Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.

The Relationship Between the Isometric Squat and Stretch Shortening Cycle Function and Sprint Acceleration Performance in Hurling Players.

ABSTRACT: Brady, CJ, Harrison, AJ, Flanagan, EP, Haff, GG, and Comyns, TM. The relationship between the isometric squat and stretch shortening cycle function and sprint acceleration performance in hurling players. J Strength Cond Res 38(6): e288-e298, 2024-The primary aim was to examine the relationship between sprint acceleration performance and the performance tests: isometric squat (ISqT), countermovement jump (CMJ), and reactive strength index (RSI). The secondary aim determined whether these tests could distinguish between sprint performance levels. Twenty-six male under-21 subjects completed the ISqT, with peak force (PF), relative PF, force at 100, 150, and 200 milliseconds (ms), and impulse (0-200 ms) measured. Jump height (JH) was calculated from the CMJ and RSI during the 10-5 repeated jump test. Subjects completed 3 × 30-m sprints with splits taken at 5, 10, 20, and 30 m. Pearson's product moment correlations were used to assess the relationships between measures, and independent samples t tests were used to determine whether differences existed in sprint ability of those in the top and bottom quartiles for force at 100 ms, CMJ, and RSI. Significant negative moderate correlations were reported between force at 100 ms and 0-5 m and 5-10 m, significant moderate and large negative correlations between CMJ and all splits and significant large correlations between RSI and splits over 5 m. Force at 100 ms distinguished between performance levels from 0 to 5 m, CMJ from 10 to 20 m, and RSI from 20 to 30 m; faster subjects produced significantly higher force, JHs, and RSI scores. Three principal components explaining 86.1% of the variation in the data set were identified: sprint times and stretch shortening cycle capabilities (33.3%), time-specific force (29.9%), and absolute and relative strength (22.8%).

Dealing with digital paralysis: Surviving a cyberattack in a National Cancer center.

INTRODUCTION: Cyberattacks represent a growing threat for healthcare delivery globally. We assess the impact and implications of a cyberattack on a cancer center in Ireland. METHODS: On May 14th 2021 (day 0) Cork University Hospital (CUH) Cancer Center was involved in the first national healthcare ransomware attack in Ireland. Contingency plans were only present in laboratory services who had previously experienced information technology (IT) failures. No hospital cyberattack emergency plan was in place. Departmental logs of activity for 120 days after the attack were reviewed and compared with historical activity records. Daily sample deficits (routine daily number of samples analyzed - number of samples analyzed during cyberattack) were calculated. Categorical variables are reported as median and range. Qualitative data were collected via reflective essays and interviews with key stakeholders from affected departments in CUH. RESULTS: On day 0, all IT systems were shut down. Radiotherapy (RT) treatment and cancer surgeries stopped, outpatient activity fell by 50%. hematology, biochemistry and radiology capacity fell by 90% (daily sample deficit (DSD) 2700 samples), 75% (DSD 2250 samples), and 90% (100% mammography/PET scan) respectively. Histopathology reporting times doubled (7 to 15 days). Radiotherapy (RT) was interrupted for 113 patients in CUH. The median treatment gap duration was six days for category 1 patients and 10 for the remaining patients. Partner organizations paused all IT links with CUH. Outsourcing of radiology and radiotherapy commenced, alternative communication networks and national conference calls in RT and Clinical Trials were established. By day 28 Email communication was restored. By day 210 reporting and data storage backlogs were cleared and over 2000 computers were checked/replaced. CONCLUSION: Cyberattacks have rapid, profound and protracted impacts. While laboratory and diagnostic deficits were readily quantified, the impact of disrupted/delayed care on patient outcomes is less readily quantifiable. Cyberawareness and cyberattack plans need to be embedded in healthcare. POLICY SUMMARY: Cyberattacks pose significant challenges for healthcare systems, impacting patient care, clinical outcomes, and staff wellbeing. This study provides a comprehensive review of the impact of the Conti ransomware attack on cancer services in Cork University Hospital (CUH), the first cyberattack on a national health service. Our study highlights the widespread disruption caused by a cyberattack including shutdown of information technology (IT) services, marked reduction in outpatient activity, temporary cessation of essential services such as radiation therapy. We provide a framework for other institutions for mitigating the impact of a cyberattack, underscoring the need for a cyberpreparedness plan similar to those made for natural disasters and the profound legacy of a cyberattack on patient care.

