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Introduction: This scoping review evaluated the efficacy/effectiveness and utilization of complementary and integrative health (CIH) therapies for pain management within the Military Health System (MHS). Specifically, it aimed to assess evidence-based modalities such as acupuncture, biofeedback, hypnosis, massage therapy, meditation, guided imagery, Tai Chi/Qi Gong, and yoga, which are part of the Veterans Administration's (VA) Whole Health program. The goal was to determine their effectiveness in military service members and understand their utilization in the MHS, as well as explore CIH research in the MHS to identify gaps. Methods: A comprehensive search of PubMed, Embase, and Ovid All EBM Reviews databases was conducted for studies published from January 1, 2014 to March 22, 2024. The search focused on CIH therapies related to pain management in military populations, yielding 433 studies. After screening for eligibility, 53 studies were included for detailed review. Studies included randomized controlled trials, case studies, large database analyses, and retrospective chart reviews. Exclusion criteria eliminated nonpeer-reviewed articles, not pain-related, not related to one of the prespecified CIH modalities (acupuncture, biofeedback, hypnosis, massage therapy, meditation, guided imagery, Tai Chi/Qi Gong, and yoga), and those not specific to the MHS. The review did not address bias due to the heterogeneity of study designs included. Results: The review identified significant evidence supporting the use of CIH modalities for pain management. Acupuncture, particularly Battlefield Acupuncture, showed immediate reduction in pain score for both acute and chronic pain. Studies of massage therapy and biofeedback demonstrated efficacy/effectiveness in reducing pain and improving functional outcomes in various musculoskeletal and stress-related disorders. Meditation and yoga were shown to be effective for chronic pain, stress management, and enhancing overall well-being. Utilization data indicated a steady increase in CIH therapy use across military facilities. Discussion: CIH therapies, particularly acupuncture, massage therapy, and yoga, appear to be effective nonpharmacologic interventions for pain management in military populations. Their growing utilization reflects the recognition of their benefits in managing chronic pain and improving quality of life among service members. Further research is needed to standardize practices and optimize utilization across the MHS. Registration of Protocol: PROSPERO 2024 CRD4202453685, 29 April 2024, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024536853.

Sport diversification provides opportunities for individuals to develop physical literacy, establish a growth mindset, become more agile in varied environments, and develop robust strategies to improve performance. One could say the same for biomechanists, who study the control and dynamics of human movements in the context of sport. Through the lens of sport, we have focused on the ongoing interaction between the nervous system, musculoskeletal system, and the environment by using integrated experimental and modelling approaches to study well-practiced, goal-directed tasks in controlled laboratory and realistic field settings. By integrating multiple sources of information in real time to provide timely, relevant, usable, and easy to understand (TRUE) feedback during skill acquisition, we have found these resources also support learning and opportunities for self-discovery of proficiencies by coaches and athletes. Managing multimodal data acquired with emerging technological advances has also benefited from the use of FAIR data management principles, where data are findable, accessible, interoperable, and reusable. By listening, clarifying goals, and exploring together with coaches and athletes, we can bridge the gaps between what we know and what we do.

