Tag: pubmed

Hand Surg Rehabil. 2021 Aug 28:S2468-1229(21)00249-8. doi: 10.1016/j.hansur.2021.08.010. Online ahead of print.

ABSTRACT

Acute peripheral nerve injuries are common and can cause physical disabilities with sensory and functional sequelae; they therefore require surgery. The aim of this study was to conduct a systematic review to assess the clinical applicability of end-to-side neurorrhaphy in peripheral nerve reconstruction, based on available evidence. We carried out a systematic review of the literature using MEDLINE/PubMed, EMBASE, Cochrane Library, Web of Science, Scielo and Scopus through March 16, 2021. Most of the selected studies were qualitative and employed nonrandomized groups of patients, without standardized scales for assessing outcomes, which made statistical analysis difficult. Efficacy varied from 24% to 81%. Factors for better outcome included the type of injury, type of injured nerve (sensory, motor or mixed), presence of an epineural window, topography, injury extension <1.3 cm, and intervention within 2 weeks of injury. Clinical studies so far lack scientific evidence on end-to-side neurorrhaphy in peripheral nerve lesions.

PMID:34464758 | DOI:10.1016/j.hansur.2021.08.010

Comput Methods Programs Biomed. 2021 Aug 18;210:106354. doi: 10.1016/j.cmpb.2021.106354. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Magnetic drug targeting (MDT) is a promising technology to improve cancer therapy. MDT describes the accumulation of drug loaded superparamagnetic iron oxide nanoparticles (SPIONs) at a desired location, e. g. a tumor, by application of a magnetic field. Here, we evaluate the effectivity of MDT for an endoscopic placement of two different configurations of magnet arrays, i. e. six magnets with same poles facing each other and a Halbach array. Compared to conventional magnet setups outside the body, this endoscopic placement gives the possibility to achieve higher magnetic field gradients inside the tumor.

METHODS: For such a MDT concept, we present FEM based simulations of MDT tracing single SPIONs in a 3D geometry of eight multibranched vessels with sizes in the range of capillaries. In these simulations, the effect of the magnetic field gradient as well as of magnet distance to the vessel geometry, magnetic flux density of the magnets, SPIONs hydrodynamic diameter and magnetic moment on the MDT effectivity is calculated. The blood flow is modelled as an incompressible Newtonian fluid and the SPIONs are suspended in the blood flow. Statistical significance of the targeting effectivity results is tested with the Mann-Whitney-U-Test.

RESULTS: The results show that the magnetic targeting effectivity is up to 32 % higher than the one calculated without the presence of a magnetic field. In the investigated vessel network, this effect on the targeting effectivity is dependent on the number of local magnetic field maxima that are approached with a high gradient and is noticeable up to 200 µm distance of the magnet to the vessel geometry.

CONCLUSIONS: We conclude that for an effective application of MDT, the magnet configuration needs to be placed close to the tumor and should yield a large number of magnetic field maxima that are approached with a high gradient.

PMID:34464768 | DOI:10.1016/j.cmpb.2021.106354

Exp Neurol. 2021 Aug 28:113853. doi: 10.1016/j.expneurol.2021.113853. Online ahead of print.

ABSTRACT

Experience-dependent white matter plasticity offers new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human translational experiment combined myelin water imaging in humans and genetic fate-mapping of oligodendrocyte lineage cells in mice to investigate whether downhill locomotor rehabilitation that emphasizes eccentric muscle actions promotes white matter plasticity and recovery in chronic, incomplete spinal cord injury (SCI). In humans, of 20 individuals with SCI that enrolled, four passed the imaging screen and had myelin water imaging before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI + DH). One individual was excluded for imaging artifacts. Uninjured control participants (n = 7) had two myelin water imaging sessions within the same day. Changes in myelin water fraction (MWF), a histopathologically-validated myelin biomarker, were analyzed in a priori motor learning and non-motor learning brain regions and the cervical spinal cord using statistical approaches appropriate for small sample sizes. PDGFRα-CreER^T2:mT/mG mice, that express green fluorescent protein on oligodendrocyte precursor cells and subsequent newly-differentiated oligodendrocytes upon tamoxifen-induced recombination, were either naive (n = 6) or received a moderate (75 kilodyne), contusive SCI at T9 and were randomized to downhill training (n = 6) or unexercised groups (n = 6). We initiated recombination 29 days post-injury, seven days prior to downhill training. Mice underwent two weeks of daily downhill training on the same 10% decline grade used in humans. Between-group comparison of functional (motor and sensory) and histological (oligodendrogenesis, oligodendroglial/axon interaction, paranodal structure) outcomes occurred post-training. In humans with SCI, downhill training increased MWF in brain motor learning regions (postcentral, precuneus) and mixed motor and sensory tracts of the ventral cervical spinal cord compared to control participants (P < 0.05). In mice with thoracic SCI, downhill training induced oligodendrogenesis in cervical dorsal and lateral white matter, increased axon-oligodendroglial interactions, and normalized paranodal structure in dorsal column sensory tracts (P < 0.05). Downhill training improved sensorimotor recovery in mice by normalizing hip and knee motor control and reducing hyperalgesia, both of which were associated with new oligodendrocytes in the cervical dorsal columns (P < 0.05). Our findings indicate that eccentric-focused, downhill rehabilitation promotes white matter plasticity and improved function in chronic SCI, likely via oligodendrogenesis in nervous system regions activated by the training paradigm. Together, these data reveal an exciting role for eccentric training in white matter plasticity and sensorimotor recovery after SCI.

