Cardiac structure and function in resistance-trained and untrained adults: A systematic review and meta-analysis.

Variations in the haemodynamic demands of specific training modalities may explain characteristic differences in cardiac structure and function amongst athletes. However, current consensus regarding these adaptations in highly resistance-trained athletes is yet to be established. The current invetsigation aimed to collate research investigating cardiac structure and function in resistance-trained athletes, exploring the defining characteristics of Athlete's Heart within these individuals. Seven electronic databases were searched. Studies which examined at least one measure of cardiac structure or function, included healthy, normotensive male or females (>18 years) and compared athletes engaged in a resistance training programme (>12 months) to an untrained group engaged in no structured training programme were included. Systematic selection and quality appraisal of articles was performed by two reviewers, with a random effects meta-analysis model applied to suitable studies. Studies were limited to orginal peer-reviewed articles published in English. Resistance-trained athletes (n = 949) demonstrated greater cardiac dimensions compared to their untrained counterparts (n = 1053). No clear impairments to systolic or diastolic cardiac function were observed in athletic population studied here. Resistance-trained athletes display some characteristics of the Athlete's Heart phenomenon, including greater wall thickening and chamber dilation compared to their untrained counterparts.

The effect of varying intensities of lower limb eccentric muscle contractions on left ventricular function.

PURPOSE: The effect of eccentric (ECC) resistance exercise (RE) on myocardial mechanics is currently unknown. METHOD: This study investigated ECC RE at varying intensities on left ventricular (LV) function using LV strain (ε), wall stress and haemodynamic parameters. Twenty-four healthy male volunteers completed ECC leg extensions at 20%, 50% and 80% of their ECC maximal voluntary contraction (MVC), whilst receiving echocardiograms. Global longitudinal ɛ, strain rate (SR), longitudinal tissue velocity, heart rate (HR), blood pressure (BP), mean arterial pressure (MAP), LV wall stress and rate pressure product (RPP) were assessed at baseline and during exercise. RESULTS: Left ventricular global ɛ, systolic SR and wall stress remained unchanged throughout. Systolic blood pressure (sBP), MAP and RPP increased at 80% and 50% intensities compared to rest (P < 0.01). Eccentric RE increased HR and peak late diastolic SR at all intensities compared to rest (P < 0.02). CONCLUSION: The findings suggest acute ECC RE may not alter main parameters of LV function, supporting future potential for wider clinical use. However, future studies must investigate the impact of multiple repetitions and training on LV function.

Unilateral Stiffness Interventions Augment Vertical Stiffness and Change of Direction Speed.

Maloney, SJ, Richards, J, Jelly, L, and Fletcher, IM. Unilateral stiffness interventions augment vertical stiffness and change of direction speed. J Strength Cond Res 33(2): 372-379, 2019-It has previously been shown that preconditioning interventions can augment change of direction speed (CODS). However, the mechanistic nature of these augmentations has not been well considered. The current study sought to determine the effects of preconditioning interventions designed to augment vertical stiffness on CODS. Following familiarization, 10 healthy males (age: 22 ± 2 years; height: 1.78 ± 0.05 m; body mass: 75.1 ± 8.7 kg) performed 3 different stiffness interventions in a randomized and counterbalanced order. The interventions were: (a) bilateral-focused, (b) unilateral-focused, and (c) a control of CODS test practice. Vertical stiffness and joint stiffness were determined preintervention and postintervention using a single-leg drop jump task. Change of direction speed test performance was assessed postintervention using a double 90° cutting task. Performances following the unilateral intervention were significantly faster than control (1.7%; p = 0.011; d = -1.08), but not significantly faster than the bilateral intervention (1.0% faster; p = 0.14; d = -0.59). Versus control, vertical stiffness was 14% greater (p = 0.049; d = 0.39) following the unilateral intervention and 11% greater (p = 0.019; d = 0.31) following the bilateral intervention; there was no difference between unilateral and bilateral interventions (p = 0.94; d = -0.08). The findings of the current study suggest that unilateral preconditioning interventions designed to augment vertical stiffness improve CODS within this experimental cohort.