Objective: To describe the incidence of cardiotoxicity in patients with anthracycline exposure who subsequently receive EPOCH for non-Hodgkin lymphoma (NHL)., Methods: We conducted a retrospective cohort study of adults with anthracycline exposure who subsequently received EPOCH for NHL at Memorial Sloan Kettering Cancer Center. The primary outcome was cumulative incidence of arrhythmia, heart failure (HF), left ventricular (LV) dysfunction, or cardiac death., Results: Among 140 patients, most had diffuse large B-cell lymphoma. Inclusive of EPOCH, median cumulative doxorubicin-equivalent dose was 364 mg/m 2 ; exposure was 400 mg/m 2 or higher in 41%. With median 36-month follow-up, 23 cardiac events were noted in 20 patients. Cumulative incidence of cardiac events at 60 months was 15% (95% confidence interval [CI]: 9%-21%). When limited to LV dysfunction/HF, cumulative incidence at 60 months was 7% (95% CI: 3%-13%), with most events occurring after the first year. Univariate analysis indicated only history of cardiac disease and dyslipidemia to be associated with cardiotoxicity; no other risk factors, including cumulative anthracycline dose, were identified., Conclusions: In this retrospective cohort, representing the largest experience in this setting with extended follow-up, cumulative incidence of cardiac events was low. Rates of LV dysfunction or HF were particularly low, suggesting infusional administration may mitigate risk despite prior exposure., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Index-based methods estimate a fixed value of groundwater vulnerability (GWV); however, the effects of time variations on this estimation have not been comprehensively studied. It is imperative to estimate a time-variant vulnerability that accounts for climatic changes. In this study, we used a Pesticide DRASTICL method separating hydrogeological factors into dynamic and static groups followed by correspondence analysis. The dynamic group is composed of depth and recharge, and the static group is composed of aquifer media, soil media, topography slope, impact of vadose zone, aquifer conductivity and land use. The model results were 42.25-179.89, 33.93-159.81, 34.08-168.74, and 45.56-205.20 for spring, summer, autumn, and winter, respectively. The results showed a moderate correlation between the model predictions and observed nitrogen concentrations with R 2  = 0.568 and a high correlation for phosphorus concentrations with R 2  = 0.706. Our results suggest that the time-variant GWV model provides a robust yet flexible method for investigating seasonal changes in GWV. This model is an improvement to the standard index-based methods, making them sensitive to climatic changes and portraying a true vulnerability estimation. Finally, the correction of the rating scale value fixes the problem of overestimation in standard models., (© 2023. The Author(s).)

One-lung ventilation (OLV) can be accomplished utilizing a double-lumen tube (DLT) and an endobronchial blocker (EBB) or intentionally placing a standard endotracheal tube (ETT) into a mainstem bronchus. However, secondary options must be available should the primary method fail. We present a case where an EBB and a fiberoptic bronchoscope (FOB) were successfully passed through a left-sided DLT to reestablish right-lung isolation after the DLT bronchial cuff was surgically damaged. We advocate competency in placing both DLTs and EBBs, as well as having EBBs readily accessible as a secondary isolation method during OLV., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Introduction: Part B of the modified Magrath regimen (IVAC) +/- rituximab (R) is recommended as standalone therapy by national guidelines for management of relapsed/refractory Burkitt lymphoma, and is used in other non-Hodgkin lymphomas (NHL). Activity of IVAC in B-cell NHL, particularly with R, and its toxicity remain incompletely described., Patients and Methods: We reviewed patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 2004 and 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity., Results: Among 54 eligible patients (median 2 prior lines of therapy), 76% had diffuse large B-cell lymphoma; 30% had central nervous system involvement at IVAC initiation. Objective response rate was 48%. At median 22-month follow-up, median progression-free and overall survival were 3.1 months and 4.9 months, respectively. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common. Febrile neutropenia occurred in 65% and did not appear to be influenced by use of antimicrobial or granulocyte colony stimulating factor prophylaxis. Mortality was attributed to treatment in 19% of evaluable patients., Conclusion: The clinical efficacy and utility of IVAC +/- R remain unclear. However, its profound hematologic toxicity and life-threatening complications despite prophylactic measures warrant careful consideration of alternatives., Competing Interests: Disclosure DJS reports consultancy for Seattle Genetics, NY Lymphoma Rounds, and Targeted Oncology, membership on an entity's board of directors or advisory committees for Seattle Genetics, Elsevier, and Karyopharm Therapeutics, research funding from Takeda Pharmaceuticals, speakers bureau for OncLive, Takeda Pharmaceuticals, Targeted Oncology, and Imedex Inc., CME writing for Elsevier, and conference in December 2019 on HL to other physicians during ASH. The other authors have no relevant financial relationships to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Ventilator associated pneumonia (VAP) rate has been tracked as a comparable quality measure but there is significant variation between types of ICUs. We sought to understand variability and improve its utility as a marker of quality., Methods: The National Trauma Database was surveyed to identify risk factors for VAP. Logistic regression, χ 2 , Student's T-test or Mann-Whitney U test were used., Results: Risk factors associated with developing VAP were: injury severity score (ISS) (OR 1.03, 95% CI 1.03 -1.04), prehospital assisted respiration (PHAR) (OR 1.10, 1.03 -1.17), thoracic injuries (OR 2.28, 1.69-3.08), diabetes (OR 1.32, 1.20 -1.46), male gender (OR 1.38, 1.28 -1.60), care at a teaching hospital (OR 1.40, 1.29 -1.47) and unplanned intubation (OR 2.76, 2.52-3.03)., Discussion: ISS, PHAR, diabetes, male gender, care at a teaching hospital and unplanned intubation are risk factors for the development of VAP. These factors should be accounted for in order to make VAP an effective quality marker.