PMID:34464653 | DOI:10.1016/j.expneurol.2021.113853

Toxicology. 2021 Aug 28:152917. doi: 10.1016/j.tox.2021.152917. Online ahead of print.

ABSTRACT

Despite the common application in pregnancy at clinical practice, it remains ambiguous whether dexamethasone (Dex) exposure can affect embryonic myogenesis. In this study, firstly we showed that 10^-6M Dex (Xin Cheng et al., 2016; Xin Cheng et al., 2017) treatment resulted in abnormal myogenesis in chicken embryos. Secondly, we demonstrated that 10^-6M Dex-induced abnormality of myogenesis resulted from aberrant cell proliferation, as well as from alteration of the differentiation process from the early stage of somitogenesis up to the late stage of myogenesis. The above-mentioned results caused by Dex exposure might be due to the aberrant gene expressions of somite formation (Raldh2, Fgf8, Wnt3a, β-catenin, Slug, Paraxis, N-cadherin) and differentiation (Pax3, MyoD, Wnt3a, Msx1, Shh). Thirdly, RNA sequencing implied the statistically significant differential gene expressions in regulating the myofibril and systemic development, as well as a dramatical alteration of retinoic acid (RA) signaling during somite development in the chicken embryos exposed to Dex. The subsequent validation experiments verified that Dex treatment indeed led to a metabolic change of RA signaling, which was up-regulated and principally mediated by FGF-ERK signaling revealed by means of the combination of chicken embryos and in vitro C2C12 cells. These findings highlight that 10^-6M Dex exposure enhances the risk of abnormal myogenesis through interfering with RA signaling during development.

PMID:34464682 | DOI:10.1016/j.tox.2021.152917

Clin Chim Acta. 2021 Aug 28:S0009-8981(21)00306-5. doi: 10.1016/j.cca.2021.08.028. Online ahead of print.

ABSTRACT

BACKGROUND: Risk-based Statistical QC strategies are recommended by the CLSI guidance for Statistical Quality Control (C24-Ed4). Using Parvin’s patient risk model, QC frequency can be determined in terms of run size, i.e., the number of patient samples between QC events. Run size provides a practical goal for planning SQC strategies to achieve desired test reporting intervals.

METHODS: A QC Frequency calculator is utilized to evaluate critical factors (quality required for test, precision and bias observed for method, rejection characteristics of SQC procedure) and also to consider patient risk as a variable for adjusting run size.

RESULTS: We illustrate the planning of SQC strategies for a HbA1c test where two levels of controls show different sigma performance, for three different HbA1c analyzers used to achieve a common quality goal in a network of laboratories, and for an 18 test chemistry analyzer where a common run size is achieved by changes in control rules and adjustments for the patient risk of different tests.

CONCLUSIONS: Run size provides a practical characteristic for adapting QC frequency to systematize the SQC strategies for multiple levels of controls or multiple tests in a chemistry analyzer. Patient risk can be an important variable for adapting run size to fit the laboratory’s desired reporting intervals for high volume continuous production analyzers.

PMID:34464612 | DOI:10.1016/j.cca.2021.08.028

Clin Pharmacol Drug Dev. 2021 Aug 31. doi: 10.1002/cpdd.1018. Online ahead of print.

ABSTRACT

The α_2C -adrenoreceptor antagonist BAY 1193397 is in development for the oral treatment of diabetic foot ulcers. Safety, tolerability, and pharmacokinetics of BAY 1193397 were investigated in 3 randomized, single-center phase 1 studies in healthy male subjects: a first-in-human study (single oral doses of 0.5-50 mg), a relative bioavailability and food effect study (single doses of 1 and 10 mg), and a multiple-dose escalation study (using 2 and 5 mg twice daily and 10 and 20 mg once daily for 9 consecutive days). BAY 1193397 was rapidly absorbed in the fasted state, peak concentrations were reached between 0.6 and 2 hours. The mean terminal half-life was in the range of 17 to 20 hours. Area under the plasma concentration-time curve and maximum concentration appeared to be dose proportional, with a negligible food effect. There were no high-accumulation effects of BAY 1193397 after repeated dosing. BAY 1193397 was safe and well tolerated. At supratherapeutic plasma concentrations, there were slight transient increases in norepinephrine levels, heart rate, and blood pressure that were more pronounced after a single dose compared to steady state and appeared to be maximum concentration dependent. The results of the presented studies support the conduct of subsequent clinical trials with BAY 1193397 in patients with diabetes and compromised microcirculation.

PMID:34464517 | DOI:10.1002/cpdd.1018

BJOG. 2021 Aug 31. doi: 10.1111/1471-0528.16895. Online ahead of print.

