Detection of fluorescent protein mechanical switching in cellulo.

The ability of cells to sense and respond to mechanical forces is critical in many physiological and pathological processes. However, determining the mechanisms by which forces affect protein function inside cells remains challenging. Motivated by in vitro demonstrations of fluorescent proteins (FPs) undergoing reversible mechanical switching of fluorescence, we investigated whether force-sensitive changes in FP function could be visualized in cells. Guided by a computational model of FP mechanical switching, we develop a formalism for its detection in Förster resonance energy transfer (FRET)-based biosensors and demonstrate its occurrence in cellulo within a synthetic actin crosslinker and the mechanical linker protein vinculin. We find that in cellulo mechanical switching is reversible and altered by manipulation of cell force generation, external stiffness, and force-sensitive bond dynamics of the biosensor. This work describes a framework for assessing FP mechanical stability and provides a means of probing force-sensitive protein function inside cells.

Determining interfacial tension and critical micelle concentrations of surfactants from atomistic molecular simulations.

Hypothesis Atomistically-detailed models of surfactants provide quantitative information on the molecular interactions and spatial distributions at fluid interfaces. Hence, it should be possible to extract from this information, macroscopical thermophysical properties such as interfacial tension, critical micelle concentrations and the relationship between these properties and the bulk fluid surfactant concentrations. Simulations and Experiments Molecular-scale interfacial of systems containing n-dodecyl ß-glucoside (APG12) are simulated using classical molecular dynamics. The bulk phases and the corresponding interfacial regions are all explicitly detailed using an all-atom force field (PCFF+). During the simulation, the behaviour of the interface is analyzed geometrically to obtain an approximated value of the critical micelle concentration (CMC) in terms of the surfactant area number density and the interfacial tension is assessed through the analysis of the forces amongst molecules. New experimental determinations are reported for the surface tension of APG12 at the water/air and at the water/n-decane interfaces. Findings We showcase the application of a thermodynamic framework that inter-relates interfacial tensions, surface densities, CMCs and bulk surfactant concentrations, which allows the in silico quantitative prediction of interfacial tension isotherms.

Nonoperative Management of Isolated Thoracolumbar Flexion Distraction Injuries: A Single-Center Study.

BACKGROUND: Nonoperative management is an appealing option for purely transosseous thoracolumbar flexion-distraction injuries given the prospects of osseous healing and restoration of the posterior tension band complex. This study seeks to examine differences in outcomes following flexion-distraction injuries after operative and nonoperative management. METHODS: This study reviews all patients at a single Level 1 trauma center from 2004 to 2022 with AO Spine B1 thoracolumbar injuries treated operatively vs nonoperatively. Inclusion criteria were age greater than 16 years, computed tomography-confirmed transosseous flexion-distraction injuries, and at least 3 months of follow-up with available imaging. The primary outcome assessed was a change in local Cobb angles, with secondary outcomes consisting of complications, time to return to work, and need for subsequent operative fixation. RESULTS: Initial Cobb angles in the operative (n = 14) vs nonoperative group (n = 13) were -5° and -13°, respectively (P = 0.225), indicating kyphotic alignment in both cohorts. We noted a significant difference in Cobb angles between cohorts at first follow-up (2.6° and -13.9°, P = 0.015) and within the operative cohort from presentation to first follow-up (P = 0.029). At the second follow-up, there was no significant difference in Cobb angles between cohorts (3.6° and -12.6°, P = 0.07). No significant differences were noted in complication rates (P = 1), time to return to work (P = 0.193), or resolution of subjective back pain (P = 0.193). No crossover was noted. CONCLUSIONS: Nonoperative management of minimally displaced transosseous flexion-distraction injuries is a safe alternative to surgery. Patient factors, such as compliance with follow-up, and location of the injury should be factored into the surgeon's management recommendation. CLINICAL RELEVANCE: Overall, no significant differences in outcomes and complications were noted following nonoperative management of AO Spine B1 injuries, indicating the potential for these injuries to be managed conservatively.

Simulating asymmetric membranes using P21 periodic boundary conditions.

