Self-Sensing of a Magnetically Actuated Prism.

We demonstrate a method for self-sensing of a magnetically actuated prism that can be used, e.g., in a feedback-loop without the need of additional sensors. In order to use the impedance of the actuation coils as a measurement parameter, we first obtained the optimal measurement frequency that is well separated from the actuation frequencies and at the same time provides the best compromise between sensitivity to the position and robustness. We then developed a combined actuation and measurement driver, and correlated its output signal to the mechanical state of the prism using a defined calibration sequence. We demonstrate that we can reliably measure the state of each actuator and determine the tilt angle of the prism with an accuracy of ±0.1∘ in the polar angle over a range of ±4∘ and ±20 mrad in the azimuthal angle.

Implementation of model explainability for a basic brain tumor detection using convolutional neural networks on MRI slices.

PURPOSE: While neural networks gain popularity in medical research, attempts to make the decisions of a model explainable are often only made towards the end of the development process once a high predictive accuracy has been achieved. METHODS: In order to assess the advantages of implementing features to increase explainability early in the development process, we trained a neural network to differentiate between MRI slices containing either a vestibular schwannoma, a glioblastoma, or no tumor. RESULTS: Making the decisions of a network more explainable helped to identify potential bias and choose appropriate training data. CONCLUSION: Model explainability should be considered in early stages of training a neural network for medical purposes as it may save time in the long run and will ultimately help physicians integrate the network's predictions into a clinical decision.

Use of Botanicals to Suppress Different Stages of the Life Cycle of Fusarium graminearum.

Fusarium head blight (FHB) is one of the most important cereal diseases worldwide, causing yield losses and contamination of harvested products with mycotoxins. Fusarium graminearum is one of the most common FHB-causing species in wheat and barley cropping systems. We assessed the ability of different botanical extracts to suppress essential stages of the fungal life cycle using three strains of F. graminearum (FG0410, FG2113, and FG1145). The botanicals included aqueous extracts from white mustard (Sinapis alba) seed flour (Pure Yellow Mustard [PYM] and Tillecur [Ti]) as well as milled Chinese galls (CG). At 2% concentration (wt/vol), PYM and Ti completely inhibited growth of mycelium of all F. graminearum strains whereas, at 1%, CG reduced the growth by 65 to 83%, depending on the strain. While PYM and Ti reduced the germination of both conidia and ascospores at 2% (wt/vol), CG was only effective in reducing conidia germination. Perithecia formation of FG0410 but not FG2113 was suppressed by all botanicals. Moreover, application of botanicals on mature perithecia led to a two- to fourfold reduction in discharge of ascospores. Using liquid chromatography (LC) with diode array detection, we quantified the principal glucosinolate component sinalbin of PYM and Ti. LC time-of-flight mass spectrometry was used to demonstrate that the bioactive matrix of CG contains different gallotannins as well as gallic and tannic acids. Possible antifungal mechanisms of the botanical matrices are discussed. The results of this study are promising and suggest that PYM, Ti, and CG should be explored further for efficacy at managing FHB.[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

PARAPAPILLARY GAMMA AND DELTA ZONES IN HIGH MYOPIA.

PURPOSE: To examine parapapillary zones gamma and delta in highly myopic eyes. METHODS: The retrospective observational study included patients attending the Tokyo high myopia clinics. Fundus photographs were morphometrically examined. RESULTS: The study population included 600 eyes (304 individuals) with a mean age of 62.7 ± 14.3 years (range: 13-90 years) and mean axial length of 29.6 ± 2.2 mm (range: 23.2-35.4 mm). In multivariate analysis (regression coefficient r:0.90), larger horizontal gamma zone diameter was correlated with wider delta zone diameter (P < 0.001; standardized regression coefficient beta: 0.81), higher ratio of vertical-to-horizontal disk diameter (P < 0.001; beta: 0.10), shorter fovea-outer gamma zone border distance (P < 0.001; beta: -0.19), longer disk-fovea distance (P < 0.001; beta: 0.18), and higher count of chorioretinal atrophic lesions (P < 0.001; beta: 0.07). Longer horizontal delta zone width was correlated with longer horizontal gamma zone diameter (P < 0.001; beta: 1.00), longer horizontal disk diameter (P < 0.001; beta: 0.15), shorter disk-fovea distance (P < 0.001; beta: -0.19), longer fovea-outer gamma zone border distance (P < 0.001; beta: 0.19), and smaller diameter of the largest chorioretinal lesion (P = 0.03; beta: -0.04). Longer width of both zones together was associated with longer horizontal disk diameter (P < 0.001; beta: 0.31), higher ratio of vertical-to-horizontal disk diameter (P = 0.001; beta: 0.18), longer disk-fovea distance (P < 0.001; beta: 0.19), shorter fovea-outer gamma zone border distance (P < 0.001; beta: -0.18), higher number of chorioretinal lesions (P < 0.001; beta: 0.30), and longer vertical distance between the superior and inferior temporal arterial arcade (P = 0.001; beta: 0.13). CONCLUSION: Larger gamma and delta zones were correlated with larger optic disk and more marked vertical optic disk rotation, longer disk-fovea distance, higher number of chorioretinal lesions, and longer temporal vascular arcade diameter. Parapapillary gamma and delta zones may develop before chorioretinal lesions develop and enlarge.

