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  • 1
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    Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. 9 ( 2022-08-30), p. 657-672
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. 9 ( 2022-08-30), p. 657-672
    Abstract: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5] , and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 〈 75, 75– 〈 90, ≥90 mg/dL, respectively; P trend 〈 0.0001) and after adjustment for low-density lipoprotein cholesterol ( P trend =0.035). Higher baseline apoB stratum was associated with greater relative ( P trend 〈 0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54] , and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, 〉 35– 〈 50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.121.057807
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 2
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    Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease : Results From the CREDENCE Trial and Meta-Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 5 ( 2021-05), p. 1545-1556
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1545-1556
    Abstract: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55–1.08] ). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61–1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19–1.32] ; n=18), and undetermined (HR, 0.54 [95% CI, 0.20–1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53–1.10] ; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR pooled , 0.96 [95% CI, 0.82–1.12]), ischemic stroke (HR pooled , 1.01 [95% CI, 0.89–1.14]), hemorrhagic stroke (HR pooled , 0.50 [95% CI, 0.30–0.83]), undetermined stroke (HR pooled , 0.86 [95% CI, 0.49–1.51]), and AF/AFL (HR pooled , 0.81 [95% CI, 0.71–0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate ( P =0.01), with protection in the lowest estimated glomerular filtration rate ( 〈 45 mL/min/1.73 m 2 ]) subgroup (HR pooled , 0.50 [95% CI, 0.31–0.79]). Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.031623
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 3
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    Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Medicine Vol. 100, No. 39 ( 2021-10-01), p. e27192-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 100, No. 39 ( 2021-10-01), p. e27192-
    Abstract: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging. We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP. We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [ R 2 ] linear = 0.466) and left striatum ( R 2 linear = 0.510). Women presented a higher DAT-BP than men (women: R 2 linear = 0.431; men: R 2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men. Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000027192
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2049818-4
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  • 4
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    Antimicrobial photodynamic chemotherapy mediated by PapaMBlue on chronic periodontal disease : Study protocol for a randomized, blind, controlled trial
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Medicine Vol. 99, No. 6 ( 2020-02), p. e18854-
    Details
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 6 ( 2020-02), p. e18854-
    Abstract: The elimination of the pathogenic microorganisms of the periodontal pocket is one of the main points for success in periodontal treatment. The objective of this study is to investigate the clinical and antimicrobial effect of papain-mediated photodynamic therapy in the clinical treatment of periodontal disease. Methods: Twenty patients with chronic periodontitis will be selected. Patients will be randomly divided into 2 groups (n = 10). Group 1 will receive conventional periodontal treatment and group 2 will receive conventional treatment and antimicrobial photodynamic therapy (PACT). Conventional treatment will consist of oral hygiene guidance, with brushing technique instructions and recommendation of daily flossing. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for scraping and root planning. The PACT will be performed at the end of each periodontal treatment session, at sites with bags ≥4 mm. PapaMblue photosensitizer will be deposited in the periodontal pockets with a syringe and a pre-irradiation time of 1 minute will be adopted. Then, the laser emitting wavelength of 660 nm, with power of 100 mW, for 2 minutes, radiant exposure of 30 J/cm 2 and power density of 250 mW/cm 2 will be applied. Patients will undergo clinical evaluations before treatment (day 1) at 30, 60, and 90 days after the end of treatment; and microbiological evaluations before and immediately after treatment. The distribution of the data within each group and the homogeneity of the variances will be verified. With this information, the most appropriate statistical test in each evaluation will be used. The sample calculation is based on the literature and the significance level of 5% will be adopted. Discussion: The combination of PACT with methylene blue in a papain gel and the conventional treatment may increase the reduction of bacteria in periodontal pockets.