Molecular dynamics (MD) simulations of symmetric lipid bilayers are now well established, while those of asymmetric ones are considerably less developed. This disjunction arises in part because the surface tensions of leaflets in asymmetric bilayers can differ (unlike those of symmetric ones), and there is no simple way to determine them without assumptions. This chapter describes the use of P21 periodic boundary conditions (PBC), which allow lipids to switch leaflets, to generate asymmetric bilayers under the assumption of equal chemical potentials of lipids in opposing leaflets. A series of examples, ranging from bilayers with one lipid type to those with peptides and proteins, provides a guide for the use of P21 PBC. Critical properties of asymmetric membranes, such as spontaneous curvature, are highly sensitive to differences in the leaflet surface tensions (or differential stress), and equilibration with P21 PBC substantially reduces differential stress of asymmetric bilayers assembled with surface area-based methods. Limitations of the method are discussed. Technically, the nonstandard unit cell is difficult to parallelize and to incorporate restraints. Inherently, the assumption of equal chemical potentials, and therefore the method itself, is not applicable to all target systems. Despite these limitations, it is argued that P21 simulations should be considered when designing equilibration protocols for MD studies of most asymmetric membranes.

Multiscale remodeling of biomembranes and vesicles.

Biomembranes and vesicles cover a wide range of length scales. Indeed, small nanovesicles have a diameter of a few tens of nanometers whereas giant vesicles can have diameters up to hundreds of micrometers. The remodeling of giant vesicles on the micron scale can be observed by light microscopy and understood by the theory of curvature elasticity, which represents a top-down approach. The theory predicts the formation of multispherical shapes as recently observed experimentally. On the nanometer scale, much insight has been obtained via coarse-grained molecular dynamics simulations of nanovesicles, which provides a bottom-up approach based on the lipid numbers assembled in the two bilayer leaflets and the resulting leaflet tensions. The remodeling processes discussed here include the shape transformations of vesicles, their morphological responses to the adhesion of condensate droplets, the instabilities of lipid bilayers and nanovesicles, as well as the topological transformations of vesicles by membrane fission and fusion. The latter processes determine the complex topology of the endoplasmic reticulum.

Plakophilin 4 controls the spatio-temporal activity of RhoA at adherens junctions to promote cortical actin ring formation and tissue tension.

Plakophilin 4 (PKP4) is a component of cell-cell junctions that regulates intercellular adhesion and Rho-signaling during cytokinesis with an unknown function during epidermal differentiation. Here we show that keratinocytes lacking PKP4 fail to develop a cortical actin ring, preventing adherens junction maturation and generation of tissue tension. Instead, PKP4-depleted cells display increased stress fibers. PKP4-dependent RhoA localization at AJs was required to activate a RhoA-ROCK2-MLCK-MLC2 axis and organize actin into a cortical ring. AJ-associated PKP4 provided a scaffold for the Rho activator ARHGEF2 and the RhoA effectors MLCK and MLC2, facilitating the spatio-temporal activation of RhoA signaling at cell junctions to allow cortical ring formation and actomyosin contraction. In contrast, association of PKP4 with the Rho suppressor ARHGAP23 reduced ARHGAP23 binding to RhoA which prevented RhoA activation in the cytoplasm and stress fiber formation. These data identify PKP4 as an AJ component that transduces mechanical signals into cytoskeletal organization.

Polyhedral Vinyl Polymer Particles Synthesized Via Solvent-Free Radical Polymerization.

Liquid marbles (LMs) with a cubic shape are created by using various vinyl monomers as an inner liquid and polymer plates with mm size as a stabilizer. The relationship between the surface tension of the vinyl monomers and formability of the LMs is investigated. LMs can be fabricated using vinyl monomers with surface tensions of 42.7-40.3 mN m-1. The cubic polymer particles are successively synthesized via free-radical polymerizations by irradiation of the cubic LMs with UV light in a solvent-free manner. In addition, controlling the number of polymer plates per one LM, the shape of the plate or the coalescence of the LMs can lead to production of polymer particles with desired forms (e.g., Platonic and rectangular solids) that correspond to the shapes of the original LMs.

A truncation mutant of adenomatous polyposis coli impairs apical cell extrusion through elevated epithelial tissue tension.

