Acute Response to Training after Returning from the Off-Season in Elite Rugby League Athletes.

The purposes of this study were to quantify the physiological response to the initial two-week preseason period in elite male rugby league (RL) athletes, and to determine if a repeated bout effect (RBE) occurs. Eighteen RL players were monitored for the initial two-week preseason period. Blood samples were collected on days (D)1, D2, D4, D5, D8, D9, D11 and D12 to measure creatine kinase (CK). Neuromuscular power was assessed on D1, D5, D8 and D12. During field-based sessions, the external training load was quantified using global positioning system technology, whilst the internal load was quantified using the training impulse and the session rating of perceived exertion. Resistance-based gym session volume was quantified by total repetitions x weight lifted. Perceived measures of fatigue and muscle soreness were assessed on all training days. Two-way (day x week) repeated measures analysis of variance and Bonferroni's corrected post-hoc tests identified significant changes. There were no significant changes in CK activity (649.2 ± 255.0 vs. 673.8 ± 299.1 µL; p = 0.63) or internal training load measures from week 1 to week 2. External training load measures including total distance (4138.1 ± 198.4 vs. 4525.0 ± 169.2 m; p < 0.001) and repeated high-intensity efforts (12.6 ± 1.8 vs. 17.5 ± 1.8 au; p < 0.001) significantly increased in week 2 compared to week 1. Internal training loads and CK activity did not change in response to an increase in external training loads during the initial preseason. The current results provide support for a 'real world' perspective of the RBE phenomenon that may be more applicable for team sport practitioners.

Community engagement to implement evidence-based practices in the HEALing communities study.

BACKGROUND: The implementation of evidence-based practices to reduce opioid overdose deaths within communities remains suboptimal. Community engagement can improve the uptake and sustainability of evidence-based practices. The HEALing Communities Study (HCS) aims to reduce opioid overdose deaths through the Communities That HEAL (CTH) intervention, a community-engaged, data-driven planning process that will be implemented in 67 communities across four states. METHODS: An iterative process was used in the development of the community engagement component of the CTH. The resulting community engagement process uses phased planning steeped in the principles of community based participatory research. Phases include: 0) Preparation, 1) Getting Started, 2) Getting Organized, 3) Community Profiles and Data Dashboards, 4) Community Action Planning, 5) Implementation and Monitoring, and 6) Sustainability Planning. DISCUSSION: The CTH protocol provides a common structure across the four states for the community-engaged intervention and allows for tailored approaches that meet the unique needs or sociocultural context of each community. Challenges inherent to community engagement work emerged early in the process are discussed. CONCLUSION: HCS will show how community engagement can support the implementation of evidence-based practices for addressing the opioid crisis in highly impacted communities. Findings from this study have the potential to provide communities across the country with an evidence-based approach to address their local opioid crisis; advance community engaged research; and contribute to the implementation, sustainability, and adoption of evidence-based practices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04111939).

Therapeutic leukocytapheresis in infants and children with leukemia and hyperleukocytosis: A single institution experience.

BACKGROUND: Hyperleukocytosis, defined as white blood cell (WBC) count above 100 × 109 /L, has high early morbidity and mortality from leukostasis-related complications, namely intracranial hemorrhage and pulmonary distress. Initiating chemotherapy without prior leukocytoreduction may lead to tumor lysis syndrome (TLS). Therapeutic leukocytapheresis (TL) is used as one leukocytoreductive intervention; however, its safety and efficacy in pediatric leukemia has not been established. The purpose of this study is to evaluate safety of TL in pediatric patients and assess the efficacy of TL in reducing WBC count in pediatric leukemia. METHODS: Retrospective chart review was conducted on 14 patients with acute lymphoblastic leukemia (ALL) and 5 with acute myeloid leukemia (AML) who underwent TL during the period 2000-2014 at a single institution. RESULTS: Mean WBC count of 19 patients who received TL was 483.2 × 109 /L (547.1 in ALL, 304.3 in AML); a portion of patients presented with central nervous system symptoms (15%), respiratory symptoms (10%), or both (10%). TL reduced WBC count (mean 50.7% reduction after a single TL procedure; additional 17.1% reduction after a second TL procedure in 6 patients). Short-term survival immediately following TL was 100% without any major procedural complication. Mean survival time in patients with AML was 1.5 years and with ALL was 6.5 years. CONCLUSIONS: TL significantly reduces WBC number in pediatric leukemia patients as young as 22 days old. In our retrospective study, TL was not associated with any significant complications and suggests that TL is a safe initial procedure in pediatric leukemia.

