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1.
Am J Transplant ; 24(5): 818-826, 2024 May.
Article in English | MEDLINE | ID: mdl-38101475

ABSTRACT

To evaluate outcomes of patients undergoing heart transplants (HTs) using an intra-aortic balloon pump (IABP) under exception status. Adult patients supported by an IABP who underwent HT between November 18, 2018, and December 31, 2020, as documented in the United Network for Organ Sharing, were included. Patients were stratified according to requests for exception status. Kaplan-Meier methodology was used to look for differences in survival between groups. A total of 1284 patients were included; 492 (38.3%) were transplanted with an IABP under exception status. Exception status patients had higher body mass index, were more likely to be Black, and had longer waitlist times. Exception status patients received organs from younger donors, had a shorter ischemic time, and had a higher frequency of sex mismatch. The 1-year posttransplant survival was 93% for the nonexception and 88% for the exception IABP patients (hazard ratio: 1.85 [95% confidence interval: 1.12-2.86, P = .006]). The most common reason for requesting an exception status was inability to meet blood pressure criteria for extension (37% of patients). The most common reason for an extension request for an exception status was right ventricular dysfunction (24%). IABP patients transplanted under exception status have an increased 1-year mortality rate posttransplant compared with those without exception status.


Subject(s)
Graft Survival , Heart Transplantation , Intra-Aortic Balloon Pumping , Tissue and Organ Procurement , Waiting Lists , Humans , Heart Transplantation/mortality , Intra-Aortic Balloon Pumping/mortality , Male , Female , Middle Aged , Waiting Lists/mortality , Survival Rate , Follow-Up Studies , Risk Factors , Adult , Prognosis , Retrospective Studies , Tissue Donors/supply & distribution , Heart Failure/surgery , Heart Failure/mortality , Heart-Assist Devices , Postoperative Complications/mortality
2.
Int J Sports Med ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38599613

ABSTRACT

This study assessed the multifaceted relations between measures of workload, psychological state, and recovery throughout an entire soccer season. A prospective longitudinal study was utilized to measure workload (GPS training load, RPE), psychological state (mental stress, mental fatigue, and mood), and recovery (sleep duration, sleep quality, and soreness), across ninety observations. Separate linear-mixed effect models were used to assess outcomes of RPE, soreness, and sleep duration. A linear mixed-effects model explained 59% of the variance in RPE following each session. Specifically, each standard deviation increase in GPS load and mental stress in the morning prior to training increased RPE by 1.46(SE=0.08) and 0.29(SE= 0.07) respectively, following that day's training. Furthermore, a significant interaction was found between several predictor variables and chronological day in the season while predicting RPE. Specifically, for each standard deviation increase in GPS load, RPE went up by 0.055 per day across the season suggesting that load had a higher impact on RPE as the season progressed. In contrast, the interaction of day by mental stress, sleep duration, and soreness continued to be stronger as the season progressed. Each linear mixed-effect model predicted a larger amount of variance when accounting for individual variations in the random effects.

3.
J Strength Cond Res ; 38(5): 957-965, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38620058

ABSTRACT

ABSTRACT: Dietze-Hermosa, MS, Montalvo, S, Gonzalez, MP, and Dorgo, S. The impact of an 8-week, resisted, sprint training program on ice skating performance in male youth ice hockey players. J Strength Cond Res 38(5): 957-965, 2024-The purposes of this randomized control study were to (a) compare the effects of an on-ice versus an overground resisted sprint training intervention and a control condition and (b) identify changes in ice skating kinematics and kinetics after training intervention participation. Twenty-four youth ice hockey players were randomly allocated into 3 groups: (a) on-ice resisted sprint training (on-ice RST); (b) overground resisted sprint training (overground RST); and (c) body weight resistance training (control). During the 8-week intervention, the 2 RST groups engaged in sled towing methods, whereas the control group engaged in a body weight resistance training program twice a week. A series of individual, repeated-measures analysis of variances with post hoc pairwise comparisons were conducted for variables of interest. An interaction effect was noted for ice skating s-cornering agility drill completion time ( p = 0.01; ηp2 = 0.36), ice skating 30-m top speed completion time ( p = 0.04; ηp2 = 0.27), step length ( p = 0.04; ηp2 = 0.26), and knee angle at touchdown ( p = 0.03; ηp2 = 0.30). The on-ice RST group displayed superior improvements across ice skating tests compared with the control group. Data show that on-ice RST has the greatest transfer effect to ice skating metrics; however, improvements in certain ice skating metrics can be observed with overground training also.


