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Langmuir : the ACS Journal of Surfaces... Jul 2022Lamellar mesophases of insoluble lipids are readily solubilized by the micellar mesophases of soluble surfactants. This simple process underscores a broad array of...
Lamellar mesophases of insoluble lipids are readily solubilized by the micellar mesophases of soluble surfactants. This simple process underscores a broad array of biochemical methodologies, including purification, reconstitution, and crystallization of membrane proteins, as well as the isolation of detergent-resistant membrane fractions. Although much is now known about the thermodynamic driving forces of membrane solubilization, the kinetic pathways by which the surfactant alters vesicular mesophases are only beginning to be appreciated. Little is known about how these interactions affect the solubilization of more complex, multilamellar mesophases. Here, we investigate how a common zwitterionic detergent affects the solubilization of a smectic, multilamellar, cylindrical mesophase of lipids, called the myelin figure. Our results reveal that myelin solubilization occurs in a multistep manner, producing a well-defined sequence of morphologically distinct intermediates to complete solubilization. The kinetic processes producing these intermediates include (1) coiling, which encompasses the formation, propagation, and tightening of extended helices; (2) thinning, which reflects the unbinding of lamellae in the smectic stacks; and (3) detachment or retraction, which either dissociates the myelinic protrusion from the source lipid mass or returns the myelinic protrusion to the source lipid mass─all in transit toward complete solubilization. These occasionally overlapping steps are most pronounced in single-lipid component myelins, while compositionally graded multicomponent myelins inhibit the coiling step and detach more frequently. Taken together, the appearance of these intermediates during the solubilization of myelins suggests a complex free-energy landscape characterizing myelin solubilization populated by metastable, morphological intermediates correlated with locally minimized changes in energy dependent upon the mesophase's composition. This then predicts the accessibility of structurally distinct, kinetic intermediates─such as loose and tight coiled helices, peeled myelins, retracted tubes, and detached protrusions─before reaching the stable ground state corresponding to a dissolved suspension of mixed surfactant-lipid micelles.
Topics: Detergents; Excipients; Lipids; Micelles; Myelin Sheath; Pulmonary Surfactants; Solubility; Surface-Active Agents
PubMed: 35816731
DOI: 10.1021/acs.langmuir.2c00774 -
Case Reports in Ophthalmology 2021Serous choroidal detachment that is caused by rhegmatogenous retinal detachment (RRD) may present a significant diagnostic challenge as delayed recognition and repair of...
Serous choroidal detachment that is caused by rhegmatogenous retinal detachment (RRD) may present a significant diagnostic challenge as delayed recognition and repair of the underlying RRD can severely impact the final anatomical and visual outcome. We report 2 consecutive patients with atypical choroidal detachments who were later found to have underlying RRDs. A 71-year-old female presented with a 1-week history of painful vision loss and floaters in the left eye. Examination revealed choroidal detachments in the nasal and temporal periphery and an overlying retinal detachment with shifting subretinal fluid. However, no retinal breaks were identified. An extensive laboratory workup and imaging of the orbits were unrevealing. She was treated with 80 mg oral prednisone daily for 2 weeks with subsequent resolution of the choroidals but persistence of the retinal detachment. Similarly, a 52-year-old male presented with a 3-week history of flashes and floaters followed by painful vision loss in the left eye 1 day prior to presentation. He had hand motion vision OS and the intraocular pressure was undetectable by hand-held tonometry OS. Dense brunescent cataract prevented adequate viewing of the posterior pole. B-scan ultrasonography revealed a funnel retinal detachment, with homogenous choroidal echogenicities suggestive of hemorrhagic choroidal detachment. Extensive laboratory workup was unrevealing. The patient was started on 60 mg oral prednisone and re-evaluated every 2 days, but ultrasonography revealed persistence of the choroidal detachment after 1 week. The diagnosis of RRD with an associated choroidal detachment should be considered, even in the absence of an identifiable causative retinal break.