Tissue tension encompasses the mechanical forces exerted on solid tissues within animal bodies, originating from various sources such as cellular contractility, interactions with neighboring cells and the extracellular matrix. Emerging evidence indicates that an imbalance in such forces can influence structural organization, homeostasis, and potentially contribute to disease. For instance, heightened tissue tension can impede apical cell extrusion, leading to the retention of apoptotic or transformed cells. In this study, we investigate the potential role of adenomatous polyposis coli (APC) in modulating tissue tension. Our findings reveal that expression of an APC truncation mutant elevates epithelial tension via the RhoA/ROCK pathway. This elevation induces morphological alterations and hampers apoptotic cell extrusion in cultured epithelial cells and organoids, both of which could be mitigated by pharmacologically restoring the tissue tension. This raises the possibility that APC mutations may exert pathogenetic effects by altering tissue mechanics.

Navigating Treatment Choices for Stress and Urgency Urinary Incontinence Using Graph Theory in Discrete Mathematics.

In this study, we propose a method for navigating the choice of treatment for stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) using graph theory in discrete mathematics. Our previous study accumulated data from 150 patients who underwent tension-free vaginal tape (TVT), transobturator tape (TOT), and vaginal non-ablation Erbium YAG laser (VEL) surgeries between 2014 and 2016. Network diagrams were created using this data. The treatments TVT, TOT, and VEL, along with patient characteristics (1-hour pad test: 1-hrPadTest, Overactive Bladder Symptom Score: OABSS), were represented as nodes and edges in the network diagram. We then employed a heuristic function to select the optimal treatment method for the patients with SUI and UUI. This process enables medical professionals to easily navigate the data for patients with both SUI and UUI concerns by calculating the shortest path connecting the 1-hrPadTest and OABSS. These results, which are consistent with those of previous studies, suggest that VEL is the optimal treatment. Unlike previous studies that employed statistical knowledge that is challenging for patients to understand, our study aids patients in visually comprehending and developing a customized treatment plan. This approach introduces a novel perspective for clinical decision-making in the treatment of urinary incontinence. To the best of our knowledge, this is the first study to apply discrete mathematics to patient decision-making for urinary incontinence treatment.

Physical properties of soft contact lens multipurpose solutions commercially available in Ghana.

Purpose: To investigate the physical properties of commercially available multipurpose soft contact lens solutions in Ghana. Methods: pH (Kelilong ICL-099 pH meter, China), osmolality (OSMOMAT 3000, GONOTEC, Germany), surface tension (Sigma 700 Tensiometer, Sweden), and viscosity (CFOC-200 Viscometer, Cannon Company, USA) of various soft contact lens multipurpose solutions (MPS) were measured in triplicates at room temperature. Viscosity measurements were also taken at 34 °C ocular surface temperature. The solutions examined were Opti-Free Replenish (OFR), Trufresh (TF), Avizor (AV), Freshlook (FL), and Refresh (RF). Results: Several solutions were largely hypo-osmotic in the range of 108-231 mOsm/kg, the exception being Avizor, which had osmolality values that were closer to human tears (301 ± 0.58 mOsm/kg). The range of pH values of the solutions (6.33-8.24, mean (SD) = 7.53 ± 0.18) fell within the reported tolerable range for the ocular surface (6.20-9.00). Surface tension values ranged from 35.86 to 42.27 mNm with a mean of 38.49 ± 2.32 mNm. The average viscosity of most solutions at room temperature (25 °C) was 1.44 ± 0.49 cP with a range of 1.04-2.15 cP. Significantly lower values ranging from 0.79 to 1.58 cP were obtained at ocular surface temperature (34 °C), p = 0.0001). Conclusions: The physical properties of many of the solutions used as MPS in Ghana are markedly variable. Nevertheless, pH, surface tension, and viscosity fall within the acceptable limits of ocular physiological tolerance; except for osmolality, which majority were outside the reported tolerable range for the ocular surface. This information may partly explain the reason some patients exhibit strong preferences for certain care systems and should aid clinical decision-making when prescribing eye care systems to patients.

Anterior variable angle locking neutralisation plate superiority over traditional tension band wiring for treating transverse patella fractures.

