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The use of local or regional anesthesia (LRA) is encouraged during transcarotid artery revascularization (TCAR) because the procedure is performed through a small incision. LRA permits neurologic evaluation during the procedure and may reduce periprocedural cardiac morbidity compared with general anesthesia (GA). There is limited and conflicting information regarding the preferred anesthesia to use during TCAR. We compared periprocedural clinical and technical complications, and intraprocedural performance metrics of TCAR performed under GA vs LRA. Patient, lesion, physician, and procedural information was collected in a worldwide quality assurance program of consecutive TCAR procedures. A composite clinical adverse event rate (death, stroke, transient ischemic attack, myocardial infarction) and a composite technical adverse event rate (aborted procedure, conversion to carotid endarterectomy, bleeding, dissection, cranial-nerve injury, device failure) in the periprocedural period were computed. Four intraprocedural performance measures (flow-reversal time, fluoroscopy time, contrast volume, and skin-to-skin time) were recorded. Deidentified data were analyzed independently at the Center for Vascular Research, University of Maryland. Poisson regressions were used to assess the impact of anesthesia type on adverse event rates. Linear regressions were used to compare performance measures. A total of 27,043 TCARs were performed by 1456 physicians between 2012 and 2021. A majority of patients (83%) received GA, and this proportion increased over time (R2 = 0.74; P <.0001). Some physicians (33.4%) used LRA in some of their procedures; only 2.7% used LRA in all of their procedures. Clinical risk factors were more common in the LRA group (P <.0001) and anatomic risk factors in the GA group (P <.0001); these differences were adjusted for in subsequent analyses. LRA was more likely to be used by vascular surgeons and by physicians with higher prior transfemoral carotid stenting experience (P <.0001). When comparing GA vs LRA, clinical adverse events (1.49%; 95% confidence interval [CI], 1.3-1.8 vs 1.55%; 95% CI, 1.2-2.0; P =.78), technical adverse events (5.6%; 95% CI, 5.2-6.2 vs 5.3%; 95% CI, 4.5-6.3; P =.47), and intraprocedural performance measures did not differ by type of anesthesia. Almost two-thirds of physicians performed TCAR exclusively under GA, and the overall proportion of procedures performed under GA increased over time. A larger fraction of patients with severe medical risk factors received LRA vs GA, whereas a larger fraction of patients with anatomic risk-factors received GA. Periprocedural clinical and technical adverse events did not differ by type of anesthesia. Intraprocedural performance metrics that drive procedural cost were similar between groups; potential differences in procedural cost driven by anesthetic choice require further study. [ABSTRACT FROM AUTHOR]

Semiflexible fiber gels such as collagen and fibrin have unique nonlinear mechanical properties that play an important role in tissue morphogenesis, wound healing, and cancer metastasis. Optical tweezers microrheology has greatly contributed to the understanding of the mechanics of fibrous gels at the microscale, including its heterogeneity and anisotropy. However, the explicit relationship between micromechanical properties and gel deformation has been largely overlooked. We introduce a unique gel-stretching apparatus and employ it to study the relationship between microscale strain and stiffening in fibrin and collagen gels, focusing on the development of anisotropy in the gel. We find that gels stretched by as much as 15 % stiffen significantly both in parallel and perpendicular to the stretching axis, and that the parallel axis is 2–3 times stiffer than the transverse axis. We also measure the stiffening and anisotropy along bands of aligned fibers created by aggregates of cancer cells, and find similar effects as in gels stretched with the tensile apparatus. Our results illustrate that the extracellular microenvironment is highly sensitive to deformation, with implications for tissue homeostasis and pathology. The inherent fibrous architecture of the extracellular matrix (ECM) gives rise to unique strain-stiffening mechanics. The micromechanics of fibrous networks has been studied extensively, but the deformations involved in its stiffening at the microscale were not quantified. Here we introduce an apparatus that enables measuring the deformations in the gel as it is being stretched while simultaneously using optical tweezers to measure its microscale anisotropic stiffness. We reveal that fibrin and collagen both stiffen dramatically already at ∼10 % deformation, accompanied by the emergence of significant, yet moderate anisotropy. We measure similar stiffening and anisotropy in the matrix remodeled by the tensile apparatus to those found between cancer cell aggregates. Our results emphasize that small strains are enough to introduce substantial stiffening and anisotropy. These have been shown to result in directional cell migration and enhanced force propagation, and possibly control processes like morphogenesis and cancer metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel device was designed to assist with microvascular arterial anastomoses. This study compares the safety and efficacy of the anastomosis-assisting device with manual suturing in an ovine model. Arteries with a diameter ranging from 2 to 4 mm were transected and anastomosed at four locations. A comparison was done between manual anastomoses and anastomoses performed with a novel anastomotic device in seven sheep. All the device-assisted anastomoses were performed by a single surgeon. At day 45 ± 7, anastomotic sites were dissected to determine patency, and samples were obtained for pathology. Thirteen of 13 (100%) samples from the Vesseal™ group demonstrated patency both on the day the anastomoses were performed and after the 45-day follow-up period. All four additional anastomoses performed using the Vesseal™ were found patent. In the hand-suturing group, six of six (100%) samples demonstrated patency on the day of the anastomoses and five of six (83%) were patent after the follow-up period. No thromboses or adverse events were observed in the anastomoses in either group. No difference in histopathology of the anastomoses was observed between the groups. The anastomosis-assisting device is a safe and efficacious alternative to hand suturing. The patency rates of device-assisted anastomoses were greater than those of manual suturing and pose no additional risk, as demonstrated by clinical observation, histopathology, and macroscopic evaluation. The Vesseal™ anastomosis-assisting device may be a viable alternative to manual suturing, with an ergonomic and intuitive design, short learning curve, and consistent results. [ABSTRACT FROM AUTHOR]