The Millennium Drought (southeastern Australia) provided a natural experiment to challenge the assumption that watershed streamflow always recovers from drought. Seven years after the drought, the runoff (as a fraction of precipitation) had not recovered in 37% of watersheds, and the number of recovered watersheds was not increasing. When recovery did occur, it was not explained by watershed wetness. For those watersheds not recovered, ~80% showed no evidence of recovering soon, suggesting persistence within a low-runoff state. The post-drought precipitation not going to runoff was found to be likely going to increased evapotranspiration per unit of precipitation. These findings show that watersheds can have a finite resilience to disturbances and suggest that hydrological droughts can persist indefinitely after meteorological droughts., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: To discuss (1) recent and emerging data for pharmacological management of untreated and relapsed/refractory (R/R) mantle cell lymphoma (MCL) with agents approved in the United States, (2) important considerations for toxicity monitoring and management, and (3) preliminary data and ongoing studies for agents in MCL-specific clinical trials. Data Sources: PubMed/MEDLINE, EMBASE, Google Scholar, product labeling, National Comprehensive Cancer Network, American Cancer Society, and ClinicalTrials.gov were searched for studies published between January 1, 2017, and January 31, 2020, and key historical trials. Study Selection and Data Extraction: Relevant studies conducted in humans and selected supporting preclinical data were reviewed. Data Synthesis: MCL is a rare but usually aggressive non-Hodgkin lymphoma that most commonly affects the older population. Traditionally, the treatment of MCL has been determined based on transplant eligibility. Newer data suggest that more tolerable frontline therapy may produce outcomes similar to intensive historical induction regimens, possibly precluding fewer patients from autologous stem cell transplant and producing better long-term outcomes in transplant-ineligible patients. In the R/R setting, novel regimens are improving outcomes and changing the landscape of treatment. Relevance to Patient Care and Clinical Practice: This review summarizes and discusses recent and emerging data for management of newly diagnosed and R/R MCL; key supportive care considerations for agents are also discussed. Conclusions: Recent study results are changing management of MCL. Although these data have complicated the picture of regimen selection, increasingly effective and tolerable therapy and additional anticipated data point to a brighter future for patients with MCL.

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of selinexor for management of relapsed multiple myeloma (MM). Data Sources: A literature search was performed of PubMed and MEDLINE databases (January 1, 2000, to November 14, 2019), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from US National Institutes of Health ClinicalTrials.gov. Queries were performed using key words selinexor, SINE, XPO1 , and Xpovio. Study Selection/Data Extraction: Human and animal studies related to the pharmacology, pharmacokinetics, efficacy, and safety of selinexor were identified. Data Synthesis: Although numerous advances have been made in MM management, there remains an unmet need for treatment of heavily relapsed/refractory disease. Selinexor is a first-in-class selective inhibitor of nuclear export, which, through inhibition of exportin-1, causes accumulation of tumor suppressor proteins, reduction in oncoproteins, and apoptosis of plasma cells. Selinexor exhibited an overall response in 26% of patients with multiply relapsed MM. Median progression-free survival was 3.7 months, and overall survival was 8.6 months. Common adverse effects include thrombocytopenia, neutropenia, fatigue, and nausea. Ongoing studies are investigating combination therapies utilizing selinexor. Relevance to Patient Care and Clinical Practice: This review describes the efficacy, safety, and clinical applicability of selinexor, a novel agent with potential to meet an unmet need in refractory MM. Conclusion: Selinexor has demonstrated activity in a heavily refractory patient population. Given the adverse effect profile and associated costs, additional studies are needed to further elucidate the appropriate clinical scenario and combinations for selinexor use.

