Nuclear Medicine

Development of a p38α-selective radioactive probe for qualitative diagnosis of cancer using SPECT Abstract Objective p38 mitogen-activated protein (MAP) kinase (p38α) has drawn attention as a new target molecule for the treatment and diagnosis of cancer, and its overexpression and activation have been reported in various types of cancer. In this study, a single photon emission computed tomography (SPECT) imaging probe of p38α was developed to noninvasively image p38α activity for effective qualitative diagnosis of cancer. Methods Pyrrolepyridine derivatives, m-YTM and p-YTM, were designed and synthesized based on the structure of the p38α-selective inhibitor. Radioactive iodine-labeled m-YTM, [125I]m-YTM, was synthesized because m-YTM greatly inhibited the phosphorylation of p38α upon examining the inhibitory effects of the compounds. After investigating the binding affinity of [125I]m-YTM to the recombinant p38α, a saturation binding experiment using activated p38α and inactive p38α was performed to determine the binding site. Uptake of [125I]m-YTM into various cancer cell lines was investigated, and the pharmacokinetics was evaluated using tumor-bearing mice. Results The inhibitory activity of m-YTM was approximately 13 times higher than that of SB203580, a p38α-selective inhibitor. The binding site of [125I]m-YTM was estimated to be the p38α activating site, similar to that of SB203580, because the [125I]m-YTM bound strongly to both activated p38α and inactive p38α. Various different cancer cells incorporated [125I]m-YTM; however, its accumulation was significantly reduced by treatment with SB203580. Pharmacokinetics study of [125I]m-YTM in B-16 tumor-bearing mice was examined which revealed high accumulation of radioactivity in tumor tissues. The ratios of radioactivity in the B-16 tumor to that in blood were 3.1 and 50 after 1 and 24 h, respectively. The ratio of radioactivity in the tumor to that in blood in the tumor-bearing mice generated using other cancer cell lines was also ≥ 1 at 1 h after the administration of the probe. Conclusions This study suggests that [123I]m-YTM has potential as a p38α imaging probe effective for various cancer types.

Development of radiolabeled bis(zinc(II)-dipicolylamine) complexes for cell death imaging Abstract Purpose Although it has been traditionally surmised that phosphatidylserine (PS) externalization is a hallmark of apoptosis, most other non-apoptotic modes of cell death, such as necrosis, are also associated with PS externalization. Bis(zinc-dipicolylamine) (ZnDPA) complexes have been reported to exhibit affinity for PS. The present study aimed to develop novel radiolabeled ZnDPA derivatives for cell death imaging in tumor after treatment with anticancer drugs. Methods [125I]IB-EG2-ZnDPA and [99mTc]Tc-MAG3-EG2-ZnDPA were designed and prepared. The stabilities of these radiotracers were determined in 0.1 M phosphate buffer (pH 7.4) or murine plasma at 37 °C, and their 1-octanol/water partition coefficients (logP) were measured. The uptake of radioactivity in cancer cells, which were preincubated in a normal medium or in a medium containing 5-FU, was measured after incubation with radiotracers. Accumulation of [99mTc]Tc-MAG3-EG2-ZnDPA in the tumor was evaluated in tumor-bearing mice treated with or without 5-FU, and then TUNEL staining was performed to detect dead cells in the tumor tissue sections. Results The radiochemical purities of [125I]IB-EG2-ZnDPA and [99mTc]Tc-MAG3-EG2-ZnDPA exceeded 95%. Although [125I]IB-EG2-ZnDPA gradually decomposing with time, more than 90% of [99mTc]Tc-MAG3-EG2-ZnDPA remained in its intact form in phosphate buffer through 6 h of incubation. Neither [125I]IB-EG2-ZnDPA nor [99mTc]Tc-MAG3-EG2-ZnDPA decomposed so much after 6-h incubation in murine plasma. [125I]IB-EG2-ZnDPA could not specifically recognize PS on the cell surface because of its high lipophilicity. Conversely, [99mTc]Tc-MAG3-EG2-ZnDPA accumulated in cancer cells after treatment with an anticancer drug both in vitro and in vivo, and its accumulation was correlated with the number of TUNEL-positive cells. However, the biodistribution of [99mTc]Tc-MAG3-EG2-ZnDPA was not suitable for imaging because of its low accumulation in tumor and high uptake in abdomen organs. Conclusion [99mTc]Tc-MAG3-EG2-ZnDPA could be useful for the early detection of treatment effects after chemotherapy. Since the signal-to-noise ratio is not enough for single photon emission computed tomography imaging, further modification is needed to improve its biodistribution and affinity for PS.

Accumulation of hypoxia imaging probe " 18 F-FMISO" in macrophages depends on macrophage polarization in addition to hypoxic state Abstract Objective Macrophages play an essential role in immune response, and are closely related to the progression of diseases such as cancer and atherosclerosis. Macrophages polarize to M1 or M2 type, which is related to the environmental hypoxic state. Previously, we found that 18F-FMISO uptake varied according to expression levels of biomolecules such as glutathione S-transferase P1 (GST-P1), which catalyzes the conjugation of glutathione to 18F-FMISO metabolites, and multidrug resistance-associated protein 1 (MRP1), which exports glutathione-18F-FMISO metabolite conjugates out of cells. However, the relationship between macrophage polarization and 18F-FMISO accumulation remains unclear. Methods Mouse peritoneal macrophages were polarized to either the M1 or M2 type, and were treated with 18F-FMISO. Then, their radioactivity after a 4 h incubation period under normoxic (21% O2) or hypoxic (1% O2) condition was measured. GST-P1 and MRP1 expression levels were measured by qRT-PCR. Results M2 macrophages exhibited a significantly higher uptake of 18F-FMISO than non-polarized (M0) macrophages, whereas M1 macrophages had a significantly lower uptake than M0 macrophages (M0: 1.05 ± 0.22, M1: 0.34 ± 0.02, M2: 4.17 ± 0.36 %dose/mg protein). The GST-P1 expression level in M1 macrophages was higher than that in M2 and M0 macrophages [GST-P1/β-actin normalized by M0: 9.0 ± 3.7 (M1), 1.2 ± 0.2 (M2)]. The MRP1 expression level in M1 macrophages was significantly higher than that in M2 and M0 macrophages [MRP1/β-actin normalized by M0 macrophages: 5.1 ± 2.1 (M1), 2.8 ± 1.0 (M2)]. Conclusions 18F-FMISO accumulation in macrophages may depend on the polarization state in addition to hypoxic condition.

Increased 18 F-FDG accumulation in the tonsils after chemotherapy for pediatric lymphoma: a common physiological phenomenon Abstract Objective Increased 18F-fluorodeoxyglucose (FDG) uptake in the tonsils after the completion of chemotherapy in patients with lymphoma may be misdiagnosed as tumor recurrence. This study aimed to investigate the changes in physiological FDG uptake in the tonsils during and after chemotherapy in pediatric patients with lymphoma. Methods A total of 47 FDG-PET/CT scans acquired from 13 pediatric patients with lymphoma (before chemotherapy [preC] = 9; during chemotherapy [durC] = 12; within 1 month after the end of chemotherapy [endC] = 11; and after achieving complete response [postC] = 15) were retrospectively included in this study. FDG uptake in the palatine tonsils was assessed using maximum standardized uptake value (SUVmax). The relative size of the palatine tonsils was calculated as the tonsil-pharyngeal ratio (TPR). Serial changes in the SUVmax and TPR were evaluated. Results The mean SUVmax was 3.7 ± 1.7, 2.6 ± 0.7, 2.3 ± 0.8, and 6.2 ± 1.6, at the preC, durC, endC, and postC scans, respectively (p < 0.0001); TPR was 59.0 ± 11.2%, 58.3 ± 9.4%, 54.4 ± 7.9%, and 62.2 ± 12.0% in these groups, respectively, with no significant inter-group differences. TPR and SUVmax showed no correlation. Conclusions Increased physiological FDG uptake in the tonsils is commonly observed after the completion of chemotherapy, even in the absence of reactive hypertrophy.