The Reliability and Magnitude of Time-Dependent Force-Time Characteristics During the Isometric Midthigh Pull Are Affected by Both Testing Protocol and Analysis Choices.

ABSTRACT: Guppy, SN, Kotani, Y, Brady, CJ, Connolly, S, Comfort, P, and Haff, GG. Title: The reliability and magnitude of time-dependent force-time characteristics during the isometric mid-thigh pull are impacted by both testing protocol and analysis choices. J Strength Cond Res 36(5): 1191-1199, 2022-This study aimed to investigate whether the use of short-duration (SHORT) isometric midthigh pull (IMTP) trials resulted in greater reliability and magnitude of time-dependent force-time characteristics than traditionally performed IMTP trials (TRAD). Fourteen subjects with >6 months' training experience with the power clean volunteered to take part in the study. Subjects performed five ∼1-second IMTP trials (SHORT) and five 5-second IMTP trials (TRAD). SHORT resulted in substantially more reliable rate of force development (RFD) measures (intraclass correlation coefficient [ICC] = 0.97-0.99; coefficient of variation [CV] = 2.6-7.0%), particularly during time bands from force-onset to 150 ms, compared with TRAD when trials were selected for analysis based on peak force (ICC = 0.66-0.83; CV = 14.1-38.5%). Selecting TRAD trials based on RFD0-200 resulted in similar reliability compared with SHORT of those same epochs (ICC = 0.97-0.99; CV = 2.5-7.8%). Furthermore, SHORT resulted in significantly greater force at specific time points, RFD, and impulse compared with TRAD trials (p = 0.001-0.033; g = -0.16 to -0.66). Based on these results, strength and conditioning professionals should use specific testing protocols (i.e., TRAD and SHORT) depending on the component of an athlete's force-generating capacity that they wish to assess and remain aware of the effect analysis choices they have on the reliability of IMTP force-time characteristics.

A comparison of manual and automatic force-onset identification methodologies and their effect on force-time characteristics in the isometric midthigh pull.

The aim of this study was to assess the agreement of three different automated methods of identifying force-onset (40 N, 5 SDs, and 3 SDs) with manual identification, during the isometric mid-thigh pull (IMTP). Fourteen resistance-trained participants with >6 months experience training with the power clean volunteered to take part. After three familiarisation sessions, the participants performed five maximal IMTPs separated by 1 min of rest. Fixed bias was found between 40 N and manual identification for time at force-onset. No proportional bias was present between manual identification and any automated threshold. Fixed bias between manual identification and automated was present for force at onset and F150. Proportional but not fixed bias was found for F50 between manual identification and all automated thresholds. Small to moderate differences (Hedges g = -0.487- -0.692) were found for F90 between all automated thresholds and manual identification, while trivial to small differences (Hedges g = -0.122--0.279) were found between methods for F200 and F250. Based on these results, strength and conditioning practitioners should not use a 40 N, 5 SDs, or 3 SDs threshold interchangeably with manual identification of force-onset when analysing IMTP force-time curve data.

Assessing the accuracy of conventional gadolinium-enhanced breast MRI in measuring the nodal response to neoadjuvant chemotherapy (NAC) in breast cancer.

Management of the axilla in the era of neoadjuvant chemotherapy for breast cancer is evolving. The aim of this study is to determine if conventional gadolinium-enhanced breast MRI can aid in evaluation of the response to neoadjuvant chemotherapy in the axilla. A retrospective review of a prospectively maintained database of patients undergoing neoadjuvant chemotherapy for breast cancer was performed. Pre and post-neoadjuvant chemotherapy MRI reports for node-positive patients were examined in conjunction with demographic data, treatment type, and final histopathology reports. One-hundred and fourteen patients with breast cancer undergoing neoadjuvant chemotherapy were included in the study. The sensitivity of magnetic resonance imaging in detecting nodal response post-neoadjuvant chemotherapy was 33.93% and the specificity was 82.76%. Magnetic resonance imaging had a positive predictive value of 65.52% and a negative predictive value of 56.47%. MRI was found to be most specific in the detection of triple-negative cancer response. Specificity was 100% in this group and sensitivity was 75%. Magnetic resonance imaging has a relatively high specificity in detecting nodal response post-neoadjuvant chemotherapy but has a low sensitivity. Alone it cannot be relied upon to identify active axillary malignancy post-neoadjuvant chemotherapy. However, given its increased specificity among certain subgroups, it may have a role in super-selecting patients suitable for sentinel lymph node biopsy post-neoadjuvant chemotherapy.

