was thinner than that of the LPS group, slight lung interstitial and alveolar exudation appeared, and a small number of inflammatory cell infiltration was found in the visfatin intervention group, indicating reduced tissue damage in lungs. After visfatin treatment, the expression of pro-apoptotic genes Bax, Bik, and p53 decreased and the expression of anti-apoptotic genes Bcl-2 and Bcl-xl increased, and expression of autophagy factors LC3 and Beclin1 decreased, indicating that visfatin inhibits apoptosis and reduces autophagy. The expression of PI3K and p-AKT was upregulated in the visfatin intervention group, the expression of AKT was downregulated, and the PI3K/AKT signaling pathway was activated. Hence, visfatin could activate the PI3K/AKT signaling pathway, reduce the apoptotic rate in alveolar epithelial cells and the level of autophagy in ALI by regulating the expression of autophagy factors, ultimately causing a protective effect on lung tissue.

MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases? Abstract MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18–22 nucleotides long and highly conserved throughout evolution. Currently, they are considered one of the fundamental regulatory mechanisms of genes expression. It has been demonstrated that miRNAs are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. More recently, the role of miRNA has also been revealed in numerous immunological and inflammatory disorders, including allergic inflammation. Specific miRNA profiles were demonstrated in asthma, allergic rhinitis and atopic dermatitis. A core set of miRNAs involved in atopic diseases include upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b, miR-155 and downregulated let-7 family, miR-193b and miR-375. Most of the involved miRNAs increase secretion of Th2 cytokines (miR-1248, miR-146b), decrease secretion of Th1 cytokines (miR-513-5p, miR-625-5p) or promote differentiation of T cells towards Th2 (miR-21, miR-19a). In asthma miR-140-3p, miR-708 and miR-142-3p play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. Some single miRNAs or, more probably, their sets hold the promise for their use as biomarkers of atopic diseases. They are also promising target of future therapies.

Conjugation of Meningococcal Lipooligosaccharides Through Their Non-Reducing Terminus Results in Improved Induction a Protective Immune Response Abstract The present studies prove that conjugation of meningococcal lipooligosaccharides through their non-reducing terminus conserves their inner epitopes resulting in conjugates potent to induce a protective immune response. Four different oligosaccharides were obtained by specific degradations of the same L7 lipooligosaccharide (L7-LOS), and each was linked to tetanus toxoid by direct reductive amination. Two were truncated oligosaccharides with incomplete inner epitopes and were obtained by mild acid hydrolysis of lipooligosaccharide. The terminal galactose of one oligosaccharide was additionally enzymatically oxidized. These oligosaccharides were conjugated through a newly exposed terminal Kdo in reducing end or through oxidized galactose localized at non-reducing end of the core, respectively. The third was a full-length oligosaccharide obtained by O-deacylation of the L7-LOS and subsequent enzymatic removal of phosphate substituents from its lipid A moiety. The fourth one was also a full-length O-deacylated lipooligosaccharide, but treated with galactose oxidase. This allowed direct conjugation to tetanus toxoid through terminal 2-N-acyl-2-deoxy-d-glucopyranose or through oxidized galactose, respectively. Comparison of the immune performance of four conjugates in mice revealed, that while each was able to induce significant level of L7-LOS-specific IgG antibody, the conjugates made with the full-length saccharides were able to induce antibodies with increased bactericidal activity against homologous meningococci. Only full-length oligosaccharides were good inhibitors of the binding of L7-LOS to the bactericidal antiserum. Moreover, induction of the significant level of the L7-LOS-specific antibody by full-length lipooligosaccharide conjugated from non-reducing end, provided also the direct evidence that internal core epitopes are fully responsible for the immunorecognition and immunoreactivity.

IgG from Non-atopic Individuals Induces In Vitro IFN-γ and IL-10 Production by Human Intra-thymic γδT Cells: A Comparison with Atopic IgG and IVIg Abstract Matured in the thymus, γδT cells can modulate the development of allergy in humans. The main γδT cell subsets have been described as interleukin (IL)-17A or interferon (IFN)-γ producers, but these cells can also produce other modulatory cytokines, such as IL-4 and IL-10. Here, we aimed to evaluate whether IgG can modulate the profile of cytokine production by γδT cells during their maturation in the thymus and after its migration to peripheral tissues. Thymic tissues were obtained from 12 infants, and peripheral blood mononuclear cells (PBMCs) were obtained from adults (both groups without an atopic background). IgG was purified from atopic and non-atopic volunteers. Thymocytes and PBMCs were cultured with purified atopic or non-atopic IgG, and intracellular cytokine production and phenotype were assessed. Mock and IVIg conditions were used as controls. IgG from non-atopic individuals induced IFN-γ and IL-10 production by thymic γδT cells, and no effect was observed on peripheral γδT cells. IL-17 production was inhibited by non-atopic IgG on thymic γδT cells and augmented by atopic IgG on peripheral γδT cells. Modulated thymic γδT cells did not produce IFN-γ and IL-10 simultaneously. We additionally evaluated the phenotype of intrathymic γδT cells and observed that IgG from all groups could induce CD25 expression and could not influence the CD28 expression of these cells. This report describes evidence revealing that IgG may influence the production of IFN-γ and IL-10 by intrathymic γδT cells depending on the donor atopic state. This observation is unprecedented and needs to be considered in further studies in the IgG immunotherapy field.

Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases Abstract Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver diseases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting also the uncertainties and the potential new eras of the research agenda.

Proportion of Cytotoxic Peripheral Blood Natural Killer Cells and T-Cell Large Granular Lymphocytes in Recurrent Miscarriage and Repeated Implantation Failure: Case–Control Study and Meta-analysis Abstract We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3–CD56+) and T-cell large granular lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recurrent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This case–control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3–CD56+ and CD8+CD57+ cells and sub-populations of CD3–CD56+ cells did not differ between cases and controls. The results for women with subsequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell proportions in RM [mean difference 3.47 (95% CI 2.94–4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82–2.45); p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral blood CD3–CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large studies are needed to develop a reliable peripheral blood marker of immune deregulation.

Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment of Type I Allergies Abstract While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.

Diverse Activity of IL-17 + Cells in Chronic Skin and Mucosa Graft-Versus-Host Disease Abstract Excessive inflammatory environment in a course of chronic graft-versus-host disease (cGvHD) is associated with T-cell trafficking into inflamed tissues. This study focused on the identification of IL-17-producing cells in the tissue biopsies of cGvHD patients. Forty-one biopsy specimens of cGvHD lesions of the skin (n = 27), gastrointestinal tract (n = 9) and oral mucosa (n = 5), examined in 24 patients, were morphologically defined according to the NIH criteria and analyzed for the presence of cellular infiltrations including: IL-17+, FOXP3+ and CCR6+ cells. IL-17+ cells were identified in 26/27 skin and in all gut and oral mucosa biopsies, being more frequent in mucosa lesions than in the skin (11/14 vs 14/26, respectively; NS: not significant). Double staining documented that CD138+/IL-17+ cells were commonly seen in the gut than in the skin (5/8 vs 3/11, respectively; NS). In the skin, cells expressing trafficking receptor CCR6+ were more frequent than IL-17+ cells compared to the mucosa (23/26 vs 2/13, respectively; p < 0.0001). CCR6 was present on a majority of IL-17+ cells in all examined skin biopsies but only in 6 out of 11 digestive tract biopsies (p = 0.0112). FOXP3+ cells were identified only in five patients (with mild lesions) at least in one biopsy. In this study group, results documented that local expansion of IL-17-producing cells in the digestive tract correlate with moderate and severe clinical symptoms of cGvHD, in contrast to the skin, where IL-17+ cells are rather scarcely present (p = 0.0301) and the course of cGvHD is slowly progressing with final organ deterioration.

