Viscosity-Sensitive Membrane Dyes as Tools To Estimate the Crystalline Structure of Lipid Bilayers.

Lipid membranes are crucial for cellular integrity and regulation, and tight control of their structural and mechanical properties is vital to ensure that they function properly. Fluorescent probes sensitive to the membrane's microenvironment are useful for investigating lipid membrane properties; however, there is currently a lack of quantitative correlation between the exact parameters of lipid organization and a readout from these dyes. Here, we investigate this relationship for "molecular rotors", or microviscosity sensors, by simultaneously measuring their fluorescence lifetime to determine the membrane viscosity, while using X-ray diffraction to determine the membrane's structural properties. Our results reveal a phase-dependent correlation between the membrane's structural parameters and mechanical properties measured by a BODIPY-based molecular rotor, giving excellent predictive power for the structural descriptors of the lipid bilayer. We also demonstrate that differences in membrane thickness between different lipid phases are not a prerequisite for the formation of lipid microdomains and that this requirement can be disrupted by the presence of line-active molecules. Our results underpin the use of membrane-sensitive dyes as reporters of the structure of lipid membranes.

Beyond Liposuction: Evolving Applications for Tumescent Anesthesia.

Tumescent anesthesia was initially developed as a safer and more effective alternative to general anesthesia in performing liposuction. Today, it is used extensively for a wide variety of surgical procedures performed by various specialties. As more surgeons have become exposed to tumescent anesthesia with its associated advantages over general anesthesia, the number of applications for this unique form of local anesthesia has skyrocketed. In this article, we will briefly discuss the basics of tumescent anesthesia, followed by a discussion of the many applications that are now being performed by various specialties. J Drugs Dermatol. 2022;21(1):86-89. doi:10.36849/JDD.6279.

Tumescent Anesthesia: A Brief History Regarding the Evolution of Tumescent Solution.

Tumescent anesthesia, initially developed as a safer and more effective alternative to general anesthesia in performing liposuction, is used extensively today for a wide array of surgical procedures performed by various specialties. The make-up of the tumescent solution is variable, and it has evolved significantly over the past 40+ years. Even prior to Jefferey Klein’s tumescent solution recorded in his article from 1987, “The Tumescent Technique for Lipo-Suction Surgery,” there were significant contributions paving the way to modern formulations.1 In this article, we attempt to provide the most comprehensive history and timeline documenting the evolution of tumescent solution to date. J Drugs Dermatol. 2021;20(12):1283-1287. doi:10.36849/JDD.6212.

Comparison of Modern Super Wide Field Microscopy Systems in Mohs Surgery.

Microscopic interpretation of frozen tissue sections is fundamental to Mohs micrographic surgery. Mohs surgeons spend a significant portion of their day at the microscope. Eye strain and fatigue, in addition to musculoskeletal strain, may increase the risk of interpretation errors as well as musculoskeletal injury.3,4,5,7 Advances in microscope systems have allowed for more efficient and reliable reading of slides as well as decreased physical strain. In particular, the advent of super wide field (SWF) microscopy, which includes lower power objective lenses as well as wider eyepieces, allows for a much larger area to be viewed, decreasing eye strain.2,5 Also, more ergonomically designed systems help to decrease musculoskeletal fatigue and injury.7 In an update to an article from Goldsberry et al, that compared older SWF microscope systems,1 we review three newer systems for comparison: Leica DM2500, Nikon Ci-L, and Olympus Bx53 (Figure 1.) Each system reviewed demonstrates ergonomic design and super wide fields of view, allowing for efficient interpretation of tissue and decreased eye strain and musculoskeletal strain compared to older systems. The Nikon Ci-L had the largest possible VFA at 490.87 mm2, 40% more area than the Olympus and 56% more area than the Leica. J Drugs Dermatol. 2021;20(10):1093-1095, doi:10.36849/JDD.6083.

Increased risk of attempted suicide in Australian veterans is associated with total and permanent incapacitation, unemployment and posttraumatic stress disorder severity.