PubMed: 34054477
DOI: 10.1159/000513220 -
Journal of Cell Science Jan 2019Epithelial tissues function as barriers that separate the organism from the environment. They usually have highly curved shapes, such as tubules or cysts. However, the...
Epithelial tissues function as barriers that separate the organism from the environment. They usually have highly curved shapes, such as tubules or cysts. However, the processes by which the geometry of the environment and the cell's mechanical properties set the epithelium shape are not yet known. In this study, we encapsulated two epithelial cell lines, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement forming a complete monolayer. MDCK monolayers detached from the alginate shell at a constant rate, whereas J3B1A monolayers detached at a low rate unless the tube radius was reduced. We showed that this detachment is driven by contractile stresses in the epithelium and can be enhanced by local curvature. This allows us to conclude that J3B1A cells exhibit smaller contractility than MDCK cells. Monolayers inside curved tubes detach at a higher rate on the outside of a curve, confirming that detachment is driven by contraction.
Topics: Alginates; Animals; Biomechanical Phenomena; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell Movement; Cells, Immobilized; Collagen; Dogs; Drug Combinations; Epithelial Cells; Laminin; Madin Darby Canine Kidney Cells; Mechanotransduction, Cellular; Mice; Organ Specificity; Proteoglycans
PubMed: 30578312
DOI: 10.1242/jcs.222372 -
Journal of Ophthalmology 2016Traumatic retinal detachments are a significant cause of morbidity. There are currently no evidence-based guidelines on the appropriate time to perform vitreoretinal... (Review)
Review
Traumatic retinal detachments are a significant cause of morbidity. There are currently no evidence-based guidelines on the appropriate time to perform vitreoretinal surgery to repair a traumatic retinal detachment. Early intervention, within seven days of the inciting trauma, may decrease proliferative vitreoretinopathy and postoperative endophthalmitis. Later intervention may yield a reduced risk of inflammation and hemorrhage, particularly in cases of concomitant open globe injuries. This article reviews the literature on the management of retinal detachments associated with ocular trauma from the years 2006 to 2016. Particular focus was placed on the timing of surgery, concomitant open globe injury, anatomical success rates, visual acuity, and complication rates. In this review, anatomical success was not significantly related to timing of intervention when compared between early and delayed intervention in eyes with and without concomitant open globe injuries. Visual acuities postoperatively varied widely despite timing of intervention due to the large variation in mechanism and extent of ocular injuries. Proliferative vitreoretinopathy was a common complication. Preliminary data indicate that endophthalmitis rates may be lower when early vitreoretinal surgery is performed. There is insufficient data to conclude whether early or delayed surgery leads to improved outcomes, highlighting the need for further research in this domain.
PubMed: 27999681
DOI: 10.1155/2016/4978973 -
Frontiers in Human Neuroscience 2020Past empirical studies have suggested that older adults preferentially use gaze-based mood regulation to lessen their negative experiences while watching an emotional...
Past empirical studies have suggested that older adults preferentially use gaze-based mood regulation to lessen their negative experiences while watching an emotional scene. This preference for a low cognitively demanding regulatory strategy leaves open the question of whether the effortful processing of a more cognitively demanding reappraisal task is really spared from the general age-related decline. Because it does not allow perceptual attention to be redirected away from the emotional source, music provides an ideal way to address this question. The goal of our study was to examine the affective, behavioral, physiological, and cognitive outcomes of positive and detached reappraisal in response to negative musical emotion in younger and older adults. Participants first simply listened to a series of threatening musical excerpts and were then instructed to either positively reappraise or to detach themselves from the emotion elicited by music. Findings showed that, when instructed to simply listen to threatening music, older adults reported a more positive feeling associated with a smaller SCL in comparison with their younger counterparts. When implementing positive and detached reappraisal, participants showed more positive and more aroused emotional experiences, whatever the age group. We also found that the instruction to intentionally reappraise negative emotions results in a lesser cognitive cost for older adults in comparison with younger adults. Taken together, these data suggest that, compared to younger adults, older adults engage in spontaneous downregulation of negative affect and successfully implement downregulation instructions. This extends previous findings and brings compelling evidence that, even when auditory attention cannot be redirected away from the emotional source, older adults are still more effective at regulating emotions. Taking into account the age-associated decline in executive functioning, our results suggest that the working memory task could have distracted older adults from the reminiscences of the threat-evoking music, thus resulting in an emotional downregulation. Hence, even if they were instructed to implement reappraisal strategies, older adults might prefer distraction over engagement in reappraisal. This is congruent with the idea that, although getting older, people are more likely to be distracted from a negative source of emotion to maintain their well-being.
