PURPOSE: To investigate and evaluate the removal time of various ophthalmic viscosurgical device (OVD)/viscoanesthetic solutions containing sodium hyaluronate 1.5% with different concentrations of lidocaine (0.5%, 1.0%, and 1.65%).

SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA.

METHODS: Six postmortem human eyes were prepared per the Miyake-Apple posterior video technique. Capsulorhexis, hydrodissection/delineation, and nuclear emulsification were performed, followed by thorough cleaning of the capsular bag using an irrigation/aspiration (I/A) tip. The time and ease of removal of 4 solutions from the capsular bag were evaluated. The solutions were Ophthalin Plus (sodium hyaluronate, 15 mg/mL) and sodium hyaluronate 15 mg/mL mixed with lidocaine 0.5%, lidocaine 1.0%, and lidocaine 1.65%. The solutions were dyed with fluorescein to enhance visualization. After the capsular bag was filled with 1 of the solutions, a posterior chamber intraocular lens was implanted. The solution was then aspirated using an automated I/A device set at 250 mm Hg of aspiration. The time required to remove most and then all the material was recorded.

RESULTS: The mean time required for removal of most of the Ophthalin Plus, viscoanesthesia 0.5%, viscoanesthesia 1%, and viscoanesthesia 1.65% solutions was 8.7 seconds +/- 2.1 (SD), 7.7 +/- 1.1 seconds, 9.7 +/- 0.6 seconds, and 6.3 +/- 1.5 seconds, respectively (P =.1). The mean time to remove all the solutions was 21.3 +/- 3.2 seconds, 19.7 +/- 2.5 seconds, 18.3 +/- 3.2 seconds, and 15.7 +/- 2.1 seconds, respectively (P =.166). No subjective difference in viscosity or consistency was found among the solutions.

CONCLUSIONS: The addition of lidocaine to the OVD solution did not significantly alter the viscosity or consistency of the solution or change its removal time from the capsular bag.

PURPOSE: To evaluate the efficacy of an intracapsular ring releasing 5-fluorouracil (5-FU) in preventing posterior capsule opacification (PCO) in rabbit eyes.

SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA, and Chu Morvan, Department d'Ophtalmologie, University of Brest, France.

METHODS: Seventeen rabbits were divided into 3 groups: Group 1, 6 rabbits (6 eyes), had phacoemulsification only (control group); Group 2, 6 rabbits (6 eyes), had phacoemulsification with implantation of an open-loop hydrogel intracapsular ring; Group 3, 5 rabbits (5 eyes), had phacoemulsification with implantation of a ring with sustained release of 0.25 microg/h of 5-FU for 9 days. All eyes were followed for 8 weeks before enucleation. Capsular bag shrinkage and the position of the intracapsular ring were assessed, and central and peripheral PCO was evaluated for intensity and area by stereomicroscopy from a posterior (Miyake-Apple) view. The residual equatorial lens epithelial cells (LECs) were counted by the same observer in histological sections. Transmission electron microscopy (TEM) of the cornea, capsular bag, and retina was done to evaluate the toxicity of 5-FU.

RESULTS: No significant difference was seen in the degree of capsular bag shrinkage in the 3 groups. The intracapsular ring was decentered in 2 eyes (1 each in Groups 2 and 3). There was a statistically significant difference (P <.05, Student t test) between Group 1 and Groups 2 and 3 in the area and intensity of central PCO. There was no difference between Groups 2 and 3 in the intensity of central PCO. No evidence of 5-FU toxicity to intraocular structures (cornea, capsular bag, and retina) was demonstrated on TEM analysis.

CONCLUSION: Implantation of an intracapsular ring may prevent central PCO after cataract surgery by mechanically blocking LEC migration toward the central visual axis. The potential pharmacological effect of 5-FU in PCO prevention was not demonstrated.

In this paper, a new optimization problem is proposed to determine the maximum distributed generation (DG) penetration level by optimally selecting types, locations and sizes of utility owned DG units. The DG penetration level could be limited by harmonic distortion because of the nonlinear current injected by inverter-based DG units and also protection coordination constraints because of the variation in fault current caused by synchronous-based DG units. Hence the objective of the proposed problem is to maximize DG penetration level from both types of DG units, taking into account power balance constraints, bus voltage limits, total and individual harmonic distortion limits specified by the IEEE-519 standard, over-current relay operating time limits, and protection coordination constraints. The DG penetration study is formulated as a nonlinear programming (NLP) problem and tested on the IEEE-30 bus looped distribution network with ten load and DG scenarios. Similarly, feasibility assessment of customer owned DG unit installations considering power quality and protection coordination is also studied. Simulation results show the effectiveness of the proposed approach, which can serve as an efficient planning tool for utility operators.

BACKGROUND: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services.

AIMS AND OBJECTIVES: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care.

METHODS: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included.

RESULTS: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible.

CONCLUSION: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.

Lipid modification of viral proteins with fatty acids of different lengths (S-acylation) is crucial for virus pathogenesis. The reaction is catalyzed by members of the DHHC family and proceeds in two steps: the autoacylation is followed by the acyl chain transfer onto protein substrates. The crystal structure of human DHHC20 (hDHHC20), an enzyme involved in the acylation of S-protein of SARS-CoV-2, revealed that the acyl chain may be inserted into a hydrophobic cavity formed by four transmembrane (TM) α-helices. To test this model, we used molecular dynamics of membrane-embedded hDHHC20 and its mutants either in the absence or presence of various acyl-CoAs. We found that among a range of acyl chain lengths probed only C16 adopts a conformation suitable for hDHHC20 autoacylation. This specificity is altered if the small or bulky residues at the cavity's ceiling are exchanged, e.g., the V185G mutant obtains strong preferences for binding C18. Surprisingly, an unusual hydrophilic ridge was found in TM helix 4 of hDHHC20, and the responsive hydrophilic patch supposedly involved in association was found in the 3D model of the S-protein TM-domain trimer. Finally, the exchange of critical Thr and Ser residues in the spike led to a significant decrease in its S-acylation. Our data allow further development of peptide/lipid-based inhibitors of hDHHC20 that might impede replication of Corona- and other enveloped viruses.

Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering mA levels by silencing either -adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating mA levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor-β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in mA modifications, as altered mA status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the mA status of target genes by controlling each other's expression and by inhibiting mA reader YTHDF3 (YTH -methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased mA and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for mA in cancer and shows that the collaboration among writers-erasers-readers sets up the mA threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that mA threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.

Rock’s hardness is one of the most investigated and important parameters which describes the strength properties of a rock mass. Laser-induced breakdown spectroscopy (LIBS) is a developing spectrochemical elemental analysis technique that is recently investigated to be used for metal hardness measurements. In this work, LIBS has been used to study the surface hardness of selected geological samples. The relationship between sample rebound test hardness, sample density and the LIBS plasma excitation temperature (Te) was investigated. It was observed that there is a linear relationship between the hardness and the density of the samples. Also, it was observed that there is a linear relation between Te and the hardness of the samples. The estimation of the surface hardness of the geological samples by measuring the Te shows the feasibility of LIBS as an easy and reliable method for geological samples’ application.

Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8 T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8 T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8 effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8 T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.