CTLA-4 Expression Inversely Correlates with Kidney Function and Serum Immunoglobulin Concentration in Patients with Primary Glomerulonephritides Abstract Major causes of chronic kidney disease are primary proliferative and nonproliferative glomerulonephritides (PGN and NPGN). However, the pathogenesis of PGN and NPGN is still not fully understood. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a T-cell membrane receptor that plays a key role in T-cell inhibition. Despite its role in autoimmunological diseases, little is known about the involvement of CTLA-4 in the pathogenesis of PGN and NPGN. The objective of this study was to determine the role of CTLA-4 in the pathogenesis of PGN and NPGN by evaluating the frequencies of T and B lymphocytes expressing CTLA-4 and the serum concentration of the sCTLA-4 isoform in patients with PGN and NPGN in relation to clinical parameters. The study included peripheral blood (PB) samples from 40 PGN and NPGN patients and 20 healthy age- and sex-matched volunteers (control group). The viable PB lymphocytes were labeled with fluorochrome-conjugated monoclonal anti-CTLA-4 antibodies and analyzed using flow cytometry. The serum concentration of sCTLA-4 was measured using ELISA. The frequencies and absolute counts of CD4+/CTLA-4+ T lymphocytes, CD8+/CTLA-4+ T lymphocytes and CD19+/CTLA-4+ B lymphocytes and the serum sCTLA-4 concentration were lower in PGN and NPGN patients that in the control group. Reduced sCTLA-4 expression was associated with a lower concentration of serum immunoglobulins. Our results indicate that deregulation of CTLA-4 expression may result in continuous activation of T cells and contribute to the pathogenesis of PGN and NPGN.

Natural Killer and Natural Killer T Cells in Juvenile Systemic Lupus Erythematosus: Relation to Disease Activity and Progression Abstract The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dimand CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Pediatrics

Planetary Pediatrics Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Jeffrey Goldhagen

Reviewer Acknowledgment Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s):

Implementation of Recommendations for Long-Acting Contraception Among Women Aged 13 to 18 Years in Primary Care Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Sharisse M. Arnold Rehring, Liza M. Reifler, Jennifer H. Seidel, Karen A. Glenn, John F. Steiner Abstract Objective Clinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system. Methods The intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013−September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians. Results Kaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7−5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9−9.8) increased significantly in clinicians who attended educational activities. Conclusions This multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change.

Impacts of a Pediatric Extracorporeal Cardiopulmonary Resuscitation (ECPR) Simulation Training Program Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Taylor Sawyer, Christopher Burke, D. Michael McMullan, Titus Chan, Hector Valdivia, Larissa Yalon, Joan Roberts Abstract Objective To examine the impacts of a large-scale simulation-based extracorporeal cardiopulmonary resuscitation (ECPR) training program in an academic children's hospital. Methods The study followed a quasi-experimental, mixed-method, time series design. Two-hour high-fidelity ECPR simulations were held monthly in the pediatric, cardiac, and neonatal intensive care units. Intensive care unit–specific cases were used in each unit. The learning objectives for all cases were the same. Each simulation included an average of 11 health care professionals, including nurses, physicians, respiratory therapist, and perfusionists. Impacts of training were examined using Kirkpatrick's 4-level model: reactions, learning, behaviors, and results. Participant surveys, semistructured interviews, facilitator observations, applied cognitive task analysis, and hospital code data were used to examine the impacts of training. Results From February 2014 to October 2016, a total of 332 health care professionals participated in 29 ECPR simulations. Participants enjoyed the simulations and reported learning gains. Applied cognitive task analysis revealed 2 specific behaviors, coordination of compressions with surgical cannulation and performing sterile compressions, that were targeted for further training. The rate of adherence to the ECPR activation protocol improved from 83% (48/58) before simulations started to 95% (92/97) after simulations (P = .02). ECPR activation time decreased from 7 minutes (interquartile range, 4–9 minutes) before simulations started to 2 minutes (interquartile range, 1–4 minutes) after simulations (P < .01). Conclusions Large-scale simulation-based ECPR training was associated with positive reactions, learning gains, behavioral change, improved adherence to the ECPR activation protocols, and faster activation times. Other children's hospital that perform ECPR should consider simulation-based training.

Justifications for Discrepancies Between Competency Committee and Program Director Recommended Resident Supervisory Roles Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Daniel J. Schumacher, Sue Poynter, Natalie Burman, Sean P. Elliott, Michelle Barnes, Caren Gellin, Javier Gonzalez del Rey, Daniel Sklansky, Lynn Thoreson, Beth King, Alan Schwartz, the APPD LEARN CCC Study Group Abstract Objective To explore justifications for differences between summative entrustment decisions made about pediatric residents by individuals who are charged with the review of residents (clinical competency committee, or CCC, members) and those who ultimately make final summative decisions about resident performance (program directors, or PDs). Methods Individual CCC member and PD supervisory role categorizations were made in the 2015 to 2016 academic year at 14 pediatric residency programs, placing residents into 1 of 5 progressive supervisory roles. When PD recommendations differed from CCC members, a free-text justification was requested. Free-text responses were analyzed using manifest content analysis. Results In total, 801 supervisory role categorizations were made by both CCC members and PDs, with the same recommendations made in 685 cases. In the 116 instances of discrepancy, PDs assigned a lower level of supervisory responsibility (n = 73) more often than a greater one (n = 43). When moving residents to a greater supervisory role category, PDs had more justifications anchored in resident performance than experience. When moving residents to a lower supervisory role categorization, PDs conversely noted experience more than performance. Conclusions PDs provide more justifications anchored in resident performance when moving residents to a greater supervisory role category compared with CCC members. However, when moving residents to a lower supervisory role categorization, they note experience more than performance. These patterns may or may not be entirely consistent with a competency-based approach and should be explored further.

The Challenges of Multisource Feedback: Feasibility and Acceptability of Gathering Patient Feedback for Pediatric Residents Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): David Mahoney, Alyssa Bogetz, Amanda Hirsch, Katherine Killmond, Elisa Phillips, Vasudha Bhavaraju, Alisa McQueen, Nicola Orlov, Rebecca Blankenburg, Caroline E. Rassbach Abstract Objective The Accreditation Council for Graduate Medical Education calls for residency programs to incorporate multisource feedback, which may include patient feedback, into resident competency assessments. Program directors face numerous challenges in gathering this feedback. This study assesses the feasibility and acceptability of patient feedback collection in the inpatient and outpatient setting at 3 institutions. Methods Patient feedback was collected using a modified version of the Communication Assessment Tool (CAT). Trained research assistants administered the CAT to eligible patients and families in pediatric ward, intensive care, and outpatient settings from July to October 2015. Completion rates and reasons for non-completion were recorded. Patient satisfaction with the CAT was assessed on a 5-point Likert scale. Results The CAT was completed by 860/1413 (61%) patients. Completion rates in the pediatric ward and intensive care settings were 45% and 38%, respectively, compared to 91% in the outpatient setting. In inpatient settings, survey non-completion was typically due to participant unavailability; this was rarely a reason in the outpatient setting. A total of 93.4% of patients were satisfied or very satisfied with using the CAT. It was found that 6.36 hours of research assistant time would be required to gather a valid quantity of patient feedback for a single resident in the outpatient setting, compared to 10.14 hours in the inpatient setting. Conclusions Although collecting feedback using our standardized protocol is acceptable to patients, obtaining sufficient feedback requires overcoming several barriers and a sizable time commitment. Feedback collection in the outpatient setting may be higher yield than in the inpatient setting due to greater patient/family availability. Future work should focus on innovative methods to gather patient feedback in the inpatient setting to provide program directors with a holistic view of their residents' communication skills.