Effect of respiratory motion on cardiac defect contrast in myocardial perfusion SPECT: a physical phantom study Abstract Objective Correction for respiratory motion in myocardial perfusion imaging requires sorting of emission data into respiratory windows where the intra-window motion is assumed to be negligible. However, it is unclear how much intra-window motion is acceptable. The aim of this study was to determine an optimal value of intra-window residual motion. Methods A custom-designed cardiac phantom was created and imaged with a standard dual-detector SPECT/CT system using Tc-99m as the radionuclide. Projection images were generated from the list-mode data simulating respiratory motion blur of several magnitudes from 0 (stationary phantom) to 20 mm. Cardiac defect contrasts in six anatomically different locations, as well as myocardial perfusion of apex, anterior, inferior, septal and lateral walls, were measured at each motion magnitude. Stationary phantom data were compared to motion-blurred data. Two physicians viewed the images and evaluated differences in cardiac defect visibility and myocardial perfusion. Results Significant associations were observed between myocardial perfusion in the anterior and inferior walls and respiratory motion. Defect contrasts were found to decline as a function of motion, but the magnitude of the decline depended on the location and shape of the defect. Defects located near the cardiac apex lost contrast more rapidly than those located on the anterior, inferior, septal and lateral wall. The contrast decreased by less than 5% at every location when the motion magnitude was 2 mm or less. According to a visual evaluation, there were differences in myocardial perfusion if the magnitude of the motion was greater than 1 mm, and there were differences in the visibility of the cardiac defect if the magnitude of the motion was greater than 9 mm. Conclusions Intra-window respiratory motion should be limited to 2 mm to effectively correct for respiratory motion blur in myocardial perfusion SPECT.

Evaluation of whole-body tumor burden with 68 Ga-PSMA PET/CT in the biochemical recurrence of prostate cancer Abstract Background 68 Ga-PSMA-PET has an increasing importance in the evaluation of prostate cancer patients due to its high sensitivity and specificity in identifying neoplastic lesions in the clinical setting of elevated prostate-specific antigen (PSA). The objective of this study was to calculate the whole-body tumor burden using volumetric quantification of lesions detected in 68Ga-PSMA-PET of prostate cancer patients with biochemical recurrence and correlate these findings with clinical and image parameters. Methods Each patient had their 68Ga-PSMA-PET analyzed for the presence of neoplastic lesions. Their PSA levels and clinical information were recorded. In positive cases, the tumor burden (TL-PSMA) was calculated with a semi-automatic software and manually, and the results are analyzed and tested. Results We analyzed 100 prostate cancer patients, mean age of 69.9 ± 9.7 years and a median PSA of 1.73 ng/dL. 68Ga-PSMA-PET identified neoplastic lesions in 72% of them. The median TL-PSMA was 55.95 ml (1.1–28,080 ml). TL-PSMA and PSA were strongly correlated (rho = 0.71, p < 0.0001, 95% CI 0.60–0.80). TL-PSMA and PSA levels groups had a significant correlation and TL-PSMA and Gleason score were independent variables associated with PSA levels (p < 0.05). Conclusion TL-PSMA strongly and independently correlates with PSA levels in prostate cancer patients and could be used as a biomarker to separate them into groups with high or low tumor burden, instead of considering only the number of lesions.

Clinicopathological predictors of positive 68 Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer following definitive therapy Abstract Objective To demonstrate the effect of clinicopathological factors on 68Ga-PSMA-11 PET/CT positivity at the time of biochemical recurrence (BCR) of localized prostate cancer (PCa) following definitive therapy. Methods We retrospectively reviewed our institutional database for PCa patients who had BCR and subsequently underwent 68Ga-PSMA-11 PET/CT between April 2014 and February 2018. A total of 51 patients who were metastasis-free before PSMA imaging and previously treated with definitive therapy (radical prostatectomy or external beam radiotherapy) for localized disease (pT1c—T3b pN0-1 cM0) were included. Results 37 out of 51 patients (72.5%) had positive 68Ga-PSMA-11 PET/CT scans. Age at diagnosis, Gleason score (GS), D'Amico risk status of PCa, initial PSA level before treatment and PSA doubling time were not associated with PSMA positivity. Pre-scan PSA levels of > 0.2 ng/ml and PSA velocity of ≥ 1 ng/ml/year were significantly associated with increased PSMA positivity, whereas history of androgen deprivation therapy showed a trend towards significance. The optimal cutoffs for distinguishing between positive and negative scans were ≥ 0.71 ng/ml for pre-scan PSA and ≥ 1.22 ng/ml/yr for PSA velocity. In multivariable analysis, log pre-scan PSA and pre-scan PSA level > 0.2 ng/ml remained significant predictors for PSMA positivity, whereas the association of PSA velocity and of ADT was lost. Conclusions In BCR of localized PCa following definitive therapy, pre-scan PSA was strongly associated with positive 68Ga-PSMA-11 scan, even at PSA levels ranging from 0.2 to 1.0 ng/ml. Therefore, clinical and pathological predictors of positive 68Ga-PSMA-11 PET/CT in PSA-only recurrence of localized prostate cancer need to be further elucidated.

18 F-NaF-PET/CT for the detection of bone metastasis in prostate cancer: a meta-analysis of diagnostic accuracy studies Abstract Purpose This meta-analysis aims to establish the diagnostic performance of 18F-NaF-PET/CT for the detection of bone metastases in prostate cancer patients. The performance of 18F-NaF-PET/CT was compared with other imaging techniques in the same cohort of patients. Methods A systematic search was performed in PubMed/Medline and EMBASE (last Updated, September 28, 2018). Studies with histopathology confirmation and/or clinical/imaging follow-up as reference standard were eligible for inclusion. Results A total of 14 studies were included. Twelve studies including 507 patients provided per-patient basis information. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristics curve (AUC) of 18F-NaF-PET/CT for the detection of bone metastases were 0.98 (95% CI 0.95–0.99), 0.90 (95% CI 0.86–0.93), 123.2 and 0.97, respectively. Seven studies provided the lesion-based accuracy information of 1812 lesions identified on 18F-NaF-PET/CT with the pooled sensitivity, specificity, DOR and AUC of 0.97 (95% CI 0.95–0.98), 0.84 (95% CI 0.81–0.87), 206.8 and 0.97, respectively. The overall diagnostic performance of 18F-NaF-PET/CT is superior to 99mTc-bone scintigraphy (AUC 0.842; P < 0.001; four studies) and 99mTc-SPECT (AUC 0.896; P < 0.001, four studies). Compared to 18F NaF-PET/CT, whole-body MRI with diffusion-weighted imaging (DWI) was shown to have lower sensitivity (0.83, 95% CI 0.68–0.93), with no significant difference in the overall performance (AUC 0.947; P = 0.18, four studies). Conclusion 18F-NaF-PET/CT has excellent diagnostic performance in the detection of bone metastases in staging and restaging of high-risk prostate cancer patients. The performance of 18F-NaF-PET/CT is superior to 99mTc bone scintigraphy and SPECT, and comparable to DWI–MRI.

