Connexin-mimetic peptide Gap 27 decreases osteoclastic activity

BACKGROUND: Bone remodelling is dependent on the balance between bone resorbing osteoclasts and bone forming osteoblasts. We have shown previously that osteoclasts contain gap-junctional protein connexin-43 and that a commonly used gap-junctional inhibitor, heptanol, can inhibit osteoclastic bone resorption. Since heptanol may also have some unspecific effect unrelated to gap-junctional inhibition we wanted to test the importance of gap-junctional communication to osteoclasts using a more specific inhibitor. METHODS: A synthetic connexin-mimetic peptide, Gap 27, was used to evaluate the contribution of gap-junctional communication to osteoclastic bone resorption. We utilised the well-characterised pit-formation assay to study the effects of the specific gap-junctional inhibitor to the survival and activity of osteoclasts. RESULTS: Gap 27 caused a remarked decrease in the number of both TRAP-positive mononuclear and multinucleated rat osteoclasts cultured on bovine bone slices. The decrease in the cell survival seemed to be restricted to TRAP-positive cells, whereas the other cells of the culture model seemed unaffected. The activity of the remaining osteoclasts was found to be diminished by measuring the percentage of osteoclasts with actin rings of all TRAP-positive cells. In addition, the resorbed area in the treated cultures was greatly diminished. CONCLUSIONS: On the basis of these results we conclude that gap-junctional communication is essential for the action of bone resorbing osteoclasts and for proper remodelling for bone

Transumbilical Totally Laparoscopic Single-Port Nissen Fundoplication: A New Method of Liver Retraction: The Istanbul Technique

Mustafa Kemal Ataturk, founder of the Turkish Republic, had guarded many German scientists of a Jewish descent before the Second World War. Dr. Rudolf Nissen was one of the outstanding surgeons who had served in the Turkish university hospitals. He had created an antireflux procedure which is named after his own name while he was working in our clinic, the CerrahpaAYa Hospital. From a laparoscopic approach, the Nissen fundoplication was the gold standard intervention for the surgical treatment of gastroesophageal reflux disease (GERD). Currently, video laparoscopic surgery is evolving quickly with the guidance of new technology. Single-port (SP) laparoscopic transumbilical surgery is one of the newest branches of advanced laparoscopy

Young, healthy males and females present cardiometabolic protection against the detrimental effects of a 7-day high-fat high-calorie diet

Purpose: High-fat, high-calorie (HFHC) diets have been used as a model to investigate lipid-induced insulin resistance. Short-term HFHC diets reduce insulin sensitivity in young healthy males, but to date, no study has directly compared males and females to elucidate sex-specific differences in the effects of a HFHC diet on functional metabolic and cardiovascular outcomes. Methods: Eleven males (24 ± 4 years; BMI 23 ± 2 kg.m−2; V̇O2 peak 62.3 ± 8.7 ml.min−1.kg−1FFM) were matched to 10 females (25 ± 4 years; BMI 23 ± 2 kg.m−2; V̇O2 peak 58.2 ± 8.2 ml.min−1.kg−1FFM). Insulin sensitivity, measured via oral glucose tolerance test, metabolic flexibility, arterial stiffness, body composition and blood lipids and liver enzymes were measured before and after 7 days of a high-fat (65% energy) high-calorie (+ 50% kcal) diet. Results: The HFHC diet did not change measures of insulin sensitivity, metabolic flexibility or arterial stiffness in either sex. There was a trend towards increased total body fat mass (kg) after the HFHC diet (+ 1.8% and + 2.3% for males and females, respectively; P = 0.056). In contrast to females, males had a significant increase in trunk to leg fat mass ratio (+ 5.1%; P = 0.005). Conclusion: Lean, healthy young males and females appear to be protected from the negative cardio-metabolic effects of a 7-day HFHC diet. Future research should use a prolonged positive energy balance achieved via increased energy intake and reduced energy expenditure to exacerbate negative metabolic and cardiovascular functional outcomes to determine whether sex-specific differences exist under more metabolically challenging conditions