    Type of Medium: Online Resource
    ISSN: 0025-7974 , 1536-5964
    URL: Article
    DOI: 10.1097/MD.0000000000018854
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2049818-4
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  • 5
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    Abstract 722: Unveiling Ccbe1 Role as a Modulator of Cardiomyocyte Differentiation
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Circulation Research Vol. 125, No. Suppl_1 ( 2019-08-02)
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. Suppl_1 ( 2019-08-02)
    Abstract: Chronic heart failure is a major unmet clinical need arising from the loss of viable and functional cardiac muscle, representing a major cause of mortality worldwide. There is a need to identify key molecules and signaling pathways acting on the coronary vasculature system towards regenerative therapies. Human induced pluripotent stem cells (hiPSC) are an attractive cell source to understand the regulatory networks involved in cardiac commitment and cardiomyocyte (CM) differentiation. Particularly, CCBE1 (collagen and calcium-EGF biding domain 1) has been studied as a secreted protein critical for lymphatic/cardiac vascular development and recent reports have proposed that CCBE1 may potentially be used to restore cardiac tissue upon heart injury, through CCBE1-mediated cardiac commitment and/or augmentation of lymphangiogenesis. Therefore, the goal of our work is to understand the molecular pathways underlying CCBE1-based cardiac commitment in loss-of-function studies. By exploring gene editing and “omics” tools we aim to unveil the molecular basis of CCBE1-induced cardiogenesis and provide novel insights towards the development of CCBE1-mediated therapeutic strategies for cardiac regenerative medicine. To selectively knock-down (KD) CCBE1 expression along hiPSC cardiac differentiation, we used modified hiPSC line with CRISPR interference technology (CRISPRi-hiPSC). The CCBE1 KD led to a reduction on the expression of cardiac troponin marker TNNT2 and on the ratios of MYH7:MYH6 and TNNI3:TNNI1. The CCBE1 KD-derived CMs also presented an immature-related ultrastructure, suggesting that CCBE1 may modulate the CM phenotype. On the other hand, the EC differentiation was not impaired by CCBE1 KD. A comprehensive and integrated characterization of the transcriptome and proteome along the differentiation in the presence or absence of CCBE1 is being pursued to identify the key players at cardiac mesoderm and cardiac progenitors stages and their interactions with CCBE1. This work opens new avenues for the identification of CCBE1-modulated proteins/pathways in cardiac commitment, which may contribute for novel cell-based or cell-free approaches towards more efficacious cardiac regenerative therapies.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/res.125.suppl_1.722
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467838-X
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  • 6
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    Mental Health and Emotional Disorders During the COVID-19 Pandemics: Prevalence and Extent in PICU Staff*
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Pediatric Critical Care Medicine Vol. 24, No. 4 ( 2023-04), p. 277-288
    Details
    In: Pediatric Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 24, No. 4 ( 2023-04), p. 277-288
    Abstract: To assess the prevalence of burnout, anxiety and depression symptoms, and posttraumatic stress disorder (PTSD) in PICU workers in Brazil during the first peak of the COVID-19 pandemic. To compare the results of subgroups stratified by age, gender, professional category, health system, and previous mental health disorders. DESIGN: Multicenter, cross-sectional study using an electronic survey. SETTING: Twenty-nine public and private Brazilian PICUs. SUBJECTS: Multidisciplinary PICU workers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Self-reported questionnaires were used to measure burnout (Maslach Burnout Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), and PTSD (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]) in 1,084 respondents. Subjects were mainly young (37.1 ± 8.4 yr old) and females (85%), with a median workload of 50 hours per week. The prevalence of anxiety and depression was 33% and 19%, respectively, whereas PTSD was 13%. The overall median burnout scores were high in the emotional exhaustion and personal accomplishment dimensions (16 [interquartile range (IQR), 8–24] and 40 [IQR, 33–44], respectively) whereas low in the depersonalization one (2 [IQR, 0–5] ), suggesting a profile of overextended professionals, with a burnout prevalence of 24%. Professionals reporting prior mental health disorders had higher prevalence of burnout (30% vs 22%; p = 0.02), anxiety (51% vs 29%; p 〈 0.001), and depression symptoms (32.5% vs 15%; p 〈 0.001), with superior PCL-5 scores for PTSD ( p 〈 0.001). Public hospital workers presented more burnout (29% vs 18.6%, p 〈 0.001) and more PTSD levels (14.8% vs 10%, p = 0.03). Younger professionals were also more burned out ( p 〈 0.05 in all three dimensions). CONCLUSIONS: The prevalence of mental health disorders in Brazilian PICU workers during the first 2020 peak of COVID-19 was as high as those described in adult ICU workers. Some subgroups, particularly those reporting previous mental disorders and younger professionals, should receive special attention to prevent future crises.