Subject(s)
Athletic Performance , Hockey , Resistance Training , Adolescent , Child , Humans , Male , Athletic Performance/physiology , Biomechanical Phenomena , Hockey/physiology , Resistance Training/methods , Skating/physiology
4.
J Card Fail ; 29(4): 473-478, 2023 04.
Article in English | MEDLINE | ID: mdl-36195201

ABSTRACT

BACKGROUND: Cardiologists performing coronary angiography (CA) and percutaneous coronary intervention (PCI) are at risk of health problems related to chronic occupational radiation exposure. Unlike during CA and PCI, physician radiation exposure during right heart catheterization (RHC) and endomyocardial biopsy (EMB) has not been adequately studied. The objective of this study was to assess physicians' radiation doses during RHC with and without EMB and compare them to those of CA and PCI. METHODS: Procedural head-level physician radiation doses were collected by real-time dosimeters. Radiation-dose metrics (fluoroscopy time, air kerma [AK] and dose area product [DAP]), and physician-level radiation doses were compared among RHC, RHC with EMB, CA, and PCI. RESULTS: Included in the study were 351 cardiac catheterization procedures. Of these, 36 (10.3%) were RHC, 42 (12%) RHC with EMB, 156 (44.4%) CA, and 117 (33.3%) PCI. RHC with EMB and CA had similar fluoroscopy time. AK and DAP were progressively higher for RHC, RHC with EMB, CA, and PCI. Head-level physician radiation doses were similar for RHC with EMB vs CA (P = 0.07). When physicians' radiation doses were normalized to DAP, RHC and RHC with EMB had the highest doses. CONCLUSION: Physicians' head-level radiation doses during RHC with EMB were similar to those of CA. After normalizing to DAP, RHC and RHC with EMB were associated with significantly higher physician radiation doses than CA or PCI. These observations suggest that additional protective measures should be undertaken to decrease physicians' radiation exposure during RHC and, in particular, RHC with EMB.


Subject(s)
Heart Failure , Percutaneous Coronary Intervention , Physicians , Radiation Exposure , Humans , Percutaneous Coronary Intervention/adverse effects , Radiation Dosage , Radiation Exposure/adverse effects , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Biopsy/adverse effects , Coronary Angiography/adverse effects
5.
J Strength Cond Res ; 37(9): 1802-1808, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-36862131

ABSTRACT

ABSTRACT: Montalvo, S, Martinez, A, Arias, S, Lozano, A, Gonzalez, MP, Dietze-Hermosa, MS, Boyea, BL, and Dorgo, S. Smartwatches and commercial heart rate monitors: a concurrent validity analysis. J Strength Cond Res 37(9): 1802-1808, 2023-The purpose of this study was to explore the concurrent validity of 2 commercial smartwatches (Apple Watch Series 6 and 7) against a clinical criterion device (12-lead electrocardiogram [ECG]) and a field criterion device (Polar H-10) during exercise. Twenty-four male collegiate football players and 20 recreationally active young adults (10 men and 10 women) were recruited and participated in a treadmill-based exercise session. The testing protocol included 3 minutes of standing still (resting), then walking at low intensity, jogging at a moderate intensity, running at a high intensity, and postexercise recovery. The intraclass correlation (ICC 2,k ), and Bland-Altman plot analyses showed a good validity of the Apple Watch Series 6 and Series 7 with increased error (bias) as jogging and running speed increased in the football and recreational athletes. The Apple Watch Series 6 and 7 are highly valid smartwatches at rest and different exercise intensities, with validity decreasing with increased running speed. Strength and conditioning professionals and athletes can confidently use the Apple Watch Series 6 and 7 when tracking heart rate; however, caution must be taken when running at moderate or higher speeds. The Polar H-10 can surrogate a clinical ECG for practical applications.


