Tag: pubmed

Res Q Exerc Sport. 2023 Jun 27:1-10. doi: 10.1080/02701367.2023.2198575. Online ahead of print.

ABSTRACT

Purpose: This study investigated acute workload (wAW), chronic workload (wCW), acute: chronic workload ratio (wACWR), training monotony (wTM), perceived load training strain indicators (wTS), and countermove- ment jump (CMJ) as indicators of wellness in one season and defined weekly variations. In addition, we analyzed the relationships between training load measurements and weekly reports. Methods: 16 elite young wrestlers were monitored daily with individual observations for 46 consecutive weeks throughout the season. Training load was obtained using the session rating of perceived effort. wSleep, wStress, wFatigue & wMuscle Soreness well-being were monitored daily using the Hooper index. Results: As a result of the analysis, it was found that there is a moderate relationship (r = 0.51, p = .003) between ACWR and w mean load (A.U.) and a high relationship (r = 0.81, p < .001) between monotony and strain. Conclusion: All variables other than ACWR, w mean load, strain, and monotony presented small and statistically insignificant relationships. These results provide coaches and practitioners with new insights into perceived loads and health changes during a season at the elite youth level.

PMID:37369136 | DOI:10.1080/02701367.2023.2198575

Res Q Exerc Sport. 2023 Jun 27:1-14. doi: 10.1080/02701367.2023.2197024. Online ahead of print.

ABSTRACT

Background and aims: Muscle strength (MS) has been associated with better cardiometabolic health prognosis. However, the result for the beneficial relationship seems to be dependent on the influence of body size in determining MS levels. We investigate the association between allometric MS indexes and its association with cardiometabolic risk factors in adolescents. Methods: It was a cross-sectional study comprising 351 adolescents (male: 44.4%; age range 14-19 years) from Southern Brazil. MS was assessed by handgrip strength and three different allometric approaches were adopted: 1) MS index based on theoretical allometric exponent; 2) MS index including body mass and height; 3) MS index including fat-free mass and height. Obesity, high blood pressure, dyslipidemia, glucose imbalance and high-sensitivity C-reactive protein were investigated as individual factors or as combinations (either as combinations of components – presence of two adverse conditions, or number of components present in an individual – 0, 1, 2, 3+ cardiometabolic risk factors). Logistic and multinomial logistic regression analyses adjusted for confounding factors were used. The statistical significance adopted was 5%. Results: MS index based on theoretical allometric exponent was associated with lower likelihood (OR: 0.54; 95% CI: 0.28 – 0.89) for the presence of three or more cardiometabolic risk factors in the same individual. Conclusion: This study suggests that MS index based on the theoretical allometric exponent can be superior to allometric MS indexes that included body mass and height, or fat-free mass and height in representing the presence of high number of cardiometabolic risk factors in adolescents.

PMID:37369134 | DOI:10.1080/02701367.2023.2197024

Biosci Rep. 2023 Jun 27:BSR20230612. doi: 10.1042/BSR20230612. Online ahead of print.

ABSTRACT

Studies examining the role of signal transducer and activator of transcription 5 (STAT5) in various cancers have produced controversial results. To address this controversy, we examined the prognostic role of STAT5a in cancer patients across multiple cancers. Transcription levels of STAT5a between tumors and normal tissues, obtained from public databases, were analyzed for statistical differences using Cox regression analysis with the outcome as overall survival and covariate of interest as high STAT5a expression. Meta-analysis was then conducted to summarize the hazard ratio estimate from the Cox regression analyses. We found that STAT5a was significantly under-expressed in breast, lung, and ovarian cancers, while STAT5a was significantly overexpressed in lymphoid neoplasm diffuse large B-cell lymphoma, glioblastoma, and glioma. High STAT5a expression was significantly associated with favorable survival in bladder cancer (lnHR = -0.8689 [-1.4087; -0.3292], p-value = 0.0016), breast cancer (lnHR = -0.7805 [-1.1394; -0.4215], p-value < 0.0001) and lung cancer (lnHR = -0.3255 [-0.6427; -0.0083], p-value = 0.0443). After adjusting for clinicopathological factors, high STAT5a expression remained significantly associated with favorable survival in breast cancer (lnHR = -0.6091 [-1.0810; -0.1372], p-value = 0.0114). These results suggest that higher STAT5a expression is associated with favorable overall survival in breast cancer, and therefore might have protective effects, and that STAT5a expression could be a potential prognostic biomarker, especially in breast cancer. However, the prognostic role of STAT5a is dependent on cancer type.

PMID:37369132 | DOI:10.1042/BSR20230612

Addict Biol. 2023 Jul;28(7):e13288. doi: 10.1111/adb.13288.