PLAYERS' PERCEPTIONS OF HOME ADVANTAGE IN THE AUSTRALIAN RUGBY LEAGUE COMPETITION.

This study was designed to pilot a survey to explore players' perception of home advantage in a rugby league. Twenty-seven players from one team with an identified home advantage believed a home advantage existed as a result of their home crowd (52%), family and friends' support (41%), normal travel (45%) and sleeping arrangements (37%), home weather conditions (48%), and familiarity with playing amenities (37%). However, the players were less definite about influences while playing away from home. The current sample of players identified differing influences, highlighting individual variations in perceived determinants. Individual interviews or focus groups will be required for further exploration.

The effects of air travel on performance measures of elite Australian rugby league players.

The current study explored the effects of short haul air travel within the same country on elite Australian rugby league (RL) players (n=12) during two away and two home games of elite competition. Physiological tests of handgrip strength and leg power were assessed along with psychological tests and perceptions of leg soreness and tiredness on the day before the game (Time 1 and Time 2) and on game day (Time 3). Game statistics of tackles and metres gained were assessed for the games analysed. Significant differences were found for daily analyses of life demands for athletes (DALDA) worse than normal responses at Time 2 (2.50 ± 3.23 vs. 3.50 ± 3.93; P=0.04), Karolinska Sleepiness Scale (KSS) at Time 2 (2.88 ± 1.51 vs. 3.71 ± 1.37; P=0.011) and leg tiredness at Time 3 (3.38 ± 1.66 vs. 2.35 ± 1.70; P=0.004) between home and away games. The analysis of game statistics identified that more metres were gained during home games (83.6 ± 49.1 vs. 63.0 ± 30.1; P=0.02) and more tackles made while playing away (18.4 ± 9.2 vs. 14.3 ± 6.7; P=0.016). The results suggest that short haul air travel without crossing time zones results in symptoms of travel fatigue but does not appear to negatively impact on elite RL players ability to perform strength and power tasks. Different game tactics (attacking vs. defensive) occurred between home and away games however, it is unclear whether travel fatigue or a home advantage (HA) is associated with this finding.

Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project.

One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1-like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that approximately half of these patients had genomic lesions leading to CRLF2 overexpression, with half of such cases harboring somatic mutations in the Janus kinases JAK1 and JAK2. To determine whether mutations in other tyrosine kinases might also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with either a Ph-like gene expression profile or other alterations suggestive of activated kinase signaling. Aside from JAK mutations and 1 FLT3 mutation, no somatic mutations were found in any other tyrosine kinases, suggesting that alternative mechanisms are responsible for activated kinase signaling in high-risk ALL.

Pre-Clinical Evaluation of rHDL Encapsulated Retinoids for the Treatment of Neuroblastoma.

Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (NB) (HRNB). The long term survival rates of HRNB in the United States are still only 30-50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL) containing fenretinide (FR) nanoparticles as a novel approach to current NB therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40 nm) and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/FR toward the NB cell lines SK-N-SH and SMS-KCNR showed 2.8- and 2-fold lower IC50 values for the rHDL encapsulated FR vs. free FR. More importantly, the IC50 value for retinal pigment epithelial cells (ARPE-19), a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100-fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and NB in particular.

Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as "best risk" if they had cleared MRD by day 8 of therapy and as "worst risk" if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing "best" and "worst" risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

Injectable skin fillers.

The list of injectable skin fillers available for soft tissue augmentation is constantly growing, giving aesthetic surgeons more options in the treatment of scars, lines, and wrinkles. Each type of filler is distinct with regard to intended use, placement technique, duration in tissue, ease of use, and cost. Physicians who are well acquainted with the strengths and weaknesses of each class of filler will be best equipped to use this rapidly expanding class of agents in serving their patients. The authors review the most commonly used injectable skin fillers and discuss their differences in terms of composition, source (eg, human, animal), intended use, placement technique, tissue duration (nonpermanent, semipermanent, or permanent), side effects, and specific advantages and disadvantages.

Epidermodysplasia verruciformis.

