Low Load Group Research Articles

Effects of High Cytomegalovirus DNA Load on Immune Reconstitution and Clinical Outcomes after Single Unrelated Cord Blood Transplantation

To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT). Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation. The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×109 /L vs 0.25×109 /L, P=0.015 and 2.53×109 /L vs 1.36×109 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8+ T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×109 /L vs 0.10×109 /L, P=0.038 and 1.62×109 /L vs 0.68×109 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively. The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8+ T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.

Relationship between systolic blood pressure load and sleep stability in patients with essential hypertension

Objective: To explore the relationship between blood pressure load and sleep stability in hypertensive patients by cardiopulmonary coupling monitoring (CPC) and 24-hour ambulatory blood pressure monitoring. Methods: One hundred and fifty-five patients with essential hypertension were divided into high load group and low load group according to whether the blood pressure load was higher than 50%. The relationship between sleep stability and systolic blood pressure load was analyzed by logistic regression. Results: After adjusting for sex, age and body mass index (BMI), logistic regression analysis showed that stable sleep was the protective factor (OR=0.736,P=0.047) for the decrease of nocturnal blood pressure load, and unstable sleep was the risk factor for increasing day time blood pressure load (OR=1.336, P=0.037) in patients with hypertension. Conclusions: The effect of sleep stability on blood pressure load is different between day and night. Stable sleep is the protective factor of nocturnal systolic blood pressure load decrease, and unstable sleep is the harmful factor of daytime systolic blood pressure load increase. Increasing sleep stability helps to reduce systolic blood pressure load.

Quantifying Water in PEM Fuel Cell Catalyst Layer with Small Angle Neutron Scattering

A polymer electrolyte membrane (PEM) fuel cell requires effective water management to achieve high performance. Balancing the water content and distribution is particularly important in a catalyst layer (CL), consisted of catalyst on carbon (typically Pt/C) covered by ionomer films. The accumulation of product water in the pores impedes reactant transport; however, simultaneously, the lack of water results in poor proton conductance in the ionomer. A diagnostic tool for measuring water content within the CL of an operating fuel cell is necessary for the development of the CL, especially for low Pt loading and non-precious metal group catalyst [1]. The common method for measuring water content in operando fuel cells is imaging based on synchrotron X-ray and neutron sources [2]. By using imaging method, water in the membrane electrode assembly (MEA) can be visualized on the micron-scale pixel resolution. However, this is not an ideal technique for probing water content in the CL for two main reasons: (1) the water in the ionomer cannot be distinguished from that in the pores, and (2) the spatial resolution is often not sufficient (as it is several times of the pixel resolution). At the French Alternative Energies and Atomic Energy Commission (CEA), we have developed in situ small angle scattering (SAS) techniques for fuel cell application based on neutron and synchrotron X-ray sources (Institut Laue-Langevin and European Synchrotron Radiation Facility). These techniques utilize focused neutron or X-ray beam to scan the areas of the MEA, each scanned point producing a scattering pattern. By radial averaging, the scattering pattern is converted into Q-range. The scattering due to the perfluorosulfonic acid (PFSA) ionomer produce a peak in the range of 0.1-0.25 Å-1, which arises from the separation between hydrophobic and hydrophilic domain. The water uptake in ionomer can be deduced from the shift of the peak position resulting from the swelling upon hydration. On the other hands, the overall water content can be obtained by either direct transmission or analyzing the high Q-range (0.4-0.45 Å-1). We previously measured liquid water accumulation (in the channels and the GDL) and water uptake in the membrane by through-plane SAS (i.e. the fuel cell is aligned perpendicular to the beam) [3]. Recently, we have further refined the custom fuel cell and SAS technique to probe water content only in the CLs. This was accomplished by developing a cell with an active area of 0.1 cm2 (0.1 mm wide in the path of the beam) and narrowing the beam size to 3 and 15 µm (for X-ray and neutron, respectively). This work will provide an overview of in situ SAS technique for fuel cells and focus on the comparison of two types of SAS investigations (neutron- vs. synchrotron X-ray-based).