Groundwater management decisions are often founded upon estimates of aquifer hydraulic properties, recharge and the rate of groundwater usage. Too often hydraulic properties are unavailable, recharge estimates are very uncertain, and usage is unmetered or infrequently metered over only recent years or estimated using numerical groundwater models decoupled from the drivers of drawdown. This paper extends the HydroSight groundwater time-series package ( http://peterson-tim-j.github.io/HydroSight/) to allow the joint estimation of gross recharge, transmissivity, storativity, and daily usage at multiple production bores. A genetic evolutionary scheme was extended from estimating time-series model parameters to also estimating time series of usage that honor metered volumes at each production bore and produces (1) the best fit with the observed hydrograph and (2) plausible estimates of actual evapotranspiration and hence recharge. The reliability of the approach was rigorously tested. Repeated calibration of models for four bores produced estimates of transmissivity, storativity, and mean recharge that varied by a factor of 0.22-0.32, 0.13-0.2, and 0.03-0.48, respectively, when recharge boundary effects were low and the error in monthly, quarterly, and biannual metered usage was generally <10%. Application to the 30 observation bores within the Warrion groundwater management area (Australia), produced a coefficient of efficiency of ≥0.80 at 22 bores and ≥0.90 at 12 bores. The aquifer transmissivity and storativity were reasonably estimated, and were consistent with independent estimates, while mean gross recharge may be slightly overestimated. Overall, the approach allows greater insights from the available data and provides opportunity for the exploration of usage and climatic scenarios., (© 2019, National Ground Water Association.)

Golf shots off uneven terrain often require modifications in address position to complete the swing successfully. This study aimed to determine how golf players coordinate the legs to regulate linear and angular impulse (about an axis passing vertically through the center of mass) while modifying the lower extremity address position during the swing. Nine highly skilled golf players performed swings with a 6-iron under the Normal, Rear Leg Up and Target Leg Up conditions. Components of linear and angular impulse generated by the rear and target legs (resultant horizontal reaction force, resultant horizontal reaction force angle, and moment arm) were quantified and compared across the group and within a player (α = .05). Net angular impulse did not change between conditions. Target leg angular impulse was greater in the Target Leg Up condition than Rear Leg Up condition. Regulation of linear and angular impulse generation occurred while increasing stance width and redirecting resultant horizontal reaction forces to be more parallel to the target line under modified address positions. Net linear impulse perpendicular to the target was near zero or slightly posterior. Net linear impulse parallel to the target was less toward the target in the Target Leg Up condition compared to Normal and Rear Leg Up conditions. These results indicate individuals utilized player specific mechanisms to coordinate the legs and regulate impulse generation during the golf swing under modified address positions.

Plasticity is an important aspect of the neural control of breathing. One well-studied form of respiratory plasticity is phrenic long-term facilitation (pLTF) induced by acute intermittent but not sustained hypoxia. Okadaic acid-sensitive protein phosphatases (PPs) differentially regulate phrenic nerve activity with intermittent vs. sustained hypoxia, at least partially accounting for pLTF pattern sensitivity. However, okadaic acid inhibits multiple serine/threonine phosphatases, and the relevant phosphatase (PP1, PP2A, PP5) for pLTF pattern sensitivity has not been identified. Here, we demonstrate that sustained hypoxia (25 min, 9-10.5% O 2 ) elicits phrenic motor facilitation in rats pretreated with bilateral intrapleural injections of small interfering RNAs (siRNAs; Accell-modified to preferentially transfect neurons, 3.33 μM, 3 days) targeting PP1 mRNA (48 ± 14% change from baseline, n = 6) but not PP2A (14 ± 9% baseline, n = 6) or nontargeting siRNAs (4 ± 10% baseline, n = 7). In time control rats (no hypoxia) treated with siRNAs ( n = 6), no facilitation was evident (-9 ± 9% baseline). siRNAs had no effect on the hypoxic phrenic response. Immunohistochemistry revealed PP1 and PP2A protein in identified phrenic motoneurons. Although PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, we were not able to verify "knockdown" in vivo after siRNA treatment. On the other hand, PP1 and PP2A siRNAs significantly decreased PP1 and PP2A mRNA in PC12 cell cultures, verifying the intended siRNA effects. In conclusion, PP1 (not PP2A) is the relevant okadaic acid-sensitive phosphatase constraining phrenic motor facilitation after sustained hypoxia and likely contributing to pLTF pattern sensitivity. NEW & NOTEWORTHY This study demonstrates that the relevant okadaic acid-sensitive Ser/Thr protein phosphatase (PP) constraining facilitation after sustained hypoxia is PP1 and not PP2A. It suggests that PP1 may be critical in the pattern sensitivity of hypoxia-induced phrenic motor plasticity.