Purpose: This paper investigates the biomechanical benefits of using hybrid constructs that combine cannulated screws with tension band wiring (TBW) cerclage compared to cannulated screws with anterior Variable Angle locking neutralisation plates (VA LNP). These enhancements can bear heavier loads and maintain the repaired patella's integrity, in contrast to traditional methods. Method: Eighteen fresh-frozen human cadaver patellae were carefully fractured transversely at their midpoints using a saw. They were then divided into two groups of nine for subsequent utilisation. Fixation methods included Cannulated Screw Fixation added with either TBW or VA LNP Fixation Technique. Cyclic loading simulations (500 cycles) were conducted to mimic knee motion, tracking fracture displacement with Optotrak. After that, the constructs were secured over a servo-hydraulic testing machine to determine the load-to-failure on axial mode. Results: The average fracture displacement for the anterior neutralisation plate group was 0.09 ± 0.12 mm, compared to 0.77 ± 0.54 mm for the tension band wiring with cannulated screw group after 500 cyclic loading. This result is statistically significant (p = 0.004). The anterior neutralisation plate group exhibited a mean load-to-failure of 1359 ± 21.53 N, whereas the tension band wiring group showed 780.1 ± 22.62 N, resulting in a significant difference between the groups (p = 0.007). Conclusion: This research highlights the superior biomechanical advantage of VA LNP over TBW for treating simple transverse patella fractures with two cannulated screws. It also highlights how the TBW is still a valuable option considering the load-to-failure limit. Level of Evidence: Not Applicable.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma.

PURPOSE: To identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study. METHODS: A total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of cirrus OCT. RESULTS: Thirty-two eyes displayed choroidal MvD (62.7 (95% CI 58.4-67.0) years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV≥1400cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P=0.023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P=0.025). CONCLUSIONS: In NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Anastomotic tension "Bridging": a risk factor for anastomotic leakage following low anterior resection.

BACKGROUND: Excessive tension at the anastomosis contributes to anastomotic leakage (AL) in low anterior resection (LAR). However, the specific tension has not been measured. We assessed whether "Bridging," characterized by the proximal colon resembling a suspension bridge above the pelvic floor, is a significant risk factor for AL following LAR for rectal cancer. METHODS: This retrospective study reviewed the medical records and laparoscopic videos of 102 patients who underwent laparoscopic LAR using the double stapling technique at Yachiyo Hospital between January 2014 and December 2023. Patients were classified based on whether they had Bridging (tight or sagging) or were in a Resting state of the proximal colon, and the association between Bridging and AL was examined. RESULTS: AL occurred in 31.3% of the Tight Bridging group, 20% of the Sagging Bridging group, and 2.2% of the Resting group (P = 0.002). The incidence of AL was significantly higher in patients with Bridging than in those without (23.2% vs. 2.2%, P = 0.003). Multivariate analysis revealed that Bridging is an independent risk factor for AL (odds ratio = 6.97; 95% confidence interval: 1.45-33.6; P = 0.016). CONCLUSIONS: The presence of Bridging is a significant risk factor for AL following LAR for rectal cancer, suggesting the need for implementing preventive measures in patients with this condition.

Mitochondrial oxygen tension in critically ill patients receiving red blood cell transfusions: a multicenter observational cohort study.

PURPOSE: Currently, there is no marker of efficacy of red blood cell (RBC) transfusion. This study describes the impact of RBC transfusion on mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in critically ill patients with anemia. METHODS: Critically ill patients with a hemoglobin concentration < 10 g/dL, for whom a single RBC unit had been ordered, were included. MitoPO2 was measured with the COMET device immediately before RBC transfusion, 0.5 h, 1 h, 3 h, and 24 h after RBC transfusion. MitoVO2 was calculated from dynamic mitoPO2 measurements during cessation of local oxygen supply. RESULTS: Sixty-three patients participated, median age 64.0 (interquartile range (IQR) 52.3-72.8) years, median hemoglobin concentration before transfusion 7.4 (IQR 7.1-7.7) g/dL. Median mitoPO2 values were 55.0 (IQR 49.6-63.0) mmHg before RBC transfusion, 51.0 (IQR 41.5-61.2) directly after and 67.3 (IQR 41.6-83.7) at 24 h after RBC transfusion. Median mitoVO2 values were 3.3 (IQR 2.1-5.9) mmHg/s before RBC transfusion, 3.7 (IQR 2.0-5.1) mmHg/s directly after, and 3.1 (IQR 2.5-4.8) mmHg/s 24 h after RBC transfusion. In the higher Hb concentration group (> 7 g/dL), we saw a dissociation of the effect of RBC transfusion on mitoPO2 versus on mitoVO2 values. MitoPO2 and mitoVO2 values were not associated with commonly used parameters of tissue perfusion and oxygenation. CONCLUSION: RBC transfusion did not alter mitoPO2 and mitoVO2 in critically ill patients with anemia. MitoPO2 and mitoVO2 values were not notably associated with Hb concentrations, parameters of severity of illness and markers of tissue perfusion or oxygenation. Given the high baseline value, it cannot be excluded nor confirmed whether RBC can improve low mitoPO2. Trial registration number NCT03092297 (registered 27 March 2017).