Medical Student Participation in Patient- and Family-Centered Rounding: A National Survey of Pediatric Clerkships Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Margaret J. Trost, Nicholas M. Potisek, L. Barry Seltz, Melanie Rudnick, Mary Rose Mamey, Michele Long, Patricia D. Quigley Abstract Objective Pediatrics rotations may be medical students' only experience with patient- and family-centered rounding (PFCR). It is unclear how students participate in or are prepared for PFCR. We surveyed national pediatrics clerkships to determine the prevalence of PFCR and the proportion providing orientation in order to inform a needs assessment for PFCR orientation. Methods A 5-item peer-reviewed survey was distributed to the Council on Medical Student Education in Pediatrics (COMSEP) membership as part of a larger survey in 2017. Institutional differences among programs performing PFCR were compared using chi-square and t-tests. Responses to 1 open-ended question were coded and grouped into broad categories using content analysis. Results The full COMSEP survey received answers from 190 participants representing 103 medical schools. Our questions received 174 responses representing 94 schools (98 training sites) and had an 85% (83/98) prevalence of student PFCR participation. Although most (n = 108; 85%) reported that their students received PFCR orientation, half (n = 62; 49%) considered orientation "informal," and only 2 reported using published curricula. After didactics, the most common orientation materials were handouts (n = 33; 26%), videos (n = 13; 10%), and role play (n = 7; 6%). Orientation was most commonly initiated at the start of clerkship (n = 62; 49%) by clerkship administration (n = 38; 30%), but 20% (n = 26) reported resident-led orientation. Qualitative responses (n = 98) were coded and organized into 4 themes; the greatest perceived challenges for medical students on PFCR were communication and anxiety. Conclusions Although most students participate in and receive orientation to PFCR, there is wide variability in the content, timing, and administration of orientation. A nationally disseminated, evidence-based orientation curriculum may reduce educational variability and better prepare students for PFCR.

Temperature-Adjusted Respiratory Rate for the Prediction of Childhood Pneumonia Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Richard G. Bachur, Kenneth A. Michelson, Mark I. Neuman, Michael C. Monuteaux Abstract Objectives As both fever and pneumonia can be associated with tachypnea, we investigated the relationship between body temperature and respiratory rate (RR) in young children and whether temperature-adjusted RR enhances the prediction of pneumonia. Methods In this retrospective cross-sectional analysis of 91,429 children < 5 years of age presenting to an urban pediatric emergency department, the relationship between triage RR and temperature was analyzed using regression analysis. We assessed the predictive value of temperature-adjusted RR for the diagnosis of pneumonia; diagnostic performance was evaluated for continuous RR as well as World Health Organization (WHO) age-based RR thresholds. Results The mean RR increased 2.6 breaths/minute for each 1°C increase in temperature. Interpatient variability was comparatively large; at any temperature, the interquartile range (75th percentile minus 25th percentile) varied from 4 to 16 breaths/minute. For predicting pneumonia, temperature- and age-adjusted RR was superior to age-adjusted RR: area under the curve (AUC) = 0.76 (95% confidence interval [CI], 0.75–0.78) versus AUC = 0.73 (95% CI, 0.72–0.75), respectively. Using WHO RR criteria, temperature-adjusted RR improved diagnostic discrimination, as the AUC increased from 0.58 (95% CI, 0.57–0.59) to 0.72 (95% CI, 0.70–0.73). Conclusions The effects of temperature on respiratory rate are modest, with a mean increase of 2.6 breaths/minute for each 1°C rise in temperature. Despite considerable interpatient variability in respiratory rates by temperature, temperature adjustment improves the diagnostic value of respiratory rate for pneumonia.

Differences in Febrile and Respiratory Illnesses in Minority Children: The Sociodemographic Context of Restrictive Parenting Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Danielle S. Roubinov, Nicole R. Bush, Nancy E. Adler, W. Thomas Boyce Abstract Objective To examine the moderating role of restrictive parenting on the relation of socioeconomic status (SES) to febrile illnesses (FIs) and upper respiratory illnesses (URIs) among ethnic minority and non-minority children. Methods Children from diverse ethnic backgrounds (Caucasian, African American, Asian, Latino, other, or multiethnic) were followed across the course of the kindergarten year. Parents reported on SES and parenting. A nurse completed 13 physical exams per child over the year to assess FIs and URIs. Results During the school year, 28% of children (n = 199, 56% ethnic minority) exhibited one or more FIs (range, 0–6) and 90% exhibited one or more URIs (range, 0–10). No main or moderating effects of SES or restrictive parenting on FIs or URIs were found among Caucasian children; however, among ethnic minority children, the relation of SES to FIs was conditional upon restrictive parenting (β = .66; P = .02), as the fewest FIs were found for lower SES minority children whose parents reported more restrictive practices. Additionally, among minority children, more restrictive parenting was marginally associated with fewer URIs (β = –.21; P = .05). Conclusions Unexpectedly, among minority children the fewest illnesses occurred among lower SES children whose parents endorsed more restrictive parenting. This may be due to unique appraisals of this rearing style among minority children in lower SES environments and its potential to influence immune functioning. Results suggest variability in the effects of parenting on offspring health and support context-specific evaluations of parenting in efforts to ameliorate early health disparities.

Concordance of Child and Parent Reports of Children's Screen Media Use Publication date: July 2019 Source: Academic Pediatrics, Volume 19, Issue 5 Author(s): Charles T. Wood, Asheley Cockrell Skinner, Jane D. Brown, Callie L. Brown, Janna B. Howard, Michael J. Steiner, Andrew J. Perrin, Cary Levine, Sophie N. Ravanbakht, Eliana M. Perrin Abstract Objective Little is known about the concordance of parent and child reports of children's media consumption, even though parents are often asked to report for their children in clinical care settings. Our objective was to understand how parent and child reports of children's media consumption differ in an era of changing screen media consumption via personal devices. Methods As part of a larger study about the reception of health-related cues from children's media, children ages 9 to 11 years (N = 114) and their parents independently completed identical questionnaires about specific media use and health behaviors. To examine concordance between child and parent reports of children's screen media use, we calculated the mean number of minutes per day and proportions reported by the child and parent and assessed concordance with t-tests and chi-square tests. Results On a typical day, children reported nearly an hour each of video and app game use, computer use, and television exposure. Overall, child and parent reports were similar, usually within 10 minutes of each other; however, among 3 measures of TV use, parents consistently reported less TV exposure than children. There was significant discordance in the percentages of parents and children reporting the presence of a TV in the child's room. Conclusions Parent and child reports of children's media use were generally concordant; however, there were important disagreements, such as TV use in the child's room and during meals. We discuss possible causes of discrepancies and implications.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Exercise and Sport Sciences Reviews