Mechanomyographic Amplitude Is Sensitive to Load-Dependent Neuromuscular Adaptations in Response to Resistance Training.

Jenkins, NDM, Miramonti, AA, Hill, EC, Smith, CM, Cochrane-Snyman, KC, Housh, TJ, and Cramer, JT. Mechanomyographic amplitude is sensitive to load-dependent neuromuscular adaptations in response to resistance training. J Strength Cond Res 35(11): 3265-3269, 2021-We examined the sensitivity of the mechanomyographic amplitude (MMGRMS) and frequency (MMGMPF) vs. torque relationships to load-dependent neuromuscular adaptations in response to 6 weeks of higher- vs. lower-load resistance training. Twenty-five men (age = 22.8 ± 4.6 years) were randomly assigned to either a high- (n = 13) or low-load (n = 12) training group and completed 6 weeks of leg extension resistance training at 80 or 30% 1RM. Before and after 3 and 6 weeks of training, mechanomyography signals were recorded during isometric contractions at target torques equal to 10-100% of the subjects' baseline maximal strength to quantify MMGRMS and MMGMPF vs. torque relationships. MMGRMS decreased from Baseline to weeks 3 and 6 in the high-load, but not low-load group, and was dependent on the muscle and intensity of contraction examined. Consequently, MMGRMS was generally lower in the high- than low-load group at weeks 3 and 6, and these differences were most apparent in the vastus lateralis (VL) and rectus femoris muscles at higher contraction intensities. MMGMPF was greater in the high- than low-load training group independent of time or muscle. The MMGRMS vs. torque relationship was sensitive to load-dependent, muscle-specific neuromuscular adaptations and suggest reductions in neuromuscular activation to produce the same absolute submaximal torques after training with high, but not low loads.

Efficient search under constraints and not working memory resources supports creative action emergence in a convergent motor task

Creative (original and functional) solutions to problems can be facilitated by guiding search behavior. According to cognitive models, when solving convergent tasks (tasks with few solutions), high available working memory (WM) resources and capacity can guide creative solution emergence via repeated (persistent) search within a solution subcategory. However, no clear associations have been found of WM capacity on creative outcomes when tasks require the individual to enact solutions in divergent doing tasks. This study further tested constraints on WM resources on search behavior and creative outcomes in a convergent doing task. Novices to combat sports were asked to repeatedly strike a target with the intent to achieve an individualized target force. In order to manipulate available WM resources, every ten strikes, participants were asked to recall and then retain a sequence of 5 digits (high load group: n = 21) or 2 digits (low load group: n = 21). The task constraints favored the functionality (or appropriateness) of a qualitatively distinct, non-obvious solution. Functionality was assessed using the force registered for each strike. Originality was assessed in terms of how infrequently actions occurred. Finally, search behavior was quantified based on changes in which limb was used and changes in which part of the limb was used from one strike to the next. There were no significant effects of WM load on creativity outcomes, solution search, or task success. Rather, task success was related to efficient search and creativity. Future research should focus on constraints (other than WM resources) that promote efficient search.

PS1019 HIGH CYTOMEGALOVIRUS VIRUS LOAD INDUCES A POTENT TUMOR‐SPECIFIC CD8+ T CELL RESPONSE AND PROTECTS PATIENT IN ACUTE MYELOID LEUKEMIA FROM RELAPSE AFTER SINGLE CORD BLOOD TRANSPLANTATION