PubMed: 32670038
DOI: 10.3389/fnhum.2020.00216 -
Graefe's Archive For Clinical and... Mar 2023There have been disparate outcomes in the few studies that have looked at anatomic success and visual acuity (VA) in chronic retinal rhegmatogenous detachment (RRD)...
PURPOSE
There have been disparate outcomes in the few studies that have looked at anatomic success and visual acuity (VA) in chronic retinal rhegmatogenous detachment (RRD) repair. Chronic retinal detachments (RD) without a posterior vitreous detachment (PVD) occur in young myopes often secondary to an atrophic hole. These patients are often asymptomatic, and studies report good surgical anatomic results. However, chronic RD with a PVD is symptomatic but presents late due to patient compliance. This paper aims to evaluate this lesser-studied chronic macula-off RD with PVD.
METHODS
After obtaining Institutional Review Board (IRB) approval, patients who had undergone surgical intervention for all diagnosis codes of RD were identified in the Denver Health Medical Center database. Medical records were reviewed, and patients found to have open-globe injuries, tractional RD due to proliferative diabetic retinopathy, macula-on detachments, and RD due to previous ocular surgery were excluded. Similarly, patients without PVD were also excluded. A total of 37 patients with PVD-type chronic macula-off RD were thus identified and preoperative characteristics, surgical intervention, and complications were analyzed.
RESULTS
The average patient age was 53.8 years. The length of RRD duration ranged from 30 to 365 days (mean 136.7 days). Twenty-six (70.3% patients had proliferative vitreoretinopathy (PVR) grade C or greater. Initial anatomic success-defined as re-attachment after one surgery-was 54.1%. The final attachment was 94.6%. Fifteen of 37 (40.5%) of the patients had issues with drop adherence, positioning, or missing post-operative appointments.
CONCLUSION
Chronic macula-off RD with a PVD should be identified as it is associated with much lower rates of initial re-attachment. Socioeconomic factors likely are the driving factor for patients with PVD-type chronic macula-off RD to present late, struggle with positioning, and have difficulty with follow-up and drop compliance. These extended periods without treatment then lead to high rates of PVR and poor initial anatomic success. However, repair of PVD-type chronic macula-off RD should still be pursued as final anatomic success is high.
Topics: Humans; Middle Aged; Retinal Detachment; Retina; Vitreous Body; Scleral Buckling; Vitreoretinopathy, Proliferative; Vitreous Detachment; Vitrectomy; Retrospective Studies
PubMed: 36289075
DOI: 10.1007/s00417-022-05876-3 -
Scientific Reports Nov 2021Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence...
Anchorage-independent growth of cancer cells in vitro is correlated to metastasis formation in vivo. Metformin use is associated with decreased breast cancer incidence and currently evaluated in cancer clinical trials. The combined treatment with metformin and 2-deoxy-D-glucose (2DG) in vitro induces detachment of viable MDA-MB-231 breast cancer cells that retain their proliferation capacity. This might be important for cell detachment from primary tumors, but the metabolic changes involved are unknown. We performed LC/MS metabolic profiling on separated attached and detached MDA-MB-231 cells treated with metformin and/or 2DG. High 2DG and metformin plus 2DG altered the metabolic profile similarly to metformin, inferring that metabolic changes are necessary but not sufficient while the specific effects of 2DG are crucial for detachment. Detached cells had higher NADPH levels and lower fatty acids and glutamine levels compared to attached cells, supporting the role of AMPK activation and reductive carboxylation in supporting anchorage-independent survival. Surprisingly, the metabolic profile of detached cells was closer to untreated control cells than attached treated cells, suggesting detachment might help cells adapt to energy stress. Metformin treated cells had higher fatty and amino acid levels with lower purine nucleotide levels, which is relevant for understanding the anticancer mechanisms of metformin.
