Analysis of Firework-Related Injuries to the Upper Extremity in the United States: 2011-2020.

INTRODUCTION: The purpose of this study is to examine and characterize patterns of injury to the upper extremity caused by fireworks in a nationally representative sample of emergency department patients from 2011 to 2020. METHODS: The National Electronic Injury Surveillance System was queried for upper-extremity injuries caused by fireworks between 2011 and 2020. RESULTS: One thousand two hundred fifty-one injuries were identified from the database representing 47,235 national cases that presented to emergency departments in the United States. Case frequency was stable during the period until 2020, which was nearly 70% higher than the previous 9-y average. Patients were generally young and male, with most cases in the 10-29-y age group and males over three times as likely to be injured as females. The most common injury was burn, and the week of July 4th accounted for 53% of cases alone. Diagnosis was also significantly associated with device type. CONCLUSIONS: These data can be used to target prevention measures and campaigns to specific patient populations most at risk of injury, specifically young males. They may also be used to highlight the impact of policy changes on availability of fireworks, the need for public health education coinciding with injury incidence peaks, and secondary pandemic effects.

Symptom resolution following a repeat concussion within the same athlete.

INTRODUCTION: Repeat sport-related concussion (SRC) is anecdotally associated with prolonged recovery. Few studies have examined repeat concussion within the same athlete. We sought to explore differences in symptom burden and recovery outcomes in an individual athlete's initial and repeat SRC. METHODS: A retrospective within-subject cohort study of athletes aged 12-23 years diagnosed with two separate SRCs from 11/2017-10/2020 was conducted. Primary outcomes were initial symptom severity and time-to-symptom-resolution. Secondary outcomes included return-to-learn (RTL) and return-to-play (RTP) duration. RESULTS: Of 868 athletes seen, 47 athletes presented with repeat concussions. Median time between concussions was 244 days (IQR 136-395). Comparing initial to repeat concussion, no differences were observed in time-to-clinic (4.3 ± 7.3vs.3.7 ± 4.6 days, p = 0.56) or initial PCSS (26.2 ± 25.3 vs. 30.5 ± 24.1, p = 0.32). While a difference was observed in time-to-symptom resolution between initial/repeat concussion (21.2 ± 16.3 vs. 41.7 ± 86.0 days, p = 0.30), this did not reach statistical significance. No significant differences were observed in time-to-RTL (17.8 ± 60.6 vs. 6.0 ± 8.3 days, p = 0.26) and RTP (33.2 ± 44.1 vs. 29.4 ± 39.1 days, p = 0.75). Repeat concussion was not associated with symptom resolution on univariate (HR 1.64, 95% CI 0.96-2.78, p = 0.07) and multivariable (HR 0.85, 95% CI 0.49-1.46, p = 0.55) Cox regression. CONCLUSION: No significant differences in symptom duration and RTP/RTL were seen between initial/repeat concussion.

Age of First Exposure to Contact Sports Is Not Associated With Worse Later-In-Life Brain Health in a Cohort of Community-Dwelling Older Men.