Background:Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Interestingly, in recent studies, CMV infections have been shown to have potential anti‐leukemia effects in acute myeloid leukemia (AML) patients after HSCT. However, studies of CMV infection on relapse after single cord blood transplantation (CBT) are limited, and the effect of the virus load on relapse has not been assessed.Aims:We hypothesize that the role of MCV on outcomes in CBT are related to virus load. In this study, we retrospectively analyzed the effect of CMV infection on two‐year outcomes in 151 patients with AML after CBT according to the virus load. Additionally, the mechanism of the possible interaction with lymphocyte subsets was also analyzed.Methods:We comparatively analyzed the outcomes of the high virus load group (CMV DNA copies ≥ 1 000/mL) and the low virus load group (CMV DNA copies &lt;1 000/mL or negative CMV DNA copy) of two years after CBT. Furthermore, in order to explore the mechanism of CMV on relapse, a smaller cohort of 26 patients with immune reconstruction data at 1, 3, 6, 9 and 12 months after transplantation were simultaneously studied, and nine healthy physical examination populations were recruited as healthy controls.Results:The results showed that the high CMV virus load group had a lower two‐year cumulative incidence of relapse (Figure A, 2.2% vs. 15.2%, p = 0.008) without an increase in non‐relapse mortality (Figure B, 20.9% vs. 22.4%, p = 0.970) than the low CMV virus load group. Furthermore, the two groups had similar overall survivals (76.8% vs. 72.4%, p = 0.746). Moreover, the proportion and absolute number of CD8+ T cells were increased in the high CMV virus load group in different months after transplantation (Figure C and D).Summary/Conclusion:In conclusion, a high CMV virus load in AML patients after CBT indicated a lower incidence of relapse, and this anti‐leukemic effect might be mediated by the CMV‐driven expansion of CD8+ T cells.image

Does low and heavy load resistance training affect musculoskeletal pain in overweight and obese women? Secondary analysis of a randomized controlled trial

BackgroundOverweight and obesity are associated with musculoskeletal pain, particularly in the female population. However, regular resistance training may positively affect these complaints. ObjectiveThe present study aimed to investigate between group differences in musculoskeletal pain in previously inactive women, allocated to three different resistance-training modalities available in health- and fitness clubs. MethodsThis is secondary analysis from a single-blinded randomized controlled trial, including healthy women (aged 18–65) with a BMI (kg/m2) ≥25. The participants were allocated to 12 weeks (3 times/weekly) of either BodyPump (high-repetition low-load group session) (n=24), heavy load resistance training with a personal trainer (n=28), non-supervised heavy load resistance training (n=19) or non-exercising controls (n=21). Primary outcome was self-reported musculoskeletal pain in ten different body parts, measured with the Standardized Nordic Pain Questionnaire, at baseline and post-test. In addition, the study included sub-analyses of the participants when they were divided into high (≥28 of 36 sessions, n=38) and low (≤27 of 36 sessions, n=22) exercise adherence. ResultsThe analysis revealed no between group differences in musculoskeletal pain in any of the ten body parts. The results did not change when the participants were divided into high versus low adherence. ConclusionsTwelve weeks of BodyPump, heavy load resistance training with a personal trainer and non-supervised heavy load resistance training did not show any effect on self-reported musculoskeletal pain in overweight women.Clinical Trial registration number: NCT01993953.(https://clinicaltrials.gov/ct2/show/NCT01993953).

Dental malocclusions are not just about small and weak bones: assessing the morphology of the mandible with cross-section analysis and geometric morphometrics

ObjectivesDental malocclusions in modern populations would be the result of small and weak jaws developing under low masticatory loads. We assess the validity of this by characterising the external and internal morphology of mandibles affected by class II and III malocclusions and comparing them with those from individuals with different masticatory load patterns.Materials and methodsCTs from up to 118 individuals exerting intensive, medium and low masticatory loads with harmonic occlusion, and from class II and III individuals, were used to compare their external shape using geometric morphometrics, as well as their internal amount and distribution of cortical bone.ResultsThe low-load groups (harmonic, class II and III occlusion) are externally more gracile than the intense and medium load groups. But more relevant in shape variation is a marked allometric pattern, which differentiates class II (small) and III (large) mandibles. Despite gracility, the relative amount of cortical bone in the low-load groups is larger than in the remaining groups.ConclusionsThere is no evidence that the modern mandible, including class II and III individuals, is intrinsically small and weak. Instead, there is a rather large degree of morphological variation, which could be linked to a lack of constraints derived from low masticatory loads. Thus, the effect of other factors such as genetics, but also basal metabolism, should be looked in more depth.Clinical relevanceDental malocclusions are a common disorder whose aetiology has not been unravelled, and several to be considered in the prevention and therapy of malocclusion.