Perspectives for Progress - Female Athlete Triad and Relative Energy Deficiency in Sport: A Focus on Scientific Rigor We examine the scientific evidence supporting The Female Athlete Triad and Relative Energy in Sport (RED-S) syndromes. More research is necessary to advance the understanding of both syndromes; however, it is premature to consider RED-S as an evidence-based syndrome. Future research should specifically define RED-S components, determine its clinical relevance, and establish the causality of relative energy deficiency on RED-S outcomes. Address for Correspondence: Nancy I. Williams, Sc.D., FACSM, FNAK, Professor and Head, Department of Kinesiology, Co-Director, Women's Health and Exercise Laboratory, The Pennsylvania State University, 276 Recreation Building, University Park, PA 16802. Email: niw1@psu.edu; Phone: 814-863-1163 Conflicts of interest; disclosure of funding: none © 2019 American College of Sports Medicine

Carbohydrate Availability as a Regulator of Energy Balance with Exercise We explore the novel hypothesis that carbohydrate availability is involved in the regulation of energy balance with exercise, via hormonal and neural signals. We propose that carbohydrate availability could play a direct mechanistic role and partially explain previously-documented relationships between a more active lifestyle and tighter control of energy balance. Corresponding author: Javier T. Gonzalez, Department for Health, University of Bath, BA2 7AY, United Kingdom. Tel: 0(+44) 1225 38 5518; E-mail: J.T.Gonzalez@bath.ac.uk, ORCID ID: 0000-0002-9939-0074. Funding: No funding was received for the preparation of this manuscript. Conflicts of interest: J.T.G. has received research funding and/or has acted as a consultant for Arla Foods Ingredients, Lucozade Ribena Suntory, Kenniscentrum Suiker and Voeding, and PepsiCo. J.A.B. has received research funding and/or has acted as a consultant for GlaxoSmithKline, Lucozade Ribena Suntory, Kellogg's, Nestlé and PepsiCo and is a scientific advisor to the International Life Sciences Institute (ILSI). D.T. has received funding and acted as a consultant for Unilever. © 2019 American College of Sports Medicine

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicine & Science in Sports & Exercise

High-Intensity Interval Training is Feasible in Women at High Risk for Breast Cancer Purpose This trial aimed to demonstrate feasibility of high-intensity interval training (HIIT) in post-menopausal, overweight/obese women at high-risk of invasive breast cancer, and explore HIIT on changes in cardiorespiratory fitness (CRF), body weight, and body mass index (BMI) compared to moderate-intensity continuous training (MICT) and usual care (UC). Methods Forty-four women were randomized to HIIT, MICT or UC for a 12-week, thrice weekly, supervised exercise intervention. HIIT included a 5-minute warm-up at 50-70% peak heart rate (HR), four cycles of four minutes at 90-100% peak HR followed by three minutes at 50-70% peak HR. MICT consisted of 41 minutes at 60-70% peak HR. Feasibility was assessed by consent, adherence, compliance and retention rates. CRF, body weight and BMI were measured at baseline and end-of-study. Repeated measures linear mixed models were used to assess within- and between-group differences. Results Average age was 63.9±8.8 years. BMI was 30.9±5.7 kg/m2. Participants completed 90% and 89% of HIIT and MICT workouts respectively, with 100% compliance to the exercise prescriptions. No serious adverse events were reported. Compared to MICT and UC, HIIT exhibited improvements in change in treadmill time (101 seconds greater than MICT, and 125 seconds greater than UC, respectively, p<0.001). Compared to UC, HIIT exhibited improvement in changes in absolute and relative VO2peak (a 0.15 increase in L/min, p=0.005; and 2.3 increase in ml/kg/min, p=0.004). There were no significant differences between groups for body weight or BMI (p>0.05). Conclusions HIIT is feasible, safe, and appears to promote greater improvements in CRF compared to MICT and UC in women at high risk for breast cancer. Correspondence: Susan C Gilchrist, MD; The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1360, Houston TX 77230-1439; Phone: 713-745-6251; Fax: 713-794-4403; sgilchrist@mdanderson.org The authors thank the NCI R25 Cancer Prevention Research Training Program (CA057730, PI: Shine Chang PhD), the MD Anderson Cancer Center/Energy Balance Assessment Supplemental Funding (PI: Susan Gilchrist MD), and the MD Anderson Cancer Center, Center for Energy Balance in Cancer Prevention and Survivorship. The authors declare that they have no conflicts of interest to disclose. The results of the present study do not constitute endorsement by the ACSM, and are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 10 May 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 American College of Sports Medicine

Data-informed Intervention Improves Football Technique and Reduces Head Impacts Introduction Although sport participation is a key contributor to the physical and mental health of children and youth, exposure to sub-concussive head impacts in football has raised concerns about safety for athletes. Purpose To demonstrate the efficacy of incorporating targeted football drills into a team's practice routine with the goal of improving players' technique, and reduce exposure to sub-concussive head impacts. Methods Seventy high-school football players (age=16.4±1.1years) were tested PRE-season using a sport-specific functional assessment. Results from the testing were used to inform the design of a pre-practice intervention aimed at improving tackling and blocking techniques, while reducing exposure to head impacts. The assessment included drills which evaluated the players' ability to safely tackle, and block, while simulating game-like situations. Testing was repeated at MID-season (internal control) without an intervention, and again at POST-season (experimental), following introduction of the pre-practice intervention between these timepoints, administered twice weekly. All testing sessions were recorded, and subsequently reviewed by trained graders based on selected criteria defined by football coaches. A subset of nineteen participants wore in-helmet accelerometers to assess the effectiveness of the intervention in decreasing head impacts during practice. Results Significant improvements in blocking and tackling techniques were observed following the introduction of the intervention (P<0.0001). Participating athletes also showed better techniques when evaluated in new game-like situations, post-season, providing evidence for proper acquisition and generalizability of these safer habits. Finally, frequency of head impacts (>15g) per practice was significantly reduced by ~30% after one month of training. Conclusion Our results suggest that data-informed methods can be used to improve coaching practices, and promote safer play, which can have a positive public health impact moving forward. Corresponding author: Douglas J. Cook, Department of Surgery, Queen's University, Room 232, 18 Stuart St. Kingston, ON K7L 3N6. Phone: 613-549-6666 ext. 3696. Fax: 613-548-1346. dj.cook@queensu.ca Results from this study are presented clearly, honestly and without fabrication, falsification, or inappropriate data manipulation. Results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare no conflict of interest. Funding from the Southeastern Ontario Academic Medical Organization (SEAMO) helped making this project possible. Accepted for publication: 7 May 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 American College of Sports Medicine