To compare outcomes of phototherapeutic keratectomy (PTK) versus epithelial debridement combined with anterior stromal puncture (ASP) or diamond burr for the treatment of recurrent corneal erosions (RCES) in a large tertiary centre. Patients with a diagnosis of RCES secondary to trauma or epithelial basement membrane dystrophy who underwent a surgical procedure between 2009 and 2019 were included in the study. The following data were collected: demographics, ocular history, prior medical treatment, ocular surgeries, intervention, complete epithelialization at postoperative week 1, recurrences, and complications. Recurrence was defined as either an objective finding of a corneal epithelial defect or symptoms suggestive of recurrent epithelial erosion on history. Recurrence rate and time to epithelialization were compared between groups. A total of 97 eyes (73 patients) were included in the study. Mean patient age was 51 ± 16.1 years, and mean follow-up was 474 days. RCES was secondary to epithelial basement membrane dystrophy in 80% (n = 78 of 97), trauma (15%, n = 15 of 97), or idiopathic (4%, n = 4 of 97). Epithelial debridement with ASP was performed in 34 eyes (35%), diamond burr in 33 eyes (33%), and PTK in 30 eyes (31%). Compared with epithelial debridement with ASP (recurrence 29.4%), the recurrence rate was significantly lower for both the diamond burr (9.1%, p = 0.031) and PTK groups (10%, p = 0.048). The diamond burr and PTK groups also had a significantly higher rate of complete epithelialization at 1 week (p < 0.05). Compared with epithelial debridement with ASP, diamond burr and PTK have significantly lower rates of recurrence and time to epithelialization and may be considered first for surgical management of RCES. [ABSTRACT FROM AUTHOR]

Breast implant rupture is associated with multiple risk factors such as implant age, manufacturer, and a history of trauma to the breast. However, the exact mechanism of breast implant rupture remains unclear. We hypothesize that repetitive minor mechanical forces on the implant collectively play a significant role in the cascade that eventually leads to its rupture. Therefore, we expect a more significant cumulative effect on the breast implant in the dominant upper limb side. Thus, we aim to ascertain whether laterality in silicone breast implant rupture is associated with the dominant upper limb. A retrospective cohort study was performed on patients with silicone breast implants who underwent an elective breast implant removal or exchange. All patients had breast augmentations for cosmetic reasons. We collected data on implant rupture laterality and limb dominance together with known risk factors like patient age, implant age, implant pocket, and implant volume. A total of 154 patients with unilateral implant rupture were included in the study. Among patients with a dominant right limb (n = 133), an ipsilateral rupture was found in 77 patients (58%) (p = 0.036), while in patients with a left dominant limb (n = 21), an ipsilateral rupture was found in 14 patients (67%), (p = 0.036). The dominant limb was a significant risk factor for ipsilateral breast implant rupture. The prevailing theory that cyclic envelope movement carries an increased rupture risk is reinforced in this study. Extensive prospective studies are needed to clarify risk factors for implant rupture further. [ABSTRACT FROM AUTHOR]