OBJECTIVE: To evaluate whether early age of first exposure to contact sports (AFE-CS) is associated with worse long-term brain health outcomes. DESIGN: A cross-sectional, survey study of older men with a history of contact sport participation was completed. SETTING: Tertiary care facility. PARTICIPANTS: A cohort of community-dwelling older men dichotomized by using AFE-CS (<12 years vs ≥12 years). INTERVENTIONS: Independent variables included a dichotomized group of AFE-CS (<12 years vs ≥12 years). MAIN OUTCOME MEASURES: Brain health outcomes measured by depression, anxiety, cognitive difficulties, and neurobehavioral symptoms. Endorsements of general health problems, motor symptoms, and psychiatric history were also collected. Age of first exposure groups was compared using t tests, χ2 tests, and multivariable linear regressions, which included the following covariates: age, number of prior concussions, and total years of contact sport. RESULTS: Of 69 men aged 70.5 ± 8.0 years, approximately one-third of the sample (34.8%) reported AFE-CS before age 12 years. That group had more years of contact sports (10.8 ± 9.2 years) compared with those with AFE-CS ≥12 (5.6 ± 4.5 years; P = 0.02). No differences were found after univariate testing between AFE-CS groups on all outcomes (P-values >0.05). Multivariable models suggest that AFE-CS is not a predictor of depression or anxiety. Those in the AFE-CS <12 group had fewer cognitive difficulties (P = 0.03) and fewer neurobehavioral symptoms (P = 0.03). CONCLUSIONS: Those with AFE-CS <12 to contact sports did not have worse long-term brain health outcomes compared with those with AFE-CS ≥12. Individuals with AFE-CS <12 had significantly lower British Columbia Cognitive Complaints Inventory and Neurobehavioral Symptom Inventory scores compared with those with AFE-CS ≥12. CLINICAL RELEVANCE: The benefits of earlier AFE-CS may outweigh the risks of head strikes and result in comparable long-term brain health outcomes.

Ethnicity Is Associated With Differing Presentation and Outcomes of Patients Undergoing Aortic Valve Replacement for Calcific Aortic Stenosis in Aotearoa New Zealand.

AIM: Surgical aortic valve replacement (SAVR) has been the gold standard for treatment of severe symptomatic aortic stenosis (AS) for decades. We examined whether ethnic differences exist in the presentation and outcomes of patients undergoing aortic valve replacement (AVR) for AS in New Zealand. METHODS: Patients of New Zealand European, Maori, and Pacific Island ethnicities undergoing SAVR with or without other procedures in New Zealand public hospitals from 2017 to 2019 were included. Major postoperative outcomes were compared between ethnic groups, with 30-day mortality being the primary outcome. RESULTS: A total of 1,175 patients were included: 1,085 European, 50 Maori, and 40 Pacific. The mean age was 71.1±9.4 years, and men accounted for more than half of all patients (69.9%). Maori (64.7±9.4 years) and Pacific (65.4±10.1 years) patients were younger when undergoing SAVR compared with European patients (71.7±9.2; analysis of variance p<0.001). Maori and Pacific patients had a higher prevalence of diabetes, poorer renal function, and worse left ventricular function; 30-day mortality was higher in Maori and Pacific compared with European patients (6% and 10% vs 2.4%, respectively; Fisher's exact test p=0.011), with odds ratio of 3.06 (95% confidence interval [CI] 0.88-10.66) for Maori patients after adjustment for EuroSCORE II and odds ratio of 5.23 (95% CI 1.79-16.07) for Pacific patients. CONCLUSIONS: There are significant differences in presentation and outcomes of patients undergoing AVR in New Zealand. Maori and Pacific patients undergo SAVR at a younger age, have more preoperative comorbidities, and have higher rates of 30-day mortality than European patients.

Cardiac Progenitor Cells and Adipocyte Stem Cells from Same Patients Exhibit In Vitro Functional Differences.

Cardiac progenitor cells (CPCs) and adipocyte stem cells (ASCs) are widely tested for their efficacy in repairing the diseased heart with varying results. However, no study has directly compared the functional efficacy of CPCs and ASCs collected from the same patient. CPCs and ASCs were isolated from the right atrial appendage and epicardial adipose tissue of the same patients, using explant culture. The flow cytometry analysis confirmed that both the cell types express common mesenchymal stem cells markers CD90 and CD105. ASCs, in addition, expressed CD29 and CD73. The wound-healing assay demonstrated that CPCs migrate faster to cover the wound area. Both cell types were resistant to hypoxia-induced cell death when exposed to hypoxia and serum deprivation; however, the ASCs showed increased proliferation. Conditioned medium (CM) collected after culturing serum-deprived CPCs and ASCs showed differential secretion patterns, with ASC CM showing an increased IGF-1 level, while CPC CM showed an increased FGF level. Only CPC CM reduced hypoxia-induced apoptosis in AC-16 human ventricular cardiomyocytes, while vascular network formation by endothelial cells was comparable between CPC and ASC CM. In conclusion, ASCs and CPCs exhibit differential characteristics within the same patient, and in vitro studies showed that CPCs have marginally superior functional efficacy.

Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells.

AIMS/HYPOTHESIS: Diabetes mellitus causes a progressive loss of functional efficacy in stem cells, including cardiac progenitor cells (CPCs). The underlying molecular mechanism is still not known. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate genes at the post-transcriptional level. We aimed to determine if diabetes mellitus induces dysregulation of miRNAs in CPCs and to test if in vitro therapeutic modulation of miRNAs would improve the functions of diabetic CPCs. METHODS: CPCs were isolated from a mouse model of type 2 diabetes (db/db), non-diabetic mice and human right atrial appendage heart tissue. Total RNA isolated from mouse CPCs was miRNA profiled using Nanostring analysis. Bioinformatic analysis was employed to predict the functional effects of altered miRNAs. MS analysis was applied to determine the targets, which were confirmed by western blot analysis. Finally, to assess the beneficial effects of therapeutic modulation of miRNAs in vitro and in vivo, prosurvival miR-30c-5p was overexpressed in mouse and human diabetic CPCs, and the functional consequences were determined by measuring the level of apoptotic cell death, cardiac function and mitochondrial membrane potential (MMP). RESULTS: Among 599 miRNAs analysed in mouse CPCs via Nanostring analysis, 16 miRNAs showed significant dysregulation in the diabetic CPCs. Using bioinformatics tools and quantitative real-time PCR (qPCR) validation, four altered miRNAs (miR-30c-5p, miR-329-3p, miR-376c-3p and miR-495-3p) were identified to play an important role in cell proliferation and survival. Diabetes mellitus significantly downregulated miR-30c-5p, while it upregulated miR-329-3p, miR-376c-3p and miR-495-3p. MS analysis revealed proapoptotic voltage-dependent anion-selective channel 1 (VDAC1) as a direct target for miR-30c-5p, and cell cycle regulator, cyclin-dependent protein kinase 6 (CDK6), as the direct target for miR-329-3p, miR-376c-3p and miR-495-3p. Western blot analyses showed a marked increase in VDAC1 expression, while CDK6 expression was downregulated in diabetic CPCs. Finally, in vitro and in vivo overexpression of miR-30c-5p markedly reduced the apoptotic cell death and preserved MMP in diabetic CPCs via inhibition of VDAC1. CONCLUSIONS/INTERPRETATION: Our results demonstrate that diabetes mellitus induces a marked dysregulation of miRNAs associated with stem cell survival, proliferation and differentiation, and that therapeutic overexpression of prosurvival miR-30c-5p reduced diabetes-induced cell death and loss of MMP in CPCs via the newly identified target for miR-30c-5p, VDAC1.

Long-chain acylcarnitine 18:1 acutely increases human atrial myocardial contractility and arrhythmia susceptibility.

