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Measuring dimensionality of cell-scaffold contacts of primary human bone marrow stromal cells cultured on electrospun fiber scaffolds

J Biomed Mater Res A. 2022 Oct 4. doi: 10.1002/jbm.a.37449. Online ahead of print.

ABSTRACT

The properties and structure of the cellular microenvironment can influence cell behavior. Sites of cell adhesion to the extracellular matrix (ECM) initiate intracellular signaling that directs cell functions such as proliferation, differentiation, and apoptosis. Electrospun fibers mimic the fibrous nature of native ECM proteins and cell culture in fibers affects cell shape and dimensionality, which can drive specific functions, such as the osteogenic differentiation of primary human bone marrow stromal cells (hBMSCs), by. In order to probe how scaffolds affect cell shape and behavior, cell-fiber contacts were imaged to assess their shape and dimensionality through a novel approach. Fluorescent polymeric fiber scaffolds were made so that they could be imaged by confocal fluorescence microscopy. Fluorescent polymer films were made as a planar control. hBSMCs were cultured on the fluorescent substrates and the cells and substrates were imaged. Two different image analysis approaches, one having geometrical assumptions and the other having statistical assumptions, were used to analyze the 3D structure of cell-scaffold contacts. The cells cultured in scaffolds contacted the fibers in multiple planes over the surface of the cell, while the cells cultured on films had contacts confined to the bottom surface of the cell. Shape metric analysis indicated that cell-fiber contacts had greater dimensionality and greater 3D character than the cell-film contacts. These results suggest that cell adhesion site-initiated signaling could emanate from multiple planes over the cell surface during culture in fibers, as opposed to emanating only from the cell’s basal surface during culture on planar surfaces.

PMID:36194510 | DOI:10.1002/jbm.a.37449

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Duloxetine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN): systematic review and meta-analysis

BMJ Support Palliat Care. 2022 Sep 8:spcare-2022-003815. doi: 10.1136/spcare-2022-003815. Online ahead of print.

ABSTRACT

INTRODUCTION: Duloxetine has previously been reported to be promising in the setting of chemotherapy-induced peripheral neuropathy (CIPN). The aim of this study was to conduct a comprehensive systematic review and meta-analysis, on the use of duloxetine in prevention and treatment of CIPN.

METHODS: PubMed, Embase and Cochrane CENTRAL were searched from database inception up until April 2022. Articles were included in this review if they reported on duloxetine use in the setting of CIPN, in a multiarm comparative human trial. A random effects DerSimonian-Laird model was used to calculate summary risk ratios (RR) and corresponding 95% CIs, comparing duloxetine to placebo. This review was registered on.

RESULTS: Seven randomised controlled trials that included 645 patients were identified. Five reported on duloxetine for treatment of CIPN, and two for prevention of CIPN. Two studies had some concern for bias. Duloxetine was statistically similar to placebo in its efficacy, both in the treatment (RR 0.92, 95% CI 0.84 to 1.01) and prevention (RR 1.02, 95% CI 0.87 to 1.19) of CIPN. Safety profile was similar, in the treatment (RR 1.31, 95% CI 0.90 to 1.89) and prevention (RR 1.52, 95% CI 0.98 to 2.38) setting.

CONCLUSION: There is currently limited evidence supporting duloxetine’s use for CIPN. There is a need for more comprehensive and higher-quality trials assessing duloxetine in the setting of CIPN, before further clinical practice recommendations.

TRIAL REGISTRATION NUMBER: PROSPERO (CRD42022327487).

PMID:36194493 | DOI:10.1136/spcare-2022-003815

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Associations of RPEL1 and miR-1307 gene polymorphisms with disease susceptibility, glucocorticoid efficacy, anxiety, depression, and health-related quality of life in Chinese systemic lupus erythematosus patients

Lupus. 2022 Oct 4:9612033221131182. doi: 10.1177/09612033221131182. Online ahead of print.

ABSTRACT

OBJECTIVE: Our present study intended to examine the associations of RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) with susceptibility, glucocorticoids (GCs) efficacy, anxiety, depression, and health-related quality of life (HRQoL) in Chinese systemic lupus erythematosus (SLE) patients.

METHODS: Initially, 1000 participants (500 SLE cases and 500 controls) were recruited for the case-control study. Then, 429 cases who received GCs were followed through 12 weeks to explore GCs efficacy, depression, anxiety, and HRQoL. We selected the iMLDR technique for genotyping: RPEL1: rs4917385 (G/T) and miR-1307: rs7911488 (A/G).