Motor Strategies Learned during Pain Are Sustained upon Pain-free Re-exposure to Task Introduction Pain affects movement planning and execution, and may interfere with the ability to learn new motor skills. Variations among previous studies suggest task-specific effects of pain on the initial acquisition and subsequent retention of motor strategies. Methods The present study assessed how acute pain in the anterior deltoid muscle affects movement accuracy of fast arm-reaching movements during force field perturbations, and upon immediate pain-free repetition of the same task. Results Despite having slower initial rate of improvement, individuals who experienced pain during training achieved the same final performance as pain-free controls. However, pain altered the strategy of muscle activation adopted to perform the task, which involved less activity of the shoulder and arm muscles. Strikingly, motor strategies developed during the first exposure to the force field were retained upon re-exposure to the same perturbation, after resolution of pain. Conclusion Although reduced muscle activation may be interpreted as metabolically efficient, it reduces joint stability and can have negative consequences for joint integrity. These results demonstrate that alternative motor strategies developed in the presence of pain can be maintained when training is resumed after resolution of pain. This effect could have deleterious consequences if it applies when learning motor skills in sports training and rehabilitation. Corresponding author: Dr Paul W. Hodges, School of Health and Rehabilitation Sciences, The University of Queenslandm, Brisbane QLD 4072, Australia, Phone: +61 7 3365 2008, E-mail: p.hodges@uq.edu.au Disclosures and Acknowledgements This study was funded by a Program Grant (APP1091302), a Senior Principal Research Fellowship (APP1102905) from the National Health and Medical Research Council (NHMRC) of Australia, and a Future Fellowship grant to TC (FT120100391). The authors have no conflicts of interest to declare. All the authors are properly listed, and all have contributed substantially to the manuscript. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 29 May 2019 © 2019 American College of Sports Medicine

Cytokine and Sclerostin Response to High-Intensity Interval Running versus Cycling Purpose This study examined whether the exercise-induced changes in inflammatory cytokines differ between impact and no-impact high intensity interval exercise, and whether they are associated with post-exercise changes in sclerostin. Methods Thirty-eight females (n=19, 22.6±2.7 years) and males (n=19, 22.3±2.4 years) performed two high-intensity interval exercise trials in random order (cross-over design): running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight repetitions of 1 min running or cycling at ≥90% maximal heart rate, separated by 1 min passive recovery intervals. Blood was collected pre-exercise, and 5 min, 1h, 24h and 48h post-exercise, and was analyzed for serum levels of interleukins (IL-1β, IL-6, IL-10), tumor necrosis factor alpha (TNF-α) and sclerostin. Results Inflammatory cytokines significantly increased over time in both sexes with some differences between trials. Specifically, IL-1β significantly increased from pre- to 5 min after both trials (23%, p<0.05), IL-6 increased 1h following both trials (39%, p<0.05), IL-10 was elevated 5 min after running (20%, p<0.05) and 1h after both running and cycling (41% and 64%, respectively, p<0.05), and TNF-α increased 5 min after running (10%, p<0.05). Sclerostin increased 5 min following both trials, with a greater increase in males than in females (62 vs 32 pg/ml in running, p=0.018; 63 vs 30 pg/ml in cycling, p=0.004). In addition, sclerostin was significantly correlated with the corresponding changes in inflammatory cytokines and 34% of the variance in its post-exercise gain score (Δ) was explained by sex and the corresponding gain scores in TNF-α, which was the strongest predictor. Conclusion A single bout of either impact or no-impact high-intensity exercise induces changes in inflammatory cytokines, which are associated with the post-exercise increase in sclerostin. Corresponding author: Panagiota Klentrou Department of Kinesiology Faculty of Applied Health Sciences Brock University 1812 Sir Isaac Brock Way St. Catharines, ON, L2S 3A1, Canada E-mail: nklentrou@brocku.ca This study was funded by a National Science Engineer Research Council of Canada (NSERC) grant to P. Klentrou (grant # 2015-04424). R. Kouvelioti holds an Ontario Trillium Scholarship. N. Kurgan holds an NSERC Doctoral Scholarship. W. Wards holds a Canada Research Chair in Bone and Muscle Development. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Conflicts of interest: The authors have no conflict of interest to declare. Accepted for publication: 14 June 2019. © 2019 American College of Sports Medicine

Extended Sleep Maintains Endurance Performance better than Normal or Restricted Sleep Purpose The cumulative influence of sleep time on endurance performance remains unclear. This study examined effects of three consecutive nights of both sleep extension and restriction on endurance cycling performance. Methods Endurance cyclists/triathletes (n=9) completed a counterbalanced crossover experiment with three conditions; sleep restriction (SR), normal sleep (NS), and sleep extension (SE). Each condition comprised seven days/nights of data collection (-2, -1, D1, D2, D3, D4, +1). Sleep was monitored using actigraphy throughout. Participants completed testing sessions on days D1-D4 that included an endurance time-trial (TT), mood, and psychomotor vigilance assessment. Perceived exertion (RPE) was monitored throughout each TT. Participants slept habitually prior to D1, however, time in bed was reduced by 30% (SR), remained normal (NS), or extended by 30% (SE) on nights D1, D2, and D3. Data were analysed using Generalised Estimating Equations. Results On nights D1, D2, and D3, total sleep time was longer (P<0.001) in the SE condition (8.6±1.0; 8.3±0.6; 8.2±0.6h, respectively), and shorter (P<0.001) in the SR condition (4.7±0.8; 4.8±0.8; 4.9±0.4h) compared with NS (7.1±0.8; 6.5±1.0; 6.9±0.7h). Compared with NS, TT performance was slower (P<0.02) on D3 of SR (58.8±2.5 vs 60.4±3.7min) and faster (P<0.02) on D4 of SE (58.7±3.4 vs 56.8±3.1min). RPE was not different between or within conditions. Compared with NS, mood disturbance was higher-, and psychomotor vigilance impaired, following SR. Compared with NS, psychomotor vigilance improved following SE. Conclusion Sleep extension for three nights led to better maintenance of endurance performance compared with normal and restricted sleep. Sleep restriction impaired performance. Cumulative sleep time affects performance by altering the perceived exertion of a given exercise intensity. Endurance athletes should sleep >8 hours per night to optimise performance. Corresponding author: Spencer S. H. Roberts, PhD Candidate School of Exercise and Nutrition Sciences, Deakin University. 221 Burwood Hwy, Burwood, Victoria, Australia, 3125 Email: rspen@deakin.edu.au The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Results do not constitute endorsement by the American College of Sports Medicine. Spencer Roberts, Wei-Peng Teo, Brad Aisbett, and Stuart Warmington declare they have no conflict of interest. The authors acknowledge the School of Exercise and Nutrition Sciences at Deakin University for funding the study. Accepted for publication: 9 June 2019. © 2019 American College of Sports Medicine

Methodological Recommendations for Menstrual Cycle Research in Sports and Exercise Introduction The aim of this review is to provide methodological recommendations for menstrual cycle research in exercise science and sports medicine based on a review of recent literature. Research in this area is growing, but often reports conflicting results and it is proposed that some of this may be explained by methodological issues. Methods This review examined the menstrual cycle verification methodologies used in recent literature on exercise performance over the menstrual cycle identified through a literature search of PubMed and SportDiscus from 2008 until 2018. Results Potential changes over the menstrual cycle are likely related to hormone fluctuations, however, only 44% of the selected studies measured the actual concentrations of the female steroid hormones estrogen and progesterone. It was shown that the likely inclusion of participants with anovulatory or luteal phase deficient cycles in combination with small participant numbers has impacted results in recent menstrual cycle research and consequently our understanding of this area. Conclusion To improve the quality of future menstrual cycle research it is recommended that a combination of three methods is used to verify menstrual cycle phase: the calendar-based counting method combined with urinary luteinizing hormone surge testing and the measurement of serum estrogen and progesterone concentrations at the time of testing. A strict luteal phase verification limit of >16 nmol·L-1 for progesterone should be set. It is also recommended that future research focusses on the inclusion of the late follicular estrogen peak. It is envisaged that these methodological recommendations will assist in clarifying some of the disagreement around the effects of the menstrual cycle on exercise performance and other aspects of exercise science and sports medicine. Corresponding author: Xanne Janse de Jonge Exercise & Sport Science Faculty of Science The University of Newcastle, Australia Central Coast Campus PO Box 127 Ourimbah NSW 2258 Australia E: X.Jansedejonge@newcastle.edu.au ORCID 0000-0003-3657-5298 Xanne Janse de Jonge, Belinda Thompson and Ahreum Han declare that they have no conflicts of interest relevant to the content of this review. The results of the present study do not constitute endorsement by ACSM. The results of this review are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. No funding was received for this review. Accepted for publication: 22 May 2019. © 2019 American College of Sports Medicine