• Combining physical therapy, NMES and high protein nutrition with standard care restored positive nitrogen balance in critically ill subjects. • The intervention group experienced less muscle lower extremity muscle loss (volume and cross-sectional area) when compared to standard care. • The intervention group experienced less delirium compared to the group who received standard care. Neuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of combining NMES and HPRO with mobility and strength rehabilitation (NMES+HPRO+PT) to standardized ICU care. To assess the effectiveness of combined NMES+HPRO+PT in mitigating sarcopenia as evidenced by CT volume and cross-sectional area when compared to usual ICU care. Additionally, we assessed the effects of the combined therapy on select clinical outcomes, including nutritional status, nitrogen balance, delirium and days on mechanical ventilation. Participants were randomized by computer generated assignments to receive either NMES+HPRO+PT or standard care. Over 14 days the standardized ICU care group (N = 23) received usual critical care and rehabilitation while the NMES+HPRO+PT group (N = 16) received 30 min neuromuscular electrical stimulation of quadriceps and dorsiflexors twice-daily for 10 days and mean 1.3 ± 0.4 g/kg body weight of high protein supplementation in addition to standard care. Nonresponsive participants received passive exercises and, once responsive, were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-sectional area measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, delirium and days on mechanical ventilation. The NMES+HPRO+PT group (N = 16) lost less lower extremity muscle volume compared to the standard care group (N = 23) and had larger mean combined thigh cross-sectional area. The nitrogen balance remained negative in the standard care group, while positive on days 5, 9, and 14 in the NMES+HPRO+PT group. Standard care group participants experienced more delirium than the NMES+HPRO+PT group. No differences between groups when comparing length of stay or mechanical ventilation days. The combination of neuromuscular electrical stimulation, high protein supplementation and mobility and strength rehabilitation resulted in mitigation of lower extremity muscle loss and less delirium in mechanically ventilated ICU patients. Trial Registration: Clinicaltrials.gov identifier: NCT02509520. Registered July 28, 2015 [ABSTRACT FROM AUTHOR]

Canonical epidermal growth factor (EGF) receptor (EGFR) activation involves the binding of seven EGFR ligands (EGFRLs); however, their extracellular dynamics remain elusive. Here, employing fluorescent probes and a tool for triggering ectodomain shedding, we show that epiregulin (EREG), a low-affinity EGFRL, rapidly and efficiently activates EGFR in Madin-Darby canine kidney (MDCK) epithelial cells and mouse epidermis. During collective cell migration, EGFR and extracellular signal-regulated kinase (ERK) activation waves propagate in an a disintegrin and metalloprotease 17 (ADAM17) sheddase- and EGFRL-dependent manner. Upon induced EGFRL shedding, low-affinity ligands EREG and amphiregulin (AREG) mediate faster and broader ERK waves than high-affinity ligands. Tight/adherens junction integrity is essential for ERK activation propagation, suggesting that tight intercellular spaces prefer the low-affinity EGFRLs for efficient signal transmission. In EREG-deficient mice, ERK wave propagation and cell migration were impaired during skin wound repair. We additionally show that heparin-binding EGF-like growth factor (HBEGF) primarily promotes surrounding cell motility. Our findings underscore the pivotal role of low-affinity EGFRLs in rapid intercellular signal transmission. [Display omitted] • EGFRL probes visualize the dynamics of individual EGFRLs in the extracellular space • Chemogenetic EGFRL shedding induces ERK activation in surrounding cells • Low-affinity EGFRLs diffuse farther compared to high-affinity ones • EREG plays a role in collective cell migration and skin wound repair in vivo Deguchi et al. find that low-affinity EGFR ligands propagate faster and farther than high-affinity ligands in epithelial cells. They demonstrate that EREG, a low-affinity ligand, contributes to skin wound healing. [ABSTRACT FROM AUTHOR]

[Display omitted] • We present work that resolves three long-standing mysteries related to the core structure of screw dislocations in BCC metals, their Peierls barrier, and the interrelation between core structure and Peierls. • We show that the compact core structure of BCC screw dislocations is characterized by local face-centered cubic stacking and the degenerate core structure is characterized by local hexagonal close-packed stacking. • We employ a decision tree model that identifies crucial physical quantities that control the core structure, namely: the HCP stability energy, the peak energy of the {1 1 2} generalized stacking fault energy cure, and the vacancy formation energy. • We further show that a compact core structure does not guarantee a single-hump Peierls barrier and that consideration of the lattice stiffnesses is required on top of the compact core. For screw dislocations in BCC metals, three mysteries have persisted, that is, compact vs degenerate core structure, single-hump vs double-hump Peierls barrier, and the relation between the core structure and Peierls barrier. We discover that the compact core consists of atoms in a FCC stacking sequence and that the degenerate core consists of atoms in a HCP stacking sequence, suggesting that BCC, FCC, and HCP must be considered to correctly capture the core structure. Informed by a machine learning model, we can generate interatomic potentials that reliably predict a compact core structure. We further show the compact core structure does not necessarily lead to the single-hump Peierls barrier. [ABSTRACT FROM AUTHOR]