Prevalent molecular alterations of the phosphoinositide 3-kinase (PI3K) pathway are found on solid tumors and are expressed in leukocytes, making it a desirable target in both solid and hematologic malignancies. In recent years, two agents targeting this pathway have been approved by the United States Food and Drug Administration, idelalisib and copanlisib, with many others under investigation. Due to the off-target effects seen with these agents, those under development have varying isoform specificity that mitigates toxicity. In this review, we attempt to illustrate the varying differences among these agents, both mechanistically as well as highlight differences in their respective adverse effect profiles., (© 2018 Pharmacotherapy Publications, Inc.)

This study aimed to understand how players coordinate the multi-joint control strategies of the rear and target legs to satisfy the lower extremity and whole-body mechanical objectives during the golf swing when hitting shots with different clubs. Highly skilled golf players (n = 10) performed golf swings with a 6-iron and a driver. Joint kinetics were calculated using ground reaction forces and segment kinematics to determine net joint moments (NJMs) during the interval of interest within the downswing. Between club difference in NJMs and 3D support moments were compared across the group and within a player. Although player-specific multi-joint control strategies arose, players generally increased target leg ankle, knee, and hip NJMs when hitting with the driver while maintaining the relative contribution to the 3D support moment. Multi-joint control strategies used to control the target and rear legs were found to be different, yet the majority of the 3D support moment was produced by NJMs about an axis perpendicular to the leg planes. These results emphasize the importance of recognizing how an individual player coordinates multi-joint control from each leg, and highlights the need to design interventions that are player and leg specific to aid in improving player performance., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The paper reviews advances and insights relevant to comparing groups when the sample sizes are small. There are conditions under which conventional, routinely used techniques are satisfactory. But major insights regarding outliers, skewed distributions, and unequal variances (heteroscedasticity) make it clear that under general conditions they provide poor control over the type I error probability and can have relatively poor power. In practical terms, important differences among groups can be missed and poorly characterized. Many new and improved methods have been derived that are aimed at dealing with the shortcomings of classic methods. To provide a conceptual basis for understanding the practical importance of modern methods, the paper reviews some modern insights related to why methods based on means can perform poorly. Then some strategies for dealing with nonnormal distributions and unequal variances are described. For brevity, the focus is on comparing 2 independent groups or 2 dependent groups based on the usual difference scores. The paper concludes with comments on issues to consider when choosing from among the methods reviewed in the paper.

Background: The objective of this study was to evaluate the short-term and long-term outcomes of adult patients with hematologic malignancies who received chemotherapy in the intensive care unit (ICU)., Methods: This was a retrospective, single-center study comparing the outcomes of patients with hematologic malignancies who received chemotherapy in the ICU with a matched cohort of ICU patients who did not receive chemotherapy. Conditional logistic regression and shared-frailty Cox regression were used to assess short-term (ICU and hospital) mortality and death by 12 months after hospital discharge, respectively., Results: One hundred eighty-one patients with hematologic malignancies received chemotherapy in the ICU. The ICU and hospital mortality rates were 25% and 42% for chemotherapy patients and 22% and 33% for non-chemotherapy patients, respectively. Higher severity of illness scores on ICU admission were significantly associated with higher ICU mortality (odds ratio, 1.07; P < .001) and hospital mortality (odds ratio, 1.05; P ≤ .001). Six-month and 12-month survival estimates posthospital discharge were 58% and 50%, respectively. Compared with the matched cohort of patients who did not receive chemotherapy, those who did receive chemotherapy had a significantly longer length of stay in the ICU (median, 6 vs 3 days; P < .001) and in the hospital (median, 22 vs 14 days; P = .024). In multivariable analysis, the patients who received chemotherapy in the ICU had a trend toward a higher risk of dying by 12 months (hazard ratio, 1.45; P = .08)., Conclusions: Short-term mortality was similar among patients with hematologic malignancies who did and did not receive chemotherapy in the ICU, although patients who received chemotherapy had increased resource utilization. These results may inform ICU triage and goals-of-care discussions with patients and their families regarding outcomes after receiving chemotherapy in the ICU. Cancer 2018;124:3025-36. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