Nomograms based on HPV load for predicting survival in cervical squamous cell carcinoma: An observational study with a long-term follow-up.

ObjectiveTo investigate the prognostic value of pretreatment human papillomavirus (HPV) viral load for cervical cancer, and to develop nomograms based on HPV load and other clinicopathological factors for long-term survival.MethodsWe conducted a prospective study on cervical squamous cell carcinoma (SCC) patients diagnosed between January 2003 and December 2008. Cervical samples were tested for HPV viral load by the Hybrid Capture II (HCII) assay before treatment and 6 months after treatment. Clinical characteristics and follow-up information were also collected. A multivariable Cox proportional hazards model was used to adjust covariates in both the radical hysterectomy (RH) treatment group and concurrent chemoradiotherapy (CCRT) treatment group to identify relevant covariates, and then nomograms were constructed and used for internal validation.ResultsA total of 520 SCC patients enrolled in this study with a median follow-up of 127 months, 360 patients received RH, whereas 160 patients received CCRT. The median HPV viral load in RH and CCRT groups was 356.10 and 294.29, respectively. Tumor size was positively correlated with high pretreatment HPV load in both groups. In CCRT group, the advanced International Federation of Gynecology and Obstetrics (FIGO) stage and enlarged retroperitoneal lymph node status determined by computed tomography (LNSCT) were correlated with low HPV load group. Initial HPV viral load, FIGO stage and lymph node metastasis were prognostic factors for RH group, whereas HPV viral load, squamous cell carcinoma antigen (SCC-Ag) level and LNSCT were identified as prognostic factors for CCRT group. Nomograms incorporating these predictors for 10-year progression-free survival (PFS) were constructed [concordance index (C-index): 0.756, 0.749].ConclusionsA low pretreatment HPV viral load is an independent prognostic factor for poor prognosis of cervical SCC and is related to other clinicopathological factors. The survival nomogram based on HPV viral load could predict the long-term prognosis.

Protective Effects of Higher Cytomegalovirus Virus Load in Patients with Acute Myeloid Leukemia after Umbilical Cord Blood Transplantation

Objective: The aim is to explore the potential relationship between the virus load of Cytomegalovirus (CMV)infection and disease relapse in acute myeloid leukemia (AML)patients after Umbilical cord blood transplantation (UCBT), The mechanism of interaction in which lymphocyte subsets may be involved is also analyzed.Design and method: All 126 patients with acute myeloid leukemia receiving a single UCB graft at the institution between Oct 2010 to Dec 2017 were enrolled in this retrospective study and engraft failure and death within 100 days excluded. All patients received common transplant processing: intensive myeloablative conditioning without ATG, Cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis. All patients had negative plasma CMV DNA prior to the transplantation and examined twice a week for at least 100 days after transplantation. CMV were measured by Quantitative real-time PCR using TaqMan (ABI)-based method. Patients were divided into three groups according to the CMV viral load within 100 days: CMV-negative groups (no relevant special treatment), <1,000/mL CMV DNA copy group (reduced immunosuppressor and close follow up) and >= 1,000 / mL CMV DNA copy group (reduced immunosuppressor, antiviral treatment and close follow up), the first group was merged into the second group due to the 92% incidence of CMV infection after UCBT .To compare the two regimens which aimed to focus on disease relapse ,non-relapse mortality (NRM),overall survivor (OS),disease free survival(DFS) ,GVHD-free /relapse-free survivor (GRFS)and graft versus host disease (GVHD) after transplantation for two years. Also, retrospectively compared the lymphocyte ratio recovery at different time points after transplantation .Results: Patients characteristic had no significant differences between high CMV virus load (>=10^3/mL) group and low CMV virus load(<10^3/mL) group. There were 63 males and 63 females with a median age of 13 years(range,1-52) and a median weight of 40 Kg (range,11-87) .The median follow-up time among survivors was 736 days (range, 100-2184).Univariate and multivariate analysis showed, high CMV load group has lower two-year cumulative incidence of relapse [(2.9% vs. 17.9%, P=0.017); adjusted HR 0.19, P=0.045], higher cumulative incidence of DFS [(88.3% vs. 63.2%, P=0.003), adjusted HR0.28, P=0.005],higher cumulative incidence of OS[(88.0% vs. 72.3%, P=0.037),adjusted HR0.35,P=0.027].The immune reconstruction data of the two groups showed that the median value of CD8+ T cells in the high CMV load group at 1, 4, 6, 9, 12, 15, 18 and 24-36 months after transplantation was higher than the low CMV load Group (30.3% vs. 13.9%, 46.8% vs. 27.6%, 46.5% vs. 27.9%, 37.0% vs. 31.5%, 37.7% vs. 20.9%, 42.3% vs. 22.8%, 30.4% vs. 23.5%, 29.1% Vs.22.1%; P=0.032, P=0.014, P=0.01, P=0.621, P=0.005, P=0.008, P=0.088, P=0.371).Conclusion: Higher CMV load within 100 days after UCBT presents lower relapse,improved OS and DFS in AML patients. At the same time, the proportion of CD8+ T cells increased significantly in patients with high CMV load after 1, 4, and 6 months after transplantation. The above data indicates that CMV virus infection may stimulates the activation of CD8+ T cells further induces a GVL effect.keywords:Cytomegalovirus,acute myeloid leukemia,cord blood transplantation,virus load, relapse. DisclosuresNo relevant conflicts of interest to declare.