TEMPORAL VASCULAR ARCADE WIDTH AND ANGLE IN HIGH AXIAL MYOPIA.

PURPOSE: Axial myopia is associated with elongation of the posterior ocular segment. The authors measured posterior fundus landmarks and assessed their associations with axial length. METHODS: Using fundus photographs, the authors measured the vertical distance between the temporal superior and temporal inferior arterial arcade (VDA) and the angle kappa between the temporal arterial arcades among other morphometric variables. RESULTS: The study included 456 eyes with a mean age of 61.2 ± 14.2 years (range: 13-88 years) and mean axial length of 29.4 ± 2.1 mm (range: 23.2-35.3 mm). Mean angle kappa was 91.3 ± 17.2° (range: 39-161°), and mean VDA was 7.93 ± 1.71 mm (range: 2.72-12.85 mm). In multivariate regression analysis, wider angle kappa was associated (regression coefficient r: 0.47) with shorter axial length (P = 0.002; beta: -0.17; B: -1.37; 95% confidence interval [CI]:-2.23 to -0.51), longer VDA (P < 0.001; beta: 0.27; B: 2.70; 95% CI: 1.85-3.54), shorter disk-foveola distance (P < 0.001; beta: -0.22; B: -4.76; 95% CI: -7.05 to -2.46), shorter vertical optic disk diameter (P = 0.002; beta: -0.14; B: -6.83; 95% CI: -11.1 to -2.56), lower number of any chorioretinal lesions (P = 0.007; beta: -0.13; B: -2.11; 95% CI: -3.63 to -0.58), and longer maximal vertical chorioretinal lesion diameter (P = 0.05; beta: 0.09; B: 0.92; 95% CI: -0.02 to 1.86). A longer VDA was associated (r: 0.31) with longer axial length (P < 0.001; beta: 0.22; B: 0.18; 95% CI: 0.10-0.25), wider angle kappa (P < 0.001; beta: 0.28; B: 0.03; 95% CI: 0.02-0.04) and higher number of chorioretinal lesions (P = 0.03; beta: 0.10; B: 0.16; 95% CI: 0.02-0.31). If eyes with chorioretinal lesions were excluded, the association between longer VDA and longer axial length was no longer statistically significant (P > 0.10). CONCLUSION: Axial elongation was correlated with decreasing angle kappa, caused by an elongation of the disk-foveola distance because of an enlargement of the gamma zone, whereas VDA remained constant. By contrast, horizontal length of macular Bruch membrane and vertical length of macular Bruch membrane were independent of axial elongation. Axial elongation did not lead to lengthening of Bruch membrane in the macular region in eyes without macular chorioretinal lesions.

Long- and short-term intravital imaging reveals differential spatiotemporal recruitment and function of myelomonocytic cells after spinal cord injury.

After spinal cord injury (SCI), resident and peripheral myelomonocytic cells are recruited to the injury site and play a role in injury progression. These cells are important for clearing cellular debris, and can modulate the retraction and growth of axons in vitro. However, their precise spatiotemporal recruitment dynamics is unknown, and their respective roles after SCI remain heavily debated. Using chronic, quantitative intravital two-photon microscopy of adult mice with SCI, here we show that infiltrating lysozyme M (LysM(+)) and resident CD11c(+) myelomonocytic cells have distinct spatiotemporal recruitment profiles, and exhibit changes in morphology, motility, phagocytic activity and axon interaction patterns over time. This study provides the first in vivo description of the influx of inflammatory and resident myelomonocytic cells into the injured spinal cord and their interactions with cut axons, and underscores the importance of precise timing and targeting of specific cell populations in developing therapies for SCI.