The Relationship Between Isometric Strength and Sprint Acceleration in Sprinters.

PURPOSE: To examine the relationships between the isometric midthigh pull (IMTP), isometric squat (ISqT), and sprint acceleration performance in track-and-field sprinters and to determine whether there are differences between men and women. METHODS: Fifteen male and 10 female sprinters performed 3 maximal-effort IMTPs, ISqTs, and 3 × 30-m sprints from blocks. RESULTS: Among the men, the results showed significant negative correlations between IMTP and ISqT peak force; relative peak force; force at 100, 150, and 200 ms; rate of force development (0-150 and 0-200 ms); and impulse (0-200 ms) and 0- to 5-m time (r = -.517 to -.714; P < .05). IMTP impulse (B = -0.582, P = .023) and ISqT relative peak force (B = -0.606, P = .017) significantly predicted 0- to 5-m time. Among the women, no IMTP or ISqT variables significantly correlated with any sprint times. Men measured significantly higher than women for all IMTP measures except relative peak force. Men were significantly faster than women at all splits. When comparing measures of the ISqT, there were no significant differences between men and women. CONCLUSIONS: Variables measured during the IMTP and ISqT significantly correlated with 0- to 5-m sprint performance in male athletes. Isometric strength can have a sizable influence on 0- to 5-m time, but in some cases, the maximum effect could be very small.

A review of the reliability of biomechanical variables produced during the isometric mid-thigh pull and isometric squat and the reporting of normative data.

The use of isometric strength testing, particularly the isometric mid-thigh pull (IMTP) has increased dramatically over the last decade. The IMTP and isometric squat (ISqT) provide one aspect of performance monitoring with variables such as peak force and rate of force development being derived from the force-time curve. The reliability of some of these variables is conflicting in the literature, and the reporting of the reliability is not standardised across the research. The majority of research only reports intraclass correlation coefficients with very few studies reporting coefficient of variation and 90% confidence intervals. Additionally, methods used to calculate variables from the force-time curve differ across studies. An aim of muscle strength testing is to provide normative values for specific sports, allowing coaches to distinguish between performance levels or evaluate the effects of training on performance. This narrative review aims to evaluate studies that have researched the reliability and/or reported normative data for both tests. Additionally, the testing protocols and the force-time curve analysis techniques utilised are discussed, concluding with practical applications for coaches on the uses and limitations of these tests. Results demonstrate that peak force is the most reliable measure and can be used to determine maximum strength capabilities.

Effect of Altering Body Posture and Barbell Position on the Within-Session Reliability and Magnitude of Force-Time Curve Characteristics in the Isometric Midthigh Pull.

Guppy, SN, Brady, CJ, Kotani, Y, Stone, MH, Medic, N, and Haff, GG. Effect of altering body posture and barbell position on the within-session reliability and magnitude of force-time curve characteristics in the isometric midthigh pull. J Strength Cond Res 33(12): 3252-3262, 2019-A large degree of variation in the position used during isometric midthigh pull (IMTP) testing and conflicting results of the effects of these changes can be found in the literature. This study investigated the effect of altering body posture and barbell position on the reliability and magnitude of force-time characteristics generated during the IMTP. Seventeen strength-power athletes (n = 11 males, height: 177.5 ± 7.0 cm, body mass: 90.0 ± 14.1 kg, age: 30.6 ± 10.4 years; n = 6 females, height: 165.8 ± 11.4 cm; body mass: 66.4 ± 13.9 kg, age: 30.8 ± 8.7 years) with greater than 6 months of training experience in the clean (1 repetition maximum: 118.5 ± 20.6 kg, 77.5 ± 10.4 kg) volunteered to undertake the experimental protocol. Subjects performed the IMTP using 4 combinations of hip and knee angles, and 2 different barbell positions. The first barbell position corresponded to the second pull of the clean, while the second rested at the midpoint between the iliac crest and the patella. Peak force (PF), time-specific force (F50, F90, F150, F200, and F250), peak rate of force development (pRFD), and impulse (IMP) time bands were reliable in all 4 testing positions examined. Statistically greater PF, F50, F90, F150, F200, F250, pRFD, and IMP0-50, IMP0-90, IMP0-150, and IMP0-200 were generated in a testing position corresponding to the second pull of the clean when compared with a bent over torso angle, regardless of the barbell position used. Moderate to large effect sizes favoring a testing position corresponding to the second pull were also found. Overall, when performing the IMTP, an upright torso and a barbell position that matches the second pull of the clean should be used.