Our group has previously demonstrated that patients with asymptomatic carotid artery stenosis (ACAS) demonstrate cognitive impairment. One proposed mechanism for cognitive impairment in patients with ACAS is cerebral hypoperfusion due to flow-restriction. We tested whether the combination of a high-grade carotid stenosis and inadequate cross-collateralization in the Circle of Willis (CoW) resulted in worsened cognitive impairment. Twenty-four patients with high-grade (≥70% diameter-reducing) ACAS underwent carotid duplex ultrasound, cognitive assessment, and 3D time-of-flight magnetic resonance angiography. The cognitive battery consisted of nine neuropsychological tests assessing four cognitive domains: learning and recall, attention and working memory, motor and processing speed, and executive function. Raw cognitive scores were converted into standardized T-scores. A structured interpretation of the magnetic resonance angiography images was performed with each segment of the CoW categorized as being either normal or abnormal. Abnormal segments of the CoW were defined as segments characterized as narrowed or occluded due to congenital aplasia or hypoplasia, or acquired atherosclerotic stenosis or occlusion. Linear regression was used to estimate the association between the number of abnormal segments in the CoW, and individual cognitive domain scores. Significance was set to P <.05. The mean age of the patients was 66.1 ± 9.6 years, and 79.2% (n = 19) were male. A significant negative association was found between the number of abnormal segments in the CoW and cognitive scores in the learning and recall (β = −6.5; P =.01), and attention and working memory (β = −7.0; P =.02) domains. There was a trend suggesting a negative association in the motor and processing speed (β = −2.4; P =.35) and executive function (β = −4.5; P =.06) domains that did not reach significance. In patients with high-grade ACAS, the concomitant presence of increasing occlusive disease in the CoW correlates with worse cognitive function. This association was significant in the learning and recall and attention and working memory domains. Although motor and processing speed and executive function also declined numerically with increasing abnormal segments in the CoW, the relationship was not significant. Since flow restriction at a carotid stenosis compounded by inadequate collateral compensation across a diseased CoW worsens cerebral perfusion, our findings support the hypothesis that cerebral hypoperfusion underlies the observed cognitive impairment in patients with ACAS. [Display omitted] [ABSTRACT FROM AUTHOR]

Asymptomatic carotid atherosclerotic stenosis (ACAS) is associated with cognitive impairment. Systemic inflammation occurs in patients with systemic atherosclerosis and is also associated with cognitive impairment. The goal of this study was to determine if cognitive impairment in patients with ACAS is the result of systemic inflammation. A cross-sectional analysis of 104 patients (63 patients with ACAS, 41 controls) with cognitive function and inflammatory biomarker assessments was performed. Venous blood was assayed for proinflammatory biomarkers (IL-1β, IL-6, IL-6R, IL-8, IL-17, tumor necrosis factor-α, matrix metalloproteinase [MMP]-1, MMP-2, MMP-7, MMP-9, vascular cell adhesion molecule, and high-sensitivity C-reactive protein). The patients also underwent comprehensive cognitive testing to compute five domain-specific cognitive scores per patient. We first assessed the associations between carotid stenosis and cognitive function, and between carotid stenosis and systemic inflammation in separate regression models. We then determined whether cognitive impairments persisted in patients with carotid stenosis after accounting for inflammation by adjusting for inflammatory biomarker levels in a combined model. Patients with ACAS and control patients differed in age, race, coronary artery disease prevalence, and education. Stenosis patients had worse cognitive scores in two domains: learning and memory (P =.05) and motor and processing speed (P =.002). Despite adjusting for inflammatory biomarker levels, patients with ACAS still demonstrated deficits in the domains of learning and memory and motor and processing speed. Although systemic atherosclerosis-induced inflammation is a well-recognized cause for cognitive impairment, our data suggest that it is not the primary underlying mechanism behind cognitive impairments seen in ACAS. Cognitive impairments in learning and memory and motor and processing speed seen in patients with ACAS persist after adjusting for systemic inflammation. Thus, alternative mechanisms should be explored to account for the observed functional impairments. [ABSTRACT FROM AUTHOR]