The efficacy of carbohydrate (CHO) ingestion during high-intensity strength and conditioning type exercise has yield mixed results. However, little is known about shorter duration high-intensity exercise such as CrossFit. The purpose of this study was to investigate the performance impact of CHO ingestion during high-intensity exercise sessions lasting approximately 30 min. Eight healthy males participated in a total of four trials; two familiarizations, a CHO trial, and a similarly flavored, non-caloric placebo (PLA) trial. CrossFit's "Fight Gone Bad Five" (FGBF) workout of the day was the exercise model which incorporated five rounds of maximal repetition exercises, wall throw, box jump, sumo deadlift high pull, push press, and rowing, followed by one minute of rest. Total repetitions and calories expended were summated from each round to quantify total work (FGBF score). No difference was found for the total work between CHO (321 ± 51) or PLA (314 ± 52) trials ( p = 0.38). There were also no main effects ( p > 0.05) for treatment comparing exercise performance across rounds. Based on the findings of this study, it does not appear that ingestion of CHO during short duration, high-intensity CrossFit exercise will provide a beneficial performance effect., Competing Interests: The authors report no conflict of interests.

The purpose of this study was to investigate the impact of ingesting an amino acid-electrolyte (AAE) beverage during upper body resistance exercise on transient muscle hypertrophy, exercise performance, markers of muscle damage, and recovery. Participants ( n = 15) performed three sets of six repetitions-bench press, lat pull down, incline press, and seated row-followed by three sets of eight repetitions at 75% of the estimated 1 repetition maximum-triceps kickback, hammer curl, triceps push down, and preacher curl-with 90 s of rest between sets. The final set of the push down/preacher curl was performed to failure. Prior to and immediately post-exercise, as well as 24, 48, and 72 h post exercise, cross-sectional muscle thickness was measured. Blood samples were collected prior to exercise, as well as 24, 48, and 72 h post-exercise for serum creatine kinase (CK) analysis. No treatment effect was found for muscle cross-sectional area, repetitions to failure, or serum CK. A main effect ( p < 0.001) was observed in the change in serum CK levels in the days following the resistance exercise session. The findings of this study suggest that the acute ingestion of a AAE beverage does not alter acute muscle thickness, performance, perceived soreness and weakness, or markers of muscle damage., Competing Interests: JohnEric W. Smith is a member of the Dymatize Nutrition Advisory Board. Other authors declare no potential conflicts of interest. Dymatize Enterprises, LLC, provided beverage powder for this study but had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

The purpose of this investigation was to examine to the influence of carbohydrate ingestion (CHOI) and carbohydrate mouth rinse (CHOR) on acute repeat maximal sprint performance. Fourteen healthy males (age: 21.7 ± 1.8 years, mass: 82.3 ± 12.3 kg) completed a total of five 15-s maximal repeat sprints on a cycle ergometer against 0.075 kg ・ kg -1 body mass each separated by 4 min of active recovery. Subjects completed four experimental trials and were randomly assigned one of four treatments: (1) CHOI, (2) CHOR, (3) placebo mouth rinse (PLAR), (4) placebo ingestion (PLAI). Subjects rinsed or ingested six 50 mL 10% CHO solutions throughout each trial. Performance variables measured included rating of perceived exertion, peak heart rate, peak and mean power output, fatigue index, and total work. Significant treatment main effects were observed for mean power output (p = 0.026), total work (p = 0.020), fatigue index (p = 0.004), and heart rate (p = 0.013). Overall mean power output and total work were significantly greater with CHOI (659.3 ± 103.0 watts, 9849.8 ± 1598.8 joules) compared with CHOR (645.8 ± 99.7 watts, 9447.5 ± 1684.9 joules, p < .05). CHOI (15.3 ± 8.6 watts/s) significantly attenuated fatigue index compared with CHOR (17.7 ± 10.4 watts/s, p < .05). Based on our findings, CHOI was more likely to provide a beneficial performance effect compared with CHOR, PLAI, and PLAR. Athletes required to complete repeat bouts of high intensity exercise may benefit from CHOI.