Global and regional left ventricular circumferential strain during incremental cycling and isometric knee extension exercise.

BACKGROUND: The objective of this study was to investigate left ventricular (LV) circumferential strain responses to incremental cycling and isometric knee extension exercises. METHODS: Twenty-six healthy male participants (age = 30 ± 6 years) were used to study LV global (GCS) and regional circumferential strain at the apex (ACS) and base (BCS) during incremental cycling at 30% and 60% work rate maximum (Wmax ) and short-duration (15 seconds contractions) isometric knee extensions at 40% and 75% maximum voluntary contraction (MVC) using two-dimensional speckle tracking echocardiography. RESULTS: During cycling (n = 22), GCS increased progressively from rest to 60% Wmax (-22.85 ± 3.26% to -29.87 ± 2.59%, P < .01). ACS increased from rest to 30% Wmax (-26.29 ± 4.84% to -36.84 ± 6.94%, P < .01) and then remained unchanged to 60% Wmax (-40.72 ± 4.06%, P = .068). BCS decreased from rest to 30% Wmax (-19.41 ± 2.79 to -17.51 ± 4.66%, P = .05) and then remained unchanged to 60% Wmax . During isometric knee extension (n = 23), GCS decreased from rest to 40% MVC (-22.63 ± 3.46 to -20.10 ± 2.78%, P < .05) and then remained unchanged to 75% MVC. Similarly, BCS decreased from rest to 40% MVC (-19.21 ± 2.58% to -13.55 ± 3.45%, P < .01) and then remained unchanged, whereas ACS did not change with exercise intensity (rest, -26.05 ± 5.34%; 40% MVC, -26.64 ± 4.53% and 75% MVC -27.22 ± 5.34%, all P > .05). CONCLUSION: Global circumferential strain increased stepwise during incremental cycling, mediated by the apex with trivial changes at the base. In contrast, GCS decreased during the isometric knee extension to 40% MVC and then plateaued, due to decreased BCS as ACS was maintained. A novel finding is that the GCS response appears to be exercise modality dependant and is the consequence of region-specific changes.

A Comparison of Bilateral and Unilateral Drop Jumping Tasks in the Assessment of Vertical Stiffness.

This study sought to compare vertical stiffness during bilateral and unilateral drop jumping. Specifically, the intersession reliabilities and force-deformation profiles associated with each task were to be examined. On 3 occasions, following familiarization, 14 healthy males (age: 22 [2] y; height: 1.77 [0.08] m; and body mass: 73.5 [8.0] kg) performed 3 bilateral, left leg and right leg drop jumps. All jumps were performed from a drop height of 0.18 m on to a dual force plate system. Vertical stiffness was calculated as the ratio of peak ground reaction force (GRF) to the peak center of mass (COM) displacement. Unilateral drop jumping was associated with higher GRF and greater COM displacement (both Ps < .001), but vertical stiffness was not different between tasks when considering individual limbs (P = .98). A coefficient of variation of 14.6% was observed for bilateral vertical stiffness during bilateral drop jumping; values of 6.7% and 7.6% were observed for left and right limb vertical stiffness during unilateral drop jumping. These findings suggest that unilateral drop jumps may exhibit greater reliability than bilateral drop jumps while eliciting similar vertical stiffness. It is also apparent that higher GRFs during unilateral drop jumping are mitigated by increased COM displacement.

Left ventricular twist mechanics during incremental cycling and knee extension exercise in healthy men.