Estimated Cardiorespiratory Fitness and Risk of Atrial Fibrillation: The HUNT Study Purpose To investigate the association between estimated cardiorespiratory fitness (eCRF) and risk of atrial fibrillation (AF), and examine how long-term changes in eCRF affects the AF risk. Methods This prospective cohort study includes data of 39 844 men and women from the HUNT2 (August 15, 1995 - June 18, 1997) and the HUNT3 study (October 3, 2006 – June 25, 2008). The follow-up period was from HUNT3 until AF diagnosis or November 30, 2015. AF diagnoses were retrieved from hospital registers and validated by medical doctors. A non-exercise test based on age, waist circumference, resting heart rate and self-reported physical activity was used to estimate CRF. Cox regression was performed to assess the association between eCRF and AF. Results The mean age was 50.6 ± 14.6 years for men and 50.2 ± 15.2 years for women. Mean follow-up time was 8.1 years. 1 057 cases of AF were documented. For men, the highest risk reduction of AF was 31% in the 4th quintile of eCRF when compared to the 1st quintile (HR, 0.69; 95% CI, 0.53-0.89). For women, the highest risk reduction was 47% in the 5th quintile when compared to the 1st quintile (HR, 0.53; 95% CI, 0.38-0.74). One metabolic equivalent increase in eCRF over a 10-year period was associated with 7% lower risk of AF (HR, 0.93; 95% CI, 0.86-1.00) Participants with improved eCRF had 44% lower AF risk compared to those with decreased eCRF (HR, 0.56; 95% CI, 0.36-0.87). Conclusion eCRF was inversely associated with AF, and participants with improved eCRF over a 10-year period had less risk of AF. These findings support the hypothesis that fitness may prevent AF. Correspondence and reprints to: Lars E. Garnvik, Department of Circulation and Medical Imaging, NTNU, Medisinsk Teknisk Forskningssenter, Post box 8905, 7491 Trondheim, Norway. E-mail: lars.e.garnvik@ntnu.no This work was supported by grants from the The Liaison Committee for education, research and innovation in Central Norway. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre, (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. We would like to thank all the participants and technicians of the HUNT study for their contributions. Conflict of interest: None declared. Accepted for publication: 14 June 2019. © 2019 American College of Sports Medicine

New On-Water Test for the Assessment of Blood Lactate Response to Exercise in Elite Kayakers Purpose Lactate thresholds are physiological parameters used to train athletes and monitor performance or training. Currently, the assessment of lactate thresholds in kayakers is performed in a laboratory setting utilizing specific ergometers; however, laboratory tests differ from on-water evaluation for several reasons. The aim of this study was to assess reliability and validity of a new on-water incremental test for the assessment of blood lactate response to exercise in flat-water kayakers. Maximal lactate steady state test (MLSS) was used as criterion measurement. Methods Eleven junior (16.5±1.9yr) élite flat-water kayakers performed: i) an incremental cardiopulmonary test up to voluntary exhaustion on a stationary kayak ergometer to determine peak oxygen uptake; ii) an on-water 1000m distance trial (T1000) to record best performance time and average speed (S1000); iii) two repetitions of on-water incremental kayaking test (WIK-test); iv) several repetitions of on-water constant speed tests to determine MLSS. Speed, heart rate and blood lactate concentrations were determined during on-water tests. Results The best performance time in T1000 was 262±13s, corresponding to an S1000 of 3.82±0.19m·s-1. Lactate threshold determined by modified Dmax method (LTDmod) during WIK-test was 2.78±1.02mmol·L-1 and the corresponding speed (SLT) was 3.34±0.16m·s-1. Test-retest reliability, calculated on SLT, was strong (ICC=0.95 and r=0.93). MLSS corresponded to 3.06±0.68mmol·L-1 and was reached at a speed (SMLSS) of 3.36±0.14m·s-1. Correlation coefficient between SLT and SMLSS was 0.90 (p=0.0001). Interestingly, a significant correlation (r=0.96, p<0.0001) was observed between SLT and S1000. Conclusions WIK-test showed good reliability and validity for the assessment of speed corresponding to LTDmod in flat-water kayakers and it could be a useful tool to monitor athletic performance. The speed value at LTDmod nicely predicted performance on 1000m. Corresponding Author: Simone Porcelli Institute of Biomedical Technologies National Research Council Via Fratelli Cervi, 93 – Segrate 20090 (MI), Italy simone.porcelli@itb.cnr.it The authors have no conflicts of interest, source of founding, or financial ties to disclose and the results of the present study do not constitute endorsement by the American College of Sport Medicine. The results of this study are presented clearly, honestly, and without fabrication, or inappropriate data manipulation. Accepted for publication: 18 June 2019. © 2019 American College of Sports Medicine

The Physiology of Auto Racing: A Brief Review Introduction Auto racing poses a unique set of physiologic challenges for athletes who compete in this sport. These challenges are not widely recognized due to the limited amount of original research in this field and the diffuse nature of this literature. The purpose of this article is to review the major physiologic challenges of auto racing and summarize what is currently known about athletes in this sport. Conclusions The physical stressors of either driving or servicing the race car are overlaid with particular environmental challenges associated with racing (e.g. thermal, noise, carbon monoxide exposure) that increase the physiological stress on motorsport athletes. Physical stress reflects the muscular work required for car control and control of posture during high gravitational (g) loads: factors that predispose athletes to fatigue. The physiologic effects of these stressors include cardiovascular stress as reflected by prolonged elevation of heart rate, cardiac output, and oxygen consumption in both driver and pit athletes during competition. Psychological stress is evident in autonomic and endocrine responses of athletes during competition. The thermal stress of having to compete wearing multi-layer fire suits and closed helmets in ambient temperatures of 50-60o C results in the ubiquitous risk of dehydration. Published data show that both drivers and pit crew members are accomplished athletes with distinct challenges and abilities. There are gaps in the literature, especially in regard to female, older adult, and child participants. Additionally, minimal literature is available on appropriate training programs to offset the physiological challenges of auto racing. Address for correspondence: Michael B. Reid, Ph.D., College of Health & Human Performance, University of Florida, 1864 Stadium Rd., Suite 200, Gainesville, FL 32611; Tel.: 352-294-1601; Fax: 352-392-3186; E-mail: michael.reid@ufl.edu. This work was supported by the University of Florida and Texas A&M University. The authors have no conflicts of interest related to this article. The facts in this article are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Content of the article does not constitute endorsement by ACSM. Accepted for Publication: 10 April 2019 © 2019 American College of Sports Medicine