Catalytic activation of unstrained C(aryl)-C(aryl) bonds in 2,2'-biphenols.

Transition-metal catalysis has emerged as an important means for C-C activation allowing mild and selective transformations. However, the current scope of C-C bonds that can be activated is primarily restricted to either highly strained systems or more polarized C-C bonds. In contrast, catalytic activation of nonpolar and unstrained C-C moieties remains an unmet challenge. Here we report a general approach for catalytic activation of the unstrained C(aryl)-C(aryl) bonds in 2,2’-biphenols. The key is utilizing the phenol moiety as a handle to install phosphinites as a recyclable directing group. Using hydrogen gas as the reductant, mono-phenols are obtained with a low catalyst loading and high functional group tolerance. This approach has also been applied to the synthesis of 2,3,4-trisubstituted phenols. Further mechanistic study suggests that the C-C activation step is mediated by a rhodium(I) mono-hydride species. Finally, a preliminary study on breaking the inert biphenolic moieties in lignin models is illustrated.

The influence of pre-season training loads on in-season match activities in professional Australian football players

ABSTRACTObjectives: To determine the impact of pre-season training loads on in-season match activity profiles in professional Australian football (AF) players.Methods: Forty-four professional AF players participated in this study. Sixty-nine pre-season training and in-season match profiles were monitored using global positioning system (GPS) microtechnology and technical statistics across two seasons. Technical performance was measured as the Player Rank score provided by Champion Data. Players were divided into three equal training load groups based on total distance accumulated during pre-season.Results: Players in the high training load (HTL) group performed more relative total and high-speed distance in matches compared with the moderate (MTL; ES = 0.73–0.86) and low (LTL; ES = 0.68–1.31) training load groups, with the differences becoming greater as the season progressed. There were no clear differences in Player Rank score between groups. There were positive relationships between pre-season high-speed running and match relative distance (p = 0.001; r = 0.417; r2 = 0.174) and match relative high-speed running (p = 0.001; r = 0.561; r2 = 0.314), which were greatest in the HTL group.Conclusions: High pre-season training loads are associated with increased physical match activities, but do not appear to impact technical performance.

Blood transcriptomic markers of Mycobacterium tuberculosis load in sputum.