RESULTS: The minor G allele of rs7911488 reduced the risk of SLE (p = .024). Four haplotypes consisting of rs4917385 and rs7911488 were associated with SLE susceptibility (p < .025). Both rs4917385 and rs7911488 were associated with anxiety symptoms and physical function (PF) in SLE patients (p < .025). The rs4917385 was associated with depression and its improvement. No statistical significance was found between RPEL1 and miR-1307 gene polymorphisms with GCs efficacy. Meanwhile, additive interaction analysis showed a significant association between RPEL1 and miR-1307 gene polymorphisms with tea consumption in anxiety.

CONCLUSION: RPEL1 and miR-1307 gene polymorphisms (rs4917385 and rs7911488) might be related to SLE susceptibility in Chinese population. Additionally, the two polymorphisms were possibly associated with depression, anxiety, and HRQoL in Chinese SLE population.

PMID:36194484 | DOI:10.1177/09612033221131182

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Running on empty: a longitudinal global study of psychological well-being among runners during the COVID-19 pandemic

BMJ Open. 2022 Sep 2;12(9):e063455. doi: 10.1136/bmjopen-2022-063455.

ABSTRACT

OBJECTIVES: There are indications that the COVID-19 pandemic has had a profound negative effect on psychological well-being. Here, we investigated this hypothesis using longitudinal data from a large global cohort of runners, providing unprecedented leverage for understanding how the temporal development in the pandemic pressure relates to well-being across countries.

DESIGN: Prospective cohort study.

SETTING: Global.

PARTICIPANTS: We used data from the worldwide Garmin-RUNSAFE cohort that recruited runners with a Garmin Connect account, which is used for storing running activities tracked by a Garmin device. A total of 7808 Garmin Connect users from 86 countries participated.

PRIMARY AND SECONDARY OUTCOME MEASURES: From 1 August 2019 (prepandemic) to 31 December 2020, participants completed surveys every second week that included the five-item WHO Well-Being Index (WHO-5). Pandemic pressure was proxied by the number of COVID-19-related deaths per country, retrieved from the Coronavirus Resource Centre at Johns Hopkins University. Panel data regression including individual- and time-fixed effects was used to study the association between country-level COVID-19-related deaths over the past 14 days and individual-level self-reported well-being over the past 14 days.

RESULTS: The 7808 participants completed a total of 125 409 WHO-5 records over the study period. We found a statistically significant inverse relationship between the number of COVID-19-related deaths and the level of psychological well-being-independent of running activity and running injuries (a reduction of 1.42 WHO-5 points per COVID-19-related death per 10 000 individuals, p<0.001).

CONCLUSIONS: This study suggests that the COVID-19 pandemic has had a negative effect on the psychological well-being of the affected populations, which is concerning from a global mental health perspective.

PMID:36194449 | DOI:10.1136/bmjopen-2022-063455

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Predicting Experimental B22 Values and the Effects of Histidine Charge States for Monoclonal Antibodies Using Coarse-Grained Molecular Simulations

Mol Pharm. 2022 Oct 4. doi: 10.1021/acs.molpharmaceut.2c00337. Online ahead of print.

ABSTRACT

Static light scattering (SLS) was used to characterize five monoclonal antibodies (MAbs) as a function of total ionic strength (TIS) at pH values between 5.5 and 7.0. Second osmotic virial coefficient (B22) values were determined experimentally for each MAb as a function of TIS using low protein concentration SLS data. Coarse-grained molecular simulations were performed to predict the B22 values for each MAb at a given pH and TIS. To include the effect of charge fluctuations of titratable residues in the B22 calculations, a statistical approach was introduced in the Monte Carlo algorithm based on the protonation probability based on a given pH value and the Henderson-Hasselbalch equation. The charged residues were allowed to fluctuate individually, based on the sampled microstates and the influence of electrostatic interactions on net protein-protein interactions during the simulations. Compared to static charge simulations, the new approach provided improved results compared to experimental B22 values at pH conditions near the pKa of titratable residues.

PMID:36194430 | DOI:10.1021/acs.molpharmaceut.2c00337

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Trends in Urethral Suspension With Robotic Prostatectomy Procedures Following Medicare Payment Policy Changes

JAMA Netw Open. 2022 Oct 3;5(10):e2233636. doi: 10.1001/jamanetworkopen.2022.33636.

ABSTRACT

IMPORTANCE: In 2016, the Centers for Medicare and Medicaid Services cut payments for robotic prostatectomy performed for Medicare beneficiaries. Although regulations mandate that billing for urethral suspension is only acceptable for preexisting urinary incontinence, reductions in reimbursement may incentivize billing for the use of this procedure in other scenarios.