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium. Additionally, we aimed to assess how LCAC 18:1 alters Ca2+ influx and spontaneous Ca2+ release in vitro. Human right atrial trabeculae (n = 32) stimulated at 1 Hz were treated with LCAC 18:1 at a range of concentrations (1-25 µM) for a 45-min period. Exposure to the LCAC induced a dose-dependent positive inotropic effect on myocardial contractility (maximal 1.5-fold increase vs. control). At the 25 µM dose (n = 8), this was paralleled by an enhanced propensity for spontaneous contractions (50% increase). Furthermore, all LCAC 18:1 effects on myocardial function were reversed following LCAC 18:1 washout. In fluo-4-AM-loaded HEK293 cells, LCAC 18:1 dose dependently increased cytosolic Ca2+ influx relative to vehicle controls and the short-chain acylcarnitine C3. In HEK293 cells expressing ryanodine receptor (RyR2), this increased Ca2+ influx was linked to an increased propensity for RyR2-mediated spontaneous Ca2+ release events. Our study is the first to show that LCAC 18:1 directly and acutely alters human myocardial function and in vitro Ca2+ handling. The metabolite promotes proarrhythmic muscle contractions and increases contractility. The exploratory findings in vitro suggest that LCAC 18:1 increases proarrhythmic RyR2-mediated spontaneous Ca2+ release propensity. The direct effects of metabolites on human myocardial function are essential to understand cardiometabolic dysfunction.NEW & NOTEWORTHY For the first time, the fatty acid metabolite, long-chain acylcarnitine 18:1, is shown to acutely increase the arrhythmia susceptibility and contractility of human atrial myocardium. In vitro, this was linked to an influx of Ca2+ and an enhanced propensity for spontaneous RyR2-mediated Ca2+ release.

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

BACKGROUND: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (M2AChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism. Impairment of these functions are hallmarks of diabetic heart disease (DHD). The role of the NNCS in DHD is unknown. The aim of this study was to examine the effect of diabetes on cardiac NNCS and determine if activation of cardiac NNCS is beneficial to the diabetic heart. METHODS: Ventricular samples from type-2 diabetic humans and db/db mice were used to measure the expression pattern of NNCS components (ChAT, CHT1, VAChT, AChE and M2AChR) and glucose transporter-4 (GLUT-4) by western blot analysis. To determine the function of the cardiac NNCS in the diabetic heart, a db/db mouse model with cardiac-specific overexpression of ChAT gene was generated (db/db-ChAT-tg). Animals were followed up serially and samples collected at different time points for molecular and histological analysis of cardiac NNCS components and prosurvival and proangiogenic signaling pathways. RESULTS: Immunoblot analysis revealed alterations in the components of cardiac NNCS and GLUT-4 in the type-2 diabetic human and db/db mouse hearts. Interestingly, the dysregulation of cardiac NNCS was followed by the downregulation of GLUT-4 in the db/db mouse heart. Db/db-ChAT-tg mice exhibited preserved cardiac and vascular function in comparison to db/db mice. The improved function was associated with increased cardiac ACh and glucose content, sustained angiogenesis and reduced fibrosis. These beneficial effects were associated with upregulation of the PI3K/Akt/HIF1α signaling pathway, and increased expression of its downstream targets-GLUT-4 and VEGF-A. CONCLUSION: We provide the first evidence for dysregulation of the cardiac NNCS in DHD. Increased cardiac ACh is beneficial and a potential new therapeutic strategy to prevent or delay the development of DHD.

Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium.

The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the proarrhythmic effect of EAT. EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-h EAT culture media (n = 8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Coculture with ß-adrenergic agonists isoproterenol (n = 4) and BRL37344 (n = 13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae (n = 10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula-developed force (maximal 2.9-fold increase, P < 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P = 0.002) and relaxation (1.8-fold increase, P = 0.007). Additionally, the postrest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca2+ handling. EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behavior in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect.

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility.

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery (n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, ß-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with ß1/2 (isoproterenol) or ß3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and ß1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute ß3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific ß3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the ß3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on ß3-adrenergic rather than ß1/2-adrenergic stimulation of EAT.

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.

Frailty in Elderly Patients Undergoing Cardiac Surgery Increases Hospital Stay and 12-Month Readmission Rate.