Subject(s)
Electrocardiography , Exercise Test , Young Adult , Humans , Male , Female , Heart Rate/physiology , Exercise , Walking/physiology
6.
Heart Lung Circ ; 31(8): 1110-1118, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35491337

ABSTRACT

BACKGROUND: The incremental utility of right ventricular (RV) strain on predicting right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation, beyond clinical and haemodynamic indices, is not clear. METHODS: Two hundred and forty-six (246) patients undergoing LVAD implantation, who had transthoracic echocardiograms pre and post LVAD, pulmonary artery pulsatility index (PAPI) measurements and Michigan risk score, were included. We analysed RV global longitudinal strain (GLS) using speckle tracking echocardiography. RVF following LVAD implantation was defined as the need for medical support for >14 days, or unplanned RV assist device insertion after LVAD implantation. RESULTS: Mean preoperative RV-GLS was -7.8±2.8%. Among all, 27% developed postoperative RVF. A classification and regression tree analysis identified preoperative Michigan risk score, PAPI and RV-GLS as important parameters in predicting postoperative RVF. Eighty per cent (80%) of patients with PAPI <2.1 developed postoperative RVF, while only 4% of patients with PAPI >6.8 developed RVF. For patients with a PAPI of 2.1-3.2, having baseline Michigan risk score >2 points conferred an 81% probability of subsequent RVF. For patients with a PAPI of 3.3-6.8, having baseline RV-GLS of -4.9% or better conferred an 86% probability of no subsequent RVF. The sensitivity and specificity of this algorithm for predicting postoperative RVF were 67% and 93%, respectively, with an area under the curve of 0.87. CONCLUSION: RV-GLS has an incremental role in predicting the development of RVF post-LVAD implantation, even after controlling for clinical and haemodynamic parameters.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Heart Failure/diagnosis , Heart Failure/surgery , Heart-Assist Devices/adverse effects , Humans , Michigan , Pulmonary Artery/diagnostic imaging , Retrospective Studies , Risk Factors , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology
7.
Am J Transplant ; 21(3): 1255-1262, 2021 03.
Article in English | MEDLINE | ID: mdl-32978873

ABSTRACT

Historically, patients with restrictive (RCM) and hypertrophic cardiomyopathy (HCM) experienced longer wait-times for heart transplant (HT) and increased waitlist mortality. Recently, a new HT allocation system was implemented in the United States. We sought to determine the impact of the new HT system on RCM/HCM patients. Adult patients with RCM/HCM listed for HT between November 2015 and September 2019 were identified from the UNOS database. Patients were stratified into two groups: old system and new system. We identified 872 patients who met inclusion criteria. Of these, 608 and 264 were classified in the old and new system groups, respectively. The time in the waitlist was shorter (25 vs. 54 days, P < .001), with an increased frequency of HT in the new system (74% vs. 68%, P = .024). Patients who were transplanted in the new system had a longer ischemic time, increased use of temporary mechanical circulatory support and mechanical ventilation. There was no difference in posttransplant survival at 9 months (91.1% vs. 88.9%) (p = .4). We conclude that patients with RCM/HCM have benefited from the new HT allocation system, with increased access to HT without affecting short-term posttransplant survival.


Subject(s)
Cardiomyopathy, Hypertrophic , Heart Transplantation , Transplants , Adult , Cardiomyopathy, Hypertrophic/surgery , Databases, Factual , Heart Transplantation/adverse effects , Humans , Retrospective Studies , United States/epidemiology , Waiting Lists
8.
J Card Fail ; 27(7): 777-785, 2021 07.
Article in English | MEDLINE | ID: mdl-33640481

ABSTRACT

BACKGROUND: The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation. METHODS AND RESULTS: Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001). CONCLUSIONS: Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.


Subject(s)
Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Pulmonary Artery/diagnostic imaging , Retrospective Studies , Risk Assessment , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/etiology
9.
J Hand Surg Am ; 46(11): 1031.e1-1031.e6, 2021 11.
Article in English | MEDLINE | ID: mdl-33375992

ABSTRACT

Tumoral calcinosis is a rare and benign subtype of calcinosis cutis, a group of disorders involving soft tissue calcium deposition. Only 250 cases have been described since 1898; hand involvement is exceedingly rare. We report a case of extensive calcinosis within the flexor sheath of the little finger. Presentation included a painful mass over the volar aspect of the little finger, restricted digit motion, and skin compromise at the site of the mass. Surgical debulking was performed resulting in restoration of finger function.