A novel biomarker, active whole skeletal total lesion glycolysis (WS-TLG), as a quantitative method to measure bone metastatic activity in breast cancer patients Abstract Objective There is no good response evaluation method for skeletal metastasis. We aimed to develop a novel quantitative method to evaluate the response of skeletal metastasis, especially lytic lesions, for treatment. Methods A method to measure active bone metastatic burden quantitatively using F-18 fluorodeoxyglucose positron emission tomography with computed tomography (FDG–PET/CT) in breast cancer patients, whole skeletal total lesion glycolysis (WS-TLG), a summation of each skeletal lesion's TLG, was developed. To identify active bone lesions, a tentative cutoff value was decided using FDG–PET/CT in 85 breast cancer patients without skeletal metastasis and 35 with skeletal metastasis by changing the cutoff value. Then, the WS-TLG method was evaluated by comparing to PET Response Criteria in Solid Tumor (PERCIST) or European Organization for Research and Treatment of Cancer (EORTC) criteria for only bone in 15 breast cancer patients with skeletal metastasis who were treated. Results A cutoff value of the standardized uptake value (SUV) = 4.0 gave 91% (77/85) specificity and 97% (34/35) sensitivity. We decided on SUV = 4.0 as a tentative cutoff value. Skeletal metastases of lytic and mixed types showed higher WS-TLG values than those of blastic or intertrabecular types, although statistical significance was not tested. All 15 patients showed agreement with PERCIST or EORTC in the therapeutic bone response. Conclusion This quantitative WS-TLG method appears to be a good biomarker to evaluate skeletal metastasis in breast cancer patients, especially lytic or mixed types. Further clinical studies are warranted to assess the clinical values of this new WS-TLG method.

Measurement of cerebral vascular reserves with I-123 IMP SPECT without an arterial input function using the microsphere model and radiopharmaceutical dose calibration Abstract Objectives Cerebral vascular reserve (CVR) is an important indicator for the management of and therapy for cerebral arterial occlusive disease (CAOD). Vasodilatory function is measured using the standard IMP-ARG method. The IMP autoradiography (IMP-ARG) method employed here uses a standardized input function, which was derived from 12 patients between 31 and 71 years of age. Because the population of elderly patients continues to increase in Japan, additional therapies are required to assess CVR in elderly patients with chronic cardiopulmonary disease or a history of smoking, in particular. Despite its popularity, alternatives to the IMP-ARG method are necessary. Here, we proposed the microsphere (MS) method without an input function. Method Using this method and the IMP-ARG method, we measured the CVRs of 18 CAOD patients. Results The CVRs derived with these two methods were significantly and linearly correlated (r = 0.89, p < 0.01). CVRs categorized by severity were also found to correspond between the two methods (κ = 0.87). Conclusions Thus, the method proposed here may serve as a supplemental to and be compatible with the IMP-ARG method for the assessment of CVR. Furthermore, the two methods, when used in conjunction, may result in less error than either would alone.

Sports Medicine

Principles of Motor Learning to Support Neuroplasticity After ACL Injury: Implications for Optimizing Performance and Reducing Risk of Second ACL Injury "As ACL injury may alter intracortical facilitation [34] and depressed intracortical inhibition is correlated with decreased quadriceps voluntary activation capability [35], external focus training may provide a means to restore quadriceps muscle activity via increasing intracortical inhibition.

Authors' Reply to Valenzuela et al: Comment on: "Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography"

Comment on: "Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography"

Behavioral Correlates of Muscular Fitness in Children and Adolescents: A Systematic Review Abstract Background Muscular fitness (MF) is considered a powerful marker of health, but the extent to which common health behaviors are associated with MF during childhood and adolescence is currently unclear. Objective We conducted a systematic review of studies investigating associations between MF (i.e., strength/power, local muscular endurance) and physical activity, sedentary behaviors, and sleep in children and adolescents. Methods A systematic search of six electronic databases was performed on 8 March, 2017. Search results were screened for relevance and studies conducted with children and adolescents (3–18 years) that explored associations between MF and physical activity, sedentary behavior, or sleep were considered eligible. Data were extracted and checked by a second author. The proportion of studies reporting a statistically significant association between each MF component and behavioral variables was calculated, and additional coding was conducted to account for risk of bias. Results There was consistent evidence for a positive association between MF and physical activity. For both MF components, there was support for objectively measured physical activity, particularly for activity of vigorous intensity. Sports participation was also consistently linked with both MF components, whereas the association with active transport was inconsistent. For both MF components, associations with sedentary behaviors were inconsistent irrespective of measurement method, and the association between MF and sleep was considered uncertain. Conclusions The available evidence supports a link between MF and physical activity, particularly for vigorous intensity activity and organized sports participation. Conversely, there is limited support for an association with sedentary behaviors, and more research exploring MF and sleep is required.

Weightlifting Overhead Pressing Derivatives: A Review of the Literature Abstract This review examines the literature on weightlifting overhead pressing derivatives (WOPDs) and provides information regarding historical, technical, kinetic and kinematic mechanisms as well as potential benefits and guidelines to implement the use of WOPDs as training tools for sports populations. Only 13 articles were found in a search of electronic databases, which was employed to gather empirical evidence to provide an insight into the kinetic and kinematic mechanisms underpinning WOPDs. Practitioners may implement WOPDs such as push press, push jerk or split jerk from the back as well as the front rack position to provide an adequate stimulus to improve not only weightlifting performance but also sports performance as: (1) the use of WOPDs is an additional strategy to improve weightlifting performance; (2) WOPDs require the ability to develop high forces rapidly by an impulsive triple extension of the hips, knees and ankles, which is mechanically similar to many sporting tasks; (3) WOPDs may be beneficial for enhancing power development and maximal strength in the sport population; and, finally, (4) WOPDs may provide a variation in training stimulus for the sports population due to the technical demands, need for balance and coordination. The potential benefits highlighted in the literature provide a justification for the implementation of WOPDs in sports training. However, there is a lack of information regarding the longitudinal training effects that may result from implementing WOPDs.

Acute Effects of Resistance Exercise on Cognitive Function in Healthy Adults: A Systematic Review with Multilevel Meta-Analysis Abstract Background Recent research has revealed a beneficial impact of chronic resistance exercise (RE) on brain function. However, it is unclear as to whether RE is also effective in an acute setting. Objective To investigate the immediate effects of a single RE session on cognitive performance in healthy adults. Methods A multilevel meta-analysis with random effects meta-regression model was used to pool the standardized mean differences (SMD) between RE and no-exercise (NEX) as well as between RE and aerobic exercise (AE). In addition to global cognitive function, effects on reported sub-domains (inhibitory control, cognitive flexibility, working memory, attention) were examined. Results Twelve trials with fair methodological quality (PEDro scale) were identified. Compared to NEX, RE had a positive effect on global cognition (SMD: 0.56, 95% CI 0.22–0.90, p = 0.004), but was not superior to AE (SMD: − 0.10, 95% CI 0.01 to − 0.20, p = 0.06). Regarding cognitive sub-domains, RE, compared to NEX, improved inhibitory control (SMD: 0.73, 95% CI 0.21–1.26, p = 0.01) and cognitive flexibility (SMD: 0.36, 95% CI 0.17–0.55, p  = 0.004). In contrast, working memory (SMD: 0.35, 95% CI − 0.05 to 0.75, p  = 0.07) and attention (SMD: 0.79, 95% CI − 0.42 to 2.00, p = 0.16) remained unaffected. No significant differences in sub-domains were found between RE and AE (p > 0.05). Conclusion RE appears to be an appropriate method to immediately enhance cognitive function in healthy adults. Further studies clearly elucidating the impact of effect modifiers such as age, training intensity, or training duration are warranted.