BACKGROUND: Cardiac surgery risk scoring systems predict operative mortality but not outcomes related to preoperative frailty. The aim of this study was to assess frailty in a cohort of older cardiac surgery patients as a predictor of postoperative outcomes. METHODS: Prospective data was collected on patients 65 years of age and older undergoing cardiac surgery between September 2015 and October 2016 at Dunedin Hospital. Frailty was assessed with the Edmonton frail scale and five-metre gait speed. The primary endpoint was length of hospital stay. Secondary outcomes included postoperative complications, major adverse events, death and 12-month readmission rate. RESULTS: Among the 96 patients, median age was 74 (interquartile range 10.5) and 65 (68%) were males. Of the sample 64 (67%) were scored as not frail, 22 (23%) as vulnerable, and 10 (10%) as frail. The median (interquartile range) postoperative days' stay were: not frail 6 (2), vulnerable 9.5 (8), and frail 15 (13). Survival analysis adjusting for EuroSCORE II, age, sex and surgery type showed that greater Edmonton Frail Scale scores were independently predictive of longer post-surgery hospital stay with a hazard ratio for discharge of 0.83 (95% confidence interval 0.76-0.91, p<0.001) per point. The Edmonton Frail Scale score was associated with the 12-month post discharge number of readmissions (adjusted incidence rate ratio 1.24 (95% confidence interval 1.13-1.37, p<0.001) per point. CONCLUSIONS: The Edmonton Frail Scale score predicts length of hospital stay post cardiac surgery and 12-month readmission rate in patients older than 65 years of age.

Sudden Dignity in the Act of Reading.

This essay argues that it is literature, and the serious reading of literature, which offers a sudden emotional experience of human dignity, realized anew through the care of its language. Case histories are provided from the work of The Reader, a charitable organization bringing live shared reading to hard-to-reach communities. The research was conducted by the Centre for Research into Reading, Literature and Society (CRILS), at the University of Liverpool. CRILS analysed the effect of literary texts on the heightened language of the participants themselves in the reading groups, revealing often neglected inner resources stirred by literature to bear the troubles and indignities of existence. These ordinary non-academic readers are able to register that emergent transformation from trouble into achievement not only vicariously through the texts they read at the time but also by seeing, later in interview, filmed excerpts of their own creative responses during the reading sessions.

Early dysregulation of cardiac-specific microRNA-208a is linked to maladaptive cardiac remodelling in diabetic myocardium.

BACKGROUND: The diabetic heart undergoes remodelling contributing to an increased incidence of heart failure in individuals with diabetes at a later stage. The molecular regulators that drive this process in the diabetic heart are still unknown. METHODS: Real-time (RT) PCR analysis was performed to determine the expression of cardiac specific microRNA-208a in right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic patients undergoing coronary artery bypass graft surgery. To determine the time-dependent changes, cardiac tissue were collected from type 2 diabetic mice at different age groups. A western blotting analysis was conducted to determine the expression of contractile proteins α- and ß-myosin heavy chain (MHC) and thyroid hormone receptor-α (TR-α), the negative regulator of ß-MHC. To determine the beneficial effects of therapeutic modulation of miR-208a, high glucose treated adult mouse HL-1 cardiomyocytes were transfected with anti-miR-208a. RESULTS: RT-PCR analysis showed marked upregulation of miR-208a from early stages of diabetes in type 2 diabetic mouse heart, which was associated with a marked increase in the expression of pro-hypertrophic ß-MHC and downregulation of TR-α. Interestingly, upregulation of miR-208a preceded the switch of α-/ß-MHC isoforms and the development of diastolic and systolic dysfunction. We also observed significant upregulation of miR-208a and modulation of miR-208a associated proteins in the type 2 human diabetic heart. Therapeutic inhibition of miR-208a activity in high glucose treated HL-1 cardiomyocytes prevented the activation of ß-MHC and hence the hypertrophic response. CONCLUSION: Our results provide the first evidence that early modulation of miR-208a in the diabetic heart induces alterations in the downstream signaling pathway leading to cardiac remodelling and that therapeutic inhibition of miR-208a may be beneficial in preventing diabetes-induced adverse remodelling of the heart.

Comparison of amateur boxing before and after the 2013 rules change and the impact on boxers' safety.