Subject(s)
Calcinosis , Hand , Calcinosis/diagnostic imaging , Calcinosis/surgery , Fingers/surgery , Hand/surgery , Humans
10.
J Hand Surg Am ; 46(12): 1088-1093, 2021 12.
Article in English | MEDLINE | ID: mdl-34474948

ABSTRACT

PURPOSE: Corticosteroid injections (CSIs) are commonly used in carpal tunnel syndrome; however, recent literature has demonstrated risk of postoperative infection associated with preoperative CSIs in other orthopedic fields. The aim of this study was to assess the relationship of CSIs and postoperative infection following carpal tunnel release (CTR). METHODS: A single-center retrospective review was conducted from 2010 to 2019 to identify patients who underwent CTR with subsequent antibiotic prescription for chart-documented wound infection. A demographically-matched cohort of 100 patients was identified for comparison. Information on patient demographics, comorbidities, injection history, and presence of postoperative infection was collected. RESULTS: Thirty-nine patients (0.67% of all CTR patients) were identified with postoperative infections, 3 of which (0.05% of all CTR patients) were deep infections. In the infection cohort, 16 of 39 (41%) patients received an injection prior to surgery, whereas 16 of 100 (16%) patients in the control cohort received an injection. History of CSI was significantly more common in patients with postoperative infection, and patients in the infection cohort had a significantly shorter average time from injection to surgery by approximately 55 days. CONCLUSIONS: Corticosteroid injections in the preoperative period are associated with postoperative infection after CTR. Proximity of injection to time of surgery plays a role, although comorbidities, the corticosteroid dose, and frequency of injection require further study to determine risk contribution. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic III.


Subject(s)
Carpal Tunnel Syndrome , Adrenal Cortex Hormones/therapeutic use , Carpal Tunnel Syndrome/drug therapy , Carpal Tunnel Syndrome/surgery , Humans , Injections , Postoperative Complications/epidemiology , Retrospective Studies
11.
J Strength Cond Res ; 35(6): 1512-1519, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34027918

ABSTRACT

ABSTRACT: Montalvo, S, Gruber, LD, Gonzalez, MP, Dietze-Hermosa, MS, and Dorgo, S. Effects of augmented eccentric load bench press training on one repetition maximum performance and electromyographic activity in trained powerlifters. J Strength Cond Res 35(6): 1512-1519, 2021-Augmented eccentric load (AEL) training has been shown to elicit greater lower-body muscular strength increases and faster performance improvements compared with traditional strength training. However, it is unknown whether AEL training could provide similar improvements in upper-body muscular strength. Therefore, this study investigated the effects of a 4-week AEL training program on bench press one repetition maximum (1RM) strength, bar kinetics and kinematics, and surface electromyography (EMG) activity. Eight competitive powerlifters completed 5 training sessions consisting of 7 sets of a single repetition with up to 5 minutes rest between sets. Each session was completed at a predetermined AEL percentage consisting of 90% 1RM for concentric and supramaximal loads ranging from 105 to 125% 1RM during the eccentric phase with the use of eccentric hooks. After 4 weeks of AEL training, 1RM performance significantly increased from pretest to posttest (116.62 ± 27.48-124.28 ± 26.96 kg, p = 0.001). In addition, EMG amplitude of the pectoralis major decreased during the 125% AEL session to 59.86 ± 15.36% of pretest 1RM EMG values (p = 0.049, effect sizes [ESs] = 0.69). Furthermore, peak power of 1RM increased by 36.67% from pretest to posttest (p = 0.036, ES = 0.58). These study findings suggest that incorporating AEL bench press training into a 4-week training cycle may be a novel strategy to improve 1RM performance in competitive powerlifters in a short period.