PURPOSE: The objective of the present study was to investigate left ventricular (LV) twist mechanics in response to incremental cycling and isometric knee extension exercises. METHODS: Twenty-six healthy male participants (age = 30.42 ± 6.17 years) were used to study peak twist mechanics at rest and during incremental semi-supine cycling at 30 and 60% work rate maximum (W max) and during short duration (15 s contractions) isometric knee extension at 40 and 75% maximum voluntary contraction (MVC), using two-dimensional speckle tracking echocardiography. RESULTS: Data presented as mean ± standard deviation or median (interquartile range). LV twist increased from rest to 30% W max (13.21° ± 4.63° to 20.04° ± 4.76°, p < 0.001) then remained unchanged. LV systolic and diastolic twisting velocities progressively increased with exercise intensity during cycling from rest to 60% W max (twisting, 88.21° ± 20.51° to 209.05° ± 34.56° s-1, p < 0.0001; untwisting, -93.90 (29.62)° to -267.31 (104.30)° s-1, p < 0.0001). During the knee extension exercise, LV twist remained unchanged with progressive intensity (rest 13.40° ± 4.80° to 75% MVC 16.77° ± 5.54°, p > 0.05), whilst twisting velocity increased (rest 89.15° ± 21.77° s-1 to 75% MVC 124.32° ± 34.89° s-1, p < 0.01). Untwisting velocity remained unchanged from rest [-90.60 (27.19)° s-1] to 40% MVC (p > 0.05) then increased from 40 to 75% MVC [-98.44 (43.54)° s-1 to -138.42 (73.29)° s-1, p < 0.01]. Apical rotations and rotational velocities were greater than basal during all conditions and intensities (all p < 0.01). CONCLUSION: Cycling increased LV twist to 30% W max which then remained unchanged thereafter, whereas twisting velocities showed further increases to greater intensities. A novel finding is that LV twist was unaffected by incremental knee extension, yet systolic and diastolic twisting velocities augmented with isometric exercise.

Do stiffness and asymmetries predict change of direction performance?

Change of direction speed (CODS) underpins performance in a wide range of sports but little is known about how stiffness and asymmetries affect CODS. Eighteen healthy males performed unilateral drop jumps to determine vertical, ankle, knee and hip stiffness, and a CODS test to evaluate left and right leg cutting performance during which ground reaction force data were sampled. A step-wise regression analysis was performed to ascertain the determinants of CODS time. A two-variable regression model explained 63% (R2 = 0.63; P = 0.001) of CODS performance. The model included the mean vertical stiffness and jump height asymmetry determined during the drop jump. Faster athletes (n = 9) exhibited greater vertical stiffness (F = 12.40; P = 0.001) and less asymmetry in drop jump height (F = 6.02; P = 0.026) than slower athletes (n  = 9); effect sizes were both "large" in magnitude. Results suggest that overall vertical stiffness and drop jump height asymmetry are the strongest predictors of CODS in a healthy, non-athletic population.

A comparison of methods to determine bilateral asymmetries in vertical leg stiffness.

Whilst the measurement and quantification of vertical leg stiffness (Kvert) asymmetry is of important practical relevance to athletic performance, literature investigating bilateral asymmetry in Kvert is limited. Moreover, how the type of task used to assess Kvert may affect the expression of asymmetry has not been properly determined. Twelve healthy males performed three types of performance tasks on a dual force plate system to determine Kvert asymmetries; the tasks were (a) bilateral hopping, (b) bilateral drop jumping and (c) unilateral drop jumping. Across all the three methods, Kvert was significantly different between compliant and stiff limbs (P < 0.001) with a significant interaction effect between limb and method (P = 0.005). Differences in Kvert between compliant and stiff limbs were -5.3% (P < 0.001), -21.8% (P = 0.007) and -15.1% (P < 0.001) for the bilateral hopping, bilateral drop jumping and unilateral drop jumping methods, respectively. All the three methods were able to detect significant differences between compliant and stiff limbs, and could be used as a diagnostic tool to assess Kvert asymmetry. Drop jumping tasks detected larger Kvert asymmetries than hopping, suggesting that asymmetries may be expressed to a greater extent in acyclic, maximal performance tasks.

Magnetic controlled growth rods versus conventional growing rod systems in the treatment of early onset scoliosis: a cost comparison.

