Probing Multidimensional Mechanical Phenotyping of Intracellular Structures by Viscoelastic Spectroscopy.

Mechanical phenotyping of complex cellular structures gives insight into the process and function of mechanotransduction in biological systems. Several methods have been developed to characterize intracellular elastic moduli, while direct viscoelastic characterization of intracellular structures is still challenging. Here, we develop a needle tip viscoelastic spectroscopy method to probe multidimensional mechanical phenotyping of intracellular structures during a mini-invasive penetrating process. Viscoelastic spectroscopy is determined by magnetically driven resonant vibration (about 15 kHz) with a tiny amplitude. It not only detects the unique dynamic stiffness, damping, and loss tangent of the cell membrane-cytoskeleton and nucleus-nuclear lamina but also bridges viscoelastic parameters between the mitotic phase and interphase. Self-defined dynamic mechanical ratios of these two phases can identify two malignant cervical cancer cell lines (HeLa-HPV18+, SiHa-HPV16+) whose membrane or nucleus elastic moduli are indistinguishable. This technique provides a quantitative method for studying mechanosensation, mechanotransduction, and mechanoresponse of intracellular structures from a dynamic mechanical perspective. This technique has the potential to become a reliable quantitative measurement method for dynamic mechanical studies of intracellular structures.

The evolution of toxic anterior segment syndrome.

PURPOSE OF REVIEW: Toxic anterior segment syndrome (TASS) is a surgical complication resulting from a noninfectious inflammatory reaction to substances used during intraocular ophthalmic surgery. Continuous reporting of new information concerning risk factors and possible causes is critical for preventing this condition. RECENT FINDINGS: The diagnosis of TASS is clinical and its main features are well known. However, new causes of TASS are emerging and being reported, as are new treatment options for managing the inflammation or its complications, and prevention guidelines are being updated. This article presents current and novel information regarding these topics. SUMMARY: Educating the medical community regarding potential causes of TASS and its prevention is necessary for improving management of TASS. Thorough investigations and reports of TASS cases are a fundamental step in achieving this goal. Still, as the complete eradication of TASS solely through prevention is unlikely, further studies regarding TASS's pathophysiology, systemic and ocular risk factors, and new treatment options are necessary.

A Single Site, Open Label Clinical Trial, Evaluating the Duration, Efficacy, and Safety of a Novel Lip Plumper.

INTRODUCTION: Lip plumpers are topical agents that offer immediate, but temporary, volumization of the lips. While these products are becoming increasingly popular and are available at multiple retailers, there is a lack of clinical studies to evaluate the efficacy, longevity, and safety of the lip plumping products. METHODS: This is a prospective, single center, clinical trial to evaluate the duration, efficacy, and safety of a lip plumping agent in two clinical visits. Lip volume and adverse event were assessed by two clinicians at various time points: 15 minutes, 1 hour, 2 hours, 3 hours, and 4 hours. RESULTS: Twenty-two subjects were enrolled in the study, and eighteen completed the study. Investigator assessments of global improvement 15 minutes after application of the lip plumping product demonstrated improvement in lip fullness in 100% of the subjects (18/18), and 1 hour post-application 67% (12/18) showed an improvement in lip fullness that was statistically significant compared to the 2-hour assessment (P less than 0.05). Subject evaluations noted improvement in lip fullness 15 minutes post-application in 94.4% (17/18) of subjects, and 1 hour post-application, 89% (16/18) of the subjects who completed the trial noted some improvement in the volume of their lips that was statistically significant compared to the 2-hour post-application time point (P less than 0.0001). Subjects noted that they did experience a tingling and heat sensation, but a majority noted that that this sensation lasted less than 15 minutes. DISCUSSION: Our study demonstrated that the lip plumping product increased lip volume in almost all patients 15 minutes post-application and showed a continued improvement in lip fullness per investigator assessments 1 hour after application. Adverse events of a tingling or heat sensation were expected and observed as the topical product contained capsaicin, cinnamon, and menthol, all of which can induce this sensation by the release of substance P. J Drugs Dermatol. 2018;17(9):999-1004.