Fuel Use During Exercise At Altitude In Women With Glucose–Fructose Ingestion Purpose: This study compared the co-ingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women. Method Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 minutes on acute exposure to HA (3375m) and at sea level (~113m). In each trial, participants ingested 1.2 g.min-1 of glucose (enriched with 13C glucose) and 0.6 g.min-1 of fructose (enriched with 13C fructose) before and every 15 minutes during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation and endogenous glucose oxidation derived from liver and muscle glycogen. Results The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (ES>0.99, P<0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6±6.1 vs. 36.0±6.1%, ES=0.56, P=0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2±1.2 vs. 3.1±0.8%, ES=0.09, P=0.635 and 5.1±1.8 vs. 5.4±1.7 grams, ES=0.19, P=0.217), and muscle glycogen (14.4±12.2% vs. 15.8±9.3%, ES=0.11, P=0.934 and 23.1±19.0 vs. 28.7±17.8 grams, ES=0.30, P=0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3±21.4 vs. 59.6±7.7 grams, ES=0.32, P=0.557). Conclusion In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity. Keys Words Acute Hypoxia, Carbon Isotope, Exogenous Carbohydrate Oxidation, Liver Glycogen, Muscle Glycogen, Plasma Glucose Oxidation Address for Correspondence: John O'Hara, Research Institute for Sport, Physical Activity and Leisure, School of Sport, Leeds Beckett University, Headingley Campus, Leeds, LS6 3QS, UK. Email: J.OHara@leedsbeckett.ac.uk The authors would like to thank all the participants for their time and effort, as well as Leeds Beckett University for funding this research. The authors declared that the results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. The authors report no conflict of interest. Accepted for publication: 10 June 2019. © 2019 American College of Sports Medicine

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Physical Medicine & Rehabilitation

Influence of anxiety and depression, self-rated return-to-work problems, and unemployment on the outcome of outpatient rehabilitation following shoulder arthroscopy Objective The objective was to research the influence of psychosocial confounders on outpatient rehabilitation after arthroscopic shoulder surgery. Design: This retrospective study included patients who underwent such rehabilitation in a single center between 01/2014 and 10/2016. Shoulder function (CSS - Constant Shoulder Score) and pain (VAS – visual analogue scale), improvements in these scores, and patient satisfaction were evaluated with regard to anxiety and depression (HADS – Hospital anxiety and depression scale), self-rated return-to-work problems (WBS - Würzburg screening), and employment status. Results The analysis included 176 patients. The mean CSS and VAS improved from 53.9±18 to 75.4±16.5 and 4.6±2.1 to 2.9±2.4cm, respectively. 84.1% of the patients were satisfied with the outcome. Unemployed patients (p=0.001) and HADS-positive ones (p=0.014) were less satisfied than their counterparts. Patients with a WBS-positive screening showed less improvement in pain (p=0.015), function (p=0.016), and satisfaction (p=0.002) than those without. Unemployed reported more pain (p=0.008) than employed patients when starting rehabilitation. At the end of rehabilitation, all psychosocial scores (HADS p=0.002; WBS p=0.001; unemployment p<0.001) negatively influenced pain, WBS (p=0.007) and unemployment (p=0.008) function. Conclusions Because we identified psychosocial factors that influence the success of outpatient shoulder rehabilitation, rehabilitation setup should be adjusted in patients with such problems. Corresponding author: PD Dr. Patrick Strube, Klinik für Orthopädie, University Hospital Jena, Campus Waldkliniken Eisenberg, Klosterlausnitzer Str. 81, 07607 Eisenberg, Germany, Tel. +49 (36691) 8 1439, Fax +49 (36691) 8 1856, e-mail: patrick.strube@uni-jena.de Author Disclosures: None of the authors has to report any competing interests or financial benefits. No funding, grant, or equipment was received for the present study. The study was not presented or published before. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Constraint-induced Movement Therapy for improving motor function of the paretic lower extremity after stroke: a case report A 56-year-old woman with chronic stroke and gait dysfunction was recruited for this study. A Lower-Extremity Constraint-Induced Movement Therapy (LE-CIMT) protocol was given consisting of 3.5 hours/day of supervised intervention activities on 10 consecutive weekdays. Motor training was intensive and involved shaping. In addition, a group of behavior management strategies was employed to induce further unsupervised practice and transference of motor skills from the laboratory to real world situations. Changes in functional mobility, walking speed, balance, level of assistance, perceived quality of movement and level of confidence while performing daily activities were assessed five times in both the baseline and intervention phases. The outcomes observed after the intervention were determined by calculating the difference between the average scores obtained in both phases. Changes in perceived quality of movement, level of confidence, level of assistance, and balance were observed. Correspondence: Sarah dos Anjos, University of Alabama at Birmingham, 1720 2nd Avenue South, SHPB360. Birmingham, AL, USA. 35.294-0001. Disclosures: The authors have no conflict of interest. No funding was received. Clinicaltrials.gov: NCT03114046 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Effects of Whole Body Vibration on Motor Impairments in Patients with Neurological Disorders: A Systematic Review Objective This systematic review was conducted to examine the effects of whole body vibration (WBV) training on motor impairments among patients with neurological disorders, and to investigate which the whole body vibration training parameters induced improvement in motor impairments. Design PubMed, SCOPUS, PEDro, REHABDATA, and web of science were searched for randomized controlled trials and Pseudo- randomized controlled trials investigated the effect of WBV on motor impairments in patients with neurological disorders. The methodological quality was rated using the Cochrane Collaboration's tool Results Twenty studies were included in this systematic review. Four studies included patients with multiple sclerosis, cerebral palsy (n=2), stroke (n=9), Parkinson's disease (n=3), spinal cord injuries (n=1), and spino-cerebellar ataxia (n=1). The results showed different evidence of benefits and non-benefits for WBV training in motor impairments outcomes. Conclusion There is weak evidence for a positive effect of short-term WBV training on spasticity of lower extremities, mobility, balance and postural control. Besides, positive effect of the long-term effect of WBV training on mobility in patients with neurological disorders. The optimal WBV training parameters in treating patients with neurological disorders remain unclear. Anas Alashram, MSc, Doctorate Student in Neurology Department, Faculty of Medicine and Surgery, University of Rome "Tor Vergata", Italy, anasalashram@gmail.com Elvira Padua, PhD, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy. elvira.padua@unisanraffaele.gov.it Giuseppe Annino, PhD, Department of Medicine System, University of Rome "Tor Vergata", Italy, g_annino@hotmail.com Correspond author: Anas R. Alashram, Deperatment of Neurology University of Rome Tor Vergata, Rome, Italy E-mail: anasalashram@gmail.com Sources of funding/acknowledgements: The authors have no source of funding or any potential conflicts of interest to disclose. Funding or grants or equipment provided for the project from any source: None. Financial benefits to the authors: None. Details of any previous presentation of the research, manuscript, or abstract in any form: None. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ultrasound Imaging for Lateral Elbow Pain: Pinpointing the Epicondylosis No abstract available