What is the Prevalence of Hip Intra-Articular Pathologies and Osteoarthritis in Active Athletes with Hip and Groin Pain Compared with Those Without? A Systematic Review and Meta-Analysis Abstract Background In athletes, hip and groin pain is considered to be associated with hip intra-articular pathologies and hip osteoarthritis (OA). A greater understanding of the relationship between hip and groin pain and imaging findings is required. Objective Our objective was to undertake a systematic review and meta-analysis to determine the prevalence of hip intra-articular pathologies and hip OA in athletes with and without hip and groin pain. Methods Seven electronic databases were searched on 29 January 2018 for studies investigating the prevalence of hip intra-articular pathologies and hip OA using X-ray, magnetic resonance imaging, magnetic resonance arthrography or computed tomography. The search, study selection, quality appraisal and data extraction were performed by two independent reviewers. When studies were considered homogenous, meta-analysis was undertaken. A strength of evidence was given to pooled results. Results Twenty studies reporting on the prevalence of hip intra-articular pathologies and hip OA in athletes were identified. Included studies were considered moderate to high risk of bias, with only three studies adjudged as low risk of bias. In asymptomatic athletes, limited evidence identified a labral tear prevalence of 54% per person and moderate evidence of 33% per hip. In symptomatic athletes, moderate evidence of a labral tear prevalence of 20% per hip was found. Moderate evidence of a cartilage defect prevalence of 10% per person was reported in asymptomatic athletes. In symptomatic athletes, cartilage defect prevalence was 7–40%. In asymptomatic athletes, the prevalence of hip OA was 0–17%, compared with 2% in symptomatic athletes. Conclusion The prevalence of hip intra-articular pathologies and hip OA in symptomatic and asymptomatic athletes is variable. Labral tears and cartilage defects appear to be seen often in athletes with and without pain. Hip OA is rarely seen in athletes either with or without hip and groin pain. Study Registration PROSPERO registration CRD42017082457.

Effect of Immobilisation on Neuromuscular Function In Vivo in Humans: A Systematic Review Abstract Background Muscle strength loss following immobilisation has been predominantly attributed to rapid muscle atrophy. However, this cannot fully explain the magnitude of muscle strength loss, so changes in neuromuscular function (NMF) may be involved. Objectives We systematically reviewed literature that quantified changes in muscle strength, size and NMF following periods of limb immobilisation in vivo in humans. Methods Studies were identified following systematic searches, assessed for inclusion, data extracted and quality appraised by two reviewers. Data were tabulated and reported narratively. Results Forty eligible studies were included, 22 immobilised lower and 18 immobilised upper limbs. Limb immobilisation ranged from 12 h to 56 days. Isometric muscle strength and muscle size declined following immobilisation; however, change magnitude was greater for strength than size. Evoked resting twitch force decreased for lower but increased for upper limbs. Rate of force development either remained unchanged or slowed for lower and typically slowed for upper limbs. Twitch relaxation rate slowed for both lower and upper limbs. Central motor drive typically decreased for both locations, while electromyography amplitude during maximum voluntary contractions decreased for the lower and presented mixed findings for the upper limbs. Trends imply faster rates of NMF loss relative to size earlier in immobilisation periods for all outcomes. Conclusions Limb immobilisation results in non-uniform loss of isometric muscle strength, size and NMF over time. Different outcomes between upper and lower limbs could be attributed to higher degrees of central neural control of upper limb musculature. Future research should focus on muscle function losses and mechanisms following acute immobilisation. Registration PROSPERO reference: CRD42016033692.

Maximal Sprint Speed and the Anaerobic Speed Reserve Domain: The Untapped Tools that Differentiate the World's Best Male 800 m Runners Abstract Recent evidence indicates that the modern-day men's 800 m runner requires a speed capability beyond that of previous eras. In addition, the appreciation of different athlete subgroups (400–800, 800, 800–1500 m) implies a complex interplay between the mechanical (aerial or terrestrial) and physiological characteristics that enable success in any individual runner. Historically, coach education for middle-distance running often emphasises aerobic metabolic conditioning, while it relatively lacks consideration for an important neuromuscular and mechanical component. Consequently, many 800 m runners today may lack the mechanical competence needed to achieve the relaxed race pace speed required for success, resulting in limited ability to cope with surges, run faster first laps or close fast. Mechanical competence may refer to the skilled coordination of neuromuscular/mechanical (stride length/frequency/impulse) and metabolic components needed to sustain middle-distance race pace and adjust to surges efficiently. The anaerobic speed reserve (ASR) construct (difference between an athlete's velocity at maximal oxygen uptake [v \(\dot{V}\) O2max]—the first speed at which maximal oxygen uptake [ \(\dot{V}\) O2max] is attained) and their maximal sprint speed (MSS) offers a framework to assess a runner's speed range relative to modern-day race demands. While the smooth and relaxed technique observed in middle-distance runners is often considered causal to running economy measured during submaximal running, little empirical evidence supports such an assumption. Thus, a multidisciplinary approach is needed to examine the underpinning factors enabling elite 800 m running race pace efficiency. Here, we argue for the importance of utilising the ASR and MSS measurement to ensure middle-distance runners have the skills to compete in the race-defining surges of modern-day 800 m running.

Principles of Motor Learning to Support Neuroplasticity After ACL Injury: Implications for Optimizing Performance and Reducing Risk of Second ACL Injury Abstract Athletes who wish to resume high-level activities after an injury to the anterior cruciate ligament (ACL) are often advised to undergo surgical reconstruction. Nevertheless, ACL reconstruction (ACLR) does not equate to normal function of the knee or reduced risk of subsequent injuries. In fact, recent evidence has shown that only around half of post-ACLR patients can expect to return to competitive level of sports. A rising concern is the high rate of second ACL injuries, particularly in young athletes, with up to 20% of those returning to sport in the first year from surgery experiencing a second ACL rupture. Aside from the increased risk of second injury, patients after ACLR have an increased risk of developing early onset of osteoarthritis. Given the recent findings, it is imperative that rehabilitation after ACLR is scrutinized so the second injury preventative strategies can be optimized. Unfortunately, current ACLR rehabilitation programs may not be optimally effective in addressing deficits related to the initial injury and the subsequent surgical intervention. Motor learning to (re-)acquire motor skills and neuroplastic capacities are not sufficiently incorporated during traditional rehabilitation, attesting to the high re-injury rates. The purpose of this article is to present novel clinically integrated motor learning principles to support neuroplasticity that can improve patient functional performance and reduce the risk of second ACL injury. The following key concepts to enhance rehabilitation and prepare the patient for re-integration to sports after an ACL injury that is as safe as possible are presented: (1) external focus of attention, (2) implicit learning, (3) differential learning, (4) self-controlled learning and contextual interference. The novel motor learning principles presented in this manuscript may optimize future rehabilitation programs to reduce second ACL injury risk and early development of osteoarthritis by targeting changes in neural networks.

Epidemiology

Umbrella reviews: what they are and why we need them

Cystic echinococcosis in unaccompanied minor refugees from Afghanistan and the Middle East to Germany, July 2016 through June 2017 Abstract Cystic echinococcosis (CE) is not covered by current refugee screening protocols. After we had detected CE among several refugees attending our clinic from Afghanistan and the Middle East, serological examinations for CE were performed for apparently healthy unaccompanied minor refugees from these regions.

The long and winding road to causality

Blood–brain barrier transcytosis genes, risk of dementia and stroke: a prospective cohort study of 74,754 individuals Abstract To test whether genetic variants in PICALM, BIN1, CD2AP, and RIN3—suggested to be involved in blood–brain barrier amyloid-β transcytosis pathways—associate with Alzheimer's disease, all dementia, suggested vascular dementia, and stroke, and whether such associations are independent of the strong ε4 APOE risk allele. In a prospective cohort study of 74,754 individuals from the general population we genotyped PICALM(rs10792832), BIN1 (rs6733839), CD2AP (rs10948363), and RIN3 (rs10498633), and generated a weighted and a simple allele score. Multifactorially adjusted hazard ratios for the fourth quartile versus the first quartile of the weighted allele score were 1.42 (95% confidence interval 1.22–1.64) for Alzheimer's disease, and 1.33 (1.19–1.48) for all dementia. For suggested vascular dementia and stroke the corresponding estimates were 1.71 (1.18–2.49) and 1.12 (1.04–1.22), respectively. Hazard ratios were similar after APOE adjustment. Genetic variants in PICALM, BIN1, CD2AP, and RIN3 are associated with increased risk of Alzheimer's disease, all dementia, and suggested vascular dementia independent of the strong APOE ε4 allele. These findings may suggest that clathrin-mediated endocytosis in clearance of amyloid-β across the blood–brain barrier is important for the integrity of both brain tissue and cerebral vessels.