Effect of Attentional Focus Strategies on the Biomechanical Performance of the Drop Jump.

Comyns, TM, Brady, CJ, and Molloy, J. Effect of attentional focus strategies on the biomechanical performance of the drop jump. J Strength Cond Res 33(3): 626-632, 2019-Motor performance can be influenced by focusing an athlete's attention through the use of verbal instructions. There is limited research on the effect of internal, neutral, and external attentional focus strategies on drop jump (DJ) performance aimed at maximizing height jumped (HJ) and minimizing ground contact time (CT). The purpose of this study was to assess the effect of attentional focus strategies on biomechanical variables related to efficient DJ performance, namely HJ, CT, reactive strength index (RSI), leg-spring stiffness, and peak and relative peak ground reaction force (GRF). Seventeen male recreationally trained subjects performed 2 DJs after listening to instructions designed to evoke an internal, external, or neutral attentional focus. In total, 6 DJs were performed in the testing session, and the order of the instructions was randomly assigned. Significance was set at p ≤ 0.05. Results indicated that, compared with the neutral strategy, the external focus resulted in significantly higher RSI (p = 0.046), peak GRF (p = 0.025), relative GRF (p = 0.02), and leg-spring stiffness (p = 0.02). No significant difference was seen in DJ CT and HJ between all 3 conditions (p ≥ 0.05). These results indicate that the use of an external focus of attention may potentially result in a more effective and efficient fast stretch-shortening cycle performance because of the augmentation of RSI and leg stiffness. More research is warranted, however, because of the lack of significant results pertaining to CT and HJ.

The Effect of Altering Body Posture and Barbell Position on the Between-Session Reliability of Force-Time Curve Characteristics in the Isometric Mid-Thigh Pull.

Seventeen strength and power athletes (n = 11 males, 6 females; height: 177.5 ± 7.0 cm, 165.8 ± 11.4 cm; body mass: 90.0 ± 14.1 kg, 66.4 ± 13.9 kg; age: 30.6 ± 10.4 years, 30.8 ± 8.7 years), who regularly performed weightlifting movements during their resistance training programs, were recruited to examine the effect of altering body posture and barbell position on the between-session reliability of force-time characteristics generated in the isometric mid-thigh pull (IMTP). After participants were familiarised with the testing protocol, they undertook two testing sessions which were separated by seven days. In each session, the participants performed three maximal IMTP trials in each of the four testing positions examined, with the order of testing randomized. In each position, no significant differences were found between sessions for all force-time characteristics (p = >0.05). Peak force (PF), time-specific force (F50, F90, F150, F200, F250) and IMP time-bands (0⁻50, 0⁻90, 0⁻150, 0⁻200, 0⁻250 ms) were reliable across each of the four testing positions (ICC ≥ 0.7, CV ≤ 15%). Time to peak force, peak RFD, RFD time-bands (0⁻50, 0⁻90, 0⁻150, 0⁻200, 0⁻250 ms) and peak IMP were unreliable regardless of the testing position used (ICC = <0.7, CV = >15%). Overall, the use of body postures and barbell positions during the IMTP that do not correspond to the second pull of the clean have no adverse effect on the reliability of the force-time characteristics generated.

A Comparison of the Isometric Midthigh Pull and Isometric Squat: Intraday Reliability, Usefulness, and the Magnitude of Difference Between Tests.