    Type of Medium: Online Resource
    ISSN: 1529-7535
    URL: Article
    DOI: 10.1097/PCC.0000000000003119
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2070997-3
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  • 7
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    Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug‐Eluting Stent Implantation: Per‐Protocol Analysis of the GLOBAL LEADERS Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Heart Association Vol. 11, No. 10 ( 2022-05-17)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 10 ( 2022-05-17)
    Abstract: In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.121.024291
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2653953-6
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  • 8
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    Abstract P047: The Protective Effect Of The D2R Against Inflammation Is Dependent On Sex And The Presence Of Hormones In Human Renal Proximal Tubule Cells.
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Hypertension Vol. 79, No. Suppl_1 ( 2022-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. Suppl_1 ( 2022-09)
    Abstract: The renal inflammatory response is regulated by the dopamine receptor D2 (D2R) and its function is impaired in the presence of DRD2 gene variants rs6276/rs6277 (SNPs). Recent reports suggest that sex plays a role in the inflammatory response. We hypothesized that sex and sex hormones affect the D2R-mediated renal inflammatory response. We studied human renal proximal tubule cells (hRPTCs) genotyped for the presence or absence of SNPs. Four cell lines were studied: 2 from female (F) or male (M) subjects not bearing SNPs (wild type [WT]) and 2 from female or male subjects bearing SNPs. We measured mRNA and protein expression of D2R, markers of inflammation (TNF-α, TGF- β1), markers of fibrosis (FN1), injury (Kim-1), and cell proliferation (Ki-67). D2R expression was highest in FWT than in FSNPs, MWT or MSNPs (P 〈 0.02; n=3/group). By contrast TNF-α, TGF- β1, FN1, Kim-1, and Ki-67 expressions were highest in MSNPs than in any of the other group (P 〈 0.05). To assess the effect of the presence of hormones in fetal bovine serum (FBS), we cultured the cell lines in media containing charcoal stripped FBS for 24 h. In the absence of hormones, D2R expression was even higher in FWT (P 〈 0.05), indicating that hormones inhibit the expression of the receptor; there were no significant differences in the other groups, suggesting that the decreased D2R expression due to the presence of SNPs is not hormone-related. The expressions of TNF-α, TGF- β1, and Kim-1 were higher (P 〈 0.05) in MSNPS than in the other groups indicating that either the decreased D2R expression or the presence of hormones per se inhibits the expression of these factors. The expression of Ki-67, however, was decreased in all groups in the absence of hormones (P 〈 0.05), indicating that hormones are necessary for cell proliferation. These results show not only that even in in vitro experiments cells derived from males have a greater response of proinflammatory factors than cells derived from females but also that in hRPTCs the presence of the D2R SNPs imparts an inflammatory phenotype, and that this impairment is dependent on sex and presence of hormones.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.79.suppl_1.P047
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2094210-2
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  • 9
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    Sigmoid Colon Perforation at CT Colonography Secondary to a Possible Obstructive Mechanism: Report of a Case
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Diseases of the Colon & Rectum Vol. 50, No. 9 ( 2007-09), p. 1478-1480
    Details
    In: Diseases of the Colon & Rectum, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 9 ( 2007-09), p. 1478-1480
    Type of Medium: Online Resource
    ISSN: 0012-3706
    URL: Article
    DOI: 10.1007/s10350-007-0309-3
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2046914-7
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  • 10
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    Influence of Position Roles on Upper Limb Force Parameters in Young Male Handball Players : 1456 Board #219 May 30 9:30 AM - 11:00 AM
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Medicine & Science in Sports & Exercise Vol. 39, No. 5 ( 2007-05), p. S216-
    Details
    In: Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. 5 ( 2007-05), p. S216-
    Type of Medium: Online Resource
    ISSN: 0195-9131
    URL: Article
    DOI: 10.1249/01.mss.0000273815.65601.5c
    RVK:
    ZX 1000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 2031167-9
    SSG: 31
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