Hospitalisation of people with dementia: evidence from English electronic health records from 2008 to 2016 Abstract Hospitalisation of people with dementia is associated with adverse outcomes and high costs. We aimed to examine general, i.e. non-psychiatric, hospitalisation rates, changes since 2008 and factors associated with admission. We also aimed to compare admission rates of people with dementia with age-matched people without dementia. We conducted a cohort study of adults ≥ 65 years, with dementia diagnosed during the 2008–2016 study window, derived from a large secondary mental healthcare database in South London, UK. We used national general hospital records to identify emergency and elective hospitalisations. We calculated the cumulative incidence and rate of hospitalisation and examined predictors of hospitalisation using negative binomial regression, with multiple imputation for missing covariate data. We calculated age-standardised admission ratio for people with dementia compared to those without. Of 10,137 people, 50.6% were admitted to hospital in the year following dementia diagnosis and 75.9% were admitted during median 2.5 years follow-up. Annual admission rate was 1.26/person-year of which 0.90/person-year were in emergency. Emergency hospitalisation rate increased throughout the study period. Compared to controls without diagnosed dementia in the catchment area, the age-standardised emergency admission ratio for people with dementia was 2.06 (95% CI 1.95, 2.18). Male, older, white and socio-economically deprived people and those with clinically significant comorbid physical illness, depressed mood, activity of daily living or living condition problems had more hospitalisations. Emergency hospitalisations of people with dementia are higher than those without, and increasing. Many factors associated with admission are social and psychological, and may be targets for future interventions that aim to reduce avoidable admissions.

Causal criteria: time has come for a revision Abstract Epidemiologists study associations but they are usually interested in causation that could lead to disease prevention. Experience show, however, that many of the associations we identify are not the causes we take an interest in (correlation is not causation). In order to proper translate association into causes, a set of causal criteria was developed 50–60 years ago and they became important tools guiding this translational process (sometimes correlation is causation). Best known of these are the Bradford Hill 'criteria'. In these last 50 years, epidemiologic theory and infrastructure have advanced rapidly without changes in these causal criteria. We think time has come to revisit the 'old' criteria to see which ones we should keep and which ones should be taken out or be replaced by new measures of association. Robustness of these criteria in attempts to make the association go away should have high priority. A group of renowned internationally recognized researchers should have this task. Since classifying associations as causes is often done in order to reduce or eliminate the exposures of concern results from conditional outcome research should also be used. We therefore suggest to add a 'consequence' criterion. We argue that a consequence criterion that provides a framework for assessing or prescribing action worthy or right in social contexts is needed. A consequence criterion will also influence how strict our causal criteria need to be before leading to action and will help in separating the 'causal discussion' and the discussion on what to do about it. A consequence criterion will be a tool in handling dilemmas over values (as social solidarity, fairness, autonomy). It will have implications for the interpretation and use of the procedural criteria of causality. Establishing interconnected procedural and consequence criteria should be a task for institutions representing and being recognized by experts, civil society and the state.

Asthma and selective migration from farming environments in a three-generation cohort study Abstract Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945–1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963–1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010–2012 and by G2 in 2013–2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0–G1 and G1–G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1–G2 (RR 1.11, 95% CI 0.81–1.52) or in G0–G1 (RR 0.99, 0.85–1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12–3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11–1.06). This pattern was not observed in analyses of G0–G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.

Identifying dementia outcomes in UK Biobank: a validation study of primary care, hospital admissions and mortality data Abstract Prospective, population-based studies that recruit participants in mid-life are valuable resources for dementia research. Follow-up in these studies is often through linkage to routinely-collected healthcare datasets. We investigated the accuracy of these datasets for dementia case ascertainment in a validation study using data from UK Biobank—an open access, population-based study of > 500,000 adults aged 40–69 years at recruitment in 2006–2010. From 17,198 UK Biobank participants recruited in Edinburgh, we identified those with ≥ 1 dementia code in their linked primary care, hospital admissions or mortality data and compared their coded diagnoses to clinical expert adjudication of their full-text medical record. We calculated the positive predictive value (PPV, the proportion of cases identified that were true positives) for all-cause dementia, Alzheimer's disease and vascular dementia for each dataset alone and in combination, and explored algorithmic code combinations to improve PPV. Among 120 participants, PPVs for all-cause dementia were 86.8%, 87.3% and 80.0% for primary care, hospital admissions and mortality data respectively and 82.5% across all datasets. We identified three algorithms that balanced a high PPV with reasonable case ascertainment. For Alzheimer's disease, PPVs were 74.1% for primary care, 68.2% for hospital admissions, 50.0% for mortality data and 71.4% in combination. PPV for vascular dementia was 43.8% across all sources. UK routinely-collected healthcare data can be used to identify all-cause dementia in prospective studies. PPVs for Alzheimer's disease and vascular dementia are lower. Further research is required to explore the geographic generalisability of these findings.

Blood pressure, hypertension and the risk of abdominal aortic aneurysms: a systematic review and meta-analysis of cohort studies Abstract Abdominal aortic aneurysms (AAA) are fatal in 80% of the cases when ruptured. Hypertension has been considered a potential risk factor for AAA; but the findings from prospective cohort studies have not been entirely consistent, nor have they been summarised in a comprehensive meta-analysis. Our aim was to conduct a systematic review and meta-analysis of cohort studies of the association between blood pressure, hypertension and AAA to clarify the strength and shape of these associations. We searched PubMed and Embase databases for relevant cohort studies up to April 30th, 2018. Random-effects models were used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs). The meta-analysis included 21 cohort studies (20 publications) with data on 28,162 cases and 5,440,588 participants. The findings indicate that the RR of AAA in hypertensive patients is 1.66 times (95% CI: 1.49–1.85, I2 = 79.3%, n = 13) that of non-hypertensive patients. In addition, there was a 14% (95% CI: 6–23%, I2 = 30.5%, n = 6) and a 28% (95% CI: 12–46%, I2 = 80.1%, n = 6) increase in the RR of AAA for every 20 mmHg and 10 mmHg increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP), respectively. The analysis of DBP showed evidence of a strong and highly significant nonlinear dose–response relationship (p < 0.001) with a steeper association from 80 mmHg and above. This meta-analysis suggests that hypertension increases the risk of developing AAA by 66%. Further studies are needed to clarify the underlying mechanism explaining the much stronger association between DBP and AAA than for SBP.

The association between weight at birth and breast cancer risk revisited using Mendelian randomisation Abstract Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10−8 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability. BW predicted by the 41-SNP IV was not associated with overall breast cancer risk in inverse-variance weighted (IVW) univariable MR analysis of genetic association data from 122,977 breast cancer cases and 105,974 controls (odds ratio = 0.86 per 500 g higher BW; 95% confidence interval 0.73–1.01). Sensitivity analyses using four alternative methods and three alternative IVs, including an IV with 59 of the 60 BW-associated SNPs, yielded similar results. Multivariable MR adjusting for the effects of the 49-SNP IV on birth length, adult height, adult body mass index, age at menarche, and age at menopause using IVW and MR-Egger methods provided estimates consistent with univariable analyses. Results were also similar when all analyses were repeated after restricting to estrogen receptor-positive or -negative breast cancer cases. Point estimates of the odds ratios from most analyses performed indicated an inverse relationship between genetically-predicted BW and breast cancer, but we are unable to rule out an association between the non-genetically-determined component of BW and breast cancer. Thus, genetically-predicted higher BW was not associated with an increased risk of breast cancer in adult life in our MR study.

