At-Home Trial of Four Different Head-Mounted Displays in Visual Rehabilitation of People with Stargardt Disease.

Purpose: To examine the potential of different head-mounted displays in the rehabilitation of individuals with visual impairment. Methods: This prospective explorative study conducted between September 2019 and August 2020 included participants with Stargardt disease with moderate to severe visual impairment and a relatively preserved peripheral visual field. AceSight, eSight 3, IrisVision Live, and Jordy were tested. After instruction and training, participants chose two head-mounted displays for home use for two weeks per device. The Canadian Occupational Performance Measure was used for evaluation. Results: Twelve participants (aged 16-53 years) tested all head-mounted displays in the clinic. Distance visual acuity and reading distance improved with all head-mounted displays and eSight and Irisvision improved near visual acuity. Six participants decided not to test the head-mounted display at home due to lack of time or energy, dizziness and discomfort, double vision and peripheral visual field limitation, or aesthetics. After home use, the participants reported improved visual function at a distance with IrisVision, AceSight, and e-Sight, whereas only AceSight improved vision during near tasks. IrisVision and eSight improved reading ability, and none of the devices improved vision during tasks involving computers. Five participants used the devices sparingly, and five avoided public use owing to aesthetics. Conclusion: We found an improvement in distance visual acuity and increased reading distance for all tested head-mounted displays. Additionally, IrisVision and eSight improved visual function at near and eSight also improved contrast vision at distance. Despite the possibility of improving vision, social stigma and device aesthetics kept the participants from using head-mounted displays in public and limited their use at home.

Highlighter: An optogenetic system for high-resolution gene expression control in plants.

Optogenetic actuators have revolutionized the resolution at which biological processes can be controlled. In plants, deployment of optogenetics is challenging due to the need for these light-responsive systems to function in the context of horticultural light environments. Furthermore, many available optogenetic actuators are based on plant photoreceptors that might crosstalk with endogenous signaling processes, while others depend on exogenously supplied cofactors. To overcome such challenges, we have developed Highlighter, a synthetic, light-gated gene expression system tailored for in planta function. Highlighter is based on the photoswitchable CcaS-CcaR system from cyanobacteria and is repurposed for plants as a fully genetically encoded system. Analysis of a re-engineered CcaS in Escherichia coli demonstrated green/red photoswitching with phytochromobilin, a chromophore endogenous to plants, but also revealed a blue light response likely derived from a flavin-binding LOV-like domain. We deployed Highlighter in transiently transformed Nicotiana benthamiana for optogenetic control of fluorescent protein expression. Using light to guide differential fluorescent protein expression in nuclei of neighboring cells, we demonstrate unprecedented spatiotemporal control of target gene expression. We implemented the system to demonstrate optogenetic control over plant immunity and pigment production through modulation of the spectral composition of broadband visible (white) light. Highlighter is a step forward for optogenetics in plants and a technology for high-resolution gene induction that will advance fundamental plant biology and provide new opportunities for crop improvement.

[Combination of a Lisfranc injury and a dislocation of the proximal tibiofibular joint].

Lisfranc injuries and dislocations of the proximal tibiofibular joint are both rare and frequently missed on initial examination. However, delayed treatment can lead to chronic instability. This is a case report of a 26-year-old man, who received both of these injuries on the same extremity from a collision during a basketball game. The dislocation of the proximal tibiofibular joint was treated with closed reduction, however the Lisfranc injury required open reduction and internal fixation. At the follow-up after ten weeks, the patient was doing well and started rehabilitation.

Leveraging the Value of CDISC SEND Data Sets for Cross-Study Analysis: Incidence of Microscopic Findings in Control Animals.

Implementation of the Clinical Data Interchange Standards Consortium (CDISC)'s Standard for Exchange of Nonclinical Data (SEND) by the United States Food and Drug Administration Center for Drug Evaluation and Research (US FDA CDER) has created large quantities of SEND data sets and a tremendous opportunity to apply large-scale data analytic approaches. To fully realize this opportunity, differences in SEND implementation that impair the ability to conduct cross-study analysis must be addressed. In this manuscript, a prototypical question regarding historical control data (see Table of Contents graphic) was used to identify areas for SEND harmonization and to develop algorithmic strategies for nonclinical cross-study analysis within a variety of databases. FDA CDER's repository of >1800 sponsor-submitted studies in SEND format was queried using the statistical programming language R to gain insight into how the CDISC SEND Implementation Guides are being applied across the industry. For each component needed to answer the question (defined as "query block"), the frequency of data population was determined and ranged from 6 to 99%. For fields populated <90% and/or that did not have Controlled Terminology, data extraction methods such as data transformation and script development were evaluated. Data extraction was successful for fields such as phase of study, negative controls, and histopathology using scripts. Calculations to assess accuracy of data extraction indicated a high confidence in most query block searches. Some fields such as vehicle name, animal supplier name, and test facility name are not amenable to accurate data extraction through script development alone and require additional harmonization to confidently extract data. Harmonization proposals are discussed in this manuscript. Implementation of these proposals will allow stakeholders to capitalize on the opportunity presented by SEND data sets to increase the efficiency and productivity of nonclinical drug development, allowing the most promising drug candidates to proceed through development.