Balance and mobility function worsen with age, more so for those with underlying chronic diseases. We recently found that asymptomatic carotid artery stenosis (ACAS) restricts blood flow to the brain and might also contribute to balance and mobility impairment. In the present study, we tested the hypothesis that ACAS is a modifiable risk factor for balance and mobility impairment. Our goal was to assess the effect of restoring blood flow to the brain by carotid revascularization on the balance and mobility of patients with high-grade ACAS (≥70% diameter-reducing stenosis). Twenty adults (age, 67.0 ± 9.4 years) undergoing carotid endarterectomy for high-grade stenosis were enrolled. Balance and mobility assessments were performed before and 6 weeks after revascularization. These included the Short Physical Performance Battery, the Berg Balance Scale, the Four Square Step Test, the Dynamic Gait Index (DGI), the Timed Up and Go test, gait speed, the Mini-Balance Evaluation Systems Test (Mini-BESTest), and the Walking While Talking complex test. Consistent with our previous findings, patients demonstrated reduced scores on the Short Physical Performance Battery, Berg Balance Scale, DGI, and Timed Up and Go test and in gait speed. Depending on the outcome measure, 25% to 90% of the patients had scored in the impaired range at baseline. After surgery, significant improvements were observed in the outcome measures that combined walking with dynamic movements, including the DGI (P =.02) and Mini-BESTest (P =.002). The proportion of patients with Mini-BESTest scores indicating a high fall risk had decreased significantly from 90% (n = 18) at baseline to 40% (n = 8) after surgery (P =.02). We used Pearson's correlations to examine the relationship between balance and mobility before surgery and the change after surgery. Patients with lower baseline DGI and Mini-BESTest scores demonstrated the most improvement after surgery (r = −0.59, P =.006; and r = −0.70, P =.001, respectively). Carotid revascularization improved patients' balance and mobility, especially for measures that combine walking and dynamic movements. The greatest improvements were observed for the patients who had been most impaired at baseline. [Display omitted] [ABSTRACT FROM AUTHOR]

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example reporting only significant findings, or reporting P values without account for multiple comparisons, or failing to indicate the number of tests performed, the scientific record can be biased. Moreover, if there is a lack of transparency in the conduct of a study and reporting of study results, it will not be possible to repeat a study in a manner that allows inferences from the original study to be reproduced or to design and conduct a different experiment whose aim is to confirm the original study's findings. The goal of this article is to discuss how P values can be used in a manner that is consistent with the scientific method, and to increase transparency and reproducibility in the conduct and analysis of nutrition research. [ABSTRACT FROM AUTHOR]

Multicellular organisms have evolved local and long-distance signaling mechanisms to synchronize development and response to stimuli among a complex network of cells, tissues, and organs. Biological timekeeping is one such activity that is suggested to be coordinated within an organism to anticipate and respond to daily and seasonal patterns in the environment. New research into the plant clock suggests circadian rhythms are communicated between cells and across long distances. However, further clarity is required on the nature of the signaling molecules and the mechanisms underlying signal translocation. Here we summarize the roles and properties of tissue-specific circadian rhythms, discuss the evidence for local and long-distance clock communication, and evaluate the potential signaling molecules and transport mechanisms involved in this system. Plants exhibit tissue-specific circadian gene expression and period length. These clocks in different tissues regulate physiological processes ranging from control of photoperiodic flowering time in the vasculature to temperature-dependent cell elongation in the epidermis. Evidence for local and long-distance communication of circadian information in plants is based on data from micrografting, tissue-specific experiments, single-cell methodologies, and mathematical modeling. These experiments demonstrate local coupling between cell-autonomous clocks and establish a hierarchical network structure for the plant clock, with the shoot apex being a dominant clock. The signaling molecules involved in communicating circadian information have yet to be determined. Possible candidates include ions, sucrose, mRNA, and proteins, which potentially move via symplastic transport. [ABSTRACT FROM AUTHOR]

Latinas are at an increased risk for diabetes and reproductive health (RH) complications with sexuality and pregnancy. This study explored the understanding of diabetes related to RH, pregnancy, unplanned pregnancies, preconceptioncounseling, tight-control, and family planning among Latina adolescents with diabetes and their mothers and explored converging themes. The qualitative descriptive study used written open-ended questions (English or Spanish) with Latina mothers (n = 13) and daughters (n = 21). Responses were transcribed. Content analysis was used by four researchers who coded and discussed themes and reached consensus. Converging themes were confirmed using Atlas.ti software. Seven themes emerged from the mother–daughter dyad: communication (awkwardness, ambivalence, styles); control (being controlled vs. controlling); consequences (fertility, complications); planning (pregnancy, being healthy, life plan, RH); support; danger, risk, and safety; and stigma. Many mother–daughter dyads were not ready to discuss RH among themselves. Cultural and familial perspectives should be considered when providing care and preconception counseling to this population. [ABSTRACT FROM AUTHOR]