Subject(s)
Resistance Training , Biomechanical Phenomena , Exercise Therapy , Humans , Muscle Strength , Muscle, Skeletal , Pectoralis Muscles
12.
J Strength Cond Res ; 35(5): 1234-1243, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33629975

ABSTRACT

ABSTRACT: Montalvo, S, Gonzalez, MP, Dietze-Hermosa, M, Eggleston, JD, and Dorgo, S. Common vertical jump and reactive strength index measuring devices: A validity and reliability analysis. J Strength Cond Res 35(5): 1234-1243, 2021-Several field-test devices exist to assess vertical jump, but they either lack proper validation or have been validated for the countermovement jump (CMJ) only. This study aimed to quantify the validity and reliability of metrics, including jump height and the calculated reactive strength index (RSI), obtained using the flight-time method from 4 different assessment devices with 3 different vertical jump modalities in comparison to a force platform (criterion assessment). The Optojump, Push-Band 2.0, MyJump2 mobile application, and What'sMyVert mobile application were used synchronously and together with the force platforms. Thirty subjects (17 males and 13 females; age ± SD: 23.37 ± 1.87 years) performed 5 repetitions of CMJ, squat jump (SQJ), and drop jump (DJ) with a standardized 90° knee flexion for all jumps. Relative reliability was determined by intraclass correlation (ICC) and absolute reliability by coefficient of variation (CV) analyses. Excellent reliability was considered as ICC > 0.9 and CV < 10%. Validity was obtained through an ordinary least products regression, ICC, and CV. Significance was set at p < 0.05. Reliability was excellent on jump height for the CMJ (ICC ≥ 0.98; CV ≤ 8.14%) for all instruments. With the exception of the Optojump, all instruments also had excellent reliability for the SQJ (ICC ≥ 0.98; CV ≤ 6.62) and DJ (ICC ≥ 0.94; CV ≤ 8.19). For the RSI metric, all instruments had excellent relative reliability (ICC ≥ 0.92), but none had excellent absolute reliability (CV ≥ 12.5%). The MyJump2 and What'sMyVert apps showed excellent validity on all jump modalities and RSI. The Optojump and Push-Band 2.0 devices both showed system and proportional bias for several jump modalities and RSI. Overall, both mobile applications may provide coaches with a cost-effective and reliable measurement of various vertical jumps.


Subject(s)
Exercise Test , Mobile Applications , Correlation of Data , Female , Humans , Male , Posture , Reproducibility of Results
13.
Acta Orthop Belg ; 87(2): 219-225, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34529373

ABSTRACT

Although distal radius fractures are quite common, bilateral distal radius fractures seldomly occur. Due to this, treatment is primarily based on surgeon experience with unilateral fractures, however bi- lateral fractures add a level of complexity : loss of functional independence. The purpose of this study was to examine a cohort of patients with bilateral distal radius fractures to identify differences in demographics, mechanism of injury, and outcomes to further our understanding of these rare injuries. 23 patients were identified retrospectively over a 5-year period that met inclusion criteria. The medical records were reviewed with multiple demographic and clinical parameters recorded and analyzed. Males were more likely to sustain high-energy mechanisms (80% vs. 53%). Patients <50 years old were more likely to sustain high-energy mechanisms (90% vs. 46%) and were more likely to be treated operatively (80% vs. 62%). The most commonly associated injury was a head injury (30%). All patients treated non-operatively reported minimal/no pain upon final follow-up where 57% of patients treated operatively noted regular pain. 75% of patients with medical comorbidities had minimal/no pain upon final follow- up. Conclusions : Patients with bilateral fractures were more likely to be younger males who suffered from higher energy mechanisms. Age was a critical factor in determining treatment strategy. Rates of associated head injuries were elevated, which is an important factor for the clinician to keep in mind when treating this population. As we further our understanding of this unique population, we can improve our treatment approaches and subsequently attain better outcomes.


Subject(s)
Radius Fractures , Cohort Studies , Demography , Humans , Male , Middle Aged , Radius Fractures/epidemiology , Radius Fractures/surgery , Retrospective Studies
14.
J Nucl Cardiol ; 26(5): 1630-1637, 2019 10.
Article in English | MEDLINE | ID: mdl-29344917