Peripheral blood transcriptome signatures that distinguish active pulmonary tuberculosis (TB) from control groups have been reported, but correlations of these signatures with sputum mycobacterial load are incompletely defined. We assessed the performance of published TB transcriptomic signatures in Haiti, and identified transcriptomic biomarkers of TB bacterial load in sputum as measured by Xpert® MTB/RIF molecular testing. People in Port au Prince, Haiti, with untreated pulmonary TB (n = 51) formed the study cohort: 19 people with low and 32 with high sputum Mycobacterium tuberculosis load. Peripheral whole blood transcriptomes were generated using RNA sequencing. Twenty of the differentially expressed transcripts in TB vs. no TB were differentially expressed in people with low vs. high sputum mycobacterial loads. The difference between low and high bacterial load groups was independent of radiographic severity. In a published data set of transcriptomic response to anti-tuberculosis treatment, this 20-gene subset was more treatment-responsive at 6 months than the full active TB signature. We identified genes whose transcript levels in the blood distinguish active TB with high vs. low M. tuberculosis loads in the sputum. These transcripts may reveal mechanisms of mycobacterial control of M. tuberculosis during active infection, as well as identifying potential biomarkers for bacterial response to anti-tuberculosis treatment.

Phosphomolybdic acid as a bifunctional catalyst for Friedel–Crafts type dehydrative coupling reaction

Phosphomolybdic acid (H3PMo12O40) was found to be a bifunctional catalyst for C─C bond formation via the dehydrative reaction of diarylmethanols with various nucleophiles, including 2‐naphthols, indoles, benzofuran and benzothiophene. The protons in the catalyst might play a critical role in the activation of alcohol, while the polyanion was advantageous for stabilizing the carbocation species. The cooperative catalytic system showed its own merits, such as high reaction rate, low catalyst loading, mild conditions, excellent yields (up to 99%) and good functional group compatibility.

Effect of a Short-term Cycle Ergometer Sprint Training Against Heavy and Light Resistances on Intraocular Pressure Responses.

The purpose of this study is to determinate the long-term effect of a cycle ergometer sprint training program against heavy and light resistances on baseline intraocular pressure (IOP), and on the acute IOP response to cycling sprints. A total 27 physically active males were randomly assigned to a heavy loads group (HLG, n=9), low loads group (LLG, n=9), and control group (CG, n=9). Participants performed 12 training sessions during 6 weeks (2 sessions per week), and each training session consisted in performing 8 cycling sprints against either heavy (HLG) or light (LLG) resistances. Before and after intervention, they performed an identical protocol, which consisted in performing maximal cycling sprints against 5 different resistances in random order. In these protocols, IOP was measured before and after each sprint by rebound tonometry. A Bayesian analysis revealed that baseline IOP was reduced in the LLG after the intervention [Bayes factor (BF01)=0.043 and effect size (ES)=1.255; pretest=15.22±0.94 mm Hg and posttest=15.39±1.02 mm Hg], whereas the HLG did not manifest any baseline IOP change (BF01=2.363 and ES=-0.205; pretest=15.28±1.44 mm Hg and posttest=14.17±1.77 mm Hg). The acute IOP response to maximal sprints was modified for the HLG, showing a more stable IOP response with heavier loads (resistance, 4 and 5) after the intervention (BF01<0.01 in both cases, and ESs=1.847 and 1.920, respectively). A short-term cycle ergometer sprint training impacts long-term IOP depending on the level of resistance imposed, showing that training with low loads permits to reduce baseline IOP, whereas training with heavy loads attenuates the acute IOP changes after sprinting against heavy loads.

Regio-selective and stereo-selective hydrosilylation of internal alkynes catalyzed by ruthenium complexes.

In this study, ruthenium(ii)-catalyzed direct hydrosilylation of internal alkynes with high regio-selectivity and stereo-selectivity is reported. This title transformation led to various vinylsilanes in good to excellent yields. This approach features mild reaction conditions, low catalyst loading, air-stability, and good functional group tolerance. Furthermore, gram-scale preparation and some transformations of vinylsilanes were carried out, which further underscored its synthetic utility and applicability.