OBJECTIVE: To assess trends and geographic variations in payments for urethral suspension with robotic prostatectomy in the context of Medicare payment policy.

DESIGN, SETTING, AND PARTICIPANTS: This US population-based retrospective cohort study analyzed data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Database for men with employer-based insurance (primary commercial or Medicare supplemental coverage) who underwent robotic prostatectomy (Current Procedural Terminology [CPT] code 55866) between 2009 and 2019.

EXPOSURES: Time period and metropolitan statistical area of patient residence.

MAIN OUTCOMES AND MEASURES: Payment for urethral suspension (CPT code 51990) with robotic prostatectomy.

RESULTS: We identified 87 774 men with prostate cancer treated with robotic prostatectomy; 3352 (3.8%) had undergone urethral suspension. The mean (SD) patient age was 59.7 (6.5) years; 16 870 patients (19.2%) had Medicare supplemental coverage. From 2015 to 2016, median payments for robotic prostatectomy changed by -$358 (-17.0%) for Medicare beneficiaries vs -$9 (0%) for commercially insured patients. With urethral suspension vs without, median (IQR) episode payments for robotic prostatectomy were higher for commercially insured men ($3678 [$3090-$4503] vs $3322 [$2601-$4306]) and Medicare beneficiaries ($2927 [$2450-$3909] vs $2379 [$2014-$3512]). Compared with men treated between 2013 and 2015, those treated between 2016 and 2017 were twice as likely to undergo urethral suspension (8.5% vs 4.1%; odds ratio, 2.17 [95% CI, 1.96-2.38]). The proportion of patients who underwent urethral suspension was stable for 2018 to 2019 and 2016 to 2017 (8.5% vs 9.0%; odds ratio, 1.06 [95% CI, 0.96-1.18]). From 2015 to 2019, the proportion of patients who underwent urethral suspension was highest in Charleston, South Carolina (92.0%), Knoxville, Tennessee (66.0%), and Columbia, South Carolina (58.0%). These regions neighbored high-volume areas without patients who underwent prostatectomy with urethral suspension (eg, 146 patients in Greenville, South Carolina, and 173 in Nashville, Tennessee).

CONCLUSIONS AND RELEVANCE: In this study, urethral suspension was associated with increased costs for patients with both commercial insurance and Medicare. Patients treated between 2016 and 2017 were more likely than those treated between 2013 and 2015 to undergo this procedure. Geographic variation in use exceeded what was expected for the preexisting condition for which billing is permitted for Medicare beneficiaries. Policy statements from professional societies highlighting appropriate billing for urethral suspension may have tempered, but not reversed, the broad adoption of this procedure.

PMID:36194414 | DOI:10.1001/jamanetworkopen.2022.33636

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Sleep health, its intraindividuality, and perceived stress in college students during the COVID-19 pandemic

J Am Coll Health. 2022 Oct 4:1-12. doi: 10.1080/07448481.2022.2128684. Online ahead of print.

ABSTRACT

Objective: To describe the changes in sleep health domains and examine the associations between the repeated measures and intraindividual variability (IIV) of these domains and perceived stress. Participants: A diverse racial and ethnic group of first-year college students (N = 23, 78.3% female, aged 17-18) attending in-person classes during the COVID-19 pandemic. Methods: Sleep health domains were determined using 7-day wrist actigraph and daily sleep diaries, and perceived stress scale was completed at 1-month intervals across 3 months. Results: Sleep timing, regularity, and alertness during daytime demonstrated statistically significant changes between three timepoints. Greater stress was associated with more irregularity (B = 2.25 [.87-3.62], p < .001), more dissatisfaction in sleep (B = .04 [.02-.19], p < .01), alertness during daytime (B = .18 [.05-.31], p < .001), and greater IIV (ie, fluctuations) in sleep satisfaction (B = .083 [.02, .15], p < .01). Conclusion: These findings offer insights for future researchers to facilitate intervention development to promote mental and sleep health among college students.

PMID:36194424 | DOI:10.1080/07448481.2022.2128684

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Long term clinical and functional venous outcomes after endovascular transvenous femoro-popliteal bypass

Int Angiol. 2022 Oct 4. doi: 10.23736/S0392-9590.22.04937-9. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral artery disease is widespread in Western societies affecting around 13% of the population above 50 years of age. Despite recent improvements of endovascular treatment, open surgical bypass is still recommended as the treatment of choice for long segment TASC D lesions. The DETOUR procedure was introduced as an endovascular alternative in cases of long-segment superficial femoral artery occlusion. This unconventional technique raises several questions regarding the effect of the bypass graft on femoral venous physiology.