Cell extract-containing medium for culture of intracellular fastidious bacteria.

The culture of fastidious microorganisms is a critical step in infectious disease studies. As a proof-of-concept experiment, we evaluated an empirical medium containing eukaryotic cell extracts for its ability to support the growth of Coxiella burnetii. Here, we demonstrate the exponential growth of several bacterial strains, including the C. burnetii Nine Mile phase I and phase II strains, and C. burnetii isolates from humans and animals. Low-oxygen-tension conditions and the presence of small hydrophilic molecules and short peptides were critical for facilitating growth. Moreover, bacterial antigenicity was conserved, revealing the potential for this culture medium to be used in diagnostic tests and in the elaboration of vaccines against C. burnetii. We were also able to grow the majority of previously tested intracellular and fastidious bacterial species, including Tropheryma whipplei, Mycobacterium bovis, Leptospira spp., Borrelia spp., and most putative bioterrorism agents. However, we were unable to culture Rickettsia africae and Legionella spp. in this medium. The versatility of this medium should encourage its use as a replacement for the cell-based culture systems currently used for growing several facultative and putative intracellular bacterial species.

Long-term in vivo imaging of normal and pathological mouse spinal cord with subcellular resolution using implanted glass windows.

Repeated in vivo two-photon imaging of adult mammalian spinal cords, with subcellular resolution, would be crucial for understanding cellular mechanisms under normal and pathological conditions. Current methods are limited because they require surgery for each imaging session. Here we report a simple glass window methodology avoiding repeated surgical procedures and subsequent inflammation. We applied this strategy to follow axon integrity and the inflammatory response over months by multicolour imaging of adult transgenic mice. We found that glass windows have no significant effect on axon number or structure, cause a transient inflammatory response, and dramatically increase the throughput of in vivo spinal imaging. Moreover, we used this technique to track retraction/degeneration and regeneration of cut axons after a 'pin-prick' spinal cord injury with high temporal fidelity. We showed that regenerating axons can cross an injury site within 4 days and that their terminals undergo dramatic morphological changes for weeks after injury. Overall the technique can potentially be adapted to evaluate cellular functions and therapeutic strategies in the normal and diseased spinal cord.

Three-dimensional imaging of small intestine morphology using non-linear optical microscopy and endogenous signals.

Two-photon microscopy (2PM) has become a gold standard for deep-tissue observations in the living animal as well as on thick samples. Using 2PM, the endofluorescence properties of biomolecules have shown an interesting potential for the imaging of tissues without any staining. In this short communication, we report a method to observe the different layers of mouse small intestine explants with subcellular resolution and without any staining or clearing. This method allows rapid observations of samples with little to no preparation thanks to the endofluorescence properties of biomolecules such as NAD(P)H or flavins and second-harmonic generation. Finally, we show different three-dimensional reconstructions of the mouse small intestine anatomy obtained with this approach to show the potential of this method in morphological studies.

Experimental Bi-axial tensile tests of spinal meningeal tissues and constitutive models comparison.

Introduction This study aims at identifying mechanical characteristics under bi-axial loading conditions of extracted swine pia mater (PM) and dura and arachnoid complex (DAC). Methods 59 porcine spinal samples have been tested on a bi-axial experimental device with a pre-load of 0.01 N and a displacement rate of 0.05 mm·s-1. Post-processing analysis included an elastic modulus, as well as constitutive model identification for Ogden model, reduced Gasser Ogden Holzapfel (GOH) model, anisotropic GOH model, transverse isotropic and anisotropic Gasser models as well as a Mooney-Rivlin model including fiber strengthening for PM. Additionally, micro-structure of the tissue was investigated using a bi-photon microscopy. Results Linear elastic moduli of 108 ± 40 MPa were found for DAC longitudinal direction, 53 ± 32 MPa for DAC circumferential direction, with a significant difference between directions (p < 0.001). PM presented significantly higher longitudinal than circumferential elastic moduli (26 ± 13 MPa vs 13 ± 9 MPa, p < 0.001). Transversely isotropic and anisotropic Gasser models were the most suited models for DAC (r2  =  0.99 and RMSE:0.4 and 0.3 MPa) and PM (r2 = 1 and RMSE:0.06 and 0.07 MPa) modelling. Conclusion This work provides reference values for further quasi-static bi-axial studies, and is the first for PM. Collagen structures observed by two photon microscopy confirmed the use of anisotropic Gasser model for PM and the existence of fenestration. The results from anisotropic Gasser model analysis depicted the best fit to experimental data as per this protocol. Further investigations are required to allow the use of meningeal tissue mechanical behaviour in finite element modelling with respect to physiological applications. STATEMENT OF SIGNIFICANCE: This study is the first to present biaxial tensile test of pia mater as well as constitutive model comparisons for dura and arachnoid complex tissue based on such tests. Collagen structures observed by semi-quantitative analysis of two photon microscopy confirmed the use of anisotropic Gasser model for pia mater and existence of fenestration. While clear identification of fibre population was not possible in DAC, results from anisotropic Gasser model depicted better fitting on experimental data as per this protocol. Bi-axial mechanical testing allows quasi-static characterization under conditions closer to the physiological context and the results presented could be used for further simulations of physiology. Indeed, the inclusion of meningeal tissue in finite element models will allow more accurate and reliable numerical simulations.