Severe Intraocular Pressure Elevation After Intracameral Healon 5 Viscoelastic Support for Postoperative Hypotony After XEN Gel Stent Insertion.

PURPOSE: The purpose of this article was to describe (i) a novel case of severe intraocular pressure (IOP) elevation due to intracameral Healon 5 for management of early postoperative (post-op) hypotony following XEN Gel Stent insertion and (ii) the management of this complication. MATERIALS AND METHODS: A case report. RESULTS: A 52-year-old man, with primary open-angle glaucoma and suboptimal left IOP control on maximally tolerated medical therapy, was managed with XEN Gel Stent insertion at another tertiary eye unit. Post-op, the IOP was 2 mm Hg with a shallow anterior chamber (AC) and choroidal effusions. Intracameral injections of Provisc on post-op days 1 and 3 failed to reverse hypotony. At 1 week post-op, persistent clinically significant hypotony was managed with Healon 5 injection into the AC. Twelve hours later, the patient experienced significant pain and reduced vision and presented to a different tertiary eye unit, where left visual acuity was hand movements, IOP was 70 mm Hg with a deep AC (complete ophthalmic viscosurgical device fill with Healon 5) and a flat drainage bleb with no external drainage. Emergency AC washout of the Healon 5 was performed with resolution of symptoms, visual acuity, and IOP control. CONCLUSIONS: We caution against the use of intracameral Healon 5 in the management of post-op hypotony following XEN Gel Stent insertion, given the potential risk for extreme IOP elevation and sight loss.

Toxic Anterior Segment Syndrome Outbreak after Cataract Surgery Triggered by Viscoelastic Substance.

PURPOSE: The purpose of this study is to present toxic anterior segment syndrome (TASS) outbreak at our clinic and discuss possible causes of TASS. MATERIALS AND METHODS: Thirty-four eyes of 34 patients developed TASS in a consecutive 2 weeks period were included in this study. Both anterior segment and fundus examinations were performed before and after uncomplicated cataract surgery. During the follow-up period, clinical features and all possible causes were evaluated including perioperative products and processing such as sterilization technique of surgical instruments, irrigating solutions, drugs, viscoelastic substance (VES), and intraocular lens. RESULTS: Patients had corneal edema, anterior chamber reactions, and decreased vision. No patient had purulent secretion, chemosis, lid involvement, and pain. At first 2 postoperative days, patients treated as infectious endophthalmitis by topical and oral antibiotics and then TASS was suspected, and patients treated completely with topical steroids. Suspected cause for TASS was VES substance, 2% sodium hyaluronate which had newly been used as VES product in phacoemulsification surgery. No new case has occurred after stopped usage of this VES product. CONCLUSION: As far as we know, this is the largest report of TASS outbreak in the shortest period from the same clinic caused by VES. Suboptimal products of surgical materials can be the cause of TASS. Close monitoring of each surgical step and elimination of causative agent can prevent the outbreaks of TASS.

Viscoelastic substance in prefilled syringe as an etiology of Toxic Anterior Segment Syndrome.