Objective: To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies., Data Sources: A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta., Study Selection/data Extraction: Studies of pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of venetoclax in lymphoid malignancies were identified., Data Synthesis: Recently, treatment of B-cell lymphoproliferative disorders has shifted from conventional cytotoxic chemotherapy to novel small-molecule inhibitors. The advent of recently Food and Drug Administration-approved oral agents ibrutinib and idelalisib has shifted the paradigm of chronic lymphocytic leukemia (CLL) treatment; however, complete remission is uncommon, and the outcome for patients progressing on these treatments remains poor. Attention has been focused on a novel target, the B-cell lymphoma-2 protein (BCL-2), which serves an essential role in regulation of apoptosis. Venetoclax has demonstrated efficacy in multiple subtypes of lymphoid malignancies, including patients with relapsed/refractory CLL harboring deletion 17p, with an overall response rate of nearly 80%. Venetoclax is generally well tolerated, with the significant adverse effect being tumor lysis syndrome, for which there are formal management recommendations., Conclusion: Venetoclax has demonstrated promising results in relapsed/refractory lymphoid malignancies, with an acceptable adverse effect profile. As the role of BCL-2 inhibition in various malignancies becomes further elucidated, venetoclax may offer benefit to a myriad other patient populations.

In the presented case, the authors describe an obese middle-aged man that presented to the emergency department for persistent oedema, scleral icterus and fatigue. He was admitted to the hospital and diagnosed with liver cirrhosis via transjugular liver biopsy. He continued to bleed from the biopsy site for 5 days from accelerated intravascular coagulation and fibrinolysis (AICF) requiring multiple transfusions of packed red blood cells, fresh-frozen plasma and cryoprecipitate. The authors then used thromboelastography (TEG) to further characterise the patient's coagulopathy, which revealed platelet inhibition. The results of the TEG significantly changed future transfusion management. Finally, the authors conducted a literature review to summarise the current literature available for the use of TEG in the management of liver cirrhosis with AICF., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Background: Carbohydrate (CHO) supplementation during endurance exercises has been shown to increase performance, but there is limited research with CHO supplementation during strength and conditioning exercises. Therefore, the purpose of this study was to examine the effects of various levels of CHO ingestion during acute testing sessions requiring participants to complete a strength and conditioning program designed for collegiate athletes., Methods: Participants ( n  = 7) performed a series of exercises while ingesting an amino-acid electrolyte control (CON) or CON plus varying levels of CHO. The CHO beverages delivered a 2:1 (glucose: fructose) ratio at rates of 15 g/h, 30 g/h, and 60 g/h. The exercise protocol consisted of a series of short sprints, full body resistance training exercises, jumping, and shuttle running. Performance measurements were taken for sprint times, repetitions until failure [bench press, bent over row, biceps curl, overhead triceps extension], summation of total repetitions for all repetitions until failure, repetitions in a set time for two-foot line jumps, and 137-m shuttle times., Results: A significant main effect ( p  < 0.05) was found in relation to CHO dose during the bench press final set repetitions to failure. Pairwise comparison with Bonferroni's correction identified that there was significant difference ( p  = 0.0024) between the dosage of 15 g/h and CON during bench press. Inferential statistics identified overall RT performance with a dosage of 15 g/h compared to 60 g/h and CON was 99.2 % (very likely) and 96.7 % (very likely) to have a beneficial effect., Conclusions: The results from this study suggest acute ingestion of CHO does not result in decrements in performance and may provide a beneficial effect to strength and conditioning performance. Strength and conditioning coaches may recommend their athletes ingest CHO during training sessions in order to maximize muscular adaptations.