PURPOSE: To evaluate the cost differences between a conventional growth rod system (CGRS) and magnetic controlled growth rods (MCGR) in treating early onset scoliosis (EOS) over a projected 5 year period. We hypothesise that the high initial outlay for MCGR would be recouped from fewer admissions and surgical procedures over the lifetime of the implant. METHODS: The costs of all aspects of treatment for 14 patients undergoing conversion from CGRS to MGRS were collected over a 3 year period. The costs of all aspects of each treatment including clinic visits, hospital stay, theatre and complications were calculated and projected over the lifetime of each device. RESULTS: The initial outlay for insertion for MCGR was £12,913 more than the CGRS. There were significant cost savings for each lengthening which projected over the 5 year lifetime amounted to a cost saving of over £8,000 per patient. CONCLUSIONS: Magnetic controlled growth rods reduce the need for multiple invasive procedures in the management of EOS. The implant has a significant projected cost saving in comparison to CGRS.

Reliability of Unilateral Vertical Leg Stiffness Measures Assessed During Bilateral Hopping.

The assessment of vertical leg stiffness is an important consideration given its relationship to performance. Vertical stiffness is most commonly assessed during a bilateral hopping task. The current study sought to determine the intersession reliability, quantified by the coefficient of variation, of vertical stiffness during bilateral hopping when assessed for the left and right limbs independently, which had not been previously investigated. On 4 separate occasions, 10 healthy males performed 30 unshod bilateral hops on a dual force plate system with data recorded independently for the left and right limbs. Vertical stiffness was calculated as the ratio of peak ground reaction force to the peak negative displacement of the center of mass during each hop and was averaged over the sixth through tenth hops. For vertical stiffness, average coefficients of variation of 15.3% and 14.3% were observed for the left and right limbs, respectively. An average coefficient of variation of 14.7% was observed for bilateral vertical stiffness. The current study reports that calculations of unilateral vertical stiffness demonstrate reliability comparable to bilateral calculations. Determining unilateral vertical stiffness values and relative discrepancies may allow a coach to build a more complete stiffness profile of an individual athlete and better inform the training process.

Mixed versus pure variants of desmoplastic melanoma: a genetic and immunohistochemical appraisal.

Desmoplastic melanoma is subclassified into pure and mixed variants with a higher rate of lymph node metastasis in the latter. Given that reasons for these biological differences are not currently known, we investigated these subtypes with techniques that included genetic and immunohistochemical analyses of 43 cases of desmoplastic melanoma (24 pure, 19 mixed). Direct DNA sequencing was performed on BRAFV600E, RET gene (coding region on exon 11) and KIT (exons 11, 13 and 17). Immunohistochemical stains were performed with antibodies to markers of significance with respect to biological potential of nevomelanocytic proliferations and/or desmoplastic melanoma (Ki-67, CD117, nestin, clusterin, SOX10 and CD271/p75NTR). Polymorphism at the RET coding region (RETp) was noted in 33% of pure (8/24 cases) versus 24% of mixed (4/17 cases); BRAFV600E was absent in all cases of pure (0/24 cases) versus 6% of mixed (1/17 cases); no mutations were found in any of the cases on analyses of exons 11, 13 and 17 of the c-KIT gene (P=NS for all). For immunohistochemical analyses of pure versus mixed: mean percentage of Ki-67 nuclear positivity was 5% (s.d.=5.6) versus 28% (s.d.=12.6, P<0.001); CD117 stained 26% (6/23 cases) versus 78% (14/18 cases, P<0.01); nestin stained 83% (n=19/23 cases) versus 89% (16/18 cases, P=NS); clusterin stained 4% (1/23 cases) versus 6% (1/18 cases, P=NS); SOX10 87% (20/23 cases) versus 94% (17/18 cases, P=NS) and CD271 stained 61% (14/23 cases) versus 67% (12/18 cases, P=NS). Increased CD117 staining in the mixed variant suggests that alterations in the KIT protein may be involved in tumor progression. In addition, the proliferative index of the mixed variant was higher than that of the pure variant.

Lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi.