Revisiting Post-Laminectomy Kyphosis and Challenges in Its Management: A Case Report.

The posterior ligamentous complex plays a pivotal role in spinal stability during complex movements, especially at the cervical vertebral level. Its disruption leads to the development of post-laminectomy kyphosis. The present case emphasizes the challenges in managing post-laminectomy kyphosis, restoring spinal alignment, and the importance of the posterior tension band as a spine stabilizer. A 19-year-old male underwent C2-C5 laminectomy for cervical C3 neurofibroma at an outside hospital. The patient remained stable for five months and then developed cervical kyphosis, leading to myelopathy. Clinical examination revealed significant neurological deficits, including spasticity, clonus, loss of hand dexterity, and sensory abnormalities. Imaging revealed C3 retrolisthesis with severe cervical kyphosis, cord compression, and myelomalacia. The management involved cervical traction with gradual increments in the weight and correction of the cervical sagittal balance. Principles of kyphotic deformity correction were applied, and C2 pedicle with C3-C5 lateral mass fixation was performed. The patient's modified Japanese Orthopaedic Association score improved from 10 to 16 at six months' follow-up. Post-laminectomy, the disruption of the posterior ligamentous complex increases the range of motion, particularly in the cervical spine, leading to instability and kyphosis. Surgical interventions such as laminoplasty, laminotomy, and laminectomy with posterior cervical fusion aim to mitigate the risk of kyphosis, with techniques such as bone-to-bone ligament-preserving laminoplasty and ultrasonic bone scalpel showing promise in further reducing the risk of kyphosis. The key determinant for the prevention of kyphosis is the integrity of the posterior ligamentous complex. The management of cervical kyphosis includes appropriate pre-operative planning, which includes the evaluation of cervical and spinopelvic parameters. For a posterior spinal approach, one may choose to consider laminotomy, laminoplasty, or laminectomy along with posterior cervical fusion.

Long-Term Postoperative Outcomes following Cionni Ring and In-the-Bag Intraocular Lens Implantation in Eyes with Subluxated Lenses.

PURPOSE: To report long-term outcomes following Cionni modified capsule tension ring (MCTR) and in-the-bag intraocular lens (IOL) implantation in subluxated lenses. STUDY DESIGN: Retrospective case series METHODS: Setting: Raghudeep Eye Hospital, India Study Population: 41 eyes of 31 patients with subluxated lenses Eyes completing a minimum of 5 years postoperative follow-up were included. INTERVENTIONS: Lens extraction, capsular bag fixation with MCTR using 9-0 polypropylene suture and in-the-bag IOL implantation were performed in all eyes. MAIN OUTCOME MEASURES: Corrected distance visual acuity (CDVA), IOL centration, posterior capsule opacification, glaucoma and retinal complications were documented at final follow up. RESULTS: The mean age of the cohort was 20.48 ± 16.46 (standard deviation, SD) years. 24 eyes (58%) were below 15 years of age at the time of surgery. Marfan's syndrome accounted for 37% cases. Mean follow-up was 9.89 ± 3.81 (SD) years. 32 eyes (74%) had a CDVA of ≥ 0.3 Log MAR at final follow up. IOL decentration was noted in 7 eyes (17%) requiring a secondary surgery. The mean duration from primary surgery to re-surgery was 8.79 years. 17 eyes (41%) required a laser capsulotomy, 88% of which were pediatric eyes. Retinal detachment occurred in 4 eyes (10%), 3 of which had Marfan's syndrome. CONCLUSION: Capsular bag fixation with an MCTR using 9-0 polypropylene and in-the-bag IOL implantation had good long term visual outcomes with an acceptable rate of serious postoperative complications in eyes with subluxated lenses. This approach allows preservation of the natural compartments of the eye and placement of an IOL in its most physiological position. However, considering a 17% rate of IOL decentration requiring surgical intervention, long term stability with non-biodegradable suture materials such as polytetrafluoroethylene as well as decentration rates following sutured/ sutureless scleral fixation should be compared.

Probing the interfacial behaviors of interfacially active and non-active asphaltenes and their impact on emulsion stability.