Health Care Analysis

Are We Justified in Introducing Carbon Monoxide Testing to Encourage Smoking Cessation in Pregnant Women? Abstract Smoking is frequently presented as being particularly problematic when the smoker is a pregnant woman because of the potential harm to the future child. This premise is used to justify targeting pregnant women with a unique approach to smoking cessation including policies such as the routine testing of all pregnant women for carbon monoxide at every antenatal appointment. This paper examines the evidence that such policies are justified by the aim of harm prevention and argues that targeting pregnant women in this way is likely to do more harm than good. Routine carbon monoxide testing is particularly problematic as it sends a message to pregnant women that they cannot be trusted either to truthfully answer questions as to whether or not they smoke, or to make decisions in the best interests of themselves and their future children in the way that non-pregnant individuals are. Further, if the aim is to reduce rates of prenatal harm, the evidence suggests that adopting a supportive and empowering approach to prenatal care is the most effective way to achieve this, something that the current policies aimed at pregnant women are in conflict with.

Between the Reasonable and the Particular: Deflating Autonomy in the Legal Regulation of Informed Consent to Medical Treatment Abstract The law of informed consent to medical treatment has recently been extensively overhauled in England. The 2015 Montgomery judgment has done away with the long-held position that the information to be disclosed by doctors when obtaining valid consent from patients should be determined on the basis of what a reasonable body of medical opinion agree ought to be disclosed in the circumstances. The UK Supreme Court concluded that the information that is material to a patient's decision should instead be judged by reference to a new two-limbed test founded on the notions of the 'reasonable person' and the 'particular patient'. The rationale outlined in Montgomery for this new test of materiality, and academic comment on the ruling's significance, has focused on the central ethical importance that the law now (rightfully) accords to respect for patient autonomy in the process of obtaining consent from patients. In this paper, we dispute the claim that the new test of materiality articulated in Montgomery equates with respect for autonomy being given primacy in re-shaping the development of the law in this area. We also defend this position, arguing that our revised interpretation of Montgomery's significance does not equate with a failure by the courts to give due legal consideration to what is owed to patients as autonomous decision-makers in the consent process. Instead, Montgomery correctly implies that doctors are ethically (and legally) obliged to attend to a number of relevant ethical considerations in framing decisions about consent to treatment, which include subtle interpretations of the values of autonomy and well-being. Doctors should give appropriate consideration to how these values are fleshed out and balanced in context in order to specify precisely what information ought to be disclosed to a patient as a requirement of obtaining consent, and as a core component of shared decision-making within medical encounters more generally.

Principles of Need and the Aggregation Thesis Abstract Principles of need are constantly referred to in health care priority setting. The common denominator for any principle of need is that it will ascribe some kind of special normative weight to people being worse off. However, this common ground does not answer the question how a plausible principle of need should relate to the aggregation of benefits across individuals. Principles of need are sometimes stated as being incompatible with aggregation and sometimes characterized as accepting aggregation in much the same way as utilitarians do. In this paper we argue that if one wants to take principles of need seriously both of these positions have unreasonable implications. We then characterize and defend a principle of need consisting of sufficientarian elements as well as prioritarian which avoids these unreasonable implications.

Evidence, Emotion and Eminence: A Qualitative and Evaluative Analysis of Doctors' Skills in Macroallocation Abstract In this analysis of the ethical dimensions of doctors' participation in macroallocation we set out to understand the skills they use, how they are acquired, and how they influence performance of the role. Using the principles of grounded moral analysis, we conducted a semi-structured interview study with Australian doctors engaged in macroallocation. We found that they performed expertise as argument, bringing together phronetic and rhetorical skills founded on communication, strategic thinking, finance, and health data. They had made significant, purposeful efforts to gain skills for the role. Our findings challenge common assumptions about doctors' preferences in argumentation, and reveal an unexpected commitment to practical reason. Using the ethics of Paul Ricoeur in our analysis enabled us to identify the moral meaning of doctors' skills and learning. We concluded that Ricoeur's ethics offers an empirically grounded matrix for ethical analysis of the doctor's role in macroallocation that may help to establish norms for procedure.

Irresponsibly Infertile? Obesity, Efficiency, and Exclusion from Treatment Abstract Many countries tightly ration access to publicly funded fertility treatments such as in vitro fertilisation (IVF). One basis for excluding people from access to IVF is their body mass index. In this paper, I consider a number of potential justifications for such a policy, based on claims about effectiveness and cost-efficiency, and reject these as unsupported by available evidence. I consider an alternative justification: that those whose subfertility results from avoidable behaviours for which they are responsible are less deserving of treatment. I ultimately stop short of endorsing or rejecting such a justification, though highlight some reasons for thinking it is unlikely to be practicable.

Risk, Overdiagnosis and Ethical Justifications Abstract Many healthcare practices expose people to risks of harmful outcomes. However, the major theories of moral philosophy struggle to assess whether, when and why it is ethically justifiable to expose individuals to risks, as opposed to actually harming them. Sven Ove Hansson has proposed an approach to the ethical assessment of risk imposition that encourages attention to factors including questions of justice in the distribution of advantage and risk, people's acceptance or otherwise of risks, and the scope individuals have to influence the practices that generate risk. This paper investigates the ethical justifiability of preventive healthcare practices that expose people to risks including overdiagnosis. We applied Hansson's framework to three such practices: an 'ideal' breast screening service, a commercial personal genome testing service, and a guideline that lowers the diagnostic threshold for hypertension. The framework was challenging to apply, not least because healthcare has unclear boundaries and involves highly complex practices. Nonetheless, the framework encouraged attention to issues that would be widely recognised as morally pertinent. Our assessment supports the view that at least some preventive healthcare practices that impose risks including that of overdiagnosis are not ethically justifiable. Further work is however needed to develop and/or test refined assessment criteria and guidance for applying them.

Why the Elective Caesarean Lottery is Ethically Impermissible Abstract In the United Kingdom the law and medical guidance is supportive of women making choices in childbirth. NICE guidelines are explicit that a competent woman's informed request for MRCS (elective caesarean in the absence of any clinical indications) should be respected. However, in reality pregnant women are routinely denied MRCS. In this paper I consider whether there is sufficient justification for restricting MRCS. The physical and emotive significance of childbirth as an event in a woman's life cannot be understated. It is, therefore, concerning that women are having their wishes ignored, and we must ascertain whether the denial of agency is justifiable. To answer this question I first demonstrate that access to MRCS is a lottery in the UK. Second, I argue that there is nothing unique about pregnancy that displaces the ethical norm of respecting patents' sufficiently autonomous choices. Thus, the starting presumption is that all informed choices regarding MRCS should be respected. To ascertain whether any restriction of MRCS is justifiable the burden of proof must be placed on those who argue that MRCS is ethically impermissible. I argue that the most common justifications in the literature against MRCS are insufficient to displace the presumption in favour of autonomous choice in childbirth. I conclude that MRCS should be available to pregnant women, and we must strive to reduce the lottery in access to choice.

Perils of Professionalization: Chronicling a Crisis and Renewing the Potential of Healthcare Management Abstract This paper critically examines efforts to "professionalize" the field of healthcare management and its corresponding costs. Drawing upon the scholarly critiques of professionalization in medicine and the broader field of management, this paper seeks to explore the symbolic role professionalization might play in the psyche of its constituents, and specifically its function as a defense against uncertainty and anxiety. This psychodynamic heuristic is then deployed to put forth the hypothesis that an ongoing crisis of professional identity continues to both propel and impede professionalization efforts in healthcare management, giving rise to a litany of standardization pressures that ultimately limit the field's potential. To mitigate these pressures, the call is made for rekindling healthcare management's moral, political, and existential aspects. Specifically, this entails engaging with the deeper themes that flow through the field: the experience of illness and what it means to suffer, the experience of life and what it means to have hope, and the experience of death and dying. It also entails squarely confronting questions of power, poverty and disease, and the pursuit of justice.