ABSTRACT

Preclinical and clinical work suggests that mifepristone may be a viable treatment for alcohol use disorder (AUD). This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD (N = 32). We assessed safety, alcohol craving and consumption, after 1-week mifepristone 600 mg/day administration, in a human laboratory study comprised of a single oral yohimbine administration (32.4 mg), a cue-reactivity procedure and alcohol self-administration. Safety was monitored by adverse events and hemodynamic parameters, alcohol craving by alcohol craving questionnaire and cue-induced saliva output. During the alcohol self-administration, we assessed alcohol pharmacokinetics, subjective effects and consumption. Outcomes were assessed using Generalized Estimating Equations and mediation analysis. Mild-moderate adverse events were reported in both conditions. There was no statistically significant difference between mifepristone and placebo in alcohol pharmacokinetics and subjective effects. Furthermore, blood pressure increased only in the placebo condition after the stress-induced laboratory procedures. Mifepristone, compared to placebo, significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a developed preclinical procedure to a human laboratory study, confirming the safety of mifepristone in people with AUD and providing evidence to its role in reducing alcohol craving under stress procedures. The lack of effects on alcohol drinking may be related to the selection of non-treatment seekers and suggests future treatment-oriented trials should investigate mifepristone in people with AUD.

PMID:37369125 | DOI:10.1111/adb.13288

Optom Vis Sci. 2023 Jun 26. doi: 10.1097/OPX.0000000000002037. Online ahead of print.

ABSTRACT

SIGNIFICANCE: New refractive technologies are consistently emerging in the optometry market, necessitating validation against current clinical standards.

PURPOSE: To compare the refractive measurements between standard digital phoropter refraction and the Chronos binocular refraction system.

METHODS: Standardized subjective refraction was conducted on 70 adult participants using two separate refraction systems. The final subjective values from both devices were compared for M, J0, and J45. The time taken to complete refraction and patient’s comfort were also evaluated.

RESULTS: Good agreement was found between the standard and Chronos refraction, with narrow mean differences (including 95% confidence intervals), and no significant bias for M (0.03, -0.05 to 0.11 D), J0 (-0.02, -0.05 to -0.01 D) and J45 (-0.01, -0.03 to 0.01 D). The bounds of the limits of agreement (LoA) of M (lower bound -0.62, -0.76 to -0.49, and upper bound 0.68, 0.54 to 0.81), J0 (lower bound -0.24, -0.29 to -0.19) and upper bound (0.19, 0.15 to 0.24), and J45 (lower bound -0.18, -0.21 to -0.14) and upper bound (0.16, 0.12 to 0.19). No significant differences were noted between the two techniques for any of the refraction components (M standard: -3.03 ± 2.42 D, novel: -3.06 ± 2.37 D, Z = 0.07, P = .47, J0 standard: 0.12 ± 0.40 D, novel: 0.15 ± 0.41 D, Z = 1.32, P = .09, J45 standard: -0.04 ± 0.19 D, novel: -0.03 ± 0.19 D, Z = 0.50, P = .31). The Chronos was significantly faster than the standard technique, with an average difference of 19 seconds (standard: 190 ± 44 seconds, novel: 171 ± 38 seconds, Z = 4.91, P < .001).

CONCLUSIONS: The final subjective refraction endpoints of the standard technique and the Chronos were well aligned in this group of adult participants, and no statistically or clinically significant differences were noted in M, J0 or J45 components. The Chronos offered improved efficiency, meeting the demands of eye care.

PMID:37369097 | DOI:10.1097/OPX.0000000000002037

Optom Vis Sci. 2023 Jun 26. doi: 10.1097/OPX.0000000000002040. Online ahead of print.

ABSTRACT

SIGNIFICANCE: When worn for myopia control in children, soft multifocal contact lenses with a + 2.50 D add reduced the accommodative response over a three-year period, but wearing them for over four years did not affect accommodative amplitudes, lag, or facility.

PURPOSE: To compare the accommodative response to a 3 D stimulus between single vision, +1.50 D add, and + 2.50 D add multifocal contact lens wearers during three years of contact lens wear, then to compare accommodative amplitude, lag, and facility between the three groups after an average of 4.7 years of wear.

METHODS: Seven- to 11-year-old BLINK Study participants were randomly assigned to wear single vision, +1.50 D add, or + 2.50 D add soft contact lenses (CooperVision, Pleasanton, CA). The accommodative response to a 3 D stimulus was measured at baseline and annually for three years. After 4.7 years, we measured objective accommodative amplitudes, lead/lag, and binocular facility with ±2.00 D flippers. We compared the three accommodative measures using multivariate analysis of variance, adjusting for clinic site, sex, and age group (7-9 or 10-11 years).

RESULTS: The +2.50 D add contact lens wearers exhibited lower accommodative response than the single vision contact lens wearers for three years, but the +1.50 D add contact lens wearers only exhibited lower accommodative response than the single vision contact lens wearers for two years. After adjustment for clinic site, sex, and age group, there were no statistically significant or clinically meaningful differences between the three treatment groups for accommodative amplitude (MANOVA, P = .49), accommodative lag (MANOVA, P = .41), or accommodative facility (MANOVA, P = .87) after an average of 4.7 years of contact lens wear.

CONCLUSIONS: Almost five years of multifocal contact lens wear did not affect the accommodative amplitude, lag, or facility of children.

PMID:37369096 | DOI:10.1097/OPX.0000000000002040

J Clin Oncol. 2023 Jun 27:JCO2202887. doi: 10.1200/JCO.22.02887. Online ahead of print.