Epidermodysplasia verruciformis is an uncommon cutaneous entity characterized by persistent human papillomavirus infection. A defect in cell-mediated immunity is the suggested causative factor. Numerous specific human papillomavirus types have been detected in this disease. Multiple nonmelanoma skin cancers are commonly seen in such patients; thus, early diagnosis is beneficial.

Basosquamous carcinoma.

BACKGROUND: Basosquamous carcinoma (BSC) is a rare cutaneous tumor that has been poorly described in the dermatologic literature. It has been depicted as an aggressive tumor with a high incidence of distant metastasis. OBJECTIVE: To examine the average extent of local tissue invasion and presence of distant metastases in cases of BSC compared with those of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: One thousand consecutive Mohs surgery cases performed between January 1993 and May 1995 at the Oschner Clinic in New Orleans, Louisiana, for histologically confirmed BCC, SCC, and BSC were reviewed. Each case was retrospectively evaluated for tumor type, anatomic location, number of Mohs stages performed, and presence of metastases at the time of surgery, as determined by chest radiograph. RESULTS: Seven hundred forty-five BCCs, 228 SCCs, and 27 BSCs (1,000 tumors total) were treated in 580 patients. The average number of stages required for clear margins in cases of BCC, SCC, and BSC was 1.62, 1.51, and 2.00, respectively. The prevalence of metastasis was 0.87% for SCC and 7.4% for BSC, which was statistically significant (P<0.001). CONCLUSION: In this retrospective study, BSCs displayed tissue invasion similar to that of BCC or SCC but had a higher frequency of pulmonary metastasis than SCC.

Confluent and reticulated papillomatosis: response to tazarotene.

Confluent and reticulated papillomatosis of Gougerot and Carteaud is an uncommon dermatosis of unclear cause that can be recalcitrant to therapy. We report the case of an 11-year-old black girl with the eruption in whom it completely cleared using tazarotene gel. The treatment was well-tolerated and we suggest considering topical tazarotene as an alternative to systemic retinoid therapy.

Periocular reconstruction.

The periocular area is a complex region with free margins and cosmetic landmarks that are easily distorted during surgical reconstruction. Repair of surgical defects should maintain both periorbital function and aesthetics. In this article we discuss the basic methods of closure (side-to-side closure, flaps, grafts and second intent healing) as they apply to the periocular area and suggest an algorhythmic approach to reconstruction by aesthetic subunit. Pertinent regional anatomy and perioperative management are also reviewed.

Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel versus clobetasol ointment in the treatment of plaque psoriasis: a pilot study.

BACKGROUND: Both calcipotriene and tazarotene have been shown to be effective in the treatment of psoriasis. No study has evaluated the effect of using both agents simultaneously. OBJECTIVE: Our purpose was to evaluate the effectiveness of combination treatment of psoriasis with calcipotriene ointment and tazarotene gel by comparing them with clobetasol ointment, a class I topical corticosteroid. A secondary objective was to evaluate the clinical compatibility of applying both agents at the same time. METHODS: This pilot study was a prospective, single-center, open-label, right/left comparison of 28 lesion pairs in 15 patients. It consisted of a 2-week treatment phase, followed by a 4-week post-treatment observation phase. RESULTS: All 15 patients completed the treatment phase of the study. At the end of the active treatment phase (end of week 2), calcipotriene- and tazarotene-treated lesions showed nearly identical reductions in scaling (P =.93), plaque elevation (P =.76), and overall lesional severity scores (P =.29) compared with their matched clobetasol-treated counterparts. Erythema improved significantly more in clobetasol-treated lesions (P <.05) during the treatment period, but differences became statistically insignificant during the post-treatment period (;P =.20). No patients had significant irritation from the treatments. During the post-treatment phase (weeks 3-6), all lesions worsened; plaque elevation returned somewhat more rapidly in calcipotriene- and tazarotene-treated lesions (P <.01), whereas changes in scaling, erythema, and overall lesional severity were not significantly different between the two treatment groups (P >.05). CONCLUSION: The nonsteroid combination of twice-daily calcipotriene ointment and once-daily tazarotene gel was not statistically different from twice-daily application of the class I corticosteroid clobetasol ointment in reducing psoriatic scaling, plaque elevation, and overall lesional severity over a 2-week period. There does not seem to be any chemical incompatibility between calcipotriene ointment and tazarotene gel that is clinically significant.