OBJECTIVES: The effect of the rules change in 2013 on amateur boxing strategy, technique and safety in comparison with pre-2013 is unknown. METHODS: Pre-2013 and post-2013 3×3 min elite level amateur boxing was compared from video footage of 29 Olympic (pre-2013) and 50 World Championship bouts (post-2013) totalling 99 male boxers (mean±SD) age: 24.3±3.2 years, height: 177.3±11.3 cm and body mass: 70.7±16.4 kg. RESULT: Many techniques that were dominant pre-2013 were used less post-2013, including: total punches thrown, rear hand punches, hook rear hand, punches landed, uppercut punches, total punches to the body (all <0.05), while movement around the ring and defensive movements were higher post-2013 (both p<0.004). Post-2013 boxers have increased their foot movement by 20% to move in and then away from their opponent, combined with long-range punches and deliberate defensive movements. The percentage of rounds where standing counts were issued changed from 9% to 3% pre-2013 to post-2013. However, pre-2013, 1.7% of bouts did not last the full duration due to referee stoppage, while post-2013, this increased to 4.2% as a result of two knockouts and eight technical knockouts. DISCUSSION AND CONCLUSION: Boxers should be aware of the large changes in technical demands of boxing. An increased risk of concussive or traumatic brain injury post-2013 is equivocal. However, an increase in skin splits and technical knockouts is apparent. It is likely that boxers believe head guard removal has made them more prone to knockouts.

The Activity Profile of Elite Male Amateur Boxing After the 2013 Rule Changes.

Davis, P, Connorton, AJ, Driver, S, Anderson, S, and Waldock, R. The activity profile of elite male amateur boxing after the 2013 rule changes. J Strength Cond Res 32(12): 3450-3455, 2018-An activity profile of competitive elite amateur boxing after the rule changes in 2013 was created from video footage to allow identification of the technical and tactical demands as well as differences between winners and losers. The study analyzed 50 World Championship bouts involving 60 male boxers (mean ± SD) of age: 23.5 ± 2.8 years, height: 176.2 ± 12.2 cm, and body mass: 71.7 ± 16.2 kg. The results establish that boxing at this level requires the ability to maintain an activity rate of ∼1.55 actions per second, consisting of ∼21 punches, ∼3.6 defensive movements, and ∼56 vertical hip movements all per-minute. Winners had a higher amount of straight punches and straight punches lead hand in round 1 (both p < 0.043) along with total punches landed in round 3 (p = 0.030). They also had a lower ratio of punches thrown to punches landed in round 3 and air punches as a percentage of missed in round 2 and 3 (both p < 0.015). The results suggest that a winning strategy must include the straight punch technique from both lead and rear hands and the ability to increase punching accuracy over subsequent rounds. Tactically, boxing has become long range with straight punches, increased defense and movement around the ring, in contrast to short-range hooks as seen pre-2013. These changes should be considered when creating new training strategies.

Hormonal responses to striking combat sports competition: a systematic review and meta-analysis.