BACKGROUND: Given the correlation between KIT mutations and immunohistochemical expression of CKIT in acral melanoma, our aim was to confirm the utility of CKIT detection as a screening tool for KIT genotyping in atypical acral nevi and to ascertain the frequency of KIT mutations in the same. DESIGN: Immunohistochemical staining for CKIT was performed and staining criteria were the following: negative = <10%, 1 = 11%-49%, and 2 = >50% of cells. Intensity grading was as follows: negative = 0, weak = 1, moderate = 2, and strong = 3. Genomic amplification was performed on KIT exons commonly mutated in acral melanomas (11, 13, and 17) from atypical acral nevi (23) ranging in severity from mild (9), moderate (10), and severe (4). The control group included acral nevi without atypia (19). For purposes of statistical analyses, cases with 11% or more staining of cells were compared with negative cases and cases with a staining intensity of 1 or higher were compared with the negatives. RESULTS: Immunohistochemical analyses revealed the following: positive staining with an intensity 1 or more in 18 of 22 (82%) of cases with atypia (5 mild; 9 moderate and 4 severe) and in 13 of 17 (76%) nevi without atypia with no statistically significant differences between both groups. Genomic analyses of exon regions revealed no abnormalities in "hotspots" frequently associated with point mutations in acral melanomas. CONCLUSIONS: Our findings indicate a lack of correlation between immunohistochemical expression of CKIT and KIT mutations in atypical acral nevi. Atypical acral nevi do not exhibit genetic alterations in KIT associated with acral melanomas.

Sedentary Behaviour-A Target for the Prevention and Management of Cardiovascular Disease.

Cardiovascular disease (CVD) is highly prevalent and can lead to disability and premature mortality. Sedentary behaviour, defined as a low energy expenditure while sitting or lying down, has been identified as an independent risk factor for CVD. This article discusses (1) the association of total sedentary time and patterns of accumulating sedentary time with CVD risk markers, CVD incidence and mortality; (2) acute experimental evidence regarding the acute effects of reducing and breaking up sedentary time on CVD risk markers; and (3) the effectiveness of longer-term sedentary behaviour interventions on CVD risk. Findings suggest that under rigorously controlled laboratory and free-living conditions, breaking up sedentary time improves cardiovascular risk markers in individuals who are healthy, overweight or obese, or have impaired cardiovascular health. Breaking up sedentary time with walking may have the most widespread benefits, whereas standing breaks may be less effective, especially in healthy individuals. There is also growing evidence that sedentary behaviour interventions may benefit cardiovascular risk in the longer term (i.e., weeks to months). Reducing and breaking up sedentary time may, therefore, be considered a target for preventing and managing CVD. Further research is needed to determine the effectiveness of sedentary behaviour interventions over the long-term to appropriately inform guidelines for the management of CVD.

Stem cell markers (cytokeratin 15, cytokeratin 19 and p63) in in situ and invasive cutaneous epithelial lesions.

The inherent longetivity of stem cells causes them to be susceptible to multiple genetic hits. Thus, it is not surprising that stem cells are implicated in the etiopathogenesis of select cutaneous neoplasms. However, most studies to date are restricted to the use of a single marker (p63, cytokeratin-15 or cytokeratin-19) and do not appear to compare distribution of stem cell markers in a spectrum of cutaneous in situ versus invasive epithelial malignancies. In this study, we evaluate expression of cytokeratin-15, cytokeratin-19, and p63 in a series of primary cutaneous epithelial lesions that include actinic keratosis (n=29), squamous cell carcinoma in situ (n=30), bowenoid papulosis (n=15) and squamous cell carcinoma, well differentiated (n=29) in order to evaluate the role of stem cell marker expression in the grading and development of in situ and invasive malignancies. For cytokeratin-15, expression was retained in actinic keratosis (38%), squamous cell carcinoma in situ (53%) and bowenoid papulosis (60%) but appeared to be lost in squamous cell carcinoma (3%) with statistically significant differences observed between groups that retained versus those that did not (P<0.05 for all three); for cytokeratin-19, patchy yet basal expression was noted in actinic keratosis (21%), patchy and suprabasal expression was noted in squamous cell carcinoma in situ (37%), bowenoid papulosis (13%) and squamous cell carcinoma (24%) with no statistically significant differences between groups; for p63, expression was retained in actinic keratosis (90%), squamous cell carcinoma in situ (87%), bowenoid papulosis (60%) and squamous cell carcinoma (100%) with no statistically significant differences between groups. In summary, our findings expand the neoplasms which involve stem cells to include cutaneous epithelial malignancies. Differential localization of each of these markers argues in favor of stem cell heterogeneity.