Our aim was to determine how skilled players regulate linear and angular impulse while maintaining balance during the golf swing. Eleven highly-skilled golf players performed swings with a 6-iron and driver. Components contributing to linear and angular impulse generated by the rear and target legs (resultant horizontal reaction force [RFh], RFh-angle, and moment arm) were quantified and compared across the group and within a player (α = .05). Net angular impulse generated by both the rear and target legs was greater for the driver than the 6-iron. Mechanisms used to regulate angular impulse generation between clubs varied across players and required coordination between the legs. Increases in net angular impulse with a driver involved increases in target leg RFh. Rear leg RFh-angle was maintained between clubs whereas target leg RFh became more aligned with the target line. Net linear impulse perpendicular to the target line remained near zero, preserving balance, while net linear impulse along the target line decreased in magnitude. These results indicate that the net angular impulse was regulated between clubs by coordinating force generation of the rear and target legs while sustaining balance throughout the task.

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKCθ, and that the relevant PKCθ is within phrenic motor neurons. Whereas spinal PKCθ inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKCθ is highly expressed in phrenic motor neurons, and PKCθ knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKCζ, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKCθ plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKCθ is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons., (Copyright © 2015 the authors 0270-6474/15/358107-11$15.00/0.)

Inflammation is characteristic of most clinical disorders that challenge the neural control of breathing. Since inflammation modulates neuroplasticity, we studied the impact of inflammation caused by prolonged intermittent hypoxia on an important form of respiratory plasticity, acute intermittent hypoxia (three, 5 min hypoxic episodes, 5 min normoxic intervals) induced phrenic long-term facilitation (pLTF). Because chronic intermittent hypoxia elicits neuroinflammation and pLTF is undermined by lipopolysaccharide-induced systemic inflammation, we hypothesized that one night of intermittent hypoxia (IH-1) elicits spinal inflammation, thereby impairing pLTF by a p38 MAP kinase-dependent mechanism. pLTF and spinal inflammation were assessed in anesthetized rats pretreated with IH-1 (2 min hypoxia, 2 min normoxia; 8 h) or sham normoxia and allowed 16 h for recovery. IH-1 (1) transiently increased IL-6 (1.5 ± 0.2-fold; p = 0.02) and inducible nitric oxide synthase (iNOS) (2.4 ± 0.4-fold; p = 0.01) mRNA in cervical spinal homogenates, (2) elicited a sustained increase in IL-1β mRNA (2.4 ± 0.2-fold; p < 0.001) in isolated cervical spinal microglia, and (3) abolished pLTF (-1 ± 5% vs 56 ± 10% in controls; p < 0.001). pLTF was restored after IH-1 by systemic NSAID administration (ketoprofen; 55 ± 9%; p < 0.001) or spinal p38 MAP kinase inhibition (58 ± 2%; p < 0.001). IH-1 increased phosphorylated (activated) p38 MAP kinase immunofluorescence in identified phrenic motoneurons and adjacent microglia. In conclusion, IH-1 elicits spinal inflammation and impairs pLTF by a spinal p38 MAP kinase-dependent mechanism. By targeting inflammation, we may develop strategies to manipulate respiratory motor plasticity for therapeutic advantage when the respiratory control system is compromised (e.g., sleep apnea, apnea of prematurity, spinal injury, or motor neuron disease)., (Copyright © 2015 the authors 0270-6474/15/356871-10$15.00/0.)

Cardiomyopathy is defined as a heterogeneous group of myocardial disorders with mechanical or electrical dysfunction. Identification of the etiology is important for accurate diagnosis, treatment and prognosis, but continues to be challenging. The ability of cardiac MRI to non-invasively obtain 3D-images of unparalleled resolution without radiation exposure and to provide tissue characterization gives it a distinct advantage over any other diagnostic tool used for evaluation of cardiomyopathies. Cardiac MRI can accurately visualize cardiac morphology and function and also help identify myocardial edema, infiltration and fibrosis. It has emerged as an important diagnostic and prognostic tool in tertiary care centers for work up of patients with non-ischemic cardiomyopathies. This review covers the role of cardiac MRI in evaluation of nonischemic cardiomyopathies, particularly in the context of other diagnostic and prognostic imaging modalities.