Striking combat sports are challenging, commonly stressing the endocrinological system based on a mixture of body-contact actions and physiological efforts. The aims of this systematic review and meta-analysis were to discuss the hormonal responses related to striking combat sports competitions and to investigate the moderator and mediator variables of the hormonal response-competition/outcome relationship. Three electronic databases (i.e., PubMed, Google Scholar and ScienceDirect) were systematically searched (up to February 2016) followed by a manual search of retrieved papers. The data showed a moderate increase in cortisol (C) (ES = 0.79; 95% CI 0.31-1.28; p = 0.001), an extremely large increase in adrenaline (ES = 4.22; 95% CI 2.62-5.82; p < 0.001), and a very large increase in noradrenaline (ES = 3.40; 95% CI 1.03-5.76; p = 0.005) and human growth hormone (HGH) levels (ES = 3.69; 95% CI 1.96-5.42; p < 0.001) immediately following the combat events, compared to the control condition i.e., "pre-combat". Furthermore, amateur athletes had a larger increase in C levels compared to highly trained athletes (ES = 2.91 [very large] vs ES = 0.56 [small]), while evening events showed greater alterations in C levels compared to morning events (ES = 1.91 [large] vs ES = 0.48 [small]), without significant differences between them (p = 0.26 and p = 0.06, respectively). The present meta-analysis also showed a small, insignificant increase in testosterone (T) (ES = 0.47 [small]; 95% CI -0.45-0.99; p = 0.074) and a decrease in insulin-like growth factor 1 levels (ES = -0.20 [trivial]; 95% CI -0.78-0.37; p = 0.486) immediately following the combat events, compared to the control condition. The type of combat sports practised, participants' gender, and the nature of competition contests (i.e., official vs simulation) did not moderate the relationship between competition and hormonal response. Additionaly, sub-analysis results showed a significant difference between younger and older athletes (Q = 4.05, p = 0.044), suggesting that after combat, younger individuals (less than 17 years of age) had a small decrease in T levels (ES = -0.58), compared with the moderate increase observed in older individuals (ES = 0.76). In conclusion, irrespective of striking combat sports types, the results showed that both official and simulated bouts are a real stressor of the hormonal system of practitioners. Coaches and applied practitioners should adopt "pre-competitive cognitive/coping strategies" to improve the psychological state that mediates the hormonal changes-competition/outcome relationship of their athletes in order to mitigate athletes' stress.

Down-regulation of miR-15a/b accelerates fibrotic remodelling in the Type 2 diabetic human and mouse heart.

Aim: Myocardial fibrosis is a well-established cause of increased myocardial stiffness and subsequent diastolic dysfunction in the diabetic heart. The molecular regulators that drive the process of fibrotic events in the diabetic heart are still unknown. We determined the role of the microRNA (miR)-15 family in fibrotic remodelling of the diabetic heart.Methods and results: Right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic (ND) patients undergoing coronary artery bypass graft surgery showed significant down-regulation of miR-15a and -15b. This was associated with marked up-regulation of pro-fibrotic transforming growth factor-ß receptor-1 (TGFßR1) and connective tissue growth factor (CTGF), direct targets for miR-15a/b and pro-senescence p53 protein. Interestingly, down-regulation of miR-15a/b preceded the development of diastolic dysfunction and fibrosis in Type 2 diabetic mouse heart. Therapeutic restoration of miR-15a and -15b in HL-1 cardiomyocytes reduced the activation of pro-fibrotic TGFßR1 and CTGF, and the pro-senescence p53 protein expression, confirming a causal regulation of these fibrotic and senescence mediators by miR-15a/b. Moreover, conditioned medium (CM) collected from cardiomyocytes treated with miR-15a/b markedly diminished the differentiation of diabetic human cardiac fibroblasts.Conclusion: Our results provide first evidence that early down-regulation of miR-15a/b activates fibrotic signalling in diabetic heart, and hence could be a potential target for the treatment/prevention of diabetes-induced fibrotic remodelling of the heart.

The Effect of Intra-Dialytic Exercise on Inflammation and Blood Endotoxin Levels.

BACKGROUND: In healthy individuals, an acute inflammatory response occurs after intense exercise due to gut ischaemia and intestinal bacterial endotoxin translocation into the bloodstream. This process maybe exacerbated in patients who exercise during dialysis due to large volume shifts experienced by many during haemodialysis (HD). The acute effect of intra-dialytic exercise on blood endotoxins and inflammation is not known. METHOD: The effect of intra-dialytic exercise on blood endotoxin and inflammation was investigated in 10 patients and compared with resting haemodialysis. Blood was measured for endotoxin and inflammatory biomarkers before and after dialysis. RESULT: With the exception of one sample, all samples tested negative for endotoxin. Intra-dialytic exercise attenuated the rise of interleukin-6, tumour necrosis factor-α and high-sensitivity C-reactive protein after the HD procedure. CONCLUSION: Intra-dialytic exercise was not associated with an observable rise in blood endotoxin, although it may ameliorate the inflammatory effects of the HD procedure. Larger studies are needed to confirm this finding.