ABSTRACT

PURPOSE: Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.

PATIENTS AND METHODS: In Cohort K of the EV-103 phase Ib/II study, cisplatin-ineligible patients with previously untreated la/mUC were randomly assigned 1:1 to receive EV as monotherapy or in combination with Pembro. The primary end point was confirmed objective response rate (cORR) per blinded independent central review. Secondary end points included duration of response (DOR) and safety. There were no formal statistical comparisons between treatment arms.

RESULTS: The cORR was 64.5% (95% CI, 52.7 to 75.1) and 45.2% (95% CI, 33.5 to 57.3) for patients treated with EV + Pembro (N = 76) and EV monotherapy (N = 73), respectively. The median DOR was not reached for the combination and was 13.2 months for monotherapy; 65.4% and 56.3% of patients who responded to the combination and monotherapy, respectively, maintained a response at 12 months. The most common grade 3 or higher treatment-related adverse events (TRAEs) in patients treated with the combination were maculopapular rash (17.1%), fatigue (9.2%), and neutropenia (9.2%). EV TRAEs of special interest (any grade) in the combination arm included skin reactions (67.1%) and peripheral neuropathy (60.5%).

CONCLUSION: EV + Pembro showed a high cORR with durable responses as 1L treatment in cisplatin-ineligible patients with la/mUC. Patients who received EV monotherapy had a response and safety profile consistent with previous studies. Adverse events for EV + Pembro were manageable, with no new safety signals observed.

PMID:37369081 | DOI:10.1200/JCO.22.02887

Menopause. 2023 Jun 27. doi: 10.1097/GME.0000000000002211. Online ahead of print.

ABSTRACT

IMPORTANCE: Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).

OBJECTIVE: The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.

EVIDENCE REVIEW: Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.

FINDINGS: A total of 44 controlled trials met the eligibility criteria (N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.

CONCLUSIONS AND RELEVANCE: Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.

PMID:37369079 | DOI:10.1097/GME.0000000000002211

J Phys Chem B. 2023 Jun 27. doi: 10.1021/acs.jpcb.3c01805. Online ahead of print.

ABSTRACT

The flow behavior of oil in nanochannels has attracted extensive attention for oil transport applications. In most, if not all, of the prior theoretical simulations, oil molecules were observed to flow steadily in nanochannels under pressure gradients. In this study, non-equilibrium molecular dynamics simulations are conducted to simulate the Poiseuille flow of oil with three different hydrocarbon chain lengths in graphene nanochannels. Contrary to the conventional perception of steady flows of oil in nanochannels, we find that oil molecules with the longest hydrocarbon chain (i.e., n-dodecane) exhibit notable stick-slip flow behavior. An alternation between the high average velocity of n-dodecane in the slip motion and the low average velocity in the stick motion is observed, with a drastic, abrupt velocity jolt of up to 40 times occurring at the transition in a stick-slip motion. Further statistical analyses show that the stick-slip flow behavior of n-dodecane molecules originates from the molecular alignment change of oil near the graphene wall. The molecular alignment of n-dodecane shows different statistical distributions under stick and slip motion states, leading to significant changes of friction forces and thus notable velocity fluctuations. This work provides new insights into the Poiseuille flow behavior of oil in graphene nanochannels and may offer useful guidelines for other mass transport applications.

PMID:37369077 | DOI:10.1021/acs.jpcb.3c01805

J Am Chem Soc. 2023 Jun 27. doi: 10.1021/jacs.3c01412. Online ahead of print.

ABSTRACT

Structural dynamics of water and its hydrogen-bonding networks play an important role in enzyme function via the transport of protons, ions, and substrates. To gain insights into these mechanisms in the water oxidation reaction in Photosystem II (PS II), we have performed crystalline molecular dynamics (MD) simulations of the dark-stable S₁ state. Our MD model consists of a full unit cell with 8 PS II monomers in explicit solvent (861 894 atoms), enabling us to compute the simulated crystalline electron density and to compare it directly with the experimental density from serial femtosecond X-ray crystallography under physiological temperature collected at X-ray free electron lasers (XFELs). The MD density reproduced the experimental density and water positions with high fidelity. The detailed dynamics in the simulations provided insights into the mobility of water molecules in the channels beyond what can be interpreted from experimental B-factors and electron densities alone. In particular, the simulations revealed fast, coordinated exchange of waters at sites where the density is strong, and water transport across the bottleneck region of the channels where the density is weak. By computing MD hydrogen and oxygen maps separately, we developed a novel Map-based Acceptor-Donor Identification (MADI) technique that yields information which helps to infer hydrogen-bond directionality and strength. The MADI analysis revealed a series of hydrogen-bond wires emanating from the Mn cluster through the Cl1 and O4 channels; such wires might provide pathways for proton transfer during the reaction cycle of PS II. Our simulations provide an atomistic picture of the dynamics of water and hydrogen-bonding networks in PS II, with implications for the specific role of each channel in the water oxidation reaction.

PMID:37369071 | DOI:10.1021/jacs.3c01412