The Prevalence and Predictors of Hypertension and the Metabolic Syndrome in Police Personnel.

Hypertension and metabolic syndrome (METSYN) are reportedly high in police forces. This may contribute to health deterioration and absenteeism in police personnel. Police forces comprise of staff in 'operational' and 'non-operational' job types but it is not known if job type is associated to hypertension and METSYN prevalence. This study aimed to explore the prevalence of hypertension and METSYN, the factors associated with the risk of hypertension and METSYN, and compare physiological, psychological, and behavioural factors between operational and non-operational police personnel. Cross-sectional data was collected from 77 operational and 60 non-operational police workers. Hypertension and METSYN were prevalent in 60.5% and 20% of operational and 60.0% and 13.6% of non-operational police personnel, respectively (p > 0.05). Operational job type, moderate organisational stress (compared with low stress) and lower high-density lipoprotein cholesterol were associated with lower odds of hypertension, whereas increasing body mass index was associated with increased odds of hypertension (p < 0.05). None of the independent variables were significantly associated with the odds of METSYN. Operational police had several increased cardiometabolic risk markers compared with non-operational police. Given the high prevalence of hypertension and METSYN in operational and non-operational personnel, occupational health interventions are needed for the police and could be informed by the findings of this study.

Fibroblast-activation protein: a single marker that confidently differentiates morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma.

Microscopically, differentiating desmoplastic trichoepithelioma from morpheaform/infiltrative basal cell carcinoma can be difficult as both show 'islands and strands of basaloid cells embedded in a sclerotic stroma'. A superficial shave biopsy further compounds the diagnostic conundrum. Although a plethora of immunohistochemical markers have been touted as being of use as adjunct histologic tools, none thus far appears to be consistent and reliable in terms of specificity and/or sensitivity. Fibroblast-activation protein, a type II membrane-bound glycoprotein belonging to the serine protease family, is expressed in the granulation tissue of healing wounds. More recently, it has been identified as a marker of reactive tumor stromal fibroblasts, as it is reportedly selectively expressed in peritumoral stromal fibroblasts of multiple epithelial cancers including cutaneous malignancies such as basal cell carcinoma. Given this, we sought to ascertain the use of fibroblast-activation protein in distinguishing morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma. Immunohistochemical staining for fibroblast-activation protein was performed on desmoplastic trichoepithelioma (n=25) and morpheaform/infiltrative basal cell carcinoma (n=25), with the control group comprising scars from reexcision specimens (n=10). As expected, fibroblast-activation protein expression was observed in stromal fibroblasts of all control cases (10 of 10, 100%). Of interest, fibroblast-activation protein expression was observed in peritumoral fibroblasts of all cases of morpheaform/infiltrative basal cell carcinoma (25 of 25, 100%) but not in any cases of desmoplastic trichoepithelioma (0 of 25, 0%). A gradient of fibroblast-activation protein expression was observed in morpheaform/infiltrative basal cell carcinoma with more intense expression noted in fibroblasts abutting the tumor cells, a less intense expression in the distal peritumoral stromal portion, and minimal to loss of expression in adjacent normal tissue. In summary, findings from this study underscore the use of fibroblast-activation protein as a histologic adjunct in confidently differentiating morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma.

The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin.