CONTEXT: Toxic Anterior Segment Syndrome (TASS) is an acute postoperative inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues. OBJECTIVE: To present etiologic investigation of two consecutive clusters of TASS. TASS outbreak and investigation: This paper presents two consecutive clusters of TASS in 15 of the 24 uneventful surgeries and the investigation carried out to find the etiology. After the occurrence of first cluster of TASS, sterilization-related etiology was explored; however, we did not find any lacunae in the sterilization and cleaning process in the operating theater (OT). Nevertheless, multiple changes in cleaning process were implemented. Still a second cluster of TASS was encountered in the following session of OT. Several other factors which include preservatives, hand gloves, intraocular lenses, medications/solutions, intraocular penetration of topically administered drugs, and viscoelastics were investigated as the possible etiology of the second consecutive cluster of TASS; however, most of them were ruled out. The newly introduced viscoelastic I-visc® 1.4% sodium hyaluronate (I medical, i-Medical Ophthalmic International GmbH, Heidelberg, Germany) was thought to be the most likely cause and was replaced with previously in use sodium hyaluronate 1.5% and lidocaine hydrochloride 1% (Visthesia, CZ, Germany) in the following session of OT. No further TASS incident was encountered after replacing the viscoelastic. CONCLUSION: Investigation revealed that 1.4% sodium hyaluronate in prefilled syringe (PFS) (I-visc® 1.4%) was the etiologic factor of two consecutive clusters of TASS. While TASS due to residual denatured ophthalamic viscosurgical devices (OVDs) is a common knowledge, current study brings out that even disposable viscoelastic material supplied in PFSs can be an etiology of TASS. It is important to recognize that contamination of OVDs with endotoxins can occur at the time of manufacturing. Therefore, in the absence of appropriate guidelines for ophthalmic preparations, endotoxin limit for medical preparations (i.e. <0.5 endotoxin units/ml) must be considered during OVD manufacture.

An in situ gelling liquid crystalline system based on monoglycerides and polyethylenimine for local delivery of siRNAs.

The development of delivery systems able to complex and release siRNA into the cytosol is essential for therapeutic use of siRNA. Among the delivery systems, local delivery has advantages over systemic administration. In this study, we developed and characterized non-viral carriers to deliver siRNA locally, based on polyethylenimine (PEI) as gene carrier, and a self-assembling drug delivery system that forms a gel in situ. Liquid crystalline formulations composed of monoglycerides (MO), PEI, propylene glycol (PG) and 0.1M Tris buffer pH 6.5 were developed and characterized by polarized light microscopy, Small Angle X-ray Scattering (SAXS), for their ability to form inverted type liquid crystalline phases (LC2) in contact with excess water, water absorption capacity, ability to complex with siRNA and siRNA release. In addition, gel formation in vivo was determined by subcutaneous injection of the formulations in mice. In water excess, precursor fluid formulations rapidly transformed into a viscous liquid crystalline phase. The presence of PEI influences the liquid crystalline structure of the LC2 formed and was crucial for complexing siRNA. The siRNA was released from the crystalline phase complexed with PEI. The release rate was dependent on the rate of water uptake. The formulation containing MO/PEI/PG/Tris buffer at 7.85:0.65:76.5:15 (w/w/w/w) complexed with 10 µM of siRNA, characterized as a mixture of cubic phase (diamond-type) and inverted hexagonal phase (after contact with excess water), showed sustained release for 7 days in vitro. In mice, in situ gel formation occurred after subcutaneous injection of the formulations, and the gels were degraded in 30 days. Initially a mild inflammatory process occurred in the tissue surrounding the gel; but after 14 days the tissue appeared normal. Taken together, this work demonstrates the rational development of an in situ gelling formulation for local release of siRNA.

Calculation of ophthalmic viscoelastic device-induced focus shift during femtosecond laser-assisted cataract surgery.

PURPOSE: To assess if a change in refractive index of the anterior chamber during femtosecond laser-assisted cataract surgery can affect the laser beam focus position. METHODS: The index of refraction and chromatic dispersion of six ophthalmic viscoelastic devices (OVDs) was measured with an Abbe refractometer. Using the Gullstrand eye model, the index values were used to predict the error in the depth of a femtosecond laser cut when the anterior chamber is filled with OVD. Two sources of error produced by the change in refractive index were evaluated: the error in anterior capsule position measured with optical coherence tomography biometry and the shift in femtosecond laser beam focus depth. RESULTS: The refractive indices of the OVDs measured ranged from 1.335 to 1.341 in the visible light (at 587 nm). The error in depth measurement of the refilled anterior chamber ranged from -5 to +7 µm. The OVD produced a shift of the femtosecond laser focus ranging from -1 to +6 µm. Replacement of the aqueous humor with OVDs with the densest compound produced a predicted error in cut depth of 13 µm anterior to the expected cut. CONCLUSIONS: Our calculations show that the change in refractive index due to anterior chamber refilling does not sufficiently shift the laser beam focus position to cause the incomplete capsulotomies reported during femtosecond laser-assisted cataract surgery.