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

COMPARISON OF GOOD AND POOR JUMPERS AS DETERMINED BY REACTIVE STRENGTH INDEX MODIFIED

Paul T. Donahue, Lindsey Legg, Hunter Haynes, Megan Rush. University of Southern Mississippi, Hattiesburg, MS. BACKGROUND: The countermovement vertical jump (CMJ) is an exercise commonly used to monitor an individual’s neuromuscular abilities. Jump height is the most commonly used variable when discussing jumping ability. This provides a gross performance metric of one’s ability, yet fails in explaining the explosiveness of an athlete as a given jump height can be achieved using differing neuromuscular strategies. This has led to the more thorough analysis of the CMJ to better understand an athlete’s explosive muscular qualities. One such variable is the reactive strength index modified (RSIm) which accounts for the kinetic outputs of the tasks (jump height) and temporal constraints that are seen in sport. Thus, the purpose of this investigation was to compare groups of high and low RSIm performers to determine what variables may contribute to the explosive qualities in collegiate female athletes. METHODS: 42 female Division 1 collegiate athletes completed two maximal effort countermovement jumps as part of their athlete monitoring program. Prior to completing testing, each participant completed a standardized dynamic warm up. Each trial was separated by thirty seconds. All trials were performed on the same portable force platform, sampling at 1000 Hz. The mean of the two trials was calculated for each variable. Groups were determined as being above or below the median RSIm (0.38) for the entire sample. Group comparisons were made using independent t-test for each of the variables of interest. RESULTS: Significant differences were seen in RSIm (0.42 ± 0.05 vs 0.32 ± 0.4) and the high RSIm group having shorter eccentric duration (548.7 ± 77.62 vs 509.72 ± 53.07 ms). Though not significantly different, a moderate to large effect sizes was seen when comparing time to take off (d= 0.55) and jump heights (d = 1.22) between groups with the high RSIm group having greater jump heights and a shorter duration of time to takeoff. CONCLUSIONS: As RSIm is calculated as the ratio of jump height over time to take off (movement initiation to point of takeoff from the ground), the difference between individuals with high RSIm values appears to be a combination of achieving greater jump height and doing so in less time as neither showed statistically significant differences between groups

THE VALIDITY OF THE VMAXPRO DURING COUNTERMOVEMENT JUMP AND BACK SQUAT PERFORMANCE

Hunter Haynes, Riley Galloway, Paul T. Donahue, Scott Piland, Nuno Oliveira. University of Southern Mississippi, Hattiesburg, MS. Background: Advances in technology have resulted in an increase in the utilization of velocity-based training in the strength and conditioning field while utilization of inertia measurement units (IMUs) shows promise. Methods: Recreationally trained participants (N=25, 28.3 ± 2.9 years) were recruited to determine the validity of the VmaxPro device for measuring performance variables in the back squat and countermovement jump (CMJ) against a gold standard forceplate. Squat variables assessed included mean concentric velocity (MCV), mean concentric power (MCP), depth, and duration while CMJ variables assessed included MCV, MCP, depth, duration, and jump height. Squat variables were assessed across 3 conditions: BW, 50% BW, and 100% BW. Results: MCV demonstrated strong correlations in the BW, 50% and 100% conditions (r= 0.965; r=.907; r= 0.827, p\u3c0.001). MCP demonstrated strong correlations across all 3 squat conditions (r= 0.979, 0.960, and 0.887, respectively). MCV and jump height demonstrated strong correlation (r= 0.6-0.79) in the countermovement jump (r=0.728 p\u3c0.001 and r=0.796 p\u3c0.001, respectively). Bland-Altman analysis demonstrated that all measurements fell within the 95% confidence interval between devices. Mean differences between measures showed a consistent overestimation produced by the VmaxPro device. Conclusion: The VmaxPro is a reasonably valid device for assessing duration, and jump height when assessing CMJ performance as compared to the force plate while demonstrating overestimation bias. For back squat performance variables, the VmaxPro proves as a reasonably valid device for assessing MCV, MCP, depth, and duration while demonstrating overestimation bias in MCV and MCP

ASSOCIATIONS BETWEEN COUNTERMOVEMENT JUMP PERFORMANCE AND BODY COMPOSITION IN FEMALE ATHLETES

Lindsey T. Legg1, Megan Rush1, Stephanie McCoy1, John C. Garner2, Paul T. Donahue1. 1University of Southern Mississippi, Hattiesburg, MS. 2Troy University, Troy, AL. BACKGROUND: Both vertical jump performance and body composition have been shown to distinguish between levels of competition in volleyball athletes. With previous investigations displaying relationships between body composition and vertical jump height using a range of instrumentation and prediction equations, limited data has been presented using gold standard measurements for both body composition and vertical jump performance. The purpose of this investigation was to examine the relationship between absolute and relative measures of body composition and vertical jump performance using gold standard measurements in a female athlete population.METHODS:14 female Division I collegiate volleyball athletes participated in this investigation (age 19.86 ± 0.86 years, height 180.61 ± 3.99 cm, body 69.93 ± 9.73 kg). Participants completed a standardized warm up prior to completing 3 countermovement jumps. Each jump was performed with a PVC dowel (\u3c1.0 kg) placed across the upper back in a high bar squat position. All trials were separated by 30 seconds of rest. All jump trials were performed using a force platform, sampling at 1000 Hz. Body composition was analyzed through total body DXA scan. Absolute and relative measure of body composition were then calculated for the total body and lower extremity. All testing was performed within a one-week period at the conclusion of the competitive season. Pearson Product Moment Correlations were used to determine the relationship between jump performance and body composition measures. RESULTS: Significant large to very large (r = 0.5 - 0.9) positive relationships were seen between total body lean and fat mass, lower extremity lean and fat mass, and CMJ force and power. Significant large (r = 0.5 - 0.7) negative relationships were present between total body fat percentage, total fat mass and CMJ jump height. CONCLUSIONS: These findings support much of the previous literature that increases in mass, regardless of composition, creates increases in force and power production during the vertical jumping task. Additionally, it should be noted that the relationship strength stayed consistent when looking between total and lower extremity absolute values of lean and fat mass to force and power production