High regional variation in prostate surgery for benign prostatic hyperplasia in Switzerland.

BACKGROUND: Among various treatment options for benign prostatic hyperplasia (BPH), surgical therapy is the most invasive. As Switzerland has the highest transurethral prostatectomy rate among OECD countries, we assessed the regional variation in prostate surgery for BPH and explored potential determinants of variation. METHODS: We conducted a population-based analysis using discharge data for men aged ≥40 years with transurethral or simple prostatectomy from all Swiss hospitals during 2013-2018. After excluding patients with genitourinary/prostate cancer, we derived hospital service areas (HSAs) by analyzing patient flows. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). We estimated the reduction in variance across HSAs of prostatectomy rates in multilevel regression models, with incremental adjustment for age, regional cultural and socioeconomic factors, disease burden, density of urologists, and the time since urologists' graduation. RESULTS: Overall, 44,253 prostatectomies (42,710 transurethral and 1543 simple) from 44 HSAs were analyzed. The mean age-standardized prostate surgery rate was 314 (range 166-500) per 100,000 men aged ≥40 years per year. The EQ was 3.01 and the SCV 5.53, indicating a high regional variation. In multivariate models, men aged 75-79 years had an 11.6-fold higher prostatectomy rate than those aged 50-54 years. French/Italian language areas had a 21% lower rate than Swiss German speaking areas. Socioeconomic factors, disease burden, and density of urologist/time since graduation were not associated with prostatectomy rates. After full adjustment, 80% of the variance in prostate surgery across HSAs remained unexplained. CONCLUSION: We found a remarkably high regional variation in prostate surgery rates for BPH within Switzerland.

Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery.

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

Optimal Flow Sensing for Schooling Swimmers.

Fish schooling implies an awareness of the swimmers for their companions. In flow mediated environments, in addition to visual cues, pressure and shear sensors on the fish body are critical for providing quantitative information that assists the quantification of proximity to other fish. Here we examine the distribution of sensors on the surface of an artificial swimmer so that it can optimally identify a leading group of swimmers. We employ Bayesian experimental design coupled with numerical simulations of the two-dimensional Navier Stokes equations for multiple self-propelled swimmers. The follower tracks the school using information from its own surface pressure and shear stress. We demonstrate that the optimal sensor distribution of the follower is qualitatively similar to the distribution of neuromasts on fish. Our results show that it is possible to identify accurately the center of mass and the number of the leading swimmers using surface only information.

Optimal allocation of limited test resources for the quantification of COVID-19 infections.

The systematic identification of infected individuals is critical for the containment of the COVID-19 pandemic. Currently, the spread of the disease is mostly quantified by the reported numbers of infections, hospitalisations, recoveries and deaths; these quantities inform epidemiology models that provide forecasts for the spread of the epidemic and guide policy making. The veracity of these forecasts depends on the discrepancy between the numbers of reported, and unreported yet infectious, individuals. We combine Bayesian experimental design with an epidemiology model and propose a methodology for the optimal allocation of limited testing resources in space and time, which maximises the information gain for such unreported infections. The proposed approach is applicable at the onset and spread of the epidemic and can forewarn of a possible recurrence of the disease after relaxation of interventions. We examine its application in Switzerland; the open source software is, however, readily adaptable to countries around the world. We find that following the proposed methodology can lead to vastly less uncertain predictions for the spread of the disease, thus improving estimates of the effective reproduction number and the future number of unreported infections. This information can provide timely and systematic guidance for the effective identification of infectious individuals and for decision-making regarding lockdown measures and the distribution of vaccines.