BACKGROUND: Military veterans have higher rates of suicidality and completed suicides compared to the general population. Previous research has demonstrated suicidal behaviour is higher in US combat veterans who are younger, suffer from posttraumatic stress disorder, depression and anxiety and score lower on measures of health. However, research on predictors of suicide for Australian veterans is limited. The aim of this study was to identify significant demographic and psychological differences between veterans with posttraumatic stress disorder who had attempted suicide and those with posttraumatic stress disorder who had not, as well as determine predictors of suicide attempts within an Australian cohort. METHODS: A retrospective analysis was conducted on 229 ex-service personnel diagnosed with posttraumatic stress disorder who had attended a Military Service Trauma Recovery Day Program as outpatients at Toowong Private Hospital from 2007 to 2014. Patients completed a battery of mental health self-report questionnaires assessing symptoms of posttraumatic stress disorder, alcohol use, anger, depression, anxiety and quality of life. Demographic information and self-reported history of suicide attempts were also recorded. RESULTS: Results indicated the average age was significantly lower, and the rates of posttraumatic stress disorder, anger, anxiety and depression symptoms were significantly higher in those veterans with history of a suicide attempt. Multivariate logistic regression analyses indicated posttraumatic stress disorder symptom severity, unemployment or total and permanent incapacity pension status significantly predicted suicide attempt history. CONCLUSION: Among a cohort of Australian veterans with posttraumatic stress disorder, psychopathology severity, unemployment and total and permanent incapacity status are significantly associated with suicidality. This study highlights the importance of early identification of posttraumatic stress disorder and psychopathology, therapeutic and social engagement, and prioritisation of tangible employment options or meaningful and goal-directed activities for veterans deemed unable to work.

Visualising the membrane viscosity of porcine eye lens cells using molecular rotors.

The plasma membranes of cells within the eye lens play an important role in metabolite transport within the avascular tissue of the lens, maintaining its transparency over the entire lifespan of an individual. Here we use viscosity-sensitive 'molecular rotors' to map the microscopic viscosity within these unusual cell membranes, establishing that they are characterised by an unprecedentedly high degree of lipid organisation.

Imaging plasma membrane phase behaviour in live cells using a thiophene-based molecular rotor.

Molecular rotors have emerged as versatile probes of microscopic viscosity in lipid bilayers, although it has proved difficult to find probes that stain both phases equally in phase-separated bilayers. Here, we investigate the use of a membrane-targeting viscosity-sensitive fluorophore based on a thiophene moiety with equal affinity for ordered and disordered lipid domains to probe ordering and viscosity within artificial lipid bilayers and live cell plasma membranes.

Measuring the Viscosity of the Escherichia coli Plasma Membrane Using Molecular Rotors.

The viscosity is a highly important parameter within the cell membrane, affecting the diffusion of small molecules and, hence, controlling the rates of intracellular reactions. There is significant interest in the direct, quantitative assessment of membrane viscosity. Here we report the use of fluorescence lifetime imaging microscopy of the molecular rotor BODIPY C10 in the membranes of live Escherichia coli bacteria to permit direct quantification of the viscosity. Using this approach, we investigated the viscosity in live E. coli cells, spheroplasts, and liposomes made from E. coli membrane extracts. For live cells and spheroplasts, the viscosity was measured at both room temperature (23°C) and the E. coli growth temperature (37°C), while the membrane extract liposomes were studied over a range of measurement temperatures (5-40°C). At 37°C, we recorded a membrane viscosity in live E. coli cells of 950 cP, which is considerably higher than that previously observed in other live cell membranes (e.g., eukaryotic cells, membranes of Bacillus vegetative cells). Interestingly, this indicates that E. coli cells exhibit a high degree of lipid ordering within their liquid-phase plasma membranes.

Imaging phase separation in model lipid membranes through the use of BODIPY based molecular rotors.