Antibiotic use among older adults on an acute care general surgery service.

BACKGROUND: Antibiotics play an important role in the treatment of many surgical diseases that affect older adults, and the potential for inappropriate use of these drugs is high. Our objective was to describe antibiotic use among older adults admitted to an acute care surgery service at a tertiary care teaching hospital. METHODS: Detailed data regarding diagnosis, comorbidities, surgery and antibiotic use were retrospectively collected for patients 70 years and older admitted to an acute care surgery service. We evaluated antibiotic use (perioperative prophylaxis and treatment) for appropriateness based on published guidelines. RESULTS: During the study period 453 patients were admitted to the acute care surgery service, and 229 underwent surgery. The most common diagnoses were small bowel obstruction (27.2%) and acute cholecystitis (11.0%). In total 251 nonelective abdominal operations were performed, and perioperative antibiotic prophylaxis was appropriate in 49.5% of cases. The most common prophylaxis errors were incorrect timing (15.5%) and incorrect dose (12.4%). Overall 206 patients received treatment with antibiotics for their underlying disease process, and 44.2% received appropriate first-line drug therapy. The most common therapeutic errors were administration of second- or third-line antibiotics without indication (37.9%) and use of antibiotics when not indicated (12.1%). There was considerable variation in the duration of treatment for patients with the same diagnoses. CONCLUSION: Inappropriate antibiotic use was common among older patients admitted to an acute care surgery service. Quality improvement initiatives are needed to ensure patients receive optimal care in this complex hospital environment.

CONTEXTE: Les antibiotiques jouent un rôle important dans de nombreux cas de chirurgie chez les adultes âgés, et le risque d'utilisation inappropriée de ces médicaments est élevé. Notre objectif était de décrire l'utilisation des antibiotiques chez les patients âgés admis au service chirurgical d'urgence d'un centre hospitalier universitaire de soins tertiaires. MÉTHODES: Nous avons recueilli de manière rétrospective les données détaillées sur le diagnostic, les comorbidités, la chirurgie et l'utilisation d'antibiotiques chez les patients de 70 ans et plus admis dans un service chirurgical d'urgence. Nous avons évalué le bien-fondé du recours aux antibiotiques (prophylaxie et traitement périopératoire) en fonction des lignes directrices publiées. RÉSULTATS: Durant la période de l'étude, 453 patients ont été admis au service chirurgical d'urgence et 229 ont subi une chirurgie. Les diagnostics les plus fréquents étaient : occlusion de l'intestin grêle (27,2 %) et cholécystite aigüe (11,0 %). En tout, 251 interventions abdominales urgentes ont été effectuées et l'antibioprophylaxie périopératoire était justifiée dans 49,5 % des cas. Les erreurs les plus fréquentes en matière de prophylaxie ont été : moment mal choisi (15,5 %) et dose incorrecte (12,4 %). En tout, 206 patients ont reçu une antibiothérapie pour un processus pathologique sous-jacent et 44,2 % ont reçu un traitement antibiotique de première intention approprié. Les erreurs thérapeutiques les plus fréquentes concernaient l'administration d'antibiotiques de deuxième ou de troisième intention sans indication (37,9 %) et l'utilisation d'antibiotiques lorsque cela n'était pas indiqué (12,1 %). On a noté une variation considérable de la durée des traitements chez des patients porteurs de diagnostics semblables. CONCLUSION: L'utilisation inappropriée des antibiotiques a été fréquente chez les patients adultes admis dans un service chirurgical d'urgence. Des initiatives s'imposent sur le plan de l'amélioration de la qualité pour s'assurer ainsi que les patients reçoivent des soins optimaux dans cet environnement hospitalier complexe.