PURPOSE: To examine the reliability and usefulness of the isometric midthigh pull (IMTP) and isometric squat (ISqT) performed at the same knee and hip angles. The scores produced in each test were compared to determine the magnitude of differences between tests. METHODS: Twenty-six male and female athletes (age, 23.6 [4.3] y; height, 1.75 [0.07] m; and body mass, 68.8 [9.7] kg) performed 2 maximal repetitions of the IMTP and ISqT following a specific warm-up. RESULTS: Maximum force, absolute peak force (PF), relative PF, allometrically scaled PF, rate of force development (0-200 and 0-250 ms), and impulse (0-300 ms) were deemed reliable (intraclass correlation coefficient [ICC] ≥.86 and coefficient of variation [CV] ≤9.4%) in the IMTP and ISqT based on predetermined criteria (ICC ≥.8 and CV ≤10%). Impulse (0-200 and 0-250 ms) was reliable in the ISqT (ICC ≥.92 and CV ≤9.9%). Participants produced significantly (P < .05) greater PF and impulse (0-300 ms) during the ISqT compared with the IMTP. When split by sex, female participants produced significantly greater PF (P = .042) during the ISqT, with no significant differences among male participants (P = .245). Both tests are capable of detecting changes in performance in maximum force and absolute PF. CONCLUSIONS: Both tests are reliable for non-time-dependent maximal strength measures when measured at the same knee and hip angles. The ISqT may be preferred when coaches want to test an athlete's true maximum lower-limb strength, especially female athletes.

The scale and nature of Viking settlement in Ireland from Y-chromosome admixture analysis.

The Vikings (or Norse) played a prominent role in Irish history but, despite this, their genetic legacy in Ireland, which may provide insights into the nature and scale of their immigration, is largely unexplored. Irish surnames, some of which are thought to have Norse roots, are paternally inherited in a similar manner to Y-chromosomes. The correspondence of Scandinavian patrilineal ancestry in a cohort of Irish men bearing surnames of putative Norse origin was examined using both slow mutating unique event polymorphisms and relatively rapidly changing short tandem repeat Y-chromosome markers. Irish and Scandinavian admixture proportions were explored for both systems using six different admixture estimators, allowing a parallel investigation of the impact of method and marker type in Y-chromosome admixture analysis. Admixture proportion estimates in the putative Norse surname group were highly consistent and detected little trace of Scandinavian ancestry. In addition, there is scant evidence of Scandinavian Y-chromosome introgression in a general Irish population sample. Although conclusions are largely dependent on the accurate identification of Norse surnames, the findings are consistent with a relatively small number of Norse settlers (and descendents) migrating to Ireland during the Viking period (ca. AD 800-1200) suggesting that Norse colonial settlements might have been largely composed of indigenous Irish. This observation adds to previous genetic studies that point to a flexible Viking settlement approach across North Atlantic Europe.

Inflammation of the respiratory tract is associated with CCL28 and CCR10 expression in a murine model of allergic asthma.

Mouse models and in vitro cell culture were used to examine airway expression of the mucosal chemokine CCL28. Low levels of constitutively expressed mRNA were observed in transformed murine epithelial cells, but high levels could be induced by stimulation. Cytokines that signal through NF-kappaB, including IL-1beta and TNF-alpha or via JAK-STAT pathway including oncostatin M induced CCL28 in airway epithelial cells in vitro. Immunohistochemistry of murine airway tissue revealed that constitutive expression of CCL28 protein in vivo was low and not ubiquitous. However, abundant expression was detected in epithelia and lymphoid aggregates following allergic sensitization and challenge with ovalbumin. This was accompanied by increased detection of cells expressing CCR10 protein and mRNA in inflamed airways. Taken together, these data support a role for CCL28 in contributing to allergen driven airway pathologies, show that proinflammatory cytokines can induce this signal and suggest a role for CCR10 expressing cells in airway inflammation.

Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters.

Infection with human papillomavirus type 16 (HPV-16) confers a high risk for the development of cervical neoplasia. Variants of this virus may interact differentially with host genetic factors, possibly altering the disease course. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible substrates for the viral oncogene product. Also, E6 variants may differ in immunogenicity by generating different peptides for presentation by polymorphic HLA molecules to specific T cells. This study examines HPV-16 E6 sequence variation in cervical carcinomas from the UK and its relationship to polymorphism of HLA and p53 and to clinical parameters. Sequence analysis of the HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequence in 38% of cases. The most common variation detected was a T to G transition at base pair 350, resulting in an amino acid change from a leucine to a valine. Overall, the frequencies of 350T and 350G sequences were similar (49. 4% and 50.6% respectively). Other mutations of lower frequencies were detected together with and independently of 350G. HPV-16 E6 sequence variation at base pair 350 did not correlate with HLA genotype or clinical outcome. There was no difference in the distribution of p53 proline and arginine alleles between HPV-16-positive cervical carcinoma patients and local controls, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma patients.