ABSTRACT

BACKGROUND: Technetium-based bone scintigraphy is rapidly becoming the most common non-invasive imaging tool in the diagnosis of Transthyretin cardiac amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m-pyrophosphate (TcPYP) in patients with ATTR. METHODS AND RESULTS: This was a retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a semiquantitative scale (grades 0 to 3) and on single-photon emission computed tomography (SPECT) with CT attenuation correction using total myocardial counts per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps), vertebral body, LV myocardium, and blood pool mean counts were calculated. In the cohort (age 78 ± 9 years, 77% male, and 30% hereditary ATTR), there was no visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT assessment. Total and blood pool-corrected uptake in the muscle groups were significantly less than myocardium and bone (P < 0.001). Blood pool-corrected muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps P = 0.69). As bony uptake decreased, there was no corresponding increase in skeletal muscle uptake. CONCLUSIONS: In patients with ATTR cardiac amyloidosis, skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and quantitative metrics, and is not significantly different in patients with grade 2 vs 3 semiquantitative uptake. The properties of this tracer may be different than TcDPD with respect to non-cardiac uptake.


Subject(s)
Amyloid Neuropathies, Familial/diagnostic imaging , Diphosphates/metabolism , Technetium/metabolism , Aged , Aged, 80 and over , Biopsy , Female , Humans , Male , Middle Aged , Muscle, Skeletal/diagnostic imaging , Retrospective Studies , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Whole Body Imaging
16.
FASEB J ; 27(10): 4279-93, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23884428

ABSTRACT

Combinations of anticancer therapies with high efficacy and low toxicities are highly sought after. Therefore, we studied the effect of polo-like kinase 1 (Plk1) inhibitors on prostate cancer cells as a single agent and in combination with histone deacetylase (HDAC) inhibitors valproic acid and vorinostat. IC50s of Plk1 inhibitors BI 2536 and BI 6727 were determined in prostate cancer cells by MTS assays. Morphological and molecular changes were assessed by immunoblotting, immunofluorescence, flow cytometry, real-time RT-PCR, and pulldown assays. Efficacy of combination therapy was assessed by MTS and clonogenic assays. IC50 values in DU145, LNCaP, and PC3 cells were 50, 75, and 175 nM, respectively, for BI 2536 and 2.5, 5, and 600 nM, respectively, for BI 6727. Human prostate fibroblasts and normal prostate epithelial cells were unaffected at these concentrations. While DU145 and LNCaP cells were solely arrested in mitosis on treatment, PC3 cells accumulated in G2 phase and mitosis, suggesting a weak spindle assembly checkpoint. Combining Plk1 inhibitors with HDAC inhibitors had synergistic antitumor effects in vitro. DMSO-treated prostate cancer cells were used as controls to study the effect of Plk1 and HDAC inhibition. Plk1 inhibitors decreased proliferation and clonogenic potential of prostate cancer cells. Hence, Plk1 may serve as an important molecular target for inhibiting prostate cancer. Combining HDAC inhibitors with BI 2536 or BI 6727 may be an effective treatment strategy against prostate cancer.


Subject(s)
Cell Cycle Proteins/antagonists & inhibitors , Histone Deacetylase Inhibitors/pharmacology , Prostatic Neoplasms/enzymology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , Pteridines/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Therapy, Combination , Humans , Hydroxamic Acids/pharmacology , Male , Valproic Acid/pharmacology , Vorinostat , Polo-Like Kinase 1
17.
Trends Endocrinol Metab ; 35(5): 425-438, 2024 May.
Article in English | MEDLINE | ID: mdl-38423898

ABSTRACT

Inflammation plays an essential role and is a common feature in the pathogenesis of many chronic diseases. The exact mechanisms through which sodium-glucose cotransporter-2 (SGLT2) inhibitors achieve their much-acclaimed clinical benefits largely remain unknown. In this review, we detail the systemic and tissue- or organ-specific anti-inflammatory effects of SGLT2 inhibitors using evidence from animal and human studies. We discuss the potential pathways through which SGLT2 inhibitors exert their anti-inflammatory effects, including oxidative stress, mitochondrial, and inflammasome pathways. Finally, we highlight the need for further investigation of the extent of the contribution of the anti-inflammatory effects of SGLT2 inhibition to improvements in cardiometabolic and renal outcomes in clinical studies.