False profile view is independently associated with serum metal levels in patients with metal-on-metal hip arthroplasty.

PURPOSE: Elevated levels of serum metal ions can be found in some patients with metal-on-metal (MoM) hip replacements. This study seeks to identify whether there is a significant association between the contact patch to rim distance (CPRD) and the anterior center edge angle (ACEA), respectively, and serum cobalt (Co) and chromium (Cr) levels in patients treated with unilateral MoM hip replacements by using standing anteroposterior and false profile view radiographs. METHODS: This is a retrospective analysis on 53 patients with either unilateral ReCap or M2a-Magnum MoM hip replacements operated in 2006 or 2007. Univariate linear regression and multivariable linear regression (MLR) analyses were performed using the CPRD and ACEA along with risk factors for elevated serum levels of Co and Cr previously suggested in the literature as explanatory variables. Serum Co and Cr were measured using inductively coupled plasma mass spectrometry. RESULTS: The MLR model showed that the same three variables (gender, CPRD and ACEA) were significantly associated with serum levels of both Co and Cr explaining approximately half of the variation. A univariate analysis showed a polynomial association between both anteversion angle and the ACEA with serum levels of Co and Cr. The vertex of the polynomial function was located at approximately 20° and 40°, respectively. CONCLUSION: Gender, CPRD and ACEA are independently associated with serum levels of Co and Cr. Both ACEA and anteversion angles have optimae associated with low serum metal levels which may be useful for post-surgery evaluation of cup positioning.

Does closed incision negative wound pressure therapy in non-traumatic major lower-extremity amputations improve survival rates?

Closed incision negative pressure wound therapy (CINPWT) has been shown to be clinically effective compared with the traditional gauze dressing, reducing surgical site infections and wound complications. We evaluated the effect of CINPWT compared with gauze dressing on the need for revision surgery and survival after non-traumatic major lower amputation. We included 309 patients undergoing 403 major lower amputations in a retrospective study from January 1, 2010 to November 23, 2017. A total of 139 patients received CINPWT, and 170 patients received stump bandage. There was no statistically significant difference between the two groups regarding the need for revision surgery (P = .45). Fourteen stump bandage patients and 15 CINPWT patients died in hospital (P = .57). One year after amputation, 55 CINPWT patients and 66 stump bandage patients had died (P = .82). Survival probabilities adjusted for age and gender 2 years after amputation were .52 (.43-.61) and .49 (.42-.58), respectively, and 3 years after amputation were .36 (.25-.50) and .39 (.32-.47), respectively. We also found no significant difference in the need for revision surgery in survival probabilities up till 3 years after amputation between patients treated with CINPWT and patients treated with gauze bandage postoperatively.

Identification of Iridoid Glucoside Transporters in Catharanthus roseus.

Monoterpenoid indole alkaloids (MIAs) are plant defense compounds and high-value pharmaceuticals. Biosynthesis of the universal MIA precursor, secologanin, is organized between internal phloem-associated parenchyma (IPAP) and epidermis cells. Transporters for intercellular transport of proposed mobile pathway intermediates have remained elusive. Screening of an Arabidopsis thaliana transporter library expressed in Xenopus oocytes identified AtNPF2.9 as a putative iridoid glucoside importer. Eight orthologs were identified in Catharanthus roseus, of which three, CrNPF2.4, CrNPF2.5 and CrNPF2.6, were capable of transporting the iridoid glucosides 7-deoxyloganic acid, loganic acid, loganin and secologanin into oocytes. Based on enzyme expression data and transporter specificity, we propose that several enzymes of the biosynthetic pathway are present in both IPAP and epidermis cells, and that the three transporters are responsible for transporting not only loganic acid, as previously proposed, but multiple intermediates. Identification of the iridoid glucoside-transporting CrNPFs is an important step toward understanding the complex orchestration of the seco-iridioid pathway.

Advances in methods for identification and characterization of plant transporter function.

Transport proteins are crucial for cellular function at all levels. Numerous importers and exporters facilitate transport of a diverse array of metabolites and ions intra- and intercellularly. Identification of transporter function is essential for understanding biological processes at both the cellular and organismal level. Assignment of a functional role to individual transporter proteins or to identify a transporter with a given substrate specificity has notoriously been challenging. Recently, major advances have been achieved in function-driven screens, phenotype-driven screens, and in silico-based approaches. In this review, we highlight examples that illustrate how new technology and tools have advanced identification and characterization of plant transporter functions.

Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors.

Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterologous expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the mAbs has major impact on the efficacy and safety of the drug and is therefore an important parameter to control during production. In this study, the effect on IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors during cultivation was investigated. The study was conducted in fed-batch mode in bioreactors with biological replicates to obtain highly controlled and comparable conditions. We assessed charge heterogeneity and glycosylation patterns of IgG. None of the eight feed additives caused statistically significant changes to cell growth or IgG productivity, compared to controls. However, the addition of 20 mM galactose did result in a reproducible increase of galactosylated IgG from 14% to 25%. On the other hand, addition of 20 mM N-acetyl-D-glucosamine (GlcNAc) reduced relative abundance of galactosylated IgG by 4%. Additionally, supplementation with 10 mM mannose slightly reduced GlcNAc occupancy of IgG. Overall, comparing the effects of IgG glycosylation, by supplementing the cell culture medium with glycosylation precursors during cultivation, revealed an application of these glycosylation precursors for modulating N-glycosylation of IgG.

Oromandibular dystonia--functional and clinical characteristics: a report on 21 cases.

OBJECTIVES: The objectives of this study were to describe subtypes, characteristics, and orofacial function of patients with oromandibular dystonia and report results of special dental importance. STUDY DESIGN: Symptoms, signs, and function were evaluated by questionnaires, video, and clinical and physiological examinations in 21 patients with primary and secondary dystonia (13 focal, 7 segmental, 1 multifocal). RESULTS: A mixture of 2 or more subtypes of jaw movements was most common (43%), and the dystonic electromyographic activity was frequent in the anterior digastric (62%) and temporal and lateral pterygoid (48%) muscles. The impact from the oromandibular dystonia was marked. The prevalence of problems with mastication and swallowing was high, as well as with hyposalivation, dental attrition, and other dental problems. CONCLUSIONS: Patients with oromandibular dystonia may present to dentists with involuntary jaw movements and other severe functional problems. Care must be adapted to the neurological disorder and may be complicated by the condition itself.

Quantifying the impact of residential heating on the urban air quality in a typical European coal combustion region.

The present investigation, carried out as a case study in a typical major city situated in a European coal combustion region (Krakow, Poland), aims at quantifying the impact on the urban air quality of residential heating by coal combustion in comparison with other potential pollution sources such as power plants, industry, and traffic. Emissions were measured for 20 major sources, including small stoves and boilers, and the particulate matter (PM) was analyzed for 52 individual compounds together with outdoor and indoor PM10 collected during typical winter pollution episodes. The data were analyzed using chemical mass balance modeling (CMB) and constrained positive matrix factorization (CMF) yielding source apportionments for PM10, B(a)P, and other regulated air pollutants namely Cd, Ni, As, and Pb. The results are potentially very useful for planning abatement strategies in all areas of the world, where coal combustion in small appliances is significant. During the studied pollution episodes in Krakow, European air quality limits were exceeded with up to a factor 8 for PM10 and up to a factor 200 for B(a)P. The levels of these air pollutants were accompanied by high concentrations of azaarenes, known markers for inefficient coal combustion. The major culprit for the extreme pollution levels was demonstrated to be residential heating by coal combustion in small stoves and boilers (>50% for PM10 and >90% B(a)P), whereas road transport (<10% for PM10 and <3% for B(a)P), and industry (4-15% for PM10 and <6% for B(a)P) played a lesser role. The indoor PM10 and B(a)P concentrations were at high levels similar to those of outdoor concentrations and were found to have the same sources as outdoors. The inorganic secondary aerosol component of PM10 amounted to around 30%, which for a large part may be attributed to the industrial emission of the precursors SO2 and NOx.

Effect of water/fuel emulsions and a cerium-based combustion improver additive on HD and LD diesel exhaust emissions.

One of the major technological challenges for the transport sector is to cut emissions of particulate matter (PM) and nitrogen oxides (NOx) simultaneously from diesel vehicles to meet future emission standards and to reduce their contribution to the pollution of ambient air. Installation of particle filters in all existing diesel vehicles (for new vehicles, the feasibility is proven) is an efficient but expensive and complicated solution; thus other short-term alternatives have been proposed. It is well known that water/diesel (W/ D) emulsions with up to 20% water can reduce PM and NOx emissions in heavy-duty (HD) engines. The amount of water that can be used in emulsions for the technically more susceptible light-duty (LD) vehicles is much lower, due to risks of impairing engine performance and durability. The present study investigates the potential emission reductions of an experimental 6% W/D emulsion with EURO-3 LD diesel vehicles in comparison to a commercial 12% W/D emulsion with a EURO-3 HD engine and to a Cerium-based combustion improver additive. For PM, the emulsions reduced the emissions with -32% for LD vehicles (mass/km) and -59% for the HD engine (mass/ kWh). However, NOx emissions remained unchanged, and emissions of other pollutants were actually increased forthe LD vehicles with +26% for hydrocarbons (HC), +18% for CO, and +25% for PM-associated benzo[a]pyrene toxicity equivalents (TEQ). In contrast, CO (-32%), TEQ (-14%), and NOx (-6%) were reduced by the emulsion for the HD engine, and only hydrocarbons were slightly increased (+16%). Whereas the Cerium-based additive was inefficient in the HD engine for all emissions except for TEQ (-39%), it markedly reduced all emissions for the LD vehicles (PM -13%, CO -18%, HC -26%, TEQ -25%) except for NOx, which remained unchanged. The presented data indicate a strong potential for reductions in PM emissions from current diesel engines by optimizing the fuel composition.