'Effective' at What? On Effective Intervention in Serious Mental Illness Abstract The term "effective," on its own, is honorific but vague. Interventions against serious mental illness may be "effective" at goals as diverse as reducing "apparent sadness" or providing housing. Underexamined use of "effective" and other success terms often obfuscates differences and incompatibilities in interventions, degrees of effectiveness, key omissions in effectiveness standards, and values involved in determining what counts as "effective." Yet vague use of such success terms is common in the research, clinical, and policy realms, with consequences that negatively affect the care offered to individuals experiencing serious mental illness. A pragmatist-oriented solution to these problems suggests that when people use success terms, they need to explain and defend the goals and supporting values embedded in the terms, asking and answering the questions, "Effective at what? For whom? How effective? And why that goal?" Practical and epistemic standards for effectiveness will likely remain plural for good reasons, but each standard should be well explained and well justified.

The Fundamental Importance of the Normative Analysis of Health

Yoga

Interdisciplinary science and yoga: The challenges ahead Govindasamy Agoramoorthy International Journal of Yoga 2019 12(2):89-90

The psycho-linguistic effects of yoga: A lexical analysis of shifts in positivity, agency, and creativity Robin Blades, David MacFadyen International Journal of Yoga 2019 12(2):91-95 Introduction: Yoga is understood in the scientific community as a powerful de-stressor. Reduced stress has been linked to improved mood, increased agency, and enhanced creativity. Objective: This study investigates these potential psychological effects of yoga by comparing two lexical data sets, composed of nearly 3000 words collected before and after yoga classes. Methods: Each word is scored along three dimensions: positivity, agency, and creativity. Positivity is calculated using SentiWords Sentiment Dictionary 1.0; agency is determined by grammatical categorization; and creativity is viewed as a function of the set distribution. Results: Analysis reveals a shift toward more positive and less agentful self-reporting after practice. No significant difference is found in creativity.Conclusion: This study provides insight into how yoga alters thought processes and affects the mental health of practitioners.

Effectiveness of adjuvant yoga therapy in diabetic lung: A randomized control trial Rajasekar Balaji, Meena Ramanathan, Ananda Balayogi Bhavanani, Pajanivel Ranganadin, Karthik Balachandran International Journal of Yoga 2019 12(2):96-102 Context: Recent studies provide ample evidence of the benefits of yoga in various chronic disorders. Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia and Sandler coined the term “Diabetic Lung” for the abnormal pulmonary function detected in diabetic patients due underlying pulmonary dysfunction. Yoga therapy may help in achieving better pulmonary function along with enhanced glycaemic control and overall health benefits. Aim: To study the effect of adjuvant yoga therapy in diabetic lung through spirometry. Settings and Design: Randomized control trial was made as interdisciplinary collaborative work between departments of Yoga Therapy, Pulmonary Medicine and Endocrinology, of MGMC & RI, Sri Balaji Vidyapeeth Puducherry. Materials and Methods: 72 patients of diabetic lung as confirmed by spirometry (<70% of expected) were randomized into control group (n=36) who received only standard medical treatment and yoga group (n=36) who received yoga training thrice weekly for 4 months along with standard medical management. Yoga therapy protocol included yogic counseling, preparatory practices, Asanas or static postures, Pranayama or breathing techniques and relaxation techniques. Hathenas of the Gitananda Yoga tradition were the main practices used. Spirometry was done at the end of the study period. Data was analyzed by Student's paired and unpaired 't' test as it passed normality. Results: There was a statistically significant (P < 0.05) reduction in weight, and BMI along with a significant (P < 0.01) improvement in pulmonary function (FEV1, FVC) in yoga group as compared to control group where parameters worsened over study period. Conclusion: It is concluded from the present RCT that yoga has a definite role as an adjuvant therapy as it enhances standard medical care and hence is even more significant in routine clinical management of diabetes, improving physical condition and pulmonary function.

The daily influences of yoga on relational outcomes off of the mat Moé; Kishida, Jacqueline Mogle, Steriani Elavsky International Journal of Yoga 2019 12(2):103-113 Background: Despite the wide array of health benefits that have been evidenced with yoga, a clear gap exists examining how yoga impacts connections with oneself and to others. Aims: The objectives of the present study were twofold: (1) to describe the day-to-day (in)variability in daily yoga practice and relational outcomes and (2) to examine the direct and indirect effects of yoga practice on relational outcomes. Methods: Community-dwelling yoga practitioners (n = 104, age range: 18–76 years) with a yoga practice of at least once a week were recruited for a 21-day daily diary study. Practitioners were asked to complete daily Internet surveys at the end of the day which included questions with respect to one's yoga practice and relational domains (i.e., mindfulness, [self-]compassion, and social connectedness). Results: Multilevel analyses revealed yoga and relational outcomes to be dynamic phenomena, indicated by substantial variation (intraclass correlations = 0.34–0.48) at the within-person level. On days when an individual practiced more yoga than their usual, greater mindfulness (b = 2.93, standard error [SE] = 0.39, P < 0.05) and self-compassion (b = 1.45, SE = 0.46, P < 0.05) were also reported. 1-1-1 multilevel mediation models demonstrated that yoga has an indirect effect on both compassion and social connectedness through increases in mindfulness at the within- and between-person levels. In models testing self-compassion as the mediator, the indirect effect of daily yoga practice on compassion was significant, although limited to the within-person level. Conclusions: These findings suggest that a routine yoga practice could positively impact how a practitioner relates to theirselves and to others, both on a day-to-day basis, and with accumulated practice.

Quasi prospective comparative study on effect of yoga among prediabetics on progression of cardiovascular risk factors Sudhanshu Kacker, Neha Saboo, Sonali Sharma, Jitender Sorout International Journal of Yoga 2019 12(2):114-119 Introduction: Prediabetic patients have higher risk for cardiovascular diseases, which further increases the rate of mortality. Reason for the rate of increase may be lack of observation, follow-up programs, and self-awareness about the conditions of disease. Lifestyle interventions such as yoga can prove to be a beneficial nonpharmacologic intervention in preventing progression of prediabetes to type 2 diabetes. This study highlights importance of short-term intervention, i.e., yoga in prediabetic patients and use it as a tool for primary prevention of diabetes. Methods: This was an interventional study among adults aged 30–50 years in RUHS college of Medical Sciences and Associated Rukmani Devi Beni Prasad Jaipuria Hospital in Jaipur city. The design of study was quasi prospective comparative study. A total of 102 prediabetic patients of age group 30–50 years were recruited from Jaipuria Hospital. These were divided into two groups: study group (Group A, n = 51) were engaged in yoga session and control group (B, n = 51) not performed any yoga session. Results: Yoga intervention resulted in a significant decline in blood glucose (P < 0.001), glycated hemoglobin (P < 0.01), lipid profile cholesterol (P < 0.01), triglyceride (P < 0.01), and low-density lipoprotein (P < 0.01), but high-density lipoprotein (P < 0.02) and very low-density lipoprotein increase (P < 0.03) but not statistically significant relative to the control group. Conclusion: Short-term yoga intervention is helpful in the control of glycemic parameters like blood glucose, glycated hemoglobin and lipid profile in prediabetic patients. This preliminary study indicates that a yoga program would be a possible risk reduction option for adults at high risk for type 2 diabetes. In addition, yoga holds promise as an approach to reducing cardiometabolic risk factors and increasing exercise self-efficacy for prediabetics performing yoga.