ABSTRACT

Many clinicians are of the opinion that observational studies may provide only “statistical associations”, but not “causal inference”. And further, that only randomized designs ensure causal interpretation. For the same reason, many medical journals have made rules for all observational studies finding significant statistical associations to be presented as just “associations” often emphasizing that a causal inference is not possible.

PMID:34464508 | DOI:10.1111/1471-0528.16895

PM R. 2021 Aug 31. doi: 10.1002/pmrj.12700. Online ahead of print.

ABSTRACT

INTRODUCTION: The 4-wheeled walker is intended to enhance balance and gait for older adults. Yet, some research suggests that walking aids increase falls risk. An understanding of the influence of age with walker use on gait performance is required.

OBJECTIVE: To examine the effect of initial 4-wheeled walker use on spatiotemporal gait parameters between younger and older adults.

DESIGN: Cross-sectional, repeated-measures.

SETTING: Community-dwelling.

PARTICIPANTS: Twenty-five younger (age: 26.5 ± 4.1 years) and 24 older (age: 68.5 ± 10.5 years) adults participated. Younger adults were aged 18-35 years, while older adults were 50 years or older. Included were people not requiring the use of a walking aid, and those able to converse in English.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE(S): Gait velocity and stride time variability were recorded using accelerometers. Gait was examined under three conditions: unassisted walking; walking with a 4-wheeled walker; and walking with a 4-wheeled walker while completing a secondary task. Conditions were performed across two walking paths: straight and figure of eight. Separate mixed-methods ANOVAs (within-subject: condition/path; between-subject: group) were used for statistical analyses.

RESULTS: Velocity was lower when walking using a walker while completing a cognitive task (P < 0.001), in the figure of eight (P < 0.001), and in older adults (P = 0.001). Stride time variability increased with walking path and condition difficulty (P < 0.001) for the straight path vs the figure of eight.

CONCLUSIONS: Using a 4-wheeled walker resulted in a slower and more inconsistent gait pattern across both age groups. Walking more complex configurations resulted in the prioritization of gait over the cognitive task while performing the dual-task conditions. No evidence of an age-related difference in the effect of initial walker use on gait was observed. Nonetheless, walkers are cognitively demanding and their introduction should warrant a clinical follow-up. This article is protected by copyright. All rights reserved.

PMID:34464511 | DOI:10.1002/pmrj.12700

Pharmacoepidemiol Drug Saf. 2021 Aug 31. doi: 10.1002/pds.5351. Online ahead of print.

ABSTRACT

PURPOSE: Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real-world setting.

METHODS: We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time-intervals. Adjusted sequence ratios (aSR) were calculated for each time-interval.

RESULTS: Within 365-days’ time-interval 1,066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa (crude sequence ratio (cSR) 0.90, 95% CI: 0.80-1.02). After adjustments for trends in prescriptions, overall a null association was found (aSR 1.00, 95% CI: 0.89-1.13). Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time-interval. A small transient increased risk was found for sleep disorders, particularly in earlier time-intervals 3 and 6 months (aSRs 1.52, 95% CI: 1.10-2.11 and 1.45, 95% CI: 1.15-1.83, respectively). Subgroup and sensitivity analyses showed similar findings.

CONCLUSIONS: Varenicline initiation was unlikely to be associated with an increased risk of taking anti-depressants nor anti-anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation. This article is protected by copyright. All rights reserved.

PMID:34464494 | DOI:10.1002/pds.5351

Hum Brain Mapp. 2021 Aug 31. doi: 10.1002/hbm.25634. Online ahead of print.

ABSTRACT

People with HIV (PWH) use cannabis at a higher rate than the general population, but the influence on neural activity is not well characterized. Cannabis use among PWH may have a beneficial effect, as neuroinflammation is known to be a critical problem in PWH and cannabis use has been associated with a reduction in proinflammatory markers. Thus, it is important to understand the net impact of cannabis use on brain and cognitive function in PWH. In this study, we collected magnetoencephalographic (MEG) brain imaging data on 81 participants split across four demographically matched groups (i.e., PWH using cannabis, controls using cannabis, non-using PWH, and non-using controls). Participants completed a visuospatial processing task during MEG. Time-frequency resolved voxel time series were extracted to identify the dynamics of oscillatory and pre-stimulus baseline neural activity. Our results indicated strong theta (4-8 Hz), alpha (10-16 Hz), and gamma (62-72 Hz) visual oscillations in parietal-occipital brain regions across all participants. PWH exhibited significant behavioral deficits in visuospatial processing, as well as reduced theta oscillations and elevated pre-stimulus gamma activity in visual cortices, all of which replicate prior work. Strikingly, chronic cannabis use was associated with a significant reduction in pre-stimulus gamma activity in the visual cortices, such that PWH no longer statistically differed from controls. These results provide initial evidence that cannabis use may normalize some neural aberrations in PWH. This study fills an important gap in understanding the impact of cannabis use on brain and cognitive function in PWH.

PMID:34464488 | DOI:10.1002/hbm.25634