In order to fully understand the dynamics of processes within biological lipid membranes, it is necessary to possess an intimate knowledge of the physical state and ordering of lipids within the membrane. Here we report the use of three molecular rotors based on meso-substituted boron-dipyrrin (BODIPY) in combination with fluorescence lifetime spectroscopy to investigate the viscosity and phase behaviour of model lipid bilayers. In phase-separated giant unilamellar vesicles, we visualise both liquid-ordered (Lo) and liquid-disordered (Ld) phases using fluorescence lifetime imaging microscopy (FLIM), determining their associated viscosity values, and investigate the effect of composition on the viscosity of these phases. Additionally, we use molecular dynamics simulations to investigate the orientation of the BODIPY probes within the bilayer, as well as using molecular dynamics simulations and fluorescence correlation spectroscopy (FCS) to compare diffusion coefficients with those predicted from the fluorescence lifetimes of the probes.

Group cognitive behaviour therapy for military service-related post-traumatic stress disorder: effectiveness, sustainability and repeatability.

OBJECTIVE: The aim of this study was to assess 12 month outcomes of Australian combat veterans with post-traumatic stress disorder (PTSD) who participated in a 6 week group-based CBT programme at the Toowong Private Hospital. The study population included 496 consecutive admissions to the programme between 1999 and 2008. METHOD: Self-report measures of PTSD, depression, anxiety, anger, alcohol use, relationship satisfaction and quality of life parameters were collected at intake and 3, 6 and 12 months post intake. RESULTS: Statistically significant and sustained improvements were noted in 12 month outcome measures for PTSD, depression, anxiety, alcohol use, anger, and quality of life. PTSD symptom reduction occurred consistently each year for 9 years and exhibited an aggregated effect size of 0.68. CONCLUSIONS: This naturalistic research demonstrates that treatment administered under clinical conditions produces equivocal magnitudes of positive change in terms of PTSD symptoms when compared with existing efficacy data in individual and group treatments. Further, these symptomatic gains are sustainable and consistently reproducible. The benefits noted from group therapy were seen as independent of whether or not individual treatment was in place.

Nucleus magnocellularis and nucleus laminaris in Belgian Waterslager and normal strain canaries.

Belgian Waterslager (BWS) canaries are characterized by a mean 30% loss of hair cells in the basilar papilla compared to other canaries, and a corresponding increase in behavioral auditory thresholds. In spite of the large number of missing and damaged sensory cells, there is on average only a 12% reduction in the number of fibers in the VIIIth nerve. In this study, we examined cell number and size, and volume of auditory nuclei, specifically in nucleus magnocellularis and nucleus laminaris in Belgian Waterslager canaries. While the overall anatomical structure and organization of these nuclei and the total number of cells in the non-BWS and BWS canaries were comparable, BWS canaries showed a significant decrease in the volume of the auditory nuclei that was attributed to a reduction in cell size. These results provide further evidence in favor of a role of the sensory epithelium in the maintenance of central auditory structures.

Temporal modulation transfer functions in the barn owl (Tyto alba).

Barn owls (Tyto alba) have evolved several specializations in their auditory system to achieve the high sensory acuity required for prey capture, including superior processing of interaural time differences and phase coding in the auditory periphery. Here, we tested whether barn owls are capable of high temporal resolution that may be a prerequisite for the accuracy in binaural processing. Temporal resolution was measured psychoacoustically and demonstrated in temporal modulation transfer functions. Four barn owls were trained in an operant task with food reward to detect sinusoidal amplitude modulations within an 800-ms gated white-noise burst or 800-ms periods of modulation in continuous white noise (spectrum levels of -5 dB and 15 dB SPL). Within the range of tested amplitude modulation frequencies from 5 Hz to 1280 Hz, barn owls' detection thresholds were lowest at 10-20 Hz. This sensitivity corresponds to an intensity-difference limen of between 0.9 dB and 1.4 dB. For all conditions, temporal modulation transfer functions showed band-pass characteristics with a high-frequency cutoff in the range of 37 Hz to 92 Hz, corresponding to minimum integration times of 4.3 ms and 1.7 ms, respectively. In summary, these data indicate a temporal resolution in the owl's auditory system that is good, but not unusual, compared to other vertebrates.