Subject(s)
Anti-Inflammatory Agents , Inflammation , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Humans , Animals , Inflammation/drug therapy , Inflammation/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Oxidative Stress/drug effects
18.
ASAIO J ; 70(2): 93-98, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37862687

ABSTRACT

Advances in left ventricular assist device technologies have led to an improvement in pump hemocompatibility and outcomes. Because of concerns of thromboembolic complications in prior generations of left ventricular assist devices, bridging with parenteral anticoagulants was routinely. Management strategies of subtherapeutic INRs and their effects on the current generation of devices deserve review. We performed analysis of the MOMENTUM 3 trial including 6 centers in the mid-America region. Patients with subtherapeutic INRs (INR < 2) occurring after the index admission underwent chart review to determine the management strategies taken by clinicians. Strategies were divided into two groups, bridging or nonbridging. Of the 225 patients included in the analysis, 130 (58%) patients had a total of 235 subtherapeutic international normalized ratio (INR) events. Most (n = 179, 76.2%) of these INRs were not bridged (n = 100 warfarin dose adjustment, n = 79 no change in warfarin dose). Among those INRs (n = 56, 23.8%) treated with bridging, approximately half (n = 30, 53.6%) were treated with subcutaneous agents and other half (n = 26, 46.4%) were treated with intravenous agents. There was no difference in individual outcomes or composite endpoints of death, rehospitalization, CVA, or bleeding events between the groups.


Subject(s)
Heart-Assist Devices , Thromboembolism , Humans , Warfarin/therapeutic use , Heart-Assist Devices/adverse effects , Anticoagulants/therapeutic use , Thromboembolism/etiology , Thromboembolism/prevention & control , Hemorrhage/etiology , International Normalized Ratio , Retrospective Studies
19.
Bull Hosp Jt Dis (2013) ; 81(1): 34-39, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36821733

ABSTRACT

The human body has evolved greatly over time and the hand has shown some of the most intricate changes. Most evolutionary experts attribute this to the greater use of tools facilitated by the early hominid's transition to a bipedal gait. Increased tool use drove these changes by providing a convincing reproductive advantage for early humans. In particular, hand adaptations resulted from two types of grips that were fundamental in our development: the precision grip and the power grip. To fully understand how these changes in development occurred, a review of evolutionary theory will be proffered and further discussion of the unique architecture of the hands of our closest living relatives compared with that of humans will follow. Finally, we will examine the two uniquely human grips, the anatomic adaptations that allowed for their development, and the reasoning behind how these grips provided a compelling reproductive advantage.


Subject(s)
Hominidae , Animals , Humans , Biological Evolution , Hand , Hand Strength , Gait
20.
Int J Exerc Sci ; 16(1): 1306-1319, 2023.
Article in English | MEDLINE | ID: mdl-38288257

ABSTRACT

Inter-limb asymmetries are the difference in performance in one limb with respect to the other. Running events in track and field are considered symmetrical while jumping and throwing events are considered asymmetrical. It is unknown if competing in these different events result in differences in inter-limb asymmetries, thus, this study compared the magnitude of jump, sprint, and morphological asymmetries in track and field athletes who compete in symmetrical and asymmetrical events. Forty-six Division I track and field athletes performed a series of vertical jumps (VJ) and broad jumps (BJ) with force platforms measuring peak force of each limb, and 30-meter fly sprints with kinematics (step length (SL), flight time (FT), and contact time (CT)) recorded during the sprints. Additionally, thirty-eight of these subjects underwent body composition analysis via dual x-ray absorptiometry to determine morphological asymmetries. Asymmetries were calculated using the symmetry index and the asymmetry measures were compared between sprinters, distance runners, throwers, and jumpers utilizing a one-way analysis of variance or Kruskal-Wallis tests with post-hoc comparisons as necessary. There were no differences in VJ, BJ, and sprint kinematic asymmetries found between groups but there were differences in leg fat mass asymmetries (H(3)=8.259, p=0.041, eta2= 0.101) as well as arm lean mass (H(3)=9.404, p=0.024, eta2=0.152), fat mass (H(3)=17.822, p<0.001, eta2=0.353), and tissue mass (H(3)=11.632, p=0.009, eta2=0.206) asymmetry measures. While morphological asymmetry differences may be present in athletes competing in different events, there does not appear to be differences in asymmetries during the VJ, BJ, and 30-m fly sprint.

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