Creation and initial validation of a picture-based version of the limitations of activity domain of the SF-36 Those with limited language comprehension or literacy face problems completing written questionnaires evaluating their health or physical status on which treatment plans are based. This brief report describes how a picture-based version of the 10 items in the limitations of activities (LoA) section of the SF-36 was developed iteratively and then piloted. Study participants: 101 community-living volunteers (58 female 43 male aged 18-93 years) educated to post-secondary level (52) high school grades 10-12 (44) and grade 9 or less (5). They first completed the picture-based SF-36LoA and described verbally and in writing what they understood each picture to mean, and then completed the English text version of the SF-36LoA domain for comparison assessment. Additional feedback suggested where pictures could be altered to increase information capture. Subjects rated their health as 26.7% excellent, 25.7% very good, 29.8% good, 10.9% fair and 6.9% poor. Analysis showed strong correlation between text-based SF-36LoA questions and the picture-based visual score – VSF-36LoA - (ICC=0.98) with question 10 correlating highest (ICC=0.90) and question 2 lowest (ICC=0.82). The VSF-36LoA is the first picture-based version of the SF-36; good correlation with the text-based version and global need warrants further development to aid those with limited literacy or language comprehension. Corresponding author: Macnab, Andrew John MD (London), Department of Pediatrics, University of British Columbia, Room C234, BC Children's Hospital, 4500 Oak Street, Vancouver, BC Canada V6H 3N1, phone: 604 875 2850, fax: 604 875 2530, ajmacnab@gmail.com Submitted to: American Journal of Physical Medicine and Rehabilitation Funding: none received Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The Usefulness of Basic Movement Scale in Hip Fracture Patients – Construct Validity from a Cross-Sectional Study Objective To investigate the validity of using total score and to examine the constitution and characteristics of the Basic Movement Scale (BMS) in post-surgery patients with hip fracture. Design The dimensionality and the threshold difficulty intervals between each score and item difficulty hierarchy of the BMS were examined using factor analysis and Rasch analysis in 37 patients admitted to our hospital between April and November 2015. Results For factor analysis, the contribution ratio of the first factor was 78.9%, that of the second factor was 6.5%, and there were no items that fit the Rasch analysis. The threshold was reversed at six of the 48 locations. The difficulty of the 12 BMS items was distributed roughly evenly among all 9 lots, with some deviation. There was one very easy item, and there were some items almost overlapping in difficulty. Conclusions The results showed a unidimensional association between the items and evaluation index. The difficulty threshold of each score was approximated to the interval scale. Therefore, the BMS has evident construct validity and enables quantitative evaluation of physical ability, assessment of the effects of daily training, and general predictions of the feasibility of patients' clinical goals. (190words) All correspondence and requests for reprints should be addressed to: Tai Takahashi, MD, PhD, Department of Social Services and Healthcare Management, School of Health and Welfare, International University of Health and Welfare, Akasaka 4-1-26, Minato-ku, Tokyo, Japan Phone: 03-5574-3900 FAX: 03-5574-3961 e-mail: taiiuhw@gmail.com) Author Disclosures: The authors have no conflicts of interest directly related to the content of this work. No funds, grants, or facilities were obtained for this project from any sources of funding, and there was no financial gain. This manuscript has not been published previously in any form. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Caring for Patients with Physical Disabilities: Assessment of an Innovative Spinal Cord Injury Session that Addresses an Educational Gap Despite the fact that one-fifth of Americans live with disability, caring for these patients is not routinely part of the undergraduate medical student curriculum. An innovative session addressing care of patients with spinal cord injury (SCI) was developed for medical students and led by physiatrists, faculty experts in communications and individuals with SCI. A mixed-method design was utilized in evaluating students' knowledge, skills and attitudes following this curriculum. Quantitative evaluation was performed with a written essay question and checklist items from an objective structured clinical examination (OSCE) station. The session was given to 296 students from 2016 to 2018. On the OSCE, 94% asked about sexual function, 85% asked about activities of daily living (ADL), 77% asked about instrumental activities of daily living (IADL) and 47% of students evaluated skin health. Students demonstrated respectful (99%) and non-judgmental (99%) attitudes with SCI standardized patients (SPs) and 91% interacted with the SP's caretaker appropriately. Themes emerged from the student survey including: the value of having real patients present during the session, exposure to physical medicine and rehabilitation (PM&R) as a specialty, and the advantage of a small group format. This session provided students with tools necessary to care for patients with SCI. Corresponding author: Janice Thomas John, DO, MS, MPH, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 500 Hofstra University, Hempstead, NY 11549, Phone: 516-463-7577 Fax: 516-463-5631; email: janice.t.john@hofstra.edu Author disclosures:Janice Thomas John DO, MS, MPH- nothing to disclose. Lauren Block MD, MPH - nothing to disclose. Adam Stein MD- nothing to disclose. Elizabeth Vasile, MPH- nothing to disclose. Maria-Louise Barilla-LaBarca MD-nothing to disclose Sources of funding: None Previous presentations: 2017 data was presented at: 1. Directors of Clinical Skills (DOCS) Annual Meeting, 2017. Boston, MA (poster). 2. Association of Academic Physiatrist (AAP) Annual Meeting, 2018 Atlanta, GA (platform presentation) Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Does performance on the American Board of Physical Medicine and Rehabilitation initial certification examinations predict future physician disciplinary actions? Objective To determine the relationship between performance on the American Board of Physical Medicine and Rehabilitation (ABPMR) primary certification examinations and the risk of subsequent disciplinary actions (DAs) by state medical boards over a physician's career. The hypothesis is that physicians who do not pass either or both of the two initial specialty certification examinations are at higher risk of disciplinary action (DA) from a state medical licensing board. Design This is a retrospective cohort study which analyzed board certification examination data from all physicians who completed Physical Medicine and Rehabilitation (PM&R) residency between 1968 and 2017. Results Matching examination and license data were available for 9,889 PM&R physicians, who received a total of 547 DA reports through the Federation of State Medical Boards. The results showed a significant correlation between failing an ABPMR certification examination and the risk of subsequent DA by a state medical board. Failure to pass either the written (Part I) or oral (Part II) examination increased the risk of subsequent DA by 5.77-fold (p< 0.0001, 95% Cl 4.07, 8.18). Conclusion Physicians in PM&R who do not pass initial certification examinations and become Board Certified are at higher risk of DA from a state medical licensing board throughout their careers. Dr. Kinney and Dr. Raddatz are employees of the American Board of Physical Medicine and Rehabilitation. No other disclosures. No funding was received for this study. Corresponding author: Carolyn L. Kinney, MD, American Board of Physical Medicine and Rehabilitation, 3015 Allegro Park Ln SW, Rochester, MN 55902, 507-282-1776, Ext. 1743, Email : ckinney@abpmr.org, Fax : 507-282-9242 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Vague Posterior Knee Discomfort in a Soccer Player: A Case Report A 24-year-old male soccer player presented with a 7-year history of left posterior knee "looseness." Evaluation 7 years ago, at the time of initial injury, revealed atraumatic ACL and PCL sprains. On re-presentation, the patient described the pain as a constant, dull ache, 3/10, but his biggest complaint was this feeling of "instability" and "looseness" where his knee would "buckle" 3-4 times a week. Physical exam was positive for grade 1 posterior drawer and grade 1 posterior sag signs. Reverse KT-1000 testing showed a 3 mm side-to-side difference. Sonographic evaluation confirmed MRI findings of PCL laxity and buckling and a small cystic lesion abutting the posteromedial margin of the distal 1/3 of the PCL. After a trial of physical therapy, the patient elected to undergo experimental injection of dextrose hyperosmolar solution. This resulted in resolution of the cyst and reverse KT-1000 measurements improved to a side-to-side difference of 1 mm. The patient's subjective feeling of "looseness" and "instability" resolved by 7 weeks. No funding was received for this study. Corresponding Author: Allison Schroeder, 2626 Tunnel Boulevard Apt 326, Pittsburgh, PA 15203, Email: aschroe1@alumni.nd.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Subtle dysmetria after a hemorrhage in the basal ganglia and lentiform nucleus No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com