Topics: Cell Line, Tumor; Cell Proliferation; Deoxyglucose; Female; Humans; Hypoglycemic Agents; Metabolome; Metabolomics; Metformin; Triple Negative Breast Neoplasms
PubMed: 34725457
DOI: 10.1038/s41598-021-98642-0 -
International Journal of Surgery Case... Sep 2022The hydrogel Scleral Buckle is a soft and pliable subtype of buckles which has been used to repair retinal breaks and detachments externally. This case represents an...
INTRODUCTION
The hydrogel Scleral Buckle is a soft and pliable subtype of buckles which has been used to repair retinal breaks and detachments externally. This case represents an unusual late orbital complication of the implant.
CASE REPORT
A 70 years old male patient presented with drooping right upper lid and eye misalignment, associated with foreign body sensation and discomfort. The patient underwent scleral buckle surgery for a rhegmatogenous retinal detachment 32 years before his presentation using a hydrogel MIRAgel® explant. Orbital imaging showed a large cystic lesion in the superolateral quadrant of the orbit indicating a fluid-filled explant.
DISCUSSION
In patients who were treated with hydrogel MIRAgel® explant for retinal breaks or detachments, detailed ophthalmic history, particular past eye surgery history, and examination, orbital imaging, and good clinical documentation. Serious orbital and neurological conditions need to be ruled out carefully.
CONCLUSION
Late orbital complications of hydrogel MIRAgel® explant might develop late after surgery and might represent a diagnostic challenge for ophthalmologists.
PubMed: 36063767
DOI: 10.1016/j.ijscr.2022.107583 -
Frontiers in Medicine 2022Polymeric biomaterials are biological or synthetic substances which can be engineered to interact with biological systems for the diagnosis or treatment of diseases.... (Review)
Review
Polymeric biomaterials are biological or synthetic substances which can be engineered to interact with biological systems for the diagnosis or treatment of diseases. These biomaterials have immense potential for treating eyes diseases, particularly the retina-a site of many inherited and acquired diseases. Polymeric biomaterials can be engineered to function both as an endotamponade agent and to prevent intraocular scarring in retinal detachment repair surgeries. They can also be designed as a drug delivery platform for treatment of retinal diseases. Finally, they can be used as scaffolds for cellular products and provide non-viral gene delivery solutions to the retina. This perspective article explains the role of polymeric biomaterials in the treatment of retinal conditions by highlighting recent advances being translated to clinical practice. The article will also identify potential hurdles to clinical translation as future research directions in the field.
PubMed: 36059842
DOI: 10.3389/fmed.2022.949543 -
Methods in Molecular Biology (Clifton,... 2018We describe a recently reported method for directly applying a known, nanonewton-scale force to the nucleus in a living, intact cell. First, a suction seal is applied on...
We describe a recently reported method for directly applying a known, nanonewton-scale force to the nucleus in a living, intact cell. First, a suction seal is applied on the nuclear surface using a micropipette. Then, the micropipette is translated away from the nucleus. The nucleus deforms and translates with the moving micropipette and then eventually detaches from the micropipette and recovers (roughly) its original shape and position. At the point of detachment, the resisting force (from the deformed nucleus and connected cytoskeleton) balances the suction force. Because the suction force is precisely known and reproducibly applied, this method therefore allows comparisons of nuclear response across disruptions to the cytoskeleton, nucleus, or cell. This method is useful for quantifying nuclear elastic properties in its native, integrated environment.
Topics: Animals; Biological Assay; Biomechanical Phenomena; Cell Nucleus; Mice
PubMed: 30141040
DOI: 10.1007/978-1-4939-8691-0_8