METHODS: We conducted a 3-year follow up study of subjects enrolled and treated in the prospective, multi-center DETOUR study at the Pauls Stradins clinical university hospital, Riga, Latvia. In total, 52 consecutive patients (54 procedures) were enrolled in this study from 2015 until 2019. We performed Venous Clinical Severity Score (VCSS) and Villalta (VS) score assessments, duplex ultrasound measuring femoral and popliteal vein diameters, venous occlusion plethysmography and digital photoplethysmography to assess and compare venous physiology at baseline and at follow-up visits every 6 months.

RESULTS: At baseline mean femoral vein diameter was 11.1mm (SD=1.5). At 36-months following intraluminal stent graft placement, mean femoral vein diameter was 11.1 mm (SD=1.7) with no evidence of enlargement of the femoral vein (p=0.2). Popliteal vein diameter was not significantly changed during 24-months of follow up (p=0.12) but showed a small (0.02mm) statistically significant decrease in diameter at 36-months compared to baseline. During the study period, only one patient (1.9%) developed clinically significant ipsilateral DVT 1-month after surgery. Clinically silent femoral venous thrombosis was documented in 8 legs during 36 month follow up. In one case the thrombus was occlusive and in 7 cases the thrombus was non-occlusive. At baseline, 48 of 52 patients (92%) had no or minor venous symptoms ((VCSS 0-2) with clinically significant venous symptoms in only 4 patients ((VCSS ≥3). At one-month follow-up, the venous clinical severity score increased in all patients compared to baseline. At 6-month follow up, the VCSS had returned to baseline in the majority of patients with no significant changes during the 3-year follow up period. At baseline, all patients had a Villalta score of 0-2 indicating minor or no venous symptoms (mean 0.4 (SD 0.7)). At the 1-month follow-up visit 3 patients (5.8%) had a VS ≥ 3 (two patients had a score of 3 and one patient a score of 4), indicating significant venous symptoms. At the 6-month visit and thereafter, all the VS in all patients had returned to baseline. Transvenous endovascular procedure did not significantly alter venous physiology in treated leg.

CONCLUSIONS: Percutaneous transvenous femoropopliteal bypass provided safe and effective lower-extremity revascularization with minimal effect on long-term venous function. The femoral and popliteal vein remained patent with no compensatory enlargement in response to the presence of the bypass graft within the femoral vein. During 3-year follow up there were no significant changes in venous symptom scores or physiologic function.

PMID:36194385 | DOI:10.23736/S0392-9590.22.04937-9

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Machine learning-based automated planning for hippocampal avoidance prophylactic cranial irradiation

Clin Transl Oncol. 2022 Oct 4. doi: 10.1007/s12094-022-02963-z. Online ahead of print.

ABSTRACT

PURPOSE: Design and evaluate a knowledge-based model using commercially available artificial intelligence tools for automated treatment planning to efficiently generate clinically acceptable hippocampal avoidance prophylactic cranial irradiation (HA-PCI) plans in patients with small-cell lung cancer.

MATERIALS AND METHODS: Data from 44 patients with different grades of head flexion (range 45°) were used as the training datasets. A Rapid Plan knowledge-based planning (KB) routine was applied for a prescription of 25 Gy in 10 fractions using two volumetric modulated arc therapy (VMAT) arcs. The 9 plans used to validate the initial model were added to generate a second version of the RP model (Hippo-MARv2). Automated plans (AP) were compared with manual plans (MP) according to the dose-volume objectives of the PREMER trial. Optimization time and model quality were assessed using 10 patients who were not included in the first 44 datasets.

RESULTS: A 55% reduction in average optimization time was observed for AP compared to MP. (15 vs 33 min; p = 0.001).Statistically significant differences in favor of AP were found for D98% (22.6 vs 20.9 Gy), Homogeneity Index (17.6 vs 23.0) and Hippocampus D mean (11.0 vs 11.7 Gy). The AP met the proposed objectives without significant deviations, while in the case of the MP, significant deviations from the proposed target values were found in 2 cases.

CONCLUSION: The KB model allows automated planning for HA-PCI. Automation of radiotherapy planning improves efficiency, safety, and quality and could facilitate access to new techniques.

PMID:36194382 | DOI:10.1007/s12094-022-02963-z

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The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials

Cardiovasc Drugs Ther. 2022 Oct 4. doi: 10.1007/s10557-022-07384-2. Online ahead of print.

ABSTRACT

PURPOSE: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy.

METHODS: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use.

RESULTS: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant.

CONCLUSION: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.

PMID:36194352 | DOI:10.1007/s10557-022-07384-2