Sweetness and other sensory properties of model fruit drinks: Does viscosity have an impact?

BACKGROUND: The impact of thickening agents and viscosity levels on sensory perception was studied in model fruit drinks. Four formulations were prepared that varied in the sweetener blend (erythritol, maltitol and/or steviol glycosides). Locust bean gum and its blends with either xanthan or carrageenan were used to adjust viscosity levels (20, 40, and 70 mPa s). The ranges of viscosity and sweetness level were selected to represent a typical concentration range in commercially available beverages. RESULTS: An increase in viscosity resulted in significant increases in pulpiness, sliminess and perceived viscosity (P-values ≤ 0.001), which were not dependent on sweeteners or hydrocolloid type. Taste perception remained largely unchanged irrespective of the hydrocolloid used. CONCLUSION: The impact of viscosity on sweetness and taste perception was much smaller in the concentrations used than has been generally reported. The effect of the type of hydrocolloid on the perception of taste attributes was greater than that of viscosity.

Nanosponges - a completely new nano-horizon: pharmaceutical applications and recent advances.

In recent years, nanosponges (NS) have gained tremendous impetus in drug delivery through nanotechnology. Nanosponges are capable of providing solutions for several formulation related problems. Through this review, scientists working in the field of nanotechnology can have an insight into the techniques of preparation, characterization and applications of NS. Owing to their small size and porous nature they can bind poorly-soluble drugs within their matrix and improve their bioavailability. They can be crafted for targeting drugs to specific sites, prevent drug and protein degradation and prolong drug release in a controlled manner. This review attempts to elaborate different schemes of synthesis of NS and their characterization. Factors affecting drug loading and release have been enumerated. Due to their advantages, NS have not only been explored for their pharmaceutical applications but also have large popularity in allied sciences, especially in water purification.

Textural interface opacity after descemet stripping automated endothelial keratoplasty: a report of 30 cases and possible etiology.

PURPOSE: Descemet stripping automated endothelial keratoplasty (DSAEK) has its own set of complications including interface abnormalities. This case series presents the largest number of patients who developed textural interface opacity (TIO) at the graft-host interface after DSAEK. METHODS: This is a retrospective multicenter case series of 30 patients from 7 institutions with the finding of TIO. Clinical information collected included donor preparation details, recipient information, and surgical technique. Clinical outcomes included best-corrected visual acuity and status of TIO appearance at the last follow-up visit. Slit-lamp photographs were analyzed and compared. RESULTS: The majority of the patients (73%) had a best-corrected visual acuity of 20/40 or better. Four of the donor tissues were prepared with a microkeratome blade with the same lot number. Six patients had a central interface space between host and donor stromal surfaces--presumed interface fluid but potentially viscoelastic. A slight majority (57%) of patients had improvement in the severity of TIO, with 20% noted to have a complete resolution of TIO (mean follow-up of 11.9 months). Two clinical types of TIO were seen: an elongated type and a punctate type. CONCLUSIONS: Most patients with TIO after DSAEK obtain good visual outcomes. TIO spontaneously improves or even resolves during follow-up without intervention. The etiology of this condition is unknown, but we propose 2 different mechanisms. The elongated type could be secondary to an irregular cut of the donor with the microkeratome blade. The punctate type may be secondary to retained viscoelastic.

Facial filler and neurotoxin complications.