Often the distinction of primary adnexal carcinoma from metastatic adenocarcinoma to skin from breast, lung, and other sites can be a diagnostic dilemma. Current markers purportedly of utility as diagnostic adjuncts include p63 and D2-40; however, their expression has been demonstrated in 11-22% and 5% of metastatic cutaneous metastases, respectively. Both cytokeratin (CK) 15 and nestin have been reported as follicular stem cell markers. We performed CK15 and nestin, as well as previously reported stains (such as p63, D2-40, and calretinin) on 113 cases (59 primary adnexal carcinomas and 54 cutaneous metastases). Expressions of p63, CK15, nestin, D2-40, and calretinin were observed in 91, 40, 37, 44, and 14% of primary adnexal carcinoma, respectively, and in 8, 2, 8, 4, and 10% of cutaneous metastases, respectively. p63 appeared to be the most sensitive marker (with a sensitivity of 91%) in detecting primary adnexal carcinomas. CK15 appeared to be the most specific marker with a specificity of 98%. Using chi(2) analysis, statistically significant P-values (<0.05) were observed for p63, CK15, nestin, and D2-40 in the distinction of primary adnexal carcinoma versus cutaneous metastases. In logistic regression and stepwise selection for predicting a primary adnexal carcinoma, statistical significance was observed for p63, CK15, and D2-40 (P-values: <0.001, 0.0275, and 0.0298, respectively) but not for nestin (P-value=0.4573). Our study indicates that diagnostic sensitivity and specificity are significantly improved using a selected panel of immunohistochemical markers, including p63, CK15, and D2-40. Positive staining with all three markers argues in favor of a primary cutaneous adnexal neoplasm.

Aerobic Training Protects Cardiac Function During Advancing Age: A Meta-Analysis of Four Decades of Controlled Studies.

BACKGROUND: In contrast to younger athletes, there is comparatively less literature examining cardiac structure and function in older athletes. However, a progressive accumulation of studies during the past four decades offers a body of literature worthy of systematic scrutiny. OBJECTIVES: We conducted a systematic review, meta-analysis and meta-regression of controlled echocardiography studies comparing left ventricular (LV) structure and function in aerobically trained older athletes (> 45 years) with age-matched untrained controls, in addition to investigating the influence of chronological age. METHODS: Electronic databases were searched from inception to January 2018 before conducting a random-effects meta-analysis to calculate pooled differences in means, effect size and 95% confidence intervals (CIs). Study heterogeneity was reported using Cochran's Q and I2 statistic. RESULTS: Overall, 32 studies (644 athletes; 582 controls) were included. Athletes had greater LV end-diastolic diameter (3.65 mm, 95% CI 2.66-4.64), interventricular septal thickness (1.23 mm, 95% CI 0.85-1.60), posterior wall thickness (1.20 mm, 95% CI 0.83-1.56), LV mass (72 g, 95% CI 46-98), LV mass index (28.17 g·m2, 95% CI 19.84-36.49) and stroke volume (13.59 mL, 95% CI 7.20-19.98) (all p < 0.01). Athletes had superior global diastolic function [ratio of early (E) to late (A) mitral inflow velocity (E/A) 0.18, 95% CI 0.13-0.24, p < 0.01; ratio of early (e') to late (a') diastolic annular tissue velocity (e'/a') 0.23, 95% CI 0.06-0.40, p = 0.01], lower A (-8.20 cm·s-1, 95% CI -11.90 to -4.51, p < 0.01) and a' (-0.72 cm·s-1, 95% CI -1.31 to -0.12, p = 0.02), and more rapid e' (0.96 cm·s-1, 95% CI 0.05-1.86, p = 0.04). Meta-regression for chronological age identified that athlete-control differences, in the main, are maintained during advancing age. CONCLUSIONS: Athletic older men have larger cardiac dimensions and enjoy more favourable cardiac function than healthy, non-athletic counterparts. Notably, the athlete groups maintain these effects during chronological ageing.

Mechanism of cell death induced by cis-3, 4', 5-trimethoxy-3'-aminostilbene in ovarian cancer.