Mycobacterium canettii Infection of Adipose Tissues.

Adipose tissues were shown to host Mycobacterium tuberculosis which is persisting inside mature adipocytes. It remains unknown whether this holds true for Mycobacterium canettii, a rare representative of the M. tuberculosis complex responsible for lymphatic and pulmonary tuberculosis. Here, we infected primary murine white and brown pre-adipocytes and murine 3T3-L1 pre-adipocytes and mature adipocytes with M. canettii and M. tuberculosis as a positive control. Both mycobacteria were able to infect 18-22% of challenged primary murine pre-adipocytes; and to replicate within these cells during a 7-day experiment with the intracellular inoculums being significantly higher in brown than in white pre-adipocytes for M. canettii (p = 0.02) and M. tuberculosis (p = 0.03). Further in-vitro infection of 3T3-L1 mature adipocytes yielded 9% of infected cells by M. canettii and 17% of infected cells by M. tuberculosis (p = 0.001). Interestingly, M. canettii replicated and accumulated intra-cytosolic lipid inclusions within mature adipocytes over a 12-day experiment; while M. tuberculosis stopped replicating at day 3 post-infection. These results indicate that brown pre-adipocytes could be one of the potential targets for M. tuberculosis complex mycobacteria; and illustrate differential outcome of M. tuberculosis complex mycobacteria into adipose tissues. While white adipose tissue is an unlikely sanctuary for M. canettii, it is still an open question whether M. canettii and M. tuberculosis could persist in brown adipose tissues.

Glaucoma in high myopia and parapapillary delta zone.

PURPOSE: To examine the prevalence of glaucomatous optic neuropathy (GON) in a medium myopic to highly myopic group of patients and its association with parapapillary gamma zone and parapapillary delta zone. METHODS: The retrospective observational hospital-based study included patients who had attended the Tokyo High Myopia Clinics within January 2012 and December 2012 and for whom fundus photographs were available. GON was defined based on the appearance of the optic nerve head on the fundus photographs. RESULTS: The study included 519 eyes (262 individuals) with a mean age of 62.0±14.3 years (range:13-89 years) and mean axial length of 29.5±2.2 mm (range:23.2-35.3mm). GON was present in 141 (27.2%; 95% confidence intervals (CI): 23.3, 31.0%) eyes. Prevalence of GON increased from 12.2% (1.7, 22.7) in eyes with an axial length of <26.5mm to 28.5% (24.4, 32.5) in eyes with an axial length of ≥26.5mm, to 32.6% (27.9, 37.2) in eyes with an axial length of ≥28mm, to 36.0% (30.5, 41.4) in eyes with an axial length of ≥29mm, and GON prevalence increased to 42.1% (35.5, 48.8) in eyes with an axial length of ≥30mm. In multivariate analysis, higher GON prevalence was associated (Nagelkerke r2: 0.28) with larger parapapillary delta zone diameter (P<0.001; odds ratio (OR):1.86;95%CI:1.33,2.61), longer axial length (P<0.001;OR:1.45;95%CI:1.26,1.67) and older age (P = 0.01;OR:1.03;95%CI:1.01,1.05). If parapapillary delta zone width was replaced by the vertical disc diameter, higher GON prevalence was associated (r2:0.24) with larger vertical optic disc diameter (P = 0.04;OR:1.70;95%CI:1.03,2.81), after adjusting for longer axial length (P<0.001;OR:1.44;95%CI:1.26,1.64) and older age (P<0.001;OR:1.04;95%CI:1.02,1.06). CONCLUSIONS: Axial elongation associated increase in GON prevalence (mean: 28.1% in a medium to highly myopic study population) was associated with parapapillary delta zone as surrogate for an elongated peripapillary scleral flange and with larger optic disc size.

Electrostatic anchoring precedes stable membrane attachment of SNAP25/SNAP23 to the plasma membrane.