The efficacy of yogic breathing exercise Bhramari pranayama in relieving symptoms of chronic rhinosinusitis K Abishek, Satvinder Singh Bakshi, Ananda Balayogi Bhavanani International Journal of Yoga 2019 12(2):120-123 Introduction: A multitude of modalities are available for the treatment of chronic rhinosinusitis, however, each has its side effects and compliance issues. Bhramari pranayama, which is a breathing exercise in the practice of yoga, offers an inexpensive and free from side effect modality in this regard. Objective: The objective of this study was to evaluate the efficacy of Bhramari pranayama in relieving the symptoms of chronic sinusitis. Methodology: A total of 60 patients with chronic sinusitis were randomly divided into two groups, one received conventional treatment of chronic sinusitis and the other group was in addition taught to practice yogic breathing exercise Bhramari pranayama. The patients were advised to practice this breathing exercise twice a day and were followed up at 1, 4, and 12 weeks using the Sino-Nasal Outcome Test (SNOT-22 score). Results: The mean SNOT-22 score in the group following the Bhramari pranayama breathing exercise using the ANOVA test improved from 39.13 ± 9.10 to 24.79 ± 8.31 (P = 0.0002), this improvement was seen by the end of 4 weeks itself and continued until the 12th week of assessment. Conclusion: Integrating regular practice of Bhramari pranayama along with the conventional management of chronic rhinosinusitis is more effective than conventional management alone.

Kinematics of suryanamaskar using three-dimensional motion capture Rajani P Mullerpatan, Bela M Agarwal, Triveni Shetty, Girish R Nehete, Omkar Subbaramajois Narasipura International Journal of Yoga 2019 12(2):124-131 Background: Suryanamaskar, a composite yogasana consisting of a sequence of 12-consecutive poses, producing a balance between flexion and extension is known to have positive health benefits for obesity and physical fitness management, upper limb muscle endurance, and body flexibility. However, limited information is available on biomechanical demands of Suryanamaskar, i.e., kinematic and kinetic. Aims: The present study aimed to explore the kinematics of spine, upper, and lower extremity during Suryanamaskar to enhance greater understanding of Suryanamaskar required for safe and precise prescription in the management of musculoskeletal disorders. Methods: Three-dimensional motion capture of Suryanamaskar was performed on 10 healthy trained yoga practitioners with 12-camera Vicon System (Oxford Metrics Group, UK) at a sampling frequency of 100 Hz using 39 retro-reflective markers. Data were processed using plug-in-gait model. Analog data were filtered at 10Hz. Joint angles of the spine, upper, and lower extremities during 12-subsequent poses were computed within Vicon Nexus. Results: Joint motion was largely symmetrical in all poses except pose 4 and 9. The spine moved through a range of 58° flexion to 44° extension. In the lower quadrant, hip moved from 134° flexion to 15° extension, knee flexed to a maximum of 140°, and 3° hyperextension. Ankle moved in a closed kinematic chain through 40° dorsiflexion to 10° plantarflexion. In the upper quadrant, maximum neck extension was76°, shoulder moved through the overhead extension of 183°–56° flexion, elbow through 22°–116° flexion, and wrist from 85° to 3° wrist extension. Conclusions: Alternating wide range of transition between flexion and extension during Suryanamaskar holds potential to increase the mobility of almost all body joints, with stretch on anterior and posterior soft tissues and challenge postural balance mechanisms through a varying base of support.

Effect of yoga on immune parameters, cognitive functions, and quality of life among HIV-positive children/adolescents: A pilot study BP Hari Chandra, Mavathur N Ramesh, Hogasandra R Nagendra International Journal of Yoga 2019 12(2):132-138 Context: HIV/AIDS individuals have problems relating to immune system, quality of life (QOL), and cognitive functions (CFs). Yoga is found to be useful in similar conditions. Hardly, any work is reported on yoga for HIV-positive adults/adolescents. Hence, this study is important. Aim: The aim of the study is to determine the effect of yoga on immune parameters, CFs, and QOL of HIV-positive children/adolescents. Settings and Design: Single-group, pre–post study with 4-month yoga intervention. Methods: The study had 18 children from an HIV/AIDS rehabilitation center for children/adolescents. CD4, CD8, CD4/CD8 ratio, and viral loads were studied. CF tests included six letter cancellation test, symbol digit modalities test, digit-span forward backward test, and Stroop tests. QOL was assessed using PedsQL-QOL and fatigue questionnaire. Depression was assessed using CDI2-SR. Statistical Analysis Used:t-test and Wilcoxon signed-rank tests, as applicable. Results: The study included 18 children/adolescents. There was improvement in general health of the participants. There was statistically significant increase in CD4 cells counts (p = 0.039) and significant decrease in viral load (p = 0.041). CD4/CD8 ratio moved to normal range. QOL significantly improved. CFs had mixed results with improved psychomotor performance (PP) and reduced executive functions. Conclusions: There was improvement in general health and immune parameters. While depression increased, QOL improved. CFs showed mixed results with improved PP and reduced executive functions.

Effect of residential yoga camp on psychosocial fitness of adolescents Astha Choukse, Amritanshu Ram, HR Nagendra International Journal of Yoga 2019 12(2):139-145 Background: Adolescence is a key phase of socialization, where improved psychosocial fitness helps to promote socioeconomic productivity in societies. Psychosocial fitness also has an impact on the academic performance, overall health, and quality of life, throughout life. The present study evaluates the effect of yoga intervention on psychosocial fitness among adolescents. Materials and Methods: A single group, pre and post yoga interventional study was carried out in three independent cohorts (batches 1, 2, and 3), having sample size of 148, 167, and 195 respectively. A 7-day integrated yoga intervention was given in a residential setting. Psychosocial assessments included social competence, empathy, altruism, parent relationship, and peer friendship. Data were collected from the participants and their parents using respective versions of the scales. While pre- and post-data were collected from all the adolescent participants, pre- and post-data from parents were collected for 340 and 43 parents only. The objective of the analyses was to evaluate the effect of the yoga program and check the consistency of these effects. Results: Significant changes (P < 0.05) were seen in social competence, empathy, and altruism in batches 2 and 3, whereas changes in batch 1 showed nonsignificant improvements. Analyses of the parental data indicated a significant improvement in parent relationship (P = 0.035) and also nonsignificant improvement in all other outcomes. Conclusion: Results suggested that yoga intervention might help in improving psychosocial fitness in adolescents. It also helped to demonstrate that administering yoga was acceptable and feasible in a residential setting.

Lifestyle - A common denominator for the onset and management of migraine headache: Complementing traditional approaches with scientific evidence MS Vasudha, NK Manjunath, HR Nagendra International Journal of Yoga 2019 12(2):146-152 Background: Ayurveda and Yoga have gained popularity in the management of various chronic health problems associated with pain including migraine headache. It is evident from both scientific as well as traditional literature that stress, diet, sleep, and exposure to extreme climatic conditions act as triggering factors for the onset of migraine. Hence, it is essential to focus on lifestyle including diet as important factors for prevention and as adjuvant factors in the management of migraine headache. Aim: The aim was to propose a new perspective to the understanding of migraine headache keeping in view the role of lifestyle including diet. Methods: Classical Ayurveda texts and traditional Yoga scriptures were used to compile information on the role of lifestyle including diet in the onset and management of migraine headache. This was complemented by PubMed-based review of scientific literature. Outcome: Ayurveda texts provide an extensive information about the basic understanding, causes, precipitating factors, and management of migraine headache, while Yoga texts refer to the concept of mental stress (adhi) leading to physical health problems (vyadhi). It is evident from the literature that diet, sleep, exposure to extreme climatic conditions, and mental stress play an important role in the onset and management of migraine headache. Conclusion: Lifestyle appears to be the common factor for both onset and management of migraine headache.