Everybody was Kung-Fu fighting—The beneficial effects of Tai Chi Qigong and self-defense Kung-Fu training on psychological and endocrine health in middle aged and older men

BackgroundHigher age is associated to a variety of physical and mental disorders. Age-related changes in steroid secretion have been suggested to be an underlying mechanism leading to frailty, depression, and sexual dysfunction. However, Tai chi qigong and similar forms of exercise have been shown to improve a great variety of health-related parameters in older individuals. MethodsWe examined 56 self-reporting healthy men actively practicing Tai chi qigong and/or self-defense Kung-fu and 55 age-matched self-reporting healthy controls. Saliva samples were obtained in a standardized procedure for subsequent quantification of circulating testosterone and cortisol levels. In addition, depressive symptoms, life satisfaction, and sexual health were assessesd via self-report questionnaires. ResultsAge was negatively associated with testosterone, while no association emerged for cortisol. Tai chi qigong and/or self-defense Kung-fu training was neither associated with testosterone nor cortisol. More weekly Tai chi qigong and/or self-defense Kung-fu training (4 or more times per week) was instead associated with a lower CT-ratio, less depressive symptoms, and higher life satisfaction compared to individuals, who trained only one to three times per week. More years of Tai chi qigong and/or self-defense Kung-fu training were associated with less depressive symptoms and higher life satisfaction but not with the CT-ratio. No significant associations emerged for Tai chi qigong and/or self-defense Kung-fu training and sexual health. When compared to the age-matched controls, there is a significant effect of Tai chi, qigong and/or self-defense Kung-fu on the CT-ratio. Contrast analyses revealed a significantly lower CT-ratio for the high training load group in contrast to the low training load group. Further, in contrast to the control group, the low training load group exhibits a significantly higher CT-ratio. For depression, contrast analyses revealed a significantly lower level of depression in the high training load group compared to the control group. ConclusionThe results indicate that Tai chi qigong and/or self-defense Kung-fu training is beneficially associated with steroid secretion patterns and mental health in aging men, when training is performed with a frequency of 4 or more trainings per week. However, the high frequency training and control group show similar steroid secretion patterns suggesting an inverted U-shaped association between Tai chi qigong and/or self-defense Kung-fu training frequency and the CT-ratio in aging men. More research is needed to elucidate the underlying mechanism of this association. Still, Tai chi qigong and/or self-defense Kung-fu training provides a promising prevention strategy against age-related physical and mental deterioration in aging men.

The Effect of Different Resistance Training Load Schemes on Strength and Body Composition in Trained Men.

The purpose of this study was to evaluate the impact of moderate-load (10 RM) and low-load (20 RM) resistance training schemes on maximal strength and body composition. Sixteen resistance-trained men were randomly assigned to 1 of 2 groups: a moderate-load group (n = 8) or a low-load group (n = 8). The resistance training schemes consisted of 8 exercises performed 4 times per week for 6 weeks. In order to equate the number of repetitions performed by each group, the moderate load group performed 6 sets of 10 RM, while the low load group performed 3 sets of 20 RM. Between-group differences were evaluated using a 2-way ANOVA and independent t-tests. There was no difference in the weekly total load lifted (sets × reps × kg) between the 2 groups. Both groups equally improved maximal strength and measures of body composition after 6 weeks of resistance training, with no significant between-group differences detected. In conclusion, both moderate-load and low-load resistance training schemes, similar for the total load lifted, induced a similar improvement in maximal strength and body composition in resistance-trained men.

Abstract P6-09-22: Detecting high mutational load ER+ breast cancer patients through Foundation One cancer gene panel mutations