HYPOTHESIS: Asphaltenes subfractions with distinct interfacial behaviors may play different roles in stabilizing oil-water emulsions. EXPERIMENTS: In this work, whole asphaltenes were separated into interfacially active asphaltenes (IAA) and interfacially non-active asphaltenes (INAA). Employing advanced nanomechanical techniques, we have explored the compositions, morphologies, sizes, adsorption, and interfacial behaviors of IAA and INAA. FINDINGS: IAA exhibits a high and unevenly distributed oxygen content, distinguishing it from INAA. In toluene, the diameters of IAA and INAA are about 60 nm and 6 nm, respectively. When adsorbed irreversibly on mica surfaces, the thickness of the IAA and INAA film was measured at âˆ¼5.5 nm or 1 nm, respectively; while in a toluene solution, the film thickness reached âˆ¼46 nm and 3.1 nm for IAA and INAA, respectively. IAA demonstrates superior interfacial activity, and elastic/viscous moduli compared to INAA at the water-toluene interface. Quantified surface force measurements reveal that IAA stabilizes water droplets in toluene at a concentration of only 10 mg/L, while INAA requires a higher concentration of 100 mg/L. This work provides the first comprehensive investigation into the adsorption and interfacial behaviors of asphaltene subfractions and provides useful insights into the asphaltenes-stabilization mechanism of emulsions.

Children and adolescents with primary headaches exhibit altered sensory profiles - a multi-modal investigation.

BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children's quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains. METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache. RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache. CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification. TRIAL REGISTRATION: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

Transcutaneous oxygen tension-guided hyperbaric oxygen therapy for preventing skin necrosis after hyaluronic acid filler injections.

Introduction: Hyaluronic acid (HA) fillers, popular for facial cosmetic enhancements, pose risks of vascular complications like skin necrosis due to arterial blockage, necessitating effective treatments such as hyperbaric oxygen therapy (HBOT). Methodology: This study presents a series of cases where measurements of transcutaneous oxygen pressure (TcPO2) informed the application of HBOT for skin necrosis induced by HA. Clinical presentation and outcomes: In cases 1 and 3, following the injection of HA, potential skin necrosis was observed. In addition to standard treatment, TcPO2 revealed values below 40 mmHg, indicating tissue hypoxia. Treatment with HBOT increased TcPO2 levels to above 200 mmHg, suggesting that HBOT could correct the hypoxia. Monitoring TcPO2 levels also aided in determining the optimal time to discontinue HBOT. In cases 2 and 4, patients received standard treatment, resulting in TcPO2 levels above 40 mmHg, indicating adequate tissue oxygenation, and no additional HBOT was administered. All four patients mentioned above showed good clinical recovery. Conclusion: This study investigates the application of TcPO2 measurement technology in aiding decisions on whether to utilize HBOT in the treatment of complications arising from HA fillers, as well as in optimizing HBOT protocols.

Cell-intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow.

Cytokinesis is the process where the mother cell's cytoplasm separates into daughter cells. This is driven by an actomyosin contractile ring that produces cortical contractility and drives cleavage furrow ingression, resulting in the formation of a thin intercellular bridge. While cytoskeletal reorganization during cytokinesis has been extensively studied, less is known about the spatiotemporal dynamics of the plasma membrane. Here, we image and model plasma membrane lipid and protein dynamics on the cell surface during leukemia cell cytokinesis. We reveal an extensive accumulation and folding of the plasma membrane at the cleavage furrow and the intercellular bridge, accompanied by a depletion and unfolding of the plasma membrane at the cell poles. These membrane dynamics are caused by two actomyosin-driven biophysical mechanisms: the radial constriction of the cleavage furrow causes local compression of the apparent cell surface area and accumulation of the plasma membrane at the furrow, while actomyosin cortical flows drag the plasma membrane toward the cell division plane as the furrow ingresses. The magnitude of these effects depends on the plasma membrane fluidity, cortex adhesion, and cortical contractility. Overall, our work reveals cell-intrinsic mechanical regulation of plasma membrane accumulation at the cleavage furrow that is likely to generate localized differences in membrane tension across the cytokinetic cell. This may locally alter endocytosis, exocytosis, and mechanotransduction, while also serving as a self-protecting mechanism against cytokinesis failures that arise from high membrane tension at the intercellular bridge.