OBJECTIVE: Stilbene derivative, cis-3, 4', 5-trimethoxy-3'-aminostilbene (stilbene 5c), is highly potent to induce cell death in ovarian cancer cells. This study is to investigate its mechanism to induce cell death. METHODS: UCI101 ovarian cancer cells were used for this study. Cell death was analyzed by Alamar blue staining. Cell cycle was analyzed by flow cytometry after PI staining. Mitochondrial potential and reactive oxygen species were determined by MitoTracker green and DCF-DA, respectively. Immunofluorescent staining was done with tubulin antibody following by confocal microscope examination. Cell lysates were collected after treatment with stilbene 5c for Western blotting analysis of various cell cycle regulators and signal transduction mediators. RESULTS: Stilbene-treated cells die in both cell cycle-dependent and -independent pathways. Low concentration (30 nM) induces cell death without cell cycle arrest. This process involves disruption of mitochondrial potential and production of ROS by a Bcl-2-independent pathway. Higher concentration of stilbene 5c arrests cell cycle in G(2)/M phase, which is supported by dephosphorylation of Cdc2 and Cdc25C, and transiently elevation of spindle checkpoint BubR1. Although phosphorylation of Chk1 and Chk2 both increases after treatment, loss of Chk1 suppresses, whereas loss of Chk2 enhances, stilbene 5c-induced cell death. Phosphorylation of Akt and Stat3, but not MAPK, is suppressed after stilbene 5c treatment. CONCLUSION: These studies provide a mechanistic insight in using stilbenes in ovarian cancer. Stilbenes could be potentially useful agents for ovarian cancer therapy and induce cell death through mitochondrial damage and cell cycle arrest.

Left Ventricular Speckle Tracking-Derived Cardiac Strain and Cardiac Twist Mechanics in Athletes: A Systematic Review and Meta-Analysis of Controlled Studies.

BACKGROUND: The athlete's heart is associated with physiological remodeling as a consequence of repetitive cardiac loading. The effect of exercise training on left ventricular (LV) cardiac strain and twist mechanics are equivocal, and no meta-analysis has been conducted to date. OBJECTIVE: The objective of this systematic review and meta-analysis was to review the literature pertaining to the effect of different forms of athletic training on cardiac strain and twist mechanics and determine the influence of traditional and contemporary sporting classifications on cardiac strain and twist mechanics. METHODS: We searched PubMed/MEDLINE, Web of Science, and ScienceDirect for controlled studies of aged-matched male participants aged 18-45 years that used two-dimensional (2D) speckle tracking with a defined athlete sporting discipline and a control group not engaged in training programs. Data were extracted independently by two reviewers. Random-effects meta-analyses, subgroup analyses, and meta-regressions were conducted. RESULTS: Our review included 13 studies with 945 participants (controls n = 355; athletes n = 590). Meta-analyses showed no athlete-control differences in LV strain or twist mechanics. However, moderator analyses showed greater LV twist in high-static low-dynamic athletes (d = -0.76, 95% confidence interval [CI] -1.32 to -0.20; p < 0.01) than in controls. Peak untwisting velocity (PUV) was greater in high-static low-dynamic athletes (d = -0.43, 95% CI -0.84 to -0.03; p < 0.05) but less than controls in high-static high-dynamic athletes (d = 0.79, 95% CI 0.002-1.58; p = 0.05). Elite endurance athletes had significantly less twist and apical rotation than controls (d = 0.68, 95% CI 0.19-1.16, p < 0.01; d = 0.64, 95% CI 0.27-1.00, p = 0.001, respectively) but no differences in basal rotation. Meta-regressions showed LV mass index was positively associated with global longitudinal (b = 0.01, 95% CI 0.002-0.02; p < 0.05), whereas systolic blood pressure was negatively associated with PUV (b = -0.06, 95% CI -0.13 to -0.001; p = 0.05). CONCLUSION: Echocardiographic 2D speckle tracking can identify subtle physiological differences in adaptations to cardiac strain and twist mechanics between athletes and healthy controls. Differences in speckle tracking echocardiography-derived parameters can be identified using suitable sporting categorizations.