Botulinum neuromodulators and injectable dermal fillers have become part of the armamentarium in the treatment of facial aging. Their successful use requires a fundamental knowledge of anatomy and physiology and a sound understanding of their risks and complications. Although neuromodulators and fillers continue to demonstrate a strong record of safety, several notable risks exist.

Feasibility study of using viscoplastic bone cement for vertebroplasty: an in vivo clinical trial and in vitro cadaveric biomechanical examination.

STUDY DESIGN: An in vivo clinical trial, and an in vitro cadaveric biomechanical and micromorphologic analysis. OBJECTIVE: To find the feasibility of using viscoplastic bone cement for vertebroplasty. SUMMARY OF BACKGROUND DATA: Vertebroplasty involved in bone cement reinforcement of fractured vertebra has shown promising clinical results. The most frequently observed complication of vertebroplasty is the cement leakage during surgery. Many methods were proposed and were successful at reducing the risk of leakage, such as creating a void within vertebra to reduce the injection pressure, increasing the cement viscosity to reduce the cement infiltration, etc. Nevertheless, a more cost-effective and safer surgery method is still the goal for many spine surgeons and researchers. METHODS: To deliver the viscoplastic bone cement into the vertebra, a unipedicular tract and a void in the vertebra was created using a curette. The viscoplastic bone cement was then delivered into the void piece by piece and tamped for compactness with a blunt end tool. For the in vitro biomechanical test, 7 thoracic vertebrae were used. The intact specimens were compressed to lose 25% of its intact height, and then augmented with viscoplastic bone cement. Postaugmentation CT scanning was taken to examine the cement distribution, leakage path, and cement filling ratio within the vertebra. Postaugmentation compression test was conducted to examine the vertebral strength and stiffness, and then compared with the intact ones. Finally, the vertebrae were cut into slices for micromorphologic analysis. RESULTS: The 6 in vivo clinical trials were all successfully operated with significant pain relief and showed no leakage during and after the surgery. The in vitro biomechanical test showed the cement augmentation significantly increased the vertebral strength (pre 3164 (229) N vs. post 3905 (484) N, P < 0.003), but tentatively decreased the vertebral stiffness (pre 1074 (74) N/mm vs. post 801 (370) N/mm, P = 0.081). The postaugmentation CT scanning showed the cement was well confined within the vertebra and the cement filling ratio was 21% (ranged from 15% to 29%). The depth that the viscoplastic bone cement infiltrated into the cancellous bone was 3.5 (0.6) mm, which is less than the depth [8.3 (2.2) mm, P < 0.001] of standard viscous bone cement vertebroplasty. CONCLUSION: Vertebroplasty using viscoplastic bone cement is clinically feasible and can effectively improve the vertebral strength and reduce the cement infiltration depth. The risk of cement leakage can also be decreased by using viscoplastic bone cement.

Toxic anterior segment syndrome following iris-supported phakic IOL implantation with viscoelastic Multivisc BD.

PURPOSE: To report on the association between Multivisc BD and toxic anterior segment syndrome (TASS) post phakic intraocular lens (IOL) implantation. METHODS: Two patients developed severe toxic anterior chamber inflammation following implantation of phakic iris fixated IOL with Multivisc BD viscoelastic. Anterior chamber washout was performed with intracameral antibiotic injection. Local antibiotics were continued until cultures were found to be negative. Thereafter, intensive local and systemic steroids were initiated and gradually tapered down. RESULTS: The inflammatory reaction disappeared completely and the visual acuity improved from hand motion to 6/9 without correction within 1 week. CONCLUSIONS: Any viscoelastic material may be contaminated by heat-stable bacterial endotoxic as it is prepared by gene-coded bacteria. It is suggested that Multivisc BD was the etiologic factor of TASS. Refractive surgeons should be aware of this rare complication of phakic IOL implantation whenever they use a new viscoelastic material.