The SNAREs SNAP25 and SNAP23 are proteins that are initially cytosolic after translation, but then become stably attached to the cell membrane through palmitoylation of cysteine residues. For palmitoylation to occur, membrane association is a prerequisite, but it is unclear which motif may increase the affinities of the proteins for the target membrane. In experiments with rat neuroendocrine cells, we find that a few basic amino acids in the cysteine-rich region of SNAP25 and SNAP23 are essential for plasma membrane targeting. Reconstitution of membrane-protein binding in a liposome assay shows that the mechanism involves protein electrostatics between basic amino acid residues and acidic lipids such as phosphoinositides that play a primary role in these interactions. Hence, we identify an electrostatic anchoring mechanism underlying initial plasma membrane contact by SNARE proteins, which subsequently become palmitoylated at the plasma membrane.

Intraocular Pressure and Glaucomatous Optic Neuropathy in High Myopia.

Purpose: To examine the association between intraocular pressure (IOP) and the prevalence of glaucomatous optic neuropathy (GON) in high myopia. Methods: The hospital-based observational study consisted of patients treated in the Tokyo High Myopia Clinics and for whom fundus photographs and IOP readings were available. The appearance of the optic nerve head on fundus photographs was the basis for the definition of GON. Results: Among 517 eyes of 261 patients (mean age: 62.1 ± 14.2 years; range: 13-89 years; mean axial length: 29.5 ± 2.2 mm; range: 23.2-35.3 mm), GON was present in 141 eyes (27.3%; 95% confidence intervals [CIs]: 23.4, 31.0). Mean IOP did not differ significantly (P = 0.53) between the glaucoma group (14.5 ± 3.3 mm Hg; median: 14 mm Hg; range: 8-38 mm Hg) and the nonglaucomatous group (14.7 ± 2.5 mm Hg; median: 14 mm Hg; range: 6-23 mm Hg). In eyes with an axial length of ≤27.4 mm, higher presence of GON was correlated only with higher IOP (P = 0.037; odds ratio [OR]:1.35; 95% CI: 1.02, 1.80). In eyes with an axial length of ≥27.5 mm, presence of GON was correlated with older age (P < 0.001; OR: 1.05; 95% CI :1.03, 1.08), longer axial length (P < 0.001; OR: 1.60; 95% CI: 1.34, 1.91), shorter vertical diameter of the temporal arterial arcade (P = 0.009; OR: 0.82; 95% CI: 0.71, 0.95), and longer minimal optic disc diameter (P = 0.002; OR: 3.07; 95% CI: 1.52, 6.21). If IOP was added to the model, it was not significantly associated with the prevalence of GON (P = 0.97; OR: 1.00; 95% CI: 0.91, 1.10). Conclusions: GON was associated with elevated IOP in myopic eyes with an axial length of ≤27.4 mm, while in more highly myopic eyes (axial length ≥27.5 mm), larger optic disc, longer axial elongation and older age-but not IOP mostly within its normal range-were factors associated with GON. Future studies may examine an abnormally low IOP to be associated with a lower GON prevalence in highly myopic eyes.

The packing density of a supramolecular membrane protein cluster is controlled by cytoplasmic interactions.

Molecule clustering is an important mechanism underlying cellular self-organization. In the cell membrane, a variety of fundamentally different mechanisms drive membrane protein clustering into nanometre-sized assemblies. To date, it is unknown whether this clustering process can be dissected into steps differentially regulated by independent mechanisms. Using clustered syntaxin molecules as an example, we study the influence of a cytoplasmic protein domain on the clustering behaviour. Analysing protein mobility, cluster size and accessibility to myc-epitopes we show that forces acting on the transmembrane segment produce loose clusters, while cytoplasmic protein interactions mediate a tightly packed state. We conclude that the data identify a hierarchy in membrane protein clustering likely being a paradigm for many cellular self-organization processes.

Synergistic activity of antibiotics combined with ivermectin to kill body lice.

Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a Parafilm™ membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P≤10(-3)), with a significant difference between groups in the production of nits (P=0.019, Kruskal-Wallis test). A high lethal effect of ivermectin alone (50ng/mL) was observed compared with the control group (log-rank test, P≤10(-3)). Fluorescence of bacteriocytes in lice treated with 20µg/mL doxycycline was lower than in untreated lice (P<0.0001, Kruskal-Wallis test). In the second series with antibiotic-ivermectin combinations, a synergistic lethal effect on treated lice (log-rank test, P<10(-6)) was observed compared with the control group at 18 days, associated with a significant decrease in the production of nits (P≤0.001, Kruskal-Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log-rank test, P=0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population.