Abstract Background: Cancer gene panels such as Foundation One are widely used clinically for aiding with cancer treatment decision-making since single point mutations in important genes and gene pathways in the tumor can point to tumor susceptibility that can be targeted with specific drugs. Tumor mutational load has more recently been proposed as a useful prognostic factor and indicator of clinical benefit in treatment with PD-1 and CTLA-4 blockade therapy. Breast cancer estrogen receptor positive patients (ER+) in particular appear to have a subset of high mutational load patients that could benefit if identified. However whole exome sequencing needed to directly measure mutational load is not yet widely available as a clinical tool. In this study we evaluate the predictive value of Foundation One cancer gene panel mutations for estimating tumor genome-wide mutational load and its use in identifying a clinically meaningful subset of breast cancer patients. Methods: The Cancer Genome Atlas breast cancer sequencing data on 569 ER+ patients was used to establish mutational load distribution. ER+ patients were divided into low mutational load and high mutational load groups according to 3 criteria: mean mutational load, the point of inflection in the mutational load distribution and the mutational load that optimally separates groups in terms of survival. Foundation One (FO) mutational load was then calculated as the number of mutations present within the 314 genes queried by the panel. FO mutational load was used to predict whether patients fell into the low or high mutational load groups found through analysis of the full exome data. Receiver Operating Characteristic (ROC) curves were constructed and optimal values for specificity and sensitivity of the FO mutational load classification were found. Results: Mean mutational load for ER+ patients was found to be 57 mutations, the point of inflection of the mutational load distribution was established at 100 mutations, and the number of mutations that best separated groups in terms of survival was 160, (HR = 6.6, p-value=0.004). FO mutational load was found to be a good predictor for the low and high classifications established by all three criteria, with areas under the curve of 0.74, 0.91 and 0.945 respectively. The optimal predictive value of the FO mutational load classification was found at 5 mutations as the cut-off, with 94.2% specificity and 88% sensitivity for predicting groups defined by survival and 95% specificity and 71% sensitivity for those defined by the mean. Conclusion: The Foundation One cancer gene panel can be used to effectively identify a clinically meaningful subgroup of ER+ patients with high mutational load. These patients may benefit from targeted treatments such as PD-1 inhibitors being offered through clinical trials. The compromise in sensitivity that results from the reduction in number of genes queried by a panel means an important proportion of patients with high mutational load will be missed but this still translates to a large improvement in the identification of these patients given the wide availability of gene panels in the clinic. Basic and clinical follow-up studies need to take place to clinically validate the high mutational load ER+ patient subgroup. Citation Format: Raska P, Abraham J, Budd T. Detecting high mutational load ER+ breast cancer patients through Foundation One cancer gene panel mutations [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-22.

418. Peripheral Blood Leucocytes, Neutralizing Antibodies and Tumor Burden as Predictive and Prognostic Factors in Patients Treated with Oncolytic Adenoviral Immunotherapy

Oncolytic immunotherapy has taken significant steps towards clinical availability for cancer patients, as the FDA recently approved Imlygic (T-Vec) for the treatment of melanoma. Despite the several oncolytic virus trials, there are no known biomarkers which could predict the treatment outcome of oncolytic virotherapy. Therefore, previous clinical experiences should be utilized as guidance for further treatment optimization and patient selection. The patients analyzed consisted of 246 patients treated with oncolytic adenovirus as a part of the Advanced Therapy Access Program which was ongoing in Helsinki 2007-2012. Taken together with the increasing understanding that immunological factors might determine the efficacy of oncolytic virotherapy, we studied whether neutralizing antibodies and peripheral blood cell counts would have prognostic and/or predictive significance in the context of oncolytic adenovirus treatments. Additionally, tumor burden was assessed both in terms of primary tumor and metastases. We observed presence of neutralizing antibodies before treatment to be correlated with shorter overall survival (p=0.028). Blood cell counts analyses revealed that patients who had high neutrophil to lymphocyte ratio at baseline had significantly shorter overall survival (p<0.001). After treatment patients demonstrated transient lymphopenia and increases in neutrophils, which varied between disease control and progressive disease groups. Patients with high total tumor load had significantly shorter overall survival compared to low tumor load group (p=0.003). Interestingly, we also found presence of liver metastases to be correlated with reduced rate of disease control (p=0.021). These data indicate possible reasons behind the nonuniform treatment outcomes frequently observed after virotherapy. Moreover, our results suggest potential approaches for treatment refinement and patient selection in the context of oncolytic immunotherapy. Given the similarity of biological effects seen with different oncolytic DNA viruses, it will be interesting to see if these results will be similar in the context of other oncolytic viruses and cancer immunotherapy approaches such as adoptive T-cell therapy and cancer vaccines.